Publications on Gynécologie Cochin Paris : chirurgie, PMA et cancers

Prise en charge thérapeutique des grossesses extra-utérines tubaires : recommandations pour la pratique clinique du Collège national des gynécologues et obstétriciens français et de la Société de chirurgie gynécologique et pelvienne

Tue, 21 Apr 2026 13:12:12 +0200

Une grossesse extra-utérine correspond à l’implantation d’une grossesse en dehors de l’utérus, le plus souvent dans une trompe (96–99 % des cas). La prise en charge dépend de deux éléments clés : l’activité de la grossesse (évolution biologique) et la présence de symptômes. En cas de forme symptomatique ou active, une prise en charge immédiate est nécessaire, généralement médicale (méthotrexate) ou chirurgicale. À l’inverse, pour les formes asymptomatiques et peu évolutives, une surveillance simple peut être proposée avec un contrôle à 48 h du taux de hCG : une baisse >15 % permet de poursuivre la surveillance, alors qu’une augmentation ou l’apparition de symptômes impose de changer de stratégie. Le traitement médical privilégie une injection unique de méthotrexate (moins d’effets secondaires), sans association systématique à la mifépristone. La chirurgie repose sur une salpingotomie ou une salpingectomie, choisie notamment en fonction du projet de fertilité.

Anxiety and depression in women with endometriosis: a comparative study across fertility contexts.

Wed, 01 Apr 2026 00:00:00 +0000

Cette étude compare l’anxiété et la dépression chez des femmes ayant une endométriose à celles sans endométriose, lors d’un parcours de stimulation ovarienne (FIV/ICSI ou préservation de la fertilité). Globalement, l’anxiété est plus fréquente chez les patientes atteintes d’endométriose, sans différence statistiquement significative. En revanche, chez les femmes en FIV/ICSI, la dépression est significativement plus fréquente en cas d’endométriose (5,5 % vs 0,8 %). Dans le groupe de préservation de fertilité, les patientes avec endométriose ont davantage recours à un suivi psychologique et à des traitements psychotropes. Un facteur clé associé à l’anxiété et/ou à la dépression est la présence de douleurs importantes lors des rapports (dyspareunie profonde sévère). Ces résultats soulignent l’importance d’intégrer un accompagnement psychologique dans la prise en charge des patientes atteintes d’endométriose, surtout en cas de douleurs sévères ou d’infertilité.

How I do… Echo-guided ethanol sclerotherapy of ovarian endometrioma using transvaginal catheterization

Sun, 01 Mar 2026 00:00:00 +0000

Description d’une technique mini-invasive de traitement des endométriomes par alcoolisation écho-guidée via cathéter transvaginal, visant à améliorer la sécurité et l’efficacité du geste.

Low risk of endometrioma infection after oocyte retrieval.

Sun, 01 Mar 2026 00:00:00 +0000

Cette étude analyse le risque d’infection d’un endométriome après une ponction ovocytaire chez des femmes prises en charge en AMP. Sur plus de 1600 procédures, les infections nécessitant un drainage chirurgical sont très rares (0,36 %), y compris lorsqu’une ponction de l’endométriome est réalisée. Une seule infection a été observée après ponction transkystique, et aucune complication grave de type sepsis n’a été rapportée. La plupart des infections ont pu être traitées simplement par drainage échoguidé, avec très peu de recours à la chirurgie. Ces résultats confirment que la ponction ovocytaire, même en présence d’un endométriome, est globalement sûre avec un risque infectieux faible.

Fertility preservation in endometriosis: current strategies and outcomes.

Sun, 01 Feb 2026 00:00:00 +0000

L’endométriose est une maladie chronique fréquente qui peut altérer la fertilité (30 à 50 % de risque d’infertilité) via plusieurs mécanismes : inflammation, atteinte ovarienne, troubles tubaires et de la réceptivité endométriale. Dans ce contexte, la préservation de la fertilité doit être envisagée, en particulier avant une chirurgie ovarienne qui peut diminuer la réserve ovarienne. La technique la plus utilisée et efficace est la congélation d’ovocytes après stimulation ovarienne, dont les chances de succès dépendent surtout de l’âge et du nombre d’ovocytes obtenus. Les protocoles de stimulation sont globalement sûrs, avec un intérêt particulier pour les protocoles antagonistes avec déclenchement par agoniste de la GnRH, permettant de réduire la douleur et le risque d’hyperstimulation. La préservation de la fertilité doit être discutée au cas par cas avec les patientes, notamment avant un geste chirurgical, même si elle n’est pas encore systématique.

Risk of cardiovascular disease and mortality among women with endometriosis: A systematic review and meta-analysis.

Sun, 01 Feb 2026 00:00:00 +0000

L’endométriose, maladie inflammatoire chronique fréquente, pourrait augmenter le risque de maladies cardiovasculaires en raison de l’inflammation et de troubles du métabolisme lipidique. Cette méta-analyse montre une augmentation modérée du risque d’AVC (+18 %), de maladie coronarienne (+36 %) et plus globalement de maladies cardiovasculaires (+16 %) chez les femmes atteintes. Cependant, ces résultats doivent être interprétés avec prudence en raison de différences entre les études et de facteurs de confusion. Ils suggèrent néanmoins l’importance d’une prévention cardiovasculaire chez ces patientes (mode de vie, facteurs de risque).

Microbiota insights in endometriosis.

Fri, 05 Dec 2025 00:00:00 +0000

Endometriosis affects approximately 10% of women of reproductive age and is characterized by the presence of endometrial-like tissue outside the uterine cavity, leading to chronic pelvic pain, infertility, and a significant reduction in quality of life. Beyond its local manifestations, endometriosis is increasingly recognized as a systemic, immune-mediated condition with multifactorial origins. In this narrative review, we provide an updated and comprehensive overview of the disease, including its pathophysiology, clinical features, and evolving conceptual frameworks. Considering the frequent digestive symptoms observed in affected patients, we summarize key findings from both animal and human studies that investigate alterations in the gut microbiota. We also review the profound immune dysregulation associated with endometriosis and explore its potential bidirectional relationship with the microbiota. Furthermore, we examine recent insights into the endometrial microbiota-an emerging field of interest given its early involvement in the disease process and its strong interconnection with the vaginal microbiome. Lastly, we highlight studies exploring the gynecological microbiota and present an updated discussion of novel therapeutic strategies, including microbiota-targeted approaches that may shape future management of this complex disease. Video Abstract.

Oestradiol and reproductive outcomes in ART: when too much of a good thing hurts.

Mon, 01 Dec 2025 00:00:00 +0000

Oestradiol plays a crucial role in reproduction, particularly in assisted reproductive technology (ART), where it can reach supraphysiological concentrations. These fluctuations occur during ovarian stimulation in fresh embryo transfer cycles and during endometrial preparation for frozen embryo transfer, potentially impacting implantation and perinatal outcomes. Oestradiol influences endometrial proliferation, receptivity, implantation and placentation, with the sensitivity of the endometrium to systemic oestrogen emerging as a key determinant of reproductive success. In fresh embryo transfer cycles, ovarian stimulation induces histological, immunological and genetic changes in the endometrium, correlating with elevated oestradiol concentrations and possibly disrupting implantation. However, this adverse effect appears time-limited, as endometrial receptivity is restored in subsequent cycles. In FET cycles, both the duration and intensity of oestradiol exposure are critical, as excessive or prolonged exposure to exogenous oestradiol may impair reproductive outcomes. Despite these potential effects, strategies to regulate oestradiol concentrations in ART remain underexplored. This review examines the physiological and pathological roles of oestradiol in natural and ART cycles, emphasizing its impact on endometrial function, implantation and pregnancy outcomes. It highlights the need for further research to define optimal oestradiol thresholds and develop personalized ART protocols that consider both oestradiol concentrations and endometrial sensitivity to improve reproductive success and obstetric outcomes. Finally, it highlights strategies aimed at modulating oestradiol exposure to optimize reproductive success.

Venous Thromboembolism Risk Associated With Relugolix-estradiol-norethisterone Acetate Combination Therapy.

Sat, 22 Nov 2025 00:00:00 +0000

BACKGROUND: Relugolix, an oral GnRH receptor antagonist, is effective in treating uterine myomas and endometriosis. However, concerns persist regarding the venous thromboembolism (VTE) risk associated with its combination with oral estradiol (E2) and norethisterone acetate (NETA). OBJECTIVE: This expert opinion evaluates the thrombotic risk of relugolix combined therapy (relugolix-CT) based on pharmacological data, clinical trials, and regulatory assessments. METHODS: A review of pivotal trials (LIBERTY 1, LIBERTY 2, SPIRIT 1, SPIRIT 2), regulatory reports (European Medicines Agency, Food and Drug Administration), and real-world safety data was conducted, focusing on hemostatic effects and VTE risk. RESULTS: Relugolix monotherapy reduces estrogen levels, leading to minor decreases in coagulation factors. While E2 and NETA mitigate hypoestrogenic effects, concerns about their prothrombotic potential remain. However, clinical trials and postmarketing surveillance have not shown a significant increase in VTE risk. A meta-analysis suggests that E2-based regimens have a lower thrombotic risk than ethinylestradiol-based therapies. CONCLUSION: The VTE risk of relugolix-CT appears lower than that of traditional combined oral contraceptives. Nonetheless, patient selection is essential, particularly for those with thrombotic risk factors. Continued real-world surveillance is crucial to refining its safety profile in clinical practice.

[Chronic inflammatory rheumatic diseases and female fertility].

Wed, 01 Oct 2025 00:00:00 +0000

Chronic inflammatory rheumatic diseases (CIRDs) are a group of diseases responsible for inflammatory joint pains and can affect young women with a desire to conceive. CIRDs can impact female fertility, although the exact effects are still not fully understood. Some studies report reduced fertility, particularly due to prolonged conception delays, which are related to multiple factors. Among these, sexual dysfunction is common due to pain and chronic fatigue. The impact of CIRDs on ovarian reserve remains controversial. Regarding treatments, disease-modifying drugs have not shown a deleterious effect on fertility, but certain teratogenic treatments should be avoided in women who wish to conceive. Furthermore, there appears to be an association between CIRDs and some gynecological conditions known causes of infertility. For patients with CIRDs, early discussion about fertility is necessary. In the case of a desire for pregnancy, preconception consultation is essential to adjust treatments, manage risks, and prepare for pregnancy under the best possible conditions. In cases of proven infertility, assisted reproductive technology is a therapeutic option. Some studies suggest that success rates may be lower than those observed in the general population. A multidisciplinary approach involving rheumatologists, gynecologists, and reproductive specialists, as well as therapeutic optimization during the preconception period, is crucial to improve the chances of conception and provide appropriate follow-up for these patients.

Endometriosis and comorbidities: molecular mechanisms and clinical implications.

Wed, 01 Oct 2025 00:00:00 +0000

Endometriosis, traditionally viewed as a gynecological condition, is increasingly recognized as a systemic disease due to its frequent association with inflammatory and autoimmune comorbidities. Recent molecular and genetic insights reveal dysregulated hormone receptor signaling, heightened inflammatory responses, and immune dysfunction as central drivers of disease progression. These discoveries offer compelling explanations for extra-pelvic symptoms and open up avenues for targeted diagnostics and therapies. This review integrates emerging evidence to highlight endometriosis as a multisystem disorder, underscoring the need for multidisciplinary care. By redefining endometriosis beyond reproductive health, this perspective encourages a broader, systemic view of women’s health and fosters innovation in precision medicine.

Identification of a very-high risk subgroup of localized endometrial carcinoma before surgery using circulating tumor DNA: a proof-of-concept study.

Wed, 01 Oct 2025 00:00:00 +0000

Cette étude montre que la détection d’ADN tumoral circulant (ctDNA) avant la chirurgie chez des patientes atteintes de cancer de l’endomètre localisé permet d’identifier un sous-groupe à très haut risque de rechute précoce. Les patientes avec ctDNA détectable ont un taux de survie sans événement nettement plus faible à 1 an (67 % vs 91 %). Ce marqueur reste prédictif indépendamment du stade ou des classifications de risque habituelles, suggérant qu’il reflète la présence de micrométastases non visibles. Ces résultats ouvrent la voie à une meilleure stratification des patientes et pourraient justifier, à terme, des traitements plus précoces ou intensifiés (néoadjuvants) chez les patientes à haut risque.

The endocrine aspects of endometriosis.

Tue, 30 Sep 2025 00:00:00 +0000

Endometriosis is a chronic gynecologic disease of reproductive-age women, causing menstrual pain and infertility. Endocrine and inflammatory mechanisms drive its development, with estrogen/progesterone imbalance contributing to extrauterine implantation and persistence of ectopic endometrial cells. Chronic pain also induces stress-related disorders, worsening the quality of life. Infertility results from inflammatory, ovarian, and endometrial changes, and adverse pregnancy outcomes are reported. Diagnosis of endometriosis is clinical and imaging based. Furthermore, gastrointestinal, urinary, or autoimmune comorbidities complicate endometriosis management. Hormonal treatments, including progestins, estro-progestins, gonadotropin-releasing hormone analogs (GnRH-a), or oral antagonists, suppress menstruation and relieve pain. The relevant endocrine aspects and the systemic comorbidities make endometriosis a syndrome that requires a multidisciplinary diagnostic and therapeutic approach.

Reply: Evaluation of methodological and analytical approaches in assessing intra-individual serum progesterone variability on frozen embryo transfer day across hormone replacement therapy cycles.

Tue, 01 Jul 2025 00:00:00 +0000

[Patient satisfaction regarding hypnosis-assisted oocyte retrieval under local anesthesia].

Sun, 01 Jun 2025 00:00:00 +0000

OBJECTIVE: To evaluate the satisfaction of patients accompanied by hypnosis during oocyte retrieval under local anesthesia. METHODS: This cohort study included patients undergoing oocyte retrieval under local anesthesia with hypnotic support provided either by a hypnotherapist or via a virtual reality headset between November 2022 and November 2023. A questionnaire was distributed after the procedure, assessing satisfaction with hypnosis for pain and anxiety management, as well as the experience of pain (visual analog scale) and anxiety (State-Trait Anxiety Inventory) during the procedure. Incomplete questionnaires and non-French-speaking patients were excluded from the analysis. The two methods of hypnosis were compared. RESULTS: Out of 600 eligible women, 209 (34.8%) were included (mean age : 34.4±4.1 years). Hypnosis was conducted by a hypnotherapist for 167 patients (79.9%) and via a virtual reality headset for 42 patients (20.1%). Satisfaction with pain management was reported by 73.7% of the participants, and with anxiety management by 86.1%. Significantly more women found hypnosis beneficial for anxiety in the hypnotherapist group compared to the virtual reality group (148/167 [88.6%] versus 32/42 [76.2%], P=0.04). The mean visual analog scale score was 5.3±2.6, and the State-Trait Anxiety Inventory score during the oocyte retrieval was 36.7±17.8. No significant differences were found between the two groups for these scores. CONCLUSIONS: Women who received hypnosis during oocyte retrieval under local anesthesia were generally satisfied with this support, finding it beneficial for pain and anxiety management. Further research is needed to optimize the patient experience during this stressful procedure.

Perioperative iron deficiency and anaemia in scheduled gynaecological surgery: An update based on findings from the PERIOPES and CARENFER studies: Iron deficiency in gynaecological surgery.

Sun, 01 Jun 2025 00:00:00 +0000

Major gynaecological surgery is a significant risk factor for intra and postoperative blood loss. Effective iron deficiency (ID) and anaemia management is critical for ensuring patient safety. The aim of this update was to take an in-depth look at two recently published studies focusing on the assessment and management of ID and anaemia in subgroups of patients undergoing gynaecological surgery from the CARENFER PBM (2023) and PERIOPES (2023 and 2024) studies. Among the 6999 patients included in the three studies, 354 involved gynaecological procedures. Within this cohort, the prevalence of preoperative ID ranged from 70 % to 78 %, with 88 % considered absolute ID, while preoperative anaemia affected 28 %-59 % of women. Indeed, several gynaecological conditions that require surgery (e.g., uterine fibroids and gynaecological malignancies) are frequently associated with significant blood loss. Nonetheless, preoperative iron workup was only performed in 5 %-33 % of the patients. Furthermore, anaemia and/or ID were only treated in 12.5 %-24 % preoperatively and 25 % postoperatively. In conclusion, there seems to be a need to optimise perioperative ID and anaemia management in gynaecologic surgery by ensuring systematic preoperative screening and treatment for anaemia and/or ID and, wherever feasible, postponing surgery if restoration of the blood mass and iron stores is considered necessary prior to surgery.

Reply: Fetal safety of dydrogesterone: clarifying the role of pharmacovigilance.

Wed, 21 May 2025 00:00:00 +0000

Identification of a very-high risk subgroup of localized endometrial carcinoma before surgery using circulating tumor DNA: a proof-of-concept study

Thu, 15 May 2025 00:00:00 +0000

Cette étude montre que la détection d’ADN tumoral circulant avant la chirurgie permet d’identifier un sous-groupe de patientes atteintes d’un cancer de l’endomètre localisé à très haut risque de rechute, suggérant la présence de métastases microscopiques non visibles.

High serum estradiol levels on the day of frozen blastocyst transfer are associated with increased early miscarriage rates in artificial cycles using transdermal estrogens.

Thu, 01 May 2025 00:00:00 +0000

STUDY QUESTION: Do serum estradiol (E2) levels on the day of frozen blastocyst transfer (FBT) affect pregnancy outcomes in hormonal replacement therapy (HRT) cycles using transdermal estrogens? SUMMARY ANSWER: E2 levels ≥313 pg/ml on the day of FBT are associated with increased early miscarriage rates (EMRs), but do not significantly impact the live birth rate (LBR). WHAT IS KNOWN ALREADY: E2 plays a crucial role in endometrial receptivity and placentation. The effect of serum E2 levels measured around the time of FBT in HRT cycles remains debated, with some studies indicating a negative impact of high E2 levels and others finding no significant difference. Currently, no studies focus exclusively on HRT cycles using transdermal estrogens, which are considered safer regarding thromboembolic complications. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analyzed 2364 patients undergoing HRT-FBT cycles at a university hospital between January 2019 and December 2022. Each patient was included only once during the study period. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study involved patients undergoing single autologous FBT under HRT with transdermal estrogens and vaginal micronized progesterone. Serum E2 levels were measured in the morning of the FBT at a single laboratory. Primary outcomes included the LBR, with secondary outcomes encompassing clinical pregnancy rates, EMRs, and neonatal outcomes (birth weight and term of delivery). Patients were categorized into three groups based on E2 levels: <25th centile (<122 pg/ml), between 25th and 75th centile (122-312 pg/ml), and >75th centile (≥313 pg/ml), and analyzed using univariate and multivariate logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 2364 patients, 590 were in the ‘<122 pg/ml’ group, 1184 in the ‘122-312 pg/ml’ group, and 590 in the ‘≥313 pg/ml’ group. The median (interquartile range) E2 level in the entire study population was 195.3 pg/ml (122.1-312.8). The LBRs across the E2 level groups were 33.7%, 31.6%, and 31.0%. Crude and adjusted odds ratios (ORs) showed no significant differences in LBR between the ‘<122 pg/ml’ and ‘≥313 pg/ml’ groups compared to the ‘122-312 pg/ml’ reference group (adjusted OR 0.9, 95% CI 0.72-1.14 and 0.9, 95% CI 0.69-1.09, respectively). The EMRs for the groups were 25.5%, 24.6%, and 30.3%, respectively. While crude analysis showed no differences between the groups, the multivariable analysis indicated that the ‘≥313 pg/ml’ group had a significantly higher risk of early miscarriage compared to the reference group (adjusted OR 1.5, 95% CI 1.06-2.18). No significant differences were observed in clinical pregnancy rates or neonatal outcomes. LIMITATIONS, REASONS FOR CAUTION: The primary limitation is the study’s retrospective design, which introduces risks of selection and confusion bias, although multivariable analysis was employed to mitigate these issues. WIDER IMPLICATIONS OF THE FINDINGS: Managing high serum E2 levels on the day of the FBT may enhance ART outcomes. Future research should aim to define optimal E2 thresholds for HRT-FBT cycles and develop personalized treatment protocols that account for individual patient variability. STUDY FUNDING/COMPETING INTEREST(S): No funding was received. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Reduced live birth rates following ART in adenomyosis patients: a matched control study.

Thu, 01 May 2025 00:00:00 +0000

STUDY QUESTION: How does adenomyosis affect live birth rates (LBRs) in women undergoing ART compared to a matched control population? SUMMARY ANSWER: Women with adenomyosis, matched with controls for age, blastocyst count, and top-quality blastocyst count, exhibited reduced LBR following IVF/ICSI treatment. WHAT IS KNOWN ALREADY: Adenomyosis, a benign uterine disorder, is believed to hinder implantation due to anatomical, hormonal, and immune disruptions. Its precise impact on LBRs following ART, however, remains controversial, with studies presenting inconsistent outcomes. It is uncertain whether adenomyosis directly reduces ART success or if confounding factors such as age or embryo quality play a more significant role. STUDY DESIGN, SIZE, DURATION: This observational study included women aged 18-42 years undergoing IVF/ICSI treatments with a freeze-all strategy from 1 January 2018 to 31 December 2022, each having at least one available blastocyst for transfer. The adenomyosis group consisted of patients with a confirmed diagnosis through pelvic MRI, interpreted by gynecologic radiologists. The control group included women without adenomyosis, who had idiopathic, tubal, and/or male factor infertility. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 285 women with adenomyosis were included. These patients were matched 1:1 with controls based on age, the number of cryopreserved blastocysts, and the number of top-quality blastocysts. The primary outcome was the cumulative LBR per patient following a single oocyte retrieval, with secondary outcomes including clinical pregnancy rate (CPR) and early miscarriage rate (EMR). Both univariate and multivariate analyses were conducted. MAIN RESULTS AND THE ROLE OF CHANCE: In this study, 285 women with adenomyosis were matched with 285 controls. The mean age was 35.4 ± 3.3 and 35.5 ± 3.4 years, respectively, with an average of 3.5 ± 2.5 and 3.6 ± 2.6 cryopreserved blastocysts and 0.4 ± 0.7 and 0.4 ± 0.5 top-quality blastocysts, respectively. In the adenomyosis group, MRI revealed internal diffuse adenomyosis in 73.7% of patients, adenomyoma in 3.5%, and external adenomyosis lesions in 46.7%. The cumulative LBR was significantly lower in the adenomyosis group compared to controls (41.4% versus 51.9%; odds ratio = 0.65, 95% CI [0.47-0.91]; P = 0.012). Similarly, the CPR was reduced in the adenomyosis group (53.3% versus 63.9%; P = 0.011). No significant difference was found in the EMR. Multivariate analysis, adjusted for confounders such as freeze-all indication, AMH levels, BMI, infertility type, and ART procedure (IVF versus ICSI), identified adenomyosis as an independent risk factor for reduced LBR (OR = 0.7, 95% CI [0.4-0.9]). These findings indicate that adenomyosis is associated with lower ART success rates. LIMITATIONS, REASONS FOR CAUTION: Patients included in this study were from a specialized referral center focusing on the management of endometriosis and adenomyosis, potentially introducing selection bias, as these women may have more severe forms of adenomyosis. WIDER IMPLICATIONS OF THE FINDINGS: For infertile women, it is crucial for practitioners to conduct comprehensive clinical and imaging assessments to detect adenomyosis. Continued research is needed to refine and personalize ART management strategies for patients affected by this condition. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received. P.V. is the co-editor-in-chief of the Journal of Endometriosis and Uterine Disorders. C.M. has received payments to her institution from Merck, Ferring, Theramex, Gedeon Richer, and Besins, as well as direct payments to her from Gedeon Richter and Ferring and honoraria from Merck Serono, Ferring, Besins, IBSA, and Organon and meeting/travel support but no payment from Ferring, Besins, and Gedeon Richter. C.C. has received grants from Merck, Ferring, Theramex, Gedeon Richter, and Besins, which were paid to his institution, and honoraria from Merck, Besins, Gedeon Richter, and Theramex, which he received directly. He has also received support for attending meetings from Besins, Gedeon Richter, and Merck but no payment. He is a founder and past-president of the Society for Endometriosis and Uterine Disorders (SEUD), an unpaid role. P.S. received grants or contracts from Merck, Ferring, Theramex, Gedeon Richter, Besins, paid to his institution, and direct payment to him for presentations and lectures from Merck, Ferring, Besins, Gedeon Richter, Theramex, IBSA, and General Electric Medical Systems. He also received travel support but no payment from Merck, Ferring, Besins, Gedeon Richter, Theramex, and IBSA. P.S. is a board member of the SEUD and an editorial board member of RBMO and GOF. C.P. has received payment for lectures and presentations from Ferring and support but no payment for attending meetings from Ferring. M.B. has received grants from Merck, Ferring, Theramex, Gedeon Richter, and Besins, which were paid to her institution, and direct payment from Merck, Ferring, Gedeon Richter, Theramex, IBSA, and Organon for lectures/presentations. She has also received support but not payment for attending meetings from Ferring and Gedeon Richter. TRIAL REGISTRATION NUMBER: Not applicable.

Adenomyosis: the missed disease.

Tue, 01 Apr 2025 00:00:00 +0000

Adenomyosis, a menstruation-related uterine disorder, refers to the presence of endometrial stroma and glands within the myometrium and is typically observed in reproductive-age women. The pathogenesis explaining the migration, persistence, proliferation and differentiation of ectopic endometrial cells includes a genetic and epigenetic background, an oestrogen/progesterone receptor imbalance and an inflammatory reaction driven by local immune dysfunction, along with fibrosis and neuroangiogenesis within the myometrium. In the past, it was thought that adenomyosis almost exclusively affected multiparous women after 40 years of age and the diagnosis was generally confirmed upon hysterectomy. Nowadays, using imaging techniques such as transvaginal ultrasonography and magnetic resonance imaging, adenomyosis is increasingly identified in young women with dysmenorrhoea, dyspareunia, abnormal uterine bleeding and heavy menstrual bleeding, and also in infertile patients. Furthermore, adenomyosis often coexists with other gynaecological conditions, such as endometriosis and uterine fibroids. Despite the improvement of non-invasive diagnostic tools, the awareness of the condition is still poor and the diagnosis is often missed, due also to a heterogeneity in clinical presentation and imaging criteria. In addition, medical and surgical management do not follow shared recommendations, even though adenomyosis requires a lifelong management plan, including pain and bleeding control, fertility preservation and pregnancy complications.

Characteristics and outcomes in endometrioma infections: a cohort of 94 cases.

Tue, 01 Apr 2025 00:00:00 +0000

Systematic review on the DNA methylation role in endometriosis: current evidence and perspectives.

Fri, 21 Feb 2025 00:00:00 +0000

BACKGROUND: Endometriosis appears to have a multilayered etiology, with genetic and epigenetic factors each contributing half of the pathogenesis. The molecular processes that underlie the onset of endometriosis are yet unclear, but it is assumed that an important contributor in the etiopathology of the disease is DNA methylation. METHODS: We conducted a systematic review of the literature regarding DNA methylation in endometriosis following PRISMA guidelines. Records were obtained from PubMed and Web of Science on May 31, 2024. Original research articles analyzing regional or genome-wide DNA methylation in patients with confirmed endometriosis (by surgery and/or histological examination) were given consideration for inclusion. Only human studies were included, and there were no restrictions on the types of tissue that was analyzed (i.e., endometrium, blood, or fetal tissue). The study selection process was run by two manual reviewers. In parallel, an adapted virtual artificial intelligence-powered reviewer operated study selection and results were compared with the manual reviewers’ selection. Studies were divided into targeted (e.g., single gene or region level) and epigenome-wide association studies. For each, we extracted a list of genes studied with precise location of CpGs analyzed and the DNA methylation status according to the groups compared. Quality assessment of studies was performed following the Newcastle-Ottawa scale. Quality of evidence was graded following the Grading of Recommendations Assessment, Development and Evaluation. RESULTS: A total of 955 studies were screened, and 70 were identified as relevant for systematic review. Our analyses displayed that endometriosis could be polyepigenetic and with alterations in specific genes implicated in major signaling pathways contributing to the disease etiopathology (cell proliferation, differentiation, and division [PI3K-Akt and Wnt-signaling pathway], cell division [MAPK pathway], cell adhesion, cell communication, developmental processes, response to hormone, apoptosis, immunity, neurogenesis, and cancer). CONCLUSION: Our systematic review indicates that endometriosis is associated with DNA methylation modifications at specific genes involved in key endometrial biological processes, particularly in the ectopic endometrium. As DNA methylation appears to be an integral component of the pathogenesis of endometriosis, the identification of DNA methylation biomarkers would likely help better understand its causes and aggravating factors as well as potentially facilitate its diagnosis and support the development of new therapeutic approaches.

Clinical Characteristics of Women with Surgical Signs of Superficial Peritoneal Endometriosis but a Negative Histology: A Nested Case-Control Study.

Sat, 01 Feb 2025 00:00:00 +0000

OBJECTIVES: The aim of this study was to investigate the clinical characteristics of women with superficial peritoneal endometriosis (SUP) diagnosed by surgery and not confirmed by histology, compared with histologically proven SUP. DESIGN: This was a single-center, nested case-control study. Participants/Materials: Patients with a surgical report of SUP (n = 390), comprising a subgroup with histological confirmation of endometriosis (n = 245) and a subgroup without it (n = 145). In addition, we enrolled a control group (n = 390) among nonpregnant patients submitted to a laparoscopy or laparotomy for a benign gynecologic condition without any macroscopic sign of endometriosis. SETTING: The review was conducted in the University hospital. METHODS: Data synthesis, descriptive statistics, chi-square test, and one-way analysis of variance followed by Tukey’s test. RESULTS: All groups had similar age, body mass index, smoking prevalence, serum anti-müllerian hormone levels and menstrual cycle patterns. However, the two SUP subgroups had the same prevalence and intensity of endometriosis symptoms. The SUP/histology-negative subgroup was more likely to have a familial history of endometriosis (14% vs. 1%) or a personal history of primary infertility (29% vs. 19%) or primary dysmenorrhea (50% vs. 33%) compared to the control group (all p <0.01). The intensity scores for dysmenorrhea, deep dyspareunia, and non-cyclic chronic pelvic pain were severer in both SUP subgroups than in the control group (p < 0.05). LIMITATIONS: The participants underwent surgery, so their symptoms may not represent groups with initial or mild disease that responded to medical treatments. Due to the retrospective design, performance bias cannot be ruled out. CONCLUSIONS: Patients with suspected SUP lesions and a negative histology had clinical characteristics resembling those with proven endometriosis. Further characterization with molecular biomarkers is needed to explain why these women are so symptomatic in the absence of histological hallmarks of the disease.

Birth defects reporting and the use of dydrogesterone: a disproportionality analysis from the World Health Organization pharmacovigilance database (VigiBase).

Thu, 02 Jan 2025 00:00:00 +0000

STUDY QUESTION: Is there an association between dydrogesterone exposure during early pregnancy and the reporting of birth defects? SUMMARY ANSWER: This observational analysis based on global safety data showed an increased reporting of birth defects, mainly hypospadias and congenital heart defects (CHD), in pregnancies exposed to dydrogesterone, especially when comparing to progesterone. WHAT IS KNOWN ALREADY: Intravaginal administration of progesterone is the standard of care to overcome luteal phase progesterone deficiency induced by ovarian stimulation in ART. In recent years, randomized controlled clinical trials demonstrated that oral dydrogesterone was non-inferior for pregnancy rate at 12 weeks of gestation and could be an alternative to micronized vaginal progesterone. Safety profiles in both mother and child were similar. However, concerns have been raised regarding an association between dydrogesterone usage during early pregnancy and CHD in offspring. STUDY DESIGN SIZE DURATION: We performed a disproportionality analysis, also called case-non-case study, similar in concept to case-control studies, using the WHO global safety database, VigiBase. The study cohort consisted of individual pregnancy-related safety reports, using the ad hoc standardized query (SMQ ‘Pregnancy and neonatal topics’). Cases of birth defects consisted of safety reports containing terms related to the ‘congenital, familial and genetic disorders’ System Organ Class from the Medical Dictionary for Regulatory Activities. Non-cases consisted of safety reports containing any other adverse event, in pregnancy-related safety reports. PARTICIPANTS/MATERIALS SETTING METHODS: Considering reports since database inception to 31 December 2021, we first compared the reporting of birth defects with dydrogesterone to that of any other drug on the database, then to any other drug used for ART. Secondly, we performed a comparison on the reporting of birth defects for dydrogesterone with progesterone. Results are presented as reporting odds ratio (ROR) and their 95% CI. For each comparison, two sensitivity analyses were performed. Finally, a case-by-case review was performed to further characterize major birth defects and sort anomalies according to classification of EUROCAT. MAIN RESULTS AND THE ROLE OF CHANCE: Study cohort consisted of 362 183 safety reports in pregnant women, among which 50 653 reports were related to the use of drugs for ART, including 145 with dydrogesterone and 1222 with progesterone. Of these, 374 (0.7%) were cases of birth defects: 60 with dydrogesterone and 141 with progesterone, including 48 and 92 cases compatible with major birth defect cases according to EUROCAT classification, respectively. Major birth defects reported with dydrogesterone were mainly genital defects such as hypospadias and CHD. A significantly higher disproportionate reporting of birth defects was found with dydrogesterone when compared to any other drug (ROR 5.4, 95% CI [3.9-7.5]), to any other ART drug (ROR 6.0, 95% CI [4.2-8.5]), and to progesterone (ROR 5.4, 95% CI [3.7-7.9]). Sensitivity analyses found consistent results. LIMITATIONS REASONS FOR CAUTION: First, under-reporting, being inherent to pharmacovigilance systems, impedes the measurement of the incidence of adverse drug reactions and can limit the sensitivity of signal detection. Second, drug causality, not being the same for all cases, is challenging for such events and requires further assessment. However, sensitivity analyses showed consistent results. WIDER IMPLICATIONS OF THE FINDINGS: This possible safety signal emphasizes the need for further investigation regarding the fetal safety profile of dydrogesterone. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. None of the authors have any financial and personal relationships with other people or organizations that could influence the design, conductor or reporting of this work. TRIAL REGISTRATION NUMBER: N/A.

Advances in gynecologic clinical practice

Wed, 01 Jan 2025 00:00:00 +0000

Article clinique portant sur l’évolution des pratiques en gynécologie et l’optimisation des stratégies thérapeutiques.

Clues to revising the conventional diagnostic algorithm for endometriosis.

Wed, 01 Jan 2025 00:00:00 +0000

Endometriosis is a complex gynecologic disorder characterized primarily by symptoms of pelvic pain, infertility, and altered quality of life. National and international guidelines highlight the diagnostic difficulties and lack of conclusive diagnostic tools for endometriosis. Furthermore, guidelines are becoming questionable at an increasingly rapid rate as new diagnostic techniques emerge. This work aims to provide a knowledge synthesis of the relevance of various diagnostic tools and to assess areas of improvement of conventional algorithms. MEDLINE and Cochrane Library databases were searched from January 2021 to December 2023 using relevant key words. Articles evaluating the diagnostic relevance and performance of various tools were included and independently reviewed by the authors for eligibility. Included studies were assessed using the GRADE and QUADAS-2 tools. Of the 4204 retrieved articles, 26 were included. While anamnesis and clinical examination do contribute to diagnostic accuracy, their level of evidence and impact on the diagnostic process remains limited. Although imaging techniques are recommended to investigate endometriosis, ultrasonography remains highly operator dependent. Magnetic resonance imaging appears to exhibit higher sensitivities than ultrasound. However, concerns persist with regards to the terminology, anatomical definition of lesions, and accuracies of both ultrasound and magnetic resonance imaging. Recently, several biological markers have been studied and cumulative evidence supports the contribution of noncoding RNAs to the diagnosis of endometriosis. Marginal improvements have been suggested for anamnesis, clinical examination, and imaging examinations. Conversely, some biomarkers, including the saliva microRNA signature for endometriosis, have emerged as diagnostic tools which inspire reflection on the revision of conventional diagnostic algorithms.

Endometrioma and reproductive outcomes: clinical implications

Wed, 01 Jan 2025 00:00:00 +0000

Analyse du rôle des endométriomes dans les résultats en médecine de la reproduction et discussion des stratégies thérapeutiques optimales.

Microbiome and gynecologic disease

Wed, 01 Jan 2025 00:00:00 +0000

Travail explorant l’impact du microbiote sur les pathologies gynécologiques et ses implications diagnostiques et thérapeutiques.

Characteristics and outcomes in endometrioma infections: a cohort of 94 cases

Fri, 08 Nov 2024 00:00:00 +0000

Étude de cohorte analysant les infections d’endométriomes, leurs caractéristiques cliniques et leur évolution, afin d’améliorer la prise en charge et d’identifier les facteurs de risque.

Infertility, IL-17, IL-33 and Microbiome Cross-Talk: The Extended ARIA-MeDALL Hypothesis.

Thu, 07 Nov 2024 00:00:00 +0000

Infertility, defined as the inability to obtain pregnancy after 12 months of regular unprotected sexual intercourse, has increased in prevalence over the past decades, similarly to chronic, allergic, autoimmune, or neurodegenerative diseases. A recent ARIA-MeDALL hypothesis has proposed that all these diseases are linked to dysbiosis and to some cytokines such as interleukin 17 (IL-17) and interleukin 33 (IL-33). Our paper suggests that endometriosis, a leading cause of infertility, is linked to endometrial dysbiosis and two key cytokines, IL-17 and IL-33, which interact with intestinal dysbiosis. Intestinal dysbiosis contributes to elevated estrogen levels, a primary factor in endometriosis. Estrogens strongly activate IL-17 and IL-33, supporting the existence of a gut-endometrial axis as a significant contributor to infertility.

Western diet promotes endometriotic lesion growth in mice and induces depletion of Akkermansia muciniphila in intestinal microbiota.

Wed, 06 Nov 2024 00:00:00 +0000

BACKGROUND: Endometriosis, affecting 10% of women in their reproductive years, remains poorly understood. Both individual and environmental unexplained factors are implicated in this heterogenous condition. This study aims to examine the influence of a Western diet on endometriosis lesion development in mice and to uncover the mechanisms involved. METHODS: Mice were fed either a control diet or a Western diet (high in fatty acids and low in fiber) for 4 weeks. Endometriosis was then surgically induced, and lesion development was monitored by ultrasound. After 7 weeks, the mice were sacrificed for analysis of lesion characteristics through RT-qPCR, immunohistochemistry, and flow cytometry. Additionally, the intestinal microbiota was assessed using 16S rRNA gene sequencing. RESULTS: Mice on the Western diet developed lesions that were significantly twice as large compared to those on the control diet. These lesions exhibited greater fibrosis and proliferation, alongside enhanced macrophage activity and leptin pathway expression. Changes in the intestinal microbiota were significantly noted after endometriosis induction, regardless of diet. Notably, mice on the Western diet with the most substantial lesions showed a loss of Akkermansia Muciniphila in their intestinal microbiota. CONCLUSIONS: A Western diet significantly exacerbates lesion size in a mouse model of endometriosis, accompanied by metabolic and immune alterations. The onset of endometriosis also leads to substantial shifts in intestinal microbiota, suggesting a potential link between diet, intestinal health, and endometriosis development.

Assessment of the Pelvic Pain Experienced by Infertile Women is of Prime Importance for Diagnosing Endometriosis.

Fri, 01 Nov 2024 00:00:00 +0000

OBJECTIVE: To provide evidence regarding the significance of painful symptoms among women suffering from infertility. DESIGN: An observational retrospective cross-sectional study. SETTINGS: University hospital-based research center. PATIENTS: Infertile patients aged between 18 and 42 years surgically explored for benign gynecological conditions between 01-2004 and 12-2020. INTERVENTIONS: For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon in the month preceding the surgery. Preoperative assessment the pain symptoms was recorded. Pain intensity was assessed with a 10cm visual analog scale (VAS). The pain was considered to be severe when the VAS score was ≥ 7. MEASUREMENTS AND MAIN RESULTS: Surgery was performed in 839 infertile women. 451 women had severe pelvic pain. Infertile patients with severe pain significantly more often had endometriosis (67.4% versus 30.7% respectively; p <.001) than infertile women without severe pelvic pain, and especially deep infiltrating lesions (43.2% versus 8.5% respectively; p <.001). Moreover, these women more often had intestinal endometriosis lesions (28.4% vs 1.8%; p <.001). After multivariable regression analysis, the presence of endometriosis, irrespective of the phenotype (superficial lesions (OR1.84 [1.19-2.86] and/or ovarian endometrioma OR 2.79 [1.70-4.59] and/or deep infiltrating endometriosis OR 4.49 [2.69-7.51]), and the presence of at least one intestine endometriosis lesion (OR6.49 [2.69-7.51] were significantly associated with severe pelvic pain. CONCLUSION: Severe pelvic pain is significantly associated with endometriosis and especially deep infiltrating lesions in a population of infertile women. These results demonstrate the importance of thorough questioning regarding pelvic pain symptoms during the initial management of infertile patients.

Microbiology and outcomes of tubo-ovarian abscesses: A 5-year cohort of 105 cases.

Fri, 01 Nov 2024 00:00:00 +0000

Reply: Sticking to the facts instead of speculating: evidence against intensive luteal phase support in endometriosis patients undergoing HRT-FET cycles.

Fri, 01 Nov 2024 00:00:00 +0000

Distribution of endometriosis phenotypes according to patients' age in adult women with surgical evaluation.

Tue, 01 Oct 2024 00:00:00 +0000

STUDY QUESTION: What is the distribution of endometriosis phenotypes according to age in adult women undergoing surgery? SUMMARY ANSWER: The phenotype of endometriosis did not significantly vary after 24 years old. WHAT IS KNOWN ALREADY: The phenotypic evolution of endometriosis over time remains unclear. While adolescents can exhibit any type of endometriosis lesions, ovarian endometriosis (OMA) and/or deep-infiltrating endometriosis (DIE) tend to increase with age in young adults. In adulthood, understanding the evolution of lesions is crucial for disease management, but the literature on this subject is limited. This study aims to examine the distribution of endometriosis phenotypes in relation to age among adult patients requiring surgical treatment. STUDY DESIGN, SIZE, DURATION: This observational cohort study included patients aged between ≥18 and ≤42 years, who underwent surgery for benign gynecological conditions at our institution between January 2004 and December 2022. A standardized questionnaire was completed for each patient during a face-to-face interview conducted by the surgeon in the month preceding surgery. Women with histologically proven endometriosis were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: The distribution of endometriosis phenotypes (isolated superficial (SUP) endometriosis, OMA ± SUP, DIE ± SUP/OMA) was compared between young adults (≤24 years) and adults (>24 years) and among adults (25-28 years, 29-33 years, 34-38 years, 39 to ≤42 years) using univariate and multivariate analysis. The distribution of different subtypes of DIE (uterosacral ligament(s), vagina, bladder, intestine, and ureter), OMA size, and intensity of pain symptoms were also examined. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1311 adult women with histologically proven endometriosis were included. In women aged 24 years or younger (n = 116), the distribution of endometriosis phenotypes differed significantly from women older than 24 years (n = 1195): The frequency of the DIE ± SUP/OMA phenotype was lower (41.4% versus 56.1%, respectively), while the rate of isolated superficial lesions was higher (from 32.0% versus 25.9%) (P = 0.001). In the group of women aged >24 years, a significantly higher proportion of vaginal DIE lesions (P = 0.012) and a lower proportion of uterosacral ligament DIE lesions (P = 0.004) were found compared to women aged ≤24 years. No significant differences were observed in terms of endometrioma size. Between the ages of 25 and 42 years, there were no significant changes in the distribution of endometriosis phenotypes after univariate and multivariate analysis. The distribution of subtype of DIE lesions did not significantly change with age between 25 and 42 years. Concerning pain symptom scores, there was a significant decrease with age for dysmenorrhea and dyspareunia. LIMITATIONS, REASONS FOR CAUTION: Inclusion of only surgical patients may have introduced a selection bias. Women referred to our center may have suffered from particularly severe clinical forms of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: This study highlights that endometriosis presentation did not change with age in adult women. Further research on endometriosis phenotype evolution is necessary to assist practitioners in clinical decisions and treatment strategies. STUDY FUNDING/COMPETING INTERESTS: None declared. TRIAL REGISTRATION NUMBER: N/A.

Progesterone levels do not differ between patients with or without endometriosis/adenomyosis both in those who conceive after hormone replacement therapy-frozen embryo transfer cycles and those who do not.

Thu, 01 Aug 2024 00:00:00 +0000

STUDY QUESTION: Do women with endometriosis who achieve a live birth (LB) after HRT-frozen embryo transfer (HRT-FET) have different progesterone levels on the day of transfer compared to unaffected women? SUMMARY ANSWER: In women achieving a LB after HRT-FET, serum progesterone levels on the day of the transfer did not differ between patients with endometriosis and unaffected patients. WHAT IS KNOWN ALREADY: In HRT-FET, several studies have highlighted the correlation between serum progesterone levels at the time of FET and LB rates. In the pathophysiology of endometriosis, progesterone resistance is typically described in the eutopic endometrium. This has led to the hypothesis that women with endometriosis may require higher progesterone levels to achieve a LB, especially in HRT-FET cycles without a corpus luteum. STUDY DESIGN, SIZE, DURATION: We conducted an observational cohort study at the university-based reproductive medicine center of our institution, focusing on women who underwent a single autologous frozen blastocyst transfer after HRT using exogenous estradiol and micronized vaginal progesterone for endometrial preparation between January 2019 and December 2021. Women were included only once during the study period. Serum progesterone levels were measured on the morning of the FET by a single laboratory. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were divided into groups based on whether they had endometriosis or not and whether they achieved a LB. The diagnosis of endometriosis was based on published imaging criteria (transvaginal sonography/magnetic resonance imaging) and/or confirmed histology. The primary outcome was progesterone levels on the day of the HRT-FET leading to a LB in patients with endometriosis compared to unaffected women. Subgroup analyses were performed based on the presence of deep infiltrating endometriosis or adenomyosis. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1784 patients were included. The mean age of the women was 35.1 ± 4.1 (SD) years. Five hundred and sixty women had endometriosis, while 1224 did not. About 179/560 (32.0%) with endometriosis and 381/1224 (31.2%) without endometriosis achieved a LB. Among women who achieved a LB after HRT-FET, there was no significant difference in the mean progesterone level on the day of the HRT-FET between those with endometriosis and those without (13.6 ± 4.3 ng/ml vs 13.2 ± 4.4 ng/ml, respectively; P = 0.302). In the subgroup of women with deep infiltrating endometriosis (n = 142) and adenomyosis (n = 100), the mean progesterone level was 13.1 ± 4.1 ng/ml and 12.6 ± 3.7 ng/ml, respectively, with no significant difference compared to endometriosis-free patients. After adjusting for BMI, parity, duration of infertility, tobacco use, and geographic origin, neither the presence of endometriosis (coefficient 0.38; 95% CI: -0.63 to 1.40; P = 0.457) nor the presence of adenomyosis (coefficient 0.97; 95% CI: -0.24 to 2.19; P = 0.114) was associated with the progesterone level on the day of HRT-FET. Among women who did not conceive, there was no significant difference in the mean progesterone level on the day of the HRT-FET between those with endometriosis and those without (P = 0.709). LIMITATIONS, REASONS FOR CAUTION: The primary limitation of our study is associated with its observational design. Extrapolating our results to other laboratories or different routes and/or dosages of administering progesterone also requires validation. WIDER IMPLICATIONS OF THE FINDINGS: This study shows that patients diagnosed with endometriosis do not require higher progesterone levels on the day of a frozen blastocyst transfer to achieve a LB in hormonal replacement therapy cycles. STUDY FUNDING/COMPETING INTEREST(S): None declared. TRIAL REGISTRATION NUMBER: N/A.

Questionnaire-based screening of adolescents and young adult women can identify markers associated with endometriosis.

Thu, 01 Aug 2024 00:00:00 +0000

STUDY QUESTION: Do adolescents and young adult women (YAW) with histologically proven endometriosis present a specific clinical history? SUMMARY ANSWER: Questionnaire screening of adolescents and YAW can identify clinical markers associated with histologically proven endometriosis. WHAT IS KNOWN ALREADY: Some validated questionaries can contribute to an earlier endometriosis diagnosis in adults. None of these scores, however, have been validated for adolescents or YAW. STUDY DESIGN, SIZE, DURATION: This was an observational cross-sectional study using prospectively recorded data performed between January 2005 and January 2020 in a single university tertiary referral centre for endometriosis diagnosis and management. After a thorough surgical examination of the abdomino-pelvic cavity, women with histologically proven endometriosis were allocated to the endometriosis group, and symptomatic women without evidence of endometriosis were allocated to the endometriosis-free control group. The endometriotic patients were allocated into two sub-groups according to their age: adolescent (≤20 years) and YAW (21-24 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Adolescents and YAW ≤24 years of age were operated for a symptomatic benign gynaecological condition with signed informed consent. A standardized questionnaire was prospectively completed in the month before the surgery and included epidemiological data, pelvic pain scores, family history of endometriosis, and symptoms experienced during adolescence. The study searched for correlations by univariate analysis to determine clinical markers of endometriosis in adolescents and YAW compared with endometriosis-free control patients. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 262 study participants, 77 women were adolescents (≤20 years of age) and 185 patients (70.6%) were YAW. The endometriosis group included 118 patients (45.0%) and 144 (55.0%) were assigned to the control group. A family history of endometriosis, absenteeism from school during menstruation, history of fainting spells during menstruation, and prescription of oral contraceptive pills for intense dysmenorrhea were significantly more frequently observed in the endometriotic patients. The prevalence and mean pain scores for dysmenorrhea, deep dyspareunia, non-cyclic chronic pelvic pain and gastrointestinal and lower urinary tract symptoms were significantly greater in the endometriosis group, as was experienced rectal bleeding. LIMITATIONS, REASONS FOR CAUTION: The study was performed in a single referral centre that treats patients with potentially more severe disease. This questionnaire was evaluated on a population of patients with an indication for endometriosis surgery, which can also select patients with more severe disease. Women with asymptomatic endometriosis were not considered in this study. These factors can affect the external validity of this study. WIDER IMPLICATIONS OF THE FINDINGS: Patient interviews are relevant to the diagnosis of endometriosis in adolescents and YAW. Combined with imaging and clinical examination, this approach will enable earlier diagnosis and treatment, while remaining non-invasive and rapid. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding from external sources. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Society of Endometriosis and Uterine Disorders forum: adenomyosis today, Paris, France, December 12, 2023.

Thu, 01 Aug 2024 00:00:00 +0000

An antibody that inhibits TGF-β1 release from latent extracellular matrix complexes attenuates the progression of renal fibrosis.

Tue, 09 Jul 2024 00:00:00 +0000

Inhibitors of the transforming growth factor-β (TGF-β) pathway are potentially promising antifibrotic therapies, but nonselective simultaneous inhibition of all three TGF-β homologs has safety liabilities. TGF-β1 is noncovalently bound to a latency-associated peptide that is, in turn, covalently bound to different presenting molecules within large latent complexes. The latent TGF-β-binding proteins (LTBPs) present TGF-β1 in the extracellular matrix, and TGF-β1 is presented on immune cells by two transmembrane proteins, glycoprotein A repetitions predominant (GARP) and leucine-rich repeat protein 33 (LRRC33). Here, we describe LTBP-49247, an antibody that selectively bound to and inhibited the activation of TGF-β1 presented by LTBPs but did not bind to TGF-β1 presented by GARP or LRRC33. Structural studies demonstrated that LTBP-49247 recognized an epitope on LTBP-presented TGF-β1 that is not accessible on GARP- or LRRC33-presented TGF-β1, explaining the antibody’s selectivity for LTBP-complexed TGF-β1. In two rodent models of kidney fibrosis of different etiologies, LTBP-49247 attenuated fibrotic progression, indicating the central role of LTBP-presented TGF-β1 in renal fibrosis. In mice, LTBP-49247 did not have the toxic effects associated with less selective TGF-β inhibitors. These results establish the feasibility of selectively targeting LTBP-bound TGF-β1 as an approach for treating fibrosis.

Authors' Reply.

Mon, 01 Jul 2024 00:00:00 +0000

Clinical signs and diagnosis of fibroids from adolescence to menopause.

Mon, 01 Jul 2024 00:00:00 +0000

The aim of this review was to provide an updated assessment of the present diagnostic tools and clinical symptoms and signs to evaluate uterine fibroids (UFs) on the basis of current guidelines, recent scientific evidence, and a PubMed and Google Scholar search for peer-reviewed original and review articles related to clinical signs and diagnosis of UFs. Approximately 50%-75% of UFs are considered nonclinically relevant. When present, the most common symptoms are abnormal uterine bleeding, pelvic pain and/or bulk symptoms, and reproductive failure. Transvaginal ultrasound is recommended as the initial diagnostic modality because of its accessibility and high sensitivity, although magnetic resonance imaging appears to be the most accurate diagnostic tool to date in certain cases. Other emerging techniques, such as saline infusion sonohysterography, elastography, and contrast-enhanced ultrasonography, may contribute to improving diagnostic accuracy in selected cases. Moreover, artificial intelligence has begun to demonstrate its ability as a complementary tool to improve the efficiency of UF diagnosis. Therefore, it is critical to standardize descriptions of transvaginal ultrasound images according to updated classifications and to individualize the use of the different complementary diagnostic tools available to achieve precise uterine mapping that can lead to targeted therapeutic approaches according to the clinical context of each patient.

Minimally invasive approaches in gynecologic surgery

Mon, 01 Jul 2024 00:00:00 +0000

Étude évaluant les techniques chirurgicales mini-invasives en gynécologie et leur impact sur les résultats postopératoires.

The modern management of uterine fibroids-related abnormal uterine bleeding.

Mon, 01 Jul 2024 00:00:00 +0000

Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large percentage of cases and may be identified incidentally using a transvaginal ultrasound or a magnetic resonance imaging scan. However, in approximately 30% of cases, UFs affect the quality of life and women’s health, with abnormal uterine bleeding and heavy menstrual bleeding being the most common complaints, along with iron deficiency (ID) and ID anemia. Medical treatments used for UFs-related abnormal uterine bleeding include symptomatic agents, such as nonsteroidal antiinflammatory drugs and tranexamic acid, and hormonal therapies, including combined oral contraceptives, gonadotropin-releasing hormone agonists or antagonists, levonorgestrel intrauterine systems, selective progesterone receptor modulators, and aromatase inhibitors. Nevertheless, few drugs are approved specifically for UF treatment, and most of them manage the symptoms. Surgical options include fertility-sparing treatments, such as myomectomy, or nonconservative options, such as hysterectomy, especially in perimenopausal women who are not responding to any treatment. Radiologic interventions are also available: uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound, and radiofrequency ablation. Furthermore, the management of ID and ID anemia, as a consequence of acute and chronic bleeding, should be taken into account with the use of iron replacement therapy both during medical treatment and before and after a surgical procedure. In the case of symptomatic UFs, the location, size, multiple UFs, or coexistent adenomyosis should guide the choice with a shared decision-making process, considering long- and short-term treatment goals expected by the patient, including pregnancy desire or wish to preserve the uterus independently of reproductive goals.

Menstrual Blood Donation for Endometriosis Research: A Cross-Sectional Survey on Women's Willingness and Potential Barriers.

Sat, 01 Jun 2024 00:00:00 +0000

An anonymous online survey in French was used to assess if endometriosis patients would be as ready as unaffected women to donate their menstrual blood for biological research on endometriosis and evaluate potential barriers to such donation. It was distributed in September 2022 by social media and two mailing lists, including a French patient organization. The questionnaire assessed participant age and brief medical history (hormonal contraception, endometriosis diagnosis, type of endometriosis), menstrual experience (menstrual blood abundance, dysmenorrhea), and whether participants would donate menstrual blood. Women who self-declared with an established endometriosis diagnosis versus no endometriosis were compared. Seven hundred seventy-eight women answered the survey. Among women with menstruation (n = 568), 78% are willing to donate menstrual blood for research. Importantly, this proportion was higher in women who declared having an established endometriosis diagnosis (83%, n = 299) compared to self-declared unaffected women (68%, n = 134, p < 0.001). The previous use of a menstrual cup and dysmenorrhea were significantly associated with the willingness to donate menstrual blood, while the use of hormonal contraception was significantly associated with an unwillingness to donate. Only the previous use of the menstrual cup had a predictive value for menstrual blood donation. No significant relationship was observed between menstrual blood donation and age, heavy menstrual bleeding and in endometriosis patients, endometriosis subtypes. In conclusion, women affected or not by endometriosis are largely willing to donate their menstrual blood for research on endometriosis, dysmenorrhea is not a barrier for donation, and women who use a menstrual cup are the more likely to donate.

A Call for New Theories on the Pathogenesis and Pathophysiology of Endometriosis.

Wed, 01 May 2024 00:00:00 +0000

Intra-individual variability of serum progesterone levels on the day of frozen blastocyst transfer in hormonal replacement therapy cycles.

Wed, 03 Apr 2024 00:00:00 +0000

STUDY QUESTION: Is there a significant intra-individual variability of serum progesterone levels on the day of single blastocyst Hormone Replacement Therapy-Frozen Embryo Transfer (HRT-FET) between two consecutive cycles? SUMMARY ANSWER: No significant intra-individual variability of serum progesterone (P) levels was noted between two consecutive HRT-FET cycles. WHAT IS KNOWN ALREADY: In HRT-FET cycles, a minimum P level on the day of embryo transfer is necessary to optimise reproductive outcomes. In a previous study by our team, a threshold of 9.8 ng/ml serum P was identified as significantly associated with the live birth rates in single autologous blastocyst transfers under HRT using micronized vaginal progesterone (MVP). Such patients may benefit from an intensive luteal phase support (LPS) using other routes of P administration in addition to MVP. A crucial question in the way towards individualising LPS is whether serum P measurements are reproducible for a given patient in consecutive HRT-FET cycles, using the same LPS. STUDY DESIGN, SIZE, DURATION: We conducted an observational cohort study at the university-based reproductive medicine centre of our institution focusing on women who underwent at least two consecutive single autologous blastocyst HRT-FET cycles between January 2019 and March 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing two consecutive single autologous blastocyst HRT-FET cycles using exogenous oestradiol and vaginal micronized progesterone for endometrial preparation were included. Serum progesterone levels were measured on the morning of the Frozen Embryo Transfer (FET), by a single laboratory. The two measurements of progesterone levels performed on the day of the first (FET1) and the second FET (FET2) were compared to evaluate the intra-individual variability of serum P levels. Paired statistical analyses were performed, as appropriate. MAIN RESULTS AND THE ROLE OF CHANCE: Two hundred and sixty-four patients undergoing two consecutive single autologous blastocyst HRT-FET were included. The mean age of the included women was 35.0 ± 4.2 years. No significant intra-individual variability was observed between FET1 and FET2 (mean progesterone level after FET1: 13.4 ± 5.1 ng/ml vs after FET2: 13.9 ± 5.0; P = 0.08). The characteristics of the embryo transfers were similar between the first and the second FET. Forty-nine patients (18.6%) had discordant progesterone levels (defined as one progesterone measurement > and one ≤ to the threshold of 9.8 ng/ml) between FET1 and FET2. There were 37/264 women (14.0%) who had high intra-individual variability (defined as a difference in serum progesterone values >75th percentile (6.0 ng/ml)) between FET1 and FET2. No specific clinical parameter was associated with a high intra-individual variability nor a discordant P measurement. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design. Moreover, only women undergoing autologous blastocyst HRT-FET with MVP were included, thereby limiting the extrapolation of the study findings to other routes of P administration and other kinds of endometrial preparation for FET. WIDER IMPLICATIONS OF THE FINDINGS: No significant intra-individual variability was noted. The serum progesterone level appeared to be reproducible in >80% of cases. These findings suggest that the serum progesterone level measured on the day of the first transfer can be used to individualize luteal phase support in subsequent cycles. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests. TRIAL REGISTRATION NUMBER: N/A.

The -'freeze-all-' strategy seems to improve the chances of birth in adenomyosis-affected women.

Fri, 01 Mar 2024 00:00:00 +0000

OBJECTIVE: To compare assisted reproductive technologies (ARTs) outcomes between fresh vs. freeze-all strategies in infertile women affected by adenomyosis. DESIGN: A single-center observational study. SETTINGS: University hospital-based research center. PATIENTS: Adenomyosis-affected women undergoing blastocyst embryo transfer after in vitro fertilization and intracytoplasmic sperm injection between January 1, 2018, and November 31, 2021. The diagnosis of adenomyosis was based on imaging criteria (i.e., transvaginal ultrasound and/or magnetic resonance imaging). INTERVENTION(S): Women who underwent a freeze-all strategy were compared with those who underwent a fresh embryo transfer (ET) strategy. MAIN OUTCOME MEASURE(S): Cumulative live birth rate (LBR). RESULTS: A total of 306 women were included in the analysis: 111 in the fresh ET group and 195 in the freeze-all group. The adenomyosis phenotype (internal diffuse adenomyosis, external focal adenomyosis, and adenomyoma) was not significantly different between the two groups. The cumulative LBR (86 [44.1%] vs. 34 [30.6%], respectively), and the cumulative ongoing pregnancy rate (88 [45.1%] vs. 36 [32.4%], respectively) were significantly higher in the freeze-all group compared with the fresh ET group. After multivariate logistic regression analysis, the freeze-all strategy in women with adenomyosis was associated with significantly higher odds of live birth compared with fresh ET (odds ratio = 1.80; 95% confidence interval = 1.02-3.16). CONCLUSION: The freeze-all strategy in women afflicted with adenomyosis undergoing ART was associated with significantly higher cumulative LBRs. Our preliminary results suggest that the freeze-all strategy is an attractive option that increases ART success rates. Additional studies, with a randomized design, should be conducted to further test whether the freeze-all strategy enhances the pregnancy rate in adenomyosis-affected women.

An integrated multi-tissue approach for endometriosis candidate biomarkers: a systematic review.

Sat, 10 Feb 2024 00:00:00 +0000

Biomarker identification could help in deciphering endometriosis pathophysiology in addition to their use in the development of non invasive diagnostic and prognostic approaches, that are essential to greatly improve patient care. Despite extensive efforts, no single potential biomarker or combination has been clinically validated for endometriosis.Many studies have investigated endometriosis-associated biological markers in specific tissues, but an integrative approach across tissues is lacking. The aim of this review is to propose a comprehensive overview of identified biomarkers based on tissue or biological compartment, while taking into account endometriosis phenotypes (superficial, ovarian or deep, or rASRM stages), menstrual cycle phases, treatments and symptoms.We searched PubMed and Embase databases for articles matching the following criteria: ’endometriosis’ present in the title and the associated term ‘biomarkers’ found as Medical Subject Headings (MeSH) terms or in all fields. We restricted to publications in English and on human populations. Relevant articles published between 01 January 2005 (when endometriosis phenotypes start to be described in papers) and 01 September 2022 were critically analysed and discussed.Four hundred forty seven articles on endometriosis biomarkers that included a control group without endometriosis and provided specific information on endometriosis phenotypes are included in this review. Presence of information or adjustment controlling for menstrual cycle phase, symptoms and treatments is highlighted, and the results are further summarized by biological compartment. The 9 biological compartments studied for endometriosis biomarker research are in order of frequency: peripheral blood, eutopic endometrium, peritoneal fluid, ovaries, urine, menstrual blood, saliva, feces and cervical mucus. Adjustments of results on disease phenotypes, cycle phases, treatments and symptoms are present in 70%, 29%, 3% and 6% of selected articles, respectively. A total of 1107 biomarkers were identified in these biological compartments. Of these, 74 were found in several biological compartments by at least two independent research teams and only 4 (TNF-a, MMP-9, TIMP-1 and miR-451) are detected in at least 3 tissues with cohorts of 30 women or more.Integrative analysis is a crucial step to highlight potential pitfalls behind the lack of success in the search for clinically relevant endometriosis biomarkers, and to illuminate the physiopathology of this disease.

Endometriosis-related infertility: severe pain symptoms do not impact assisted reproductive technology outcomes.

Thu, 01 Feb 2024 00:00:00 +0000

STUDY QUESTION: Do severe endometriosis-related painful symptoms impact ART live birth rates? SUMMARY ANSWER: Severe pain symptoms are not associated with reduced ART live birth rates in endometriosis patients. WHAT IS KNOWN ALREADY: ART is currently recognized as one of the main therapeutic options to manage endometriosis-related infertility. Presently, no data exist in the literature regarding the association between the core symptom of the disease, e.g. pain and ART reproductive outcomes. STUDY DESIGN, SIZE, DURATION: Observational cohort study of 354 endometriosis patients, who underwent ART at a tertiary care university hospital, between October 2014 and October 2021. Diagnosis of endometriosis was based on published imaging criteria using transvaginal sonography and magnetic resonance imaging, and histologically confirmed in women who had a previous history of endometriosis surgery (n = 127, 35.9%). PARTICIPANTS/MATERIALS, SETTING, METHODS: The intensity of painful symptoms related to dysmenorrhea (DM), dyspareunia (DP), noncyclic chronic pelvic pain, gastrointestinal (GI) pain, or lower urinary tract pain was evaluated using a 10-point visual analog scale (VAS), before ART. Severe pain was defined as having a VAS of 7 or higher for at least one symptom. The main outcome measure was the cumulative live birth rate (CLBR) per patient. We analyzed the impact of endometriosis-related painful symptoms on ART live births using univariable and multivariate analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Three hundred and fifty-four endometriosis patients underwent 711 ART cycles. The mean age of the population was 33.8 ± 3.7 years, and the mean duration of infertility was 3.6 ± 2.1 years. The distribution of the endometriosis phenotypes was 3.1% superficial endometriosis, 8.2% ovarian endometrioma, and 88.7% deep infiltrating endometriosis. The mean VAS scores for DM, DP, and GI pain symptoms were 6.6 ± 2.7, 3.4 ± 3.1, and 3.1 ± 3.6, respectively. Two hundred and forty-two patients (68.4%) had severe pain symptoms. The CLBR per patient was 63.8% (226/354). Neither the mean VAS scores for the various painful symptoms nor the proportion of patients displaying severe pain differed significantly between patients who had a live birth and those who had not, based on univariate and multivariate analyses (P = 0.229). The only significant factors associated with negative ART live births were age >35 years (P < 0.001) and anti-Müllerian hormone levels <1.2 ng/ml (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The diagnosis of endometriosis was based on imaging rather than surgery. This limitation is, however, inherent to the design of most studies on endometriosis patients reverting to ART first. WIDER IMPLICATIONS OF THE FINDINGS: Rather than considering a single argument such as pain, the decision-making process for choosing between ART and surgery in infertile endometriosis patients should be based on a multitude of aspects, including the patient’s choice, the associated infertility factors, the endometriosis phenotypes, and the efficiency of medical therapies in regard to pain symptoms, through an individualized approach guided by a multidisciplinary team of experts. STUDY FUNDING/COMPETING INTEREST(S): No funding; no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Investigating the medical journey of endometriosis-affected women: Results from a cross-sectional web-based survey (EndoVie) on 1,557 French women.

Thu, 01 Feb 2024 00:00:00 +0000

OBJECTIVE: To investigate the medical journey and the quality of life of French endometriosis-affected women, from the onset of the symptoms to the therapeutic management. STUDY DESIGN: Between January 15th 2020 and February 3rd 2020, a prospective cross-sectional web-based survey was conducted among women diagnosed with endometriosis. The questionnaire included 52 questions distributed in five sections (screening, sociodemographic characteristics, impacts on quality of life, SF36 questionnaire, management of endometriosis and proposals for care improvement). RESULTS: One thousand five hundred fifty-seven endometriosis-affected women aged of 42±12.8 years answered the questionnaire. On average, 7 years elapsed between the first symptoms (at 23.8 ± 10.2 years) and the diagnosis (31.0 ± 8.9 years). The mean number of symptoms was 4.6 ± 2.3, with 82 % of women experiencing pain scores between 7 and 10/10. Following diagnosis, 66 % women received a medical treatment, mostly hormonal treatments (45 %), with a significant decrease in pain intensity (VAS scores after treatment = 4.9 ± 2.7, p < 0.001). Most women (62 %) had already been operated, among whom 22 % by laparotomy. Finally, patients reported numerous impacts on their daily lives, particularly on the sexual, psychological, and physical fields. The overall mean score of quality of life was 4.3 ± 2.6 /10. CONCLUSION: This large prospective web-based survey underlines that the journey of women with endometriosis is long and difficult until diagnosis and efficient treatment. It emphasizes the urgent need to reduce the diagnostic delay and thereby the burden of endometriosis on women’s lives. Moreover, the creation of referral multidisciplinary centers appears to be crucial to improve the management of the disease.

Reduced fertility in an adenomyosis mouse model is associated with an altered immune profile in the uterus during the implantation period.

Fri, 05 Jan 2024 00:00:00 +0000

STUDY QUESTION: Does a reduction in fertility and/or systemic immune cell change occur during the early implantation period in a mouse model of adenomyosis? SUMMARY ANSWER: A reduction in fertility was observed in mice with adenomyosis, coinciding with local and systemic immune changes observed during the implantation period. WHAT IS KNOWN ALREADY: Adenomyosis is a pathology responsible for impaired fertility in humans, with a still unclear pathophysiology. One hypothesis is that changes in immune cells observed in adenomyosis-affected uteri may alter fertility, notably the physiological immune environment necessary for successful implantation and a healthy pregnancy. STUDY DESIGN, SIZE, DURATION: Randomly selected CD-1 female neonatal pups were orally dosed by administration of tamoxifen to induce adenomyosis (TAM group), while others received solvent only (control group). From 6 weeks of life, CD-1 mice of both groups were mated to study impaired fertility and related local and/or systemic immune cell changes during the early implantation period. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: To evaluate fertility and pregnancy outcomes, ultrasound imaging was performed at E (embryonic day) 7.5 and E11.5 to count the number of gestational sacs and the number of resorptions in eight mice of the TAM group and 16 mice of the control group. The mice were sacrificed at E18.5, and morphometric, functional (quantitative reverse transcription PCR; RT-qPCR), and histological analyses were performed on the placentas. To identify local and/or systemic immune changes during the early implantation period, 8 mice of the TAM group and 12 mice of the control group were sacrificed at E4.5. Uterine horns and spleens were collected for flow cytometry and RT-qPCR analyses to study the immune cell populations. To investigate the profile of the cytokines secreted during the early implantation period at the systemic level, supernatants from stimulated spleen cells were analyzed by multiplex immunoassay analysis. MAIN RESULTS AND THE ROLE OF CHANCE: By ultrasound imaging, we observed a lower number of implantation sites (P < 0.005) and a higher number of resorptions (P < 0.001) in the TAM group, leading to smaller litters (average number of fetuses per litter: 1.00 [0.00; 5.25] in the TAM group versus 12.00 [9.50; 13.75] in the control group (P < 0.001). Histological and morphometric analyses of the placentas at E18.5 showed a higher junctional/labyrinthine area ratio in the TAM group (P = 0.005). The expression levels of genes that play a role in vascularization and placental growth (Vegf (P < 0.001), Plgf (P < 0.005), Pecam (P < 0.0001), and Igf2 (P = 0.002)) were reduced in the TAM group. In the TAM group, the percentages of macrophages, natural killer (NK) cells, and dendritic cells (DC) were significantly decreased in the uterus around the implantation period. However, the number of M1 macrophages was increased. Both macrophages and DC had an increased activation profile (higher expression of MCHII, P = 0.012; CD80, P = 0.015; CCR7, P = 0.043 for macrophages, and higher expression of CD206, P = 0.018; CXCR4, P = 0.010; CCR7, P = 0.006, MCHII, P = 0.010; and CD80, P = 0.012 for DC). In spleen, an increase in the activation of macrophages (CCR7, P = 0.002; MCHII, P = 0.001; and CD80, P = 0.034) and DC was observed in the TAM group (CCR7, P = 0.001; MCHII, P = 0.001; Ly6C, P = 0.015). In the uteri and the spleen, we observed increased percentages of CD4+ T lymphocytes (P = 0.0237 and P = 0.0136, respectively) in the TAM group and, in the uteri, an increased number of regulatory T cells (P = 0.036) compared with the controls. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: This study is limited by the use of an animal model and the lack of intervention. WIDER IMPLICATIONS OF THE FINDINGS: These data support involvement of innate and adaptive immune cells in the implantation failure and the increased rate of resorption observed in the mouse model of adenomyosis. This substantiates the need for additional research in this domain, with the goal of addressing fertility challenges in women affected by this condition. STUDY FUNDING/COMPETING INTEREST(S): None.

Effects of Ulipristal Acetate on Reactive Oxygen Species and Proinflammatory Cytokine Release by Epithelial and Stromal Cells from Human Endometrium and Endometriosis.

Mon, 01 Jan 2024 00:00:00 +0000

Endometriosis is a condition characterized by increased oxidative stress and chronic inflammation, which can be treated with progestins and other progesterone receptor ligands. However, some patients are refractory to this treatment and the reason is uncertain. Here we investigated the effects of the selective progesterone receptor modulator ulipristal acetate (UPA) on proliferation, reactive oxygen species (ROS), and proinflammatory cytokine production by endometriotic cells and endometrial cells from women with histologically proven endometriosis (n = 22) and endometriosis-free controls (n = 6). Epithelial and stromal cells were isolated and treated in triplicate for 24 h with 1 μM, 10 μM, or 100 μM UPA. Cells were tested for proliferation and ROS production, while cell supernatants were assayed for interleukin (IL)-6, C-C motif chemokine ligand 2 (CCL2), and tumor necrosis factor (TNF)-α concentrations. Proliferation, ROS production, and IL-6 and CCL2 secretion were increased in non-stimulated epithelial and stromal cells from endometriotic lesions compared to endometrial cells from endometriosis patients and controls. UPA induced a dose-dependent increase of cell proliferation only in endometriosis, while enhancing ROS production by all cell types evaluated. UPA reduced CCL2 production in controls but failed to do that in endometriosis, whereas TNF-α was undetectable. We conclude that treatment of endometriotic cells with UPA stimulated in vitro proliferation and ROS production and failed to revert the proinflammatory cytokine excess that characterized these cells, unravelling possible mechanisms of drug resistance in the treatment of endometriosis.

Update on the management of endometriosis-associated pain in France.

Wed, 01 Nov 2023 00:00:00 +0000

The French National College of Obstetricians and Gynecologists (CNGOF) published guidelines for managing endometriosis-associated pain in 2018. Given the development of new pharmacological therapies and a review that was published in 2021, most national and international guidelines now suggest a new therapeutic approach. In addition, a novel validated screening method based on patient questionnaires and analysis of 109-miRNA saliva signatures, which combines biomarkers and artificial intelligence, opens up new avenues for overcoming diagnostic challenges in patients with pelvic pain and for avoiding laparoscopic surgery when sonography and MRI are not conclusive. Dienogest (DNG) 2 mg has been a reimbursable healthcare expense in France since 2020, and, according to recent studies, it is at least as effective as combined hormonal contraception (CHC) and can be used as an alternative to CHC for first-line treatment of endometriosis-associated pain. Since 2018, the literature concerning the use of DNG has grown considerably, and the French guidelines should be modified accordingly. The levonorgestrel intrauterine system (LNG IUS) and other available progestins per os, including DNG, or the subcutaneous implant, can be offered as first-line therapy, gonadotropin-releasing hormone (GnRH) agonists with add-back therapy (ABT) as second-line therapy. Oral GnRH antagonists are promising new medical treatments for women with endometriosis-associated pain. They competitively bind to GnRH receptors in the anterior pituitary, preventing native GnRH from binding to GnRH receptors and from stimulating the secretion of luteinizing hormone and follicle-stimulating hormone. Consequently, estradiol and progesterone production is reduced. Oral GnRH antagonists will soon be on the market in France. Given their mode of action, their efficacy is comparable to that of GnRH agonists, with the advantage of oral administration and rapid action with no flare-up effect. Combination therapy with ABT is likely to allow long-term treatment with minimal impact on bone mass. GnRH antagonists with ABT may thus be offered as second-line treatment as an alternative to GnRH agonists with ABT. This article presents an update on the management of endometriosis-associated pain in women who do not have an immediate desire for pregnancy.

Hepatotoxicity of AKR1C3 Inhibitor BAY1128688: Findings from an Early Terminated Phase IIa Trial for the Treatment of Endometriosis.

Fri, 01 Sep 2023 00:00:00 +0000

INTRODUCTION: BAY1128688 is a selective inhibitor of aldo-keto reductase family 1 member C3 (AKR1C3), an enzyme implicated in the pathology of endometriosis and other disorders. In vivo animal studies suggested a potential therapeutic application of BAY1128688 in treating endometriosis. Early clinical studies in healthy volunteers supported the start of phase IIa. OBJECTIVE: This manuscript reports the results of a clinical trial (AKRENDO1) assessing the effects of BAY1128688 in adult premenopausal women with endometriosis-related pain symptoms over a 12-week treatment period. METHODS: Participants in this placebo-controlled, multicenter phase IIa clinical trial (NCT03373422) were randomized into one of five BAY1128688 treatment groups: 3 mg once daily (OD), 10 mg OD, 30 mg OD, 30 mg twice daily (BID), 60 mg BID; or a placebo group. The efficacy, safety, and tolerability of BAY1128688 were investigated. RESULTS: Dose-/exposure-dependent hepatotoxicity was observed following BAY1128688 treatment, characterized by elevations in serum alanine transferase (ALT) occurring at around 12 weeks of treatment and prompting premature trial termination. The reduced number of valid trial completers precludes conclusions regarding treatment efficacy. The pharmacokinetics and pharmacodynamics of BAY1128688 among participants with endometriosis were comparable with those previously found in healthy volunteers and were not predictive of the subsequent ALT elevations observed. CONCLUSIONS: The hepatotoxicity of BAY1128688 observed in AKRENDO1 was not predicted by animal studies nor by studies in healthy volunteers. However, in vitro interactions of BAY1128688 with bile salt transporters indicated a potential risk factor for hepatotoxicity at higher doses. This highlights the importance of in vitro mechanistic and transporter interaction studies in the assessment of hepatoxicity risk and suggests further mechanistic understanding is required. CLINICAL TRIAL REGISTRATION: NCT03373422 (date registered: November 23, 2017).

Oocyte donation outcomes in endometriosis patients with multiple IVF failures.

Tue, 01 Aug 2023 00:00:00 +0000

RESEARCH QUESTION: What are the reproductive outcomes and the prognostic factors of live birth rates in patients with endometriosis referred to oocyte donation after multiple IVF failures? DESIGN: Observational cohort study including all women with endometriosis-related infertility and two or more failed IVF/intracytoplasmic sperm injection (ICSI) cycles referred to oocyte donation between January 2013 and June 2022. Endometriosis was diagnosed based on published imaging criteria, and was confirmed histologically in women who had a history of surgery for endometriosis. The main outcome measured was the cumulative live birth rate (CLBR). The characteristics of women who had a live birth were compared with those who did not using univariate and multivariate analysis to identify determinant factors of fertility outcome. RESULTS: Fifty-seven patients underwent 90 oocyte donation cycles after 244 failed autologous IVF cycles. The mean ± SD age of the population was 36.8 ± 3.3 years, with a mean duration of infertility of 3.6 ± 2.2 years, and a mean number of autologous IVF/ICSI cycles of 4.4 ± 2.3 cycles per patient. Three patients (5.3%) had superficial peritoneal endometriosis, two patients (3.5%) had ovarian endometriomas, and 52 patients (91.2%) had deep infiltrating endometriosis, among which 30 patients (57.7%) had bowel lesions. Thirty patients (52.6%) had associated adenomyosis. Overall, CLBR per patient was 36/57 (63.2%). After multivariate analysis, only being nulligravida (P=0.002) remained an independent negative predictive factor of the live birth rate. Previous surgery did not impact reproductive outcomes. CONCLUSION: This study suggests that oocyte donation appears to be a viable option to optimize the live birth rate in women with endometriosis-related infertility and recurrent IVF failures.

Severe pelvic pain is associated with sexual abuse experienced during childhood and/or adolescence irrespective of the presence of endometriosis.

Tue, 01 Aug 2023 00:00:00 +0000

STUDY QUESTION: Is endometriosis associated with childhood and/or adolescent sexual abuse? SUMMARY ANSWER: Endometriosis is not associated with a history of sexual abuse, unlike the presence of severe pelvic pain. WHAT IS KNOWN ALREADY: Several studies have highlighted a link between pelvic pain and sexual abuse during childhood/adolescence. Moreover, an inflammatory state has been described in patients with a history of childhood maltreatment. Given that inflammation and pelvic pain are two entities often encountered with endometriosis, several teams have investigated whether endometriosis is associated with abuse during childhood/adolescence. However, the results are conflicting, and the link between sexual abuse and the presence of endometriosis and/or pain is hard to disentangle. STUDY DESIGN, SIZE, DURATION: A survey nested in a cohort study of women surgically explored for benign gynecological indications at our institution between January 2013 and January 2017. For each patient, a standardized questionnaire was completed during a face-to-face interview with the surgeon in the month preceding the surgery. Pelvic pain symptoms (dysmenorrhea, deep dyspareunia, non-cyclic chronic pelvic pain, and gastrointestinal or lower urinary tract symptoms) and their intensities were assessed with a 10 cm visual analog scale (VAS). Pain was considered to be severe when the VAS score was ≥7. PARTICIPANTS/MATERIALS, SETTING, METHODS: A 52-question survey was sent in September of 2017 to evaluate abuses, especially sexual abuse during childhood and/or adolescence, and the psychological state during childhood and adolescence. The survey was structured to cover the following sections: (i) abuses and other life events during childhood and adolescence; (ii) puberty and body changes; (iii) onset of sexuality; and (iv) family relationships during childhood and adolescence. The patients were divided into groups according to whether or not they exhibited histologically proven endometriosis. Statistical analyses were conducted using univariate and multivariate logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Two hundred and seventy-one patients answered all the questions of the survey: 168 with (endometriosis group) and 103 without endometriosis (control group). The mean ± SD overall population age was 32.2 ± 5.1 years. There were 136 (80.9%) and 48 (46.6%) women who experienced at least one severe pelvic pain symptom in the endometriosis and the control groups, respectively (P < 0.001). No differences were found between the two study groups regarding the following characteristics: (i) a history of sexual, physical, or emotional abuse; (ii) a history of abandonment or bereavement; (iii) the psychological state regarding puberty; and (iv) the family relationships. After multivariable analysis, we found no significant association between endometriosis and a history of sexual abuse during childhood and/or adolescence (P = 0.550). However, the presence of at least one severe pelvic pain symptom was independently associated with a history of sexual abuse (odds ratio = 3.6, 95% CI (1.2-10.4)). LIMITATIONS, REASONS FOR CAUTION: Evaluation of the psychological state during childhood and/or adolescence can be subject to recall bias. In addition, selection bias is also a possibility given that some of the patients surveyed did not return the questionnaire. WIDER IMPLICATIONS OF THE FINDINGS: Severe gynecological painful symptoms in women with or without histologically proven endometriosis may be linked to sexual abuse experienced during childhood and/or adolescence. Patient questioning about painful symptoms and abuses is important to provide comprehensive care to the patients, from a psychological to a somatic point of view. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests. TRIAL REGISTRATION NUMBER: N/A.

IVF/ICSI Outcomes After a Freeze-All Strategy: an Observational Cohort Study.

Sat, 01 Jul 2023 00:00:00 +0000

In order to inform patients undergoing ART regarding their chances for motherhood, it seems useful to describe -‘freeze all-’ outcomes according to the different potential indications. The goal of this study was to examine the impact of a -‘freeze-all approach-’ on the cumulative live birth rate (cLBR) according to the indication. It is a cohort study including women who had undergone ovarian stimulation (OS) using an antagonist protocol with GnRH agonist triggering between 09.2016 and 09.2018 followed by a freeze-all cycle of blastocyst embryos. The ART outcomes were compared between the two main indications of the freeze-all strategy which were in our cohort: risk of ovarian hyperstimulation syndrome (OHSS) and endometriosis. The ART outcomes were also described for the others indications (inadequate endometrium and/or premature progesterone elevation at trigger day, two or more previous ART failures, and autoimmune disease and/or a high risk of thromboembolic disease (AI and/or TE risk)). In total, 658 women were included. The cLBR in the total population was 37.7% (248/658). The cLBR was significantly higher in the -‘OHSS risk-’ group (133/281, 47.3%) than in the -’endometriosis-’ group (69/190, 36.3%) (p = 0.017). No significant differences were noted regarding perinatal outcomes, except a significantly higher risk of placenta praevia (PP) observed in the -’endometriosis-’ group (10.1%) (p = 0.002). The -‘freeze-all approach-’ yielded good results in terms of the cLBR and especially in case of OHSS risk. These data should be taken into account when informing patients about the ART strategy and their chances of motherhood.

Magnetic resonance imaging presentation of diffuse and focal adenomyosis before and after pregnancy.

Sat, 01 Jul 2023 00:00:00 +0000

RESEARCH QUESTION: Is there a change in magnetic resonance imaging (MRI) criteria of diffuse and focal phenotypes of adenomyosis before and after pregnancy? DESIGN: A retrospective, monocentric, observational study in a single academic tertiary referral centre for endometriosis diagnosis and management. Women were followed for symptomatic adenomyosis, and without a prior history of surgery who give birth after 24+0 weeks. For each patient, pelvic MRI pre- and post-pregnancy was performed by two experienced radiologists with the same image acquisition protocol. Diffuse and focal adenomyosis MRI presentation were analysed before and after pregnancy. RESULTS: Between January 2010 and September 2020, of the 139 patients analysed, 96 (69.1%) had adenomyosis at MRI distributed as follow: 22 (15.8%) presented diffuse adenomyosis, 55 (39.6%) focal adenomyosis and 19 (13.7%) both phenotypes. The frequency of isolated diffuse adenomyosis on MRI was significantly lower before versus after pregnancy (n = 22 [15.8%] versus n = 41 [29.5%], P = 0.01). The frequency of isolated focal adenomyosis was significantly higher before pregnancy than after pregnancy (n = 55 [39.6%] versus n = 34 [24.5%], P = 0.01). The mean volume of all focal adenomyosis lesions on MRI decreased significantly after pregnancy, from 6.7 ± 2.5 mm3 to 6.4 ± 2.3 mm3, P = 0.01. CONCLUSION: The current data indicate that, based on MRI, there is an increase in diffuse adenomyosis and a decrease in focal adenomyosis after pregnancy.

Decrease of dysmenorrhoea with hormonal treatment is a marker of endometriosis severity.

Mon, 01 May 2023 00:00:00 +0000

RESEARCH QUESTION: Is a decrease in dysmenorrhoea after suppressive hormonal therapy a marker of the endometriosis phenotype and of greater disease severity? DESIGN: Retrospective observational cohort study conducted in a French university hospital, between January 2004 and December 2019. Non-pregnant women aged younger than 42 years, who tested for dysmenorrhoea relief after suppressive hormonal therapy before surgery, and who had histological confirmation of endometriosis, were included. The comparisons were carried out according to the results of the suppressive hormonal test. RESULTS: Of the 578 histologically proven endometriosis patients with preoperative pain symptoms, the rate of dysmenorrhoea decrease after suppressive hormonal therapy was 88.2% (n = 510). These patients had a higher incidence of deep infiltrating endometriosis (DIE) intestinal lesions (45.7% [233/510] versus 30.8% [21/68], P = 0.01) and an increased rate of multiple DIE lesions (two or more) (72.8% [287/394] versus 56.4% [22/39], P = 0.02). After multivariate analysis, decrease of dysmenorrhoea after suppressive hormonal therapy remained significantly associated with the severe DIE phenotype (adjusted OR 3.9, 95% CI 2.0 to 7.6, P < 0.001). CONCLUSION: In women with endometriosis, a decrease of dysmenorrhoea after suppressive hormonal therapy is associated with the DIE phenotype and is a marker of greater severity.

Adolescent endometriosis: prevalence increases with age on magnetic resonance imaging scan.

Sat, 01 Apr 2023 00:00:00 +0000

OBJECTIVE: To evaluate the prevalence on magnetic resonance imaging (MRI) of ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) in adolescents presenting with severe dysmenorrhea. DESIGN: Prospective study. SETTING: Clinic. PATIENT(S): A total of 345 adolescents aged 12-20 years referred to the radiologic MRI department unit between September 2019 and June 2020. INTERVENTION(S): Multiplanar pelvic MRI with cine MRI was performed. Data on the medical history with systematic questioning were collected for each patient before the scan. MAIN OUTCOME MEASURE(S): Data on the endometriosis phenotypes (OMA and/or DIE), distribution of anatomical lesions, and adenomyosis were evaluated and recorded using a dedicated MRI spreadsheet. Myometrial contractions were systematically reported for each case. The data were correlated with the characteristics of the patients and severity of painful symptoms evaluated using a visual analog scale. RESULT(S): The prevalence rates of endometriosis and adenomyosis were 39.3% (121 patients) and 11.4% (35 patients), respectively. Among the adolescents with endometriosis, 25 (20.7%) presented with OMA, and 107 (88.4%) presented with DIE. The odds ratios (confidence intervals) for each pairwise comparison between the age distributions were 2.3 (1.4-3.8) for 15-18 vs. <15 years of age and 3.3 (1.2-8.5) for 18-20 vs. <15 years of age, highlighting a predominance of cases after 18 years of age. Uterine contractions were visualized in 34.4% of cases, with no particular association with endometriosis. No clinical risk factor was identified as being particularly associated with endometriosis. Notably, the visual analog scale score was the same for cases with and without endometriosis. CONCLUSION(S): Severe endometriosis phenotypes (OMA and/or DIE) can be observed in adolescents with intense dysmenorrhea, with a linear increase in prevalence over time resulting in a clear predominance after 18 years of age. Endometriosis in adolescents is a challenging clinical problem with a long delay in diagnosis. Imaging can help reduce this delay in young patients with suggestive symptoms. CLINICAL TRIAL REGISTRATION NUMBER: NCT05153512.

Comparison between CT-enterography and MR-enterography for the diagnosis of right-sided deep infiltrating endometriosis of the bowel.

Sat, 01 Apr 2023 00:00:00 +0000

OBJECTIVE: To compare computed tomography-enterography (CTE) and magnetic resonance-enterography (MRE) in the detection of right-sided bowel deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: Fifty women with DIE who underwent preoperatively CTE and MRE were included. CTE and MRE were first analyzed separately by two independent readers who analyzed five bowel segments (cecum, appendix, ileocecal junction, distal ileum and proximal small bowel [i.e., proximal ileum and jejunum]) for the presence of DIE and then interpreted in consensus. CTE, MRE and CTE with MRE were compared in terms of sensitivity, specificity and accuracy. Interobserver agreement was assessed with kappa (κ) test. RESULTS: Using the reference standard 25 out 250 bowel segments were involved by DIE in 18 women and 225 were free of DIE. Sensitivity, specificity, and accuracy of CTE were 60% (95% confidence interval [CI]: 39-79), 93% (95% CI: 89-96) and 90% (95% CI: 85-93) for Reader 1, respectively, and 52% (95% CI: 31-72), 99% (95% CI: 97-100) and 94% (95% CI: 91-97) for Reader 2, with no differences in sensitivity (P = 0.564) and specificity (P = 0.181) between readers and fair interobserver agreement (κ = 0.37). For MRE these figures were 52% (95% CI: 31-72), 92% (95% CI: 88-95) and 88% (95% CI: 84-92) for Reader 1 and 60% (95% CI: 39-79), 99% (95% CI: 96-100) and 95% (95% CI: 91-97) for Reader 2, with no differences in sensitivity (P = 0.157) and specificity (P = 0.061) between readers and fair interobserver agreement (κ = 0.31). Significant differences in sensitivity (20%; 95% CI: 7-41) were found between CTE + MRE vs. CTE alone for Reader 1 and vs. MRE alone for Reader 2 (P = 0.041 for both) CONCLUSION: CTE and MRE have not different sensitivities and convey only fair interobserver agreement but are highly specific for the diagnosis of right-sided bowel DIE. CTE and MRE are complementary because they improve the detection of DIE implants when used in combination.

Embryo transfer learning using medical simulation tools: a comparison of two embryo transfer simulators.

Wed, 01 Mar 2023 00:00:00 +0000

INTRODUCTION: Embryo transfer(ET) is one of the main procedures to become pregnant by assisted reproductive technology(ART). Simulation training is a way to improve the skills of clinicians. The objective of this study was to evaluate the interest of trainees in learning embryo transfer using simulators. MATERIAL AND METHODS: An observational study was conducted at the University hospital-based research center. Trainees, comprising midwives and resident or graduated gynecologists, who attended the medical training for infertility and ART in June 2019, were included. They trained on two ET simulators (Simulator A and B) and complete an anonymously online questionnaire. A sub-group analysis focusing on graduated gynecologists not performing ET in current practice, was performed. RESULTS: Thirty-two trainees were included. Trainees felt that ET simulators should be used in medical education to promote learning how to perform the ET procedure (n=26, 81.3% for Simulator A and n=21, 65.5% for Simulator B; p=0.31). The use of both simulators improved the level of self-confidence (81.3% and 75.0% respectively; p=0.55). Significant differences in the global and in the subgroup analysis (n=24) in favor of Simulator A were observed regarding learning the precision of the ET procedure (p<0.01), the pathway to introduce the catheter into the uterine cavity (p<0.05), and the guidance for proper placement of the catheter into the uterine cavity (p=0.03). In the subgroup analysis of graduated gynecologists not performing ET in current practice, Simulator A was found more realistic for the visualization of the introduction of the catheter into the uterine cavity (p=0.01) and more useful to learn about difficult cases (p=0.03). CONCLUSION: Students expressed a high level of interest in ET simulators to improve their skills. Although the simulators displayed some differences regarding learning the precision of the ET procedure, both improved the level of self-confidence. This new learning method needs to be further developed in order to offer to trainees the most realistic simulators. TRIAL REGISTRATION: This study was approved for publication by the Ethics Review Committee of the Cochin University Hospital (CLEP) (n° AAA-2020-08016) retrospectively registered.

A real-world study of ART in France (REOLA) comparing a biosimilar rFSH against the originator according to rFSH starting dose.

Sun, 01 Jan 2023 00:00:00 +0000

BACKGROUND: Since the first launch of a biosimilar recombinant follicle stimulating hormone (rFSH), Bemfola®, in Europe in 2014, it has been possible to study in routine clinical care throughout France the effectiveness of a biosimilar rFSH including according to different rFSH starting doses. METHODS: REOLA was a non-interventional, retrospective, real world study using anonymized data from 17 Assisted Reproductive Technology (ART) centres’ data management systems across France including 2,319 ART ovarian stimulation cycles with Bemfola® and 4,287 ART ovarian stimulation cycles with Gonal-f®. For both products, four populations were studied according to starting dose of rFSH: < 150 IU, 150 - 224 IU, 225 - 299 IU and ≥ 300 IU. The primary endpoint was the cumulative live birth rate (cLBR) per commenced ART ovarian stimulation cycle including all subsequent fresh and frozen-thawed embryo transfers starting during a follow up period of at least 1 year following oocyte retrieval. RESULTS: A direct relationship of increasing rFSH starting dose with increasing age, increasing basal FSH, decreasing AMH and increasing body mass index was noted. No clinically relevant differences were seen in all outcomes reported, including the cLBR, between Bemfola® and Gonal-f®, but for both drugs, an association was seen with increasing rFSH starting dose and decreasing cLBR. CONCLUSIONS: The REOLA study demonstrates that the cLBR with Bemfola® is very similar to Gonal-f® across all patient subpopulations. The cLBR is inversely related to the rFSH starting dose irrespective of the drug used, and the REOLA study provides reassurance of the clinical effectiveness of a biosimilar rFSH used in a real world setting.

Clinical Diagnosis and Early Medical Management for Endometriosis: Consensus from Asian Expert Group.

Mon, 12 Dec 2022 00:00:00 +0000

This work provides consensus guidance regarding clinical diagnosis and early medical management of endometriosis within Asia. Clinicians with expertise in endometriosis critically evaluated available evidence on clinical diagnosis and early medical management and their applicability to current clinical practices. Clinical diagnosis should focus on symptom recognition, which can be presumed to be endometriosis without laparoscopic confirmation. Transvaginal sonography can be appropriate for diagnosing pelvic endometriosis in select patients. For early empiric treatment, management of women with clinical presentation suggestive of endometriosis should be individualized and consider presentation and therapeutic need. Medical treatment is recommended to reduce endometriosis-associated pelvic pain for patients with no immediate pregnancy desires. Hormonal treatment can be considered for pelvic pain with a clinical endometriosis diagnosis; progestins are a first-line management option for early medical treatment, with oral progestin-based therapies generally a better option compared with combined oral contraceptives because of their safety profile. Dienogest can be used long-term if needed and a larger evidence base supports dienogest use compared with gonadotropin-releasing hormone agonists (GnRHa) as first-line medical therapy. GnRHa may be considered for first-line therapy in some specific situations or as short-term therapy before dienogest and non-steroidal anti-inflammatory drugs as add-on therapy for endometriosis-associated pelvic pain.

Influence of endometrioma size on ART outcomes.

Thu, 01 Dec 2022 00:00:00 +0000

RESEARCH QUESTION: Does endometrioma size affect the number of oocytes retrieved after ovarian stimulation in women with endometriosis-related infertility undergoing IVF/intracytoplasmic sperm injection (ICSI)? DESIGN: Cohort study of infertile women with unilateral or bilateral endometrioma(s) associated with deep infiltrating endometriosis, undergoing their first IVF/ICSI cycle between January 2014 and November 2021. A total of 326 women with an adequate imaging work-up with transvaginal ultrasound and/or magnetic resonance imaging performed by senior radiologists before the start of ovarian stimulation was included. Prognostic factors associated with the number of oocytes retrieved were analysed. IVF/ICSI outcomes were compared between five groups defined according to the largest endometrioma diameter (<2, 2 to <4, 4 to <6, 6 to <8 and ≥8 cm). RESULTS: Factors that significantly reduced the number of oocytes retrieved after adjustment by multiple linear regression were women’s age (regression coefficient -0.18; 95% confidence interval [95% CI] -0.31 to-0.06; P = 0.005), smoking habit (-2.02; 95% CI -3.42 to -0.62; P = 0.005), day 3 FSH concentration (-0.20; 95% CI -0.39 to -0.02; P = 0.031) and a previous history of surgery for ovarian endometriosis (-1.32; 95% CI -2.63 to -0.02; P = 0.047). Antral follicle count and oestradiol concentration on the trigger day were positively correlated with the number of oocytes retrieved (0.14; 95% CI 0.08 to 0.19; P < 0.001 and 0.003; 95% CI 0.002 to 0.004; P < 0.001, respectively). The mean number of oocytes retrieved was not significantly different between the five groups (P = 0.413), nor were the cumulative live birth rate, the number of cancelled cycles and perinatal outcomes. CONCLUSIONS: No significant difference in the number of oocytes retrieved was observed according to endometrioma size. This study suggests that ovarian stimulation can be of benefit to women irrespective of the endometrioma size.

Clinical factors associated with low serum progesterone levels on the day of frozen blastocyst transfer in hormonal replacement therapy cycles.

Mon, 31 Oct 2022 00:00:00 +0000

STUDY QUESTION: Which factors are associated with low serum progesterone (P) levels on the day of frozen embryo transfer (FET), in HRT cycles? SUMMARY ANSWER: BMI, parity and non-European geographic origin are factors associated with low serum P levels on the day of FET in HRT cycles. WHAT IS KNOWN ALREADY: The detrimental impact of low serum P concentrations on HRT-FET outcomes is commonly recognized. However, the factors accounting for P level disparities among patients receiving the same luteal phase support treatment remain to be elucidated, to help clinicians predicting which subgroups of patients would benefit from a tailored P supplementation. STUDY DESIGN, SIZE, DURATION: Observational cohort study with 915 patients undergoing HRT-FET at a tertiary care university hospital, between January 2019 and March 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing single autologous blastocyst FET under HRT using exogenous estradiol and vaginal micronized progesterone for endometrial preparation. Women were only included once during the study period. The serum progesterone level was measured in the morning of the FET, in a single laboratory. Independent factors associated with low serum P levels (defined as ≤9.8 ng/ml, according to a previous published study) were analyzed using univariate and multivariate logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Two hundred and twenty-six patients (24.7%) had a low serum P level, on the day of the FET. Patients with a serum P level ≤9.8 ng/ml had a lower live birth rate (26.1% vs 33.2%, P = 0.045) and a higher rate of early miscarriage (35.2% vs 21.5%, P = 0.008). Univariate analysis showed that BMI (P < 0.001), parity (P = 0.001), non-European geographic origin (P = 0.001), the duration of infertility (P = 0.018) and the use of oral estradiol for endometrial preparation (P = 0.009) were significantly associated with low serum P levels. Moreover, the proportion of active smokers was significantly lower in the ’low P concentrations’ group (P = 0.002). After multivariate analysis, BMI (odds ratio (OR) 1.06 95% CI (1.02-1.11), P = 0.002), parity (OR 1.32 95% CI (1.04-1.66), P = 0.022), non-European geographic origin (OR 1.70 95% CI (1.21-2.39), P = 0.002) and active smoking (OR 0.43 95% CI (0.22-0.87), P = 0.018) remained independent factors associated with serum P levels ≤9.8 ng/ml. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is its observational design, leading to a risk of selection and confusion bias that cannot be ruled out, although a multivariable analysis was performed to minimize this. WIDER IMPLICATIONS OF THE FINDINGS: Extrapolation of our results to other laboratories, or other routes and/or doses of administering progesterone also needs to be validated. There is urgent need for future research on clinical factors affecting P concentrations and the underlying pathophysiological mechanisms, to help clinicians in predicting which subgroups of patients would benefit from individualized luteal phase support. STUDY FUNDING/COMPETING INTEREST(S): No funding/no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Discovery and validation of a transcriptional signature identifying homologous recombination-deficient breast, endometrial and ovarian cancers.

Sat, 01 Oct 2022 00:00:00 +0000

BACKGROUND: Molecular alterations leading to homologous recombination deficiency (HRD) are heterogeneous. We aimed to identify a transcriptional profile shared by endometrial (UCEC), breast (BRCA) and ovarian (OV) cancers with HRD. METHODS: Genes differentially expressed with HRD genomic score (continuous gHRD score) in UCEC/BRCA/OV were identified using edgeR, and used to train a RNAseq score (ridge-regression model) predictive of the gHRD score (PanCanAtlas, N = 1684 samples). The RNAseq score was applied in independent gynaecological datasets (CARPEM/CPTAC/SCAN/TCGA, N = 4038 samples). Validations used ROC curves, linear regressions and Pearson correlations. Overall survival (OS) analyses used Kaplan-Meier curves and Cox models. RESULTS: In total, 656 genes were commonly up/downregulated with gHRD score in UCEC/BRCA/OV. Upregulated genes were enriched for nuclear/chromatin/DNA-repair processes, while downregulated genes for cytoskeleton (gene ontologies). The RNAseq score correlated with gHRD score in independent gynaecological cancers (R² = 0.4-0.7, Pearson correlation = 0.64-0.86, all P < 10-11), and was predictive of gHRD score >42 (RNAseq HRD profile; AUC = 0.95/0.92/0.78 in UCEC/BRCA/OV). RNAseq HRD profile was associated (i) with better OS in platinum-treated advanced TP53-mutated-UCEC (P < 0.001) and OV (P = 0.013), and (ii) with poorer OS (P < 0.001) and higher benefit of adjuvant chemotherapy in Stage I-III BRCA (interaction test, P < 0.001). CONCLUSIONS: UCEC/BRCA/OV with HRD-associated genomic scars share a common transcriptional profile. RNAseq signatures might be relevant for identifying HRD-gynaecological cancers, for prognostication and for therapeutic decision.

Uterine disorders and iron deficiency anemia.

Sat, 01 Oct 2022 00:00:00 +0000

Abnormal uterine bleeding (AUB) is a clinical entity which can lead to iron deficiency anemia. Classification according to the acronym PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy, and hyperplasia; coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not otherwise classified) provides a structured approach to establish the cause of AUB. The goal of this review is to discuss the different mechanisms and the relationship between uterine disorders and AUB. Heavy menstrual bleeding, a subgroup of AUB, is more closely related to the presence of uterine fibroids. The relationship between heavy menstrual bleeding and uterine fibroids remains poorly characterized, particularly the understanding of endometrial function in women with structural myometrial features such as leiomyomas. A number of theories have been proposed in the literature and are discussed in this review. Uterine adenomyosis is also a frequent cause of AUB, and its pathogenesis is still far from being fully elucidated. The mechanisms contributing to its development are multifactorial. Many theories lean toward invasion of the myometrium by endometrial cells. Both clinical and basic studies favor the theory of direct invasion, although de novo development of adenomyosis from Müllerian rests or stem cells has not been ruled out. Development of adenomyotic lesions involves repeated tissue injury and repair. In addition, this review describes the other causes of AUB such as endometrial polyps, cesarean scar defects, and uterine vascular abnormalities. Endometrial polyps are often asymptomatic, but approximately 68% of women have concomitant AUB. Histologic alterations in the lower uterine segment in patients who had undergone cesarean sections were identified and may explain the cause of AUB.

Development of a core outcome set and outcome definitions for studies on uterus-sparing treatments of adenomyosis (COSAR): an international multistakeholder-modified Delphi consensus study.

Thu, 25 Aug 2022 00:00:00 +0000

STUDY QUESTION: What outcomes should be reported in all studies investigating uterus-sparing interventions for treating uterine adenomyosis? SUMMARY ANSWER: We identified 24 specific and 26 generic core outcomes in nine domains. WHAT IS KNOWN ALREADY: Research reporting adenomyosis treatment is not patient-centred and shows wide variation in outcome selection, definition, reporting and measurement of quality. STUDY DESIGN, SIZE, DURATION: An international consensus development process was performed between March and December 2021. Participants in round one were 150 healthcare professionals, 17 researchers and 334 individuals or partners with lived experience of adenomyosis from 48 high-, middle- and low-income countries. There were 291 participants in the second round. PARTICIPANTS/MATERIALS, SETTING, METHODS: Stakeholders included active researchers in the field, healthcare professionals involved in diagnosis and treatment, and people and their partners with lived experience of adenomyosis. The core component of the process was a 2-step modified Delphi electronic survey. The Steering Committee analysed the results and created the final core outcome set (COS) in a semi-structured meeting. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 241 outcomes was identified and distilled into a ’long list’ of 71 potential outcomes. The final COS comprises 24 specific and 26 generic core outcomes across nine domains, including pain, uterine bleeding, reproductive outcomes, haematology, urinary system, life impact, delivery of care, adverse events and reporting items, all with definitions provided by the Steering Committee. Nineteen of these outcomes will apply only to certain study types. Although not included in the COS, the Steering Committee recommended that three health economic outcomes should be recorded. LIMITATIONS, REASONS FOR CAUTION: Patients from continents other than Europe were under-represented in this survey. A lack of translation of the survey might have limited the active participation of people in non-English speaking countries. Only 58% of participants returned to round two, but analysis did not indicate attrition bias. There is a significant lack of scientific evidence regarding which symptoms are caused by adenomyosis and when they are related to other co-existent disorders such as endometriosis. As future research provides more clarity, the appropriate review and revision of the COS will be necessary. WIDER IMPLICATIONS OF THE FINDINGS: Implementing this COS in future studies on the treatment of adenomyosis will improve the quality of reporting and aid evidence synthesis. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was received for this work. T.T. received a grant (grant number 2020083) from the South Eastern Norwegian Health Authority during the course of this work. T.T. receives personal fees from General Electrics and Medtronic for lectures on ultrasound. E.R.L. is the chairman of the Norwegian Endometriosis Association. M.G.M. is a consultant for Abbvie Inc and Myovant, receives research funding from AbbVie and is Chair of the Women’s Health Research Collaborative. S.-W.G. is a board member of the Asian Society of Endometriosis and Adenomyosis, on the scientific advisory board of the endometriosis foundation of America, previous congress chair for the World Endometriosis Society, for none of which he received personal fees. E.S. received outside of this work grants for two multicentre trials on endometriosis from the National Institute for Health Research UK, the Rosetrees Trust, and the Barts and the London Charity, he is a member of the Medicines and Healthcare Products Regulatory Agency (MHRA), Medicines for Women’s Health Expert Advisory Group, he is an ambassador for the World Endometriosis Society, and he received personal fees for lectures from Hologic, Olympus, Medtronic, Johnson & Johnson, Intuitive and Karl Storz. M.H. is member of the British Society for Gynaecological Endoscopy subcommittee. No other conflict of interest was declared. TRIAL REGISTRATION NUMBER: N/A.

Unbiased In Silico Analysis of Gene Expression Pinpoints Circulating miRNAs Targeting KIAA1324, a New Gene Drastically Downregulated in Ovarian Endometriosis.

Wed, 24 Aug 2022 00:00:00 +0000

Objective: To identify circulating miRNAs associated with ovarian endometriosis (OMA), and to analyze candidate genes targeted by these miRNAs. Methods: Putative regulating miRNAs were identified through an original bioinformatics approach. We first queried the miRWalk 2.0 database to collect putative miRNA targets. Then, we matched it to a transcriptomic dataset of OMA. Moving from gene expression in the tissue to possible alterations in the patient plasma, a selection of these miRNAs was quantified by qRT-PCR in plasma samples from 93 patients with isolated OMA and 95 patients surgically checked as free from endometriosis. Then, we characterized the genes regulated by more than one miRNA and validated them by immunohistochemistry and transfection experiments on endometrial cell primary cultures obtained from endometrial biopsies of 10 women with and without endometriosis with miRNA mimics. Stromal and epithelial cells were isolated and cultured separately and gene expression levels were measured by RT-qPCR. Results: Eight miRNAs were identified by bioinformatics analysis. Two of them were overexpressed in plasma from OMA patients: let-7b-5p and miR-92a-3p (p < 0.005). Three miRNAs, let-7b and miR-92a-3p, and miR-93-5p potentially targeted KIAA1324, an estrogen-responsive gene and one of the most downregulated genes in OMA. Transfection experiments with mimics of these two miRNAs showed a strong decrease in KIAA1324 expression, up to 40%. Immunohistochemistry revealed a moderate-to-intense staining for KIAA1324 in the eutopic endometrium and a faint-to-moderate staining in the ectopic endometrium for half of the samples, which is concordant with the transcriptomic data. Discussion and Conclusion: Our results suggested that KIAA1324 might be involved in endometriosis through the downregulating action of two circulating miRNAs. As these miRNAs were found to be overexpressed, their quantification in plasma could provide a tool for an early diagnosis of endometriosis.

ENDOCELL-Seud: a Delphi protocol to harmonise methods in endometrial cell culturing.

Mon, 22 Aug 2022 00:00:00 +0000

IN VITRO: culturing of endometrial cells obtained from the uterine mucosa or ectopic sites is used to study molecular and cellular signalling relevant to physiologic and pathologic reproductive conditions. However, the lack of consensus on standard operating procedures for deriving, characterising and maintaining primary cells in two- or three-dimensional cultures from eutopic or ectopic endometrium may be hindering progress in this area of research. Guidance for unbiased in vitro research methodologies in the field of reproductive science remains essential to increase confidence in the reliability of in vitro models. We present herein the protocol for a Delphi process to develop a consensus on in vitro methodologies using endometrial cells (ENDOCELL-Seud Project). A steering committee composed of leading scientists will select critical methodologies, topics and items that need to be harmonised and that will be included in a survey. An enlarged panel of experts (ENDOCELL-Seud Working Group) will be invited to participate in the survey and provide their ratings to the items to be harmonised. According to Delphi, an iterative investigation method will be adopted. Recommended measures will be finalised by the steering committee. The study received full ethical approval from the Ethical Committee of the Maastricht University (ref. FHML-REC/2021/103). The study findings will be available in both peer-reviewed articles and will also be disseminated to appropriate audiences at relevant conferences. LAY SUMMARY: Patient-derived cells cultured in the lab are simple and cost-effective methods used to study biological and dysfunctional or disease processes. These tools are frequently used in the field of reproductive medicine. However, the lack of clear recommendations and standardised methodology to guide the laboratory work of researchers can produce results that are not always reproducible and sometimes are incorrect. To remedy this situation, we define here a method to ascertain if researchers who routinely culture cells in the lab agree or disagree on the optimal laboratory techniques. This method will be used to make recommendations for future researchers working in the field of reproductive biology to reproducibly culture endometrial cells in the laboratory.

Potential competing risk of death in older high-risk endometrial carcinoma patients: Results from a multicentric retrospective cohort.

Mon, 01 Aug 2022 00:00:00 +0000

INTRODUCTION: Adjuvant therapeutic decisions in older endometrial carcinoma (EC) patients are challenged by a balance between more frequent aggressive EC and comorbidities. We assessed whether EC and comorbidities are competing or cumulative risks in older EC patients. METHODS: All consecutive patients treated for FIGO stage I-IV EC in two University Hospitals in Paris between 2010 and 2017 were retrospectively included. Patients were categorized as: <70 years (y), >70y without comorbidity (fit), and > 70y with a Charlson comorbidity index>3 (comorbid). Association between high-risk EC (2021-ESGO-ETRO-ESP) or comorbidity, and disease-specific-survival (DSS), was evaluated using Cox model (estimation of cause-specific hazard ratio (CSHR), and Fine-Gray model (subdistribution HR) to account for competing events (death unrelated with EC). RESULTS: Overall, 253 patients were included (median age = 67y, IQR[59-77], median follow-up = 61.5 months, [44.4-76.8]). Among them, 109 (43%) were categorized at high-risk (proportion independent of age), including 67 (26%) who had TP53-mutated tumors. Comorbidity and high-risk group were both associated with all-cause mortality (HR = 4.09, 95%CI[2.29; 7.32] and HR = 3.21, 95%CI [1.69; 6.09], respectively). By multivariate analysis, patients with high-risk EC exhibited poorer DSS, regardless of age/comorbidity (Adjusted-CSHR = 6.62, 95%CI[2.53;17.3]; adjusted-SHR = 6.62 95%CI[2.50;17.5]). Patients>70y-comorbid with high-risk EC had 5-years cumulative incidences of EC-related and EC-unrelated death of 29% and 19%, respectively. In patients <70y, 5-years cumulative incidence of EC-related and EC-unrelated death were 25% and < 1% (one event), respectively. CONCLUSION: High-risk EC patients are exposed to poorer DSS regardless of age/comorbidities, comorbidities and cancer being two cumulative rather than competing risks. Our results suggest that age/comorbidity alone should not lead to underestimate EC-specific survival.

Presence of adenomyosis at MRI reduces live birth rates in ART cycles for endometriosis.

Thu, 30 Jun 2022 00:00:00 +0000

STUDY QUESTION: What is the impact of adenomyosis on the live birth rate (LBR) in women affected by endometriosis women undergoing ART? SUMMARY ANSWER: For women undergoing ART, the presence of adenomyosis at MRI, especially T2 high-signal intensity spots within the myometrium, has a negative impact on the LBR. WHAT IS KNOWN ALREADY: Adenomyosis is a common gynecological disease. The development of imaging techniques for the diagnosis has led to several adenomyosis phenotypes being described, and fertility issues appear to vary according to the characteristics of the lesions. What makes assessment of the impact of adenomyosis on fertility issues even more difficult is its frequent association with endometriosis, which is another known risk factor of infertility. Although data suggest that adenomyosis may worsen the ART prognosis, there is no clear consensus regarding the impact of adenomyosis on ART outcomes in women affected by endometriosis. STUDY DESIGN, SIZE, DURATION: This was an observational study that included phenotyped patients with endometriosis, aged between 18 and 42 years, who underwent IVF/ICSI treatment in a tertiary care center between June 2015 and July 2018. Only women who had undergone a pelvic MRI during the pre-therapeutic ART workup were retained for this study. The MRI data were interpreted by radiologists who had expertise in gynecological MRI. PARTICIPANTS/MATERIALS, SETTING, METHODS: A continuous series of 202 women affected by endometriosis was included. The women were monitored until four ART cycles had been completed, until delivery, or until discontinuation of treatment before the completion of four cycles. The primary outcome was the delivery of at least one live infant after up to four IVF/ICSI cycles. The patient and the MRI characteristics were compared between the women who achieved a live birth versus those who did not. MAIN RESULTS AND THE ROLE OF CHANCE: The patients’ mean age was 32.5 ± 3.7 years. Deep infiltrating endometriosis was present in 90.1% (182/202) of the included population. Adenomyosis (lesions of the internal and/or the external myometrium) was found in 71.8% (145/202) of the included women. The cumulative LBR was 57.4% (116/202). The women who gave birth were significantly younger (32.0 ± 3.3 versus 33.3 ± 4.1, P = 0.026) and had significantly better ovarian reserve parameters (anti-Müllerian hormone levels, antral follicle count) than those who did not. The presence of adenomyosis, irrespective of the phenotype (76/116 (65.5%) versus 69/86 (80.2%), respectively, P = 0.022) and the presence of T2 high-signal intensity myometrial spots (27/116 (23.3%) and 37/86 (43.0%), respectively, P = 0.003) was significantly less frequent in the group of women who gave birth versus those who did not. After multivariate analysis, the presence of adenomyosis (odds ratio (OR): 0.48, 95% CI (0.29-0.99), P = 0.048) and the presence of T2 high-signal intensity myometrial spots (OR: 0.43, 95% CI (0.22-0.86), P = 0.018) were independently found to be associated with a decrease in the cumulative chance of live birth. LIMITATIONS, REASONS FOR CAUTION: The inclusion of patients from a referral center specialized in the management of women affected by endometriosis could constitute a selection bias, as these women may have had particularly severe forms of adenomyosis and/or endometriosis. A sensitive issue is that there is no consensual classification of adenomyosis and several lesions of adenomyosis can co-exist. Therefore, a comparison of fertility outcomes between women with and without adenomyosis is difficult to perform in practice. WIDER IMPLICATIONS OF THE FINDINGS: In women exhibiting endometriosis, the practitioner should perform an appropriate imaging workup to search for adenomyosis, identify prognostic factors, and personalize the patient management strategy in the setting of ART. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained and there were no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Highly Specific Droplet-Digital PCR Detection of Universally Methylated Circulating Tumor DNA in Endometrial Carcinoma.

Wed, 01 Jun 2022 00:00:00 +0000

BACKGROUND: No circulating biomarker is available for endometrial carcinoma (EC). We aimed to identify DNA positions universally hypermethylated in EC, and to develop a digital droplet PCR (ddPCR) assay for detection of hypermethylated circulating tumor DNA (meth-ctDNA) in plasma from patients with EC. METHODS: DNA positions hypermethylated in EC, and without unspecific hypermethylation in tissue/cell types releasing circulating cell-free DNA in plasma, were identified in silico from TCGA/Gene Expression Omnibus (GEO) data. A methylation-specific ddPCR (meth-ddPCR) assay following bisulfite conversion of DNA extracted from plasma was optimized for detection of meth-ctDNA according to dMIQE guidelines. Performances were validated on a retrospective cohort (n = 78 tumors, n = 30 tumor-adjacent tissues), a prospective pilot cohort (n = 33 stage I-IV patients), and 55 patients/donors without cancer. RESULTS: Hypermethylation of zinc finger and SCAN domain containing 12 (ZSCAN12) and/or oxytocin (OXT) classified EC samples from multiple noncancer samples with high diagnostic specificity/sensitivity [>97%; area under the curve (AUC) = 0.99; TCGA/GEO tissues/blood samples]. These results were confirmed in the independent retrospective cohort (AUC = 0.99). Meth-ddPCR showed a high analytical specificity (limit of blank = 2) and sensitivity (absolute lower threshold of detection = 50 pgmethDNA/mLplasma). In the pilot cohort, meth-ctDNA was detected in pretreatment plasma samples from 9/11 and 5/20 patients with advanced and non-advanced EC, respectively. 2 of 9 patients had ctDNA detected after macroscopic complete surgery and experienced progression within 6 months. No healthy donors had any copy of hypermethylated DNA detected in plasma. CONCLUSIONS: Meth-ddPCR of ZSCAN12/OXT allows a highly specific and sensitive detection of ctDNA in plasma from patients with EC and appears promising for personalized approaches for these patients.

Pregnancy, fertility concerns and fertility preservation procedures in a national study of French breast cancer survivors.

Wed, 01 Jun 2022 00:00:00 +0000

RESEARCH QUESTION: What are the real-life oncofertility practices in young women diagnosed with breast cancer? DESIGN: The FEERIC (FErtility, prEgnancy, contRaceptIon after breast Cancer in France) study is a web-based cohort study launched with the French collaborative research platform Seintinelles. The current work is based on the enrolment self-administered questionnaire of 517 patients with prior breast cancer diagnosis, free from relapse and aged 18 to 43 years at inclusion (from 12 March 2018 to 27 June 2019). RESULTS: Median age at breast cancer diagnosis was 33.6 years and 424 patients (82.0%) received chemotherapy. Overall, 236 (45.6%) patients were offered specialized oncofertility counselling, 181 patients underwent at least one fertility preservation procedure (FPP); 125 (24.2%) underwent one or more FPP with material preservation (oocytes n = 108, 20.9%; embryos n = 31, 6.0%; ovarian cryopreservation n = 6, 1.2%) and 78 patients received gonadotrophin-releasing hormone agonists (15.1%). With a median follow-up of 26.9 months after the end of treatments, 133 pregnancies had occurred in 85 patients (16.4%), including 20 unplanned pregnancies (15.0%). Most of the pregnancies were natural conceptions (n = 113, 87.6%), while 16 (12.4%) required medical interventions. For the planned pregnancies, median time to the occurrence of an ongoing pregnancy was 3 months. Patients who had an unplanned pregnancy reported lower rates of information on the consequences of the treatments on fertility (P = 0.036) at diagnosis. CONCLUSIONS: Most of the patients were not offered proper specialized oncofertility counselling at the time of breast cancer diagnosis. Naturally conceived pregnancies after breast cancer were much more frequent than pregnancies resulting from the use of cryopreserved gametes. Adequate contraceptive counselling seems as important as information about fertility and might prevent unplanned pregnancies.

[How I do… an ultrasound guided drainage of a complicated pelvic inflammatory disease?].

Tue, 01 Mar 2022 00:00:00 +0000

Development and validation of a RNAseq signature for prognostic stratification in endometrial cancer.

Tue, 01 Mar 2022 00:00:00 +0000

BACKGROUND: Despite recent advances in endometrial carcinoma (EC) molecular characterization, its prognostication remains challenging. We aimed to assess whether RNAseq could stratify EC patient prognosis beyond current classification systems. METHODS: A prognostic signature was identified using a LASSO-penalized Cox model trained on TCGA (N = 543 patients). A clinically applicable polyA-RNAseq-based work-flow was developed for validation of the signature in a cohort of stage I-IV patients treated in two Hospitals [2010-2017]. Model performances were evaluated using time-dependent ROC curves (prediction of disease-specific-survival (DSS)). The additional value of the RNAseq signature was evaluated by multivariable Cox model, adjusted on high-risk prognostic group (2021 ESGO-ESTRO-ESP guidelines: non-endometrioid histology or stage III-IVA orTP53-mutated molecular subgroup). RESULTS: Among 209 patients included in the external validation cohort, 61 (30%), 10 (5%), 52 (25%), and 82 (40%), had mismatch repair-deficient, POLE-mutated, TP53-mutated tumors, and tumors with no specific molecular profile, respectively. The 38-genes signature accurately predicted DSS (AUC = 0.80). Most disease-related deaths occurred in high-risk patients (5-years DSS = 78% (95% CI = [68%-89%]) versus 99% [97%-100%] in patients without high-risk). A composite classifier accounting for the TP53-mutated subgroup and the RNAseq signature identified three classes independently associated with DSS: RNAseq-good prognosis (reference, 5-years DSS = 99%), non-TP53 tumors but with RNAseq-poor prognosis (adjusted-hazard ratio (aHR) = 5.75, 95% CI[1.14-29.0]), and TP53-mutated subgroup (aHR = 5.64 [1.12-28.3]). The model accounting for the high-risk group and the composite classifier predicted DSS with AUC = 0.84, versus AUC = 0.76 without (p = 0.01). CONCLUSION: RNA-seq profiling can provide an additional prognostic information to established classification systems, and warrants validation for potential RNAseq-based therapeutic strategies in EC.

Low serum progesterone affects live birth rate in cryopreserved blastocyst transfer cycles using hormone replacement therapy.

Tue, 01 Mar 2022 00:00:00 +0000

RESEARCH QUESTION: Does serum progesterone concentration on the day of vitrified-warmed embryo transfer affect live birth rate (LBR) with hormonal replacement therapy (HRT) cycles? DESIGN: Observational cohort study of patients (n = 915) undergoing single autologous vitrified-warmed blastocyst transfer under HRT using vaginal micronized progesterone. Women were included once, between January 2019 and March 2020. Serum progesterone concentration was measured by a single laboratory on the morning of embryo transfer. The primary end point was LBR. Univariate and multivariate logistic regression models were used for statistical analyses. RESULTS: Median (25th-75th percentile) serum progesterone concentration on the day of embryo transfer was 12.5 ng/ml (9.8-15.3). The LBR was 31.5% (288/915) in the overall population. No significant differences were found in implantation rates (40.7% versus 44.9%); LBR was significantly lower in women with a progesterone concentration ≤25th percentile (≤9.8 ng/ml) (26.1% versus 33.2%, P = 0.045) versus women with a progesterone concentration >25th percentile. This correlated with a significantly higher early miscarriage rate (35.9% versus 21.6%, P = 0.005). After adjusting for potential confounding factors in multivariate analysis, low serum progesterone levels (≤9.8 ng/ml) remained significantly associated with lower LBR (OR 0.68 95% CI 0.48 to 0.97). CONCLUSION: A minimum serum progesterone concentration is needed to optimize reproductive outcomes in HRT cycles with single autologous vitrified-warmed blastocyst transfer. Whether modifications of progesterone administration routes, dosage, or both, can improve pregnancy rates needs further study so that treatment of patients undergoing HRT cycles can be further individualized.

[Adenomyosis pathophysiology: An unresolved enigma].

Tue, 01 Feb 2022 00:00:00 +0000

Adenomyosis is a chronic benign uterine disease characterized by the presence of endometrial glands and stroma within the myometrium. It is a heterogeneous disease, presenting various clinical forms, depending on the location of the ectopic lesions within the myometrium. Adenomyosis can be responsible for several symptoms such as dysmenorrhea, abnormal uterine bleeding and/or infertility. Its pathophysiology is a real conundrum and several theories have been proposed: development of adenomyosis lesion could initiate de novo from Mullerian rests or from stem cells. Moreover, multiple factors could be involved in initiating lesions, including specific hormonal, immune and/or genetic changes. The objective of this review is to provide an update on adenomyosis pathophysiology, in particular on the various theories proposed concerning the invasion of the myometrium by endometrial cells and the inducing mechanisms, and to study the link between the physiopathology, the symptoms and the medical treatments.

ART Outcomes After Hysteroscopic Proximal Tubal Occlusion Versus Laparoscopic Salpingectomy for Hydrosalpinx Management in Endometriosis Patients.

Tue, 01 Feb 2022 00:00:00 +0000

The objective of this paper is to compare assisted reproductive technology (ART) cumulative live birth rates after hysteroscopic proximal tubal occlusion and laparoscopic salpingectomy in endometriosis patients, for management of hydrosalpinx. This is an observational cohort study at a university hospital, including all endometriosis patients with hydrosalpinges undergoing ART, between January 2013 and December 2018. The patients underwent either laparoscopic salpingectomy or hysteroscopic proximal tubal occlusion with Essure® when laparoscopy was not an option (extensive pelvic adhesions at exploratory laparoscopy or a history of multiple abdominal surgeries with frozen pelvis). The diagnosis of endometriosis was based on published imaging criteria using transvaginal sonography (TVUS) and magnetic resonance imaging (MRI). Endometriosis patients with hydrosalpinges diagnosed by hysterosalpingography and/or TVUS and/or MRI were included. The primary outcome was the cumulative live birth rate. A total of 104 patients were included in the study; 74 underwent laparoscopic salpingectomy and 30 underwent proximal tubal occlusion with Essure®. The Essure® group had longer infertility durations (58.9 ± 30.0 months vs. 39.5 ± 19.1 months, p = 0.002) and a higher incidence of associated adenomyosis (76.7% vs. 39.1%, p < 0.001) than the salpingectomy group. The cumulative live birth rate was 56.6% after 44 ART cycles in the Essure® group and 40.5% after 99 ART cycles in the salpingectomy group (p = 0.13). In a population of endometriosis patients undergoing ART, women treated by Essure® for management of hydrosalpinx have similar cumulative live birth rates as women treated by laparoscopic salpingectomy.

Association Between Endometriosis Phenotype and Preterm Birth in France.

Tue, 01 Feb 2022 00:00:00 +0000

IMPORTANCE: Endometriosis is an inflammatory disease with a heterogeneous presentation that affects women of childbearing age. Given the limitations of previous retrospective studies, it is still unclear whether endometriosis has adverse implications for pregnancy outcomes. OBJECTIVE: To evaluate the association between the presence of endometriosis and preterm birth and whether the risk varied according to the disease phenotype. DESIGN, SETTING, AND PARTICIPANTS: This cohort study with exposed and unexposed groups was conducted in 7 maternity units in France from February 4, 2016, to June 28, 2018. Participants included women with singleton pregnancies who were followed up before 22 weeks’ gestation along with their newborns delivered at or after 22 weeks’ gestation. The final follow-up occurred in July 2019. Data were analyzed from October 7, 2020, to February 7, 2021. EXPOSURES: Women in the endometriosis group had a documented history of endometriosis and were classified according to 3 endometriosis phenotypes: isolated superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA; potentially associated with SUP), and deep endometriosis (DE; potentially associated with SUP and OMA). Women in the control group did not have a history of clinical symptoms of endometriosis before their current pregnancy. MAIN OUTCOMES AND MEASURES: The primary outcome was preterm birth between 22 weeks and 36 weeks 6 days of gestation. Association between endometriosis and the primary outcome was assessed through univariate and multivariate logistic regression analyses and was adjusted for the following risk factors associated with preterm birth: maternal age, body mass index (calculated as weight in kilograms divided by height in meters squared) before pregnancy, country of birth, parity, previous cesarean delivery, history of myomectomy and hysteroscopy, and preterm birth. The same analysis was performed according to the 3 endometriosis phenotypes (SUP, OMA, and DE). RESULTS: Of the 1351 study participants (mean [SD] age, 32.9 [5.0] years) who had a singleton delivery after 22 weeks of gestation, 470 were assigned to the endometriosis group (48 had SUP [10.2%], 83 had OMA [17.7%], and 339 had DE [72.1%]) and 881 were assigned to the control group. No difference was observed in the rate of preterm deliveries before 37 weeks 0 days of gestation between the endometriosis and control groups (34 of 470 [7.2%] vs 53 of 881 [6.0%]; P = .38). After adjusting for confounding factors, endometriosis was not associated with preterm birth before 37 weeks’ gestation (adjusted odds ratio, 1.07; 95% CI, 0.64-1.77). The results were comparable for the different disease phenotypes (SUP: 6.2% [3 of 48]; OMA: 7.2% [6 of 83]; and DE: 7.4% [25 of 339]; P = .84). CONCLUSIONS AND RELEVANCE: This cohort study found no association between endometriosis and preterm birth, and the disease phenotype did not appear to alter the result. Monitoring the pregnancy beyond the normal protocols or changing management strategies for women with endometriosis may not be warranted to prevent preterm birth.

A new validated screening method for endometriosis diagnosis based on patient questionnaires.

Mon, 10 Jan 2022 00:00:00 +0000

BACKGROUND: The time between symptoms onset and endometriosis diagnosis is usually long. The negative impacts of delayed endometriosis diagnosis can affect patients and health outcomes. METHODS: We conducted a case-control study using clinical symptoms and epidemiological data extracted from a prospective pre-operative patient questionnaire compared between patients with histologically proven endometriosis and patients with no endometriosis at surgical exploration from 2005 to 2018, in a French referral center. We used the beta coefficients of the significant variables introduced in a multiple regression model to devise a score (score 1), evaluated by the area under the curve (or C-index), with three levels, defined by a score between 1 and ≥ 25: (i) highly specific, identifying correctly the patients without the disease; (ii) highly sensitive, identifying the patients with the disease; and (iii) a level maximizing sensitivity and specificity for the best classification of the whole population. To minimize patient self-evaluation of pain, we devised a second score (score 2) with the same method and levels and scores definition, excluding visual analog scale pain scores, except for dysmenorrhea. These scores were validated on an internal and external population. FINDINGS: Score 1 had a C-index of 0.81 (95% CI [0.79-0.83]). Results for the three score 1 levels were: ≥ 25: specificity of 91% (95% CI [89-93]); < 11: sensitivity of 91% (95% CI [89-93]); ≥ 18: specificity of 75% (95% CI [72-78]) and sensitivity of 73% (95% CI [70-76]). Score 2 had a C-index of 0.75 (95% CI [73-77]). The three levels of score 2 were: ≥ 24: specificity of 82% (95% CI [80-85]); < 7: sensitivity of 92% (95% CI [90-94]); ≥ 17: specificity of 62% (95% CI [58-65]) and sensitivity of 78% (95% CI [75-81]). The two scores were internally and externally validated. INTERPRETATION: A score based only on a patient questionnaire could allow identification of a population at high risk of endometriosis. This strategy might help referral to specialized radiologists for a non-surgical endometriosis scan. FUNDING: None.

Endometriosis increases the rate of spontaneous early miscarriage in women who have adenomyosis lesions.

Sat, 01 Jan 2022 00:00:00 +0000

RESEARCH QUESTION: In women with radiologically diagnosed adenomyosis, is the presence of endometriosis associated with a higher rate of miscarriage? DESIGN: An observational cohort study of women who received medical care for benign gynaecological conditions between May 2005 and May 2018. Women who had adenomyosis lesions visualized by uterine magnetic resonance imaging (MRI) were included. Women who had never been pregnant were excluded. Women with adenomyosis identified by MRI but who did not have endometriosis lesions (control group) were compared with women with adenomyosis and endometriosis lesions (study group). Primary outcome was rate of a previous history of early miscarriage. RESULTS: A total of 214 pregnancies in the study group and 53 pregnancies in the control group were analysed. The rate of a previous miscarriage was significantly higher among women with adenomyosis and endometriosis lesions compared with women in the control group (61/214 [28.5%] versus 6/53 [11.3%], respectively, P = 0.009). A multivariable generalized estimating equation logistic regression model, adjusted for adenomyosis and endometriosis phenotypes, found that the association between endometriosis and adenomyosis significantly increased the risk of miscarriage (OR 3.2, 95% CI 1.1 to 9.65). The risk was significantly higher with deep infiltrating endometriosis (OR 4.37, 95% CI 1.32 to 14.53). CONCLUSIONS: Women affected by endometriosis had a significantly higher rate of previous spontaneous miscarriage than women without endometriosis with adenomyosis lesions identified by MRI. Mechanistic studies are needed to establish the complex link between the presence of endometriosis and adenomyosis and the rate of spontaneous miscarriage.

Adenomyosis: An update regarding its diagnosis and clinical features.

Wed, 01 Dec 2021 00:00:00 +0000

Adenomyosis is a common gynecologic disease characterized by invasion of endometrial glands and stroma within the myometrium. Clinically, it can result in abnormal uterine bleeding, pelvic pain, and infertility. Adenomyosis has historically been diagnosed by histology of hysterectomy specimens. As a result of the development of imaging techniques, the diagnosis is nowadays possible by means of transvaginal pelvic ultrasound or pelvic magnetic resonance imaging. The use of pelvic imaging has demonstrated the existence of different forms of adenomyosis, notably allowing distinction between lesions of the external myometrium and those of the internal myometrium. The epidemiological and clinical characteristics may depend on the anatomical location of the adenomyosis lesions. In order to provide the best management for women with adenomyosis, the objective of this review is to provide an update regarding the diagnosis of adenomyosis and its clinical features according to the different adenomyosis phenotypes.

[Endometriosis and adenomyosis].

Mon, 01 Nov 2021 00:00:00 +0000

Diffuse adenomyosis, focal adenomyosis, ovarian endometrioma, superficial endometriosis and deep infiltrating adenomyosis are all defined by the presence of an endometrioid tissue in an ectopic location that is at distance from the endometrium. Although frequently associated, these lesions represent different clinico-pathological entities that the pathologist should recognized. Herein, we review the clinical and pathological features of these entities, as well as related current physiopathological understandings and differential diagnoses that could be raised by some morphological variants. The statistical association between endometriosis and several ovarian tumors, mainly endometrioid and clear cell carcinomas and seromucinous borderline tumors is well established and we present some molecular and morphological features that support this transformation potential.

Fertility preservation for patients affected by endometriosis should ideally be carried out before surgery.

Mon, 01 Nov 2021 00:00:00 +0000

RESEARCH QUESTION: What prognostic factors relate to a high oocyte yield in fertility preservation for women affected by endometriosis? DESIGN: Observational cohort study conducted in a tertiary care university hospital between April 2015 and January 2019. Women who had undergone fertility preservation with ovarian stimulation for oocytes and embryo vitrification for endometriosis were included. Prognostic factors associated with the number of oocytes retrieved after the first ovarian stimulation were analysed. RESULTS: A total of 146 women who had undergone 258 ovarian stimulation cycles were included; 82 (56.2%) had undergone more than one ovarian stimulation cycle; 72.6% had at least one endometrioma lesion; and 36.3% had previously undergone surgery for endometriosis. After adjustment by multiple linear regression, the factors that significantly reduced the number of oocytes retrieved were previous history of surgery for ovarian endometriosis (coefficient -1.08; 95% CI -2.02 to -0.15; P = 0.024); women’s age (-0.21; 95% CI -0.41 to -0.01; P = 0.039); and total dose of gonadotrophin used (-0.01; 95% CI -0.01 to -0.00; P = 0.047). Anti-Müllerian hormone serum level and gravidity positively correlated with an increase in the number of oocytes retrieved (1.65; 95% CI 1.13 to 2.17; P < 0.001 and 3.30; 95% CI 0.91 to 5.68; P = 0.007, respectively) after the first ovarian stimulation cycle. CONCLUSION: A history of surgery for ovarian endometriosis was associated with significantly lower oocyte yields. Fertility preservation should be integrated into endometriosis management. Fertility preservation should ideally be made available to the patient before surgery.

Surgical Management of Urinary Tract Endometriosis: A 1-year Longitudinal Multicenter Pilot Study at 31 French Hospitals (by the FRIENDS Group).

Mon, 01 Nov 2021 00:00:00 +0000

STUDY OBJECTIVE: To describe the surgical management and risks of postoperative complications of patients with urinary tract endometriosis in France in 2017. DESIGN: Multicenter retrospective cohort pilot study. SETTING: Departments of gynecology at 31 expert endometriosis centers. PATIENTS: All women managed surgically for urinary tract endometriosis from January 1, 2017, to December 31, 2017. We distinguished patients with isolated bladder endometriosis or isolated ureteral endometriosis (IUE) from those with endometriosis in both locations (mixed locations [ML]). INTERVENTIONS: Surgeons belonging to the French Colorectal Infiltrating Endometriosis Study (FRIENDS) group enrolled patients who filled a 24-item questionnaire on the day of the inclusion and 3 months later. Data were collected on operative routes, surgical management, and postoperative complications according to the Clavien-Dindo classification in a single anonymized database. MEASUREMENTS AND MAIN RESULTS: A total of 232 patients from 31 centers were included. Isolated bladder endometriosis was found in 82 patients (35.3%), IUE in 126 patients (54.4%), and ML in 24 patients (10.3%). Surgery was performed by laparoscopy, laparotomy, or robot-assisted laparoscopy in 74.1%, 11.2%, and 14.7% of the cases, respectively. Among the 150 ureteral lesions (IUE and ML), 114 were managed with ureterolysis (76%), 28 with ureteral resection (18.7%), 4 with nephrectomy (2.7%), and 23 with cystectomy (15.3%). Concerning bladder endometriosis, a partial cystectomy was performed in 94.3% of the cases. We reported 61 postoperative complications (26.3%): 44 low-grade complications according to the Clavien-Dindo classification (18%), 16 grade III complications (7%), and 1 grade IV complication (peritonitis). CONCLUSION: The surgical management of ureteral and bladder endometriosis is usually feasible and safe through laparoscopic surgery. Ureteral resection, when necessary, is more strongly associated with laparotomy and with more complications than other procedures. Prospective controlled studies are still mandatory to assess the best surgical management for patients.

Surgical management of endometriotic women with pregnancy intention in France: A national snapshot of centers performing a high volume of endometriosis procedures.

Fri, 01 Oct 2021 00:00:00 +0000

OBJECTIVE: To provide a snapshot of the surgical management of endometriosis in French high-volume activity centers. METHODS: Analysis of prospectively collected data between November 2015 and May 2017 in 21 centers with a high volume of endometriosis surgery in France. Each facility could include up to 40 patients undergoing laparoscopy for endometriosis. Data were collected before and two months after surgery. RESULTS: 361 patients were enrolled in the study. Twenty-seven patients (7.48%) were lost to follow-up at the month 2 visit. Endometriosis stage was I-II in 33.70% of patients and III-IV in 66.30%. Uterosacral ligament resection was the most frequently performed procedure (50.97%) followed by rectal surgery (31.58%), ovarian procedures for endometrioma, procedures for ureters (21.33%) and the bladder (11.91%). Antiadhesion agents were employed in 215/361 (59.56%) patients. The median length of hospital stay after surgery was 2 (IQR 1 - 4) days. Post-operative complications were recorded in 9.34% of patients. Rectovaginal fistulae occurred in 8 patients (2.41%), pelvic abscess in 4 (1.20%) and bladder atony in 3 (0.90%). 17 patients (5.14%) required a second surgical procedure after a median time of 31 days (IQR 9 - 81). Two months after surgery, 95.09% of patients reported being satisfied or very satisfied with the surgery. CONCLUSION: Our study shows that surgical management of endometriosis in centers with a high volume of endometriosis surgery, mainly concerns women presenting with severe disease and deep localizations, with an overall risk of major complications inferior to 10% and a high rate of patient satisfaction.

Immune cells and Notch1 signaling appear to drive the epithelial to mesenchymal transition in the development of adenomyosis in mice.

Wed, 29 Sep 2021 00:00:00 +0000

The epithelial to mesenchymal transition (EMT) has been implicated in the development of adenomyosis, along with dysregulated immune responses. Inflammation potentially induces Notch signaling, which could promote this EMT. The objective of this study was to investigate the involvement of immune cells and Notch1-mediated EMT in the development of adenomyosis. Adenomyosis was induced in 18 CD-1 mice by neonatal oral administration of tamoxifen (TAM group), while 18 neonates received vehicle only (Control group). Their uteri were sampled at 30, 60 or 90 days of age. Immune cell markers (Cd45, Ly6c1, Cd86, Arginine1, Cd19, Cd4, Cd8), Notch1 and its target genes (Hey1, Hey2, Hes1, Hes5) and biomarkers of EMT (E-Cadherin, Vimentin, Tgfb, Snail1, Slug, Snail3) were analyzed by quantitative RT-PCR and immunohistochemistry. Activated-Notch1 protein was measured by western blot. Aberrant expression of immune cell markers was observed in the uteri of mice as they developed adenomyosis. The expression of inflammatory cell markers, notably M1 macrophages and natural killer cells, was increased from Day 30 in the TAM group compared to controls, followed by an increase in the Cd4 marker (T cells) at Day 60. Conversely, expression of the Cd19 marker (B cells) was significantly reduced at all of the stages studied. Notch1 signaling was also highly activated compared to controls at Day 30 and Day 60. Concomitantly, the levels of several markers for EMT were also higher. Therefore, the activation of Notch1 coincides with aberrant expression of immune and EMT markers in the early development of adenomyosis.

Genomics of Endometriosis: From Genome Wide Association Studies to Exome Sequencing.

Wed, 07 Jul 2021 00:00:00 +0000

This review aims at better understanding the genetics of endometriosis. Endometriosis is a frequent feminine disease, affecting up to 10% of women, and characterized by pain and infertility. In the most accepted hypothesis, endometriosis is caused by the implantation of uterine tissue at ectopic abdominal places, originating from retrograde menses. Despite the obvious genetic complexity of the disease, analysis of sibs has allowed heritability estimation of endometriosis at ~50%. From 2010, large Genome Wide Association Studies (GWAS), aimed at identifying the genes and loci underlying this genetic determinism. Some of these loci were confirmed in other populations and replication studies, some new loci were also found through meta-analyses using pooled samples. For two loci on chromosomes 1 (near CCD42) and chromosome 9 (near CDKN2A), functional explanations of the SNP (Single Nucleotide Polymorphism) effects have been more thoroughly studied. While a handful of chromosome regions and genes have clearly been identified and statistically demonstrated as at-risk for the disease, only a small part of the heritability is explained (missing heritability). Some attempts of exome sequencing started to identify additional genes from families or populations, but are still scarce. The solution may reside inside a combined effort: increasing the size of the GWAS designs, better categorize the clinical forms of the disease before analyzing genome-wide polymorphisms, and generalizing exome sequencing ventures. We try here to provide a vision of what we have and what we should obtain to completely elucidate the genetics of this complex disease.

Adenomyosis is associated with specific proton nuclear magnetic resonance ((1)H-NMR) serum metabolic profiles.

Thu, 01 Jul 2021 00:00:00 +0000

OBJECTIVE: To determine whether the adenomyosis phenotype affects the proton nuclear magnetic resonance (1H-NMR)-based serum metabolic profile of patients. DESIGN: Cohort study. SETTING: University hospital-based research center. PATIENTS: Seventy-seven patients who underwent laparoscopy for a benign gynecologic condition. INTERVENTIONS: Pelvic magnetic resonance imaging and collection of a venous peripheral blood sample were performed during the preoperative workup. The women were allocated to the adenomyosis group (n = 32), or the control group (n = 45). The adenomyosis group was further subdivided into two groups: diffuse adenomyosis of the inner myometrium (n = 14) and focal adenomyosis of the outer myometrium (n = 18). Other adenomyosis phenotypes were excluded. MAIN OUTCOME MEASURES: Metabolomic profiling based on 1H-NMR spectroscopy in combination with statistical approaches. RESULTS: The serum metabolic profiles of the patients with adenomyosis indicated lower concentrations of 3-hydroxybutyrate, glutamate, and serine compared with controls. Conversely, the concentrations of proline, choline, citrate, 2-hydroxybutyrate, and creatinine were higher in the adenomyosis group. The focal adenomyosis of the outer myometrium and the diffuse adenomyosis phenotypes also each exhibited a specific metabolic profile. CONCLUSION: Serum metabolic changes were detected in women with features of adenomyosis compared with their disease-free counterparts, and a number of specific metabolic pathways appear to be engaged according to the adenomyosis phenotype. The metabolites with altered levels are particularly involved in immune activation as well as cell proliferation and cell migration. Nevertheless, this study did find evidence of a correlation between metabolite levels and symptoms thought to be related to adenomyosis. Further studies are required to determine the clinical significance of these differences in metabolic profiles.

[Endometriosis: A new paradigm!].

Tue, 01 Jun 2021 00:00:00 +0000

Assisted reproductive technology outcomes in women with a chronic viral disease.

Tue, 01 Jun 2021 00:00:00 +0000

OBJECTIVE: The aim of this study was to evaluate the cumulative live birth rate in women undergoing in-vitro fertilization/intracytoplasmic-sperm-injection (IVF/ICSI) according to the type of chronic viral infection [HIV, hepatitis-B virus (HBV) and hepatitis-C virus (HCV)]. DESIGN: A cohort study. SETTING: A tertiary-care university hospital. PARTICIPANTS: Women with a chronic viral illness HIV, HBV or HCV- were followed until four IVF/ICSI cycles had been completed, until delivery or until discontinuation of the treatment before the completion of four cycles. MAIN OUTCOME MEASURES: The primary outcome was the cumulative live birth rate after up to four IVF/ICSI cycles. RESULTS: A total of 235 women were allocated to the HIV-infected group (n = 101), the HBV-infected group (n = 114) and the HCV-infected group (n = 20). The cumulative live birth rate after four cycles was significantly lower in the HIV-infected women than in those with HBV [39.1%, 95% confidence interval (95% CI): 17.7-60.9 versus 52.8%, 95% CI: 41.6-65.5, respectively; P = 0.004]. Regarding the obstetrical outcomes, the mean birth weight was lower in the HIV-infected women than in those with HBV or HCV. Multivariate analysis indicated that the age, the anti-Müllerian hormone and the number of cycles performed were significantly associated with the chances of a live birth. CONCLUSION: HIV-infected women had lower cumulative live birth rate than women with chronic hepatitis, and this was due to less favourable ovarian reserve parameters. These findings underscore the need to better inform practitioners and patients regarding fertility issues and the importance of early fertility assessment. However, larger studies are necessary to gain more in-depth knowledge of the direct impact of HIV on live birth rates.

Imaging for evaluation of endometriosis and adenomyosis.

Tue, 01 Jun 2021 00:00:00 +0000

Endometriosis and adenomyosis are two frequent diseases that impair women’s quality of life by causing pain and infertility. Both endometriosis and adenomyosis are heterogeneous diseases that manifest as different forms. Adenomyosis may be described as diffuse adenomyosis, focal adenomyosis especially of the outer myometrium and cystic adenomyoma. Endometriosis has three phenotypes: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). These two diseases are closely linked, and it is now clear that adenomyosis can either arise on its own or coexist with endometriosis. There is a strong clinical relationship between endometriosis and adenomyosis according to their respective phenotypes. Various classifications are available to describe both diseases. Transvaginal ultrasonography (TVUS) and/or pelvic magnetic resonance imaging (MRI) are the first examination performed when endometriosis or adenomyosis are suspected. These two imaging techniques, used in a combination manner, allow accurate description of both endometriosis and adenomyosis, to assess the diagnosis and to improve clinical and surgical care. In this review, we described the different imaging aspects of endometriosis and adenomyosis to help the less experienced radiologist or gynecologist in the diagnosis and evaluation of those diseases.

Infertility in women with bowel endometriosis: first-line assisted reproductive technology results in satisfactory cumulative live-birth rates.

Mon, 01 Mar 2021 00:00:00 +0000

OBJECTIVE: To evaluate the assisted reproductive technology (ART) cumulative live-birth rate (LBR) in a cohort of bowel endometriosis patients with no prior history of surgery for endometriosis. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENT(S): One hundred and one consecutive infertile bowel-endometriosis patients with no prior history of surgery for endometriosis in whom the diagnosis of endometriosis was based on published imaging criteria using transvaginal sonography and magnetic resonance imaging. INTERVENTION(S): First-line ART. MAIN OUTCOME MEASURE(S): Cumulative LBR, with statistical analysis via Kaplan Meier method with a -‘conservative-’ method, whereby it was assumed that no live births took place for patients who did not return. RESULT(S): Between January 2016 and December 2018, 101 bowel endometriosis patients underwent 176 ART cycles. The mean number of deep-infiltrating endometriosis lesions per patient was 3 ± 0.9, with a mean number of bowel lesions of 1.3 ± 0.6. Seventy-three percent of the patients had associated endometriomas, and 88.1% had associated adenomyosis. Overall, the cumulative LBR after four ART cycles was 64.4%, using the conservative Kaplan-Meier method. CONCLUSION(S): The ART cumulative LBR was very satisfactory (64.4%) in bowel endometriosis patients with no prior history of surgery for endometriosis. In light of these data, clinicians should carefully weigh the pros and cons before systematically referring infertile bowel endometriosis patients to fertility-preserving surgery because as first-line ART appears to offer satisfactory results.

The freeze-all strategy after IVF: which indications?

Mon, 01 Mar 2021 00:00:00 +0000

The freeze-all strategy is gaining popularity worldwide as an alternative to the conventional fresh embryo transfer. It consists of cryopreservation of the entire embryo cohort and the embryo transfer in a subsequent cycle that takes place separately from ovarian stimulation. The freeze-all strategy was initially a ‘rescue’ strategy for women at high risk of ovarian hyperstimulation syndrome; however, this approach has been extended to other indications as a scheduled strategy to improve implantation rates. This assumes that ovarian stimulation can alter endometrial receptivity in fresh cycles owing to the effect of supraphysiological levels of steroids on endometrial maturation. The procedure, however, has not been associated with increased live birth rates in all infertile couples, and concerns have been raised about the occurrence of several adverse perinatal outcomes. It is, therefore, crucial to identify in which subgroups of patients a freeze-all strategy could be beneficial. The aim of this review is to summarize current scientific research in this field to highlight potential indications for this strategy and to guide clinicians in their daily practice.

Adenomyosis of the inner and outer myometrium are associated with different clinical profiles.

Mon, 25 Jan 2021 00:00:00 +0000

STUDY QUESTION: Do adenomyosis phenotypes such as external or internal adenomyosis, as diagnosed by MRI, have the same clinical characteristics? SUMMARY ANSWER: External adenomyosis was found more often in young and nulliparous women and was associated with deep infiltrating endometriosis, whereas, in contrast, internal adenomyosis was more often associated with heavy menstrual bleeding (HMB) but no differences were noted in terms of pain symptoms. WHAT IS KNOWN ALREADY: Adenomyosis is characterized by the presence of endometrial glands and stroma deep within the myometrium, giving rise to dysmenorrhea, pelvic pain and menorrhagia. Various forms have been described, including adenomyosis of the outer myometrium (external adenomyosis), which corresponds to lesions separated from the junctional zone (JZ), and adenomyosis of the inner myometrium (internal adenomyosis), which is mostly characterized by endometrial implants scattered throughout the myometrium and enlargement of the JZ. Although the pathogenesis of adenomyosis is not clearly understood, several lines of evidence suggest that these two phenotypes could have distinct origins. The clinical presentation of different forms of adenomyosis in patients warrants further investigation. STUDY DESIGN, SIZE, DURATION: This was an observational study that used data collected prospectively in non-pregnant patients aged between 18 and 42 years who had undergone surgical exploration for benign gynecological conditions at our institution between May 2005 and May 2018. Only women with a pelvic MRI performed by a senior radiologist during the preoperative work-up were retained for this study. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon in the month preceding the surgery. The women’s histories (notably their age, gravidity, history of surgery and associated endometriosis), as well as clinical symptoms such as the pain intensity, presence of menorrhagia and infertility, were noted. PARTICIPANTS/MATERIALS, SETTING, METHODS: A pelvic MRI was performed in 496 women operated at our center for a benign gynecological disease who had provided signed informed consent. Of these, 248 women had a radiological diagnosis of adenomyosis. Based on the MRI findings, the women were diagnosed as having external and/or internal adenomyosis. The women were allocated to two groups according to the adenomyosis phenotype (only external adenomyosis vs only internal adenomyosis). Women exhibiting an association of both adenomyosis forms were analyzed separately. MAIN RESULTS AND THE ROLE OF CHANCE: In all, following the MRI findings, 109 women (44.0%) exhibited only external adenomyosis, while 78 (31.5%) had only internal adenomyosis. The women with external adenomyosis were significantly younger (mean ± SD; 31.9 ± 4.6 vs 33.8 ± 5.2 years; P = 0.006), more often nulligravid (P ≤ 0.001) and more likely to exhibit an associated endometriosis (P < 0.001) compared to the women in the internal adenomyosis group. Moreover, the women exhibiting internal adenomyosis significantly more often had a history of previous uterine surgery (P = 0.002) and HMB (62 (80%) vs 58 (53.2%), P < 0.001) compared to the women with external adenomyosis. No differences in the pain scores (i.e. dysmenorrhea, non-cyclic pelvic pain and dyspareunia) were observed between the two groups. LIMITATIONS, REASONS FOR CAUTION: The exclusive inclusion of surgical patients could constitute a possible selection bias, as the women referred to our center may have suffered from particularly severe clinical symptoms. WIDER IMPLICATIONS OF THE FINDINGS: Further studies are needed to explore the pathogenesis by which these types of adenomyosis occur. This could help with the development of new treatment strategies specific for each entity. STUDY FUNDING/COMPETING INTEREST(S): none. TRIAL REGISTRATION NUMBER: N/A.

Impact of Endometriosis on Life-Course Potential: A Narrative Review.

Thu, 07 Jan 2021 00:00:00 +0000

Endometriosis may exert a profound negative influence on the lives of individuals with the disorder, adversely affecting quality of life, participation in daily and social activities, physical and sexual functioning, relationships, educational and work productivity, mental health, and well-being. Over the course of a lifetime, these daily challenges may translate into limitations in achieving life goals such as pursuing or completing educational opportunities; making career choices or advancing in a chosen career; forming stable, fulfilling relationships; or starting a family, all of which ultimately alter one’s life trajectory. The potential for endometriosis to impact the life course is considerable, as symptom onset generally occurs at a time of life (menarche through menopause, adolescence through middle age) when multiple life-changing and trajectory-defining decisions are made. Using a life-course approach, we examine how the known effects of endometriosis on life-domain satisfaction may impact health and well-being across the life course of affected individuals. We provide a quasi-systematic, narrative review of the literature as well as expert opinion on recommendations for clinical management and future research directions.

Immunological changes associated with adenomyosis: a systematic review.

Mon, 04 Jan 2021 00:00:00 +0000

BACKGROUND: Adenomyosis is a benign gynecological disorder associated with subfertility, pelvic pain and abnormal uterine bleeding that have significant consequences for the health and quality of life of women. Histologically, it is defined as the presence of ectopic endometrial islets within the myometrium. Its pathogenesis has not yet been elucidated and several pieces of the puzzle are still missing. One process involved in the development of adenomyosis is the increased capacity of some endometrial cells to infiltrate the myometrium. Moreover, the local and systemic immune systems are associated with the onset of the disease and with maintaining it. Numerous observations have highlighted the activation of immune cells and the release of immune soluble factors in adenomyosis. The contribution of immunity occurs in conjunction with hormonal aberrations and activation of the epithelial to mesenchymal transition (EMT) pathway, which promotes migration of endometrial cells. Here, we review current knowledge on the immunological changes in adenomyosis, with the aim of further elucidation of the pathogenesis of this disease. OBJECTIVE AND RATIONALE: The objective was to systematically review the literature regarding the role of the immune system in development of adenomyosis in the inner and the outer myometrium, in humans. SEARCH METHODS: A systematic review of published human studies was performed in MEDLINE, EMBASE and Cochrane Library databases from 1970 to February 2019 using the combination of Medical Subject Headings (MeSH): Adenomyosis AND (‘Immune System’ OR ‘Gonadal Steroid Hormones’), and free-text terms for the following search terms (and their variants): Adenomyosis AND (immunity OR immune OR macrophage OR ’natural killer cell’ OR lymphocyte* OR leucocyte* OR HLA OR inflammation OR ‘sex steroid’ OR ’epithelial to mesenchymal transition’ OR ‘EMT’). Studies in which no comparison was made with control patients, without adenomyosis (systemic sample and/or eutopic endometrium), were excluded. OUTCOMES: A total of 42 articles were included in our systematic review. Changes in innate and adaptive immune cell numbers were described in the eutopic and/or ectopic endometrium of women with adenomyosis compared to disease-free counterparts. They mostly described an increase in lymphocyte and macrophage cell populations in adenomyosis eutopic endometrium compared to controls. These observations underscore the immune contributions to the disease pathogenesis. Thirty-one cytokines and other markers involved in immune pathways were studied in the included articles. Pro-inflammatory cytokines (interleukin (IL) 6, IL1β, interferon (IFN) α, tumor necrosis factor α, IFNγ) as well as anti-inflammatory or regulatory mediators (IL10, transforming growth factor β…) were found to be elevated in the eutopic endometrium and/or in the ectopic endometrium of the myometrium in women with adenomyosis compared to controls. Moreover, in women affected by adenomyosis, immunity was reported to be directly or indirectly linked to sex steroid hormone aberrations (notably changes in progesterone receptor in eutopic and ectopic endometrium) in three studies and to EMT in four studies. WIDER IMPLICATIONS: The available literature clearly depicts immunological changes that are associated with adenomyosis. Both systemic and local immune changes have been described in women affected by adenomyosis, with the coexistence of changes in inflammatory as well as anti-inflammatory signals. It is likely that these immune changes, through an EMT mechanism, stimulate the migration of endometrial cells into the myometrium that, together with an endocrine imbalance, promote this inflammatory process. In light of the considerable impact of adenomyosis on women’s health, a better understanding of the role played by the immune system in adenomyosis is likely to yield new research opportunities to better understand its pathogenesis.

Risk of small for gestational age is reduced after frozen compared with fresh embryo transfer in endometriosis.

Fri, 01 Jan 2021 00:00:00 +0000

RESEARCH QUESTION: What are the perinatal outcomes and especially the risk of small for gestational age (SGA) babies born after frozen versus fresh embryo transfer in mothers affected by endometriosis undergoing treatment with assisted reproductive technology (ART)? DESIGN: A cohort study conducted between November 2012 and October 2017, in which infertile women with endometriosis undergoing ART and achieving singleton pregnancies that lasted beyond 12 weeks of gestation were included. Pregnancies obtained after a frozen embryo transfer (FET) were compared with those obtained after a fresh embryo transfer. A total of 339 pregnant women were included: 112 patients in the fresh embryo transfer group and 227 in the FET group. The main outcome was the rate of SGA. Secondary analyses were performed for adverse pregnancy outcomes and perinatal complications. RESULTS: Of the included women, 109/112 (97.3%) and 222/227 (97.8%) delivered a live child after at least 24 weeks of gestation in the fresh and in the frozen embryo transfer groups, respectively (P = 0.53). The risk of SGA decreased after a FET compared with a fresh embryo transfer (odds ratio [OR] 0.49 [0.25-0.98], P = 0.04) after multivariable analysis. The mean birthweight and the gestational age at delivery were not significantly different between the two study groups. Other pregnancy and perinatal complications were not statistically different between the two study populations. CONCLUSIONS: The present study of endometriosis-affected women found a significantly lower risk of SGA in patients undergoing frozen, mainly blastocyst, embryo transfer compared with patients undergoing fresh, mainly cleavage stage, embryo transfer.

Focal adenomyosis is associated with primary infertility.

Tue, 01 Dec 2020 00:00:00 +0000

OBJECTIVE: To study the association between adenomyosis and infertility, according to the adenomyosis phenotype as diagnosed by magnetic resonance imaging (MRI). DESIGN: A single-center, cross-sectional study. SETTING: University hospital-based research center. PATIENT(S): Patients between 18 and 42 years of age who were surgically explored for benign gynecological conditions at our institution between May 2005 and May 2018. Only women with uterine MRIs performed by a senior radiologist were retained for this study. INTERVENTION(S): Primary and secondary infertile women were compared with women without infertility. In addition, the women were diagnosed according to the MRI findings as having adenomyosis (focal adenomyosis of the outer myometrium [FAOM] and/or diffuse adenomyosis phenotypes) or no adenomyosis. MAIN OUTCOME MEASURE(S): Primary and secondary infertility-associated factors. RESULT(S): A total of 496 women were included in the study population. Three groups were compared: a no infertility group (n = 361), a primary infertility group (n = 84), and a secondary infertility group (n = 51). Among them, 248 women did not present adenomyosis lesions and 248 women had a radiological diagnosis of adenomyosis. The presence of FAOM was significantly associated with primary infertility. Diffuse adenomyosis was not found to be associated with infertility. The distribution of endometriosis or leiomyomas was not significantly different between the groups. After a multinomial regression model including the women’s age and associated endometriosis or leiomyoma, the presence of FAOM was identified as an independent associated factor of primary infertility (adjusted odds ratio 1.9; 95% confidence interval 1.1-3.3). CONCLUSION(S): The presence of FAOM was associated with primary infertility. This study opens the door to future clinical and basic studies aimed at better characterization of FAOM and its infertility-related physiopathology.

The follicular fluid metabolome differs according to the endometriosis phenotype.

Tue, 01 Dec 2020 00:00:00 +0000

RESEARCH QUESTION: Is there a follicular fluid-specific metabolic profile in deep infiltrating endometriosis (DIE) depending on the presence of an associated ovarian endometrioma (OMA) that could lead to the identification of biomarkers for diagnosis and prognosis of the disease? DESIGN: In this prospective cohort study, proton nuclear magnetic resonance (1H-NMR) experiments were carried out on 50 follicular fluid samples from patients presenting with DIE, associated or not associated with an OMA, and 29 follicular fluid samples from patients with infertility caused by a tubal obstruction. RESULTS: Concentrations of glucose, citrate, creatine and amino acids such as tyrosine and alanine were lower in women with DIE than control participants, whereas concentrations of lactate, pyruvate, lipids and ketone bodies were higher. Metabolic analysis revealed enhanced concentrations of glycerol and ketone bodies in patients with OMA, indicative of an activation of lipolysis followed by beta-oxidation. Concentrations of lactate and pyruvate were increased in patients without OMA, whereas the concentration of glucose was decreased, highlighting activation of the anaerobic glycolysis pathway. Differences in concentrations of amino acids such as threonine and glutamine were also statistically relevant in discriminating between the presence or absence of OMA. CONCLUSIONS: Results indicate a mitochondrial dysregulation in endometriosis phenotypes, with a modified balance between anaerobic glycolysis and beta-oxidation in OMA phenotypes that could affect the fertility of women with endometriosis. As the composition of the follicular fluid has been shown to be correlated with oocyte development and outcome of implantation after fertilization, these findings may help explain the high level of infertility in these patients.

Macrophage Immune Memory Controls Endometriosis in Mice and Humans.

Tue, 03 Nov 2020 00:00:00 +0000

Endometriosis is a frequent, chronic, inflammatory gynecological disease characterized by the presence of ectopic endometrial tissue causing pain and infertility. Macrophages have a central role in lesion establishment and maintenance by driving chronic inflammation and tissue remodeling. Macrophages can be reprogrammed to acquire memory-like characteristics after antigenic challenge to reinforce or inhibit a subsequent immune response, a phenomenon termed -’trained immunity.-’ Here, whereas bacille Calmette-Guérin (BCG) training enhances the lesion growth in a mice model of endometriosis, tolerization with repeated low doses of lipopolysaccharide (LPSlow) or adoptive transfer of LPSlow-tolerized macrophages elicits a suppressor effect. LPSlow-tolerized human macrophages mitigate the fibro-inflammatory phenotype of endometriotic cells in an interleukin-10 (IL-10)-dependent manner. A history of severe Gram-negative infection is associated with reduced infertility duration and alleviated symptoms, in contrast to patients with Gram-positive infection history. Thus, the manipulation of innate immune memory may be effective in dampening hyper-inflammatory conditions, opening the way to promising therapeutic approaches.

Endometriosis phenotypes are associated with specific serum metabolic profiles determined by proton-nuclear magnetic resonance.

Thu, 01 Oct 2020 00:00:00 +0000

RESEARCH QUESTION: What is the correlation between serum metabolic profile and endometriosis phenotype? DESIGN: A pilot study nestled in a prospective cohort study at a university hospital, including 46 patients with painful endometriosis who underwent surgery and 21 controls who did not have macroscopic endometriotic lesions. Endometriosis was strictly classified into two groups of 23 patients each: endometrioma (OMA) and deep infiltrating endometriosis (DIE). Serum samples were collected before surgery for metabolomic profiling based on proton-nuclear magnetic resonance spectroscopy in combination with statistical approaches. Comparative identification of the metabolites in the serum from endometriosis patients and from controls was carried out, including an analysis according to endometriosis phenotype. RESULTS: The serum metabolic profiles of the endometriosis patients revealed significantly lower concentrations of several amino acids compared with the controls, whereas the concentrations of free fatty acids and ketone bodies were significantly higher. The OMA and the DIE phenotypes each had a specific metabolic profile, with higher concentrations of two ketone bodies in the OMA group, and higher concentrations of free fatty acids and lipids in the DIE group. CONCLUSION: Proton-nuclear magnetic resonance-based metabolomics of serum samples were found to have ample potential for identifying metabolic changes associated with endometriosis phenotypes. This information may improve our understanding of the pathogenesis of endometriosis.

Focal adenomyosis of the outer myometrium and deep infiltrating endometriosis severity.

Thu, 01 Oct 2020 00:00:00 +0000

OBJECTIVE: To determine whether the presence of focal adenomyosis of the outer myometrium (FAOM) at preoperative magnetic resonance imaging is associated with the severity of deep infiltrating endometriosis. DESIGN: Observational cross-sectional study involving 255 symptomatic deep infiltrating endometriosis patients. Comparisons were performed according to the presence of FAOM. SETTING: University hospital. PATIENT(S): Women with a preoperative magnetic resonance imaging and complete surgical exeresis of endometriotic lesions with histologically documented deep infiltrating endometriosis. INTERVENTION(S): Surgical management for deep infiltrating endometriosis. MAIN OUTCOME MEASURE(S): The presence of multiple deep infiltrating endometriosis lesions, the mean number and location of deep infiltrating endometriosis lesions, and the mean total revised American Society for Reproductive Medicine scores. RESULT(S): The prevalence of FAOM at preoperative magnetic resonance imaging in the 255 patients with deep infiltrating endometriosis was 56.5%. The mean number of deep infiltrating endometriosis lesions was significantly higher in the FAOM(+) group than in the FAOM(-) group: 3.5 ± 2.1 vs. 2.2 ± 1.5. The mean total revised American Society for Reproductive Medicine score was higher in case of FOAM coexisting with deep infiltrating endometriosis. After adjusting for confounding factors, the presence of FAOM was significantly associated with multiple deep lesions. CONCLUSION(S): FAOM was significantly associated with greater deep infiltrating endometriosis severity. This needs to be integrated into the management strategy. Furthermore, a pathogenic link between deep infiltrating endometriosis and FAOM cannot be excluded.

Impact of Supraphysiological Estradiol Serum Levels on Birth Weight in Singletons Born After Fresh Embryo Transfer.

Tue, 01 Sep 2020 00:00:00 +0000

In assisted reproductive technology, high estradiol (E2) levels at trigger may increase the risk of low birth weight (LBW). Our objective was to investigate the impact of supra-physiological E2 levels at trigger, on the rate of LBW in singleton pregnancies following fresh embryo transfers (ET), in a center that typically employs the ‘freeze-all’ strategy in case of high E2 levels, to prevent ovarian hyper stimulation syndrome risk. A cohort study was conducted in a university hospital between November 2012 and January 2017. The main inclusion criterion was having a live birth (LB) singleton (≥ 24 weeks of gestation) after a fresh-ET. Four groups were defined according to the E2 level at trigger, as quartiles of the entire patient population. The main measured outcome was the rate of LBW. 497 fresh-ET led to LB. Mean E2 level was 1608.4 ± 945.5 pg/ml. The groups were allocated as follows: 124LB in the Group E2 < 25 percentile(p) (1106.5 pg/ml), 124LB in the Group E2 [25p-50p] (1106.5-1439 pg/ml), 124LB in the Group E2[50p-75p] (1440-1915 pg/ml), and 125LB in the Group E2 > 75p (>1915 pg/ml). There was no significant difference in the rate of LBW (Group E2 < 25p, n = 8/124, (6.5%); Group E2[25p-50p], n = 15/124, (12.1%); Group E2 [50p-75p], n = 13/124, (10.4%); and Group E2 > 75p, n = 10/12, (8.1%); (p = 0.43)). After multivariate analysis, E2 level at trigger was not significantly correlated to the rate of LBW. In our cohort, E2 level on the day of hCG trigger was not associated with increased odds of LBW after fresh embryo transfers.

Tobacco consumption is associated with slow-growing day-6 blastocysts.

Tue, 30 Jun 2020 00:00:00 +0000

OBJECTIVE: To investigate if there are any obvious clinical factors associated with delayed blastulation at day 6 (D6) compared with day 5 (D5). DESIGN: Monocentric observational cohort study from November 2012 to December 2018. SETTING: Tertiary-care academic medical center. PATIENTS: A total of 941 women with an entire cohort of exclusively D5 blastocysts compared with 162 patients with a cohort of exclusively D6 blastocysts. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Clinical characteristics and data related to the ovarian stimulation protocols. RESULTS: After univariate analysis, a significantly higher proportion of women who were active smokers was found in the D6 group compared with the D5 group (n = 22/162 [13.6%] vs. n = 82/941 [8.7%]). In addition, the women in the D6 group had a higher rank number of assisted reproductive technology (ART; total no. of ART cycles performed: 2.1 ± 1.4 vs. 1.6 ± 1.1) and a lower antral follicle count (AFC; 18.7 ± 11.3 vs. 22.2 ± 12.8). Moreover, fertilization with the use of intracytoplasmic sperm injection was used more frequently in the D6 group compared with the D5 group. Logistic regression analysis adjusted for confounders highlighted several independent predictors for reaching blastocyst stage at D6 rather than D5: being an active smoker, previous ART cycles, and a lower AFC. CONCLUSIONS: Obtaining an exclusively D6 blastocyst cohort is independently associated with women who are active smokers, previous ART cycles, and a lower AFC. These findings provide evidence, to be confirmed by further studies, that women who are active smokers could greatly benefit from smoking cessation before undergoing ART.

Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure.

Thu, 18 Jun 2020 00:00:00 +0000

BACKGROUND: Despite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis. OBJECTIVE AND RATIONALE: We review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments. SEARCH METHODS: We performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment. OUTCOMES: Progesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase and 17 beta-hydroxysteroid dehydrogenase type 1. Progestins inhibit cell proliferation, inflammation, neovascularisation and neurogenesis in endometriosis. However, progesterone receptor expression is reduced and disrupted in endometriotic lesions, with predominance of the less active isoform (PRA) over the full-length, active isoform (PRB), due to epigenetic abnormalities affecting the PGR gene transcription. Oxidative stress is another mechanism involved in progesterone resistance in endometriosis. Among the molecular targets of progesterone in the normal endometrium that resist progestin action in endometriotic cells are the nuclear transcription factor FOXO1, matrix metalloproteinases, the transmembrane gap junction protein connexin 43 and paracrine regulators of estradiol metabolism. Compared to other phenotypes, deep endometriosis appears to be more resistant to size regression upon medical treatments. Individual genetic characteristics can affect the bioavailability and pharmacodynamics of hormonal drugs used to treat endometriosis and, hence, explain part of the variability in the therapeutic response. WIDER IMPLICATIONS: Medical treatment of endometriosis needs urgent innovation, which should start by deeper understanding of the disease core features and diverse phenotypes and idiosyncrasies, while moving from pure hormonal treatments to drug combinations or novel molecules capable of restoring the various homeostatic mechanisms disrupted by endometriotic lesions.

[How I do… Resection of the uterosacral ligament by laparoscopy with nerve sparing in 6 steps].

Fri, 01 May 2020 00:00:00 +0000

Identification of TP53 mutated group using a molecular and immunohistochemical classification of endometrial carcinoma to improve prognostic evaluation for adjuvant treatments.

Fri, 01 May 2020 00:00:00 +0000

INTRODUCTION: Molecular classification of endometrial carcinoma has been proposed to predict survival. However, its role in patient management remains to be determined. We aimed to identify whether a molecular and immunohistochemical classification of endometrial carcinoma could improve decision-making for adjuvant therapy. METHODS: All consecutive patients treated for endometrial carcinoma between 2010 and 2017 at Cochin University Hospital were included. Clinical risk of relapse was based on European Society for Medical Oncology-European Society of Gynaecological Oncology-European SocieTy for Radiotherapy & Oncology (ESMO-ESGO-ESTRO) consensus. The clinical event of interest was event-free survival. Formalin-fixed paraffin-embedded tissue samples were processed for histopathological analysis and DNA extraction. The nuclear expression of mismatch repair and TP53 proteins was analyzed by immunohistochemistry. Next-generation sequencing of a panel of 15 genes including TP53 and POLE was performed using Ampliseq panels on Ion Torrent PGM (ThermoFisher). Tumors were allocated into four molecular groups using a sequential method based on next-generation sequencing and immunohistochemistry data: (1) POLE/ultramutated-like; (2) MSI/hypermutated-like (mismatch repair-deficient); (3) TP53-mutated (without POLE mutations or mismatch repair deficiency); (4) not otherwise specified (the remaining tumors). RESULTS: 159 patients were included; 125 tumors were available for molecular characterization and distributed as follows: (1) POLE/ultramutated-like: n=4 (3%); (2) MSI/hypermutated-like: n=35 (30%); (3) TP53-mutated: n=30 (25%); and (4) not otherwise specified: n=49 (42%). Assessing the TP53 status by immunohistochemistry only rather than next-generation sequencing would have misclassified 6 tumors (5%). TP53-mutated tumors were associated with poor prognosis, independently of International Federation of Gynecology and Obstetrics (FIGO) stage and histological grade (Cox-based adjusted hazard ratio (aHR) 5.54, 95% CI 2.30 to 13.4), and independently of clinical risk of relapse (aHR 3.92, 95% CI 1.59 to 9.64). Among patients with FIGO stage I-II tumors, 6 (38%) TP53-mutated tumors had low/intermediate clinical risk of relapse and did not receive adjuvant chemotherapy or radiotherapy. CONCLUSION: Endometrial carcinoma molecular classification identified potentially under-treated patients with poor molecular prognosis despite being at low/intermediate clinical risk of relapse. Consideration of molecular classification in adjuvant therapeutic decisions should be evaluated in prospective trials.

Migraine in relation with endometriosis phenotypes: Results from a French case-control study.

Fri, 01 May 2020 00:00:00 +0000

BACKGROUND: Studies have shown a significant association between migraine and endometriosis, but no study has explored the relationship between migraine and endometriosis phenotypes: Superficial peritoneal endometriosis, ovarian endometrioma, and deep infiltrating endometriosis. METHODS: We conducted a case-control study using data collected from 314 women aged 18 to 42 years who had undergone surgery for benign gynecological conditions between January 2013 and December 2015. All women completed a self-administered headache questionnaire according to the IHS classification. Cases (n = 182) are women with histologically proven endometriosis and controls are women (n = 132) without endometriosis. Occurrence of migraine was studied according to endometriosis phenotypes. RESULTS: Migraine prevalence in cases was significantly higher compared with controls (35.2% vs. 17.4%, p = 0.003). The risk of endometriosis was significantly higher in migrainous women (OR = 2.62; 95% CI = 1.43-4.79). When we take into account endometriosis phenotypes, the risk of ovarian endometrioma and deep infiltrating endometriosis were significant (OR = 2.78; 95% CI = 1.11-6.98 and OR = 2.51; 95% CI = 1.25-5.07, respectively). In women with endometriosis, the intensity of chronic non-cyclical pelvic pain was significantly greater for those with migraine (visual analogic scale (VAS) = 3.6 ± 2.9) compared with the women without headache (VAS = 2.3 ± 2.8, p = 0.0065). CONCLUSION: Our study shows a significant association between migraine and endometriosis. In clinical practice, women of reproductive age who suffer from migraine should be screened for endometriosis criteria in order to optimise the medical and therapeutic care of this condition.

Diagnosing adenomyosis: an integrated clinical and imaging approach.

Wed, 15 Apr 2020 00:00:00 +0000

BACKGROUND: Adenomyosis is a benign uterine disorder where endometrial glands and stroma are pathologically demonstrated within the uterine myometrium. The pathogenesis involves sex steroid hormone abnormalities, inflammation, fibrosis and neuroangiogenesis, even though the proposed mechanisms are not fully understood. For many years, adenomyosis has been considered a histopathological diagnosis made after hysterectomy, classically performed in perimenopausal women with abnormal uterine bleeding (AUB) or pelvic pain. Until recently, adenomyosis was a clinically neglected condition. Nowadays, adenomyosis may also be diagnosed by non-invasive techniques, because of imaging advancements. Thus, a new epidemiological scenario has developed with an increasing number of women of reproductive age with ultrasound (US) or magnetic resonance imaging (MRI) diagnosis of adenomyosis. This condition is associated with a wide variety of symptoms (pelvic pain, AUB and/or infertility), but it is also recognised that some women are asymptomatic. Furthermore, adenomyosis often coexists with other gynecological comorbidities, such as endometriosis and uterine fibroids, and the diagnostic criteria are still not universally agreed. Therefore, the diagnostic process for adenomyosis is challenging. OBJECTIVE AND RATIONALE: We present a comprehensive review on the diagnostic criteria of adenomyosis, including clinical signs and symptoms, ultrasound and MRI features and histopathological aspects of adenomyotic lesions. We also briefly summarise the relevant theories on adenomyosis pathogenesis, in order to provide the pathophysiological background to understand the different phenotypes and clinical presentation. The review highlights the controversies of multiple existing criteria, summarising all of the available evidences on adenomyosis diagnosis. The review aims also to underline the future perspective for diagnosis, stressing the importance of an integrated clinical and imaging approach, in order to identify this gynecological disease, so often underdiagnosed. SEARCH METHODS: PubMed and Google Scholar were searched for all original and review articles related to diagnosis of adenomyosis published in English until October 2018. OUTCOMES: The challenge in diagnosing adenomyosis starts with the controversies in the available pathogenic theories. The difficulties in understanding the way the disease arises and progresses have an impact also on the specific diagnostic criteria to use for a correct identification. Currently, the diagnosis of adenomyosis may be performed by non-invasive methods and the clinical signs and symptoms, despite their heterogeneity and poor specificity, may guide the clinician for a suspicion of the disease. Imaging techniques, including 2D and 3D US as well as MRI, allow the proper identification of the different phenotypes of adenomyosis (diffuse and/or focal). From a histological point of view, if the diagnosis of diffuse adenomyosis is straightforward, in more limited disease, the diagnosis has poor inter-observer reproducibility, leading to extreme variations in the prevalence of disease. Therefore, an integrated non-invasive diagnostic approach, considering risk factors profile, clinical symptoms, clinical examination and imaging, is proposed to adequately identify and characterise adenomyosis. WIDER IMPLICATIONS: The development of the diagnostic tools allows the physicians to make an accurate diagnosis of adenomyosis by means of non-invasive techniques, representing a major breakthrough, in the light of the clinical consequences of this disease. Furthermore, this technological improvement will open a new epidemiological scenario, identifying different groups of women, with a dissimilar clinical and/or imaging phenotypes of adenomyosis, and this should be object of future research.

Selective inhibition of TGFβ1 activation overcomes primary resistance to checkpoint blockade therapy by altering tumor immune landscape.

Wed, 25 Mar 2020 00:00:00 +0000

Despite breakthroughs achieved with cancer checkpoint blockade therapy (CBT), many patients do not respond to anti-programmed cell death-1 (PD-1) due to primary or acquired resistance. Human tumor profiling and preclinical studies in tumor models have recently uncovered transforming growth factor-β (TGFβ) signaling activity as a potential point of intervention to overcome primary resistance to CBT. However, the development of therapies targeting TGFβ signaling has been hindered by dose-limiting cardiotoxicities, possibly due to nonselective inhibition of multiple TGFβ isoforms. Analysis of mRNA expression data from The Cancer Genome Atlas revealed that TGFΒ1 is the most prevalent TGFβ isoform expressed in many types of human tumors, suggesting that TGFβ1 may be a key contributor to primary CBT resistance. To test whether selective TGFβ1 inhibition is sufficient to overcome CBT resistance, we generated a high-affinity, fully human antibody, SRK-181, that selectively binds to latent TGFβ1 and inhibits its activation. Coadministration of SRK-181-mIgG1 and an anti-PD-1 antibody in mice harboring syngeneic tumors refractory to anti-PD-1 treatment induced profound antitumor responses and survival benefit. Specific targeting of TGFβ1 was also effective in tumors expressing more than one TGFβ isoform. Combined SRK-181-mIgG1 and anti-PD-1 treatment resulted in increased intratumoral CD8+ T cells and decreased immunosuppressive myeloid cells. No cardiac valvulopathy was observed in a 4-week rat toxicology study with SRK-181, suggesting that selectively blocking TGFβ1 activation may avoid dose-limiting toxicities previously observed with pan-TGFβ inhibitors. These results establish a rationale for exploring selective TGFβ1 inhibition to overcome primary resistance to CBT.

Deep Infiltrating Endometriosis: a Previous History of Surgery for Endometriosis May Negatively Affect Assisted Reproductive Technology Outcomes.

Sat, 01 Feb 2020 00:00:00 +0000

For patients with endometriosis-related infertility, the impact of previous surgery for endometriosis before assisted reproductive technology (ART) remains controversial, particularly in cases of deep infiltrating endometriosis (DE). To study the impact of previous surgery for endometriosis on ART cumulative live-birth rates in DE patients, a retrospective cohort study included 222 DE patients who underwent ART. DE diagnosis was based on strict imaging criteria and histological confirmation of the disease for women with a previous history of surgery for endometriosis. ART outcomes were compared for patients with and without a previous history of surgery for endometriosis. The main outcome measures were cumulative live-birth rates (CLBR). Prognostic factors were identified by comparing women who became pregnant and those who did not, using an adjusted multiple logistic regression model. Two hundred twenty-two DE patients underwent a total of 440 ART cycles (including fresh and associated frozen-thawed embryo transfers). One hundred fifty-five women (69.8%) had a prior history of surgery for endometriosis. The CLBR was 26% after four ART cycles in the -‘previous history of surgery for endometriosis-’ group, while it reached 51.3% after four cycles (p < 0.001) in patients who had not previously undergone surgery for endometriosis. After multivariate analysis, a previous history of surgery for endometriosis (p = 0.001) and a past surgery for endometrioma (p = 0.005) were established as independent factors associated with lower pregnancy rates. Our preliminary results suggest that for DE patients, a previous history of surgery for endometriosis may be associated with negative ART outcomes.

High Levels of Anti-GM-CSF Antibodies in Deep Infiltrating Endometriosis.

Wed, 01 Jan 2020 00:00:00 +0000

Endometriosis is a chronic hormono-dependent inflammatory gynecological disease. Endometriosis can be subdivided into three forms: superficial peritoneal implants, endometrioma, and deep infiltrating endometriosis (DIE). Inflammation is a typical feature of endometriosis with overproduction of prostaglandins, chemokines, and cytokines, like granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is a hematopoietic growth factor and immune modulator which belongs to the group of cytokines that actively participate in inflammatory reactions. GM-CSF autoantibodies (Ab) are described in inflammatory diseases such as Crohn disease and ulcerative colitis where high concentrations of anti-GM-CSF Ab are correlated with severity, complications, and relapses. We have evaluated the presence of anti-GM-CSF Ab in the serum of 106 patients with endometriosis and 92 controls using a home-made enzyme-linked immunosorbent assay (ELISA) and correlated the results with the form and severity of the disease. We found that anti-GM-CSF Ab level is significantly increased in the sera of patients with endometriosis compared to controls and is associated with the severity of the disease especially in patients with deep endometriosis (p < 0.0001) with the highest number of lesions (p = 0.0034), including digestive involvement (p = 0.0041). We also found a correlation between these levels of anti-GM-CSF Ab and the number of lesions in DIE patients (r = 0.913). In this way, searching anti-GM-CSF Ab in endometriosis patient sera could be of value for patient follow-up and put further insight into the role of inflammation and of GM-CSF in endometriosis pathogenesis.

Superficial Peritoneal Endometriosis: Clinical Characteristics of 203 Confirmed Cases and 1292 Endometriosis-Free Controls.

Wed, 01 Jan 2020 00:00:00 +0000

The aim of this study was to characterize a large sample of women with superficial peritoneal endometriosis (SUP) and no other types of endometriosis in order to test the association of SUP with gynecologic symptoms. We included 203 cases of histologically proven SUP and 1292 endometriosis-free controls diagnosed between January 2004 and July 2017. The participants were non-pregnant patients aged 18 to 42 years submitted to a laparoscopy or laparotomy for a benign gynecologic condition. We excluded all cases of ovarian endometrioma, deep infiltrating endometriosis, and women who had previously undergone an endometriosis surgery. All patients underwent face-to-face interviews, thorough preoperative physical examination, and transvaginal ultrasound. Pain severity was assessed preoperatively through an 11-point numerical rating scale. The association of SUP with gynecologic symptoms was adjusted for potential confounders using multivariable logistic regression. The presence of SUP was associated with lower body weight (59.8 vs. 63.5 kg) and body mass index (21.8 vs. 23.3 kg/m2), and a higher frequency of smoking habit (41.6% vs. 32.8%) and of positive familial history of endometriosis (7.0% vs. 2.3%). Moreover, SUP was associated with an increased risk of primary infertility (adjusted prevalence ratio [PR] 1.83, 95% confidence interval [CI] 1.46-2.24), moderate to intense dysmenorrhea (PR 1.43, 95% CI 1.31-1.52), and moderate to intense deep dyspareunia (PR 1.50, 95% CI 1.25-1.75). In conclusion, in this large surgical series, isolated SUP was independently associated to primary infertility and moderate to severe painful symptoms.

The Ovarian Response After Follicular Versus Luteal Phase Stimulation with a Double Stimulation Strategy.

Wed, 01 Jan 2020 00:00:00 +0000

The double-ovarian stimulation strategy has been proposed to optimize the number of oocytes retrieved within the shortest possible timeframe. The objective of this study is to explore the effectiveness of luteal phase (LP) ovarian stimulation as compared to the previous follicular phase (FP) stimulation in a double stimulation strategy. We conducted an observational cohort study of women scheduled for a double stimulation protocol between March 2014 and June 2017, who had completed the FP controlled ovarian stimulation (COS 1) and started the LP stimulation (COS 2) in the same cycle. Women received equivalent daily doses of gonadotropins in combination with GnRH-antagonist protocol for both the COS 1 and the COS 2 performed during the same cycle. Ovulation was triggered using GnRH-agonist in the two stimulations. The primary outcome was the number of oocytes retrieved. A total of 77 patients were included in the analysis. The number of oocytes retrieved after COS 1 was significantly higher than after the COS 2 (5.25 ± 3.38 for COS 1 versus 3.83 ± 3.14 for COS 2; p = 0.001). The duration of the stimulation was significantly shorter, the total dose of injected gonadotropins was significantly lower, and the estradiol level on the trigger day was significantly higher with COS 1 as compared to COS 2. Stimulation during the LP in a double-successive stimulation strategy results in a lower ovarian response as compared to the FP equivalent daily dose stimulation.

Associated ileocaecal location is a marker for greater severity of low rectal endometriosis.

Sun, 01 Dec 2019 00:00:00 +0000

OBJECTIVE: To determine whether ileocaecal endometriosis (ICE) is a marker for low rectal endometriosis (LRE) severity. DESIGN: Retrospective cohort study. SETTING: France. POPULATION AND SAMPLE: Analysis of 375 colorectal resections performed in women undergoing complete surgery for LRE from January 1995 to December 2015 in a university centre for endometriosis. METHODS: Univariate and multivariate analysis of anatomical, postoperative clinical, and long-term outcomes according to presence of ICE. MAIN OUTCOMES AND MEASURES: Mean number and type of deep infiltrating endometriosis (DIE) lesions, the existence of an associated endometrioma, and mean total American Society for Reproductive Medicine (ASRM) score. RESULTS: The prevalence of ICE was 25.6%. Primary end-point data showed that women with ICE had a significantly higher adjusted number of DIE lesions (OR = 1.43, 95% CI 1.02-3.03; P = 0.048), higher prevalence of endometriomas (OR = 1.91, 95% CI 1.04-3.51; P = 0.044), more associated DIE sigmoid lesions (OR = 2.12, 95% CI 1.07-3.91; P = 0.025), and a higher mean total ASRM score (OR = 2.07, 95% CI 1.12-4.14; P = 0.025). Women with ICE resected during the surgical procedure for LRE did not have more adverse postoperative clinical outcomes than ICE-negative patients. CONCLUSION: Ileocaecal endometriosis was significantly associated with greater LRE severity. In a complete surgical resection strategy, combining resection of ICE and LRE did not appear to increase postoperative rates of complications, morbidity or recurrence, nor did it seem to impair long-term clinical outcomes. TWEETABLE ABSTRACT: In women with low rectal endometriosis, 25% have an associated ileocaecal location that is a marker for severity.

Rethinking mechanisms, diagnosis and management of endometriosis.

Fri, 01 Nov 2019 00:00:00 +0000

Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus, which causes pelvic pain and infertility. This disease should be viewed as a public health problem with a major effect on the quality of life of women as well as being a substantial economic burden. In light of the considerable progress with diagnostic imaging (for example, transvaginal ultrasound and MRI), exploratory laparoscopy should no longer be used to diagnose endometriotic lesions. Instead, diagnosis of endometriosis should be based on a structured process involving the combination of patient interviews, clinical examination and imaging. Notably, a diagnosis of endometriosis often leads to immediate surgery. Therefore, rethinking the diagnosis and management of endometriosis is warranted. Instead of assessing endometriosis on the day of the diagnosis, gynaecologists should consider the patient’s ’endometriosis life’. Medical treatment is the first-line therapeutic option for patients with pelvic pain and no desire for immediate pregnancy. In women with infertility, careful consideration should be made regarding whether to provide assisted reproductive technologies prior to performing endometriosis surgery. Modern endometriosis management should be individualized with a patient-centred, multi-modal and interdisciplinary integrated approach.

Magnetic resonance imaging presentation of deep infiltrating endometriosis nodules before and after pregnancy: A case series.

Fri, 04 Oct 2019 00:00:00 +0000

OBJECTIVE: To compare the magnetic resonance imaging (MRI) features of deep infiltrating endometriosis (DIE) lesions before and after pregnancy. DESIGN: Retrospective study. SETTING: A single French university tertiary referral hospital. PATIENTS: Twenty-one women without a prior history of surgery for endometriosis with a radiological diagnosis by MRI with two sets of examinations performed before and after pregnancy. INTERVENTIONS: The volumes of the lesions were compared using the same protocol before and after pregnancy based on MRI (1.5 T) examinations by a single experienced radiologist who is a referring practitioner for image-based diagnosis of endometriosis. MAIN OUTCOME MEASURE(S): The DIE lesion volume. MEASUREMENTS AND MAIN RESULTS: Between October 2012 and December 2016, a total of 21 patients (67 lesions) were included and compared before and after pregnancy. The mean time interval between the MRI before pregnancy and delivery was 19.6 ± 8.5 months (median: 17.6, IQR 13.5-25.2 months). The mean time interval between delivery and the MRI after pregnancy was 11.0 ± 6.4 months (median: 8.3, IQR 6-15.2 months). The mean overall DIE lesion volume by MRI was significantly higher before pregnancy compared to after pregnancy (2,552 ± 3,315 mm3 vs. 1,708 ± 3,266 mm3, respectively, p < 0.01). The mean volume by MRI of the largest lesion of each patient was significantly higher before pregnancy compared to after pregnancy (4,728 ± 4,776 mm3 vs. 3165 ± 5299 mm3; p < 0.01). CONCLUSION: Our data indicate a favorable impact of pregnancy on DIE lesion volumes as measured by MRI.

The Deferred Embryo Transfer Strategy Seems Not to be a Good Option After Repeated IVF/ICSI Cycle Failures.

Sun, 01 Sep 2019 00:00:00 +0000

OBJECTIVE: The aim of this study was to assess whether a deferred frozen-thawed embryo transfer (Def-ET) offers any benefits compared to a fresh ET strategy in women who have had 2 or more consecutive in vitro fertilization (IVF)/intracytoplasmic injection (ICSI) cycle failures. DESIGN: An observational cohort study in a tertiary referral care center including 416 cycles from women with a previous history of 2 or more consecutive IVF/ICSI failures cycles. Both Def-ET and fresh ET strategies were compared using univariate and multivariate logistic regression models. The main outcome measured was the cumulative live birth rate (CLBR). RESULTS: A total of 416 cycles were included in the analysis: 197 in the fresh ET group and 219 in the Def-ET group. The CLBR was not significantly different between the fresh and Def-ET groups (58/197 [29.4%] and 57/219 [26.0%], respectively, P = .437). In addition, after the first ET, there was no significant difference in the live birth rate between the fresh ET and Def-ET groups (50/197 [25.4%] vs 44/219 [20.1%], respectively). Multivariate logistic regression analysis indicated that compared to the fresh strategy, the Def-ET strategy was not associated with a higher probability of live birth. CONCLUSIONS: In cases with 2 or more consecutive prior IVF/ICSI cycle failures, a Def-ET strategy did not result in better ART outcomes than a fresh ET strategy.

Age at menarche does not correlate with the endometriosis phenotype.

Tue, 23 Jul 2019 00:00:00 +0000

OBJECTIVE: To evaluate the association between the endometriosis phenotype and the age at menarche. DESIGN: An observational, cross-sectional study using prospectively collected data (Canadian Task Force classification II-2). SETTING: Single university tertiary referral center. PATIENTS: To be eligible, women had to have undergone their 1st complete surgical exeresis of endometriotic lesions. For each patient, a standardized questionnaire was completed the month before the surgery. Endometriotic lesions were classified into 3 phenotypes: superficial peritoneal endometriosis (SUP), endometrioma (OMA), or deep infiltrating endometriosis (DIE). Patients were divided into 3 groups: early menarche (< 12 years), typical menarche (≥ 12 and ≤ 13 years) and late menarche (> 13 years). The groups were compared in terms of general characteristics, medical history, disease phenotype, and disease severity. INTERVENTIONS: Surgical management for a benign gynecologic condition. MAIN OUTCOME MEASURE(S): Correlation between the endometriosis phenotype and the age at menarche. MEASUREMENTS AND MAIN RESULTS: From January 2004 to December 2016, 789 women with histologically confirmed endometriosis were enrolled in the study. The mean age at menarche was 12.9 ± 1.6 years of age, (range 9 to 18). The mean age at menarche and the mean time interval between menarche and the 1st surgery for endometriosis were not significantly different between the three phenotypes (SUP, OMA, DIE). When women with early menarche, typical menarche, or late menarche were compared, no differences were observed in terms of the endometriosis phenotype and the anatomical distribution of the endometriotic lesions. CONCLUSION: For women operated for the first time for endometriosis, age at menarche is not associated with the disease phenotype.

B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice.

Mon, 08 Jul 2019 00:00:00 +0000

STUDY QUESTION: What are the effects of B lymphocyte inactivation or depletion on the progression of endometriosis? SUMMARY ANSWER: Skewing activated B cells toward regulatory B cells (Bregs) by Bruton’s tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect. WHAT IS KNOWN ALREADY: A polyclonal activation of B cells and the presence of anti-endometrial autoantibodies have been described in a large proportion of women with endometriosis though their exact role in the disease mechanisms remains unclear. STUDY DESIGN, SIZE, DURATION: This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation. PARTICIPANTS/MATERIALS, SETTING, METHODS: After syngeneic endometrial transplantation, murine endometriotic lesions were compared between treated and control mice using volume, weight, ultrasonography, histology and target genes expression in lesions. Phenotyping of activated and regulatory B cells, T lymphocytes and macrophages was performed by flow cytometry on isolated spleen and peritoneal cells. Cytokines were assayed by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis. In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinib-treated mice compared to anti-CD20 and control mice. Depletion of B cells using an anti-CD20 antibody had no effect on activity and growth of endometriotic lesions and neither on the macrophages, compared to control mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: It is still unclear whether B cell depletion by the anti-CD20 or inactivation by Ibrutinib can prevent establishment and/or progression of endometriosis in humans. WIDER IMPLICATIONS OF THE FINDINGS: Further investigation may contribute to clarifying the role of B cell subsets in human endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant of Institut National de la Santé et de la Recherche Médicale and Paris Descartes University. None of the authors has any conflict of interest to disclose.

Role of thyroid dysimmunity and thyroid hormones in endometriosis.

Tue, 11 Jun 2019 00:00:00 +0000

Endometriosis is characterized by the presence of ectopic endometrial cells outside the uterine cavity. Thyroid autoimmunity has been associated with endometriosis. This work investigated the potential pathophysiological link between endometriosis and thyroid disorders. Transcripts and proteins involved in thyroid metabolism are dysregulated in eutopic and ectopic endometrium of endometriotic patients, leading to resistance of ectopic endometrium to triiodothyronine (T3) action and local accumulation of thyroxine (T4). Thyroid-stimulating hormone (TSH) acts as a proliferative and prooxidative hormone on all endometria of endometriosis patients and controls, whereas T3 and T4 act to specifically increase ectopic endometrial cell proliferation and reactive oxygen species (ROS) production. Mouse studies confirmed the data gained in vitro since endometriotic implants were found to be bigger when thyroid hormones increased. A retrospective analysis of endometriosis patients with or without a thyroid disorder revealed an increased chronic pelvic pain and disease score in endometriotic patients with a thyroid disorder.

Serum antimüllerian hormone concentration increases with ovarian endometrioma size.

Wed, 01 May 2019 00:00:00 +0000

OBJECTIVE: To examine whether serum antimüllerian hormone (AMH) levels correlate with the size of ovarian endometrioma (OMA). DESIGN: An observational cross-sectional study. SETTING: University hospital. PATIENT(S): Two hundred and sixty-seven nonpregnant women, aged 18-42 years, with no prior history of surgery for endometriosis and a histologically documented ovarian cyst. INTERVENTION(S): Surgical management for a benign ovarian cyst. MAIN OUTCOME MEASURE(S): Correlation between serum AMH concentration and cyst size according to OMA and non-OMA benign cyst. RESULT(S): Women with OMA were compared with a control group of women who had non-OMA benign ovarian cysts. The AMH assay samples were collected less than a month before the surgery. Between January 2004 and September 2016, 148 women were allocated to the OMA group and 119 to the non-OMA benign cyst group. The AMH concentrations were not statistically significantly different between the two groups (3.7 ± 2.8 ng/mL vs. 4.1 ± 3.3 ng/mL). A multiple linear regression model accounting for potential confounders revealed that the log10 of the serum AMH concentration positively correlated with the log10 of the OMA cyst volume (R2 = 0.23; coefficient = 0.05; 95% CI, 0.007-0.10). CONCLUSION(S): In women no prior history of surgery for endometriosis, serum AMH levels increased with cyst size in cases of OMA.

Clinical diagnosis of endometriosis: a call to action.

Mon, 01 Apr 2019 00:00:00 +0000

Endometriosis can have a profound impact on women’s lives, including associated pain, infertility, decreased quality of life, and interference with daily life, relationships, and livelihood. The first step in alleviating these adverse sequelae is to diagnose the underlying condition. For many women, the journey to endometriosis diagnosis is long and fraught with barriers and misdiagnoses. Inherent challenges include a gold standard based on an invasive surgical procedure (laparoscopy) and diverse symptomatology, contributing to the well-established delay of 4-11 years from first symptom onset to surgical diagnosis. We believe that remedying the diagnostic delay requires increased patient education and timely referral to a women’s healthcare provider and a shift in physician approach to the disorder. Endometriosis should be approached as a chronic, systemic, inflammatory, and heterogeneous disease that presents with symptoms of pelvic pain and/or infertility, rather than focusing primarily on surgical findings and pelvic lesions. Using this approach, symptoms, signs, and clinical findings of endometriosis are anticipated to become the main drivers of clinical diagnosis and earlier intervention. Combining these factors into a practical algorithm is expected to simplify endometriosis diagnosis and make the process accessible to more clinicians and patients, culminating in earlier effective management. The time has come to bridge disparities and to minimize delays in endometriosis diagnosis and treatment for the benefit of women worldwide.

Reduced α-2,6 sialylation regulates cell migration in endometriosis.

Fri, 01 Mar 2019 00:00:00 +0000

STUDY QUESTION: Is endometriosis associated with aberrant sialylation patterns and what is the potential impact of such anomalies on cell migratory properties? SUMMARY ANSWER: The reduced α-2,6 sialylation patterns in the peritoneal fluid of endometriosis-affected women and in stromal and epithelial cells from endometriotic lesions could be associated with enhanced cell migration. WHAT IS KNOWN ALREADY: Endometriosis is considered to be a benign disease although, like cancer, it has the characteristic of being an invasive disease with cells that have an enhanced capacity to migrate. Aberrant sialylation has been reported in various malignancies and it has been linked to tumour invasion and metastasis. STUDY DESIGN, SIZE, DURATION: We conducted a prospective laboratory study in a tertiary-care university hospital. We investigated non-pregnant patients who were <42 years of age (n = 273) when they underwent surgery for a benign gynaecological condition. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population consisted of 102 women with histologically proven endometriosis and 71 endometriosis-free controls, who underwent a complete surgical exploration of the abdominopelvic cavity. Peritoneal fluids were collected during the surgical procedures, and endometrial and endometriotic biopsies were performed on all of the patients to generate stromal and epithelial primary cell cultures. The expression of α-2,6-sialyltransferase (ST6GALNAC1) was studied in eutopic and ectopic endometria of endometriosis patients and in eutopic endometria of controls by reverse transcription followed by quantitative real-time polymerase chain reaction (RT-qPCR). The α-2,6 sialylation levels were measured by ELISA in the peritoneal fluids of patients and controls and by western-blot in primary endometrial and endometriotic cell cultures using Sambucus nigra agglutinin (SNA), an α-2,6 sialic acid-binding lectin. A transwell migration assay after incubation of the cells with neuraminidase was also performed to evaluate the impact of desialylation on eutopic endometrial stromal cell migration. MAIN RESULTS AND THE ROLE OF CHANCE: ST6GALNAC1 gene expression was significantly lower in endometriotic lesions compared to that in eutopic endometrium of endometriosis-affected patients and healthy endometrium (16-fold for both; P < 0.01). We observed a significant reduction in SNA levels in the peritoneal fluids of endometriosis-affected women compared to control women (median optic density (OD), 0.257; range, 0.215-0.279 versus median OD, 0.278; range 0.238-0.285; P < 0.01), as well as in stromal (mean OD, 705 907; standard error of the mean (SEM), 141 549 versus mean OD, 1.16 × 106; SEM, 107,271; P < 0.05) and epithelial (mean OD, 485 706; SEM, 179 681 versus mean OD, 1.25 × 106; SEM, 232 120; P < 0.05) ectopic endometriotic cells compared to control eutopic cells, indicating reduced α-2,6 sialylation. Finally, in the transwell migration assay, the eutopic endometrial cells of endometriosis patients migrated significantly more into the lower chamber after incubation with neuraminidase, indicating enhanced migration by these cells after desialylation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Our control group involved patients operated for benign gynaecological conditions (e.g. tubal infertility, uterine fibroids or ovarian cysts) which may also be associated with altered sialylation patterns. WIDER IMPLICATIONS OF THE FINDINGS: The hyposialylation pattern of endometriotic cells appeared to be associated with enhanced migratory abilities, which might contribute to the establishment of early endometriotic implants. Further research is needed to confirm these findings, as this could lead to new potential therapeutic targets for this complex disorder. STUDY FUNDING AND COMPETING INTEREST(S): No external funding was received and there are no conflicts of interest.

The Disease Phenotype of Adenomyosis-Affected Women Correlates With Specific Serum Cytokine Profiles.

Fri, 01 Feb 2019 00:00:00 +0000

BACKGROUND: Adenomyosis (ADE) is an enigmatic uterine disorder. Several types have been previously described: diffuse adenomyosis (DIF-ADE), focal adenomyosis (FOC-ADE), and association of focal and diffuse lesions (FOC/DIF-ADE). Abnormal immune phenomena have been described that may provide an understanding of the pathophysiology of adenomyosis. However, the immune imbalance in adenomyosis is however still poorly understood. OBJECTIVE: To compare serum cytokine profiles for the various adenomyosis phenotypes in adenomyosis versus disease-free women. MATERIALS AND METHODS: This cohort study included 80 women. Based on the magnetic resonance imaging (MRI) findings, the women were allocated to the ADE group (n = 60) and the control group (n = 20). The ADE group was further subdivided according to the phenotype: DIF-ADE, FOC-ADE, and FOC/DIF-ADE. For all of the women, serum cytokine levels were assayed by multiplex immunoassay. RESULTS: Serum levels of interleukin (IL) 23 (237.77 pg/mL ± 70.97 in the ADE-group versus 1855.04 ± 1411.33 in the control group, P = .019), IL25 (31.98 ± 8.54 vs 222.08 ± 170.90, respectively, P = .006), IL31 (10.13 ± 3.83 vs 91.51 ± 71.21, respectively, P = .034), IL33 (3.77 ± 1.23 vs 17.86 ± 11.49, respectively, P = .016), and IL17F (16.29 ± 2.35 vs 30.12 ± 8.29, respectively, P = .042) were significantly lower in the women with adenomyosis when compared to the controls In the FOC/DIF-ADE group, the serum levels of IL23, IL31, IL25, and IL33 were significantly lower when compared to the control group. CONCLUSION: Serum levels of IL23, IL31, IL25, and IL33 were lower in women exhibiting adenomyosis forms with associated diffuse and focal lesions when compared with controls. The pathogenesis of adenomyosis may be associated with an immunotolerant process that is more pronounced in associated FOC/DIF-ADE.

Factors associated with deep infiltrating endometriosis versus ovarian endometrioma in China: a subgroup analysis from the FEELING study.

Sat, 22 Dec 2018 00:00:00 +0000

BACKGROUND: To compare potential factors associated with deep infiltrating endometriosis (DIE) versus ovarian endometrioma (OMA) among endometriosis patients in China. METHODS: A subgroup analysis of factors associated with DIE versus OMA was performed in Chinese women from the FEELING study. This study included 156 OMA patients and 78 DIE patients. Retrospective information on symptoms and previous medical history was collected via face-to-face interviews; patients also completed a questionnaire to provide information on current habits. Univariate and multivariate logistic regression analyses were conducted to identify potential factors that are associated with DIE versus OMA. RESULTS: From univariate analysis, women who were married, at older age, had any siblings, prior pregnancy, or longer time since age at menarche on the day of visit were more likely to be diagnosed with DIE (P < 0.05). Also, the incidence of previous uterine surgery, menstrual and ovulatory disorders, deep dyspareunia, and gastrointestinal symptoms during menstruation were major factors that were significantly associated with the diagnosis of DIE (P < 0.05). Multivariate analysis showed that women with any siblings, gastrointestinal symptoms during menstruation, or eating a greater number of fruit/vegetables per day were more likely to be diagnosed with DIE. Meanwhile, eating organic food and experiencing stress were major factors that are associated with the diagnosis of OMA. CONCLUSIONS: The findings provide additional information on the potential risk factors that are associated with DIE, compared with OMA among Chinese endometriosis patients. The results may help to better understand DIE versus OMA, and aid in earlier risk stratification and diagnosis of the patients. TRIAL REGISTRATION: NCT01351051 . Registered 10 May 2011.

Ovarian endometriosis and infertility: in vitro fertilization (IVF) or surgery as the first approach?

Sat, 01 Dec 2018 00:00:00 +0000

The interval between oocyte retrieval and frozen-thawed blastocyst transfer does not affect the live birth rate and obstetrical outcomes.

Fri, 19 Oct 2018 00:00:00 +0000

BACKGROUND: The ‘Freeze all’ strategy, which consists of cryopreservation of all embryos after the ovarian stimulation has undergone extensive development in the past decade. The time required for the endometrium to revert to a prestimulation state after ovarian stimulation and thus the optimal time to perform a deferred embryo transfer after the stimulation has not been determined yet. OBJECTIVE: To investigate the impact of the time from oocyte retrieval to frozen-thawed blastocyst transfer (FBT) on live birth rate (LBR), obstetrical and neonatal outcomes, in ‘Freeze-all’ cycle. MATERIALS AND METHODS: We conducted a large observational cohort study in a tertiary care university hospital including four hundred and seventy-four first autologous FBT performed after ovarian stimulation in ‘freeze all’ cycles. Reproductive outcomes were compared between FBT performed within the first menstrual cycle after the oocyte retrieval (‘cycle 1’ group) or delayed FBT (‘cycle ≥ 2’ group). The main Outcome Measure was the Live birth rate. RESULT(S): A total of 188 FBT were included in the analysis in the ‘cycle 1’ group and 286 in the ‘cycle ≥ 2’ group. No significant differences were found between FBT performed within the first menstrual cycle after oocyte retrieval (the ‘cycle 1’ group) and delayed FBT (the ‘cycle ≥ 2’ group) in terms of the live birth rate [59/188 (31.38%) vs. 85/286 (29.72%); p = 0.696] and the miscarriage rate [20/82 (24.39%) vs. 37/125 (29.60%), respectively; p = 0.413]. The obstetrical and neonatal outcomes were also not significantly different between the two groups. CONCLUSION: Our study did not detect statistically significant differences in the LBR for FBT performed within the first menstrual cycle after oocyte retrieval versus FBT following subsequent cycles. Embryo-endometrium interaction after a FBT does not appear to be impaired by potential adverse effects of COS whatever the number of cycle between oocyte retrieval and embryo transfer.

Leiomyomatous uterus and preterm birth: an exposed/unexposed monocentric cohort study.

Mon, 01 Oct 2018 00:00:00 +0000

BACKGROUND: The risk of preterm birth may increase in the presence of uterine leiomyomas during pregnancy. Whether myomectomy abrogates this risk has never been studied. OBJECTIVE: Our aim was to evaluate the association between the presence of uterine leiomyomas during pregnancy and preterm birth and, if an association exists, to evaluate its persistence in case of a history of myomectomy. STUDY DESIGN: This exposed/unexposed monocentric retrospective cohort study included all women with singleton pregnancies delivering >22 weeks in a tertiary university hospital maternity unit from January 2011 through September 2015. Women with a leiomyomatous uterus were compared to women with no myomas. Women in the leiomyomatous uterus group were women with uterine leiomyoma(s) during pregnancy (≥1 leiomyoma, measuring ≥20 mm or multiple leiomyomas whatever the size) seen on at least 1 obstetric ultrasound without history of myomectomy, or women with a history of myomectomy (removal of ≥1 leiomyoma, measuring ≥20 mm or multiple leiomyomas whatever the size) by hysteroscopy, laparoscopy, or laparotomy with or without persistent leiomyomas. The association between leiomyomatous uterus and preterm birth was assessed through univariate and multivariable logistic regression. RESULTS: Among the 19,866 women in the cohort, 301 (1.5%) had a leiomyomatous uterus (154 unoperated women and 147 operated women). The rate of premature delivery was 12.0% in the leiomyomatous uterus group and 8.4% in the nonleiomyomatous uterus group. After adjusting for the risk factors for preterm birth, leiomyomatous uterus was significantly associated with preterm birth (adjusted odds ratio, 2.5; 95% confidence interval, 1.7-3.7). This association was significant for unoperated women (adjusted odds ratio, 2.7; 95% confidence interval, 1.6-4.6) as well as operated women (adjusted odds ratio, 2.3; 95% confidence interval, 1.3-3.9) when compared to the nonleiomyomatous uterus group. CONCLUSION: Uterine leiomyomas are associated with preterm birth and this association persists after myomectomy.

Oligo-anovulation is not a rarer feature in women with documented endometriosis.

Mon, 01 Oct 2018 00:00:00 +0000

OBJECTIVE: To study the prevalence of oligo-anovulation in women suffering from endometriosis compared to that of women without endometriosis. DESIGN: A single-center, cross-sectional study. SETTING: University hospital-based research center. PATIENT (S): We included 354 women with histologically proven endometriosis and 474 women in whom endometriosis was surgically ruled out between 2004 and 2016. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Frequency of oligo-anovulation in women with endometriosis as compared to that prevailing in the disease-free reference group. RESULTS: There was no difference in the rate of oligo-anovulation between women with endometriosis (15.0%) and the reference group (11.2%). Regarding the endometriosis phenotype, oligo-anovulation was reported in 12 (18.2%) superficial peritoneal endometriosis, 12 (10.6%) ovarian endometrioma, and 29 (16.6%) deep infiltrating endometriosis. CONCLUSION(S): Endometriosis should not be discounted in women presenting with oligo-anovulation.

Shedding light on the fertility preservation debate in women with endometriosis: a swot analysis.

Mon, 01 Oct 2018 00:00:00 +0000

Endometriosis, a hormone-dependant condition affecting around 10% of women in their reproductive years, has frequent consequences on fertility. Indeed, a proportion of women will require assisted reproductive techniques or surgery in order to achieve pregnancy. Recent refining of stimulation protocols and vitrification techniques has created new possibilities in the field of fertility preservation. As a consequence, oocyte vitrification is now discussed not only in oncologic situations, but also in other conditions at risk of altered ovarian reserve and poor fertility outcome. In endometriosis, various mechanisms can impair ovarian function and diminish ovarian, particularly bilateral or repeated cystectomy. Fertility preservation could represent an option for women with endometriosis but still remains controversial. In order to shed some light on this complex subject and to outline different issues at stake we conducted a SWOT analysis highlighting strengths, weaknesses, opportunities and threats of oocyte vitrification in women with endometriosis.

Endometriosis and ART: A prior history of surgery for OMA is associated with a poor ovarian response to hyperstimulation.

Mon, 20 Aug 2018 00:00:00 +0000

BACKGROUND: Many women whose fertility may have been impaired by endometriosis require assisted reproductive technology (ART) in order to become pregnant. However, the influence of ovarian endometriosis (OMA) on ovarian responsiveness to hyperstimulation has not been clearly established. OBJECTIVE: To evaluate the risk of a poor ovarian response (POR) to stimulation and ART outcomes in women with OMA. MATERIALS AND METHODS: We conducted a large observational controlled matched cohort study in a tertiary care university hospital between 01/10/2012 and 31/12/2015. After matching by age and anti-Müllerian hormone (AMH) levels, 201 infertile women afflicted with OMA (the OMA group) and 402 disease-free women (the control group) undergoing an ART procedure were included in the study. The main outcomes that we measured were a POR to hyperstimulation (i.e., ≤ 3 oocytes retrieved, or cancelled cycles), the clinical pregnancy rate, and the live birth rate. All of the women with endometriosis underwent a pre-ART work-up, in order to obtain an accurate diagnosis and staging of their disease. An OMA diagnosis was based on published imaging criteria (obtained by transvaginal sonography or magnetic resonance imaging) or on histological analysis for patients with a prior history of endometriosis surgery. The statistical analyses were conducted using univariate and multivariate logistic regression models. RESULTS: The incidence of a POR to hyperstimulation was significantly higher for the OMA group than for the control group [62/201 (30.8%) versus 90/402 (22.3%), respectively; p = 0.02]. However, no significant differences were found between the OMA and the control group in terms of the clinical pregnancy rate [53/151 (35%) versus 134/324 (41.3%), respectively; p = 0.23] and the live birth rate [39/151 (25.8%) versus 99/324 (30.5%), respectively; p = 0.33]. By multivariate analysis, a prior history of surgery for OMA was found to be an independent factor associated with a POR to stimulation [OR = 2.1; 95% CI: 1.1-4.0], unlike OMA without a prior history of surgery [OR: 1.5; 95% CI: 0.9-2.2]. CONCLUSION: The presence of OMA during ART treatment increased the risk of a POR to hyperstimulation, although the live birth rate was not affected. Furthermore, having OMA and having previously undergone surgery for OMA was identified as an independent risk factor for a POR.

Anterior Focal Adenomyosis and Bladder Deep Infiltrating Endometriosis: Is There a Link?

Sun, 01 Jul 2018 00:00:00 +0000

STUDY OBJECTIVE: To evaluate the association between bladder deep infiltrating endometriosis (DIE) and anterior focal adenomyosis of the outer myometrium (aFAOM) diagnosed by preoperative magnetic resonance imaging (MRI). DESIGN: An observational, cross-sectional study using prospectively collected data (Canadian Task Force classification II-2). SETTING: Single university tertiary referral center. PATIENTS: All nonpregnant women younger than 42 years who had undergone complete surgical exeresis of endometriotic lesions. For each patient a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding the surgery. Only women with preoperative standardized uterine MRI were retained for this study. INTERVENTIONS: Thirty-nine women with histologically proven bladder DIE and an available preoperative MRI were enrolled in the study. Patients were divided into 2 groups: women with aFAOM (aFAOM (+), n = 19) and women without aFAOM (aFAOM (-), n = 20). Both groups were compared for general characteristics, medical history, MRI findings, and disease severity. MEASUREMENTS AND MAIN RESULTS: Nineteen patients (48.7%) with bladder DIE had aFAOM at preoperative MRI. The rate of associated diffuse adenomyosis was similar in the 2 groups (63.2% [n = 12] vs 73.7% [n = 14]; p = .48). The rate of an associated ovarian endometrioma (OMA) was significantly lower in the aFAOM (+) group (10.5% [n = 2] vs 40.0% [n = 8]; p = .03). There were fewer associated intestinal DIE lesions in the aFAOM (+) group compared with the aFAOM (-) group (26.3% vs 75.0%; p = .02), with lower involvement of the pouch of Douglas (26.3% vs 70%; p < .01). Total American Society for Reproductive Medicine score was significantly lower in the aFAOM (+) group (13.8 ± 12.2 vs 62.2 ± 46.2; p < .01). CONCLUSION: aFAOM is present in only half of women with bladder DIE and appears to be associated with lower associated posterior DIE.

Immunology of endometriosis.

Sun, 01 Jul 2018 00:00:00 +0000

The pathophysiology of endometriosis is not completely understood, but an aberrant immune response in the peritoneal environment seems to be crucial for the proliferation of ectopic endometrial cells - as those cells escape apoptosis and peritoneal cavity immunosurveillance. The growth of endometrial implants leads to the recruitment of a large number and diversity of immune cells and intense inflammation with increased pro-inflammatory cytokines, growth factors, and angiogenesis. There is substantial evidence of aberrant function of almost all types of immune cells in women with endometriosis: decreased T cell reactivity and NK cytotoxicity, polyclonal activation of B cells and increased antibody production, increased number and activation of peritoneal macrophages, and changes in inflammatory mediators. New clinical treatments for endometriosis are an urgent need, especially nonhormonal drugs. The study of immunology may clarify its role in the pathogenesis of endometriosis and contribute to the development of new therapeutic strategies.

Prolonged estrogen (E2) treatment prior to frozen-blastocyst transfer decreases the live birth rate.

Tue, 01 May 2018 00:00:00 +0000

STUDY QUESTION: How does the duration of estrogen (E2) treatment prior to frozen-blastocyst transfers affect the live birth rate (LBR)? SUMMARY ANSWER: Prolonged E2 exposure as part of artificial endometrial preparation (AEP) significantly decreases the LBR after autologous frozen-thawed blastocyst transfer. WHAT IS KNOWN ALREADY: One effective method for endometrial preparation prior to frozen embryo transfer is AEP, a sequential regimen with E2 and progesterone, which aims to mimic the endocrine exposure of the endometrium in a normal cycle. Nevertheless, the optimal duration of E2 administration prior to transfer remains unknown. STUDY DESIGN, SIZE, DURATION: An observational cohort study was conducted in a tertiary care university hospital between 01/07/2012 and 31/12/2015. The main inclusion criteria was having a single frozen-thawed blastocyst transfer with an AEP using exogenous E2. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1377 frozen-thawed blastocyst transfers were assigned to four groups according to the duration of the E2 administration prior to the embryo transfers. These comprised a ‘≤21 days’ group (n = 330), a ‘22-28 days’ group (n = 665), a ‘29-35 days’ group (n = 289) and a ‘36-48 days’ group (n = 93). The ‘≤21 days’ group’ was taken as the reference group. The main measured outcome was the LBR following frozen-thawed blastocyst transfers. Statistical analysis was conducted using univariate and multivariate logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE: LBR significantly decreased when the E2 exposure prior to the frozen-thawed blastocyst transfer exceeded 28 days: OR = 0.66; 95% CI [0.46-0.95]; P = 0.026 and OR = 0.49 [0.27-0.89]; P = 0.018, respectively, for the ‘29 to 35 days’ group and for the ‘36 to 48 days’ group compared to the reference group. Early pregnancy loss rates significantly increased when the E2 exposure lasted more than 35 days prior to the frozen-thawed blastocyst transfer (OR = 2.37 [1.12-5.05]; P = 0.025 vs. the reference group). After multivariate logistic regression, E2 exposure lasting more than 28 days prior to the frozen-thawed blastocyst transfer was associated with a decrease in the LBR, for the ‘29-35 days’ group (OR = 0.65; [0.45-0.95]; P = 0.044) as for the ‘36-48 days’ group (OR = 0.49; [0.26-0.92]; P = 0.035), vs. the reference group. LIMITATIONS, REASONS FOR CAUTION: One limitation is linked to the observational design of this study. WIDER IMPLICATIONS OF THE FINDINGS: In order to give patients the best chance to obtain a live birth after frozen-thawed blastocyst transfer, the length of E2 exposure prior to the frozen-blastocyst transfer should not exceed 28 days. This study provides new insight in regard to endometrial preparation using AEP prior to frozen-blastocyst transfer. STUDY FUNDING/COMPETING INTEREST(S): No funding and no competing interest.

The definition of Endometriosis Expert Centres.

Tue, 01 May 2018 00:00:00 +0000

Endometriosis is a common condition that causes pain and infertility. It can lead to absenteeism and also to multiple surgeries with a consequent risk of impaired fertility, and constitutes a major public health cost. Despite the existence of numerous national and international guidelines, the management of endometriosis remains suboptimal. To address this issue, the French College of Gynaecologists and Obstetricians (CNGOF) and the Society of Gynaecological and Pelvic Surgery (SCGP) convened a committee of experts tasked with defining the criteria for establishing a system of care networks, headed by Expert Centres, covering all of mainland France and its overseas territories. This document sets out the criteria for the designation of Expert Centres. It will serve as a guide for the authorities concerned, to ensure that the means are provided to adequately manage patients with endometriosis.

The deferred embryo transfer strategy improves cumulative pregnancy rates in endometriosis-related infertility: A retrospective matched cohort study.

Mon, 09 Apr 2018 00:00:00 +0000

BACKGROUND: Controlled ovarian stimulation in assisted reproduction technology (ART) may alters endometrial receptivity by an advancement of endometrial development. Recently, technical improvements in vitrification make deferred frozen-thawed embryo transfer (Def-ET) a feasible alternative to fresh embryo transfer (ET). In endometriosis-related infertility the eutopic endometrium is abnormal and its functional alterations are seen as likely to alter the quality of endometrial receptivity. One question in the endometriosis ART-management is to know whether Def-ET could restore optimal receptivity in endometriosis-affected women leading to increase in pregnancy rates. OBJECTIVE: To compare cumulative ART-outcomes between fresh versus Def-ET in endometriosis-infertile women. MATERIALS AND METHODS: This matched cohort study compared def-ET strategy to fresh ET strategy between 01/10/2012 and 31/12/2014. One hundred and thirty-five endometriosis-affected women with a scheduled def-ET cycle and 424 endometriosis-affected women with a scheduled fresh ET cycle were eligible for matching. Matching criteria were: age, number of prior ART cycles, and endometriosis phenotype. Statistical analyses were conducted using univariable and multivariable logistic regression models. RESULTS: 135 in the fresh ET group and 135 in the def-ET group were included in the analysis. The cumulative clinical pregnancy rate was significantly increased in the def-ET group compared to the fresh ET group [58 (43%) vs. 40 (29.6%), p = 0.047]. The cumulative ongoing pregnancy rate was 34.8% (n = 47) and 17.8% (n = 24) respectively in the Def-ET and the fresh-ET groups (p = 0.005). After multivariable conditional logistic regression analysis, Def-ET was associated with a significant increase in the cumulative ongoing pregnancy rate as compared to fresh ET (OR = 1.76, CI95% 1.06-2.92, p = 0.028). CONCLUSION: Def-ET in endometriosis-affected women was associated with significantly higher cumulative ongoing pregnancy rates. Our preliminary results suggest that Def-ET for endometriosis-affected women is an attractive option that could increase their ART success rates. Future studies, with a randomized design, should be conducted to further confirm those results.

[Definition of endometriosis expert centres].

Thu, 01 Mar 2018 00:00:00 +0000

OBJECTIVES: The Collège national des gynécologues obstétriciens français (CNGOF), in agreement with the Société de chirurgie gynécologique et pelvienne (SCGP), has set up a commission in 2017 to define endometriosis expert centres, with the aim of optimizing endometriosis care in France. METHODS: The committee included members from university and general hospitals as well as private facilities, representing medical, surgical and radiological aspects of endometriosis care. Opinion of endometriosis patients’ associations was obtained prior to writing this work. The final text was presented and unanimously validated by the members of the CNGOF Board of Directors at its meeting of October 13, 2017. RESULTS: Based on analysis of current management of endometriosis and the last ten years opportunities in France, the committee has been able to define the contours of endometriosis expert centres. The objectives, production specifications, mode of operation, missions and funding for these centres were described. The following missions have been specifically defined: territorial organization, global and referral care, communication and teaching as well as research and evaluation. CONCLUSION: Because of its daily impact for women and its economic burden in France, endometriosis justifies launching of expert centres throughout the country with formal accreditation by health authorities, ideally as part of the National Health Plan.

[Definition, description, clinicopathological features, pathogenesis and natural history of endometriosis: CNGOF-HAS Endometriosis Guidelines].

Thu, 01 Mar 2018 00:00:00 +0000

Endometriosis and adenomyosis are histologically defined. The frequency of endometriosis cannot be precisely estimated in the general population. Endometriosis is considered a disease when it causes pain and/or infertility. Endometriosis is a heterogeneous disease with three well-recognized subtypes that are often associated with each other: superficial endometriosis (SUP), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). DIE is frequently multifocal and mainly affects the following structures: the uterosacral ligaments, the posterior vaginal cul-de-sac, the bladder, the ureters, and the digestive tract (rectum, recto-sigmoid junction, appendix). The role of menstrual reflux in the pathophysiology of endometriosis is major and explains the asymmetric distribution of lesions, which predominate in the posterior compartment of the pelvis and on the left (NP3). All factors favoring menstrual reflux increase the risk of endometriosis (early menarche, short cycles, AUB, etc.). Inflammation and biosteroid hormones synthesis are the main mechanisms favoring the implantation and the growth of the lesions. Pain associated with endometriosis can be explained by nociception, hyperalgia, and central sensitization, associated to varying degrees in a single patient. Typology of pain (dysmenorrhea, deep dyspareunia, digestive or urinary symptoms) is correlated with the location of the lesions. Infertility associated with endometriosis can be explained by several non-exclusive mechanisms: a pelvic factor (inflammation), disrupting natural fertilization; an ovarian factor, related to oocyte quality and/or quantity; a uterine factor disrupting implantation. The pelvic factor can be fixed by surgical excision of the lesions that improves the chance of natural conception (NP2). The uterine factor can be corrected by an ovulation-blocking treatment that improves the chances of getting pregnant by in vitro fertilization (NP2). The impact of endometrioma exeresis on the ovarian reserve (NP2) should be considered when a surgery is scheduled. Endometriosis is a multifactorial disease, resulting from combined action of genetic and environmental factors. The risk of developing endometriosis for a first-degree relative is five times higher than in the general population (NP2). Identification of genetic variants involved in the disease has no implication for clinical practice for the moment. The role of environmental factors, particularly endocrine disrupters, is plausible but not demonstrated. Literature review does not support the progression of endometriosis over time, either in terms of the volume or the number of the lesions (NP3). The risk of acute digestive occlusion or functional loss of a kidney in patients followed for endometriosis seems exceptional. These complications were revealing the disease in the majority of cases. IVF does not increase the intensity of pain associated with endometriosis (NP2). There is few data on the influence of pregnancy on the lesions, except the possibility of a decidualization of the lesions that may give them a suspicious aspect on imaging. The impact of endometriosis on pregnancy is debated. There is an epidemiological association between endometriosis and rare subtypes of ovarian cancer (endometrioid and clear cell carcinomas) (NP2). However, the relative risk is moderate (around 1.3) (NP2) and the causal relationship between endometriosis and ovarian cancer is not demonstrated so far. Considering the low incidence of endometriosis-associated ovarian cancer, there is no argument to propose a screening or a risk reducing strategy for the patients.

[Management of assisted reproductive technology (ART) in case of endometriosis related infertility: CNGOF-HAS Endometriosis Guidelines].

Thu, 01 Mar 2018 00:00:00 +0000

The management of endometriosis related infertility requires a global approach. In this context, the prescription of an anti-gonadotropic hormonal treatment does not increase the rate of non-ART (assisted reproductive technologies) pregnancies and it is not recommended. In case of endometriosis related infertility, the results of IVF management in terms of pregnancy and birth rates are not negatively affected by the existence of endometriosis. Controlled ovarian stimulation during IVF does not increase the risk of endometriosis associated symptoms worsening, nor accelerate the intrinsic progression of endometriosis and does not increase the rate of recurrence. However, in the context of IVF management for women with endometriosis, pre-treatment with GnRH agonist or with oestrogen/progestin contraception improve IVF outcomes. There is currently no evidence of a positive or negative effect of endometriosis surgery on IVF outcomes. Information on the possibilities of preserving fertility should be considered, especially before surgery.

Live birth rate following frozen-thawed blastocyst transfer is higher with blastocysts expanded on Day 5 than on Day 6.

Thu, 01 Mar 2018 00:00:00 +0000

STUDY QUESTION: The aim of this study was to evaluate the live birth rate (LBR) after frozen-thawed Day 5 (D5) and Day 6 (D6) blastocyst transfers. SUMMARY ANSWER: LBR following frozen-thawed blastocyst transfer is significantly lower with D6 than with D5 blastocyst regardless of embryo quality. WHAT IS KNOWN ALREADY: During fresh embryo transfer cycles, pregnancy rates (PR) are significantly higher when transferring blastocysts expanded on D5 compared with slow developing blastocysts (D6). In programmed thawed blastocyst transfer (TBT) cycles, the same clinical outcomes should be expected when transferring D5 or D6 blastocysts because of endometrial/embryonic synchronization due to hormonal priming of endometrial receptivity. However, the impact of delayed blastocyst expansion at D6 on clinical outcomes remains unclear. Some reports have shown higher PRs after D5 TBT compared with those of D6, while others have shown equivalent TBT outcomes after D5 and D6 cryopreserved blastocysts transfers. STUDY, DESIGN, SIZE, DURATION: This retrospective cohort follow-up study included 1347 single autologous frozen-thawed blastocyst transfers performed between January 2012 and December 2015 at a tertiary care university hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: All of the patients scheduled for TBT were allocated to two groups according to the day of blastocyst expansion: on D5 (n = 994) or on D6 (n = 353). The primary outcome was LBR per embryo transfer in the first blastocyst thawing cycle. Secondary outcomes were clinical pregnancy rate (cPR), early miscarriage rate and neonatal outcomes following TBT for the two groups. Statistical analyses were conducted using univariate and multivariate logistic regression model. MAIN RESULTS AND THE ROLE OF CHANCE: The LBR was significantly increased in the D5 group compared to the D6 group [294/994 (29.6%) versus 60/353 (17.0%); P < 0.001]. The cPR was also higher when blastocysts were vitrified on D5 compared with those vitrified on D6 [429/994 (43.2%) versus 95/353 (26.9%); P < 0.001]. No significant differences were found between groups in terms of early miscarriage rate (P = 0.862). More good-quality embryos (defined as an B3-B4 or B5 embryo ≥BB according to the grading scale proposed by Gardner) were transferred in the D5 group than in the D6 group [807 (81.2%) versus 214 (60.6%); P < 0.001]. However, a comparison of TBT cycles with equal embryo quality (good versus low) also supported the superiority of D5 blastocysts. Concerning neonatal outcomes, the D5 group infants had a lower mean birth weight compared to those of the D6 group (P = 0.001). In addition, a significantly shorter gestational age at birth is reported in the D5 blastocyst group as compared to the D6 group (P = 0.004). After multivariate logistic regression taking into account potential confounders such as the women’s age, number of previous IVF/ICSI procedures, the day of the blastocyst vitrification (D5 or D6) and embryo quality, blastocyst expansion at D6 was independently associated with a significant decrease in LBR compared to D5 expanded-blastocysts (OR 0.52; 95% CI 0.38-0.72; P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The poor predictive value of the morphological approach in embryo selection could constitute a limitation in this study. However, blastocyst quality was evaluated similarly in both groups. WIDER IMPLICATIONS OF THE FINDINGS: The LBR following frozen-thawed blastocyst transfer was significantly lower with D6 than with D5 blastocysts, regardless of their quality. These results could affect cryopreservation procedures as they suggest that the use of D5-expanded blastocysts for TBT may be preferred in order to shorten the time of conceiving. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. None of the authors have any competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Extended culture of poor-quality supernumerary embryos improves ART outcomes.

Thu, 01 Feb 2018 00:00:00 +0000

PURPOSE: The aims of this study were to investigate the possible benefits of extending the culture of poor-quality day-2 embryos (PQE) versus good-quality embryos (GQE) and to identify factors associated with pregnancy and live birth when transferring frozen-thawed blastocysts originating from GQE and PQE. METHODS: This is a retrospective cohort follow-up study performed between November 2012 and February 2015 at the IVF Laboratory Unit of Cochin University Hospital (Paris, France) including 3108 day-2 supernumerary embryos resulting from 1237 IVF/ICSI cycles. RESULTS: Total blastulation rate was 67.2% from GQE and 48.7% from PQE. Percentage of good-quality blastocysts was 60.7 and 47.9% respectively including 14.7 and 7.3% top-quality blastocysts. A total of 150 blastocysts originating from GQE and 729 from PQE were frozen, and then, 37 and 164 were thawed and transferred respectively resulting in 19 (51.4%) and 61 (37.9%) clinical pregnancies with 13 (35.1%) deliveries from GQE and 32 (19.9%) from PQE (p = 0.046) without any difference in neonatal outcomes. Quality of blastocysts that resulted in live birth was similar in the two groups. Women < 35 years old and day-5 blastocyst expansion were predictive of pregnancy and live birth. CONCLUSIONS: (i) PQE are able to reach the blastocyst stage, to implant, and to give healthy babies and (ii) women age and day of blastocyst expansion are predictive of pregnancy and live birth.

Pathogenesis of adenomyosis: an update on molecular mechanisms.

Wed, 01 Nov 2017 00:00:00 +0000

Adenomyosis is a uterine disorder becoming more commonly diagnosed in women of reproductive age because of diagnostic imaging advancements. The new epidemiological scenario and the clinical evidence of pelvic pain, abnormal uterine bleeding and infertility are changing the classic perspective of adenomyosis as a premenopausal disease. In the last decade, the evaluation of multiple molecular mediators has improved our knowledge of pathogenic mechanisms of adenomyosis, supporting that this is an independent disease from endometriosis. Although they share common genetic mutations and epigenetic changes in sex steroid hormone receptors and similar inflammatory mediators, an increasing number of recent studies have shown pathogenic pathways specific for adenomyosis. A PubMed search up to October 2016 summarizes the key mediators of pain, abnormal uterine bleeding and infertility in adenomyosis, including sex steroid hormone receptors, inflammatory molecules, extracellular matrix enzymes, growth factors and neuroangiogenic factors.

The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors.

Fri, 15 Sep 2017 00:00:00 +0000

Herein we describe the discovery of IDX21437 35b, a novel RPd-aminoacid-based phosphoramidate prodrug of 2’-α-chloro-2’-β-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes. A biochemical study revealed that the metabolism of 35b was mainly attributed to carboxyesterase 1 (CES1), an enzyme which is underexpressed in HCV Huh-7-derived replicon cells. Furthermore, due to its metabolic activation, 35b was efficiently processed in liver cells compared to other cell types, including human cardiomyocytes. The selected RP diastereoisomeric configuration of 35b was assigned by X-ray structural determination. 35b is currently in Phase II clinical trials for the treatment of HCV infection.

[Bowel endometriosis and infertility: Do we need to operate?].

Fri, 01 Sep 2017 00:00:00 +0000

Endometriosis is a benign chronic inflammatory disease, whose pathogenesis is still unclear. Endometriosis is responsible for infertility and/or pelvic pain. One of the most important features of the disease is the heterogeneity (clinical and anatomical: superficial peritoneal, ovarian and/or deep infiltrating lesions). Bowel involvement constitutes one particularly severe form of the disease, affecting 8-12% of women with deep endometriosis. In case of associated infertility, bowel endometriosis constitutes a real therapeutic challenge for gynecologists. Indeed, while complete resection of the lesions alleviates pain and seems to improve spontaneous fertility, surgery remains technically challenging and may cause severe complications. Reverting to assisted Reproductive Technology (ART) is another valuable therapeutic option regarding pregnancy rates. Thus, the choice between surgical management or ART is still debated. Benefits and risks of these two options should be considered and discussed before planning treatment. In the present study, we aimed to answer the question: Bowel endometriosis and infertility: do we need to operate?

Alteration of Nrf2 and Glutamate Cysteine Ligase expression contribute to lesions growth and fibrogenesis in ectopic endometriosis.

Fri, 01 Sep 2017 00:00:00 +0000

The redox-sensitive nuclear factor erythroid-derived 2-like 2 (NRF2) controls endogenous antioxidant enzymes’ transcription and protects against oxidative damage which is triggered by inflammation and known to favor progression of endometriosis. Glutamate Cysteine Ligase (GCL), a target gene of NRF2, is the first enzyme in the synthesis cascade of glutathione, an important endogenous antioxidant. Sixty-one patients, with thorough surgical examination of the abdominopelvic cavity, were recruited for the study: 31 with histologically-proven endometriosis and 30 disease-free women taken as controls. Expressions of NRF2 and GCL were investigated by quantitative RT-PCR and immunohistochemistry in eutopic and ectopic endometria from endometriosis-affected women and in endometrium of disease-free women. Ex vivo stromal and epithelial cells were extracted and purified from endometrial and endometriotic biopsies to explore expression of NRF2 and GCL in both stromal and epithelial compartments by western blot. Finally, in order to strengthen the role of NRF2 in endometriosis pathogenesis, we evaluated the drop of NRF2 expression in a mouse model of endometriosis using NRF2 knockout (NRF2-/-) mice. The mRNA levels of NRF2 and GCL were significantly lower in ectopic endometria of endometriosis-affected women compared to eutopic endometria of disease-free women. The immunohistochemical analysis confirmed the decreased expression of both NRF2 and GCL in ectopic endometriotic tissues compared to eutopic endometria of endometriosis-affected and disease-free women. Immunoblotting revealed a significant decreased of NRF2 and GCL expression in epithelial and stroma cells from ectopic lesions of endometriosis-affected women compared to eutopic endometria from controls. Using a murine model of endometriosis, NRF2-/- implants were more fibrotic compared to wild-type with an increased weight and volume. These findings indicate that expression of the transcription factor NRF2 and its effector GCL are both profoundly deregulated in endometriotic lesions towards increased growth and fibrogenetic processes.

Does GnRH Agonist Triggering Control Painful Symptom Scores During Assisted Reproductive Technology? A Retrospective Study.

Fri, 01 Sep 2017 00:00:00 +0000

OBJECTIVE: The aim of this study was to assess the progression of pain symptoms during assisted reproductive technology (ART) cycles following administration of GnRH agonist (GnRHa) versus human chorionic gonadotrophin (hCG) triggering. DESIGN: Observational cohort study. SETTING: A tertiary care university hospital in France. POPULATION: Patients who underwent ART programs. METHODS: Between January 01, 2014, and June 31, 2014, 122 cycles were allocated to 2 groups: GnRHa triggering with a scheduled differed embryo transfer (n = 57) or hCG triggering with a fresh embryo transfer (n = 70). Pelvic pain scores were evaluated using a visual analog scale (VAS) with regard to dysmenorrhea, dyspareunia, noncyclic pelvic pain, gastrointestinal, and lower urinary tract pain. The total VAS score was defined as the sum of the scores for the various symptoms. Evaluations were carried out twice: during the synchronization treatment prior to ovarian stimulation and during a final evaluation 3 weeks postretrieval. The data were processed using univariate and multivariate logistic regression models. MAIN OUTCOME MEASURES: Trends for total VAS change (ie, final VAS score - synchronization VAS score). RESULTS: For both groups, pain increased during the ART procedure. Trends for the total VAS change revealed that the increase in pain was significantly less in the -‘GnRHa triggering-’ group compared to the -‘hCG triggering-’ group (3.77 ± 7.73 and 6.50 ± 6.57, P < .05, respectively). Multivariate logistic regression indicated that GnRHa triggering was associated with less of an increase in pain compared to hCG triggering (odds ratio = 0.31, 95% confidence interval 0.13-0.71, P < .05). CONCLUSION: Compared to hCG, GnRHa triggering limits pain symptom progression in the period immediately after ART.

The role of the B lymphocytes in endometriosis: A systematic review.

Fri, 01 Sep 2017 00:00:00 +0000

The physiopathology of endometriosis is not completely understood and its progression is associated with a local and systemic inflammatory reaction. It is important to clarify the potential role of the immune system to better understand its implication in the pathogenesis of endometriosis, which includes the study of the role of B cells and antibodies. The aim of this study was to review the literature about the role of B lymphocytes in endometriosis. A search for -’endometriosis-’, -‘B cells-’ and -‘B lymphocytes-’ in databases resulted in 140 citations; after applying inclusion and exclusion criteria, a total of 22 studies were assessed. The analyzed samples in the studies varied and different markers and techniques were used by the authors to evaluate the direct or indirect role of B lymphocytes in endometriosis. Most studies demonstrated increased number and/or activation of B cells while seven studies found no difference and two studies showed decreased number of B cells. Increased B lymphocytes and excessive production of autoantibodies in endometriosis have been described in the literature, but their role in the development of the disease is not well understood. Moreover, the association of these factors with clinical symptoms, location and severity of the disease has not been investigated. Further studies are necessary to clarify the role of B cells in the development of endometriosis and propose new therapeutic strategies such as the use of drugs that target these cells.

Dysregulation of the ADAM17/Notch signalling pathways in endometriosis: from oxidative stress to fibrosis.

Sat, 01 Jul 2017 00:00:00 +0000

STUDY QUESTION: Is oxidative stress associated with the A disintegrin and metalloproteases (ADAM) metallopeptidase domain 17 (ADAM17)/Notch signalling pathway and fibrosis in the development of endometriosis? SUMMARY ANSWER: Oxidative stress is correlated with hyperactivation of the ADAM17/Notch signalling pathway and a consequent increase in fibrosis in patients with endometriosis. WHAT IS KNOWN ALREADY: It is nowadays accepted that oxidative stress plays an important role in the onset and progression of endometriosis. Oxidative stress is able to induce the synthesis of some members of the ‘ADAM’ family, such as ADAM17. ADAM17/Notch signalling is dysregulated in other profibrotic and inflammatory diseases. STUDY DESIGN, SIZE, DURATION: This was a prospective laboratory study conducted in a tertiary-care university hospital between January 2011 and April 2013. We investigated non-pregnant, younger than 42-year-old patients (n = 202) during surgery for a benign gynaecological condition. PARTICIPANTS/MATERIALS, SETTING, METHODS: After complete surgical exploration of the abdominopelvic cavity, 121 women with histologically proven endometriosis and 81 endometriosis-free control women were enrolled. Peritoneal fluid (PF) samples were obtained from all the study participants during surgery in order to detect advanced oxidation protein products (AOPPs) and metalloproteinase activity of ADAM17. Stromal cells from endometrial specimens (n = 8) were obtained from endometrium of control patients (Cs), and from eutopic (Es) and ectopic (Ps) endometrium of patients with deep infiltrating endometriosis (DIE) (n = 8). ADAM17, Notch and the fibrosis markers α-smooth muscle actin (α-SMA) and type-I collagen were assessed using immunoblotting in all the endometrial samples obtained. Additionally, fibrosis was assessed after using Notch cleavage inhibitors (DAPT and FLI-06). Notch and fibrosis were also evaluated after stimulation of stromal endometrial cells with ADAM17 purified protein, increasing concentrations of H2O2 and primary cell culture supernatants. MAIN RESULTS AND THE ROLE OF CHANCE: Patients with DIE presented higher PF AOPP and ADAM17 protein levels than controls (P < 0.01 and P < 0.05, respectively). In addition, these two markers were positively correlated (r = 0.614; P < 0.001). At the cellular level, ADAM17 activity was increased in Es and Ps compared to Cs (P < 0.001 and P < 0.01, respectively). Furthermore, Ps presented hyperactivation of Notch signalling (P < 0.05) and augmentation of fibrosis markers (P = 0.009 for α-SMA and P = 0.015 for type-I collagen) compared to controls. The use of DAPT and FLI-06 reduced both fibrosis markers in Ps but not in Cs. Stimulation with ADAM17, H2O2 and Ps supernatant culture significantly increased Notch and fibrosis in both Ps and Cs. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: The control group consisted of women who underwent surgery for benign gynaecological conditions, which could lead to biases because some of these conditions may cause alterations in oxidative stress and the ADAM17/Notch pathways. The small sample size of endometrial biopsies used for each group of patients (n = 8) is a limitation of the study, and results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: We propose a novel pathway in endometriosis pathogenesis that correlates oxidative stress, hyperactivation of ADAM17/Notch signalling and a consequent increase in fibrosis. This study suggests that Notch signalling plays a key role in the fibrotic processes that take place in ectopic lesions of patients with DIE, as already observed in other pro-fibrotic diseases. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by grants from University Paris Descartes, INSERM and Fundación Alfonso Martín Escudero. The authors have no competing interests to declare.

Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes.

Sat, 01 Jul 2017 00:00:00 +0000

STUDY QUESTION: What is the relationship between endometriosis phenotypes superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), deep infiltrating endometriosis (DIE) and the adenomyosis appearance by magnetic resonance imaging (MRI)? SUMMARY ANSWER: Focal adenomyosis located in the outer myometrium (FAOM) was observed more frequently in women with endometriosis, and was significantly associated with the DIE phenotype. WHAT IS KNOWN ALREADY: An association between endometriosis and adenomyosis has been reported previously, although data regarding the association between MRI appearance of adenomyosis and the endometriosis phenotype are currently still lacking. STUDY DESIGN, SIZE, DURATION: This was an observational, cross-sectional study using data prospectively collected from non-pregnant patients who were between 18 and 42 years of age, and who underwent surgery for symptomatic benign gynecological conditions between January 2011 and December 2014. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding the surgery. Only women with preoperative standardized uterine MRIs were retained for this study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Surgery was performed on 292 patients with signed consent and available preoperative MRIs. After a thorough surgical examination of the abdomino-pelvic cavity, 237 women with histologically proven endometriosis were allocated to the endometriosis group and 55 symptomatic women without evidence of endometriosis to the endometriosis free group. The existence of diffuse or FAOM was studied in both groups and according to surgical endometriosis phenotypes (SUP, OMA and DIE). MAIN RESULTS AND THE ROLE OF CHANCE: Adenomyosis was observed in 59.9% (n = 175) of the total sample population (n = 292). Based on MRI, the distribution of adenomyosis was as follows: isolated diffuse adenomyosis (53 patients; 18.2%), isolated FAOM (74 patients; 25.3%), associated diffuse and FAOM (48 patients; 16.4%). Diffuse adenomyosis (isolated and associated to FAOM) was observed in one-third of the patients regardless of whether they were endometriotic patients or endometriosis free women taken as controls (34.2% (81 cases) versus 36.4% (20 cases)); P = 0.764. Among endometriotic women, diffuse adenomyosis (isolated and associated to FAOM) failed to reach significant correlation with the endometriosis phenotypes (SUP, 20.0% (8 cases); OMA, 45.2% (14 cases) and DIE, 35.5% (59 cases); P = 0.068). In striking contrast, there was a significant increase in the frequency of FAOM in endometriosis-affected women than in controls (119 cases (50.2%) versus 5.4% (3 cases); P < 0.001). FAOM correlated with the endometriosis phenotypes, significantly with DIE (SUP, 7.5% (3 cases); OMA, 19.3% (6 cases) and DIE, 66.3% (110 cases); P < 0.001). LIMITATIONS, REASONS FOR CAUTION: There was a possible selection bias due to the specificity of the study design, as it only included surgical patients in a referral center that specializes in endometriosis surgery. Therefore, women referred to our center may have suffered from particularly severe forms of endometriosis. This could explain the high number of women with DIE (166/237-70%) in our study group. This referral bias for women with severe lesions may have amplified the difference in association of FAOM with the endometriosis-affected patients compared to women without endometriosis. Furthermore, according to inclusion criteria, women in the endometriosis free group were symptomatic women. This may introduce some bias as symptomatic women may be more prone to have associated adenomyosis that in turn could have been overrepresented in the endometriosis free group. Whether this selection could have introduced a bias in the relationship between endometriosis and adenomyosis remains unknown. WIDER IMPLICATIONS OF THE FINDINGS: This study opens the door to future epidemiological, clinical and mechanistic studies aimed at better characterizing diffuse and focal adenomyosis. Further studies are necessary to adequately determine if diffuse and focal adenomyosis are two separate entities that differ in terms of pathogenesis. STUDY FUNDING/COMPETING INTEREST(S): No funding supported this study. The authors have no conflict of interest to declare.

Serum Osteopontin Levels Are Decreased in Focal Adenomyosis.

Mon, 01 May 2017 00:00:00 +0000

We investigated whether serum osteopontin (OPN) levels are different according to specific phenotypes of adenomyosis and endometriosis. We conducted a prospective laboratory study in a university referral center for endometriosis between May 2005 and May 2013 and included 148 nonpregnant women, younger than 42 years, undergoing surgery for a benign gynecological condition and who had a preoperative pelvic magnetic resonance imaging (MRI). The presence of focal and/or diffuse adenomyosis was determined by pelvic MRI, and women were classified into 3 groups: no-adenomyosis (No-AM), isolated diffuse adenomyosis (DIF-AM), and focal adenomyosis with or without diffuse adenomyosis (FOC-AM). After complete surgical exploration of the pelvic cavity, the presence and type of endometriosis was surgically determined and histologically confirmed. We distinguished 4 phenotypes: no endometriosis, superficial peritoneal endometriosis (SUP), ovarian endometrioma, and deep infiltrating endometriosis (DIE). Osteopontin levels were measured by enzyme-linked immunosorbent assay in serum samples obtained in all participants in the month preceding surgery. Our results show lower OPN levels in women with focal adenomyosis compared to adenomyosis-free controls. Our results also show a decrease in OPN levels in women with associated DIE and focal adenomyosis compared to women with SUP. Various serum biomarkers have been studied in the context of endometriosis severity and subtypes, whereas data on serum markers of adenomyosis are scarce. Both entities are often associated, and adenomyosis could be a confounding factor influencing results. Future research on serum biomarkers should describe subtypes of adenomyosis and endometriosis and analyze results according to well-defined subtypes.

[Conservative management of endometrioma in women undergoing in vitro fertilization].

Wed, 01 Mar 2017 00:00:00 +0000

Endometriosis is a chronic disease. The pathogenesis is actually still unclear. Endometriosis is responsible for infertility and/or pelvic pain. One of the most important features of the disease is the heterogeneity (clinical and anatomical). Among the different phenotypes of endometriosis, the ovarian endometrioma seems to most important lesion in the management of endometriosis-related infertility. Surgical treatment is associated to a decrease of the ovarian reserve and a potential detrimental effect on in vitro fecondation (IVF) outcomes. Thus, the choice between conservative or surgical management of endometrioma before IVF is actually debated. The advantages and drawback of surgical and conservative management should be discussed before to plan the treatment. In the present review, we aimed at assessing the risks of a conservative management of endometrioma as compared to surgery before IVF.

Assisted reproduction technique outcomes for fresh versus deferred cryopreserved day-2 embryo transfer: a retrospective matched cohort study.

Wed, 01 Mar 2017 00:00:00 +0000

Ovarian stimulation could adversely affect endometrial receptivity and consequently embryo implantation. One emerging strategy is the ‘freeze-all’ approach. Most studies have focused on blastocyst transfers, with limited research on day-2 deferred cryopreserved embryo transfers. In this large retrospective cohort study, outcomes were compared between day-2 fresh versus deferred cryopreserved embryo transfers. After matching by age and number of previous cycles, 325 cycles were included in the fresh group and 325 in the deferred cryopreserved embryo transfers group: no significant differences were found between groups in implantation (0.20 ± 0.33 versus 0.17 ± 0.31, respectively) and ongoing pregnancy rates (21.85% versus 18.46%). Independent predictors for ongoing pregnancy after a multiple logistic regression analysis were the women’s age (OR = 0.92; 95% CI 0.88 to 0.97), body mass index (OR = 0.94; 95% CI 0.89 to 0.99), the number of two pronuclei embryos (OR = 1.19; 95% CI 1.04 to 1.40) and at least one grade 1 embryo transferred (OR = 1.97; 95% CI 1.26 to 3.05). In the case of a day-2 embryo transfer, outcomes after treatment with assisted reproduction techniques are similar for fresh versus deferred cryopreserved embryo transfers when pre-transfer progesterone exposures are similar in the two groups.

Prognostic factors for assisted reproductive technology in women with endometriosis-related infertility.

Wed, 01 Mar 2017 00:00:00 +0000

BACKGROUND: Assisted reproductive technology is one of the therapeutic options offered for managing endometriosis-associated infertility. Yet, published data on assisted reproductive technology outcome in women affected by endometriosis are conflicting and the determinant factors for pregnancy chances unclear. OBJECTIVE: We sought to evaluate assisted reproductive technology outcomes in a series of 359 endometriosis patients, to identify prognostic factors and determine if there is an impact of the endometriosis phenotype. STUDY DESIGN: This was a retrospective observational cohort study, including 359 consecutive endometriosis patients undergoing in vitro fertilization or intracytoplasmic sperm injection, from June 2005 through February 2013 at a university hospital. Endometriotic lesions were classified into 3 phenotypes-superficial peritoneal endometriosis, endometrioma, or deep infiltrating endometriosis-based on imaging criteria (transvaginal ultrasound, magnetic resonance imaging); histological proof confirmed the diagnosis in women with a history of surgery for endometriosis. Main outcome measures were clinical pregnancy rates and live birth rates per cycle and per embryo transfer. Prognostic factors of assisted reproductive technology outcome were identified by comparing women who became pregnant and those who did not, using univariate and adjusted multiple logistic regression models. RESULTS: In all, 359 endometriosis patients underwent 720 assisted reproductive technology cycles. In all, 158 (44%) patients became pregnant, and 114 (31.8%) had a live birth. The clinical pregnancy rate and the live birth rate per embryo transfer were 36.4% and 22.8%, respectively. The endometriosis phenotype (superficial endometriosis, endometrioma, or deep infiltrating endometriosis) had no impact on assisted reproductive technology outcomes. After multivariate analysis, history of surgery for endometriosis (odds ratio, 0.14; 95% confidence ratio, 0.06-0.38) or past surgery for endometrioma (odds ratio, 0.39; 95% confidence ratio, 0.18-0.84) were independent factors associated with lower pregnancy rates. Anti-müllerian hormone levels <2 ng/mL (odds ratio, 0.51; 95% confidence ratio, 0.28-0.91) and antral follicle count <10 (odds ratio, 0.27; 95% confidence ratio, 0.14-0.53) were also associated with negative assisted reproductive technology outcomes. CONCLUSION: The endometriosis phenotype seems to have no impact on assisted reproductive technology results. An altered ovarian reserve and a previous surgery for endometriosis and/or endometrioma are associated with decreased pregnancy rates.

[Corifollitropin alfa compared to daily FSH in controlled ovarian stimulation for oocyte donors].

Wed, 01 Feb 2017 00:00:00 +0000

OBJECTIVES: To demonstrate that corifollitropin alfa is as effective as daily FSH in controlled ovarian stimulation of oocyte donors. METHODS: From January 2013 to October 2015, 77 cycles controlled ovarian stimulation, derived from a continuous cohort of 77 oocyte donors, were analyzed. After synchronization by oestroprogestatif or estrogens, ovarian stimulation was started by corifollitropin alfa (Group corifollitropin alfa) or by daily FSH (Group daily FSH). In both groups, a GnRH antagonist was used for the prevention of premature surge of luteinizing hormone (LH). The induction of ovulation was induced by a GnRH agonist. The duration of treatment, estradiol rate, numbers of mature oocytes, fertilization rate, clinical and ongoing pregnancies rates were evaluated in the two groups. RESULTS: There is no difference for the age, the markers of ovarian reserve and the duration of treatment. The average rate of estradiol on the eighth day of the stimulation is lower for the corifollitropin alfa (845±694.5 vs 1742±1177.3, P<0.001), there is no difference in the number of mature oocytes retrieved (14.4 vs 13.4, P=0.979), with a fertilization rate significantly higher in the corifollitropin alfa group (59.8% vs 49.3%, P<0.001). The rate of ongoing pregnancies is higher but without reaching significant difference in this same group (36.6% vs 26%, P=0.277). CONCLUSION: As compared to daily FSH, corifollitropin alfa, in oocyte donors offers, advantages in terms of ease of use with identical efficiency.

Recent insights on the genetics and epigenetics of endometriosis.

Wed, 01 Feb 2017 00:00:00 +0000

Endometriosis is a gynecologic disease affecting up to 10% of the women and a major cause of pain and infertility. It is characterized by the implantation of functional endometrial tissue at ectopic positions generally within the peritoneum. This complex disease has an important genetic component with a heritability estimated at around 50%. This review aims at providing recent insights into the genetic bases of endometriosis, and presents a detailed overview of evidence of epigenetic alterations specific to this disease. In the future, these alterations may constitute therapeutic targets for pharmacological compounds able to modify the epigenetic code.

Reply: Should we also work on an international informed consent for endometriosis surgery?

Wed, 01 Feb 2017 00:00:00 +0000

Consensus on Recording Deep Endometriosis Surgery: the CORDES statement.

Tue, 01 Nov 2016 00:00:00 +0000

Erratum for Hum Reprod. 2016 Jun;31(6):1219-23. doi: 10.1093/humrep/dew067.

History of Uterine Surgery Is Not Associated With an Increased Severity of Bladder Deep Endometriosis.

Tue, 01 Nov 2016 00:00:00 +0000

STUDY OBJECTIVE: To analyze whether a history of uterine surgery correlates with disease severity in patients with bladder deep infiltrating endometriosis (DIE). DESIGN: This was an observational, cross-sectional study using data collected prospectively (Canadian Task Force classification II-2). SETTING: A single university tertiary referral center. PATIENTS: We included all nonpregnant women younger than age 42 years who had undergone complete surgical exeresis of endometriotic lesions. For each patient, a standardized questionnaire was completed during a face-to-face interview that was conducted by the surgeon in the month preceding the surgery. INTERVENTIONS: One hundred seven women with histologically proven bladder DIE were enrolled in this study. For the purpose of the study, the women were assigned to 2 groups before surgery: a study group that included women with a history of a scarred uterus (SU) (SU+, n = 16) and a control group that included women without SU (SU-, n = 99). Both groups were compared in terms of their general characteristics, medical histories, surgical findings, and the severity of the disease. MEASUREMENTS AND MAIN RESULTS: Patient age and body mass index were higher for the SU+ group as compared to the SU- group (37.9 ± 5.6 vs 32.2 ± 4.7, p < .01, and 24.7 ± 4.9 vs 21.9 ± 2.9, p = .03, respectively). Preoperative painful symptom scores did not differ between the 2 groups. No significant difference was observed in the rates of history for surgery for endometriosis (n = 11 [68.7%] vs n = 49 [53.8], p = .27). Comparison of the anatomic distribution of the lesions did not reveal a significant difference. The total American Society for Reproductive Medicine score did not differ between the groups (32.0 ± 34.4 vs 35.5 ± 34.5, p = .71). The incidence rate of isolated bladder DIE did not differ between the 2 study groups (n = 6 [37.5%] vs n = 40 [43.9%], p = .79). CONCLUSION: SU before surgery for endometriosis was observed in 14.9% of cases of bladder DIE; however, this was not related to an increased severity of the disease. This observational study hence does not appear to support the pathophysiologic hypothesis of a transmyometrial source for bladder DIE.

MR diagnosis of diaphragmatic endometriosis.

Tue, 01 Nov 2016 00:00:00 +0000

PURPOSE: To evaluate magnetic resonance imaging (MRI) for diaphragmatic endometriosis diagnosis. MATERIALS AND METHODS: Over a 2-year period, all diaphragmatic MRI performed in the context of diaphragmatic endometriosis were reviewed. Axial and coronal fat-suppressed T1- and T2-weighted sequences were analyzed by two independent readers for the presence of nodules, plaque lesions, micronodule clustering, or focal liver herniation. MR abnormalities were correlated to surgical findings in women surgically treated. Interobserver agreement was assessed by κ statistics. RESULTS: Twenty-three women with diaphragmatic endometriosis criteria comprised the population; 14 had surgical confirmation and nine had symptoms relief with hormonal treatment. MRI sensitivity was 83 % (19/23; 95 % confidence interval [CI]: 68, 98) for reader 1 and 78 % (18/23; 95 % CI: 61, 95) for reader 2. Kappa value was 0.86 (95 % CI: 0.47, 1.00). Readers 1 and 2 detected 35 and 36 lesions, respectively, all right-sided and agreed for 32 lesions on the type, location, and signal. Lesions were mostly nodules (23/32, 72 %), predominantly posterior (28/32, 87.5 %) and hyperintense on T1 (20/32, 63 %). MRI was negative for both readers in 2 surgically treated patients with small nodules or isolated diaphragmatic holes. CONCLUSION: MRI allows diaphragmatic endometriosis diagnosis with 78 to 83 % sensitivity and excellent interobserver agreement. KEY POINTS: • MRI allows the diagnosis of diaphragmatic endometriosis with up to 83 % sensitivity. • Diaphragmatic endometriosis lesions are better depicted on fat-suppressed T1-weighted sequences. • Diaphragmatic lesions, mostly hyperintense nodules, are right-sided and predominantly posterior. • MRI can help in timely diagnosis of diaphragmatic endometriosis.

[Risk of perinatal complication and egg donation: Role of resorting to cross-border care?].

Sat, 01 Oct 2016 00:00:00 +0000

OBJECTIVES: In France, egg donation is covered by Social insurance among women<43 years old. Because of shortage of egg donor, women aged 43 years or more cannot resort to egg donation in French infertility centers, leading them to turn to the foreign centers having practices different and less regulated than in France. We are thus brought to take care of the pregnancy and of the delivery of these women. Our objective was to estimate if the perinatal risks are more important after egg donation abroad than in case of egg donation in a French center. MATERIAL AND METHODS: Retrospective study between January, 2010 and April, 2013, comparing women having had an egg donation to Cochin then having delivered in the maternity hospital of their choice (n=88) and the women having had an egg donation abroad then having delivered in the Port-Royal maternity (n=121). First, the modalities of egg donation were compared between the Cochin hospital and the foreign centers. Second, the obstetric and perinatal outcomes were compared between both groups, then by stratifying according to the type of pregnancy (singleton or multiple). RESULTS: Among women having had an egg donation abroad, the age of the donor was lower (25.7 vs. 31.7, P=0.001), the average number of embryos transferred higher (2.1±0.6 vs. 1.7±0.5, P=0.001) and the rate of multiple pregnancies higher (47.9% vs. 9.1%, P=0.001) than among women having had an egg donation at Cochin. We observed after egg donation abroad compared to egg donation at Cochin, a birth weight significantly lower (2678±745g vs. 3045±682g, P=0.001) and a prevalence of intrauterine growth retardation higher (11.1% vs. 4.2%, P=0.04). Among singletons, abnormal placentation was more frequent in case of egg donation abroad (17.5% vs. 5.1%, P=0.02). In case of twin pregnancy, we highlighted very high rates of complications, without significant difference according to the place where egg donation was practiced. CONCLUSION: We observed an increased risk of intrauterine growth retardation after egg donation abroad, which could essentially be explained by the association between advanced maternal age and multiple gestation. For other obstetric and perinatal complications, the differences between both groups were less important than expected, but very high in both groups, whether the egg donation was realized in France or abroad. The complications seem mainly due to the multiple gestations, justifying the transfer of a single embryo whenever possible.

Urocortin and corticotrophin-releasing hormone receptor type 2 mRNA are highly expressed in deep infiltrating endometriotic lesions.

Sat, 01 Oct 2016 00:00:00 +0000

Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) are the most severe forms of endometriosis, but different pathogenetic mechanisms and clinical symptoms distinguish these two forms. Corticotrophin-releasing hormone (CRH) and urocortin (Ucn) are endometrial neuropeptides involved in tissue differentiation and inflammation. The expression of CRH, Ucn, Ucn2, CRH-receptors (type-1 and type-2) and inflammatory enzymes phospholipase-A2 group IIA (PLA2G2A) and cycloxygenase-2 (COX2) were evaluated in OMA (n = 22) and DIE (n = 26). The effect of CRH or Ucn on COX2 mRNA expression was evaluated in cultured human endometrial stromal cells. In DIE lesions, CRH, Ucn and CRH-R2 mRNA levels were significantly higher than in OMA (P < 0.01, P < 0.001 and P < 0.05, respectively); DIE lesions showed a higher expression of COX2 (P < 0.01) and PLA2G2A (P < 0.05) mRNA than OMA, which was positively correlated with CRH-R2 mRNA expression (P < 0.05). Intense immunostaining for CRH and Ucn was shown in DIE. Treatment of cultured endometrial stromal cells with Ucn significantly increased COX2 mRNA expression (P < 0.01); this effect was reversed by the CRH-R2 antagonist astressin-2B. In DIE, DIE lesions highly express neuropeptide and enzyme mRNAs, supporting a strong activation of inflammatory pathways.

Correlation Between the Clinical Parameters and Tissue Phenotype in Patients Affected by Deep-Infiltrating Endometriosis.

Thu, 01 Sep 2016 00:00:00 +0000

The current study aimed to identify and validate an applicable immunohistochemistry panel including Ki-67, c-MYC, estrogen receptor-α (ER-α), and progesterone receptor isoforms A/B (PR-A/B) in correlation with clinicopathological parameters in patients affected by deep infiltrating endometriosis. Tissue microarrays were prepared from a cohort of 113 patients. Phenotypic profile of the panel molecules was evaluated in glands and stroma in parallel with microvessels and stroma density measurements. Principal component analysis was performed on 8 immunohistochemical variables, 2 histological variables, and 8 subgroups of clinical parameters. The immunohistochemical profiling showed consistent Ki-67 immunostaining in 17.9% of the samples and c-MYC in 83.1%, while intense ER-α immunoreactivity was detected in 84% of the samples and PR-A/B isoforms in 24.1% of them. The combination of clinical parameters and tissue phenotype allowed a stratification of endometriosis-affected patients. Such novel phenotypical and clinical correlation could be helpful in the future studies for a better stratification of the disease aiming at a personalized patient care.

Endometriosis-related infertility: ovarian endometrioma per se is not associated with presentation for infertility.

Mon, 01 Aug 2016 00:00:00 +0000

STUDY QUESTION: Is there an association between the endometriosis phenotype and presentation with infertility? SUMMARY ANSWER: In a population of operated patients with histologically proven endometriosis, ovarian endometrioma (OMA) per se is not associated with an increased risk of presentation with infertility, while previous surgery for endometriosis was identified as a risk factor for infertility. WHAT IS KNOWN ALREADY: The increased prevalence of endometriosis among subfertile women indicates that endometriosis impairs reproduction for reasons that are not completely understood. STUDY DESIGN, SIZE, DURATION: This was an observational, cross-sectional study using data prospectively collected in all non-pregnant patients aged between 18 and 42 years, who were surgically explored for benign gynaecological conditions at our institution between January 2004 and March 2013. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Surgery was performed in 2208 patients, of which 2066 signed their informed consent. Of the 1059 women with a visual diagnosis of endometriosis, 870 had histologically proven endometriosis and complete treatment for their endometriotic lesions, including 307 who presented with infertility. Univariate analysis and multiple logistic regression analysis were performed to determine factors associated with infertility. MAIN RESULTS AND THE ROLE OF CHANCE: The following variables were identified as risk factors for endometriosis-related infertility: age >32 years (odds ratio [OR] = 1.9; 95% confidence interval [CI]: 1.4-2.4), previous surgery for endometriosis (OR = 1.9; 95% CI: 1.3-2.2), as well as peritoneal superficial endometriosis (OR = 3.1; 95% CI: 1.9-4.9); Conversely, previous pregnancy was associated with a lower rate of infertility (OR = 0.7; 95% CI: 0.6-0.9 and OR = 0.6; 95% CI: 0.4-0.9, respectively). OMA is not selected as a significant risk factor for infertility. LIMITATIONS, REASON FOR CAUTION: The selection of our study population was based on a surgical diagnosis. We cannot exclude that infertile women with OMA associated with a diminished ovarian reserve, as assessed during their infertility work-up, were referred less frequently to surgery and might therefore be underrepresented. In addition we cannot exclude that our group of infertile women present associated other causes of infertility. WIDER IMPLICATIONS OF THE FINDINGS: Identification of risk and preventive factors of endometriosis-related infertility can help improve clinical and surgical management of endometriosis in the setting of infertility. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: None.

Factors and Regional Differences Associated with Endometriosis: A Multi-Country, Case-Control Study.

Mon, 01 Aug 2016 00:00:00 +0000

INTRODUCTION: The present study aimed to investigate clinical, lifestyle, and environmental factors associated with endometrioma (OMA) and/or deep infiltrating endometriosis (DIE) as determined by case-control comparison [women with superficial peritoneal endometriosis (SUP) or no endometriosis], and compare differences between factor associated with endometriosis at a national level. METHODS: This was three countries (China, Russia, and France), case-control study in 1008 patients. Patients were identified and enrolled during their first routine appointment with their physician post-surgery for a benign gynecologic indication, excluding pregnancy. Retrospective information on symptoms and previous medical history was collected via face-to-face interviews; patients also completed a questionnaire to provide information on current habits. For every DIE patient recruited (n = 143), two women without endometriosis (n = 288), two SUP patients (n = 288), and two OMA patients (n = 288) were recruited. RESULTS: For the overall population, factors significantly associated (P ≤ 0.05) with DIE or OMA [Odds ratio (OR) >1] were: previous use of hormonal treatment for endometriosis [OR 6.66; 95% confidence interval (CI) 4.05-10.93]; previous surgery for endometriosis (OR 1.95; 95% CI 1.11-3.43); and living or working in a city or by a busy area (OR 1.66; 95% CI 1.09-2.52). Differences between regions with regard to the diagnosis, symptomatology, and treatment of endometriosis exist. CONCLUSION: The findings provide insight into potential risk factors for endometriosis and differences between regions in terms of endometriosis management and symptomatology. Further investigations are required to confirm the associations found in this study. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01351051. FUNDING: Ipsen.

Risks of tubo-ovarian abscess in cases of endometrioma and assisted reproductive technologies are both under- and overreported.

Mon, 01 Aug 2016 00:00:00 +0000

OBJECTIVE: To study possible associations among endometriosis, pelvic infectious disease, and ART. DESIGN: Retrospective cohort analysis over 4 consecutive years, based on medical records and insurance coding in a tertiary endometriosis reference center. SETTING: Tertiary university-based reference center for endometriosis. PATIENT(S): We retrieved all charts carrying the diagnoses infectious process and endometriosis in 2009-2012. Each chart was individually analyzed for categorization of the infectious episode and determining whether ART had been performed. MAIN OUTCOME MEASURE(S): Hospitalization for acute infection in women with known endometriosis and possible past ART. INTERVENTION: Retrospective insurance codes-triggered chart analysis. RESULT(S): Ten patients were admitted for an acute infection with fever, acute abdomen syndrome, elevated white blood cell count, and adnexal mass. Three women had oocyte retrieval, and an endometrioma was present 16, 57, and 102 days earlier. In one patient, the complication occurred 37 days after a cesarean section without prior ART. In the remaining six cases tubo-ovarian abscesses (TOAs) occurred spontaneously in endometriosis women who never had ART. Medical treatment succeeded in only two patients, and the remaining eight needed laparoscopic drainage. In 6 out of those 8 cases, laparoscopic drainage was a second-stage measure justified by failure to respond to antibiotic therapy. CONCLUSION(S): Our data indicate that some putative complications of ART and endometrioma may actually not be linked to ART, but rather constitute sporadic occurrences in endometriosis. Furthermore, TOAs occurring in women with endometriosis are best treated by early surgical drainage together with intravenous antibiotics.

Role of the protein kinase BRAF in the pathogenesis of endometriosis.

Mon, 01 Aug 2016 00:00:00 +0000

OBJECTIVE: Mitogen-activated protein kinases (MAPKs) are involved in the proliferation and survival of endometriotic lesions. Vemurafenib (PLX4032) is a novel protein kinase inhibitor that targets BRAF, a member of the MAPK pathway. The present study tested the in vitro and in vivo effects of PLX4032 on endometriotic cells. RESEARCH DESIGN AND METHODS: We conducted a laboratory study in a tertiary-care university hospital from January 2013 to September 2013. We enrolled a cohort of 40 patients: 20 with histologically proven endometriosis and 20 unaffected women. A thorough surgical examination of the abdominopelvic cavity was performed on all of the study participants. Ex vivo stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from both sets of patients. Proliferation, apoptosis, pERK/ERK ratio, cell cycle regulation (Cyclin D1 and CDK4) and inflammation (PTGS2) were explored with and without PLX4032 treatment. Human endometriotic lesions were implanted into 40 nude mice that were separated into two groups according to PLX4032 or vehicle treatment, which they received for four weeks, before sacrifice and histological examination. RESULTS: Treating endometriotic cells with PLX4032 abrogated the phosphorylation of ERK, significantly reducing the pERK/ERK ratio in both epithelial and stromal cells from endometriotic women compared to the controls (p < 0.05). In addition, treatment with PLX4032 significantly decreased proliferation in both stromal and epithelial cells with a concomitant decrease in Cyclin D1/CDK4 complex and PTGS2 levels. Using a murine model of endometriosis, we observed that PLX4032-treated mice displayed a significant decrease in implant volume compared to the initial size; a slight, but non-significant, increase in size was observed in the vehicle-treated mice. CONCLUSION: Our data suggest that MAPKs and BRAF are involved in the pathogenesis of endometriosis. PLX4032-induced inhibition of BRAF controlled endometriotic growth, both in vitro and in vivo, and could constitute a promising target for the treatment of endometriosis.

Surgical treatment: Myomectomy and hysterectomy; Endoscopy: A major advancement.

Fri, 01 Jul 2016 00:00:00 +0000

Uterine fibroids affect 25% of women worldwide. Symptomatic women can be treated by either medical or surgical treatment. Development of endoscopic surgery has widely changed the management of myoma. Currently, although laparoscopic or laparoscopic robot-assisted myomectomies or hysterectomies are common, there has been no consensual guideline concerning the surgical techniques, operative route, and usefulness of preoperative treatment. Hysteroscopy management is a major advancement avoiding invasive surgery. This study deals with a literature review concerning surgical management of fibroids.

Consensus on Recording Deep Endometriosis Surgery: the CORDES statement.

Wed, 01 Jun 2016 00:00:00 +0000

STUDY QUESTION: Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? SUMMARY ANSWER: A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. WHAT IS KNOWN ALREADY: Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. STUDY DESIGN, SIZE, DURATION: International expert consensus based on a systematic review of literature. PARTICIPANTS/MATERIALS, SETTING, METHODS: Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. MAIN RESULTS AND THE ROLE OF CHANCE: We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. LIMITATIONS, REASONS FOR CAUTION: The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the recommendations presented here. WIDER IMPLICATIONS OF THE FINDINGS: This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population. STUDY FUNDING/COMPETING INTERESTS: None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD. TRIAL REGISTRATION NUMBER: N/A.

Increased rate of spontaneous miscarriages in endometriosis-affected women.

Sun, 01 May 2016 00:00:00 +0000

STUDY QUESTION: Were spontaneous miscarriages more frequent in women with histologically proven endometriosis when compared with endometriosis-free controls? SUMMARY ANSWER: Endometriosis-affected women display a significantly higher rate of previous spontaneous miscarriages than endometriosis-free controls. WHAT IS KNOWN ALREADY: The association between endometriosis and miscarriages has long been debated without reaching a consensus. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study comparing exposed women (endometriosis) and control (without endometriosis) regarding the incidence of miscarriages. All study participants underwent surgery for benign gynaecological conditions in a tertiary-care university hospital between January 2004 and March 2013. After thorough surgical examination of the abdominopelvic cavity, 870 women with histologically proven endometriosis were allocated to the endometriosis group and 981 unaffected women to the control group. Only previously pregnant women were finally included for the study analysis: 284 women in the endometriosis group and 466 in the control group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected preoperatively using a structured questionnaire. Among women with at least one pregnancy before the surgery, the type and number of the different previous first trimester pregnancies outcomes were studied. Previous history of miscarriage was studied according to the existence of previous infertility history and the disease severity (revised American Fertility Society and surgical classification). MAIN RESULTS AND THE ROLE OF CHANCE: Four hundred and seventy-eight pregnancies in endometriosis-affected women and 964 pregnancies in controls were analysed. The previous miscarriage rate was significantly higher in women with endometriosis compared with the controls (139/478 [29] versus 187/964 [19%], respectively; ITALIC! P < 0.001). After a subgroup analysis, the miscarriage rates of women with endometriosis and the controls were, respectively: 20 versus 12% ( ITALIC! P = 0.003) among women without a previous history of infertility and 53 versus 30% ( ITALIC! P < 0.001) for women with a previous history of infertility. After using a random-effects Poisson regression and adjusting for confounding factors, we found a significantly increased incidence rate ratio (IRR) for miscarriages in women with endometriosis (adjusted IRR: 1.70, 95% confidence interval: 1.34-2.16). LIMITATIONS, REASONS FOR CAUTION: There is a possible selection bias due to the specificity of the study design which included only surgical patients. In the control group, certain of the surgical gynaecological conditions, such as fibroids, ovarian cysts or tubal pathologies, might be associated with higher spontaneous miscarriage rates. In the endometriosis group, asymptomatic women were less likely to be referred for surgery and might therefore be underrepresented. WIDER IMPLICATIONS OF THE FINDINGS: This study opens the doors to future, more mechanistic studies to establish the exact link between endometriosis and spontaneous miscarriage rates. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. The authors have no conflicts of interest to declare.

Decreased ovarian reserve in HIV-infected women.

Sun, 24 Apr 2016 00:00:00 +0000

OBJECTIVE: To evaluate HIV directly or indirectly related altered ovarian function, using serum anti-Müllerian hormone (AMH) levels in HIV-infected women as compared with seronegative women. DESIGN: We conducted a matched cohort study from January 2008 to December 2013 in a tertiary university centre. Two hundred and one HIV-infected women requesting assisted reproductive technology and 603 age and cause of infertility-matched HIV seronegative women were enrolled in this study. METHODS: All data were prospectively collected using a semistructured questionnaire. Serum AMH levels in HIV-infected women and matched controls were compared. To find out the contributing factors to increased serum AMH levels in HIV-infected women, a backward multiple linear regression was performed. RESULTS: Serum AMH levels were significantly lower in HIV-infected group as compared with seronegative controls (3.0 ± 2.8 vs 3.7 ± 3.5 ng/ml; respectively, P = 0.001). Looking for factors associated with altered AMH among HIV-infected women, an association has been shown between tubal disease and a further decrease in serum AMH levels (2.4 ± 2.4 vs 3.4 ± 3.0 ng/ml; respectively, P = 0.011). Among HIV-infected women, after multivariate linear regression analysis, we showed that increased age, BMI and viral load were associated with decreased serum AMH levels whereas in striking contrast an increase in CD4⁺ cell count was associated with an increase of serum AMH levels. CONCLUSION: Serum AMH levels were lower in the HIV-infected group than in the control group. Age, BMI, CD4⁺ cell count and viral load were the independent contributors affecting serum AMH levels among HIV-infected women.

Different Expression of Hypoxic and Angiogenic Factors in Human Endometriotic Lesions.

Fri, 01 Apr 2016 00:00:00 +0000

Endometriosis is associated with local angiogenic and hypoxic mechanisms. Indeed, peritoneal fluid of women with endometriosis generates a specific microenvironment to support the growth and development of ectopic endometrial tissues. The association between proangiogenic markers and hypoxic processes in different endometriosis phenotypes was investigated in the present study, analyzing the expression of several genes, related to hypoxic signaling pathway and involved in angiogenic processes, in nonpregnant women with different forms of endometriosis. Samples of ovarian endometrioma (OMA; n = 16) or deep infiltrating endometriosis (DIE; n = 11) were collected, and in addition, control endometrium was collected from healthy women by hysteroscopy. The gene expression of the hypoxia-inducible factors (HIF) 1/2α, protease-activated receptors (PARs) ¼, and vascular endothelial growth factor (VEGF) A was evaluated by quantitative reverse-transcription polymerase chain reaction. Ovarian endometrioma expresses high levels of HIF-1/2α, PAR-1/4, and VEGF-A, while DIE did not show significantly different gene expression compared to endometrium from unaffected women. A positive correlation between the expression of HIF-1/2α and VEGF-A mRNA was observed in OMA. The overall data point out that the heterogeneity of the disease reflects differences in expression levels of genes associated with hypoxia and angiogenesis, suggesting that such conditions may have an active role in the development of the disease.

Endometriosis-related infertility: assisted reproductive technology has no adverse impact on pain or quality-of-life scores.

Fri, 01 Apr 2016 00:00:00 +0000

OBJECTIVE: To evaluate the impact of assisted reproduction technology (ART) on painful symptoms and quality of life (QoL) in women who have endometriosis as compared with disease-free women. DESIGN: Prospective controlled, observational cohort study. SETTING: University hospital. PATIENT(S): Two hundred and sixty-four matched-pairs of endometriosis and disease-free women undergoing ART. INTERVENTION(S): Assessment of pain evolution using visual analogue scale (VAS) during ART; QoL assessment with the Fertility Quality of Life (FertiQoL) tool. MAIN OUTCOME MEASURE(S): VAS pain intensities relative to dysmenorrhea, dyspareunia, noncyclic chronic pelvic pain (NCCPP), gastrointestinal pain, lower urinary tract pain; trends for VAS change between postretrieval and baseline evaluation; FertiQoL score; and statistical analyses conducted using univariate and adjusted multiple linear regression models. RESULT(S): After excluding canceled cycles and patients lost to follow-up observation, 102 women with endometriosis and 104 disease-free women were retained for the study. The trends for VAS change between the postretrieval and baseline evaluations in the women with endometriosis compared with the disease-free women revealed a statistically significant pain decrease for dysmenorrhea (-1.35 ± 3.23 and 0.61 ± 4.00) and dyspareunia (-1.19 ± 2.58 and 0.14 ± 2.06). For NCCPP, gastrointestinal symptoms, and lower urinary tract symptoms, there were no statistically significant differences between the groups. After multiple linear regression, no worsening of pain was observed in the endometriosis group as compared with disease-free group. In addition subgroup analysis according to endometriosis phenotype failed to show any increase of pain. The quality of life in the endometriosis group was comparable to that of the disease-free group. CONCLUSION(S): Assisted reproduction technology did not exacerbate the symptoms of endometriosis or negatively impact QoL in women with endometriosis as compared with disease-free women.

Abdominal emergencies during pregnancy.

Tue, 01 Dec 2015 00:00:00 +0000

Abdominal emergencies during pregnancy (excluding obstetrical emergencies) occur in one out of 500-700 pregnancies and may involve gastrointestinal, gynecologic, urologic, vascular and traumatic etiologies; surgery is necessary in 0.2-2% of cases. Since these emergencies are relatively rare, patients should be referred to specialized centers where surgical, obstetrical and neonatal cares are available, particularly because surgical intervention increases the risk of premature labor. Clinical presentations may be atypical and misleading because of pregnancy-associated anatomical and physiologic alterations, which often result in diagnostic uncertainty and therapeutic delay with increased risks of maternal and infant morbidity. The most common abdominal emergencies are acute appendicitis (best treated by laparoscopic appendectomy), acute calculous cholecystitis (best treated by laparoscopic cholecystectomy from the first trimester through the early part of the third trimester) and intestinal obstruction (where medical treatment is the first-line approach, just as in the non-pregnant patient). Acute pancreatitis is rare, usually resulting from trans-ampullary passage of gallstones; it usually resolves with medical treatment but an elevated risk of recurrent episodes justifies laparoscopic cholecystectomy in the 2nd trimester and endoscopic sphincterotomy in the 3rd trimester. The aim of the present work is to review pregnancy-induced anatomical and physiological modifications, to describe the main abdominal emergencies during pregnancy, their specific features and their diagnostic and therapeutic management.

Activation of the MAPK/ERK Cell-Signaling Pathway in Uterine Smooth Muscle Cells of Women With Adenomyosis.

Tue, 01 Dec 2015 00:00:00 +0000

We investigated whether the myometrium might be intrinsically different in women with adenomyosis. We studied whether the mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPKs/ERKs) and phosphoinositide 3-kinase/mammalian target of rapamycin/AKT (PI3K/mTOR/AKT) cell-signaling pathways, implicated in the pathogenesis of endometriosis, might also be activated in uterine smooth muscle cells (uSMCs) of women with adenomyosis and measured the production of reactive oxygen species (ROS), proinflammatory mediators that modulate cell proliferation and have been shown to activate the MAPK/ERK pathway in endometriosis. The uSMC cultures were derived from myometrium biopsies obtained during hysterectomy or myomectomy in women with adenomyosis and controls with leiomyoma. Proliferation of uSMCs and in vitro activation of the MAPK/ERK cell-signaling pathway were increased in women with adenomyosis compared to controls. The activation of the PI3K/mTOR/AKT pathway was not significant. The ROS production and ROS detoxification pathways were not different between uSMCs of women with adenomyosis and controls suggesting an ROS-independent activation of the MAPK/ERK pathway. Our results also provide evidence that protein kinase inhibitors and the rapanalogue temsirolimus can control proliferation of uSMCs in vitro suggesting an implication of the MAPK/ERK and the PI3K/mTOR/AKT pathways in proliferation of uSMCs in women with adenomyosis and leiomyomas.

Inhibition of MAPK and VEGFR by Sorafenib Controls the Progression of Endometriosis.

Tue, 01 Sep 2015 00:00:00 +0000

INTRODUCTION: Sorafenib is a strong multikinase inhibitor targeting 2 different pathways of endometriosis pathogenesis: RAF kinase and vascular endothelial growth factor receptor (VEGFR). We investigate whether Sorafenib could control the growth of endometriotic lesions both in vitro and in vivo. METHODS: Stromal primary cells were extracted from endometrial and endometriotic biopsies from patients with (n = 10) and without (n = 10) endometriosis. Proliferation, apoptosis, mitogen-activated protein kinases, and VEGFR-2 autophosphorylation were explored with and without Sorafenib treatment. Human endometriotic lesions were implanted in 30 nude mice randomized according to Sorafenib or placebo treatment. RESULTS: Treating endometriotic cells with Sorafenib abrogated the phosphorylation of extracellular signal-regulated kinase in stromal cells of women with endometriosis compared to controls. In addition, this study highlights the antiangiogenic role of Sorafenib which translates as a decreased phosphorylated VEGFR-2-VEGFR-2 ratio in endometriosis. Using a xenogenic mouse model of endometriosis, we confirmed that Sorafenib regulates the endometriosis activity in vivo by targeting endometriosis-related proliferation and inflammation. CONCLUSION: Our data suggest that Sorafenib controls the growth of endometriotic lesions in vitro and in vivo.

Pathogenetic Mechanisms of Deep Infiltrating Endometriosis.

Tue, 01 Sep 2015 00:00:00 +0000

Endometriosis is a benign gynecologic disease, affecting women of reproductive age associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. Ovarian endometrioma (OMA), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) are, till now, recognized as major phenotypes. The discussion is to know whether they share the same pathogenetic mechanisms. Till today, DIE is recognized as the most severe clinical form of endometriosis and has a complex clinical management. The DIE lesions have been considered in the present article, without distinguishing between the anterior (bladder) or the posterior (vagina, uterosacral ligaments, rectum, and ureter) compartment. The present knowledge indicates that hormonal function (estrogen and progesterone receptors) and immunological factors, such as peritoneal macrophages, natural killer cells, and lymphocytes, are critically altered in DIE. The aggressive behavior of DIE may be explained by the highly decreased apoptosis (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kB], B-cell lymphoma 2 [Blc-2], and anti-Mullerian hormone) and by the increased proliferation activity related to oxidative stress (NF-kB, reactive oxygen species, extracellular regulated kinase (ERK), advanced oxidation protein product). Invasive mechanisms are more expressed (matrix metalloproteinases and activins) in DIE in comparison to the OMA and SPE. Correlated with the increased invasiveness are the data on very high expression of neuroangiogenesis (nerve growth factor, vascular endothelial growth factor, and intercellular adhesion molecule) genes in DIE. Therefore, at the present time, several of the DIE pathogenetic features result specific in comparison to other endometriosis phenotypes, pleading for the existence of a specific entity. These evidence of specific pathogenetic features of DIE may explain the more severe symptomatology related to this form of endometriosis and suggest possible future target medical treatments.

Fusion imaging for evaluation of deep infiltrating endometriosis: feasibility and preliminary results.

Wed, 01 Jul 2015 00:00:00 +0000

OBJECTIVE: Magnetic resonance imaging (MRI) and ultrasound scanning complement each other in screening for and diagnosis of endometriosis. Fusion imaging, also known as real-time virtual sonography, is a new technique that uses magnetic navigation and computer software for the synchronized display of real-time ultrasound and multiplanar reconstructed MR images. Our aim was to evaluate the feasibility and ability of fusion imaging to assess the main anatomical sites of deep infiltrating endometriosis (DIE) in patients with suspected active endometriosis. METHODS: This prospective study was conducted over a 1-month period in patients referred to a trained radiologist for an ultrasound-based evaluation for endometriosis. Patients with a prior pelvic MRI examination within the past year were offered fusion imaging, in addition to the standard evaluation. All MRI examinations were performed on a 1.5-T MRI machine equipped with a body phased-array coil. The MRI protocol included acquisition of at least two fast spin-echo T2-weighted orthogonal planes. The Digital Imaging Communications in Medicine dataset acquired at the time of the MRI examination was loaded into the fusion system and displayed together with the ultrasound image on the same monitor. The sets of images were then synchronized manually using one plane and one anatomical reference point. The ability of this combined image to identify and assess the main anatomical sites of pelvic endometriosis (uterosacral ligaments, posterior vaginal fornix, rectum, ureters and bladder) was evaluated and compared with that of standard B-mode ultrasound and MRI. RESULTS: Over the study period, 100 patients were referred for ultrasound examination because of endometriosis. Among them were 20 patients (median age, 35 (range, 27-49) years) who had undergone MRI examination within the past year, with a median (range) time interval between MRI and ultrasound examination of 171 (1-350) days. All 20 patients consented to undergo additional evaluation by fusion imaging. However, in three (15%) cases, fusion imaging was not technically possible because of changes since the initial MRI examination resulting from either interval surgery (n = 2; 10%) or pregnancy (n = 1; 5%). Data acquisition, matching and fusion imaging were performed in under 10 min in each of the other 17 cases. The overall ability of each technique to identify and assess the main anatomical landmarks of endometriosis was as follows: uterosacral ligaments: ultrasound, 88% (30/34); MRI, 100% (34/34); fusion imaging, 100% (34/34); posterior vaginal fornix: ultrasound, 88% (30/34); MRI, 100% (34/34); fusion imaging, 100% (34/34); rectum: ultrasound, 100% (17/17); MRI, 82.3% (14/17); fusion imaging, 100% (17/17); ureters: ultrasound, 0%; MRI, 100% (34/34); fusion imaging, 100% (34/34); and bladder: ultrasound, 100%; MRI, 100%; fusion imaging, 100%. CONCLUSION: Fusion imaging is feasible for the assessment of endometriotic lesions. Because it combines information from both ultrasound and MRI techniques, fusion imaging allows better identification of the main anatomical sites of DIE and has the potential to improve the performance of ultrasound and MRI examination.

Deep endometriosis infiltrating the recto-sigmoid: critical factors to consider before management.

Fri, 01 May 2015 00:00:00 +0000

BACKGROUND: Deep endometriosis invading the bowel constitutes a major challenge for the gynecologist. In addition to the greater impact on pain, the high incidence of surgical morbidity involved with bowel endometriosis poses a therapeutic dilemma for the surgeon. Intestinal involvement by deep endometriotic nodules has been estimated to occur in 8-12% of women with endometriosis. Individual and clinical factors, pre-operative morphologic characteristics from imaging, surgical considerations and impact on quality of life are critical variables that should be considered in determining the best therapeutic strategy for a patient with deep endometriosis involving the sigmoid and/or the rectum. Pre-operative planning is fundamental for defining the optimal therapeutic strategy; patient counseling of treatment options, and when surgery is indicated, involvement of a multidisciplinary surgical team is required. METHODS: The PubMed and Cochrane database were searched for all original and review articles published in English, French and Italian, until June 2014. Search terms included ‘deep endometriosis’, ‘surgical and clinical approach’, ‘bowel disease’, ‘quality of life’, ‘management of deep endometriosis’. Special attention was paid to articles comparing features of discoid and segmental resection. RESULTS: The rationale for the best therapeutic options for patients with deep endometriosis has been shown and an evidence-based treatment algorithm for determining when and which surgical intervention may be required is proposed. In deciding the best treatment option for patients with deep endometriosis involving the sigmoid and rectum, it is important to understand how the different clinical factors and pre-operative morphologic imaging affect the algorithm. Surgery is not indicated in all patients with deep endometriosis, but, when surgery is chosen, a complete resection by the most appropriate surgical team is required in order to achieve the best patient outcome. CONCLUSION: In women with deep endometriosis, surgery is the therapy of choice for symptomatic patients when deep lesions do not improve with a medical treatment.

Urinary endometriosis: MR imaging appearance with surgical and histological correlations.

Wed, 01 Apr 2015 00:00:00 +0000

OBJECTIVES: The goals of the study were to describe the MR imaging features of endometriosis of the urinary tract and identify those that suggest intrinsic involvement of ureteric wall. MATERIALS AND METHODS: Thirty-five women with proven urinary tract endometriosis and who had preoperative MR imaging between 2001 and 2011 were included retrospectively. MR images were intrepreted by one junior and one senior radiologists. To characterize the intrinsic parietal involvement, the ureteric circumference involved by the lesion of endometriosis was noted. RESULTS: Thirty-eight ureteric and 13 bladder lesions were analyzed. They were found in association in nine women. Ureteric lesions were bilateral in seven women. Of the 38 ureteric lesions, 27 were extrinsic and 11 intrinsic at histopathological analysis. Sixteen women with extrinsic lesions and 10 with intrinsic ones were correctly identified on MR imaging. When the ureter was included less than 360° in the lesion, extrinsic involvement was confirmed in 80% of cases. CONCLUSION: MR imaging appears to be more sensitive (91%vs 82%) but less specific (59% vs 67%) than surgery for the diagnosis of intrinsic form of ureteric location.

Soluble ligands for the NKG2D receptor are released during endometriosis and correlate with disease severity.

Mon, 16 Mar 2015 00:00:00 +0000

BACKGROUND: Endometriosis is a benign gynaecological disease. Abundant bulk of evidence suggests that patients with endometriosis have an immunity dysfunction that enables ectopic endometrial cells to implant and proliferate. Previous studies show that natural killer cells have a pivotal role in the immune control of endometriosis. METHODS AND FINDINGS: This is a prospective laboratory study conducted in a tertiary-care university hospital between January 2011 and April 2013. We investigated non-pregnant, younger than 42-year-old patients (n= 202) during surgery for benign gynaecological conditions. After complete surgical exploration of the abdominopelvic cavity, 121 women with histologically proven endometriosis and 81 endometriosis-free controls women were enrolled. Patients with endometriosis were classified according to a surgical classification in three different types of endometriosis: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE). Peritoneal fluid samples were obtained from all study participants during the surgery in order to detect soluble NKG2D ligands (MICA, MICB and ULBP-2). When samples with undetectable peritoneal fluid levels of MICA, MICB and ULBP-2 were excluded, MICA ratio levels were significantly higher in endometriosis patients than in controls (median, 1.1 pg/mg; range, 0.1-143.5 versus median, 0.6 pg/mg; range, 0.1-3.5; p=0.003). In a similar manner peritoneal fluid MICB levels were also increased in endometriosis-affected patients compared with disease-free women (median, 4.6 pg/mg; range, 1.2-4702 versus median, 3.4 pg/mg; range, 0.7-20.1; p=0.001). According to the surgical classification, peritoneal fluid soluble MICA, MICB and ULBP-2 ratio levels were significantly increased in DIE as compared to controls (p=0.015, p=0.003 and p=0.045 respectively). MICA ratio levels also correlated with dysmenorrhea (r=0.232; p=0.029), total rAFS score (r=0.221; p=0.031) and adhesions rAFS score (r=0.221; p=0.031). CONCLUSIONS: We demonstrate a significant increase of peritoneal fluid NKG2D ligands in women with endometriosis especially in those cases presenting DIE. This study suggests that NKG2D ligands shedding is a novel pathway in endometriosis complex pathogenesis that impairs NK cell function.

Low birth weight is strongly associated with the risk of deep infiltrating endometriosis: results of a 743 case-control study.

Fri, 13 Feb 2015 00:00:00 +0000

The influence of intrauterine environment on the risk of endometriosis is still controversial. Whether birth weight modifies the risk of endometriosis in adulthood remains an open question. For this purpose, we designed a case-control study involving 743 women operated on for benign gynecological indications from January 2004 to December 2011. Study group included 368 patients with histologically proven endometriosis: 54 superficial endometriosis (SUP), 79 endometriomas (OMA) and 235 deep infiltrating endometriosis (DIE). Control group included 375 patients without endometriosis as surgically checked. Mean birth weights were compared between patients and controls, according to endometriosis groups and rAFS stages. Mean birth weight was significantly lower for patients with endometriosis as compared to controls (3,119 g ± 614 and 3,251 g ± 557 respectively; p = 0.002). When compared to controls, patients with DIE had the lowest birth weight with a highly significant difference (3,103 g ± 620, p = 0.002). In univariate analysis, patients with low birth weight (LBW), defined as a BW < 2,500 g, had a higher risk of endometriosis, especially DIE, as compared to the reference group (OR = 1.5, 95%CI: 1.0-2.3 and OR = 1.7, 95%CI: 1.0-2.7, respectively). Multivariate analysis, adjusted on ethnicity and smoking status, showed the persistence of a significant association between endometriosis and LBW with a slight increase in the magnitude of the association (aOR = 1.7, 95%CI: 1.0-2.6 for endometriosis, aOR = 1.8; 95%CI: 1.1-2.9 for DIE). In conclusion, LBW is independently associated with the risk of endometriosis in our population. Among patients with LBW, the risk is almost two-times higher to develop DIE. This association could reflect common signaling pathways between endometriosis and fetal growth regulation. There is also the possibility of a role played by placental insufficiency on the development of the neonate’s pelvis and the occurrence of neonatal uterine bleeding that could have consequences on the risk of severe endometriosis.

Identification of susceptibility genes for peritoneal, ovarian, and deep infiltrating endometriosis using a pooled sample-based genome-wide association study.

Wed, 04 Feb 2015 00:00:00 +0000

Characterizing genetic contributions to endometriosis might help to shorten the time to diagnosis, especially in the most severe forms, but represents a challenge. Previous genome-wide association studies (GWAS) made no distinction between peritoneal endometriosis (SUP), endometrioma (OMA), and deep infiltrating endometriosis (DIE). We therefore conducted a pooled sample-based GWAS and distinguished histologically confirmed endometriosis subtypes. We performed an initial discovery step on 10-individual pools (two pools per condition). After quality control filtering, a Monte-Carlo simulation was used to rank the significant SNPs according to the ratio of allele frequencies and the coefficient of variation. Then, a replication step of individual genotyping was conducted in an independent cohort of 259 cases and 288 controls. Our approach was very stringent but probably missed a lot of information due to the Monte-Carlo simulation, which likely explained why we did not replicate results from -‘classic-’ GWAS. Four variants (rs227849, rs4703908, rs2479037, and rs966674) were significantly associated with an increased risk of OMA. Rs4703908, located close to ZNF366, provided a higher risk of OMA (OR = 2.22; 95% CI: 1.26-3.92) and DIE, especially with bowel involvement (OR = 2.09; 95% CI: 1.12-3.91). ZNF366, involved in estrogen metabolism and progression of breast cancer, is a new biologically plausible candidate for endometriosis.

Endometriosis also affects the decidua in contact with the fetal membranes during pregnancy.

Sun, 01 Feb 2015 00:00:00 +0000

STUDY QUESTION: Are the fetal membranes of women affected with endometriosis similar to those from disease-free women? SUMMARY ANSWER: Decidua of women with endometriosis is able to generate endometriotic-like lesions in contact with the fetal membranes. WHAT IS KNOWN ALREADY: Eutopic endometrium of women affected with endometriosis presents compromised properties. Endometrium undergoes decidualisation to accept and to further control the conceptus development during pregnancy. Decidualized endometrium is in close contact with the chorionic membrane and forms the choriodecidual layer, a major maternal-fetal interface. STUDY DESIGN, SIZE, DURATION: This is a laboratory case-control study involving diseased versus control samples. Eleven case samples and 11 control samples were collected from women in a tertiary care/research center between November 2011 and December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were consecutive pregnant women affected with confirmed endometriosis and disease free women, who underwent Cesarean section before labor for obstetrical indication. The choriodecidual tissues were characterized using histology, immunohistochemistry, transcriptomic and whole genome CpG methylation analyses. MAIN RESULTS AND THE ROLE OF CHANCE: We demonstrate for the first time the presence of endometriotic-like lesions within the decidual side of the choriodecidua of the fetal membranes from women affected with severe endometriosis. Fetal membranes from women affected with endometriosis exhibited glandular components in the choriodecidual layer surrounded by enlarged decidualized cells disseminated along the entire membrane surface. Significant deregulation (variation of expression ≥2, P-value ≤0.05) was observed for 2773 genes known to be enriched in processes involved in glandular function, endocrine and nervous system, neoangiogenesis, and autoimmune disease. CpG methylation analysis revealed 5999 differentially methylated regions with a P-value ≤0.05. LIMITATIONS, REASONS FOR CAUTION: We studied women who delivered at term by Cesarean section before labor, following an uneventful pregnancy. Notwithstanding this, one cannot exclude that the presence of disseminated endometriotic lesions within the choriodecidual layer of the fetal membranes may disturb the anatomical integrity and/or the function of the membranes in some women with endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Our results shed new light on the capability of the diseased decidua to develop lesions not only at ectopic autologous locations, but also on the semi-allogenous fetal membranes, a particularly immunotolerant environment.

Increased serum cancer antigen-125 is a marker for severity of deep endometriosis.

Sun, 01 Feb 2015 00:00:00 +0000

STUDY OBJECTIVE: To determine whether cancer antigen-125 (CA-125) levels are increased in women with endometriosis, especially in those with endometriomas (OMAs), deep infiltrating lesions (DIE), and superficial endometriosis (SUP) compared with controls without endometriosis in a large cohort of operated women. DESIGN: Cross-sectional study (Canadian Task Force classification II-2). SETTING: Tertiary-care university hospital. PATIENTS: Four hundred six women with histologically proven endometriosis and 279 women without endometriosis. INTERVENTIONS: Surgical examination of the abdomino-pelvic cavity. MEASUREMENTS AND MAIN RESULTS: Preoperative serum CA-125 antigen levels were evaluated by electrochemoluminescence immunoassay in women with endometriosis and controls. Correlations between serum CA-125 levels and clinical and anatomical characteristics of disease severity were examined. Women with endometriosis displayed higher mean serum CA-125 levels compared with disease-free controls (50.1 ± 62.4 U/mL vs 22.5 ± 25.2 U/mL; p ≤ .001). CA-125 levels were significantly increased in women with OMA (60.8 ± 63.5 U/mL) and DIE (55.2 ± 68.7 U/mL) compared with women with SUP (23.2 ± 24.5 U/mL) and controls (22.5 ± 25.2 U/mL). There was no difference in CA-125 levels between patients with SUP and controls and between patients with OMA and DIE. CA-125 serum levels were correlated with DIE severity: the mean number of DIE lesions and worst DIE lesion. CONCLUSION: Serum CA-125 levels were significantly increased in women with severe forms of endometriosis, OMA, and DIE lesions. In addition, elevated serum Ca-125 levels were associated with more severe and extended DIE lesions. In women with superficial peritoneal lesions, CA-125 levels were not different from women without endometriosis.

Protein oxidative stress markers in peritoneal fluids of women with deep infiltrating endometriosis are increased.

Thu, 01 Jan 2015 00:00:00 +0000

STUDY QUESTION: Are protein oxidative stress markers [thiols, advanced oxidation protein products (AOPP), protein carbonyls and nitrates/nitrites] in perioperative peritoneal fluid higher in women with histologically proven endometriosis when compared with endometriosis-free controls? SUMMARY ANSWER: Protein oxidative stress markers are significantly increased in peritoneal fluids from women with deep infiltrating endometriosis with intestinal involvement when compared with endometriosis-free controls. WHAT IS KNOWN ALREADY: Endometriosis is a common gynaecologic condition characterized by an important inflammatory process. Various source of evidence support the role of oxidative stress in the development of endometriosis. STUDY DESIGN, SIZE, DURATION: We conducted a prospective laboratory study in a tertiary-care university hospital between January 2011 and December 2012, and included 235 non-pregnant women, younger than 42 year old, undergoing surgery for a benign gynaecological condition. PARTICIPANTS/MATERIALS, SETTING, METHODS: After complete surgical exploration of the abdomino-pelvic cavity, 150 women with histologically proven endometriosis and 85 endometriosis-free controls women were enrolled. Women with endometriosis were staged according to a surgical classification in three different phenotypes of endometriosis: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) and deeply infiltrating endometriosis (DIE). Perioperative peritoneal fluids samples were obtained from all study participants. Thiols, AOPP, protein carbonyls and nitrates/nitrites were assayed in all peritoneal samples. MAIN RESULTS AND THE ROLE OF CHANCE: Concentrations of peritoneal AOPP were significantly higher in endometriosis patients than in the control group (median, 128.9 µmol/l; range, 0.3-1180.1 versus median, 77.8 µmol/l; range, 0.8-616.1; P < 0.001). In a similar manner concentrations of peritoneal nitrates/nitrites were higher in endometriosis patients than in the control group (median, 24.8 µmol/l; range, 1.6-681.6 versus median, 18.5 µmol/l; range, 1.6-184.5; P < 0.05). According to the surgical classification, peritoneal fluids protein AOPP and nitrates/nitrites were significantly increased only in DIE samples when compared with controls (P < 0.001 and P < 0.05; respectively), whereas the others forms of endometriosis (SUP and OMA) showed non-statistically significant increases. We found positive correlations between peritoneal fluids AOPP concentrations, nitrites/nitrates levels and the total number of intestinal DIE lesions (r = 0.464; P < 0.001 and r = 0.366; P = 0.007; respectively). LIMITATIONS, REASONS FOR CAUTION: Inclusion of only surgical patients may constitute a possible selection bias. In fact, our control group involved women who underwent surgery for benign gynaecological conditions. This specificity of our control group may lead to biases stemming from the fact that some of these conditions, such as fibroids, ovarian cysts or tubal infertility, might be associated with altered peritoneal proteins oxidative stress markers. WIDER IMPLICATIONS OF THE FINDINGS: We demonstrate the existence of a significantly increased protein oxidative stress status in peritoneal fluid from women with endometriosis especially in cases of DIE with intestinal involvement. This study opens the way to future more mechanistics studies to determine the exact role of protein oxidative stress in the pathogenesis of endometriosis. Even if an association does not establish proof of cause and effect, these intrinsic biochemical characteristics of endometriosis may lead to the evaluation of therapeutic approaches targeting oxidative imbalance. STUDY FUNDING/COMPETING INTERESTS: No funding was used for this study. The authors have no conflict of interest.

Dual ovarian stimulation is a new viable option for enhancing the oocyte yield when the time for assisted reproductive technnology is limited.

Mon, 01 Dec 2014 00:00:00 +0000

Ovarian stimulation improves assisted reproductive technology outcome by increasing the number of oocytes available for insemination and in-vitro handling. A recent Duplex protocol features a dual stimulation, with the second stimulation started immediately after the first oocyte retrieval. Remarkably, the Duplex protocol is unexpectadly well tolerated by women and provides twice as many oocytes and embryos as a regular antagonist protocol in less than 30 days.

[Endometriosis: increasing concentrations of serum interleukin-1β and interleukin-1sRII is associated with the deep form of this pathology].

Sat, 01 Nov 2014 00:00:00 +0000

OBJECTIVES: To assess interleukin-1β (IL-1β) and its inhibitory soluble interleukin-1 receptor type II (IL-1sRII) levels into the serum of patients with various forms of endometriosis and normal women, and investigate the correlation with disease activity. PATIENTS AND METHODS: In this prospective laboratory study (2005-2010), 510 women with histologically proven endometriosis and 93 endometriosis-free controls have been enrolled. Laparoscopic complete exploration of the abdominopelvic cavity and blood samples have been performed in each patient. For each serum, IL-1β and IL-1sRII have been evaluated using Elisa. RESULTS: IL-1β and IL-1sRII have been respectively detectable in 64% and 54.6% of serum samples from all 603 women studied. IL-1β was higher in women with deep infiltrating endometriosis (DIE) (mean 10.0pg/mL [0.005-416.2]) than in endometriosis-free women (mean 0.5pg/mL [0.01-1.7], P<0.01) or in women with superficial endometriosis (SUP) (mean 0.6pg/mL [0.1-2.9], P<0.01). Also, IL-1sRII was higher in DIE (mean 236.7pg/mL [0.9-6975]) than in the witness group (mean 85.0pg/mL [1-235.2], P<0.05) or in SUP (mean 85.1pg/mL [0.6-302], P<0.01). CONCLUSION: This study highlights both a marked significant increase in serum IL-1β and IL-1sRII levels in DIE compared to SUP and normal women and suggests that a defect in the control of IL-1 can impact the pathophysiology of endometriosis.

An update on the pharmacological management of adenomyosis.

Sat, 01 Nov 2014 00:00:00 +0000

INTRODUCTION: Adenomyosis, characterized by the infiltration of the myometrium by ectopic endometrial islets, is a common condition that causes dysmenorrhea, abnormal uterine bleeding and infertility. Different treatment options exist, including medical and surgical treatments. The most commonly used medications are NSAIDs, progestogens and GnRH agonists (GnRHas). AREAS COVERED: We conducted a literature search for in vitro and animal studies, randomized and non-randomized studies, systematic reviews and ongoing trials registered on ClinicalTrials.gov. There are almost no well-conducted randomized controlled trials on the pharmacological treatment of adenomyosis and the information collected from published studies is insufficient. Several therapeutic targets have been identified through animal and in vitro studies, and it is hoped that they will lead to further clinical studies on new compounds and treatment targets in this heterogeneous disease. EXPERT OPINION: Hysterectomy is very effective at treating women with symptomatic adenomyosis who have completed their wish of pregnancy. For women with a future desire of pregnancy medical treatments remain the best options. Progestogens and GnRHas are the most frequently used long-term treatments for abnormal uterine bleeding and pain symptoms. In assisted reproductive techniques long agonist stimulation protocols and pretreatment with GnRHas for differed embryo transfer seem to improve pregnancy rates.

Association of history of surgery for endometriosis with severity of deeply infiltrating endometriosis.

Wed, 01 Oct 2014 00:00:00 +0000

OBJECTIVE: To assess whether a history of surgery for endometriosis could be considered as a marker for disease severity. METHODS: This cross-sectional study included 780 women with histologically proven endometriosis who underwent surgery. We compared 309 patients with a history of surgery for endometriosis (study group) with 471 patients who did not receive prior surgical intervention (control group). Multivariate logistic regression was performed to assess the risk of deeply infiltrating endometriosis (defined by invasion of the muscularis by endometriotic tissue). RESULTS: Patients with a history of surgery displayed an increased prevalence of deeply infiltrating endometriosis (242 patients [78.3%] compared with 210 patients [44.6%], respectively; P<.001). Moreover, the study group showed significantly higher stage, mean total (P<.001), and mean adhesions (P<.001) scores based on the American Society for Reproductive Medicine classification system. Furthermore, history of previous surgery remained independently associated with the presence of deeply infiltrating endometriosis (compared with superficial endometriosis and ovarian endometrioma grouped together) in multivariate regression analysis, which adjusted for preoperative pain scores, age, body mass index, smoking habits, oral contraceptive pill use, infertility, and parity (adjusted odds ratio 2.96, 95% confidence interval 1.99-4.39; P<.001). The number of previous surgeries for endometriosis correlated significantly with lesion severity. Among women presenting with deeply infiltrating endometriosis (n=452), surgical history was significantly associated with a higher mean number of deeply infiltrating endometriosis lesions (3.1 ± 1.9 compared with 2.6 ± 1.8; P=.001) and with increased severity of deeply infiltrating endometriosis lesions, especially in the case of intestinal lesions (159 patients [66.0%] compared with 77 patients [37%], P<.001). CONCLUSION: A history of surgery for endometriosis correlates with the presence and severity of deeply infiltrating endometriosis, which underlines the necessity of a thorough preoperative assessment and a complete information of these patients before undertaking subsequent surgeries. LEVEL OF EVIDENCE: : II.

FOXL2 in human endometrium: hyperexpressed in endometriosis.

Wed, 01 Oct 2014 00:00:00 +0000

The present study investigated expression and protein localization of FOXL2 messenger RNA (mRNA) in endometrium of healthy women and in patients with endometriosis during endometrial cycle. In endometriotic lesions, FOXL2 mRNA and protein were evaluated and a possible correlation with activin A mRNA expression changes was also studied. Endometrium was collected from healthy women (n = 52) and from women with endometriosis (n = 31) by hysteroscopy; endometriotic tissues were collected by laparoscopy (n = 38). FOXL2 gene expression analysis in endometrium of healthy women showed a significant expression and no significant changes in mRNA levels between proliferative and secretory phases; a similar pattern was observed in endometrium of patients with endometriosis. Immunohistochemical evaluation showed that FOXL2 protein localized in stromal and glandular cells and colocalized with SUMO-1. FOXL2 mRNA expression was 3-fold higher in endometriosis than in healthy endometrium (P < .01) and a positive correlation between FOXL2 and activin A mRNA was found (P < .05) in endometriosis. In conclusion, FOXL2 mRNA expression and its protein localization do not change during endometrial cycle in eutopic endometrium from healthy individuals or patients with endometriosis; the hyperexpression of FOXL2 in endometriotic lesions suggests an involvement of this transcriptional regulator, probably associated with activin A expression and related to the pathogenesis of endometriosis.

ABO and Rhesus blood groups and risk of endometriosis in a French Caucasian population of 633 patients living in the same geographic area.

Wed, 27 Aug 2014 00:00:00 +0000

OBJECTIVES: The identification of epidemiological factors increasing the risk of endometriosis could shorten the time to diagnosis. Specific blood groups may be more common in patients with endometriosis. STUDY DESIGN: We designed a cross-sectional study of 633 Caucasian women living in the same geographic area. Study group included 311 patients with histologically proven endometriosis. Control group included 322 patients without endometriosis as checked during surgery. Frequencies of ABO and Rhesus groups in the study and control groups were compared using univariate and multivariate analyses. RESULTS: We observed a higher proportion of Rh-negative women in the study group, as compared to healthy controls. Multivariate analysis showed that Rh-negative women are twice as likely to develop endometriosis (aOR = 1.90; 95% CI: 1.20-2.90). There was no significant difference in ABO group distribution between patients and controls. There was no difference when taking into account either the clinical forms (superficial endometriosis, endometrioma, and deep infiltration endometriosis) or the rAFS stages. CONCLUSION: Rh-negative women are twice as likely to develop endometriosis. Chromosome 1p, which contains the genes coding for the Rhesus, could also harbor endometriosis susceptibility genes.

A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma.

Fri, 01 Aug 2014 00:00:00 +0000

STUDY QUESTION: Is it possible to detect associated deep infiltrating endometriosis (DIE) before surgery for patients operated on for endometriomas using a preoperative clinical symptoms questionnaire? SUMMARY ANSWER: A diagnostic score of DIE associated with endometriomas using four clinical symptoms defined a high-risk group where the probability of DIE was 88% and a low-risk group with a 10% probability of DIE. WHAT IS KNOWN ALREADY: Many clinical symptoms are already known to be associated with DIE but they have not yet been used to build a clinical prediction model. STUDY DESIGN, SIZE, DURATION: We built a diagnostic score of DIE based on a case control study of 326 consecutive patients operated on for an endometrioma between January 2005 and October 2011: 164 had associated DIE (DIE+) and 162 had no DIE (DIE-). We derived the score on a training sample obtained from a random selection of 2/3 of the population (211 patients, 101 DIE+, 110 DIE-), and validated the results on the remaining third (115 patients, 63 DIE+, 52 DIE-). The gold standard for the diagnosis of DIE was based on surgical exploration and histological diagnosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were consecutive patients aged 18-42 years who underwent surgery for an endometrioma with histological confirmation and complete treatment of their endometriotic lesions: data for these women were extracted from a prospective database including a standardized preoperative questionnaire. On the training dataset, variables associated with DIE in a univariate analysis were introduced in a multiple logistic regression and selected by a backward stepwise procedure and a Jackknife procedure. A diagnostic score of DIE was built with the scaled/rounded coefficients of the multiple regression. Two cut-off values delimitated a high and a low risk group, and their diagnostic accuracy was tested on the validation dataset. MAIN RESULTS AND THE ROLE OF CHANCE: Four variables were independently associated with DIE: visual analogue scale of gastro-intestinal symptoms ≥5 or of deep dyspareunia >5 (adjusted diagnostic odds ratio (aDOR) = 6.0, 95% confidence interval (CI) [2.9-12.1]), duration of pain greater than 24 months (aDOR = 3.8, 95% CI [1.9-7.7]), severe dysmenorrhoea (defined as the prescription of the oral contraceptive pill for the treatment of a primary dysmenorrhoea or the worsening of a secondary dysmenorrhoea) (aDOR = 3.8, 95% CI [1.9-7.6]) and primary or secondary infertility (aDOR = 2.5, 95% CI [1.2-4.9]). The sum of these variables weighted by their rounded/scaled coefficients constituted the score ranging from 0 to 53. A score <13 defined a low-risk group where the probability of DIE was 10% (95% CI [7-15] with a sensitivity of 95% (95% CI [89-98]) and a negative likelihood ratio of 0.1 (95% CI [0.0-0.3]). A score ≥35 defined a high-risk group where the probability of DIE was 88% (95% CI [83-92%]), with a specificity of 94% (95% CI [87-97]), and a positive likelihood ratio of 8.1 (95% CI [3.9-17.0]). The performance of the score was confirmed on the validation dataset with 11% of DIE+ patients having a score <13 (sensibility: 95%) and 90% of DIE+ patients having a score ≥35 (specificity: 94%). LIMITATION, REASONS FOR CAUTION: This study was performed in a department specialized in DIE management. Score accuracy could be different in less specialized centres. WIDER IMPLICATIONS OF THE FINDINGS: This score could have a major clinical impact on the time of diagnosis, the management of DIE and could reduce the cost of investigations by helping to identify high-risk patients, while preserving the quality of care. STUDY FUNDING/COMPETING INTERESTS: The authors have no competing interests to declare. No grant supported the study.

In vitro activity and resistance profile of samatasvir, a novel NS5A replication inhibitor of hepatitis C virus.

Fri, 01 Aug 2014 00:00:00 +0000

The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein is a clinically validated target for drugs designed to treat chronic HCV infection. This study evaluated the in vitro activity, selectivity, and resistance profile of a novel anti-HCV compound, samatasvir (IDX719), alone and in combination with other antiviral agents. Samatasvir was effective and selective against infectious HCV and replicons, with 50% effective concentrations (EC50s) falling within a tight range of 2 to 24 pM in genotype 1 through 5 replicons and with a 10-fold EC50 shift in the presence of 40% human serum in the genotype 1b replicon. The EC90/EC50 ratio was low (2.6). A 50% cytotoxic concentration (CC50) of >100 μM provided a selectivity index of >5 × 10(7). Resistance selection experiments (with genotype 1a replicons) and testing against replicons bearing site-directed mutations (with genotype 1a and 1b replicons) identified NS5A amino acids 28, 30, 31, 32, and 93 as potential resistance loci, suggesting that samatasvir affects NS5A function. Samatasvir demonstrated an overall additive effect when combined with interferon alfa (IFN-α), ribavirin, representative HCV protease, and nonnucleoside polymerase inhibitors or the nucleotide prodrug IDX184. Samatasvir retained full activity in the presence of HIV and hepatitis B virus (HBV) antivirals and was not cross-resistant with HCV protease, nucleotide, and nonnucleoside polymerase inhibitor classes. Thus, samatasvir is a selective low-picomolar inhibitor of HCV replication in vitro and is a promising candidate for future combination therapies with other direct-acting antiviral drugs in HCV-infected patients.

Synthesis of 2'-O,4'-C-alkylene-bridged ribonucleosides and their evaluation as inhibitors of HCV NS5B polymerase.

Sun, 15 Jun 2014 00:00:00 +0000

The synthesis of 2’-O,4’-C-methylene-bridged bicyclic guanine ribonucleosides bearing 2’-C-methyl or 5’-C-methyl modifications is described. Key to the successful installation of the methyl functionality in both cases was the use of a one-pot oxidation-Grignard procedure to avoid formation of the respective unreactive hydrates prior to alkylation. The 2’-C-methyl- and 5’-C-methyl-modified bicyclic guanosines were evaluated, along with the known uracil-, cytosine-, adenine-, guanine-LNA and guanine-ENA nucleosides, as potential antiviral agents and found to be inactive in the hepatitis C virus (HCV) cell-based replicon assay. Examination of the corresponding nucleoside triphosphates, however, against the purified HCV NS5B polymerase indicated that LNA-G and 2’-C-methyl-LNA-G are potent inhibitors of both 1b wild type and S282T mutant enzymes in vitro. Activity was further demonstrated for the LNA-G-triphosphate against HCV NS5B polymerase genotypes 1a, 2a, 3a and 4a. A phosphorylation by-pass prodrug strategy may be required to promote anti-HCV activity in the replicon assay.

[Urinary functional disorders bound to deep endometriosis and to its treatment: review of the literature].

Sun, 01 Jun 2014 00:00:00 +0000

Lower urinary tract disorders in case of deep endometriosis are common (up to 50% of patients), although often masked by pelvic pain. They result from damage to the pelvic autonomic nervous system by direct infiltration of these structures by endometriotic lesions or surgical trauma (especially in resection of the uterosacral ligaments, rectum or vagina). These are mainly sensory disturbances and bladder voiding dysfunction. They impact quality of life and could be responsible for long-term complications (recurrent urinary tract infections on a persistent residual urine or pelvic floor disorders due to chronic thrusting). It is therefore important to diagnose and treat early these troubles by well-conducted interviews or standardized questionnaires. Different drug treatments have been proposed, such as cholinergics or prokinetics, but their effectiveness has not been demonstrated yet. Neuromodulation of the superior hypogastric plexus for treatment of refractory atonic bladder with persistent urinary retention after surgery seems promising but should be confirmed by further studies. To date, standard treatment of urinary retention after surgery remains self-catheterization. In terms of prevention, surgical nerve sparing techniques have been developed in order to minimize intraoperative injury of pelvic nerve plexus and reduce postoperative morbidity.

Measurement of hs-CRP is irrelevant to diagnose and stage endometriosis: prospective study of 834 patients.

Sun, 01 Jun 2014 00:00:00 +0000

OBJECTIVE: The pathogenesis of endometriosis is associated with an inflammatory process. Here, we assessed if the levels of high-sensitivity C-reactive protein (hs-CRP) in serum could constitute an effective method for detecting systemic inflammation during endometriosis. STUDY DESIGN: This was a prospective, laboratory-based study, which was carried out in a tertiary care university hospital. Patients with histologically proven endometriosis (n = 370) and unaffected women (n = 464) were enrolled from January 2005 through December 2009. We performed complete surgical excision of endometriotic lesions with pathological analysis. In addition, hs-CRP levels were determined through a particle-enhanced immunoturbidimetric method. The hs-CRP levels were measured in both controls and women with endometriosis according to the established surgical classifications of endometriosis: superficial peritoneal endometriosis, endometrioma, and deep infiltration endometriosis. Also, hs-CRP levels were evaluated according to hormonal treatment and menstrual cycle. RESULTS: The hs-CRP serum levels did not statistically differ between women with endometriosis and controls (median in ng/mL [range]: 0.82 [0.04-42.89] vs 0.9 [0.03-43.73], respectively; P = .599). Moreover, subgroup analysis revealed no difference among superficial peritoneal endometriosis, endometrioma, deep infiltration endometriosis, and controls: 0.8 (0.15-13.35), 0.81 (0.04-38.82), 0.83 (0.09-42.89), and 0.9 (0.03-43.73), respectively; P = .872. Furthermore, no effect was observed regarding hormonal treatment or menstrual cycle. CONCLUSION: Although endometriosis is an inflammatory disease, we failed to identify any systemic changes in hs-CRP serum levels. Therefore, hs-CRP analysis appears to be irrelevant to the diagnosis and staging of endometriosis.

Role of the CXCL12-CXCR4 axis in the development of deep rectal endometriosis.

Sun, 01 Jun 2014 00:00:00 +0000

Immunological and angiogenetic factors enhance the implantation of endometrial cells in the peritoneal cavity. The aim of this work was to determine the role of the CXCL12-CXCR4 axis in the attraction and the peritoneal implantation of endometriotic stromal cells in deep infiltrating endometriosis (DIE). Biopsies of DIE nodules were obtained from 14 patients undergoing surgical treatment for DIE with low rectal involvement and from 12 patients without macroscopic endometriosis undergoing laparoscopy. CXCR4 expression was evaluated by Western blot analysis and flow cytometry in eutopic endometrial cells and DIE stromal cells in primary cultures derived from the biopsies. CXCL12-induced migration of DIE eutopic endometrial stromal cells was evaluated by transwell migration. CXCL12 was assayed in peritoneal fluids by ELISA. CXCR4 expression was higher in eutopic endometrial stromal cells than in control endometrial cells (p<0.05) and in DIE stromal cells (p<0.05). Eutopic endometrial stromal cells were more attracted by CXCL12 than control cells (p<0.01). CXCL12 was higher in DIE peritoneal fluids than in controls (p<0.05). CXCR4 was down-regulated in deep infiltrating endometriotic stromal cells. The CXCL12-CXCR4 axis plays a role in the attraction of eutopic endometrial cells into the peritoneal cavity, and the down-regulation of CXCR4 in resident endometriotic cells could cause their arrest in situ.

Hormonal therapy deregulates prostaglandin-endoperoxidase synthase 2 (PTGS2) expression in endometriotic tissues.

Sat, 01 Mar 2014 00:00:00 +0000

CONTEXT: Endometriosis is a common gynecologic condition characterized by an important inflammatory process mediated by the prostaglandin pathway. Oral contraceptives are the treatment of choice for symptomatic endometriotic women. However the effects of oral contraceptives use and prostaglandin pathway in endometriotic women are actually still unknown. OBJECTIVE: To investigate the expression of prostaglandin pathway key genes in endometriotic tissue, affected or not by hormonal therapy, as compared with healthy endometrial tissue. DESIGN: This was a comparative laboratory study. SETTING: This study was conducted in a tertiary-care university hospital. PATIENTS: Seventy-six women, with (n = 46) and without (n = 30) histologically proven endometriosis. MAIN OUTCOME MEASURES: Prostaglandin-endoperoxidase synthase (PTGS)1, PTGS2, prostaglandin E receptor (PTGER)1, PTGER2, PTGER3, and PTGER4 mRNA levels in endometrium of disease-free women and in eutopic and ectopic endometrium of endometriosis-affected women. PTGS2 expression was further investigated by immunohistochemistry, using specific monoclonal antibodies. PTGS2 expression was analyzed at mRNA and protein levels and correlated with taking hormonal treatment. RESULTS: PTGS2 expression was significantly increased in eutopic and ectopic endometrium as compared with healthy tissue (induction of 9.6- and 6.3-fold, respectively; P = .001). PTGS2 immunoreactivity increased gradually from normal endometrium to eutopic and ectopic endometrium (h-score of 96.7 ± 55.0, 128.3 ± 66.1, and 226.7 ± 62.6, respectively, P < .001). PTGER2, PTGER3, and PTGER4 expression increased significantly and gradually from normal to eutopic and ectopic endometrium, whereas PTGER1 remained unchanged. Patients under hormonal treatment had a higher PTGS2 expression at transcriptional and protein levels as compared with those without treatment (P = .002 and P = .025, respectively). CONCLUSIONS: Prostaglandin pathway is strongly deregulated in eutopic and ectopic endometrium of women suffering from endometriosis for the benefit of an increased PTGS2 expression. We show for the first time that hormonal treatment appears to enhance even more PTGS2 expression. These results contribute to explain why medical treatment could fail to control endometriosis progression.

AMH concentration is not related to effective time to pregnancy in women who conceive naturally.

Sat, 01 Feb 2014 00:00:00 +0000

This study determined whether anti-Müllerian hormone (AMH) concentration influences the time necessary to conceive a live-born child–effective time to pregnancy (eTTP)–in a population of women who conceived naturally. This is an observational study of 87 women with a planned spontaneous pregnancy resulting in a live birth. eTTP was assessed retrospectively by a questionnaire and AMH was measured in a frozen serum sample from first trimester of pregnancy. eTTP was correlated with age (r=-0.24, P=0.02), but not with AMH (r=-0.10) or body mass index (r=0.05). With logistic regressions, the only variable that affected the probability of pregnancy within 3 or 6 months was age, irrespective of whether an AMH concentration limit of 1.0 ng/ml or 2.0 ng/ml was chosen. In conclusion, this study suggests that there is no relationship between AMH concentration and eTTP and therefore speaks against determining AMH in women who are not infertile for the purpose of predicting their chances of pregnancy. The findings are concordant with previous reports describing AMH as a quantitative but not a qualitative marker of ovarian reserve and therefore does not reflect a woman’s ability to become pregnant. Anti-Müllerian hormone (AMH) is secreted by small growing ovarian follicles and reflects a woman’s ovarian reserve - the number of primordial follicles at a given time. AMH concentrations has been extensively studied in infertile women but there are only scarce data on AMH in non-infertile women. Our objective was to determine whether AMH concentrations influence the time necessary to conceive a live-born child - also called effective time to pregnancy (eTTP) - in a population of women who conceived naturally. We conducted an observational study between 2007 and 2009 in which we assessed eTTP retrospectively in 87 women who had delivered a live-born child and measured AMH in a frozen blood sample collected during the first trimester of pregnancy. The results of our study show, as expected, a decrease of AMH concentrations as age increases but no relationship between AMH and eTTP. In conclusion, our study results suggest AMH concentrations do not influence the time necessary to conceive a live-born child spontaneously and therefore speak against determining AMH in women who are not infertile for the purpose of predicting their chances of pregnancy. Our findings are concordant with previous reports describing AMH as a quantitative but not a qualitative marker of ovarian function that does therefore not reflect a woman’s ability to become pregnant.

[Recurrence of pain after surgery for deeply infiltrating endometriosis: How does it happen? How to manage?].

Wed, 01 Jan 2014 00:00:00 +0000

Recurrence of deep endometriosis remains a major issue in the management of endometriosis. The main cause for recurrence appears to be an incomplete excisional surgery. Therefore, the goal of the primary surgery should be the complete resection of all endometriotic lesions. If surgical skills cannot meet this objective it seems preferable to refer the patient to a center with a recognized expertise in this field rather than performing an incomplete surgery. It seems also possible to tailor the indications according to the symptoms, especially when endometriosis affects the bladder in association with an asymptomatic vaginal and/or rectal involvement. This strategy does not increase the rate of recurrence. Postoperative medical treatment based on ovarian function suppression is attractive as it diminishes the recurrence rate. Facing the recurrence, appropriate assessment of the benefit risk balance must be performed. Medical treatment is an option. When surgery is chosen, it seems interesting to discuss carefully the indication of hysterectomy with bilateral oophorectomy, especially for women over 40 years old with no desire for pregnancy and/or symptomatic adenomyosis. Risks of induced ovarian castration must be taken into account.

[Surgical treatments of presumed benign ovarian tumors].

Sun, 01 Dec 2013 00:00:00 +0000

The surgical management of presumed benign ovarian tumors (PBOT) must ensure complete removal of the cyst, reduce the risk of recurrence (especially in case of endometrioma), prevent any risk of tumor dissemination, and must preserve healthy ovarian tissue. Asymptomatic PBOT should not be punctured. Expectation is preferable to puncture. Laparoscopy is the gold standard for surgical treatment. Single-port laparoscopy is feasible and being evaluated. Peritoneal exploration and peritoneal cytology are conventionally performed. Ovarian cystectomy, oophorectomy and salpingo-oophorectomy are the standard techniques. Suture after cystectomy is not recommended. The extraction of the cyst using an endoscopic bag is recommended. Peritoneal washing after surgery is recommended. The use of anti-adhesions barriers is not recommended routinely. In case of dermoid cyst, cystectomy by mesial incision may decrease the risk of intraoperative rupture. In case of endometrioma, the intraperitoneal cystectomy is recommended as first-line surgery. Exclusive bipolar coagulation should be avoided because of increased risk of recurrence and lower pregnancy rates. There is no argument to support the use of plasma energy and CO2 laser in the treatment of endometriomas. Ethanol sclerotherapy may be proposed in patients with recurrent endometriomas after surgery and referred to medically assisted procreation, although there is no comparative trial with cystectomy.

Management of infertility today.

Sun, 01 Dec 2013 00:00:00 +0000

Risk and safety management in infertility and assisted reproductive technology (ART): from the doctor's office to the ART procedure.

Sun, 01 Dec 2013 00:00:00 +0000

Risk and safety management (RSM) is receiving increasing attention in medicine, with the goals of reducing medical error and increasing quality of care. The principles and tools of RSM can and should be applied to assisted reproductive technology (ART), a field that has already made significant progress in reducing the undesirable and sometimes dangerous consequences of treatment. ART is a prime area of medicine to contribute and help to lead the application of RSM and patient safety because it has been ahead of many other fields of medicine in standardizing treatment, certifying and auditing practitioners, and reporting standardized outcomes, and because treatments are applied to otherwise healthy individuals where exposure to risk may be less acceptable.

The changing prevalence of infertility.

Sun, 01 Dec 2013 00:00:00 +0000

Infertility is a major, multifaceted issue worldwide whose prevalence is increasing in both high- and low-income countries. The reasons are numerous, and may differ among world regions, but lifestyle and nutritional factors, epidemic infections, and sexually transmitted diseases are major determinants in most latitudes. Three other reasons may explain the increasing incidence of infertility. First, owing to the widespread use of contraception, the choice of delaying the first pregnancy until the third decade of life places men and women at higher risk for sexually transmitted diseases, and women at higher risk for uterine fibroids, endometriosis, polycystic ovary syndrome, and chronic anovulation. Second, prolonged exposure to chronic stress and environmental pollutants may play a critical role in decreasing fertility. Third, gonadotoxic oncologic treatments allow many patients to survive cancer, at the cost of their fertility. This consideration may justify the development of treatments that preserve fertility.

In women, the reproductive harm of toxins such as tobacco smoke is reversible in 6 months: basis for the -'olive tree-' hypothesis.

Tue, 01 Oct 2013 00:00:00 +0000

Increased serum oxidative stress markers in women with uterine leiomyoma.

Fri, 09 Aug 2013 00:00:00 +0000

BACKGROUND: Uterine leiomyomas (fibroids) are the most common gynaecological benign tumors in premenopausal women. Evidences support the role of oxidative stress in the development of uterine leiomyoma. We have analysed oxidative stress markers (thiols, advanced oxidized protein products (AOPP), protein carbonyls and nitrates/nitrites) in preoperative sera from women with histologically proven uterine leiomyoma. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a laboratory study in a tertiary-care university hospital. Fifty-nine women with histologically proven uterine leiomyoma and ninety-two leiomyoma-free control women have been enrolled in this study. Complete surgical exploration of the abdominopelvic cavity was performed in each patient. Preoperative serum samples were obtained from all study participants to assay serum thiols, AOPP, protein carbonyls and nitrates/nitrites. Concentrations of serum protein carbonyl groups and AOPP were higher in leiomyoma patients than in the control group (p=0.005 and p<0.001, respectively). By contrast, serum thiol levels were lower in leiomyoma patients (p<0.001). We found positive correlations between serum AOPP concentrations and total fibroids weight (r=0.339; p=0.028), serum AOPP and serum protein carbonyls with duration of infertility (r=0.762; p=0.006 and r=0.683; p=0.021, respectively). CONCLUSIONS/SIGNIFICANCE: This study, for the first time, reveals a significant increase of protein oxidative stress status and reduced antioxidant capacity in sera from women with uterine leiomyoma.

Profibrotic interleukin-33 is correlated with uterine leiomyoma tumour burden.

Thu, 01 Aug 2013 00:00:00 +0000

STUDY QUESTION: Are interleukin-33 (IL-33) serum levels higher in women with uterine leiomyoma compared with controls without leiomyoma? SUMMARY ANSWER: Serum IL-33 is elevated in women with uterine leiomyoma and correlated with features of uterine leiomyoma tumour burden, namely fibroid number, size and weight. WHAT IS KNOWN ALREADY: Uterine leiomyomas are the most common benign tumours in premenopausal women associated with major tissue fibrosis. IL-33 is a cytokine involved in fibrotic disorders. The potential role of IL-33 in leiomyoma has not been reported before. STUDY DESIGN, SIZE, DURATION: This is a prospective laboratory study conducted in a tertiary-care university hospital between January 2005 and December 2010. We investigated non-pregnant, 42-year-old patients (n = 151) during surgery for a benign gynaecological condition. PARTICIPANTS/MATERIALS, SETTING, METHODS: After complete surgical exploration of the abdominopelvic cavity, 59 women with histologically proved uterine leiomyoma and 92 leiomyoma-free control women were enrolled. Women with endometriosis or past history of ovarian malignancy and borderline tumours were not included. The control group included women with benign ovarian cysts, paratubal cysts or tubal defects without any evidence of uterine leiomyoma. For each patient, a structured questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. Serum samples were obtained in the month preceding the surgical procedures according to the menstrual phase or hormonal therapy. IL-33 was measured in sera by enzyme-linked immunosorbent assay, and correlation of IL-33 concentration with the extent and severity of the disease was investigated. MAIN RESULTS AND THE ROLE OF CHANCE: IL-33 was detected in 32 (54.2%) women with leiomyoma and 18 (19.6%) controls (P < 0.001). Serum IL-33 was higher in women with leiomyoma (median, 140.1 pg/ml; range, 7.5-2247.7) than in controls (median, 27.8 pg/ml; range, 7.5-71.6; P = 0.002). We found positive correlations between serum IL-33 concentration and leiomyoma features, such as fibroid weight (r = 0.630; P = 0.001) and size (r = 0.511; P = 0.018) and the number of fibroids (r = 0.503; P = 0.003). LIMITATIONS, REASONS FOR CAUTION: There was a possible selection bias due to inclusion of only surgical patients. Therefore our control group consisted of women who underwent surgery for benign gynaecological conditions. This may lead to biases stemming from the fact that certain of these conditions, such as tubal infertility or ovarian cysts, might be associated with altered serum IL-33 levels. WIDER IMPLICATIONS OF THE FINDINGS: We demonstrate for the first time that elevated serum IL-33 levels are associated with the existence of uterine leiomyoma. However, even if an association does not constitute proof of cause and effect, investigating the mechanisms that underlie fibrogenesis associated with leiomyomas is a step towards understanding this enigmatic disease. This study opens the doors to future, more mechanistics studies to establish the exact role of IL-33 in uterine leiomyomas pathogenesis. STUDY FUNDING/COMPETING INTEREST(S): No funding, no conflict of interest.

[Endometriosis-associated ovarian cancers: pathogenesis and consequences on daily practice].

Sat, 01 Jun 2013 00:00:00 +0000

Endometriosis is considered as a tumor-like lesion under the World Health Organization (WHO) classification of ovarian tumors. Data from large cohort and case-control studies indicate that patients with a history of endometriosis have an increased risk of ovarian cancer. Recent findings suggest an association between endometriosis and the entire type 1 ovarian tumors group including clear-cell, endometrioid and low-grade serous carcinomas. However, current evidence is lacking to draw definitive conclusion whether this association represents causality or the sharing of common risk factors. Nevertheless, assumption that endometriosis could be a precursor of malignancy raises many issues about serial screening, surgical management and surveillance of endometriosis. Beyond these concerns, endometriosis-associated ovarian cancers seem to be a genuine clinical entity as regards clinicopathological features. In view of the high incidence of endometriosis (10 % of women of childbearing age), the low incidence of endometriosis-associated ovarian cancers and the psychological consequences for those women, systematic screening and surgical exploration seem very questionable in this context.

An update on the pharmacological management of endometriosis.

Fri, 01 Feb 2013 00:00:00 +0000

INTRODUCTION: Endometriosis is a common disease that causes pain symptoms and/or infertility in women in their reproductive years. The disease is characterised by the presence of endometrium-like tissue - glands and stroma - outside the uterine cavity. Different treatment options exist for endometriosis including medical and surgical treatments or a combination of the two approaches. The most commonly used medications are non-steroidal anti-inflammatory drugs, GnRH agonists, androgen derivatives such as danazol, combined oral contraceptive pills, progestogens and more recently the levonorgestrel intrauterine system. AREAS COVERED: The authors review current medical treatments used for symptomatic endometriosis and also discuss new treatment approaches. The authors conducted a literature search for randomised controlled trials related to medical treatments of endometriosis in humans, searched the Cochrane library for reviews and also searched for registered trials that have not yet been published on ClinicalTrials.gov. EXPERT OPINION: The medical treatment of endometriosis is effective at treating pain and preventing recurrence of disease after surgery. Remarkably, the oral contraceptive pill taken continuously is as effective as GnRH-a, while causing far less side-effects. Conversely, no treatment currently exists for enhancing fecundity in women whose infertility is associated with endometriosis. As all existing therapies of endometriosis are contraceptive, great efforts should be targeted at researching novel products that reduce the disease expression without shuttering ovulation.

Interleukin-19 and interleukin-22 serum levels are decreased in patients with ovarian endometrioma.

Tue, 01 Jan 2013 00:00:00 +0000

OBJECTIVE: To determine the serum levels of interleukin (IL)-10 family ILs in women with ovarian endometriosis and investigate the correlation of these levels with disease activity. DESIGN: A case-control laboratory study. SETTING: Tertiary-care university hospital. PATIENT(S): Two hundred nineteen women, with (n = 112) and without (n = 107) endometriosis. INTERVENTION(S): Complete surgical excision with pathological analysis. MAIN OUTCOME MEASURE(S): Blood samples were obtained during surgical procedures. IL-10, -19, -20, and -22 were assayed by ELISA in sera, and the concentrations correlated with the extent and the severity of the disease. RESULT(S): IL-19 was detectable in 18.3% and IL-22 in 47.9% of sera samples from all 219 women studied. Serum IL-19 was lower in women with endometriosis (median, 292.7 pg/mL; range, 32.2-1,339.3) than in endometriosis-free women (median, 1,035.8 pg/mL; range, 32.2-2,000.0). In addition, serum IL-22 levels were decreased in women affected by endometriosis (median, 352.0 pg/mL; range, 31.2-1,392.2) as compared with endometriosis-free women (median, 709.2 pg/mL; range, 73.3-2,012.0). We found significant correlations between serum IL-22 concentrations and intensity of deep dyspareunia (r = -0.303) and noncyclic chronic pelvic pain (r = -0.212). IL-19 was correlated with the intensity of deep dyspareunia (r = -0.749). CONCLUSION(S): Serum IL-19 and IL-22 are decreased in women with ovarian endometrioma. IL-10 family ILs may be involved in the pathogenesis of endometriosis.

Visceral and subcutaneous adipose tissue from lean women respond differently to lipopolysaccharide-induced alteration of inflammation and glyceroneogenesis.

Mon, 03 Dec 2012 00:00:00 +0000

OBJECTIVE: Experimental endotoxaemia induces subcutaneous adipose tissue inflammation and systemic insulin resistance in lean subjects. Glyceroneogenesis, by limiting free fatty acids (FFA) release from adipocytes, controls FFA homoeostasis and systemic insulin sensitivity. The roles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in metabolic deregulation are intrinsically different. We compared the effect of lipopolysaccharide (LPS) on the inflammation profiles of SAT and VAT explants from lean women, as well as on glyceroneogenesis, to test whether these two fat depots have intrinsically different responses to this metabolic endotoxin. DESIGN: Abdominal SAT and VAT explants from eight lean women were treated in vitro with LPS. Their inflammatory status was evaluated by cytokine gene expression and secretion; glyceroneogenesis was evaluated by cytosolic phosphoenolpyruvate carboxykinase activity and FFA vs glycerol release. RESULTS: In the basal state, the cytokine status and expression of macrophage markers were lower in SAT than VAT. In the presence of 100 ng ml(-1) LPS, SAT exhibited a strong inflammatory response (increased interleukin-6 and tumor necrosis factor-α expression) and increased release of FFA due to inhibition of glyceroneogenesis, whereas VAT was only mildly affected. The effects of LPS on both tissues were blocked by the nuclear factor-κB (NF-κB) inhibitor, parthenolide. A significant effect of LPS on VAT occurred only at 1 μg ml(-1) LPS. CONCLUSION: SAT explants from lean women are more sensitive to LPS-induced NF-κB activation than are VAT explants, leading to a depot-specific dysfunction of FFA storage. As SAT is the major player in FFA homoeostasis, this SAT dysfunction could be associated with visceral fat hypertrophy and systemic lipid disorders.

In women with endometriosis anti-Müllerian hormone levels are decreased only in those with previous endometrioma surgery.

Thu, 01 Nov 2012 00:00:00 +0000

STUDY QUESTION: Are anti-Müllerian hormone (AMH) levels lower in women with endometriosis, notably those with endometriomas (OMAs) and deep infiltrating lesions, compared with controls without endometriosis? SUMMARY ANSWER: Endometriosis and OMAs per se do not result in lower AMH levels. AMH levels are decreased in women with previous OMA surgery independently of the presence of current OMAs. WHAT IS KNOWN ALREADY: The impact of endometriosis and OMAs per se on the ovarian reserve is controversial. Most previous studies have been conducted in infertile women. The strength of our study lies in the following points: (i) the selection of women undergoing surgery and not only according to the presence of infertility, (ii) the classification of women with endometriosis and controls based on strict surgical and histological criteria. STUDY DESIGN, SIZE, DURATION: Cross-sectional study using data prospectively collected in all non-pregnant <42-year-old patients, who were surgically explored for a benign gynaecological condition at a university tertiary referral centre between 2004 and 2008. For each patient, a structured questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. AMH levels were measured in serum samples drawn in the month preceding surgery, without regard to menstrual phase or hormonal therapy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Operations were done on 1262 women between 2004 and 2008, of which 1133 signed the informed consent. Of the 566 women with a visual diagnosis of endometriosis, 411 had histologically proven endometriosis. Frozen serum samples for the AMH measurement were available in 313 of them. Out of the 554 women without visual endometriosis and without past endometriosis surgery, 413 had a frozen serum sample for the AMH measurement. Univariate analysis examined AMH levels according to baseline patient characteristics, the presence and type of endometriosis (superficial lesion, OMA, deep infiltrating lesion) and previous OMA surgery. Analysis of variance-covariance then examined the effects of co-variables on AMH levels. Finally, logistic regressions were conducted to examine the odds ratio (OR) of having AMH levels <1 ng/ml according to the same co-variables. MAIN RESULTS AND THE ROLE OF CHANCE: The difference in AMH levels between women with endometriosis and controls did not reach significance (3.6 ± 3.1 versus 4.1 ± 3.4 ng/ml, P = 0.06). Analysis of variance-covariance demonstrated that AMH levels significantly decreased with age (P < 0.001) and in women with prior OMA surgery irrespective of whether OMAs were present or not at the time of study (P < 0.05). Logistic regression revealed that two major factors were related to AMH levels <1 ng/ml: (i) age (compared with <29 years; 30-34 years OR = 3.1, 95% CI: 1.5-6.4, P = 0.01; 35-39 years OR = 7.0, 95% CI: 3.5-14.1, P = 0.001; ≥40 years OR = 20.8, 95% CI: 9.1-47.4, P = 0.001) and (ii) prior OMA surgery (OR = 3.0, 95% CI: 1.4-6.41, P = 0.01). LIMITATIONS, REASONS FOR CAUTION: The selection of our study population was based on a surgical diagnosis. Women with an asymptomatic form of endometriosis are therefore not included in our study. We cannot exclude that infertile women with OMAs associated with a diminished ovarian reserve, as assessed during their infertility work-up, were less likely to be referred for surgery and might therefore be underrepresented. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that OMAs per se do not diminish the ovarian reserve reflected by AMH levels but that alterations seen in women with endometriosis are a deleterious consequence of OMA surgery. These findings should be taken into account in the decision to operate OMAs in women with a desire for future pregnancy. STUDY FUNDING: none. Potential competing interests: none.

Ovarian endometrioma but not deep infiltrating endometriosis is associated with increased serum levels of interleukin-8 and interleukin-6.

Sat, 01 Sep 2012 00:00:00 +0000

Cytokines, and specifically interleukin 6 (IL-6) and interleukin 8 (IL-8), have been associated with the pathogenesis of endometriosis. We studied serum concentrations of IL-6 and IL-8 in patients with deep infiltrating endometriosis (DIE) or ovarian endometriomas (OE), but no other forms of associated endometriosis disease type. We carried out a case-control study including 19 patients with OE alone (OE group), 14 patients with DIE alone (DIE group) and 24 healthy patients without endometriosis (C group). Serum concentrations of IL-6 and IL-8 were measured in the three groups of patients. Serum levels of both IL-6 and IL-8 were significantly higher in the OE group. A high positive correlation was found between serum IL-6 and IL-8 levels in the OE group but not in the DIE and C groups. Serum IL-8 alone achieved the highest predictive value of the presence of OE (adjusted OR: 1.44; sensitivity: 78.2%; specificity: 76.2%). The combination of IL-6 and IL-8 levels did not significantly improve the discrimination between subjects with OE and those with DIE over that of IL-8. OE but not DIE are associated with increased serum levels of IL-6 and IL-8, and thus these may become useful tools for discriminating OE alone from DIE.

Retrieving oocytes from small non-stimulated follicles in polycystic ovary syndrome (PCOS): in vitro maturation (IVM) is not indicated in the new GnRH antagonist era.

Wed, 01 Aug 2012 00:00:00 +0000

It has been two decades since pregnancies have been obtained through in vitro maturation (IVM) of germinal vesicle-stage oocytes retrieved from non-stimulated ovaries. This technique first offered in PCOS cannot be recommended today in this indication because the results do not match those of regular ART, and new GnRH antagonist and agonist-trigger protocols reliably prevent OHSS.

Inflammation: a link between endometriosis and preterm birth.

Sun, 01 Jul 2012 00:00:00 +0000

Endometriosis is a chronic inflammatory disease affecting women’s health. Pain and infertility are the major symptoms caused by a hormonal/immunological dysfunction, which causes an endometrial impairment. The same pathogenetic mechanisms are also associated with preterm birth: hormones, cytokines, neurohormones, and growth factors interact in modulating extracellular matrix and prostaglandin secretion, thus activating the inflammatory process in placental membranes and myometrium. An overlap of molecules and mechanisms may explain the evidence that preterm birth is a common outcome in pregnant patients with endometriosis.

Serum and peritoneal interleukin-33 levels are elevated in deeply infiltrating endometriosis.

Sun, 01 Jul 2012 00:00:00 +0000

BACKGROUND: Interleukin 33 (IL-33) is a cytokine involved in fibrotic disorders. We have analyzed IL-33 levels in the sera and peritoneal fluids of women with various forms of endometriosis and investigated the correlation with disease activity. METHODS: We conducted a prospective laboratory study in a tertiary-care university hospital between January 2005 and December 2010. Five hundred and ten women with histologically proven endometriosis and 132 endometriosis-free controls were enrolled in this study. Complete surgical exploration of the abdominopelvic cavity was performed in each patient. Blood samples and peritoneal fluids were obtained before and during surgical procedures, respectively. IL-33 was measured by an enzyme-linked immunosorbent assay in sera and peritoneal fluids, and the concentrations correlated with the extent and the severity of endometriotic lesions. RESULTS: IL-33 was detectable in 23.1% of serum samples from all 642 women studied and 75.0% of peritoneal fluid samples studied (44 women with endometriosis and 36 controls). Serum IL-33 was higher in deeply infiltrating endometriosis (DIE) (median, 104.9 pg/ml; range, 8.0-104.9) than in endometriosis-free women (median, 61.3 pg/ml; range, 7.5-526.0; P = 0.022) or in women affected by superficial endometriosis (median, 36.8 pg/ml; range, 7.5-179.0; P < 0.001). Peritoneal IL-33 was higher in DIE than in endometriosis-free women (median, 642.0 pg/ml; range, 25.9-3350.6 versus median, 194.2 pg/ml; range, 12.7-1818.2, respectively; P = 0.003). We found positive correlations between serum IL-33 concentration and intensity of dysmenorrhea (r = 0.174; P = 0.028) and gastrointestinal symptoms (r = 0.199; P = 0.027), total number of DIE lesions (r = 0.224; P = 0.016) and the worst DIE lesion (r = 0.299; P < 0.001). CONCLUSIONS: In spite of the number of samples with undetectable levels, serum IL-33 is abnormally elevated in women with endometriosis and principally in DIE. Elevated serum IL-33 is correlated with the intensity of preoperative painful symptoms, and with the extent and severity of the DIE. IL-33 may be considered as a novel cytokine involved in the pathogenesis of DIE.

Genetic polymorphisms of DNMT3L involved in hypermethylation of chromosomal ends are associated with greater risk of developing ovarian endometriosis.

Tue, 01 May 2012 00:00:00 +0000

Endometrioma is a common ovarian cyst associated with pain and infertility, but its pathogenesis remains enigmatic. Demonstration of the subtelomeric location of hypermethylation in endometrioma has been reported by genome-wide profiling of methylated promoters. Recently, rs113593938, a polymorphism in the DNA methyltransferase 3-like (DNMT3L) gene has been associated with subtelomeric hypomethylation. We investigated the association between endometrioma and rs113593938, rs8129776, rs7354779, and rs2276248, which were chosen for thoroughly covering the locus of interest. We enrolled 127 patients with histologically proved endometrioma and no associated deep endometriotic lesions and 317 healthy subjects for a case-control genetic association study. Genotyping was performed after PCR amplification of the region encompassing the polymorphisms, restriction enzyme digestion, and detection of fragments on an agarose gel. Differences in genotype and allele distributions between cases and controls were tested for each polymorphism separately using the χ(2) test. The rs8129776 was significantly associated with endometrioma (P = 0.003). Haplotype analysis showed a higher risk for the patients carrying the ACCC+T haplotypes for rs8129776, rs7354779, rs113593938, and rs2276248 (odds ratio, 7.15; 95% CI, 2.63 to 19.44). We report, for the first time to our knowledge, the association of DNMT3L genetic variants and endometrioma; DNMT3L expression itself was not modified. Our study constitutes a first milestone toward a plausible role of DNMT3L in the establishment of specific DNA methylation patterns in endometrioma.

[Intestinal endometriosis].

Sun, 01 Apr 2012 00:00:00 +0000

Endometriosis affects 6 to 10 % of all women of childbearing age. Intestinal involvement is defined by muscularis infiltration and has been estimated to occur in 8 % to 12 % of women with endometriosis. The most common sites are rectum, sigmoid and ileocaecal junction. In most cases, intestinal endometriosis is associated with deep infiltrating endometriosis, multifocal and aggressive form of endometriosis, responsible for refractory pelvic pain and infertility. The symptoms are nonspecific but are characterized by cyclic exacerbation of pain. The preoperative work-up includes a rectal endoscopic ultrasonography, a transvaginal ultrasonography, a pelvic magnetic resonance imaging and a multidetector CT scan. There is currently no cure other than surgical removal of lesions. Medical treatments are based on a hormone used to block ovarian function.

Sphingosine pathway deregulation in endometriotic tissues.

Sun, 01 Apr 2012 00:00:00 +0000

OBJECTIVE: To investigate key genes expression of the sphingosine-1-phosphate pathway in endometriotic tissues. DESIGN: A case-control laboratory study. SETTING: Tertiary care university hospital. PATIENT(S): A total of 31 women, with (n = 16) and without (n = 15) endometriosis took part in the study. INTERVENTION(S): After surgical excision with pathological analysis, endometrial specimens were obtained from women affected or not by endometriosis. MAIN OUTCOME MEASURE(S): SPHK1-2, SGPP1-2, SGPL1, SPHKAP, and S1PR1-5 messenger RNA expression by quantitative real-time polymerase chain reaction (PCR) in the endometrium of 15 disease-free women, 16 eutopic and 16 ectopic endometrium of endometriosis-affected women. The S1PR1 and S1PR2 expression were further investigated by immunohistochemistry. RESULT(S): The SGPP2 expression was decreased in eutopic and ectopic endometrium of endometriosis-affected women (1.7- and 16.7-fold, respectively). The SGPP1, weakly expressed in healthy endometrium, is up-regulated in endometriosis-affected women (11.9- and 64.7-fold, respectively), but its expression remains low. The SGPL1 expression was decreased in ectopic endometrium (3.3-fold) and SPHKAP expression was increased in ectopic endometrium (112.6-fold) compared with endometrium of disease-free women. In endometriosis-affected women, S1PR3 expression was decreased in eutopic and ectopic endometrium (2.1- and 6.3-fold, respectively); S1PR2 and S1PR1 expression was increased in eutopic (2.5-fold) and ectopic endometrium (2.6-fold). These increases were confirmed at the protein levels by immunohistochemistry. CONCLUSION(S): Expression of the enzymes implicated in the regulation of the sphingosine-1-phosphate level balance and of its receptors is overall heavily deregulated in endometriotic lesions in favor of a decreased sphingosine-1-phosphate catabolism. Our results plead for a role of the sphingosine pathway in establishing and survival of endometriotic lesions.

New treatment strategies and emerging drugs in endometriosis.

Fri, 23 Mar 2012 00:00:00 +0000

Introduction: Endometriosis, histologically defined as the presence of endometrium-like tissue - glands and stroma - that develops outside of the uterine cavity, is still an enigmatic disease responsible for pelvic pain and infertility. The current treatments of endometriosis are surgery and hormonal therapies that act by suppressing ovulation and/or directly on steroid receptors located in endometriotic lesions. Areas covered: New hormonal and non-hormonal therapies are being developed for the treatment of endometriosis-related pain. The authors review the state of advancement and the results of novel treatments studied in registered trials ( www.ClinicalTrials.gov ). Cellular signaling pathways activated in endometriotic cells, which constitute potential targets for future treatments, are also described. Expert opinion: Therapeutic research efforts should focus on identifying and testing substances capable of acting locally on the lesions themselves, without interfering with ovulation, in order to be efficacious on both pain symptoms and infertility.

Ovarian endometrioma: severe pelvic pain is associated with deeply infiltrating endometriosis.

Thu, 01 Mar 2012 00:00:00 +0000

BACKGROUND: The objective of this study was to evaluate the significance of severe preoperative pain for patients presenting with ovarian endometrioma (OMA). METHODS: Three hundred consecutive patients with histologically proven OMA were enrolled at a single university tertiary referral centre between January 2004 and May 2010. Complete surgical excision of all recognizable endometriotic lesions was performed for each patient. Pain intensity was assessed with a 10-cm visual analogue scale (VAS). Pain was considered as severe when VAS was ≥ 7. Prospective preoperative assessment of type and severity of pain symptoms (VAS) was compared with the peroperative findings (surgical removal and histological analysis) of endometriomas and associated deeply infiltrating endometriosis. Correlations were sought with univariate analysis and a multiple regression logistic model. RESULTS: After multiple logistic regression analysis, uterosacral ligaments involvement was related with a high severity of chronic pelvic pain [odds ratios (OR) = 2.1; 95% confidence interval (CI): 1.1-4.3] and deep dyspareunia (OR = 2.0; 95% CI: 1.1-3.5); vaginal involvement was related with a higher intensity of lower urinary symptoms (OR = 13.4; 95% CI: 3.2-55.8); intestinal involvement was related with an increased severity of dysmenorrhoea (OR = 5.2; 95% CI: 2.7-10.3) and gastro-intestinal symptoms (OR = 7.1; 95% CI: 3.3-15.3). CONCLUSIONS: In case of OMA, severe pelvic pain is significantly associated with deeply infiltrating lesions. In this situation, the practitioner should perform an appropriate preoperative imaging work-up in order to evaluate the existence of associated deep nodules and inform the patient in order to plan the surgical intervention strategy.

Deep infiltrating endometriosis is associated with markedly lower body mass index: a 476 case-control study.

Sun, 01 Jan 2012 00:00:00 +0000

BACKGROUND: An inverse association between BMI and endometriosis has been reported but remains controversial. We decided to evaluate the association between BMI and the different types of endometriosis, classified as superficial endometriosis (SUP), deep infiltrating endometriosis (DIE) and ovarian endometrioma (OMA). METHODS: From a prospective database of patients who underwent gynecological surgery between February 2005 and October 2008, we compared 238 patients with a histological diagnosis of endometriosis to 238 age- and smoking-status-matched controls using a prospective preoperative questionnaire and surgical data. Numerical variables means were compared for matched pairs, and non-parametric variables using Wilcoxon test. The Odds ratios for all types of endometriosis adjusted for confounding variables were computed according to predefined BMI groups [1(<18.5), 2 (≥18.5 and <22), 3(≥22 and <25), 4(≥25)], taking Group 3 as the reference population. RESULTS: BMI was significantly lower for all 238 patients (21.70 ± 3.7 versus 23.29 ± 4.1, P < 0.001), for 101 OMA patients (21.88 ± 3.8 versus 22.99 ± 4, P < 0.038), and for 97 DIE patients (21.35 ± 3.4 versus 23.35 ± 3.8, P < 0.001) compared with their own controls, but not for the 40 SUP patients. Patients in Group 1 had adjusted odds ratios as high as 3.3 [95% confidence interval (CI): 1.6-6.8] for DIE and 2.7 (95% CI: 1.1-6.8) for OMA; in Group 2, the adjusted oddd ratios were 2.6 (95% CI: 1.3-5.5) for DIE and 2.9 (95% CI: 1.5-5.4) for OMA. CONCLUSIONS: Endometriotic patients have lower BMI than age- and smoking-status-matched controls, independent of confounding variables. Patients with the lowest BMI (<18.5) are at a high risk of DIE.

The value of growth hormone supplements in ART for poor ovarian responders.

Tue, 01 Nov 2011 00:00:00 +0000

Recently, three meta-analyses have concluded that cotreatment with GH improves assisted reproduction outcome in poor controlled ovarian stimulation responders. Although generally GH supplements did not increase controlled ovarian stimulation response or number of oocytes, the supplements improved pregnancy and live-birth rates-thus speaking for an effect on oocyte quality.

Markers of adult endometriosis detectable in adolescence.

Sat, 01 Oct 2011 00:00:00 +0000

Endometriosis, a disease of young females that is possibly a devastating ailment requiring surgery, appears to be associated with certain features encountered in adolescence. First among these symptoms is the history of severe and lasting dysmenorrhea at the time of adolescence and the need to use oral contraceptives (OCs) for alleviating dysmenorrhea that failed to respond to nonsteroidal anti-inflammatory drugs (NSAIDs). Further awareness about existing associations between certain symptoms experienced at adolescence and the later development of endometriosis is important. Indeed, the possibility of diagnosing endometriosis earlier when suggested by clinical history could lead to less extensive surgery and thus, less damage. Experimental verification of this insight, however, is needed before the concept that early diagnosis means lesser destructive surgery can be ascertained.

Gynaecological endoscopic evaluation of 4% icodextrin solution: a European, multicentre, double-blind, randomized study of the efficacy and safety in the reduction of de novo adhesions after laparoscopic gynaecological surgery.

Mon, 01 Aug 2011 00:00:00 +0000

BACKGROUND: Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept(®)) in the reduction of de novo adhesion incidence compared to lactated Ringer’s solution (LRS). METHODS: Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed. RESULTS Of 498 patients randomized, 330 were evaluable (160 LRS–75% myomectomy/25% endometriotic cysts; 170 Adept–79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥ 1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P < 0.001) and number of suture knots (P < 0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related. CONCLUSIONS: The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.

Infertility and endometriosis: a need for global management that optimizes the indications for surgery and ART.

Mon, 01 Aug 2011 00:00:00 +0000

Endometriosis causes pelvic pain and infertility. Infertility results from effects of endometriosis exerted in the pelvic cavity, in the ovaries and/or on the uterus. Medical treatment effective on pain and at preventing disease recurrence following surgery is of no use for improving the chances of conceiving naturally. Surgery however improves the chances of conceiving in the 12-18 months afterward. Endometriosis through extension of the disease to the ovaries may harm ovarian response to COS needed in ART. Surgery for endometrioma(s) may further reduce ovarian responses to COS in case of endometriosis. Remarkably however, reduced ovarian responses due to endometriosis are not necessarily associated with reduced oocyte quality and ART outcome. Pre-ART treatment with oral contraceptives (OC) improves ART outcome in case of ovarian endometriosis particularly, if endometriomas are present at the time of oocyte retrieval. This measure requires however that a proper OC-FSH/hMG interval is respected and that -‘LH-’ effects are provided during the ovarian stimulation, using either hMG or small doses of hCG. These latter precautions prevent the adverse outcome reported in case of pre-ART use of OC when ovarian stimulation is conducted using r-FSH exclusively.

Oral contraceptives and endometriosis: the past use of oral contraceptives for treating severe primary dysmenorrhea is associated with endometriosis, especially deep infiltrating endometriosis.

Mon, 01 Aug 2011 00:00:00 +0000

BACKGROUND: The relationship between the use of oral contraception (OC) and endometriosis remains controversial. We therefore compared various characteristics of OC use and the surgical diagnosis of endometriosis histologically graded as superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) or deep infiltrating endometriosis (DIE). METHODS: This cross-sectional study included 566 patients without visible endometriosis at surgery as controls, and 410 patients with histologically proven endometriosis, categorized by their worst lesions as SUP n = 47, OMA n = 120 and DIE n = 243. Personal data, including on OC use, were prospectively collected during standardized interviews. Statistical analysis was performed using unconditional logistic regression. RESULTS: Past OC users had an increased incidence of endometriosis (adjusted odd ratios (OR) = 2.79, 95% confidence interval (CI) 1.74-5.12, P = 0.002) of any revised American Fertility Society stage. Women who had previously used OC for severe primary dysmenorrhea were even more frequently diagnosed with endometriosis (adjusted OR = 5.6, 95% CI 3.2-9.8), especially for DIE (adjusted OR = 16.2, 95% CI 7.8-35.3). Women who had previously used OC for other reasons also had an increased risk of endometriosis, but to a lesser extent (adjusted OR = 2.6, 95% CI 1.8-4.1). The age at which OC was initiated, duration of OC use and free interval from last OC use were not significantly different between control and endometriosis women, irrespective of histological grading. Current OC users did not show an increased prevalence of endometriosis (OR = 1.22, 95% CI 0.6-2.52). CONCLUSIONS: Our data indicate that a history of OC use for severe primary dysmenorrhea is associated with surgical diagnosis of endometriosis, especially DIE, later in life. However, this does not necessarily mean that use of OC increases the risk of developing endometriosis. Past use of OC for primary dysmenorrhea may serve as a marker for women with endometriosis and DIE.

The mTOR/AKT inhibitor temsirolimus prevents deep infiltrating endometriosis in mice.

Mon, 01 Aug 2011 00:00:00 +0000

Deep infiltrating endometriosis (DIE) is a particular clinical and histological entity of endometriosis responsible for chronic pelvic pain and infertility. Here we characterize the proliferative phenotype of DIE cells, to explore the cellular and molecular mechanisms that could explain their aggressive potential. In addition, the inhibition of mTOR/AKT pathway was tested, as a potential treatment of DIE. Included were 22 patients with DIE and 12 control patients without endometriosis. Epithelial and stromal cells were extracted from biopsies of eutopic endometrium and deep infiltrating endometriotic nodules from patients with DIE. Cell proliferation was determined by thymidine incorporation. Oxidative stress was assayed by spectrofluorometry. The ERK and mTOR/AKT pathways were analyzed in vitro by Western blot and for AKT in vivo in a mouse model of DIE. The proliferation rate of eutopic endometrial cells and of deep infiltrating endometriotic cells from DIE patients was higher than that of endometrial cells from controls. The hyperproliferative phenotype of endometriotic cells was associated with an increase in endogenous oxidative stress, and with activation of the ERK and mTOR/AKT pathways. mTOR/AKT inhibition by temsirolimus decreased endometriotic cell proliferation both in vitro and in vivo in a mouse model of DIE. Blocking the mTOR/AKT pathway offers new prospects for the treatment of DIE.

The steroidogenic factor-1 protein is not expressed in various forms of endometriosis but is strongly present in ovarian cortical or medullary mesenchymatous cells adjacent to endometriotic foci.

Thu, 30 Jun 2011 00:00:00 +0000

Steroidogenic factor-1 (SF-1) protein expression was not observed in any form of endometriosis (peritoneal, ovarian, or deep infiltrating endometriosis), which suggests that SF-1 locally produced by endometrial or stromal cells may not play a major role in the development of endometriosis. However, the strong expression of SF-1 in cortical and medullary ovarian mesenchymatous cells may be capable of creating a favorable steroidogenic environment and the development of the disease.

Galectin-3 is overexpressed in various forms of endometriosis.

Sun, 01 May 2011 00:00:00 +0000

Endometriosis is an enigmatic disease of unknown etiology and pathogenesis, which is defined as the presence of endometrial glands and stroma outside the uterus. The most widely accepted theory to explain endometriosis is probably the transplantation of an endometrial fragment during menstruation to ectopic sites, but the development of endometriosis is extremely complex and includes the adherence to the peritoneal surface and secondary invasion of the underlying tissues. In this study, we have investigated the potential role of galectin-3 (gal-3), a member of a group of carbohydrate-binding proteins, which plays a major role in cell adhesion, migration, angiogenesis, and invasion. The expression of gal-3 has been carried out by immunohistochemistry, according to the different phases of cycle in 50 cases of endometriosis (peritoneal endometriosis: n=10; ovarian endometriosis: n=10; deeply infiltrating endometriosis: n=30) and in 34 cases of eutopic endometrium (10 without endometriosis and 24 with endometriosis). In the proliferative and secretory phases of the cycle, the nuclear and membranous gal-3 expression was higher, first in each variant of the endometriosis than in the eutopic endometrium (P<0.05), and second in the eutopic endometrium of women with endometriosis than in eutopic endometrium of women without endometriosis. Our data suggest that gal-3 may have a potential role in the development of endometriosis.

Multiplying recipients paired with oocyte donors optimizes the use of donated oocytes.

Fri, 01 Apr 2011 00:00:00 +0000

OBJECTIVE: To review donor-egg assisted reproductive technology (ART) activity using young fertile donors (<37 years of age) paired with multiple recipients. DESIGN: Age-matched cohort study. SETTING: Tertiary ART center at Cochin Hospital, Paris. PATIENT(S): A total of 125 oocyte donors and 361 age-matched control subjects. Donated oocytes were attributed to 163 different recipients undertaking 258 transfer cycles. INTERVENTION(S): Donor-egg and regular ART. MAIN OUTCOME MEASURE(S): Controlled ovarian hyperstimulation (COH) outcome-oocytes provided-was compared in donors and control subjects. Clinical pregnancy (cPR), ongoing pregnancy (oPR), and implantation (IR) rates per transfer in recipients were compared with age-matched controls. IRs were analyzed in the various recipients as a function of the number of oocytes harvested. RESULT(S): COH outcome was similar in donors and control subjects. cPR (37.5%), oPR (28.4%), and IR (24.4%) were slightly but significantly lower in donor-egg recipients compared with control subjects (44.9%, 37.4%, and 31.8%, respectively). More embryos (average +2.06) were transferred fresh and fewer frozen. In recipients, IRs were independent from the number of oocytes received in the donor. CONCLUSION(S): Multiplying recipients paired with oocyte donors slightly lowered per-transfer outcome, but enabled more (average +2.06) embryos to be transferred fresh.

Questioning patients about their adolescent history can identify markers associated with deep infiltrating endometriosis.

Tue, 01 Mar 2011 00:00:00 +0000

OBJECTIVE: To investigate whether the clinical history, particularly of the adolescence period, contains markers of deeply infiltrating endometriosis (DIE). DESIGN: Cross-sectional study. SETTING: Universitary tertiary referral center. PATIENT(S): Two hundred twenty-nine patients operated on for endometriosis. Endometriotic lesions were histologically confirmed as non-DIE (superficial peritoneal endometriosis and/or ovarian endometriomas) (n = 131) or DIE (n = 98). INTERVENTION(S): Surgical excision of endometriotic lesions with pathological analysis of each specimens. MAIN OUTCOME MEASURE(S): Epidemiological data, pelvic pain scores, family history of endometriosis, absenteeism from school during menstruation, oral contraceptive (OC) pill use. RESULT(S): Patients with DIE had significantly more positive family history of endometriosis (odds ratio [OR] = 3.2; 95% confidence interval [CI]: 1.2-8.8) and more absenteeism from school during menstruation (OR = 1.7; 95% CI: 1-3). The OC pill use for treating severe primary dysmenorrhea was more frequent in patients with DIE (OR = 4.5; 95% CI: 1.9-10.4). Duration of OC pill use for severe primary dysmenorrhea was longer in patients with DIE (8.4 ± 4.7 years vs. 5.1 ± 3.8 years). There was a higher incidence of OC pill use for severe primary dysmenorrhea before 18 years of age in patients with DIE (OR = 4.2; 95% CI: 1.8-10.0). CONCLUSION(S): The knowledge of adolescent period history can identify markers that are associated with DIE in patients undergoing surgery for endometriosis.

Glyceroneogenesis is inhibited through HIV protease inhibitor-induced inflammation in human subcutaneous but not visceral adipose tissue.

Tue, 01 Feb 2011 00:00:00 +0000

Glyceroneogenesis, a metabolic pathway that participates during lipolysis in the recycling of free fatty acids to triglycerides into adipocytes, contributes to the lipid-buffering function of adipose tissue. We investigated whether glyceroneogenesis could be affected by human immunodeficiency virus (HIV) protease inhibitors (PIs) responsible or not for dyslipidemia in HIV-infected patients. We treated explants obtained from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depots from lean individuals. We observed that the dyslipidemic PIs nelfinavir, lopinavir and ritonavir, but not the lipid-neutral PI atazanavir, increased lipolysis and decreased glyceroneogenesis, leading to an increased release of fatty acids from SAT but not from VAT. At the same time, dyslipidemic PIs decreased the amount of perilipin and increased interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) secretion in SAT but not in VAT. Parthenolide, an inhibitor of the NFκB pathway, counteracted PI-induced increased inflammation and decreased glyceroneogenesis. IL-6 (100 ng) inhibited the activity of phosphoenolpyruvate carboxykinase, the key enzyme of glyceroneogenesis, in SAT but not in VAT. Our data show that dyslipidemic but not lipid-neutral PIs decreased glyceroneogenesis as a consequence of PI-induced increased inflammation in SAT that could have an affect on adipocytes and/or macrophages. These results add a new link between fat inflammation and increased fatty acids release and suggest a greater sensitivity of SAT than VAT to PI-induced inflammation.

HIV-positive patients undertaking ART have longer infertility histories than age-matched control subjects.

Tue, 01 Feb 2011 00:00:00 +0000

OBJECTIVE: To review 5 years of assisted reproductive treatments (ART) provided to couples affected by human immunodeficiency virus (HIV). DESIGN: Age-matched cohort study. SETTING: University-based tertiary center. PATIENT(S): Couples in whom the male (n = 87), female (n = 57), or both (n = 17) partners were HIV infected. The first ART cycle was compared with three sets of age-matched control subjects (3-to-1) which included 261, 171, and 51 couples, respectively. INTERVENTION(S): ART in HIV-infected couples and age-matched controls. MAIN OUTCOME MEASURE(S): Infertility duration and ART outcome. RESULT(S): When initiating ART, all three HIV-infected groups had longer infertility histories, computed from when conception was attempted or infertility diagnosed, compared with noninfected age-matched control subjects. Outcome, however, was not different when only the male or female partner was infected, though with a trend toward higher cancellation and lower pregnancy rates. When both partners were HIV infected, cancellation were higher and pregnancy rates lower (12% versus 41.2%), than in age-matched control subjects. CONCLUSION(S): Our data showed longer infertility histories in all HIV-infected couples when undertaking their first ART. Outcome, however, was not altered when only one partner–male or female–was HIV infected. Efforts should therefore aim at assuring that HIV-infected couples access ART as promptly as their noninfected counterparts.

Antiproliferative effects of cannabinoid agonists on deep infiltrating endometriosis.

Wed, 01 Dec 2010 00:00:00 +0000

Deep infiltrating endometriosis (DIE) is characterized by chronic pain, hyperproliferation of endometriotic cells and fibrosis. Since cannabinoids are endowed with antiproliferative and antifibrotic properties, in addition to their psychogenic and analgesic effects, cannabinoid agonists have been evaluated in DIE both in vitro and in vivo. The in vitro effects of the cannabinoid agonist WIN 55212-2 were evaluated on primary endometriotic and endometrial stromal and epithelial cell lines extracted from patients with or without DIE. Cell proliferation was determined by thymidine incorporation and production of reactive oxygen species by spectrofluorometry. ERK and Akt pathways were studied by immunoblotting. Immunoblotting of α-smooth muscle actin was studied as evidence of myofibroblastic transformation. The in vivo effects of WIN 55212-2 were evaluated on Nude mice implanted with human deep infiltrating endometriotic nodules. The in vitro treatment of stromal endometriotic cells by WIN 55212-2 decreased cell proliferation, reactive oxygen species production, and α-smooth muscle actin expression. The decrease in cell proliferation induced by WIN 55212-2 was not associated with a decrease in ERK activation, but was associated with the inhibition of Akt activation. WIN 55212-2 abrogated the growth of endometriotic tissue implanted in Nude mice. Cannabinoid agonists exert anti-proliferative effects on stromal endometriotic cells linked to the inhibition of the Akt pathway. These beneficial effects of cannabinoid agonists on DIE have been confirmed in vivo.

Increased nerve density in deep infiltrating endometriotic nodules.

Wed, 01 Dec 2010 00:00:00 +0000

BACKGROUND/AIMS: Deep infiltrating endometriosis is a very painful condition and the mechanism of pain is still poorly understood. Pain and hyperalgesia can partly be explained by an increased number of nerve structures in the painful lesion. In order to clarify this issue, we assessed the nerve density in deep infiltrating endometriotic nodules of the posterior vagina and in the adjacent healthy vaginal tissue of the same patient. METHODS: A prospective clinical and pathological study of 31 cases of deep infiltrating vaginal endometriotic nodules was conducted. Fifteen patients were in the proliferative phase and 16 in the secretory phase. The nerve density was studied by immunohistochemistry with the monoclonal antibody NF against neurofilaments in deep infiltrating endometriosis and in the adjacent unaffected vaginal tissue in the proliferative and in the secretory phases. Neurofilaments constitute the main structural elements of neuronal axons and dendrites. RESULTS: The nerve density was significantly different in the endometriotic nodule than in the adjacent unaffected vaginal tissue (p = 0.0013). The same significant difference was found between endometriotic nodules and the unaffected vagina in the proliferative phase (p = 0.009) and in the secretory phase (p = 0.04). This difference was not significant between the proliferative and the secretory phases in the endometriotic lesions and in the controls. CONCLUSIONS: We hypothesize that the significantly increased number of nerve structures in the endometriotic nodules may contribute to the occurrence of severe and neuropathic pain that characterizes these lesions.

Use of oral contraceptives in women with endometriosis before assisted reproduction treatment improves outcomes.

Wed, 01 Dec 2010 00:00:00 +0000

In women with endometriosis, including those with endometriomas, 6 to 8 weeks of continuous use of oral contraception (OC) before assisted reproduction treatment (ART) maintains ART outcomes comparable with the outcomes of age-matched controls without endometriosis. In contrast, ART outcomes are markedly compromised in endometriosis patients who are not pretreated with OC. Ovarian responsiveness to stimulation was not altered by 6 to 8 weeks’ use of pre-ART OC, including in poor responders with endometriomas.

[Deep bladder endometriosis: how do I...to perform a laparoscopic partial cystectomy?].

Mon, 01 Nov 2010 00:00:00 +0000

Smoking habits of 411 women with histologically proven endometriosis and 567 unaffected women.

Mon, 01 Nov 2010 00:00:00 +0000

Smoking habits did not influence either the risk of any form of endometriosis (superficial peritoneal endometriosis, ovarian endometriomas, and deep infiltrating endometriosis) and did not correlate with the revised American Fertility Society stages or scores.

Antiproliferative effects of anastrozole, methotrexate, and 5-fluorouracil on endometriosis in vitro and in vivo.

Fri, 01 Oct 2010 00:00:00 +0000

OBJECTIVE: To investigate the effects of antiproliferative drugs (anastrozole, methotrexate, and 5-fluorouracil [5-FU]) on the proliferation of endometriotic cells in vitro and in vivo. DESIGN: Ex vivo study on human endometrial and endometriotic cells in culture; establishment of a murine model using mice implanted with human endometriosis. SETTING: University research center. PATIENT(S): Ten patients with ovarian endometrioma, 10 patients with deep infiltrating endometriosis, and 10 patients without endometriosis. INTERVENTION(S): Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. Cells were treated in vitro with anastrozole, methotrexate, progesterone, or 5-FU. Human endometriotic lesions were implanted in nude mice. Mice were treated with 5-FU or phosphate-buffered saline during 4 weeks before sacrifice and extraction of the endometriotic implants. MAIN OUTCOME MEASURE(S): Stromal and epithelial cell proliferation and pathology score of endometriotic implants. RESULT(S): Although anastrozole, methotrexate, and progesterone were ineffective, 5-FU significantly decreased the proliferation of endometriotic cells in vitro and controlled the growth of both cells from ovarian endometrioma and deep infiltrating endometriosis. CONCLUSION(S): Considering common features between endometriotic cells and tumor cells, the use of 5-FU could be an option in the management of severe endometriosis.

Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo.

Fri, 01 Oct 2010 00:00:00 +0000

Endometriosis affects 6-10% of women in their reproductive years, causing chronic pelvic pain and infertility. Its pathogenesis remains poorly understood and current treatments, based on hormonal therapy or surgery, are often insufficient. The purpose of our study was to investigate the role of the ERK pathway in the development of endometriosis and to test the effects of protein kinase inhibitors on the proliferation of endometriotic cells in vitro and in vivo. We studied ex vivo human endometrial and endometriotic cells in culture. Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. The ERK pathway was explored by western blot on cell lysates and by ELISA on total crushed specimens of endometrium. Cells in culture were treated with A771726, PD98059, and U0126. Human endometriotic lesions were implanted in nude mice. Mice were treated with A771726, leflunomide, PD98059, U0126 or PBS during 2 weeks before sacrifice and extraction of the endometriotic implants for histological examination. We found that the ERK pathway was significantly activated in endometriotic cells and in endometrial cells from patients with endometriosis compared to endometrial cells of control patients, both by ELISA and by western blot. This phenomenon was associated with an increased proliferation of endometriotic cells compared to endometrial cells. Treating endometriotic cells with A771726, PD98059 or U0126 abrogated the phosphorylation of ERK and significantly decreased the cellular proliferation in vitro. In vivo, A771726, leflunomide, PD98059, and U0126 controlled the growth of endometriotic implants in the mouse model of endometriosis. Our study shows that protein kinase inhibitors could be new candidates to treat endometriosis. However, further studies are needed to evaluate their effects and tolerability in humans.

Research resource: genome-wide profiling of methylated promoters in endometriosis reveals a subtelomeric location of hypermethylation.

Wed, 01 Sep 2010 00:00:00 +0000

Several lines of evidence indicate that endometriosis could be partially due to selective epigenetic deregulations. Promoter hypermethylation of some key genes, such as progesterone receptor and aromatase, has been associated with the silencing of these genes and might contribute to the disease. However, it is unknown whether global alterations in DNA methylation patterns occur in endometriosis and to what extent they are involved in its pathogenesis. We conducted a whole-genome scanning of methylation status in more than 25,000 promoters, using methylated DNA immunoprecipitation with hybridization to promoter microarrays. We detailed the methylation profiles for each subtype of the disease (superficial endometriosis, endometriomas, and deep infiltrating endometriosis) and compared them with the profile obtained for the eutopic endometrium. In line with the current theory of the endometrial origin of endometriosis, the overall methylation profile was highly similar between the endometrium and the lesions. It showed promoter regions consistently hypomethylated or hypermethylated (more than 1.5-times, as compared with endometrium) and others specific to one given subtype. Albeit there was no systematic correlation between promoter methylation and expression of nearby genes, 35 genes had both methylation and expressional alterations in the lesions. These genes, reported here for the first time, might be of interest in the development of endometriosis. In addition, hypermethylated regions were located at the ends of the chromosomes, whereas hypomethylated regions were randomly distributed all along the chromosomes. We postulated that this original observation might participate to the chromosomal stability and protect the endometriotic lesion against malignancy.

Endometriosis and infertility: pathophysiology and management.

Sat, 28 Aug 2010 00:00:00 +0000

Endometriosis and infertility are associated clinically. Medical and surgical treatments for endometriosis have different effects on a woman’s chances of conception, either spontaneously or via assisted reproductive technologies (ART). Medical treatments for endometriosis are contraceptive. Data, mostly uncontrolled, indicate that surgery at any stage of endometriosis enhances the chances of natural conception. Criteria for non-removal of endometriomas are: bilateral cysts, history of past surgery, and altered ovarian reserve. Fears that surgery can alter ovarian function that is already compromised sparked a rule of no surgery before ART. Exceptions to this guidance are pain, hydrosalpinges, and very large endometriomas. Medical treatment-eg, 3-6 months of gonadotropin-releasing hormone analogues-improves the outcome of ART. When age, ovarian reserve, and male and tubal status permit, surgery should be considered immediately so that time is dedicated to attempts to conceive naturally. In other cases, the preference is for administration of gonadotropin-releasing hormone analogues before ART, and no surgery beforehand. The strategy of early surgery, however, seems counterintuitive because of beliefs that milder non-surgical options should be offered first and surgery last (only if initial treatment attempts fail). Weighing up the relative advantages of surgery, medical treatment and ART are the foundations for a global approach to infertility associated with endometriosis.

[Neurotrophins and pain in endometriosis].

Thu, 01 Jul 2010 00:00:00 +0000

OBJECTIVES: To evaluate the expression of five members of the neurotrophins family in ovarian endometriotic cyst (endometrioma) (OMA), compared to eutopic endometrium (EE) and to examine the correlation between the levels of induction and the pain intensity. PATIENTS AND METHODS: Twelve Caucasian women in luteal phase, operated for painful stage IV endometriosis were assigned to 2 groups according to a total Visual Analog Scale (tVAS) score above 15 or below 10. tVAS takes into account all VAS scores for dysmenorrhea, deep dyspareunia, non cyclic chronic pelvic pain, gastrointestinal and lower urinary symptoms. Samples of OMA and EE were processed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for NGF, BDNF, NT-3, NT-4/5 and NTRK2 mRNA expression. Expression levels in OMA were compared to those in EE on one hand and between two groups of 6 mild painful and 6 highly painful patients on the other. RESULTS: All neurotrophins were significantly higher expressed in OMA than in EE, in particular NGF and BDNF (induction ratios: 20.6 and 9.7, respectively). In contrast, no correlation was observed between induction ratios and pain intensity. CONCLUSION AND DISCUSSION: This is the first study reporting an over-expression of all neurotrophins in endometriosis, as only NGF was previously documented. It confirms the central role of this family in the genesis and modulation of pain in endometriosis. Anti-neurotrophin selective therapy might be a promising way of analgesia in the future.

[Endometriosis and genetics: what responsibility for the genes?].

Sat, 01 May 2010 00:00:00 +0000

Endometriosis is a very frequent and debilitating disease responsible for a considerable socio-economic toll. In spite of that, its pathogenesis remains enigmatic. Endometriosis is hold for a multifactorial pathology resulting from the mixed effects of environmental and genetic factors. To date, few susceptibility factors have been reported, with the exception of some polymorphisms in estrogen and progesterone receptors. Large-scale expressional studies have clearly demonstrated that endometriosis is a hormone-dependant disease, characterized by three main features: (i) inflammation, (ii) excessive production of estrogens, and (iii) progesterone resistance. Endometriosis is also considered as a benign metastatic disease, closely linked to cancer. However, the risk of malignant transformation appears to be very limited, likely by a systematic repression of the genes involved in cell cycle and a specific regulation of the HOX genes. Lastly, endometriosis might result from abnormalities of the eutopic endometrium, which show the same molecular alterations than the ectopic endometrium, to a lesser extent however. These alterations, possibly occurring during the embryonic life through epigenetic and genetic predisposition, could lead to an earlier and non-invasive diagnosis for endometriosis.

Complete surgery for low rectal endometriosis: long-term results of a 100-case prospective study.

Sat, 01 May 2010 00:00:00 +0000

OBJECTIVE: We conducted a prospective study to assess the long-term results of complete surgery for low rectal endometriosis (LRE), paying particular attention to surgical complications, functional results, and disease recurrence after a follow-up of at least 5 years. SUMMARY BACKGROUND DATA: Deep infiltrating endometriosis (DIE) may infiltrate the midlow rectum and lead to severe pelvic pain. Complete resection of LRE is reluctantly considered by young women of childbearing age. METHODS: From 1995 to 2003, 100 women with severe pelvic pain and previous incomplete surgery (n=82) underwent complete open surgery for LRE after thorough preoperative imaging work-up. This included total or subtotal rectal excision with combined resection of all extrarectal endometriotic lesions. Univariate analysis of predictive factors for transient neurogenic bladder and surgical complications was performed. Mean follow-up was 78+/-15 months. RESULTS: All patients underwent rectal resection with straight coloanal (n=16) or low colorectal anastomosis (n=84). A concomitant extrarectal procedure was required in all instances, including gynecologic procedures (n=100), additional intestinal (n=45), and urologic (n=23) resections. A fertility-preserving procedure was possible in 92% of the patients. Mean numbers of DIE and endometriotic lesions were 3.9+/-1.4 and 5.5+/-1.6 per patient, respectively. There were no deaths and the surgical morbidity rate was 16%. Sixteen patients developed a transient peripheral neurogenic bladder, which was more frequently observed after colonanal anastomosis (P<0.001) or concomitant hysterectomy (P<0.01) and in patients with more than 4 DIE lesions (P<0.05). At last follow-up, 94 patients had complete (n=83) or very satisfactory (n=11) relief of symptoms. Urine voiding and fecal continence was satisfactory in all cases. There was no recurrence of colorectal and/or urologic endometriosis and the overall DIE recurrence rate was 2%. CONCLUSIONS: Complete surgery for LRE provides excellent long-term functional results in 94% of the patients, provided all extraintestinal endometriotic lesions are resected during the same surgical procedure. In that setting, the overall 5-year recurrence rate is very low.

Severe ureteral endometriosis: the intrinsic type is not so rare after complete surgical exeresis of deep endometriotic lesions.

Sat, 01 May 2010 00:00:00 +0000

OBJECTIVE: To evaluate the rate of intrinsic ureteral endometriosis in patients presenting with severe ureteral endometriosis. DESIGN: Observational study between June 1992 and December 2007. SETTING: University tertiary referral center. PATIENT(S): Twenty-nine patients presenting deeply infiltrating endometriosis (DIE) with severe ureteral endometriosis. Severe ureteral endometriosis was defined as DIE lesions causing significant obstruction to the urinary flow with ureteral stenosis. INTERVENTION(S): Complete surgical exeresis of DIE lesions. MAIN OUTCOME MEASURE(S): Pre- and peroperative evaluation associated with histologic analysis. Intrinsic ureteral endometriosis was defined as presence of DIE lesions infiltrating the ureteral muscularis. RESULT(S): In a series of 627 patients with histologic proved DIE, we observed 29 (4.6%) patients with severe ureteral endometriosis. Ureteral lesions (n = 34) were right sided in 7 (24.1%) patients, left sided in 17 (58.6%) patients, and bilateral in 5 (17.3%) patients. Eleven (37.9%) patients presented intrinsic lesions. Out of the 34 ureteral lesions 13 (38.2%) were intrinsic. In cases of radical ureteral surgery (n = 21 patients; n = 24 ureteral lesions) intrinsic ureteral DIE was observed in 52.4% (11 cases) of the patients and in 54.2% (13 cases) of the ureteral lesions. CONCLUSION(S): The prevalence of intrinsic ureteral endometriosis is underestimated. This result must be taken into account when specifying the surgical modalities for patients presenting with severe ureteral endometriosis.

Steroidogenic factor-1 expression in ovarian endometriosis.

Sat, 01 May 2010 00:00:00 +0000

Steroidogenic factor-1 (SF-1), a major protein regulating the complex cascade of steroidogenis, has been postulated to play a role in ovarian endometriosis. However, the expression in situ of SF-1 in ovarian endometriosis is unknown. To shed light on its presence, the expression of SF-1 was studied by immunohistochemistry in 30 cases of ovarian endometriosis (proliferative, n=15; secretory phase, n=15) and in 10 cases of normal eutopic endometrium coming from the same patients. No SF-1 immunoreactivity was observed in glands or endometrial stroma from ovarian endometriosis or eutopic endometrium. In contrast, a strong immunoreactivity was observed in the adjacent ovarian cortical or medullary mesenchymatous cells in all the cases examined independently of the cycle’s phases. Contrary to the earlier reported hypothesis, our data showed for the first time the absence of SF-1 expression in glands and endometrial stroma from ovarian endometriosis and eutopic endometrium. However, the strong expression of SF-1 observed in cortical and medullary ovarian mesenchymatous cells adjacent to endometriosis, suggests a potential role for these cells in locally induced steroidogenesis.

Estrogen and progesterone receptors in smooth muscle component of deep infiltrating endometriosis.

Thu, 01 Apr 2010 00:00:00 +0000

OBJECTIVE: To analyze the expression of estrogen (ER) and progesterone (PR) receptors in the smooth muscle component (SMC) of deep infiltrating endometriosis (DIE). DESIGN: A prospective clinical and pathologic study of 60 cases of DIE. SETTING: University Hospital Department of Gynacology. PATIENT(S): Sixty patients with symptomatic DIE (uterosacral endometriosis n = 14; bladder endometriosis n = 10; colonic endometriosis n = 16; rectovaginal endometriosis n = 20). INTERVENTION(S): Laparoscopic surgery. MAIN OUTCOME MEASURE(S): The expression of ER and PR was studied by immunohistochemistry in the SMC directly around endometriotic foci and at distance (at least >1.5 cm) from them in correlation with proliferative and secretory phases of cycle. RESULTS: The ER and PR were present in the SMC of DEI in each location excepting colonic endometriosis where ER were absent. Independently of cycle’s phases the PR were more abundant than ER. With the exception of rectovaginal endometriosis, where the ER and PR were more abundant in the proliferative than in the secretory phase, in other locations the ER and PR did not differ significantly with cycle’s phases. Last, if ER and PR were more abundant in SMC around endometriotic foci than at a distance from them. However, the difference was not significant. CONCLUSIONS: Our data substantially confirm for the first time that in various forms of DIE, ER and PR are present not only in glands and stroma but also in the smooth muscle major histologic component of this disease.

Surgery for bladder endometriosis: long-term results and concomitant management of associated posterior deep lesions.

Thu, 01 Apr 2010 00:00:00 +0000

BACKGROUND: Deep infiltrating endometriosis (DIE) is presented as a disease with high recurrence risk. Bladder DIE is the most frequent location in cases of urinary endometriosis. Surgical removal has been recommended for bladder DIE but long-term outcomes remains unevaluated. The objectives of this study are to evaluate the rate of recurrence after partial cystectomy for patients presenting with bladder DIE and to outline the surgical modalities for handling associated posterior DIE nodules. METHODS: Seventy-five consecutive patients with histologically proved bladder DIE were enrolled at a single tertiary academic center between June 1992 and December 2007. A partial cystectomy was performed for each patient. Complete surgical exeresis of all associated symptomatic DIE lesions was carried out during the same surgical procedure. Bladder DIE patients were classified into three groups: patients with isolated bladder DIE (Group A); patients with associated symptomatic posterior DIE (Group B); patients with associated asymptomatic posterior DIE (Group C). Bladder DIE recurrence was defined as a clinical reappearance of the disease or radiological evidence that mandated a new surgical procedure. We assessed pelvic pain symptoms pre- and post-operatively using a 10-cm visual analogue scale. RESULTS: In a series of 627 patients with DIE, we observed 75 patients (12%) with bladder DIE. With a 50.9 +/- 44.6 months mean follow-up after partial cystectomy no patient presented evidence of bladder DIE recurrence. Post-operatively, we observed a significant improvement with respect to pain symptoms, with only two patients (2.7%) developing major complications during follow-up. Among patients with non-operated associated asymptomatic posterior DIE lesions (n = 15), a second surgical procedure indicated for pain symptoms was necessary in only one patient (6.7%). CONCLUSIONS: For patients presenting with bladder DIE, no patients required further surgery for bladder recurrence after radical surgery consisting in partial cystectomy. Exeresis of associated posterior DIE nodules is indicated only when they are symptomatic.

Cancer and fecundity issues mandate a multidisciplinary approach.

Mon, 01 Feb 2010 00:00:00 +0000

OBJECTIVE: To review the existing options for preserving fecundity in young cancer patients, outlining the differences that exist in each individual cancer situation and how these affect our choice of fecundity-preserving measures. DESIGN: Review the pathophysiology data on ovarian function that serve for outlining the advantages and/or drawbacks of certain fecundity-preserving measures such as ovarian freezing and emergency IVF. Provide support arguments for outlining the need for setting locally rooted cancer and fecundity task forces that throw the bases for a multidisciplinary approach in this field. SETTING: Review of literature data. PATIENT(S): Women of reproductive age affected with different types of cancer. MAIN OUTCOME MEASURE(S): Outcome of selected emergency fertility preserving measures such as ovarian tissue freezing followed by grafting or emergency IVF. RESULT(S): When performed in the 30s-the typical age for breast cancer, the most frequently encountered cancer in women of reproductive age, ovarian freezing hampers ovarian recovery and the chances for spontaneous pregnancy. CONCLUSION(S): Based on a review of the different situations encountered, we recommend that fecundity-preserving measures offered to young cancer patients, including ovarian freezing and emergency IVF, emanate from multidisciplinary approaches.

Th1 and Th2 ummune responses related to pelvic endometriosis.

Fri, 01 Jan 2010 00:00:00 +0000

OBJECTIVE: This study analyzed the relationship between clinical characteristics of endometriosis and Th1/Th2 immune response patterns. METHODS: A prospective study was performed with 65 patients with endometriosis (Group A) and 33 without the disease (Group B). Measurement of IL 2, 4 and 10, TNF-alpha and IFN-gamma was carried out in peripheral blood and peritoneal fluid. RESULTS: Serum TNF-alpha was higher in patients with endometriosis who had deep dyspareunia compared to controls (mean 4.5 pg/ml and 2.3 pg/ml, p<0.05). Among these patients (n=32), 65.5% had deep endometriosis. Patients with endometriosis and infertility had higher IL-2 concentrations in peritoneal fluid than controls (mean 5.9 pg/ml and 0.2 pg/ml, p<0.05). Among these patients (n=22), 63.5% (n=14) had deep endometriosis. A higher concentration of IL-10 was also observed in patients with ovarian endometriosis when compared to those without this type of disease, as well as when compared to control group patients (mean 50 pg/ml, 18.7 pg/ml and 25.7 pg/ml, p<0.05). CONCLUSIONS: These results suggest that when specific clinical data are associated with a higher production of certain cytokines, there is a Th1 response pattern that may be related to deep infiltrating endometriosis.

Total laparoscopic hysterectomy for benign uterine pathologies: obesity does not increase the risk of complications.

Tue, 01 Dec 2009 00:00:00 +0000

BACKGROUND: This study was designed to investigate the intra-operative characteristics and the risk of intra- and post-operative complications in cases of total laparoscopic hysterectomy (TLH) in overweight, obese and non-obese patients. METHODS: This cohort study includes all patients undergoing TLH for benign pathologies between January 1993 and June 2007 in Cochin university hospital (Paris). Demographic and surgical data were analysed. A comparison between overweight and obese patients versus non-obese patients and multivariate analyses were performed. RESULTS: Of 1460 patients undergoing TLH, 101 patients (6.9%) had a BMI of 30 or higher and 338 (23.2%) were overweight. After adjustment with respect to the patients’ characteristics and past history (age, parity, past history of laparotomies, previous Cesarean section, menopausal status), no significant difference was found whether in terms of intra-operative (haemorrhage, transfusion, thrombosis, ureter, bladder or bowel injuries) or post-operative complications (hyperthermia, infections, fistula). Concerning the intra- and post-operative characteristics of these patients, only a significantly longer operating time was noted in the case of obesity (RR = 1.80; CI 95%: 1.16-2.81). CONCLUSIONS: In our experience, provided that the operating technique is meticulous, the intra- and post-operative complications are not increased in the case of obesity, although the operating time is longer.

Associated ovarian endometrioma is a marker for greater severity of deeply infiltrating endometriosis.

Sat, 01 Aug 2009 00:00:00 +0000

OBJECTIVE: To investigate whether an associated ovarian endometrioma is a marker for severity of deep infiltrating endometriosis (DIE). DESIGN: Observational study between June 1992 and December 2005. SETTING: University tertiary referral center. PATIENT(S): Five hundred patients with histologically assessed DIE. INTERVENTION(S): Complete surgical exeresis of deep endometriotic lesions. MAIN OUTCOME MEASURE(S): Severity of the disease was quantified according to the mean number of DIE lesions and the type of main lesion. RESULT(S): In patients with associated ovarian endometrioma, the number of single isolated DIE lesions was statistically significantly lower (41.9% vs. 61.1%). The mean number of DIE lesions was statistically significantly higher in patients presenting with an associated ovarian endometrioma (2.51 +/- 1.72 vs. 1.64 +/- 1.0). For patients with associated ovarian endometrioma DIE lesions were more severe with an increased rate of vaginal, intestinal, and ureteral lesions. CONCLUSION(S): Associated ovarian endometrioma is a marker for the severity of the DIE. In a clinical context suggestive of DIE, when there is an ovarian endometrioma, the practitioner should investigate the extent of the disease to check for severe and multifocal DIE lesions.

Reactive oxygen species controls endometriosis progression.

Wed, 01 Jul 2009 00:00:00 +0000

Endometriosis is associated with chronic inflammation, and reactive oxygen species (ROS) are proinflammatory mediators that modulate cell proliferation. We have investigated whether the dysregulation of ROS production in endometriotic cells correlates with a pro-proliferative phenotype and can explain the spreading of this disease. Stromal and epithelial cells were purified from ovarian endometrioma and eutopic endometrium from 14 patients with endometriosis to produce four primary cell lines from each patient. ROS production, detoxification pathways, cell proliferation, and mitogen-activated protein kinase pathway activation were studied and compared with epithelial and stromal cell lines from 14 patients without endometriosis. Modulation of the proliferation of endometriosis by N-acetyl-cysteine, danazol, and mifepristone was tested in vitro and in 28 nude mice implanted with endometriotic tissue of human origin. Endometriotic cells displayed higher endogenous oxidative stress with an increase in ROS production, alterations in ROS detoxification pathways, and a drop in catalase levels, as observed for tumor cells. This increase in endogenous ROS correlated with increased cellular proliferation and activation of ERK1/2. These phenomena were abrogated by the antioxidant molecule N-acetyl-cysteine both in vitro and in a mouse model of endometriosis. Human endometriotic cells display activated pERK, enhanced ROS production, and proliferative capability. Our murine model shows that antioxidant molecules could be used as safe and efficient treatments for endometriosis.

[How does peritoneal fluid flow influence anatomical distribution of endometriotic lesions?].

Wed, 01 Apr 2009 00:00:00 +0000

Endometriosis is a common disease in gynecology. Many theories were proposed to explain the endometriosis pathogenesis. The distribution of the endometriosis lesions seems to be interesting in order to understand the endometriosis pathogenesis. This distribution is asymmetric. This asymmetric distribution of endometriosis is explained by the anatomy of the peritoneal cavity and by the intraperitoneal fluids. It strongly confirms the role of menstrual regurgitation and peritoneal fluid in the endometriosis genesis. The similar asymmetric distribution for all types of endometriosis (superficial lesions, ovarian endometriosis cyst, deep endometriosis) is an argument in favor of a unique origin for the different types of lesions.

Absence of association between a functional polymorphism of ALOX15 gene and infertility in endometriosis.

Wed, 01 Apr 2009 00:00:00 +0000

The aim of the present study, involving 463 women of reproductive age, was to evaluate for the first time the relationship between endometriosis, endometriosis-related infertility, and a recently described functional polymorphism in the ALOX15 gene, reported to be essential for implantation. In our study population, ALOX15 -292 C/T was not correlated either with the risk of developing an endometriosis or with the risk of infertility.

Incidence and risk factors of bladder injuries during laparoscopic hysterectomy indicated for benign uterine pathologies: a 14.5 years experience in a continuous series of 1501 procedures.

Wed, 01 Apr 2009 00:00:00 +0000

BACKGROUND: Laparoscopic hysterectomy is indicated as an alternative to laparotomy when the vaginal route is potentially difficult because of an immobile uterus and a poor vaginal accessibility. The aim of this study was to evaluate the rate, the risk factors for bladder injuries in a series of 1501 laparoscopic hysterectomies indicated for benign uterine pathologies. METHODS: This study was conducted retrospectively from January 1993 to 2000 and prospectively from 2001 to July 2007.The indications, patients’ characteristics and complications were recorded. The overall rate of bladder injuries, the comparison of means (t test) and percentages (exact chi(2) test) between the cases and the population with no injury, the odd ratios (OR) and multivariate analysis were performed using the statistical package for the social sciences software. RESULTS: The rate of bladder injuries was 1% (15 patients). Risks factors were previous Caesarian section [OR: 4.33, 95% confidence interval (CI): 1.53-12.30] and previous laparotomy (OR: 4.69, 95% CI: 1.59-13.8). The rate of injury decreases with the surgeons’ experience and reaches a plateau of 0.4% after 100 hysterectomies performed. CONCLUSIONS: The rate of bladder injury during total laparoscopic hysterectomy is low and decreases with the surgeon’s experience. Bladder injury is not linked to an increase of post-operative morbidity when recognized and repaired during the same laparoscopic procedure. The comparison with other routes of hysterectomies should take into account these risk factors.

Preoperative work-up for patients with deeply infiltrating endometriosis: transvaginal ultrasonography must definitely be the first-line imaging examination.

Sun, 01 Mar 2009 00:00:00 +0000

BACKGROUND: Transvaginal ultrasonography (TVUS) has important advantages compared with transrectal ultrasonography (TRUS): it is less invasive, is cost-effective, is a familiar and well-accepted approach, and anesthesia is not required. We compared the accuracy of TVUS and TRUS for diagnosing rectal wall involvement in patients presenting with histologically proved deeply infiltrating endometriosis (DIE). METHODS: Prospective study of 134 patients with histologically proved DIE underwent preoperative investigations using both TVUS and TRUS. The radiologist (TVUS) and sonographer (TRUS) were unaware of the clinical findings but knew that DIE was suspected. RESULTS: DIE was confirmed histologically for all the patients. A rectal wall involvement was histologically proved for 75 patients (56%). For the diagnosis of infiltration of the intestinal wall, TVUS and TRUS, respectively, had a sensitivity of 90.7% and 96.0%, a specificity of 96.5% and 100.0%, a positive predictive value of 97.1% and 100.0% and a negative predictive value of 88.9% and 95.2%. CONCLUSIONS: TVUS and TRUS have similar degrees of accuracy for predicting intestinal involvement. TVUS must be the first-line imaging process to perform for patients presenting with clinically suspected DIE. The question for the coming years is to define if it is necessary for TRUS to be carried out systematically in cases of clinically suspected DIE.

[Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications].

Thu, 01 Jan 2009 00:00:00 +0000

Republished from Hum Reprod Update. 2005 Nov-Dec;11(6):595-606. doi: 10.1093/humupd/dmi029. The relationship between chronic pelvic pain symptoms and endometriosis is unclear because painful symptoms are frequent in women without this pathology, and because asymptomatic forms of endometriosis exist. Our comprehensive review attempts to clarify the links between the characteristics of lesions and the semiology of chronic pelvic pain symptoms. Based on randomized trials against placebo, endometriosis appears to be responsible for chronic pelvic pain symptoms in more than half of confirmed cases. A causal association between severe dysmenorrhoea and endometriosis is very probable. This association is independent of the macroscopic type of the lesions or their anatomical locations and may be related to recurrent cyclic microbleeding in the implants. Endometriosis-related adhesions may also cause severe dysmenorrhoea. There are histological and physiopathological arguments for the responsibility of deeply infiltrating endometriosis (DIE) in severe chronic pelvic pain symptoms. DIE-related pain may be in relation with compression or infiltration of nerves in the subperitoneal pelvic space by the implants. The painful symptoms caused by DIE present particular characteristics, being specific to involvement of precise anatomical locations (severe deep dyspareunia, painful defecation) or organs (functional urinary tract signs, bowel signs). They can thus be described as -’location indicating pain-’. A precise semiological analysis of the chronic pelvic pain symptoms characteristics is useful for the diagnosis and therapeutic.

Clinical uses of anti-Müllerian hormone assays: pitfalls and promises.

Thu, 01 Jan 2009 00:00:00 +0000

OBJECTIVE: To investigate whether the controversy about fluctuations of anti-Müllerian hormone (AMH) levels during the menstrual cycle results from differences between the immunoassays currently available: the Beckman Coulter Immunotech kit (Fullerton, CA) and the Diagnostic Systems Laboratories kit (Webster, TX). DESIGN: Prospective trial. SETTING: Fertility clinics of two tertiary university hospitals. PATIENT(S): One hundred sixty-eight blood samples from three different populations. Serial samples at set intervals from the LH surge were taken in a fourth population of 10 volunteers. INTERVENTION(S): We remeasured AMH levels by using the Diagnostic Systems Laboratories kit in 168 blood samples in which AMH initially had been measured by using the Beckman Coulter assay. We also conducted serial AMH measurements (n = 7) during the menstrual cycle of 10 women. MAIN OUTCOME MEASURE(S): Linear regression of AMH levels determined by using 2 different assays and analysis of variance of serial measurements in the menstrual cycle. RESULT(S): We found a linear relationship between the 2 methods, with a correlation coefficient of 0.88. When repeated individual AMH measures were longitudinally analyzed in relation to the LH surge, a slight but significant decrease was observed after ovulation. CONCLUSION(S): Differences in AMH fluctuations during the menstrual cycle reported in recent publications do not result from the use of different AMH assays. The changes in AMH levels after ovulation are slight, yet statistically significant. However, the fluctuations observed are smaller than intercycle variability and therefore are not clinically relevant as far as AMH measurements for clinical purposes are concerned. In daily practice, AMH therefore can be measured anytime during the menstrual cycle.

Gonadotropin-releasing hormone agonists for endometriosis.

Thu, 25 Dec 2008 00:00:00 +0000

N Engl J Med. 2008 Dec 25;359(26):2844; author reply 2844-5. doi: 10.1056/NEJMc082087. Gonadotropin-releasing hormone agonists for endometriosis. de Ziegler D, Borghese B, Chapron C.

Surgical management of cervical intraepithelial neoplasia in HIV-infected women.

Mon, 01 Dec 2008 00:00:00 +0000

OBJECTIVE: Rates higher than 50% of positive margin after surgical treatment of cervical intraepithelial neoplasia (CIN) have been reported in HIV-infected women. We evaluated the efficacy of two excisional procedures, loop excision of the transformation zone (LLETZ) and electrosurgical conisation, in obtaining complete excision of CIN in HIV-infected patients. STUDY DESIGN: Eighty HIV-infected women with CIN or suspicion of cervical cancer underwent 86 surgical excisions. The indication of surgical modalities depended on both the size and location of the lesion and on the length of the cervix. Univariate logistic regression was used to identify factors associated with positive surgical margins. RESULTS: Preoperative colposcopy failed to visualize the entire transformation zone in 39% of cases, and showed that 93% of the lesions had endocervical extension. LLETZ was performed in 30 cases and electrosurgical conisation in 56 cases. Resection was complete, with negative margins, in 77% of cases (95% confidence interval, CI: 62-92%) after LLETZ and in 71% of case (95% CI: 60-83%) after electrosurgical resection. Residual disease was mostly located in the endocervical portion of histological specimen. During follow-up late complications such as cervical stenosis or unsatisfactory colposcopy were not observed. CONCLUSION: Endocervical extension of CIN being frequent among HIV-infected women, LLETZ should not be the preferred procedure. Appropriate surgical management leading in reducing the rate of positive margins may help decreasing the risk of persistence or recurrence of lesions.

Gene expression profile for ectopic versus eutopic endometrium provides new insights into endometriosis oncogenic potential.

Sat, 01 Nov 2008 00:00:00 +0000

Endometriosis is a common gynecological disorder characterized by pain and infertility, where the lesions disseminate everywhere in the body with a preference for the pelvis. In that, it could be regarded as a benign metastatic disease, because its issue is not fatal. However, the molecular bases of this intriguing clinical condition are not well known. The objective of this study is to characterize the transcriptome differences between eutopic vs. ectopic endometrium with a special interest in pathways involved in cancerogenesis. We performed two hybridizations in technical replicate on highly specific long oligonucleotides microarrays (NimbleGen), with cDNA prepared from six-patients pools, where the same patient provided both eutopic and ectopic endometrium (endometriomas). To confirm the expression microarrays data, quantitative RT-PCR validation was performed on 12 individuals for 20 genes. Over 8000 transcripts were significantly modified (more than twice) in the lesions corresponding to 5600 down- or up-regulated genes. These were clustered through DAVID Bioinformatics Resources into 55 functional groups. The data are presented in a detailed and visual way on 24 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways implemented with induction ratios for each differentially expressed gene. An outstanding control of the cell cycle and a very specific modulation of the HOX genes were observed and provide some new evidence on why endometriosis only very rarely degenerates into cancer. The study constitutes a noteworthy update of gene profiling in endometriosis, by delivering the most complete and reliable list of dysregulated genes to date.

Working to improve implantation.

Fri, 01 Aug 2008 00:00:00 +0000

Fertil Steril. 2008 Aug;90(2):461-2; author reply 462-3. doi: 10.1016/j.fertnstert.2008.05.084. Epub 2008 Jul 14. Working to improve implantation. de Ziegler D, Wolf JP, Chapron C.

Pre-hCG elevation of plasma progesterone: good, bad or otherwise.

Tue, 01 Jul 2008 00:00:00 +0000

Hum Reprod Update. 2008 Jul-Aug;14(4):393. doi: 10.1093/humupd/dmn020. Epub 2008 Jun 2. Pre-hCG elevation of plasma progesterone: good, bad or otherwise. de Ziegler D, Bijaoui G, Chapron C.

[FSH and IVF management: the best and worst case scenarios].

Sun, 01 Jun 2008 00:00:00 +0000

OBJECTIVE: A recent meta-analysis covering 21 studies shows that, when taken in isolation, the basal FSH level (commonly used to assess the ovarian reserve) is a poor indicator of successful in vitro fertilization (IVF) outcome. PATIENTS AND METHODS: We present a personal series of 3592 IVF procedures. Analysis of the results compares the age and basal FSH values, based on a statistical analysis that is essentially descriptive. RESULTS: When FSH levels are high, the pregnancy rate remains acceptable in young women (<38 years); it drops sharply, however, in older women. In each age group, the rate of spontaneous miscarriage does not increase according to FSH level. The pregnancy rate is better in young women with high FSH levels than in older women with normal FSH levels. DISCUSSION AND CONCLUSION: The results presented agree with the studies published in the literature, which suggest that FSH is a prognostic factor for the quantity of oocytes obtained (ovarian reserve) while age defines the quality of the oocyte: it is this difference in quantity, and not in quality, which makes the difference between cases of poor and normal response to IVF. In young women at least, a high FSH level is not a contra-indication in principle for IVF.

Peritoneal fluid flow influences anatomical distribution of endometriotic lesions: why Sampson seems to be right.

Sun, 01 Jun 2008 00:00:00 +0000

Endometriosis is a frequent pathology for which the dominant signs and symptoms are pelvic pain and infertility. The physiopathology remains the subject of controversy. Four physiopathological hypotheses have been put forward: regurgitation, metaplasia, induction and (vascular and lymphatic) embolization. The anatomical distribution of endometriotic lesions would appear to be fundamental for a better understanding of Sampson’s menstrual regurgitation theory of endometriosis. Analysis of the results in the literature and comparison with our experience clearly shows that the distribution of endometriotic lesions is asymmetrical in several respects. Abdominopelvic anatomy and peritoneal fluid flow can explain this asymmetrical distribution of endometriotic lesions in the great majority of cases. These observations are a very strong argument in favour of the crucial role played by tubal regurgitation and the peritoneal fluid in the physiopathology of endometriosis. The similarity in anatomical distribution of endometriomas, superficial and deeply invasive endometriotic lesions would tend to indicate a common origin for these different types of lesions.

Genetic polymorphisms of matrix metalloproteinase 12 and 13 genes are implicated in endometriosis progression.

Thu, 01 May 2008 00:00:00 +0000

BACKGROUND: Matrix metalloproteinases (MMPs) may contribute to endometriosis. We tested whether eight functional polymorphisms of these genes could modify the risk of endometriosis. METHODS: In this case-control study, 227 endometriosis and 241 controls were genotyped for MMP1 -1607 1G/2G, MMP2 -1575 G/A (MMP2.1), -1306 C/T (MMP2.2), MMP3 -1612 5A/6A, MMP7 -153 C/T (MMP7.1), -181 A/G (MMP7.2), MMP12 -82 A/G and MMP13-77 A/G. Association between MMP genotypes and superficial (SUP), deep infiltrating (DIE) and endometriomas (OMA) was tested for each polymorphism separately, using unconditional logistic regression and then for combined genotypes, using the combination test. RESULTS: When considering all cases, MMP2 polymorphisms were found to be significant, mainly due to DIE (P = 0.023). A small difference between SUP and controls was found for MMP7.2 (P = 0.032) and MMP12 (P = 0.035), in the absence of correction for multiple testing. Using the combination test, the best association when comparing SUP with controls was obtained for MMP12-MMP13 (P = 0.004) for the combined genotype A/G-A/A (odds ratio = 27.60, 95% confidence interval: 2.80-272.40). CONCLUSIONS: These data show a potential role for MMP12 -82 A/G and MMP13 -77 A/G combined polymorphisms in superficial endometriosis. As no association was found with deep infiltrating endometriosis, this combination of polymorphisms might protect from a more in-depth penetration of tissues.

Lymph node involvement and lymphovascular invasion in deep infiltrating rectosigmoid endometriosis.

Thu, 01 May 2008 00:00:00 +0000

OBJECTIVE: To analyze the lymph node involvement by endometriotic foci in rectosigmoid endometriosis and to correlate it with clinical and histological parameters including the presence of lymphovascular invasions, which could explain this lymph node involvement. DESIGN: A prospective study of 26 consecutive cases of rectosigmoid endometriosis between January 2005 and January 2007. SETTING: A multidisciplinary study including clinical and pathological data. PATIENT(S): Twenty-six patients with symptomatic rectosigmoid endometriosis. INTERVENTION(S): Laparoscopic surgery with pathological analysis of each specimen. MAIN OUTCOME MEASURE(S): Involvement of lymph nodes by endometriotic foci was correlated with the size and the wall layers affected by endometriotic lesions, the number of lymph nodes retrieved, and the presence of lymphovascular invasions demonstrated by D2-40, a specific antibody to lymphatic vessels. RESULT(S): Lymph node involvement by endometriosis was observed in 11 of the 26 patients (42.3%) and correlated with the size of the lesions, the number of lymph nodes retrieved, and the presence of lymphovascular invasions, which were observed in 36.3% of cases. CONCLUSION(S): Our data confirm that lymph node involvement by endometriotic foci is a frequent event in rectosigmoid endometriosis and may result at least partially from a lymphatic spread of the disease.

Urohemoperitoneum during pregnancy with consequent fetal death in a patient with deep endometriosis.

Sat, 01 Mar 2008 00:00:00 +0000

A 25-year-old woman with unoperated deep endometriosis of the uterosacral ligament suddenly experienced severe abdominal pain, hematuria, hemoperitoneum, and intrauterine death at 31 weeks’ gestation. Surgical intervention revealed active hemorrhage arising from right uterine artery and interruption of the ureter in an area of previously documented but not treated endometriotic nodule. Histologic examination confirmed presence of decidualized endometriosis at this site. Urohemoperitoneum during pregnancy is a rare but possible complication in women carrying deep peritoneal endometriotic nodules.

Müllerianosis.

Mon, 01 Oct 2007 00:00:00 +0000

Müllerianosis may be defined as an organoid structure of embryonic origin; a choristoma composed of müllerian rests–normal endometrium, normal endosalpinx, and normal endocervix–singly or in combination, incorporated within other normal organs during organogenesis. A choristoma is a mass of histologically normal tissue that is -’not normally found in the organ or structure in which it is located-’ (Choristoma, 2006). Müllerian choristomas are a subset of non-müllerian choristomas found throughout the body. Histologically, endometrial-müllerianosis and endometriosis are both composed of endometrial glands and stroma, but there the similarity ends. Their pathogenesis is different. Sampson faced the same difficulty with pathogenesis and nomenclature when he wrote: -‘The nomenclature of misplaced endometrial or müllerian lesions is a difficult one to decide upon.-’ -‘The term müllerian would be inclusive and correct, but unfortunately it suggests an embryonic origin.-’ Sampson then divided -‘misplaced endometrial or müllerian tissue-’ into -‘four or possibly five groups, according to the manner in which this tissue reached its ectopic location-’ (Sampson, 1925). Sampson’s classification of heterotopic or misplaced endometrial tissue is based on pathogenesis: 1) -‘direct or primary endometriosis-’ [adenomyosis]; -‘a similar condition occurs in the wall of the tube from its invasion by the tubal mucosa-’ [endosalpingiosis]; 2) -‘peritoneal or implantation endometriosis;-’ 3) -’transplantation endometriosis;-’ 4) -‘metastatic endometriosis;-’ and 5) -‘developmentally misplaced endometrial tissue. (I admit the possibility of such a condition, but have never been able to appreciate it.)-’ (Sampson, 1925). It is precisely this condition -‘developmentally misplaced endometrial tissue,-’ [müllerianosis] that is the subject of this review.

[Diethylstilbestrol exposure in utero. Polemics about metroplasty. The pros].

Sat, 01 Sep 2007 00:00:00 +0000

The diethylstilbestrol (DES) is a synthetic estrogen which was prescribed from 1941 onwards for the prevention of miscarriage. As well as a possible risk of cancer, another side effect of this treatment was the possible abnormality of the genitalia in the female issue of the prescribed user. Apart from possibly having a hypoplasic uterus, the patient is also prone, in the case where she has an undersized uterus, to having a much narrower than normal cavity. Consequently, there is a tendency for an excess of muscle tissue on the uterus walls. This can be observed on a RMN. The most significant characteristics of this abnormality are: constriction rings around the proximal uterine segment, a T shaped uterus, uterus with an arched base. The idea of the plastic enlargement operation (metroplasty) is to widen the cavity by making careful incisions of the excess muscle tissue located on the uterus wall. The objective of this is to obtain a triangular shaped cavity taking care though to weaken the walls themselves. 61 patients were treated. We observed 37 pregnancies after 16 months with 30 ongoing pregnancies. Generally, the anatomic results are excellent but it is difficult to measure the functional results of the success rate in future pregnancies. The reason for this is the enlarging of the cavity alone does not guarantee successful fertility. There are other problems to take into account e.g. implantation, miscarriage and premature labor. There are risks with this operation, such as placenta percreta, a possible rupture of the uterus, though this can happen at any time with DES patients. This operation can only be recommended once a thorough examination of the patient has been made.

Cytosolic aspartate aminotransferase, a new partner in adipocyte glyceroneogenesis and an atypical target of thiazolidinedione.

Fri, 10 Aug 2007 00:00:00 +0000

We show that cytosolic aspartate aminotransferase (cAspAT) is involved in adipocyte glyceroneogenesis, a regulated pathway that controls fatty acid homeostasis by promoting glycerol 3-phosphate formation for fatty acid re-esterification during fasting. cAspAT activity, as well as the incorporation of [(14)C]aspartate into the neutral lipid fraction of 3T3-F442A adipocytes was stimulated by the thiazolidinedione (TZD) rosiglitazone. Conversely, the ratio of fatty acid to glycerol released into the medium decreased. Regulation of cAspAT gene expression was specific to differentiated adipocytes and did not require any peroxisome proliferator-activated receptor gamma (PPARgamma)/retinoid X receptor-alpha direct binding. Nevertheless, PPARgamma is indirectly necessary for both cAspAT basal expression and TZD responsiveness because they are, respectively, diminished and abolished by ectopic overexpression of a dominant negative PPARgamma. The cAspAT TZD-responsive site was restricted to a single AGGACA hexanucleotide located at -381 to -376 bp whose mutation impaired the specific RORalpha binding. RORalpha ectopic expression activated the cAspAT gene transcription in absence of rosiglitazone, and its protein amount in nuclear extracts is 1.8-fold increased by rosiglitazone treatment of adipocytes. Finally, the amounts of RORalpha and cAspAT mRNAs were similarly increased by TZD treatment of human adipose tissue explants, confirming coordinated regulation. Our data identify cAspAT as a new member of glyceroneogenesis, transcriptionally regulated by TZD via the control of RORalpha expression by PPARgamma in adipocytes.

Monarc transobturator sling system for the treatment of female urinary stress incontinence: results of a post-operative transvaginal ultrasonography.

Wed, 01 Aug 2007 00:00:00 +0000

The aim of the study was to determine Monarc (American Medical Systems) sling position after surgical treatment of stress urinary incontinence (SUI) through the transobturator approach. A total of 54 consecutive women with SUI were evaluated post-operatively with transvaginal ultrasound. A concomitant hysterectomy was performed in ten cases and a concomitant prolapse surgery in six cases. Ultrasound measurements include urethral length, the distance between the upper edge of the sling and the bladder neck (BN-S) and the BN-S/U ratio. The mean distance between the transobturator tape and the bladder neck was found to be 12.6 +/- 3.2 mm in the group of patients who underwent the transobturator procedure alone, 13 +/- 3.1 mm in the transobturator plus hysterectomy group and 12 +/- 2.8 mm in the transobturator plus prolapse group. The superior tape margin was at the mid-urethra in 81.5% of patients and always at a distance greater than 7 mm from the bladder neck. Eight patients did not have satisfactory results after the surgery. Only in one out of these eight patients was the transobturator sling not found to be at the mid-urethra. The superior tape margin of the Monarc sling remained at the level of mid-urethra in the majority of cases. It was never located too proximally beneath the bladder neck.

Ureteral complications from laparoscopic hysterectomy indicated for benign uterine pathologies: a 13-year experience in a continuous series of 1300 patients.

Sun, 01 Jul 2007 00:00:00 +0000

BACKGROUND: The aim of this study was to evaluate the risk of ureteral injuries and to discuss how to avoid their occurence after laparoscopic hysterectomy indicated for benign uterine pathologies. METHODS: This observational study covers the period from January 1993 to December 2005 (retrospective study from 1993 to 2000 and prospective from 2001). We reviewed incidence, methods of diagnosis and management of ureteral injuries. RESULTS: The rate of ureteral injuries was 0.3% (four patients). Three patients presented a ureteral fistula diagnosed secondarily some time after the operation. The fourth patient presented a ureteral injury that was diagnosed peroperatively. Three out of four of the lesions were observed on the right side. In every case, there were preoperative risk factors connected with a past history of surgery, or the lateral location of uterine myomas. All four patients needed ureterovesical reimplantation. The outcome was good in all four cases. CONCLUSIONS: The rate of ureter complications after laparoscopic hysterectomy is low and comparable to that observed after hysterectomy by laparotomy. The risk should not prevent laparoscopic hysterectomy being used more widely. Prevention depends on training in the technique and the surgeon’s experience.

Bladder endometriosis: getting closer and closer to the unifying metastatic hypothesis.

Fri, 01 Jun 2007 00:00:00 +0000

OBJECTIVE: It has been hypothesized that bladder endometriotic nodules are an independent form of endometriosis that should be considered a distinct clinical entity. If this is true, the frequency of nonvesical endometriotic lesions in affected patients should be similar to the prevalence of the disease in the general population (about 10%). The aim of the study was to evaluate the presence of other forms of endometriosis in patients with bladder endometriotic nodules. DESIGN: Case series. SETTING: Two gynecologic surgical units. PATIENT(S): Fifty-eight women with large bladder endometriotic nodules. INTERVENTION(S): To evaluate the concomitant presence of other forms of endometriosis. MAIN OUTCOME MEASURE(S): Presence of superficial peritoneal implants, ovarian endometriomas, adhesions, and extravesical deep peritoneal endometriosis. RESULT(S): The presence of superficial peritoneal implants, ovarian endometriomas, adhesions, and extravesical deep peritoneal endometriosis was observed in 58.6% (95% confidence interval [CI]: 45.2-71.2), 44.8% (95% CI: 32.2-58.2), 81.0% (95% CI: 68.4-89.6), and 27.6% (95% CI: 16.7-40.8) of cases, respectively. The presence of at least one of them was documented in 87.9% of cases (95% CI: 76.7-94.3). CONCLUSION(S): Endometriotic nodules of the bladder are frequently associated with other forms of pelvic endometriosis. This result does not support the vision that bladder endometriotic nodules should be considered an independent form of the disease.

Treatment of symptomatic uterine fibroids.

Thu, 24 May 2007 00:00:00 +0000

N Engl J Med. 2007 May 24;356(21):2218-9; author reply 2219. Treatment of symptomatic uterine fibroids. Borghese B, Chapron C.

Intramedullary endometriosis of the conus medullaris: case report.

Thu, 01 Mar 2007 00:00:00 +0000

Neurosurgery. 2007 Mar;60(3):E582; author reply E582. doi: 10.1227/01.NEU.0000255370.11605.43. Intramedullary endometriosis of the conus medullaris: case report. Batt RE, Yeh J, Smith RA, Martin DC, Chapron C.

Umbilical endometriosis.

Thu, 01 Feb 2007 00:00:00 +0000

J Eur Acad Dermatol Venereol. 2007 Feb;21(2):280-1. doi: 10.1111/j.1468-3083.2006.01854.x. Umbilical endometriosis. Farhi D, Zimmermann U, Chapron C, Dupin N.

[Surgical treatment of rectal endometriosis].

Mon, 01 Jan 2007 00:00:00 +0000

Intestinal endometriosis accounts for 8-12% of all endometriosis and rectal involvement is most often encountered in the context of deep pelvic infiltration. Intestinal symptoms, often nonspecific, are most typically seen as painful defecation or constipation worsening in the premenstrual period associated with pelvic pain, dysmenorrheal, dyspareunia, and infertility. Physical examination should include a pelvic exam under anesthesia. Endorectal ultrasound best evaluates rectal muscle invasion, while pelvic MRI and CT will evaluate the full extent of pelvic involvement and other GI sites of implantation. Only radical extirpative surgery of all intestinal, urologic, deep pelvic, and adnexal sites of endometriosis will permit relief of pain, prevent recurrence, and hopefully preserve fertility. In view of the frequency of extra-intestinal sites of involvement and technical difficulties augmented by previous surgical interventions, open laparotomy remains the preferred approach. A laparascopic approach would be reserved only for well-selected patients presenting with isolated colorectal involvement.

Surgical routes and complications of hysterectomy for benign disorders: a prospective observational study in French university hospitals.

Mon, 01 Jan 2007 00:00:00 +0000

BACKGROUND: Despite the advantages of the vaginal and laparoscopic approaches, most hysterectomies carried out involve laparotomy. The objective of this prospective observational multicentre study was to examine the routes and complications of hysterectomy for benign disorders. METHODS: Of the 15 university hospitals belonging to Collégiale de Gynécologie-Obstétrique de Paris-Ile de France, 12 participated in this study that took place between June and December 2004. We analysed the characteristics of the patients, the indications for hysterectomy and intra- and post-operative complications (and their determinants) according to the surgical approach. RESULTS: In total, 634 women underwent hysterectomy for benign disorders during the study period. The patients’ mean age (+/-SD), BMI, parity and previous Caesarean sections were 51.4 +/- 10.3 years, 25 +/- 5.7 kg/m(2), 2 +/- 1.6 children and 0.2 +/- 0.6, respectively. Hysterectomy was performed by the laparoscopic, laparoscopically assisted vaginal hysterectomy (LAVH), laparotomic and vaginal routes in 19.1, 8.2, 24.4 and 48.3% of cases, respectively. The operating time was shorter with the vaginal route than with laparoscopy, laparotomy and LAVH (P < 0.0001). Intra- and post-operative complications were significantly more frequent in the laparotomic group (18%) compared with the vaginal group (8.2%), the laparoscopic group (5.8%) and the LAVH group (8.2%) (P < 0.0001). In a multivariate logistic regression model, obesity [odds ratio (OR): 2.84, 95% confidence interval (CI): 1.53-5.27, P = 0.001], history of pelvic surgery (OR: 2.47, 95% CI: 1.39-4.39, P = 0.002) and history of Caesarean section (OR: 2.04, 95% CI: 1.01-4.1, P = 0.046) were significantly associated with intra- and post-operative complications. Laparoconversion was necessary in 36 cases (7.5%) overall and was more frequent with laparoscopy and LAVH than with the vaginal route (P < 0.0001). CONCLUSIONS: This study confirms that the vaginal route is increasingly used for hysterectomy in France and that it is the route of choice for benign disorders.

Image analysis measurements of the microvascularisation in endometrium, superficial and deep endometriotic tissues.

Wed, 01 Nov 2006 00:00:00 +0000

The aim of this study was to evaluate precisely the microvascularisation of endometrium, superficial and deep endometriotic lesions, in progestin-treated and non-treated patients suffering from endometriosis. METHODS: A population of 66 women was constituted. Immunohistochemistry was carried out with a specific marker of the endothelial cells (CD31). The number of vessels and the vessel area were assessed by a computer image analysis system. RESULTS: The number of vessels per mm2 were 211, 216, 225 and the vessel area was 270, 141 and 194 microm2, respectively in endometria, superficial and deep endometriotic lesions of untreated women. In endometria, superficial and deep endometriotic lesions of progestin-treated women the number of vessels were respectively 129, 149, and 181 per mm2 and the vessel area was 369, 474 and 254 microm2. CONCLUSION: Statistically significant data indicate that endometriotic lesions are heterogeneous and suggest that progestin treatment induces a reduction in number and a concomitant dilation of microvessels with more microvascular changes in endometrium and superficial endometriotic lesions than in deep endometriotic lesions.

Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis.

Wed, 01 Nov 2006 00:00:00 +0000

OBJECTIVE: To detect and quantify mast cells in peritoneal, ovarian, and deep infiltrating endometriosis and to study the relationship between mast cells and nerves in endometriosis. DESIGN: Prospective histological and immunohistochemical study. SETTING: University of Brussels, Belgium. PATIENT(S): Sixty-nine women undergoing laparoscopic excision of endometriosis for pain. Thirty-seven biopsies of normal tissue were obtained from women without endometriosis. INTERVENTION(S): Excision of endometriosis from different anatomical locations. MAIN OUTCOME MEASURE(S): Immunohistochemistry with chymase and tryptase to confirm the presence of mast cells and activated mast cells, respectively, in endometriotic lesions. Quantification of mast cells, activated mast cells, and degranulating mast cells in the different locations of endometriosis. Study of the relationship between mast cells and nerves by quantifying mast cells located less than 25 mum from nerves immunohistochemically stained with S-100 protein. Preoperative pain score evaluation by visual analogue scales. RESULT(S): Patients with deeply infiltrating lesions had significantly higher preoperative pain scores than patients with peritoneal or ovarian endometriosis. Mast cells and degranulating mast cells are significantly more abundant in endometriotic lesions than in nonaffected tissues. Deep infiltrating lesions show a significantly higher number of mast cells, activated mast cells, and mast cells located <25 microm from nerves than peritoneal and ovarian lesions. We found significantly more degranulating mast cells in deep infiltrating lesions than in peritoneal lesions. CONCLUSION(S): The presence of increased activated and degranulating mast cells in deeply infiltrating endometriosis, which are the most painful lesions, and the close histological relationship between mast cells and nerves strongly suggest that mast cells could contribute to the development of pain and hyperalgesia in endometriosis, possibly by a direct effect on nerve structures.

Deeply infiltrating endometriosis: pathogenetic implications of the anatomical distribution.

Sat, 01 Jul 2006 00:00:00 +0000

BACKGROUND: To investigate whether knowledge of the anatomical distribution of histologically proven deeply infiltrating endometriosis (DIE) lesions contributes to understanding the pathogenesis. METHODS: Observational study between June 1992 and December 2004 (retrospective study between 1992 and 2000; prospective study between 2001 and 2004). Continuous series of 426 patients suffering from pelvic pain who underwent complete surgical exeresis of DIE. DIE lesions were classified according to four different possibilities: (i) Firstly, DIE lesions were classified as located in the anterior or posterior pelvic compartment. (ii) Secondly, DIE were classified as left, median and right. (iii) Thirdly, DIE lesions were classified as pelvic or abdominal. (iv) Fourthly, DIE lesions that could present in a right and/or left location were classified as unilateral or bilateral. RESULTS: These 426 patients presented 759 histologically proven DIE lesions: bladder (48 lesions; 6.3%); uterosacral (USL) (400 lesions; 52.7%); vagina (123 lesions; 16.2%); ureter (16 lesions; 2.1%) and intestine (172, 22.7%). DIE lesions are significantly more often located in the pelvis (n=730 lesions) than in the abdomen (n=29 lesions) (P<0.0001). Pelvic DIE lesions are significantly more often located in the posterior compartment of the pelvis [682 DIE lesions (93.4%) versus 48 DIE lesions (6.6%); P<0.0001]. Pelvic DIE lesions are significantly more frequently located on the left side. For patients with unilateral pelvic DIE lesions, the anatomical distribution is significantly different in the three groups: left (172 lesions; 32.0%), median (284 lesions; 52.8%) and right (82 lesions; 15.2%) (P<0.0001). For patients with lateral lesions, left DIE lesions (172 lesions; 67.8%) were found significantly more frequently than right DIE lesions (82 lesions; 32.2%) (P<0.0001). A similar predisposition was observed when we included patients with bilateral pelvic DIE lesions (P=0.0031). The same significantly asymmetric distribution is observed for total (pelvic and abdominal) DIE lesions. CONCLUSIONS: Our results demonstrate that distribution of DIE lesions is asymmetric. It is possible that this is related to the anatomical difference between the left and right hemipelvis and to the flow of peritoneal fluid. These findings support the hypothesis that retrograde menstruation of regurgitated endometrial cells is implicated in the pathogenesis of DIE.

Is thrombotic microangiopathy associated with antitumoral activity?

Thu, 01 Jun 2006 00:00:00 +0000

Gynecol Oncol. 2006 Jun;101(3):549-50. doi: 10.1016/j.ygyno.2006.01.044. Epub 2006 Mar 9. Is thrombotic microangiopathy associated with antitumoral activity? Chopin N, Alexandre J, Chapron C, Moachon L, Goldwasser F.

Rosiglitazone controls fatty acid cycling in human adipose tissue by means of glyceroneogenesis and glycerol phosphorylation.

Fri, 12 May 2006 00:00:00 +0000

Control of fatty acid homeostasis is crucial to prevent insulin resistance. During fasting, the plasma fatty acid level depends on triglyceride lipolysis and fatty acid re-esterification within fat cells. In rodents, Rosiglitazone controls fatty acid homeostasis by stimulating two pathways in the adipocytes, glyceroneogenesis and glycerol phosphorylation, that provide the glycerol 3-phosphate necessary for fatty acid re-esterification. Here, we analyzed the functionality of both pathways for controlling fatty acid release in subcutaneous adipose tissue samples from lean and overweight women before and after Rosiglitazone ex vivo treatment. In controls, pyruvate, used as a substrate of glyceroneogenesis, could contribute to the re-esterification of up to 65% of the fatty acids released after basal lipolysis, whereas glycerol phosphorylation accounted for only 14 +/- 9%. However, the efficiency of glyceroneogenesis diminished as body mass index (BMI) of women increased. After Rosiglitazone treatment, increase of either pyruvate- or glycerol-dependent fatty acid re-esterification was strictly correlated to that of phosphoenolpyruvate carboxykinase and glycerol kinase, the key enzymes of each pathway, but depended on BMI of the women. Whereas the Rosiglitazone responsiveness of glyceroneogenesis was rather constant according to the BMI of the women, glycerol phosphorylation was mostly enhanced in lean women (BMI < 27). Overall, these data indicate that, whereas glyceroneogenesis is more utilized than glycerol phosphorylation for fatty acid re-esterification in human subcutaneous adipose tissue in the physiological situation, both are solicited in response to Rosiglitazone but with lower efficiency when BMI is increased.

Diagnosis of endometriosis with imaging: a review.

Wed, 01 Feb 2006 00:00:00 +0000

Endometriosis corresponds to ectopic endometrial glands and stroma outside the uterine cavity. Clinical symptoms include dysmenorrhoea, dyspareunia, infertility, painful defecation or cyclic urinary symptoms. Pelvic ultrasound is the primary imaging modality to identify and differentiate locations to the ovary (endometriomas) and the bladder wall. Characteristic sonographic features of endometriomas are diffuse low-level internal echos, multilocularity and hyperchoic foci in the wall. Differential diagnoses include corpus luteum, teratoma, cystadenoma, fibroma, tubo-ovarian abscess and carcinoma. Repeated ultrasound is highly recommended for unilocular cysts with low-level internal echoes to differentiate functional corpus luteum from endometriomas. Posterior locations of endometriosis include utero-sacral ligaments, torus uterinus, vagina and recto-sigmoid. Sonographic and MRI features are discussed for each location. Although ultrasound is able to diagnose most locations, its limited sensitivity for posterior lesions does not allow management decision in all patients. MRI has shown high accuracies for both anterior and posterior endometriosis and enables complete lesion mapping before surgery. Posterior locations demonstrate abnormal T2-hypointense, nodules with occasional T1-hyperintense spots and are easier to identify when peristaltic inhibitors and intravenous contrast media are used. Anterior locations benefit from the possibility of MRI urography sequences within the same examination. Rare locations and possible transformation into malignancy are discussed.

Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications.

Tue, 01 Nov 2005 00:00:00 +0000

Republished in Gynecol Obstet Fertil. 2009 Jan;37(1):57-69. doi: 10.1016/j.gyobfe.2008.08.016. The relationship between chronic pelvic pain symptoms and endometriosis is unclear because painful symptoms are frequent in women without this pathology, and because asymptomatic forms of endometriosis exist. Our comprehensive review attempts to clarify the links between the characteristics of lesions and the semiology of chronic pelvic pain symptoms. Based on randomized trials against placebo, endometriosis appears to be responsible for chronic pelvic pain symptoms in more than half of confirmed cases. A causal association between severe dysmenorrhoea and endometriosis is very probable. This association is independent of the macroscopic type of the lesions or their anatomical locations and may be related to recurrent cyclic micro-bleeding in the implants. Endometriosis-related adhesions may also cause severe dysmenorrhoea. There are histological and physiopathological arguments for the responsibility of deeply infiltrating endometriosis (DIE) in severe chronic pelvic pain symptoms. DIE-related pain may be in relation with compression or infiltration of nerves in the sub-peritoneal pelvic space by the implants. The painful symptoms caused by DIE present particular characteristics, being specific to involvement of precise anatomical locations (severe deep dyspareunia, painful defecation) or organs (functional urinary tract signs, bowel signs). They can thus be described as location indicating pain. A precise semiological analysis of the chronic pelvic pain symptoms characteristics is useful for the diagnosis and therapeutic management of endometriosis in a context of pain.

ESHRE guideline for the diagnosis and treatment of endometriosis.

Sat, 01 Oct 2005 00:00:00 +0000

The objective was to develop recommendations for the diagnosis and treatment of endometriosis and its associated symptoms. A working group was convened comprised of practising gynaecologists and experts in evidence-based medicine from Europe, as well as an endometriosis self-help group representative. After reviewing existing evidence-based guidelines and systematic reviews, the expert panel met on three occasions for a day during which the guideline was developed and refined. Recommendations based solely on the clinical experience of the panel were avoided as much as possible. The entire ESHRE Special Interest Group for Endometriosis and Endometrium was given the opportunity to comment on the draft guideline, after which it was available for comment on the ESHRE website for 3 months. The working group then ratified the guideline by unanimous or near-unanimous voting; finally, it was approved by the ESHRE Executive Committee. The guideline will be updated regularly, and will be made available at http://www.endometriosis.org/guidelines.html with hyperlinks to the supporting evidence, and the relevant references and abstracts. For women presenting with symptoms suggestive of endometriosis, a definitive diagnosis of most forms of endometriosis requires visual inspection of the pelvis at laparoscopy as the ‘gold standard’ investigation. However, pain symptoms suggestive of the disease can be treated without a definitive diagnosis using a therapeutic trial of a hormonal drug to reduce menstrual flow. In women with laparoscopically confirmed disease, suppression of ovarian function for 6 months reduces endometriosis-associated pain; all hormonal drugs studied are equally effective although their side-effects and cost profiles differ. Ablation of endometriotic lesions reduces endometriosis-associated pain and the smallest effect is seen in patients with minimal disease; there is no evidence that also performing laparoscopic uterine nerve ablation (LUNA) is necessary. In minimal-mild endometriosis, suppression of ovarian function to improve fertility is not effective, but ablation of endometriotic lesions plus adhesiolysis is effective compared to diagnostic laparoscopy alone. There is insufficient evidence available to determine whether surgical excision of moderate-severe endometriosis enhances pregnancy rates. IVF is appropriate treatment especially if there are coexisting causes of infertility and/or other treatments have failed, but IVF pregnancy rates are lower in women with endometriosis than in those with tubal infertility. The management of severe/deeply infiltrating endometriosis is complex and referral to a centre with the necessary expertise is strongly recommended. Patient self-help groups can provide invaluable counselling, support and advice.

High rate of recurrence of cervical intraepithelial neoplasia after surgery in HIV-positive women.

Mon, 01 Aug 2005 00:00:00 +0000

OBJECTIVE: Our study investigated the rate of recurrence of cervical intraepithelial neoplasia (CIN) in HIV-positive women after surgery in the era of highly active antiretroviral therapy (HAART). METHODS: One hundred twenty-one HIV-positive women were followed-up with cytology, colposcopy, and histology after surgery for CIN. We conducted univariate and multivariate analyses to determine the relation between recurrence of CIN and risk factors using Cox proportional hazard models with left truncation. RESULTS: The rate of recurrence of any CIN was 22.3 per 100 patient-years and the rate of high-grade CIN was 8.6 per 100 patient-years during 166 and 279 patient-years of follow-up, respectively. In multivariate analysis, a positive margin was associated with a risk of recurrence of any CIN (relative risk [RR] = 3.5, 95% confidence interval [CI]: 1.2-9.8) and a risk of recurrence of high-grade CIN (RR = 9.0, 95% CI: 2.2-36.5). CD4 counts <200 cells/mm were associated with a risk of recurrence of any CIN (RR = 9.4, 95% CI: 2.7-32.7) but not with a risk of recurrence of high-grade CIN. HAART exhibited a protective effect on the recurrence of any CIN (RR = 0.3, 95% CI: 0.1-0.7) and of high-grade CIN (RR = 0.2, 95% CI: 0.1-0.7). CONCLUSION: CD4 cell counts <200/mm(3) and a positive margin were predictors of recurrence, whereas HAART had a strong protective effect. Although surgery is highly effective in immunocompetent patients, it seems to be effective only in preventing progression to cancer in HIV-infected women.

Total laparoscopic hysterectomy: preoperative risk factors for conversion to laparotomy.

Fri, 01 Jul 2005 00:00:00 +0000

STUDY OBJECTIVE: To identify the preoperative factors affecting the risk of conversion to laparotomy during total laparoscopic hysterectomy (TLH) indicated for benign conditions (surgery performed in cases of genital prolapse and/or urinary stress incontinence was excluded). DESIGN: Retrospective comparative study (Canadian Task Force classification II-2). SETTING: University tertiary referral center for gynecologic endoscopic surgery. PATIENTS: Four hundred sixteen consecutive patients who underwent TLH during the first 5 years of our experience performing TLH. INTERVENTION: Total laparoscopic hysterectomy. MEASUREMENTS AND MAIN RESULTS: The rate of conversion to laparotomy was 7% (29 patients). Factors that were found to be independently related to the risk of conversion to laparotomy are the following: body mass index (adjusted OR 1.09; 95% CI 1.01-1.18); uterine width on transvaginal ultrasonography (US) between 8 and 10 cm (adjusted OR 4.01; 95% CI 1.54-10.45); uterine width on US greater than 10 cm (adjusted OR 9.17; 95% CI 2.74-30.63); lateral myoma measuring greater than 5 cm on US (adjusted OR 3.57; 95% CI 0.97-13.17); history of adhesion-causing abdominopelvic surgery (adjusted OR 2.92; 95% CI 1.23-6.94). CONCLUSION: Transvaginal US evaluation is essential before performing TLH. Awareness of the risk factors for conversion to laparotomy is essential for proper patient information and better selection of patients.

Complications of laparoscopy: an inquiry about closed versus open-entry technique.

Fri, 01 Apr 2005 00:00:00 +0000

Am J Obstet Gynecol. 2005 Apr;192(4):1352; author reply 1352-3. doi: 10.1016/j.ajog.2004.10.611. Complications of laparoscopy: an inquiry about closed versus open-entry technique. Pierre F, Chapron C.

Operative management of deeply infiltrating endometriosis: results on pelvic pain symptoms according to a surgical classification.

Tue, 01 Mar 2005 00:00:00 +0000

STUDY OBJECTIVE: To assess the results of complete surgical excision for patients with painful functional symptoms in a context of histologically proven deeply infiltrating endometriosis (DIE). DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: One hundred thirty-two patients with pelvic pain symptoms and histologically proved DIE. The DIE lesions were classified according to surgical classification: uterosacral ligaments (USL), vagina, bladder, or intestine. INTERVENTION: Complete surgical excision of DIE lesions. MEASUREMENTS AND MAIN RESULTS: A retrospective analysis was made of medical, operative, and pathologic reports as well as of questionnaires mailed to patients. Efficiency of surgical excision was assessed according to two methods: objective evaluation (numerical rating scale) and subjective evaluation (patients were asked to classify the improvement after surgery with one of the following: excellent, satisfactory, slight, or no improvement). For each symptom, the mean scores according to the numerical rating scale were significantly lower postoperatively. The difference between the preoperative and postoperative scores was 5.2 points +/- 3.6 for dysmenorrhea, 4.6 points +/- 3.1 for deep dyspareunia, 4.4 points +/- 3.7 for painful defecation during menstruation, 4.9 +/- 3.2 for lower urinary tract symptoms during menses, and 4.6 points +/- 3.4 for noncyclic chronic pelvic pain. Comparable results were observed for patients in each group according to the surgical classification of their DIE lesions: USL (n = 78 patients); vagina (n = 25 patients); bladder (n = 13 patients); and intestine (n = 16 patients). Subjective evaluation showed that the improvement was considered to be excellent in 40.2% of women (53 patients), satisfactory in 42.4% (56 patients), slight in 14.4% (19 patients), and nonexistent in 3.0% (4 patients). The patients’ characteristics (i.e., age, gravidity, parity, body mass index, preoperative medical treatment, follow-up after surgery, number and location of DIE lesions, revised American Fertility Society stage, associated endometrioma) did not differ significantly according to whether the improvement was considered to be excellent (Group A: 53 patients) or not (Group B: 79 patients). Among the infertile patients (n = 78; 59.1%), there was no difference in pain improvement if the patient was pregnant or not in the 42 women who achieved pregnancy after the surgery. CONCLUSION: Complete surgical excision of DIE lesions results in a statistically significant reduction in painful functional symptoms. These results are observed whatever the main location of DIE lesions. The patients’ preoperative characteristics have no significant influence on the result.

Presurgical diagnosis of posterior deep infiltrating endometriosis based on a standardized questionnaire.

Tue, 01 Feb 2005 00:00:00 +0000

BACKGROUND: To derive a diagnostic model based on symptoms and history as assessed by a standardized questionnaire to predict posterior deep infiltrating endometriosis (DIE) among women with chronic pelvic pain symptoms. METHODS: 134 women scheduled for laparoscopy for chronic pelvic pain symptoms completed a standardized self-administered questionnaire, specifically designed for the study. We compared the symptoms of the women with posterior DIE diagnosed at laparoscopy with those of the women with other disorders, and used multiple logistic regression analysis to select the best combination of symptoms for predicting posterior DIE. Cross-validation was performed with the jackknife method. RESULTS: 51 women (38.1%) were diagnosed with posterior DIE and 83 with other disorders (61.9%). The following variables were independent predictors for posterior DIE: painful defecation during menses, severe dyspareunia (visual analogic scale > or =8), pain other than noncyclic, and previous surgery for endometriosis. The cross-validation procedure leads to a simplified diagnostic model that uses two independent predictors: painful defecation during menses and severe dyspareunia. The sensitivity of this model for diagnosing posterior DIE was 74.5%, its specificity was 68.7%, its positive likelihood ratio was 2.4, and its negative likelihood ratio was 0.4. It correctly classified 70.9% of our sample into a high-risk (with either severe dyspareunia or painful defecation during menses) and a low-risk (neither symptom) group. CONCLUSIONS: Standardized evaluation of painful symptoms is useful for screening women so that they may have adequate exploration and counselling before laparoscopic surgery for pelvic pain symptoms.

Surgical management of deeply infiltrating endometriosis: an update.

Wed, 01 Dec 2004 00:00:00 +0000

Deeply infiltrating endometriosis (DIE) manifests itself mainly in the form of pain, predominantly deep dyspareunia, and painful functional symptoms that are aggravated monthly during menstruation, with the semiology being directly correlated with the location of the lesions (bladder, rectum). A workup to assess the extent of the disease is necessary to establish an accurate map of the DIE lesions, which is the essential condition to perform complete exeresis. The treatment of first intention is surgical, because medical treatments are only palliative in the majority of cases. Successful treatment depends on achieving radical surgical exeresis. Analysis of the anatomical distribution of the DIE lesions allows a -‘surgical classification-’ to be proposed to standardize the modalities of surgical treatment. Further studies are needed to specify the place and modalities of medical treatments preoperatively and postoperatively.

Evidence for asymmetric distribution of lower intestinal tract endometriosis.

Mon, 01 Nov 2004 00:00:00 +0000

Ureteral endometriosis: the role of magnetic resonance imaging.

Mon, 01 Nov 2004 00:00:00 +0000

In six women out of 792 who underwent magnetic resonance imaging (MRI) for management of deep infiltrating endometriosis (DIE), ureteral involvement was suspected. Ureteral endometriosis was identified as a hypointense nodule on T2- weighted images and hyperintense foci on T1-weighted images. Magnetic resonance urography detected obstruction and hydronephrosis in half the women. Detection with MRI of periureteral involvement (extrinsic endometriosis) in four women rather than ureteral wall lesions (intrinsic endometriosis) in two women is an original finding from this series. Magnetic resonance imaging features were correlated and matched with intraoperative and pathologic findings. Magnetic resonance imaging is a useful preoperative tool for the diagnosis and assessment of ureteral endometriosis in rare cases when such lesions have been suspected.

Accuracy of rectal endoscopic ultrasonography and magnetic resonance imaging in the diagnosis of rectal involvement for patients presenting with deeply infiltrating endometriosis.

Sun, 01 Aug 2004 00:00:00 +0000

OBJECTIVE: To compare the accuracy of rectal endoscopic ultrasonography (REU) and magnetic resonance imaging (MRI) for predicting rectal wall involvement in patients presenting histologically proven deeply infiltrating endometriosis (DIE). METHODS: This was a retrospective study of a continuous series of 81 patients presenting histologically proven DIE who underwent preoperative investigations using both REU and MRI. The sonographer and the radiologist, who were unaware of the clinical findings and patient history, but knew that DIE was suspected, were asked whether there was involvement of the digestive wall. RESULTS: Rectal DIE was confirmed histologically in 34 of the 81 (42%) patients. For the diagnosis of rectal involvement, sensitivity, specificity and positive and negative predictive value for REU were 97.1%, 89.4%, 86.8% and 97.7% and for MRI they were 76.5%, 97.9%, 96.3% and 85.2%. CONCLUSION: The sensitivity and negative predictive value of REU were higher than those of MRI suggesting that REU performs better than MRI in the diagnosis of rectal involvement for patients presenting with DIE. Prospective studies with a large number of patients are needed in order to validate these preliminary results.

Deeply infiltrating endometriosis originates from the retrocervical area.

Sun, 01 Aug 2004 00:00:00 +0000

J Am Assoc Gynecol Laparosc. 2004 Aug;11(3):440; author reply 440-1. doi: 10.1016/s1074-3804(05)60066-7. Deeply infiltrating endometriosis originates from the retrocervical area. Chapron C, Chopin N, Borghese B, Foulot H.

Prospective evaluation of the learning curve of laparoscopic-assisted vaginal hysterectomy in a university hospital.

Sat, 01 May 2004 00:00:00 +0000

STUDY OBJECTIVE: To prospectively analyze the learning curve of laparoscopic-assisted vaginal hysterectomy (LAVH) in a surgical team and evaluate if length of surgery can be reduced safely. DESIGN: Prospective observational study (Canadian Task Force classification II-2). SETTING: Department of obstetrics and gynecology in a university-affiliated hospital. PATIENTS: One hundred and sixty consecutive women undergoing LAVH performed between January 1, 1998 and April 30, 2001. INTERVENTION: LAVH (AAGL Classification System for Laparoscopic Hysterectomy III-B-3). MEASUREMENTS AND MAIN RESULTS: The primary parameter evaluated was length of surgery. Patients were grouped in cohorts of 10, in order to perform a time curve that would assist us in evaluation of the learning process. Once the plateau was reached, we evaluated the process before and after this plateau (groups 1 [learning stage] and 2 [second stage], respectively). Average length of surgery was 126 minutes (range, 60-260). Length of surgery was 138 minutes (range, 75-260) in the learning stage (first 80 cases) and 112 minutes (range, 60-225) in the second stage (p <.0001). Total rate of complications was 11.6%. There were three major complications, and they occurred before the plateau. There were 15 minor complications (9.67%), 8 during the first stage and 7 in the second stage, (p =.9; NS). A second learning curve excluding LAVH with associated surgeries was obtained. The average length of surgery for the first stage was 133 minutes (range, 75-205) and 102 minutes for the second stage (range, 60-130) (p >.0001). CONCLUSION: Analysis of the learning curve demonstrated that the length of surgery in LAVH could be reduced without increasing the number of complications.

[Chronic pelvic pain and endometriosis].

Mon, 01 Dec 2003 00:00:00 +0000

Chronic pelvic pain and endometriosis remain two of the most perplexing problems in gynaecology. In some women, the problem is to determine whether or not endometriosis causes the pain they are consulting for. Deep pelvic endometriosis presents essentially in the form of a painful syndrome dominated by deep dyspareunia and painful functional symptoms that recur according to the menstrual cycle. The semiology is directly correlated with the location of the lesions (bladder, rectum). Lesions of the utero-sacral ligaments are the most frequent deeply infiltrating endometriosis lesions. The following variables are related to the severity of dysmenorrhoea: number of previous surgical procedures for endometriosis, score in the revised American Fertility Society classification, extensiveness of adnexal adhesion, Douglas obliteration, size of the posterior deeply infiltrating endometriosis implant, extent of the sub-peritoneal infiltration by the posterior deeply infiltrating endometriosis. It is essential to investigate (clinically and with magnetic resonance imaging) these deep endometriosis lesions and to draw up a precise map, which is the only way to be sure that exeresis will be complete. Surgery remains the first intention treatment, whereas medical treatment is only palliative in the majority of cases. Success of treatment depends on how radical surgical exeresis is. Operative laparoscopy is efficient for bladder, utero-sacral ligaments and vaginal deeply infiltrating endometriosis. However, indications for laparotomy still exist, notably for bowel lesions. Based on analysis of the anatomical distribution of deep pelvic endometriosis lesions, a -‘surgical classification-’ is proposed with the aim of establishing standard modes for surgical treatment. Further studies are required to clarify the place and modes for pre- and postoperative medical treatment.

Complications during set-up procedures for laparoscopy in gynecology: open laparoscopy does not reduce the risk of major complications.

Mon, 01 Dec 2003 00:00:00 +0000

OBJECTIVE: To compare the risk of major complications during the set-up procedures for laparoscopy according to whether the classic technique (creation of the pneumoperitoneum followed by introduction of the optics trocar) or open laparoscopy is used. METHODS: Comparison was made of two retrospective series each carried out in a department promoting one of the two techniques. The setting was a university-affiliated hospital. Two groups of patients were compared: group A, classic laparoscopy, n = 8324; group B, open laparoscopy, n = 1562. We investigated the set-up procedures of operative laparoscopy according to the rules of classic or open laparoscopy. RESULTS: The risk of failure requiring conversion to laparotomy is significantly higher in the group of patients who underwent open laparoscopy [three cases (0.19%) vs. 0 case (0.0%); p = 0.004]. The risk of major complications is comparable in the two groups [group A, four cases (0.05%) vs. group B, three cases (0.19%); p = 0.08]. In the classic laparoscopy group there were four major complications: one injury to the aorta and three bowel injuries. In the open laparoscopy group there were three major complications: two bowel injuries and one postoperative occlusion. CONCLUSIONS: Open laparoscopy does not reduce the risk of major complications during the set-up procedures for laparoscopy. Randomized prospective trials are indispensable for comparing the risks involved with the classic technique and those of open laparoscopy.

[Traumatic dissection of the internal carotid artery: malignant supratentorial infarction and decompressive treatment].

Sat, 01 Nov 2003 00:00:00 +0000

We present a case report of a thirty-six-year-old right-handed female. She suffered with a malignant space-occupying supratentorial ischemic stroke caused by a traumatic cervical internal carotid artery dissection. She had a car accident and, initially, presented with a normal examination. In two days, she became comatose (Glasgow Coma Scale score was 5) with complete left hemiplegia, right mydriasis and required respiratory assistance despite the medical treatment. It was decided to perform a large right frontotemporoparietal bone flap with large dural plasty. Eighteen months later, with intensive rehabilitation, the results of neuropsychological testing were normal, and the Barthel Index score was 90. The indications for decompressive surgery in malignant space-occupying supratentorial ischemic stroke remains controversial. The age, general condition, neurological examination (consciousness, pupils, deficit), extent of parenchymal hypodensity and attenuated corticomedullary contrast on the brain CT, degree of midline shift, presence of uncal hernation, disparition of the visibility of the mesencephalic cisterns and third ventricle, high level of the intracranial pressure, and perhaps the results of the perfusion-and diffusion-weighted MRI, are the elements to decide (or not decide) decompressive surgery.

Evidence for asymmetric distribution of sciatic nerve endometriosis.

Fri, 01 Aug 2003 00:00:00 +0000

OBJECTIVE: To investigate if a lateral asymmetry exists in the distribution of endometriotic lesions of the sciatic nerve. DATA SOURCES: All articles on sciatic nerve endometriosis identified by MEDLINE and EMBASE database searches were retrieved, and additional reports were collected by systematically reviewing all references. Monographs on endometriosis published in the last 15 years were consulted. METHODS OF STUDY SELECTION: We considered articles in which the presence of an endometriotic lesion of the sciatic nerve and the affected side were assessed. We also included reports lacking histological examination of sciatic nerve specimens but with a surgical diagnosis of pelvic endometriosis. Two authors abstracted data independently on standardized forms. The number of women and the side of the lesion were obtained from individual studies, and the combined frequency of left- and right-side sciatic nerve endometriosis in published reports was computed. TABULATION, INTEGRATION, AND RESULTS: Thirty-two reports including 63 subjects were selected. Endometriosis of the sciatic nerve was on the right side in 41 patients, on the left in 20, and bilateral in two. Considering only patients with unilateral sciatic nerve endometriosis, the observed proportion of right-side lesions (41 of 61 [67.2%]; 95% confidence interval 54.0%, 78.7%) significantly differed from the expected proportion of 50% (chi(2)(1) 7.23, P =.007). Among the 16 cases of histological demonstration of endometriosis infiltrating sciatic nerve roots or fibers, ten had it on the right side (62.5%) and six on the left. Twenty-six of the 38 subjects (68.4%) with surgical demonstration of pelvic endometriosis but without histopathologic evidence of direct sciatic nerve involvement were affected by right cyclic sciatica. CONCLUSION: The finding that two thirds of patients with sciatic nerve endometriosis had right-side lesions constitutes further evidence against the coelomic metaplasia theory. The interposition of the sigmoid colon between the regurgitated endometrial cells implanted on the left posterolateral pelvic peritoneum seems to protect the left lumbosacral plexus and sciatic nerve.

[The endoscopic operating room OR 1].

Tue, 01 Apr 2003 00:00:00 +0000

During the last few years, the development of surgical laparoscopy has been the major turning point, and the most important progress in the field of surgery. The specific installation requirements of surgical laparoscopy, as well as the technological progress proper to this surgical technique, justify the need of a new organization of the operating theatre. The new operating room OR 1 is especially designed to fit and satisfy the requirements of a modern operating theatre, where surgical laparoscopy plays a major role. The organization and the design of this new operating room (OR 1) rely on 2 main concepts: architectural, and computerized, through 2 PC systems SCB and AIDA. The main objectives of this new concept are: allowing the surgeon to control and command all the functions and the instruments, as well as the lighting of the room and the operating field; managing the surgical data and images required for medical files; establishing a communication network either from the inside or outside the sterile zone.

Deep infiltrating endometriosis: relation between severity of dysmenorrhoea and extent of disease.

Tue, 01 Apr 2003 00:00:00 +0000

BACKGROUND: Little is known about the precise nature of the relationship between dysmenorrhoea (DM) and endometriosis. Our aim was to evaluate the relationship between the severity of DM in women with posterior deep infiltrating endometriosis (DIE) and indicators of the extent of their disease. METHODS: Various indicators of the extent of DIE were recorded during surgery in 209 women. The severity of their DM was assessed with a pain scale. The scale was retrospective for 155 women and prospective for 54. Correlations were sought with an ordinal logistic regression model with cumulative odds. RESULTS: On univariate analysis the following variables were related to the severity of DM: number of previous surgical procedures for endometriosis; revised American Fertility society classification; extensiveness of adnexal adhesion; Douglas obliteration; size of the posterior DIE implant; extent of the sub-peritoneal infiltration by the posterior DIE (rectal, vaginal or both versus sub-peritoneal only). Current infertility was associated with less severe DM. After multiple regression analysis, presence of a rectal or vaginal infiltration by the posterior DIE and extensiveness of adnexal adhesion were the only factors that remained related to DM severity. CONCLUSIONS: The concept of ‘very deep infiltrating endometriosis’, defined as implants invading the wall of the pelvic organ, should be tested in future classification systems specifically addressed to the prediction of endometriosis-related pain.

[Deep pelvic endometriosis: management and proposal for a -'surgical classification-'].

Sat, 01 Mar 2003 00:00:00 +0000

Deep pelvic endometriosis presents essentially in the form of a painful syndrome dominated by deep dyspareunia and painful functional symptoms that recur according to the menstrual cycle, with the semiology directly correlated with the location of the lesions (bladder, rectum). It is essential to investigate these deep endometriosis lesions and draw up a precise map, which is the only way to be sure that exeresis will be complete. The treatment of first intention remains surgery, and medical treatment is only palliative in the majority of cases. Success of treatment depends on how radical surgical exeresis is. Based on analysis of the anatomical distribution of deep pelvic endometriosis lesions, a -‘surgical classification-’ is proposed with the aim of establishing standard modes for surgical treatment. Further studies are required to clarify the place and modes for pre- and postoperative medical treatment.

Coagulation or excision of ovarian endometriomas?

Sat, 01 Mar 2003 00:00:00 +0000

A systematic review was undertaken to determine whether coagulation or laser vaporization of endometriomas is associated with an increase in the risk of cyst recurrence compared with excision of the pseudocapsule. In the four comparative trials identified, endometrioma recurrence was reported in 39 of 212 (18.4%) women treated with coagulation or laser vaporization compared with 19 of 295 (6.4%) in those who underwent cystectomy. The odds ratios of endometrioma recurrence ranged from 1.41 to 9.38 with 95% CIs including unity in two studies. The common odds ratio was 3.09 (95% CI 1.78-5.36). Coagulation or laser vaporization of endometriomas without excision of the pseudocapsule seems to be associated with a significant increase in risk of cyst recurrence.

Anatomical distribution of deeply infiltrating endometriosis: surgical implications and proposition for a classification.

Wed, 01 Jan 2003 00:00:00 +0000

BACKGROUND: Deeply infiltrating endometriosis (DIE) is recognized as a specific entity responsible for pain. The distribution of locations and their contribution to surgical management has not been previously studied. METHODS: Medical, operative and pathological reports of 241 consecutive patients with histologically proven DIE were analysed. DIE lesions were classified as: (i). bladder, defined as infiltration of the muscularis propria; (ii). uterosacral ligaments (USL), as DIE of the USL alone; (iii). vagina, as DIE of the anterior rectovaginal pouch, the posterior vaginal fornix and the retroperitoneal area in between, and (iv). intestine, as DIE of the muscularis propria. RESULTS: A total of 241 patients presented 344 DIE lesions: USL (69.2%; 238); vaginal (14.5%; 50); bladder (6.4%; 22); intestinal (9.9%; 34). The proportion of isolated lesions differed significantly according to the DIE location: 83.2% (198) for USL DIE; 56.0% (28) for vaginal DIE; 59.0% (13) for bladder DIE; 29.4% (10) for intestinal DIE (P < 0.0001). The total number of DIE lesions varied significantly according to the location (P < 0.0001). In 39.1% of cases (9/23) intestinal lesions were multifocal. Only 20.6% (seven cases) of intestinal DIE were isolated and unifocal. CONCLUSIONS: Multifocality must be considered during the pre-operative work-up and surgical treatment of DIE. We propose a surgical classification based on the locations of DIE. Operative laparoscopy is efficient for bladder, USL and vaginal DIE. However, indications for laparotomy still exist, notably for bowel lesions.

[Utility of rectal endoscopic ultrasonography for digestive involvement of pelvic endometriosis. Technique and results].

Sun, 01 Dec 2002 00:00:00 +0000

Intestinal endometriosis present in up to 37% of cases is difficult to diagnose and treatment remains complex. Until recently barium enema and colonoscopy are the only two diagnostic tools. However there were many drawbacks and technical limitations due to the particular development of the endometrial lesions with frequent respect of the mucosa. Digestive involvement was often preoperative discovery and treatment was frequently incomplete. Development of endoscopic ultrasonography has improved the potential for preoperative diagnosis of digestive endometriosis. Many publications have now demonstrated its utility. Compared to other imaging techniques endoscopic ultrasonography has better sensibility close to 100%. Endoscopic ultrasonography is superior to Magnetic Resonance Imaging for the diagnosis of rectosigmoid endometriosis. Magnetic Resonance Imaging however gives a largest view of the pelvis. Using preoperatively endoscopic ultrasonography in patients who are at risk of digestive involvement will help to choose between different therapeutic modalities and surgical techniques.

Histologic appearance of endometriosis infiltrating uterosacral ligaments in women with painful symptoms.

Fri, 01 Nov 2002 00:00:00 +0000

STUDY OBJECTIVE: To describe the histologic appearance of deep endometriosis infiltrating the uterosacral ligaments (USL). DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: One hundred forty-nine women with pain due to endometriosis. INTERVENTION: Resection of one or both USL. MEASUREMENTS AND MAIN RESULTS: One hundred seventy-two USL were examined by histology after unilateral resection in 126 patients (84.6%) and bilateral resection in 23 (15.4%). Two-thirds of women (122, 70.9%) had a classic appearance of endometriosis. Lesions of myoproliferative endometriosis with a histologic appearance of so-called adenomyotic nodules were observed in 25 (14.5%). Associated fibrosis was most frequent in patients with positive compared with negative histology (85, 69.7% vs 18, 36.0%). CONCLUSION: Anatomicopathologic lesions of deep endometriosis infiltrating the USL are heterogeneous. Adenomyotic nodules are not frequently observed.

Management of ovarian endometriomas.

Fri, 01 Nov 2002 00:00:00 +0000

The efficiency of medical therapy as a unique treatment for endometrioma has not been demonstrated. Operative laparoscopic management is the ‘gold standard’ for surgical treatment, and there are no indications to prescribe medical treatment before cystectomy. Post-operative administration of low-dose cyclic oral contraceptives does not significantly affect the long-term recurrence of endometriosis after surgical treatment. In case of infertility, the management of endometriomas is controversial. Recurrent ovarian surgery is not recommended.

Anatomopathological lesions of bladder endometriosis are heterogeneous.

Tue, 01 Oct 2002 00:00:00 +0000

OBJECTIVE: To present the anatomopathological characteristics of deep bladder endometriosis. DESIGN: Descriptive anatomapathological study. SETTING: A university hospital department of gynecological surgery. PATIENT(S): Eleven consecutive patients complaining of pelvic pain and painful urinary functional symptoms. INTERVENTION(S): Laparoscopic partial cystectomy. MAIN OUTCOME MEASURE(S): Macroscopic and microscopic characteristics of deep bladder endometriosis lesions. RESULT(S): Deep bladder endometriosis lesions were extremely heterogeneous, not only in any one patient but also from one patient to another. Bladder muscularis propria presented three aspects: [1] hyperplasia of the fibromuscular tissue (4/11); [2] simple dissociation of the smooth muscle fiber bundles with no veritable -‘disorganization-’ (4/11); [3] simple thickening of the interstitial collagen network, or sclerosis (3/11). A histological adenomyotic nodule aspect was only observed in one patient (9%). CONCLUSION(S): Bladder endometriosis is an enigmatic disease. No hypothesis can be proposed as a single explanation for its pathogenesis.

Relation between pain symptoms and the anatomic location of deep infiltrating endometriosis.

Tue, 01 Oct 2002 00:00:00 +0000

OBJECTIVE: To investigate whether specific types of pelvic pain are correlated with the anatomic locations of deeply infiltrating endometriosis (DIE). DESIGN: Retrospective data analysis. SETTING: University tertiary referral center. PATIENT(S): Two hundred and twenty-five women with pelvic pain symptoms and DIE. INTERVENTION(S): During surgery, we recorded the anatomic locations of DIE implants and associated endometriosis. MAIN OUTCOME MEASURE(S): We studied the incidence of pelvic pain symptoms including severe dysmenorrhea, deep dyspareunia, noncyclic chronic pelvic pain, painful defecation during menstruation, urinary tract symptoms, and gastrointestinal symptoms as related to the location of DIE. RESULT(S): The frequency of severe dysmenorrhea increased with Douglas pouch adhesions and decreased with parity. The frequency of dyspareunia increased with a uterosacral ligament DIE location and decreased when it involved the bladder. The frequency of noncyclic chronic pelvic pain was higher when it involved the bowel and was lower for women who were treated for infertility. The frequency of painful defecation during menstruation was higher when DIE involved the vagina; lower urinary tract symptoms were more frequent when DIE involved the bladder and less frequent in women with a lower body mass index. Gastrointestinal symptoms were associated with bowel or vaginal DIE locations. CONCLUSION(S): The types of pelvic pain are related to the anatomic location of DIE. Knowledge of the characteristics of pelvic pain symptoms is important in the preoperative assessment of patients with suspected DIE.

Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a meta-analysis.

Wed, 01 May 2002 00:00:00 +0000

BACKGROUND: Laparoscopic surgery presents a large number of advantages over laparotomy. The goal of this work was to check whether these benefits outweigh any greater risk of complications. METHODS: The study design was a meta-analysis of published data from prospective randomized clinical trials (RCT). For the period 1966 to June 2000 we searched Medline and Cochrane Controlled Trial Registers and asked the investigators for further details. Meta-analysis was carried out with the Cochrane review manager software RevMan 4.1. RESULTS: A total of 27 prospective RCT including 3611 women (1809 treated by operative laparoscopy and 1802 treated by laparotomy) were enrolled in the meta-analysis. The overall risk of complications was significantly lower for patients operated by laparoscopic surgery [relative risk (RR) 0.59; 95% confidence interval (CI) 0.50-0.70]. There was no statistically significant difference concerning the risk of major complications with respect to the approach used (RR 1.0; 95% CI 0.60-1.65). The risk of minor complications was significantly lower for patients operated by laparoscopic surgery (RR 0.55; 95% CI 0.45-0.66). Concerning the risks of readmission, second procedure and blood transfusion, there was no difference between the two groups. Identical results were found when we performed a sensitivity analysis including or excluding studies according to the methodological score. Subgroup analysis according to how serious the surgery was (minor, major, advanced) showed a significant increase in the risk of transfusion for advanced procedures performed by laparotomy. CONCLUSIONS: Laparoscopic surgery is not inherently dangerous for patients presenting benign gynaecological pathologies. The potential risk of complications should no longer be advanced as an argument against using laparoscopic surgery rather than laparotomy for an operation when the indication allows the choice.

Routine clinical examination is not sufficient for diagnosing and locating deeply infiltrating endometriosis.

Wed, 01 May 2002 00:00:00 +0000

STUDY OBJECTIVE: To determine whether routine clinical examination is sufficient for the diagnosis and establishing the location of deeply infiltrating endometriosis (DIE). DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. Patients. One hundred sixty women with histologically proved deeply infiltrating endometriosis. MEASUREMENTS AND MAIN RESULTS: Speculum examination allowed endometriotic lesions to be viewed in only 14.4% (23) of patients, and a classic, painful, spheric nodule was palpated in only 43.1% (69). Results of routine clinical examination varied significantly with location of DIE. Whereas a nodule was found in 80.0% (24) of patients with vaginal endometriosis, this rate dropped to only 35.3% (6) and 33.3% (34) in those with DIE of the digestive tract and uterosacral ligaments, respectively (p <0.0001). CONCLUSION: High locations of DIE lesions at the level of uterosacral ligaments, bottom of the pouch of Douglas, and upper one-third of the posterior vaginal wall explain why results of routine clinical examination are so poor. The term -‘deep endometriosis infiltrating the rectovaginal septum-’ is generally incorrect in the true anatomic sense.

[Laparoscopic treatment of genital prolapse: lateral utero-vaginal suspension with 2 meshes. Results of a series of 47 patients].

Fri, 01 Feb 2002 00:00:00 +0000

We report our experience with a new technique to treat genital prolapse: the laparoscopic lateral suspension with two meshes. This is a prospective longitudinal study of 47 women with genital prolapse. With a mean follow-up of 15.2 +/- 10 months (1-39), the anatomical result was perfect in 78.7% of the cases (37 patients). From the functional point of view, 89.3% were satisfied (42 patients). These good preliminary results need to be confirmed by other extensive studies.

Comparison of magnetic resonance imaging and transvaginal ultrasonography in diagnosing bladder endometriosis.

Fri, 01 Feb 2002 00:00:00 +0000

STUDY OBJECTIVE: To take recent progress in magnetic resonance imaging (MRI) into account to determine its accuracy compared with that of transvaginal ultrasonography (TVUS) in diagnosing bladder endometriosis. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Twelve women with histologically proved bladder endometriosis. INTERVENTION: Magnetic resonance imaging with body and endocavitary coils and TVUS. MEASUREMENTS AND MAIN RESULTS: Although TVUS was normal in four patients, MRI enabled endometriotic lesions to be detected in all patients. Magnetic resonance imaging with endocavitary coil established the existence of deep infiltration in three patients when muscularis involvement was not visible with the body coil. In seven women MRI determined how far deep posterior endometriotic lesions extended, whereas with TVUS this was impossible to see. Conclusion. MRI had advantages over TVUS in diagnosing small lesions of associated posterior deep endometriotic lesions. The endocavitary coil gave better results than the phased-array coil for diagnosing deep infiltration. These results are important in that they help guide surgical management.

[Management of endometriosis ovarian cysts].

Thu, 01 Nov 2001 00:00:00 +0000

The efficacy of medical treatment as unique treatment for endometrioma is not demonstrated. Operative laparoscopic management is the gold standard for surgical treatment. There is no indication to prescribe preoperatively medical treatment before cystectomy. Post-operative administration of low-dose cyclic oral contraceptive does not significantly affect long-term recurrence rate of endometriosis after surgical treatment. In cases of infertility, management of endometriomas is controversial. Recurrent ovarian surgery is not recommended.

Recurrence of leiomyomata after laparoscopic myomectomy.

Thu, 01 Nov 2001 00:00:00 +0000

STUDY OBJECTIVE: To assess recurrence of leiomyomata after laparoscopic myomectomy (LM) and evaluate predictive factors of recurrence. DESIGN: Observational study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: One hundred ninety-six women. INTERVENTION: Laparoscopic myomectomy with mean follow-up of 47 months. MEASUREMENTS AND RESULTS: Myoma recurrence included recurrence of initial symptomatology before LM, recurrence at clinical examination, and appearance of a myoma 2 cm or larger on ultrasound examination. Recurrence was observed in 45 patients (22.9%). The mean time before recurrence was 42 months (range 4-95 mo). Eight women (4.08%) required reoperation. The cumulative recurrence risk was 12.7% at 2 years and 16.7% at 5 years. Predictive factors for recurrence were number of myomas and nulliparity. CONCLUSION: According to our results, the cumulative rate of myoma recurrence within 5 years appears greater after LM than after laparotomy. However, this should not lead us to reject laparoscopy, which has many advantages compared with laparotomy, in particular its low morbidity.

[Complications of laparoscopy in gynecology].

Sat, 01 Sep 2001 00:00:00 +0000

In the field of surgery the development of operative laparoscopy has been one of the most important steps forward over the past fifteen years. This technique has become the surgical treatment of choice for a number of indications in gynaecology. The advantages of laparoscopy as compared with laparotomy are weil known, and assessment of the risk of complications is essential. A multicentric study was carried out in seven top French centres for laparoscopic gynaecological surgery. This series runs over a period of nine years and covers 29,966 diagnostic and operative laparoscopies. The risk of complications has been assessed according to the complexity of the laparoscopic procedure in question. The means of diagnosis and treatment of the complications have been analysed together with the importance of the surgeon’s degree of experience. The mortality rate is 3.33 per hundred thousand laparoscopies. The overall complication rate is 4.64 per thousand laparoscopies (139 cases). The rate of complications requiring laparotomy is 3.20 per thousand (96 cases). The complication rate is significantly correlated with the complexity of the laparoscopic procedure (p = 0.0001). One out of three complications (34.1%; 43 cases) occurred while setting up for laparoscopy, and one out of four complications (28.6%) were not diagnosed during the operation. As new indications for laparoscopic surgery in gynaecology have appeared, there has been a parallel and statistically significant increase in the rate of urological complications (p = 0.001). Increased experience of the surgeons has had three consequences: a statistically significant drop in the number of bowel injuries (p = 0.0003), a drop in the rate of complications requiring laparotomy for those laparoscopic surgical procedures which are weil-defined (p = 0.01) and a change in the way complications are treated, with a significant increase in the proportion of incidents treated by laparoscopy (p = 0.0001). Laparoscopic surgery is a reliable technique. The risk of complications exists whatever the indication for laparoscopy. None of the phases in the operation must be neglected. The risk of accidents being overlooked means that the methods for postoperative follow-up must be adapted, bearing in mind the shorter hospital stay. The part played by the surgeon’s experience raises the major problem of practitioner training.

Laparoscopic myomectomy fertility results.

Sat, 01 Sep 2001 00:00:00 +0000

The appearance of uterine myomas has been linked to infertility. It has been suggested that surgical management of myomas by laparoscopic myomectomy improves fertility rates in these group of patients. In this paper we initially describe specific aspects of the surgical technique of laparoscopic myomectomy including the set-up, precise technique for hysteroromy, enucleation of the myoma, suturing of the uterus, and extraction of the myoma. We detail recent findings that demonstrate improved fertility rates in women undergoing laparoscopic myomectomy. We recommend that, when criteria for selection of patients is strictly adhered to and patients present with no other associated infertility, laparoscopic myomectomy be used to increase the implantation rate.

Management of deep endometriosis.

Sat, 01 Sep 2001 00:00:00 +0000

Deep endometriosis is defined as an endometriotic lesion that penetrates the retroperitoneal space for a distance of > or =5 mm. Deep endometriosis is extremely active, occurs in phase with eutopic endometrium, evolves progressively with age, and is most often located in the pouch of Douglas, the rectovaginal septum, the uterosacral ligaments, and occasionally in the uterovesical fold. These lesions are associated with pelvic pain, the intensity of which is proportional to the depth of penetration. It is clear that choice of treatment depends on the location of the endometriotic lesion. In this paper we describe our methods for the initial diagnosis and subsequent treatment of deep endometriosis. These include consultation and clinical examination protocols, use of rectal endoscopic ultrasonography (EUS), magnetic resonance imaging (MRI), and transvaginal ultrasonography techniques in diagnosis and surgical treatment approaches.

Adhesion formation after laparoscopic resection of uterosacral ligaments in women with endometriosis.

Wed, 01 Aug 2001 00:00:00 +0000

STUDY OBJECTIVE: To analyze the risk of postoperative adhesions in women who undergo laparoscopic surgical management of deep endometriosis infiltrating the uterosacral ligaments (USL). DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Forty-six women with deep endometriosis infiltrating the USL. INTERVENTION: Laparoscopic resection of all USL with deep endometriotic lesions and excision of all other endometriotic lesions, followed by second-look laparoscopy. MEASUREMENTS AND MAIN RESULTS: At second-look laparoscopy, 15 patients (32.6%) had no adhesions at the site where the USL had been resected, 24 (52.2%) had filmy avascular adhesions, and 7 (15.2%) had dense or vascular adhesions. No patient had adhesions of the binding type. Only two factors, the revised American Fertility Association (rAFS) score at initial laparoscopy and surgical modality (unilateral resection of the right USL, unilateral resection of the left USL, bilateral resection of USL) had a statistically significant influence on the risk of postoperative adhesions occurring. After adjustment, the relation with initial rAFS stage and surgical modality remained significant in the stepwise logistic regression model. CONCLUSION: These encouraging results are particularly interesting for patients with infertility due to pelvic pain syndrome. Second-look laparoscopy should not be performed routinely after laparoscopic management of deep endometriosis infiltrating the USL. We propose that it be reserved for women with rAFS stages III and IV endometriosis, especially when lesions are located on the left side.

Laparoscopic myomectomy: predicting the risk of conversion to an open procedure.

Wed, 01 Aug 2001 00:00:00 +0000

BACKGROUND: Laparoscopic myomectomy (LM) has some advantages over laparotomy; however, it is reputed to be technically difficult, and the risk of conversion to laparotomy might be an obstacle in using this procedure. The aim of this study was to identify the pre-operative factors affecting the risk of conversion to an open procedure (either laparoscopic assisted myomectomy or laparotomy), and to develop a simple prediction model based on available pre-operative data with the use of multiple logistic regression. METHODS: A total of 426 women presenting with a subserous or intramural myoma measuring 20 mm or more underwent LM between March 1989 and October 1999. Of these patients, 378 had successful LM. Forty eight patients [11.3%, 95% confidence interval (CI) 8.3–14.3] had a conversion to an open procedure. A total of 265 women had adequate pre-operative ultrasonography (US) and were used for the analysis. RESULTS: The best prediction model included four pre-operative factors that were found to be independently related to the risk of conversion: size > or = 50 mm at US (adjusted OR = 10.3; 95% CI = 2.8–37.9), intramural type (adjusted OR = 4.3; 95% CI = 1.3–14.5), anterior location (adjusted OR = 3.4; 95% CI = 1.3-9.0) and pre-operative use of gonadotrophin-releasing hormone (GnRH) agonists (adjusted OR = 5.4; 95% CI = 2.0–14.2). The regression coefficients were then scaled and rounded to integers to provide an estimate of the risk for conversion. For a given patient with selected characteristics the predicted risk varied from 0–73%. CONCLUSIONS: This prediction model provides a useful tool that enables multiple criteria to be taken into account simultaneously to help select cases for LM. GnRH agonists should been used only in selected cases. US evaluation is essential before performing LM.

Potentiation response of cultured human uterine leiomyoma cells to various growth factors by endothelin-1: role of protein kinase C.

Tue, 01 May 2001 00:00:00 +0000

OBJECTIVE: Factors responsible for the abnormal proliferation of myometrial cells that accompanies leiomyoma formation are unknown, although steroid hormones and peptide growth factors have been implicated. We hypothesized that endothelin-1 (ET-1) is a physiological regulator of tumor growth. DESIGN: In this study, we investigated the role of ET-1 on growth of human leiomyoma cells and its synergistic effect with growth factors, as well as the signaling pathway involved in this interaction. METHODS: Leiomyoma cell proliferation was assayed by [H]thymidine incorporation and cell number. Protein kinase C (PKC) isoforms were analyzed by Western blot using specific antibodies. RESULTS: ET-1 on its own was unable to stimulate DNA synthesis but potentiated the leiomyoma cell growth effects of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), IGF-I and IGF-II. The failure of a protein tyrosine kinase (PTK) inhibitor, tyrphostin 51, to affect the potentiating effect of ET-1, supports the hypothesis of non-involvement of PTK in this process. The inhibition of PKC by calphostin C or its down-regulation by phorbol 12,13-dibutyrate (PDB) eliminated the potentiating effect of ET-1, but did not block cell proliferation induced by the growth factors alone. Five PKC isoforms (alpha, beta1, epsilon, delta and zeta) were detected in leiomyoma cells, but only phorbol ester-sensitive PKC isoforms (PKCalpha, epsilon and delta) contribute to the potentiating effect of leiomyoma cell growth by ET-1. CONCLUSIONS: We have demonstrated that ET-1 potentiates leiomyoma cell proliferation to growth factors through a PKC-dependent pathway. These findings suggest a possible involvement of ET-1 in the pathogenesis of leiomyomas.

Laparoscopically assisted vaginal management of deep endometriosis infiltrating the rectovaginal septum.

Sun, 01 Apr 2001 00:00:00 +0000

BACKGROUND: Two aims: 1) To assess the results of laparoscopically assisted vaginal management of deep endometriosis infiltrating the rectovaginal septum (RVS); 2) to pinpoint the differences between this procedure and that used for deep endometriotic lesions located on the uterosacral ligaments (USL). METHODS: Descriptive retrospective study. Twenty-nine consecutive patients operated for deep endometriosis infiltrating the RVS were included in this series. RESULTS: One patient only (3.5%) presented a major complication of the recto-vaginal fistula type. After a one step reoperation under anesthesia, the post operative history was uncomplicated and no sequelae are to be deplored. With respect to dysmenorrhea (DM), deep dyspareunia (DP) and chronic pelvic pain (CPP), there was an improvement in respectively 91.7% (22 patients), 100% (24 patients) and 92.9% (13 patients) of cases. For each of these 3 symptoms the median score according to the visual analog scale was significantly lower after the operation (for DM: 7.6+/-2.0 versus 1.7+/-2.6; for DP 7.5+/-1.9 versus 0.5+/-1.1; for CPP 5.9+/-2.8 versus 1.4+/-3.2) (p<0.0001). CONCLUSIONS: These results demonstrate that provided the surgeon is highly skilled in laparoscopy, operative laparoscopy is efficient for the treatment of patients presenting painful symptoms related to deep endometriotic infiltrating the RVS. From the technical point of view the rectum must be freed, leaving the deep endometriotic nodule attached to the posterior wall of the vagina. Resection of the whole lesion requires the posterior wall of the vagina to be resected, whereas ureterolysis is often unnecessary. So for lesions located on the RVS the vagina is opened systematically, unlike the situation when resecting deep endometriotic lesions infiltrating the USL. Deep pelvic endometriosis is not synonymous with endometriosis of the RVS. Lesions truly infiltrating the RVS represent only a small proportion of all deep endometriosis lesions.

[Fibroma: surgical myomectomy or embolization or GnRH analogs? Does myomectomy by laparoscopy have a justifiable place in the therapeutic strategy today?].

Mon, 01 Jan 2001 00:00:00 +0000

[Major vascular complications from gynecologic laparoscopy].

Fri, 01 Dec 2000 00:00:00 +0000

OBJECTIVE: To specify the circumstances of occurence, the means of diagnosis, the risk factors and the means of prevention for major vascular injuries (MVI) during gynecologic laparoscopic procedure. STUDY DESIGN: Retrospective case review study of 24 patients. RESULTS: Twenty-four patients with 31 MVI were identified. The average age of the patients was 32.8 +/- 10.6 years and the mean body index mass was 22.4 +/- 4.0 kg/m2. Three of four of the MVI occurred during the setting-up phase of laparoscopy (19 cases; 79.2%). In five cases (20.8%) MVI occurred during the laparoscopic surgical procedure. Fifteen of the MVI occurring during the set up phase were secondary to insertion of the umbilical trocar and four to insertion of the needle used to create the pneumoperitoneum. A minimum of six MVI secondary to insertion of the umbilical trocar were observed with disposable trocars. In every case diagnosis was performed during the laparoscopic procedure. Five patients (20.8%) died and three others (12.5%) presented serious complications (phlebitis (one case); ischemia (two cases) with a reoperation for one patient). CONCLUSION: MVI are rare but serious complications of gynecologic laparoscopy. Prevention relies on the surgeon’s experience and strict respect of the safety rules. In the vast majority of cases, it is necessary to convert to laparotomy immediately, calling in a vascular surgeon.

Comparison of endoscopic ultrasound and magnetic resonance imaging in severe pelvic endometriosis.

Fri, 01 Dec 2000 00:00:00 +0000

Deep pelvic endometriosis may lead to severe pain, the treatment of which may require complete surgical resection of lesions. Digestive infiltration is a difficult therapeutic problem. Preoperative diagnosis is difficult and digestive infiltration may remain unknown with incomplete resection and sometimes repeated surgery. Both magnetic resonance imaging (MRI) and endoscopic ultrasonography are able to detect rectosigmoid infiltration but their usefulness in the preoperative staging is still to be evaluated. The aim of this work was to evaluate and compare both techniques in the preoperative detection of deep pelvic endometriosis, particularly digestive infiltration. PATIENTS AND METHODS: From 1996 to 1998, 48 women with painful deep pelvic endometriosis had preoperative imaging exploration with endoscopic ultrasonography and MRI, and were operated on in order to attempt complete endometriosis resection. Patients were proposed for laparoscopic resection if endoscopic ultrasonography and/or MRI did not reveal digestive infiltration or for open resection if endoscopic ultrasonography and/or MRI were positive for digestive infiltration. RESULTS: Endoscopic ultrasonography and/or MRI led to suspicion of digestive endometriosis in 16 patients. Surgical resection was performed in 12 and digestive wall invasion was histologically demonstrated. At final follow-up, all patients had a dramatic decrease of their symptoms. The remaining 4 patients refused digestive resection and had only laparoscopic gynecologic resection. Infiltration although not histologically proven was very likely both on operative findings and clinical evolution. Digestive infiltration was preoperatively excluded in the 32 other patients. All had a laparoscopic treatment without digestive resection and pain diminished in all patients. In the 12 patients group who had digestive resection, digestive infiltration was correctly diagnosed by endoscopic ultrasonography in all cases (no false negative) whereas MRI, even with the use of endocoil antenna, led to correct diagnosis in 8 out of 12 cases. When endoscopic ultrasonography was negative for digestive infiltration, laparoscopic resection of lesions at surgery appeared complete in all cases. For the 16 patients with presumed digestive infiltration, sensitivity of endoscopic ultrasonography and MRI was 100 and 75% respectively, with a 100% specificity in both cases. MRI appeared very accurate for the detection of ovarian endometriotic locations. MRI was more sensitive but less specific than endoscopic ultrasonography for the diagnosis of isolated endometriotic recto-vaginal septum and utero-sacral ligaments lesions. CONCLUSION: Endoscopic ultrasonography was the best technique for the diagnosis of digestive endometriotic infiltration, which complicates the therapeutic strategy. MRI, however, allows more complete staging of other pelvic endometriotic lesions.

Expression of endothelin receptors in human myometrium during pregnancy and in uterine leiomyomas.

Wed, 01 Nov 2000 00:00:00 +0000

The distribution of mRNAs for endothelinA and B (ET(A) and ET(B)) receptors and their binding properties was studied in human nonpregnant and pregnant term myometrium and in uterine leiomyomas. ET(A)- and ET(B)-receptors functionally coupled to phospholipase C (PLC) coexisted in myometrial tissues, but only the functional ET(A)-receptor subtype was detected in leiomyomas. ET(A)-receptor mRNA and three other spliced variants were distributed in all tissue studied. We reported an increase in the proportion of ET(A)-receptors coupled to PLC in term pregnant myometrium when compared to nonpregnant tissue. These results suggest that upregulation of the myometrial ET(A)-receptors may account for or contribute to the control of normal development and growth of human myometrium during pregnancy. They also support a pathological role for the endothelin-1 (ET-1)/ET(A)-receptor system in leiomyoma development.

Laparoscopic myomectomy: a current view.

Wed, 01 Nov 2000 00:00:00 +0000

Since 1990 laparoscopic myomectomy (LM) has provided an alternative to laparotomy when intramural and subserous myomata are to be managed surgically. However, this technique is still the subject of debate. Based on their own experience together with data from the literature, the authors report on the situation today regarding the operative technique for LM and the risks and benefits of the technique as compared with myomectomy by laparotomy. The operative technique comprises four main phases: hysterotomy; enucleation; suture of the myomectomy site and extraction of the myoma. LM offers the possibility of a minimally invasive approach to treat medium-sized (<9 cm) subserous and intramural myomata by surgery when there are only two or three of them. When conducted by experienced surgeons, the risk of peri-operative complications is no higher using this technique. Use of the laparoscopic route could reduce the haemorrhagic risk associated with myomectomy. LM could reduce also the risk of post-operative adhesions as compared with laparotomy. Spontaneous uterine rupture seems to be rare after LM but further studies are needed before it can be said whether the strength of the hysterotomy scars after LM is equivalent to that obtained after laparotomy. The risk of recurrence seems to be higher after LM than after myomectomy performed by laparotomy.

Recurrence of leiomyomata after myomectomy.

Wed, 01 Nov 2000 00:00:00 +0000

Abdominal myomectomy (by laparotomy or by laparoscopy) enables all the myomata to be excised while maintaining reproductive function. The actual risk of recurrence after abdominal myomectomy is difficult to assess because of methodological problems. Studies using life-table analysis find a cumulative risk of clinically significant recurrence of approximately 10% at 5 years for myomectomy by laparotomy. This risk probably underestimates the true prevalence of myomata as assessed by systematic ultrasound investigation. After laparoscopic myomectomy there appears to be a greater risk of recurrence. In one third of cases, recurrence becomes the reason for a hysterectomy. The risk of recurrence increases when there is more than one myoma. The use of gonadotrophin-releasing hormone agonists preoperatively could increase the risk of recurrence. Persistence or recurrence of the myoma thus reduces the chances of conception or taking a pregnancy full term after the myomectomy. It is essential to obtain the most complete exeresis possible in order to reduce the risk of recurrence to a minimum. However, it is inevitable that small, undetectable nuclei will remain within the myometrium whatever approach is used (laparoscopy or laparotomy). It would be an advantage to know what the growth factors are and how to identify groups at high risk of recurrence so that the treatment strategies could be better adapted and appropriate prophylactic methods developed.

[Total hysterectomy: laparoscopy or vaginal route? Arguments in favor of laparoscopy].

Fri, 01 Sep 2000 00:00:00 +0000

Open laparoscopy: the way forward.

Fri, 01 Sep 2000 00:00:00 +0000

BJOG. 2000 Sep;107(9):1179; author reply 1179-80. doi: 10.1111/j.1471-0528.2000.tb11124.x. Open laparoscopy: the way forward. Pierre F, Marret H, Chapron C.

Prognostic factors of reproductive outcome after myomectomy in infertile patients.

Tue, 01 Aug 2000 00:00:00 +0000

The objective of this study was to identify the prognostic factors for conception after myomectomy carried out in cases of infertility. A total of 91 infertile patients presenting at least one subserous or intramural myoma measuring >2 cm underwent myomectomy. The characteristics of the patients, myomata and associated infertility factors were collected in a uniform and systematic way. A postal questionnaire was sent to patients. For each of the various factors studied, the specific cumulative probability of spontaneous intrauterine conception was estimated using the Kaplan-Meier method. Multiple regression analysis was then carried out using Cox’s proportional hazards model. The cumulative probability of spontaneous intrauterine conception at 2 years follow-up was 44% (95% confidence interval: 32-56%). The cumulative probability of conception was less after removal of a posterior or intramural myoma, after a sutured hysterotomy, and when accompanied by a male factor, associated tubal or ovulation pathology. The cumulative probability of conception was greater after ablation of myomata responsible for menometrorrhagia. The size, deforming effect on the cavity and age played no role in our sample. Our results indirectly suggest that post myomectomy adhesions could have an adverse effect on fertility. Myomata responsible for menometrorrhagia are also the cause of infertility. In the presence of an associated male, tubal or ovulatory factor, the results were poor and it was not possible to determine if a myomectomy should be performed in these cases in order to enhance fertility.

[The primary entry point in gynecologic laparoscopy].

Sat, 01 Jul 2000 00:00:00 +0000

Rectosigmoid endometriosis: endoscopic ultrasound features and clinical implications.

Sat, 01 Jul 2000 00:00:00 +0000

BACKGROUND AND STUDY AIMS: The main area of the gastrointestinal tract affected by deep pelvic endometriosis is the rectosigmoid colon in 3-37% of cases. Due to the risk of infiltration and the clinical symptoms of endometriosis, with pain and infertility, the condition may require surgical resection. Preoperative imaging diagnosis of rectosigmoid involvement is therefore important. Rectal endoscopic ultrasonography (EUS), which is already used for the staging of anorectal carcinoma and submucosal lesions, may be a promising technique for this indication. The present study was conducted in order to describe the endosonographic appearance of rectosigmoid endometriosis, and to define the potential relevance of the technique to the choice of resection method. PATIENTS AND METHODS: Between 1993 and 1997, 46 women (mean age 31) with deep pelvic endometriosis underwent imaging investigations and surgical resection. The clinical and imaging findings, and the surgical and histological features identified–mainly with regard to infiltration of the rectal wall–were compared retrospectively. The impact of the EUS findings on the decision on whether or not to carry out resection, either by laparoscopy or open abdominal surgery, was also examined. RESULTS: When there was deep pelvic endometriosis with suspected rectal wall infiltration, EUS showed normal anatomy in nine patients, endometriotic lesions without rectal wall infiltration in 12, and typical rectal infiltration in 25. The lesions were confirmed by the surgical findings during therapeutic laparoscopy (n = 22) and laparotomy (n = 25), as well as by clinical follow-up. Rectal wall infiltration, demonstrated in all cases using EUS, had initially been suspected on the basis of clinical examinations, rectoscopy, barium enema, computed tomography, and magnetic resonance imaging in 62%, 50%, 33%, 67% and 66% of cases, respectively. CONCLUSIONS: EUS is a simple and noninvasive technique capable of correctly diagnosing rectal wall infiltration in deep pelvic endometriosis. It may be helpful in determining the choice between laparoscopy and laparotomy when complete resection is indicated.

The detection of astrovirus in sludge biosolids using an integrated cell culture nested PCR technique.

Sat, 01 Jul 2000 00:00:00 +0000

The work presented here demonstrates the utility of the integrated cell culture-reverse transcriptase-polymerase chain reaction (ICC-RT-PCR) coupled with nested PCR to detect human astroviruses and enteroviruses in sludge biosolids. Viruses were concentrated by beef extract elution and organic flocculation prior to analysis by a plaque assay and ICC-RT-PCR. Astroviruses were detected in all but one sample and all of the samples were positive for enteroviruses. We have demonstrated the prevalence and frequency ofastrovirus in sludge and validated the ICC-RT-PCR/nested PCR technique as a useful tool to detect viruses in sludge.

[Management of fibroma. Recommendations for clinical practice].

Thu, 01 Jun 2000 00:00:00 +0000

[Treatment of ectopic pregnancy in 2000].

Thu, 01 Jun 2000 00:00:00 +0000

Operative laparoscopy is currently the best treatment for pregnancy (EP). As with laparotomy, laparoscopic treatment of EP can be either conservative (salpingotomy or radical (salpingectomy). After conservative laparoscopic treatment, failures are diagnosed by monitoring the drop in beta-hCG levels. Fertility results after laparoscopic treatment of EP are comparable with those observed after similar treatment by laparotomy. Better knowledge o the risk factors of EP, development of hCG assays using serum progesterone and high resolution sonography using vaginal probes allow early diagnosis of EP and a nonsurgical approach in more than 30% of cases. When inclusion criteria are strict, methotrexate administered by local injection or systemically (1mg/kg) in a single dose or in combination with mifepristone gives a 90 to 95% success rate. Whatever treatment protocol is used, fertility prognosis after EP is not correlated to the features of EP but depends mainly on patient age and past history.

Detection of astroviruses, enteroviruses, and adenovirus types 40 and 41 in surface waters collected and evaluated by the information collection rule and an integrated cell culture-nested PCR procedure.

Thu, 01 Jun 2000 00:00:00 +0000

We evaluated the use of an integrated cell culture-reverse transcription-PCR (ICC-RT-PCR) procedure coupled with nested PCR to detect human astroviruses, enteroviruses, and adenovirus types 40 and 41 in surface water samples that were collected and evaluated by using the Information Collection Rule (ICR) method. The results obtained with the ICC-RT-PCR-nested PCR method were compared to the results obtained with the total culturable virus assay-most-probable-number (TCVA-MPN) method, the method recommended by the U.S. Environmental Protection Agency for monitoring viruses in surface and finished waters. Twenty-nine ICR surface water samples were analyzed. Viruses were concentrated by using filter adsorption-beef extract elution and organic flocculation techniques, and then the preparations were evaluated for viruses by visualizing cytopathic effects in the Buffalo green monkey kidney (BGMK) cell line. In the ICC-RT-PCR-nested PCR technique we used Caco-2 cells to propagate astroviruses and enteroviruses (ICC step), and we used BGMK cells to propagate adenovirus types 40 and 41, as well as enteroviruses. Fifteen of the 29 samples (51.7%) were positive for astrovirus as determined by the ICC-RT-PCR-nested PCR method, and eight of these samples (27.5%) contained infectious astrovirus. Seventeen of the 29 samples (58.6%) were positive for enteroviruses when the BGMK cell line was used, and six (27.6%) of these samples were determined to be infectious. Fourteen of the 29 samples (48.3%) were positive for adenovirus types 40 and 41, and 11 (37.9%) of these samples were determined to be infectious. Twenty-seven of the 29 samples (93.1%) were positive for a virus, and 19 (68.9%) of the samples were positive for an infectious virus. Only 5 of the 29 samples (17.2%) were positive as determined by the TCVA-MPN method. The ICC-RT-PCR-nested PCR method provided increased sensitivity compared to the TCVA-MPN method.

Pregnancy outcome and deliveries following laparoscopic myomectomy.

Sat, 01 Apr 2000 00:00:00 +0000

Uterine rupture after myomectomy by laparotomy is not a common occurrence. Some case reports of uterine rupture after laparoscopic myomectomy (LM) raise the question of the quality of the uterine scar produced when this technique is performed. In order to assess the outcome of pregnancies and deliveries after LM and to assess the risk of uterine rupture, we performed an observational study. Questionnaires were mailed to all women who had had LM for at least one intramural or subserosal myoma of more than 20 mm diameter and who were aged <45 years. Ninety-eight patients became pregnant at least once after LM, giving a total of 145 pregnancies. Among the 100 patients who had delivery, there were three cases of spontaneous uterine rupture. Because only one of these uterine ruptures occurred on the LM scar, the risk of uterine rupture was 1.0% (95% CI 0.0-5. 5%). Seventy-two patients (72.0%) had trials of labour. Of these, 58 (80.6%) were delivered vaginally. There was no uterine rupture during the trials of labour. Spontaneous uterine rupture seems to be rare after LM. This risk should not deter the use of LM if needed. When performing LM, particular care must be given to the uterine closure.

Total hysterectomy for benign pathologies: direct costs comparison between laparoscopic and abdominal hysterectomy.

Sat, 01 Apr 2000 00:00:00 +0000

OBJECTIVES: The aim of this study is a direct costs comparison between laparoscopic and abdominal total hysterectomy when theses procedures are indicated for benign pathologies. STUDY DESIGN: To this end we compared the direct costs of total laparoscopic hysterectomy (TLH) calculated from a series of 105 patients with that obtained for a comparable series of 30 patients who underwent hysterectomy by laparotomy. RESULTS: The direct costs of total hysterectomy for a benign pathology by laparoscopic surgery and laparotomy are comparable (respectively 7693 French francs (FF) and 7759 FF). Whatever the type of operation the cost for staff represents 60% of the total cost. Expenditure for staff during the operation represents 41.0% of the total cost of TLH (3154 FF/7693 FF) whereas it represents only 31.0% of the cost of the operation when carried out by laparotomy (2406 FF/7759 FF) (P<0.0001). Inversely the expenditure due to staff during the post operative phase represents 24.1% of the total cost of the operation when laparotomy is used (1875 FF/7759 FF) and only 13.4% of the cost of the operation by laparoscopic surgery (1029 FF/7693 FF) (P<0.0001). When the operation uses laparoscopic surgery the increase in expenditure during the surgical act is compensated by the statistically significant shortening in the hospital stay. Expenditure connected with the laparoscopic surgery equipment is minimal compared to the costs connected with the staff. CONCLUSION: Provided that TLH is carried out with reusable laparoscopic surgery equipment, by skilled surgeons working in suitable hospital structures making the particularly heavy investment in laparoscopic surgery equipment economically viable, TLH is an economically viable technique as an alternative to laparotomy.

[Laparoscopy and bladder endometriosis].

Wed, 01 Mar 2000 00:00:00 +0000

Partial cystectomy is in the great majority of the cases the treatment of choice for patients with bladder endometriosis. The aim is to assess the methods, indications and results of operative laparoscopy for patients presenting with bladder endometriosis. We perform a descriptive retrospective study of 13 cases. All patients presenting with bladder endometriosis infiltrating the bladder muscularis between January 1, 1993 and June 30, 1998 were included in this series. It was possible to treat bladder endometriosis in all the patients by performing a laparoscopic partial cystectomy. With an average follow-up of 29.3 +/- 24.6 months (range 4-77) the results are satisfactory. Neither peri- nor postoperative complications were observed. The patients experienced an improvement in their condition, with complete disappearance of the urinary symptoms in every case. No recurrence of the functional urological symptoms occurred. Provided the surgeons are skilled and the lesions require no ureteral reimplantation, operative laparoscopy is a valid alternative to laparotomy for partial cystectomy.

Ureteral injuries after laparoscopic hysterectomy.

Wed, 01 Mar 2000 00:00:00 +0000

Hum Reprod. 2000 Mar;15(3):733-4. doi: 10.1093/humrep/15.3.733. Ureteral injuries after laparoscopic hysterectomy. Chapron C, Dubuisson JB.

[Initial access for laparoscopic gynecologic surgery. French Society of Endoscopic Gynecology, International Society of Pelvic Surgery and the National College of French Gynecologists-Obstetricians].

Tue, 01 Feb 2000 00:00:00 +0000

Reproductive outcome after laparoscopic myomectomy in infertile women.

Sat, 01 Jan 2000 00:00:00 +0000

OBJECTIVE: To assess reproductive outcome after laparoscopic myomectomies for interstitial and/or subserosal myomas in infertile women with or without associated infertility factors. STUDY DESIGN: In this observational study, 91 women with infertility for one year and at least one interstitial and/or subserosal myoma > 20 mm were treated with laparoscopic myomectomy. All patients were mailed questions about fertility and pregnancy outcome. Cumulative pregnancy rates were calculated by the Kaplan-Meier method. The log rank test and Cox’s model were used for comparing the spontaneous pregnancy rate in patients with and without associated infertility factors. RESULTS: The mean age of the patients was 35 +/- 4 years. The mean duration of infertility was 44 +/- 33 months. Twenty-five patients (27.5%) had no associated infertility factors, and 66 (72.5%) had one or more. The mean size of the largest myomas was 45 +/- 19 mm. The mean number of myomas removed was 2.0 +/- 1.4. Eighty-six patients had laparoscopic myomectomy (94.5%), and five had laparoscopically assisted myomectomy (5.5%). There were no conversions to laparotomy. Ten patients were lost to follow-up (11.0%). Among the 91 patients treated surgically, 81 (89.0%) of them were evaluated. Forty-three (53.1%) conceived, resulting in a total of 51 pregnancies. The two-year overall cumulative conception rate was 51.2% (95% confidence interval [CI], 39.2-63.2%). The two-year spontaneous pregnancy rate was 43.9% (95% CI, 32.1-55.7%). This rate was 69.9% (95% CI, 50.3-89.5%) for patients with no associated factors and 31.5% (95% CI, 18.4-44.6%) for patients with associated factors (P < .001). This result was not affected by adjusting for age or duration of infertility. CONCLUSION: Laparoscopic myomectomy seems to be a good procedure for patients with myomas and no other infertility factors. In cases with associated infertility factors, the need for myomectomy has to be studied.

[Indications and modalities of conservative surgical treatment of interstitial and sub-serous myomas].

Mon, 01 Nov 1999 00:00:00 +0000

Laparoscopic management of bladder endometriosis.

Mon, 01 Nov 1999 00:00:00 +0000

BACKGROUND: To assess the methods, indications and results of operative laparoscopy for patients presenting with bladder endometriosis. METHODS: Descriptive retrospective study. All the patients presenting with bladder endometriosis infiltrating the bladder muscularis between January 1, 1993 and June 30, 1998 were included in this series. RESULTS: It was possible to treat bladder endometriosis in all the patients by performing a laparoscopic partial cystectomy. With an average follow-up of 31.6 months (range 6-61) the results are satisfactory. Neither per- nor postoperative complications were observed. The patients experienced an improvement in their condition, with complete disappearance of the urinary symptoms in every case. No recurrence of the functional urological symptoms occurred. CONCLUSIONS: Provided the surgeons are skilled and the lesions require no ureteral reimplantation, operative laparoscopy is a valid alternative to laparotomy for partial cystectomy.

[Ovarian puncture: supposed functional cysts].

Fri, 01 Oct 1999 00:00:00 +0000

Hysterectomy techniques used for benign pathologies: results of a French multicentre study.

Fri, 01 Oct 1999 00:00:00 +0000

The objective of this study was to assess the techniques by which hysterectomies are carried out and to determine the rate of total laparoscopic hysterectomy (TLH). A transversal multicentre study was conducted in 23 gynaecology and obstetrics departments of French University Hospital Centres. The study population comprised only those patients for whom hysterectomy was indicated for benign disease without genital prolapse or urinary stress incontinence. Whereas the rates of performance of hysterectomy by laparotomy and by the vaginal route are comparable [respectively 40.0% (94 patients) and 46.8% (110 patients)], the rate of performance of TLH is only 13.2% (31 patients). All 23 centres (100%) carried out hysterectomy by laparotomy and 21 centres (91.3%) carried out vaginal hysterectomy; however, only nine centres (39.1%) carried out TLH. Only seven centres (30.4%) performed all three types of operation. Of the eight centres whose rate of vaginal hysterectomy was >60%, six (75%) did not carry out TLH. The study suggests that the usage of the TLH technique appears to be limited. The extent of surgical training is a major factor in the choice of technique for hysterectomy.

[Endothelin receptors in benign human tumours of uterine muscle].

Wed, 01 Sep 1999 00:00:00 +0000

The endothelins (ET1, ET2, ET3) are a family of peptides that exert vasoactive and mitogenic effects. ETs bind to at least two subtypes of receptors: the ETA subtype is ET1 selective whereas the ETB subtype binds ET1, ET2 and ET3. By RT-PCR, we detected ETA receptor mRNA and ETB receptor mRNA in leiomyoma and in homologous myometrium distal from the tumor. Despite the presence of four spliced variants of ETA receptors, we identified a single class of ETA-binding sites. The level of ETB receptor mRNA was found to be higher in myometrium versus leiomyomas. Using complementary pharmacologic approach, we demonstrated the predominance of ETA receptors in normal myometrium (75% of total receptors). Both ETA and ETB transcripts coexist in leiomyomas, but we have reported only ETA binding sites. Because of growth properties of ET1, we suggest a role for this peptide in the tumoral development of human uterine smooth muscle.

[Profound endometriosis and infertility. Fertility results after laparoscopic treatment of profound endometriosis infiltrating the uterosacral ligaments].

Wed, 01 Sep 1999 00:00:00 +0000

Estrogen receptors (ERalpha/ERbeta) in normal and pathological growth of the human myometrium: pregnancy and leiomyoma.

Tue, 01 Jun 1999 00:00:00 +0000

The distributions of the mRNAs for estrogen receptors (ERalpha and ERbeta) and their binding properties in myometria of pregnant and nonpregnant women and in leiomyoma were studied. RT-PCR analysis indicated that the term pregnancy myometria had little ERalpha mRNA, whereas the amounts of ERbeta mRNAs in pregnant or nonpregnant myometria appeared to be similar. Both ERalpha and ERbeta mRNA were greater in certain leiomyoma than in normal nonpregnant myometria. The binding kinetics revealed that two specific binding sites (with high or low affinity) for 17beta-estradiol were present in the nonpregnant myometrium. Only the low-affinity binding sites were detectable in late-pregnancy myometria and in leiomyoma, and their capacities were increased two- to threefold (P < 0.001) in leiomyoma. The pregnancy- and leiomyoma-related changes in myometrial ER status, especially the low concentration of ERalpha mRNA and the lack of high-affinity ER in pregnant women, plus the increased ERalpha and ERbeta mRNAs and the increased low-affinity ER in some leiomyoma, suggest that the redistribution of ER subtypes is associated with the pathological and/or normal growth of the myometrium.

Magnetic resonance imaging characteristics of deep endometriosis.

Thu, 01 Apr 1999 00:00:00 +0000

The aim of this study was to describe magnetic resonance (MR) imaging findings in histopathologically proven deep endometriosis infiltrating the uterosacral ligaments, the pouch of Douglas, the rectum or the bladder. Twenty patients presenting with a clinical suspicion of deep endometriosis underwent preoperative MR imaging. Sagittal and axial fast T2- and axial T1-weighted spin echo MR sequences were performed. Four patients had post-contrast images. MR results, including morphology and signal intensity of each lesion, were compared to intraoperative gross appearance and histopathology. Histopathology diagnosed 24 lesions of deep endometriosis in the uterosacral ligaments (n = 12), the pouch of Douglas (n = 2), the rectum (n = 3), the bladder (n = 7). Uterosacral ligaments with deep endometriosis were statistically different from normal uterosacral ligaments for proximal nodularity (P = 0.001). There was no difference in signal intensity between normal and abnormal uterosacral ligaments. Contrast-enhanced SE images in four patients with detrusor invasion showed an interruption of the hypointense detrusor by the enhancing bladder endometriosis. Rectal endometriosis was missed in two of three patients and showed non-specific rectal wall thickening in one patient. It is concluded that MR imaging can diagnose deep endometriosis of uterosacral ligaments, the bladder and the pouch of Douglas, but lacks sensitivity in detecting rectal endometriosis without rectal distension.

[Surgical treatment of endometriosis].

Mon, 01 Feb 1999 00:00:00 +0000

The treatment of first intention for endometriosis must be surgery. In cases of infertility the surgical treatment of choice is laparoscopic surgery, maybe in conjunction with the medical treatment and possibly followed-up by a second-look. When there is pelvic pain, the treatment relies on complete exeresis of the endometriotic lesions. In this context, laparoscopic surgery is as efficient as laparotomy for dealing with ovarian endometriomas, deep endometriosis infiltrating the uterosacral ligaments, the rectovaginal septum and the bladder. However, in the majority of cases bowel endometriosis is still an indication to operate by laparotomy.

Fertility after laparoscopic management of deep endometriosis infiltrating the uterosacral ligaments.

Mon, 01 Feb 1999 00:00:00 +0000

The aim of this study was to evaluate fertility outcome after laparoscopic management of deep endometriosis infiltrating the uterosacral ligaments (USL). From January 1993 to December 1996, 30 patients who presented with no other infertility factors were treated using laparoscopic surgery. The overall rate of intrauterine pregnancy (IUP) was 50.0% (15 patients). Only one of these 15 pregnancies was obtained using in-vitro fertilization techniques (IVF). The cumulative IUP rate for the 14 pregnancies which occurred spontaneously was 48.5% at 12 months (95% confidence interval 28.3-68.7). The rate of spontaneous pregnancies was not significantly correlated with the revised American Fertility Society (rAFS) classification. The rate of IUP was 47.0% (eight cases) for patients with stage I or II endometriosis and 46.1% (six cases) for the patients presenting stage III or IV endometriosis (not significant). These encouraging preliminary results show that in a context of infertility it is reasonable to associate classic treatment for endometriosis (e.g. lysis, i.p. cystectomy, biopolar coagulation of superficial peritoneal endometriotic lesions) with resection of deep endometriotic lesions infiltrating the USL. Apart from the benefit with respect to the pain symptoms from which these patients suffer, it is possible to use laparoscopic surgery with substantial retroperitoneal dissection and enable half of the patients to become pregnant. These results also raise the question of the influence of deep endometriotic lesions on infertility.

Gastrointestinal injuries during gynaecological laparoscopy.

Mon, 01 Feb 1999 00:00:00 +0000

A retrospective case review study was carried out on gastrointestinal injuries which occur during gynaecological laparoscopy. Fifty-six patients with 62 gastrointestinal injuries were identified. One-third of the complications (32.2%) occurred during the installation phase for laparoscopy. Four of the six complications attributed to electrosurgery were secondary to the use of monopolar coagulation. Diagnosis of these gastrointestinal injuries was made during surgery in only 20 patients (35.7%). The mean time before diagnosis was 4.0 +/- 5.4 (range 0-23) days. Treatment of these complications was performed by laparoscopic surgery in 16.1% of cases. Prevention relies on the surgeon’s experience, strict observance of the safety rules, perfect familiarity with the physical properties of the instruments used, systematic use of bowel preparation for patients presenting a risk of bowel complications, systematic supervision of the route taken by the trocars, meticulous inspection on completion of surgery of all areas where bowel adhesiolysis has been used and, in case of any doubt, tests for leakage involving the rectosigmoid. For patients with a risk of bowel complications, the creation of a pneumoperitoneum and performing a mini laparoscopy in the left hypochondrium can be the judicious option.

Operative management of deep endometriosis infiltrating the uterosacral ligaments.

Mon, 01 Feb 1999 00:00:00 +0000

STUDY OBJECTIVE: To describe and assess the efficacy of laparoscopic surgical treatment for patients with pain and deep endometriosis located on the uterosacral ligaments. DESIGN: Retrospective analysis (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: One hundred ten consecutive women with deep endometriosis infiltrating uterosacral ligaments. INTERVENTION: Operative laparoscopic management of endometriosis. MEASUREMENTS AND MAIN RESULTS: Improvement was reported in 82.3% (70/85) of patients with severe dysmenorrhea and was considered satisfactory in 82.8% (58/70). Improvement also occurred in 88.2% (75/85) of women with deep dyspareunia, and was considered satisfactory in 88.0% (66/75). CONCLUSION: Provided the surgeon is highly skilled in laparoscopy, operative laparoscopy is efficient for the treatment of painful symptoms related to deep endometriosis infiltrating uterosacral ligaments. (J Am Assoc Gynecol Laparosc 6(1):31-37, 1999)

Predicting risk of complications with gynecologic laparoscopic surgery.

Mon, 01 Feb 1999 00:00:00 +0000

Obstet Gynecol. 1999 Feb;93(2):318-9. Predicting risk of complications with gynecologic laparoscopic surgery. Chapron C, Dubuisson JB.

[Myomectomy by laparoscopy and infertility: status of the controversy].

Thu, 01 Oct 1998 00:00:00 +0000

The ratio between benefit and risk of laparoscopic myomectomy in infertile patients is controversial. Based on literature data and their personal experience, the authors discuss the place of laparoscopic myomectomy in the care of infertile patients.

Results and role of rectal endoscopic ultrasonography for patients with deep pelvic endometriosis.

Sat, 01 Aug 1998 00:00:00 +0000

The objective of this work was to assess the advantages and the role of rectal endoscopic ultrasonography (EUS) when establishing evidence of infiltration of the rectal wall in patients with proven deep pelvic endometriosis. To this end we performed a retrospective study between July 1993 and December 1996 of a continuous series of 38 patients who presented with deep pelvic endometriosis which was confirmed histologically. The EUS results were considered normal in nine cases (23.7%). In 12 cases (31.6%) EUS revealed an image compatible with infiltration of the uterosacral ligaments and/or the rectovaginal septum without any associated bowel infiltration. In 17 cases (44.7%) EUS revealed an image compatible with deep infiltration of the intestinal wall. Sixteen of these 17 patients underwent laparotomy with bowel resection. The histological results confirmed in each of these 16 patients (100%) that there was deep infiltration of the intestinal wall by endometriotic lesions. The seventeenth patient refused such major surgery by laparotomy, and underwent partial laparoscopy due to the risk of bowel injury. For the 21 patients with no EUS evidence of rectal infiltration complete laparoscopic surgical exeresis was achieved in every case (100%) without broaching the intestinal wall. These preliminary results enable us to state that EUS, which is a simple and non-invasive technique, provides a reliable indication as to the presence of deep bowel infiltration in patients with retroperitoneal endometriotic lesions. EUS used pre-operatively enables patients to be selected for treatment via laparotomy or by laparoscopic surgery.

Second look after laparoscopic myomectomy.

Sat, 01 Aug 1998 00:00:00 +0000

The goal of this study was to assess the risk of adhesions after laparoscopic myomectomy. To this end our enquiry was based on observations with a prospective collection of data. Between October 26, 1990 and October 1, 1996, 45 patients underwent a second look after laparoscopic myomectomy. Seventy-two myomectomy sites were checked. The overall rate of postoperative adhesion was 35.6% per patient. The rate of adhesions per myomectomy site was 16.7%. The factors which influenced the occurrence of an adhesion on the myomectomy site were posterior location of the myoma and the existence of sutures. The rate of adhesions on the adnexa after laparoscopic myomectomy was 24.4%. The factors which influenced the occurrence of adnexal adhesions were another surgical procedure carried out at the same time, the existence of adhesions prior to the operation and posterior location of the myoma. The rate of adhesions after laparoscopic myomectomy is low and the adhesions rarely involved the adnexa. We recommend that a second-look laparoscopy be carried out systematically after laparoscopic myomectomy in patients desiring pregnancy.

Single suture laparoscopic tubal re-anastomosis.

Sat, 01 Aug 1998 00:00:00 +0000

The goal of this article is to report our experience and review recent articles obtained for laparoscopic tubal sterilization reversal. The technique we describe is ‘single suture laparoscopic tubal re-anastomosis’. This technique is simple and atraumatic and requires only one stitch in the tube. After preparing the tube stumps and bringing the edges of the mesosalpinx together, laparoscopic anastomosis is achieved by one stitch placed at ‘12 o’clock’ on the antimesial edge of the tube. Between May 1994 and June 1997 we operated on 32 patients using this technique and carried out 48 tubal sterilization reversals. For the patients who underwent postoperative hysterosalpingography during the first or second month after the operation, the rate of patency was 87.5% (42/48). The overall intrauterine pregnancy rate was 53.1% (17 out of 32 patients). The overall delivery rate was 40.6% (13 out of 32 patients). The intrauterine pregnancy rate for the 17 patients who were aged 38 years or under was 58.8% (10 out of 17 patients). Laparoscopic tubal sterilization reversal is feasible with a simplified technique. Review of the publications concerning laparoscopic microsurgical tubal anastomosis confirms satisfactory fertility results. The surgeon should be experienced in microsurgical tubal anastomosis by laparotomy as well as operative laparoscopic procedures.

[Uterus and diethylstilbestrol: which examinations, which antecedents for an active management? Which treatments?].

Wed, 01 Jul 1998 00:00:00 +0000

Diethylstilbestrol (DES) was widely prescribed to pregnant women from 1946 to 1977. This resulted in multiple abnormalities of the genital tract. Many studies show an increased incidence of infertility, ectopic pregnancy, spontaneous abortions and premature delivery. For women with certain abnormalities such as a construction of the upper uterine cavity, with or without a T configuration of the uterus, hysteroscopic metroplasty is feasible with good anatomic and functional results.

A French survey on gynaecological laparoscopy.

Wed, 01 Jul 1998 00:00:00 +0000

[Extra-uterine pregnancy. Etiology, diagnosis, course of disease, treatment].

Fri, 01 May 1998 00:00:00 +0000

Rev Prat. 1998 May 1;48(9):1037-9. [Extra-uterine pregnancy. Etiology, diagnosis, course of disease, treatment]. Dubuisson JB, Chapron C.

Surgical complications of diagnostic and operative gynaecological laparoscopy: a series of 29,966 cases.

Wed, 01 Apr 1998 00:00:00 +0000

A multicentre study was carried out in seven top French centres for laparoscopic gynaecological surgery. This series covers a period of 9 years, in which 29,966 diagnostic and operative laparoscopic operations were performed. The risk of complications has been assessed according to the complexity of the laparoscopic procedure in question. The means of diagnosis and treatment of the complications have been analysed, together with the importance of the surgeon’s degree of experience. The mortality rate was 3.33 per 100,000 laparoscopies. The overall complication rate was 4.64 per 1000 laparoscopies (n = 139). The rate of complications requiring laparotomy was 3.20 per 1000 (n = 96). The complication rate was significantly correlated with the complexity of the laparoscopic procedure (P = 0.0001). One in three complications (34.1%; n = 43) occurred while setting up for laparoscopy, and one in four (28.6%) were not diagnosed during the operation. As new indications for laparoscopic surgery in gynaecology have appeared, there has been a parallel and statistically significant increase in the rate of urological complications (P = 0.001). Increased experience by the surgeons has had three consequences: a statistically significant drop in the number of bowel injuries (P = 0.0003), a drop in the rate of complications requiring laparotomy for those laparoscopic surgical procedures that are well defined (P = 0.01), and a change in the way complications are treated, with a significant increase in the proportion of incidents treated by laparoscopy (P = 0.0001).

Laparoscopic management of organic ovarian cysts: is there a place for frozen section diagnosis?

Sun, 01 Feb 1998 00:00:00 +0000

Only benign ovarian cysts can be treated by laparoscopic surgery. Although clinical examination and the results of pre-operative work-up do make a real contribution in indicating the benign or malignant nature of cysts, only histology can provide the absolute diagnosis. In this context, the goal of this study was to establish whether there is any advantage in performing frozen section during laparoscopic surgical management of organic ovarian cysts. Between January 1989 and March 1996, 228 patients underwent an adnexectomy for an ovarian mass. After the pre-operative work-up and the diagnostic phase of laparoscopy, 26 patients (11.4%) presented with suspected signs of malignancy restricted purely to the ovary. These 26 patients underwent a laparoscopic adnexectomy with extraction of the excised tissues using an endoscopic bag, followed by frozen section. For all these patients the results of the frozen section concluded that the lesion was benign. In every case the definitive histological results confirmed the frozen section findings. This strategy enabled us to avoid laparotomy, especially for the nine post-menopausal patients whose adnexal masses appeared to be complex by ultrasound. These encouraging preliminary results need to be confirmed by a larger series of patients, so as to specify the place of frozen section in the laparoscopic surgical management of organic ovarian cysts.

[Total hysterectomy for benign pathologies. Laparoscopic surgery does not seem to increase the risk of complications].

Thu, 01 Jan 1998 00:00:00 +0000

OBJECTIVE: To assess the risk of complications of total laparoscopic hysterectomy (TLH). SETTING: University Hospital, Surgical Gynecological team. DESIGN: Retrospective study of 313 patients. For all the patients a total laparoscopic hysterectomy was performed. Every part of the operation was carried out via laparoscopy, from the adnexal phase (conservative or radical) to the colpotomy. All hemostasis was carried out by electrosurgery (bipolar coagulation). All the instruments are reusable. RESULTS: The rate of conversion to laparotomy was 6.7% (21 patients). For the patients who underwent a TLH (292 cases; 92.3%) the overall complication rate was 9.95% (29 patients). The rate of patients presented a complication which required a further operation was 1.4% (4 patients). The rate of patients presented a complication which required a re-hospitalization was 2.0% (6 patients). The rate of major urinary injury was 2.5% (6 cases): bladder injury (4 patients; 1.35%); vesico-vaginal fistula (1 case; 0.35%); ureteral complication (1 case; 0.35%). The rate of postoperative febrile morbidity was 5.8% (17 patients). CONCLUSIONS: These encouraging results mean that, provided the surgeons are experienced in laparoscopic surgery, total laparoscopic hysterectomy technique would appear not to have a higher rate of complications than hysterectomy via laparotomy or the vaginal route.

Complications of laparoscopy: a prospective multicentre observational study.

Mon, 01 Dec 1997 00:00:00 +0000

Br J Obstet Gynaecol. 1997 Dec;104(12):1419-20. doi: 10.1111/j.1471-0528.1997.tb11017.x. Complications of laparoscopy: a prospective multicentre observational study. Chapron C, Dubuisson JB, Querleu D, Pierre F.

Appropriate treatment for tubal pregnancy?

Sat, 01 Nov 1997 00:00:00 +0000

Fertil Steril. 1997 Nov;68(5):945-7. doi: 10.1016/s0015-0282(97)90362-9. Appropriate treatment for tubal pregnancy? Chapron C, Dubuisson JB.

Major vascular injuries during gynecologic laparoscopy.

Sat, 01 Nov 1997 00:00:00 +0000

BACKGROUND: This study was undertaken to report our experience with major vascular injuries in gynecologic laparoscopy in order to specify the circumstances under which they occurred, the means of diagnosis, the risk factors, and the means for prevention. STUDY DESIGN: Retrospective case review study. RESULTS: Seventeen patients with 21 major vascular injuries were identified. The average age of the patients was 33.8 +/- 11.6 years, and the mean body index mass was 21.6 +/- 3.08 kg/m2. Three of four of the accidents occurred during the set-up phase of laparoscopy (13 cases; 76.5%), and in 4 cases (23.5%) the accident occurred during the laparoscopic surgery procedure. Eleven (84.6%) of the complications occurring during the set-up phase were secondary to insertion of the umbilical trocar and 2 (15.4%) to insertion of the needle used to create the pneumoperitoneum (P-needle). Half (6 cases; 54.5%) of the major vascular injuries secondary to insertion of the umbilical trocar were observed when reusable trocars were used. In every case, the diagnosis was made during the operation. Two patients died, and two others presented a serious complication (phlebitis; acute ischemia requiring reoperation). CONCLUSIONS: Major vascular injuries are rare but serious complications of laparoscopic surgery. Prevention of these accidents relies on the surgeon’s experience and scrupulous respect of the safety rules. In the vast majority of cases, it is necessary to convert to laparotomy immediately, calling in a vascular surgeon.

Laparoscopic myomectomy. Operative technique and results.

Fri, 26 Sep 1997 00:00:00 +0000

Total laparoscopic hysterectomy. Indications, results, and complications.

Fri, 26 Sep 1997 00:00:00 +0000

[Is there still a role for laparotomy in tubal infertility surgery?].

Mon, 01 Sep 1997 00:00:00 +0000

Laparoscopic myomectomy and myolysis.

Fri, 01 Aug 1997 00:00:00 +0000

The indications for operative laparoscopy have expanded greatly over the past decade as its many advantages over laparotomy have become recognized. Laparoscopic myomectomy as a technique is now clearly described. A monopolar hook is used for the uterine incision. After atraumatic enucleation of the myoma, the myometrium and serosa are usually sutured, especially if the incision is deep or more than 2 cm long. Myomas can be removed by posterior colpotomy. However, the development of an electrical cutting device permits easier and quicker removal of the myoma through the suprapubic puncture site. Only complicated myomas or those which give rise to persistent symptoms despite properly prescribed medical treatment, together with those which grow rapidly, require surgery. These satisfactory preliminary results must not mask the fact that laparoscopic myomectomy is lengthy and difficult, reserved for experienced surgeons with a thorough familiarity with endoscopic sutures. Under these conditions, laparoscopic myomectomy is possible, even for large myomas (5 cm and over) located purely intramurally. However, there are limits, and it is preferable to schedule myomas measuring over 8 cm and multiple myomectomy (over two) for laparotomy. Although the preliminary results are encouraging, the risk of adhesiogenesis on the uterine scar, the quality of the uterine suture and the fertility results need to be assessed in the near future.

Laparoscopy for adnexal torsion in pregnant women.

Tue, 01 Jul 1997 00:00:00 +0000

OBJECTIVE: To report on six cases of adnexal torsion in pregnant women treated by operative laparoscopy. STUDY DESIGN: A retrospective study. Between January 1989 and March 1996, 26 patients with adnexal torsion were treated by operative laparoscopy. Of these patients, six were pregnant (23%). The types of operative procedure and outcome were studied. RESULTS: Adnexal torsion occurred between 6 and 13 weeks of amenorrhea. Two cases involved hyperstimulation, 3 cases a functional cyst and 1 case a dermoid cyst. In 4 cases laparoscopic treatment consisted of untwisting followed by puncture of the ovarian cyst; in 1 case it involved intraperitoneal cystectomy and in another simple untwisting of the adnexa. The immediate postoperative history was uncomplicated. In one patient with ovarian hyperstimulation, torsion recurred three weeks after the initial operation. No miscarriages occurred. CONCLUSION: In the hands of skilled surgeons, laparoscopy is well suited to the diagnosis and treatment of adnexal torsion occurring during the first trimester of pregnancy. Beyond 16 weeks or when there is any suspicion of torsion on a suspected tumor, it is preferable to use laparotomy.

[Laparoscopic surgery of ovarian tumors during pregnancy].

Thu, 01 May 1997 00:00:00 +0000

During the first trimester of the pregnancy, the management of benign ovarian cyst can be performed by laparoscopy. When ovarian tumor is bulky, suspicious and after 16 to 20 weeks this treatment must be realised by laparotomy.

Salpingo-oophorectomy for adnexal masses. Place and results for operative laparoscopy.

Thu, 01 May 1997 00:00:00 +0000

OBJECTIVES: The aim of the study is to specify the place, modalities and results of operative laparoscopy when adnexectomy is indicated in a patient presenting with an adnexal mass. STUDY DESIGN: A retrospective analysis of the 186 patients who underwent adnexectomy for an adnexal mass between January 1, 1989 and December 31, 1994. RESULTS: The operation took place via laparotomy in 34.9% of cases (65 patients) and by laparoscopic surgery in 65.1% of cases (121 patients). All the patients presenting a malignant ovarian lesion (15 cases) were operated by laparotomy. For these patients the laparotomy was decided from the outset in 7 cases and there was a conversion to laparotomy decided during the diagnostic phase of laparoscopy in 8 cases. The preoperative workup (clinical examination, study of past history, trans vaginal ultrasonography, doppler, tumoral markers etc.) together with the diagnostic phase of laparoscopy provide 100% sensitivity, a positive predictive value of 50% and a negative predictive value of 100% for diagnosis of malignancy. CONCLUSION: These results demonstrate that provided a strict selection system is used, it is possible to carry out adnexectomy using laparoscopic surgery in 70.8% of cases (121/171) for patients with benign adnexal mass.

The role of laparoscopy in the diagnosis and management of heterotopic pregnancies.

Thu, 01 May 1997 00:00:00 +0000

The object of this report is to discuss diagnosis and treatment of heterotopic pregnancies. Thirteen consecutive cases referred to our institution are reviewed. In 54% of cases the heterotopic pregnancy was asymptomatic. The ectopic pregnancy was visualized prior to surgery in 69% of the cases. The treatment was surgical in every case and performed laparoscopically in 77% of cases. Ten patients underwent salpingectomy and three salpingostomy. In all, 60% of intrauterine pregnancies that were viable at the time of diagnosis of the heterotopic pregnancy had a favourable outcome. Diagnosis of heterotopic pregnancy is difficult. Laparoscopy allows both diagnosis and treatment, and the outcome of the intrauterine pregnancy is comparable to that obtained with laparotomy.

ESHRE guidelines for training, accreditation and monitoring in gynaecological endoscopy. European Society for Human Reproduction and Embryology. Committee of Special Interest Group on Reproductive Surgery.

Tue, 01 Apr 1997 00:00:00 +0000

Hysterectomy with adnexectomy. Can operative laparoscopy offer advantages?

Tue, 01 Apr 1997 00:00:00 +0000

OBJECTIVE: To investigate whether laparoscopic surgery has the advantage of reducing the rate of laparotomies when a patient with no genital prolapse needs a total hysterectomy associated with unilateral and bilateral adnexectomy. STUDY DESIGN: Retrospective study carried out between January 1993 and December 1995. All patients (96) with no prolapse, pelvic floor relaxation or stress urinary incontinence and scheduled for total hysterectomy with adnexectomy were included in the study. RESULTS: Laparotomy was required in 12.5% of cases (12 patients). For the 84 patients (87.5%) who underwent laparoscopic hysterectomy, the mean duration of the operation was 142.6 +/- 33.9 minutes, and the mean uterine weight was 209.7 +/- 129.4 g. The rate of laparotomy dropped steadily as the surgeon acquired experience. Whereas the rate of laparotomy was 30.5% (7 patients) in 1993, it was 10.8% (4 patients) in 1994 and fell to 2.8% (1 patient) in 1995. CONCLUSION: When adnexectomy needs to be performed with hysterectomy, in the majority of cases it should be carried out by laparotomy. Operative laparoscopy enables the rate of laparotomy to be reduced to < 15%. The existence of an adnexal mass not suspected to be malignant indicates operative laparoscopy.

Proximal tubal occlusion: is there an alternative to microsurgery?

Tue, 01 Apr 1997 00:00:00 +0000

Fertility outcome following microsurgical tubocornual anastomosis by laparotomy was evaluated. A total of 131 women presenting pure proximal occlusion, whether bilateral or in one tube only, were treated between January 1978 and December 1993. Subsequent fertility was studied in 120 patients, 11 being patients lost to follow-up. Cumulative intrauterine pregnancy (IUP) rate, evaluated by life-table analysis, was 68% at 24 months. The overall IUP rate, calculated from a group of 120 women with follow-up > or = 2 years, and including births and miscarriages, was 70% after 2 years. Comparisons of the cumulative IUP rates show that the fertility outcome is significantly better if the woman is aged < or = 36 years and if tubocornual anastomosis is carried out bilaterally. These results from our personal series confirm that microsurgical tubocornual anastomosis is still of prime importance in the treatment of pure proximal occlusions. Nevertheless, considerable progress in the fields of tubal catheterization, Falloposcopy and in-vitro fertilization techniques raises the question of the management of patients presenting with a proximal tubal occlusion. Here we define the indications for microsurgical tubocornual anastomosis.

Place and modalities of laparoscopy in surgical management of suspected adnexal masses.

Sun, 01 Dec 1996 00:00:00 +0000

Only benign adnexal masses are suitable for treatment by operative laparoscopy. Ovarian cancer must always be managed by midline laparotomy. In our experience the preoperative workup (clinical examination, study of past history, trans vaginal ultrasonography, doppler, tumoral markers etc.) together with the diagnostic phase of laparoscopy provide a sensitivity value of 100%, a positive predictive value of 50% and a negative predictive value of 100% for diagnosis of malignancy. Provided a strict selection, laparoscopy is reliable both for the diagnosis and the management of benign ovarian masses.

Is total laparoscopic hysterectomy a safe surgical procedure?

Fri, 01 Nov 1996 00:00:00 +0000

Total hysterectomy via laparoscopy is a recently developed technique. Assessment of a new surgical technique, once the operation has been shown to be feasible, requires an evaluation of the risks of complications. Here we report our cumulative 3 year experience with laparoscopic hysterectomy in a total of 222 patients. The overall complication rate was 10.0%. We did not observe any haemorrhage complications requiring another operation. Four patients (1.8%) were re-admitted to hospital but only two of them (0.9%) had to be operated upon again (one vesico-vaginal fistula and one vaginal cuff wound separation). These encouraging results mean that, provided the surgeons are experienced in laparoscopic surgery, total laparoscopic hysterectomy technique would appear not to have a higher rate of complications than hysterectomy via laparotomy or the vaginal route.

Hysterectomy for patients without previous vaginal delivery: results and modalities of laparoscopic surgery.

Tue, 01 Oct 1996 00:00:00 +0000

The great majority of hysterectomies in nulliparous patients have been carried out via laparotomy. The purpose of this study was to establish whether laparoscopic surgery can be of use in an attempt to reduce the number of laparotomies when hysterectomy is indicated in patients without previous vaginal delivery. A retrospective study was carried out on 66 women who had not had a previous vaginal delivery who underwent hysterectomy from January 1993 to May 1995. Laparotomy was required for only 19.7% of cases (13 patients). For the 53 patients (80.3%) who underwent laparoscopic hysterectomy, the average duration of the operation was 152.24 +/- 45.7 min, and the average weight of the uterus was 238.3 +/- 154.1 g. The duration of the laparoscopic operation was correlated in a statistically significant fashion with the weight of the uterus (P = 0.0005), the necessity of associated procedures during the hysterectomy (P = 0.01) and the surgeons’ experience (P = 0.01). These results demonstrated that laparoscopic surgery decreases the number of laparotomies necessary for patients with no previous vaginal delivery who require hysterectomy. When vaginal access is poor, simple laparoscopic preparation is inadequate and the only possibility of avoiding laparotomy is to carry out the hysterectomy entirely via the laparoscopic route.

Diagnosis and management of organic ovarian cysts: indications and procedures for laparoscopy.

Sun, 01 Sep 1996 00:00:00 +0000

In the field of gynaecological surgery, the past few years have been significant due to the development of operative laparoscopy. Originally recommended for the diagnosis of female infertility, over the past 15 years laparoscopy has acquired the standing of a surgical discipline in its own right. Laparoscopic surgical treatment of ovarian cysts, whether conservative or radical, has now been completely standardized. The aim of this work is to specify the indications, procedures and risks involved with this surgery as applied to organic ovarian cysts. Only benign ovarian cysts are suitable for treatment by laparoscopic surgery; ovarian cancer must always be handled by classic surgery using a mid-line laparotomy. Given that clinical and other pre-operative investigations can give only an indication, ovarian lesions require surgical investigation to diagnose the histological type. Laparoscopy appears to be as reliable as laparotomy when assessing whether an ovarian tumour is malignant. The risk of parietal contamination and peritoneal dissemination if a malignancy is not recognized means that, if there are no signs of extra-ovarian extension, adnexectomy is mandatory whenever there is the slightest doubt. This adnexectomy must obey two important rules: it must be accomplished without rupturing the cyst, and the cyst must be placed, intact, inside an endoscopic bag before being extracted. Provided that all stages of the procedure, from pre-operative work-up to the initial diagnostic phase of the laparoscopy, are carried out meticulously, laparoscopic surgery is reliable for both the diagnosis and the management of benign organic-ovarian cysts.

Laparoscopic treatment of ovarian dermoid cysts.

Mon, 01 Jul 1996 00:00:00 +0000

Am J Obstet Gynecol. 1996 Jul;175(1):234-5. doi: 10.1016/s0002-9378(96)70290-9. Laparoscopic treatment of ovarian dermoid cysts. Chapron C, Dubuisson JB.

Salpingectomy - the laparoscopic surgical choice for ectopic pregnancy.

Sat, 01 Jun 1996 00:00:00 +0000

The aim of this study was to assess the fertility outcome after ectopic pregnancy (EP) treated by laparoscopic salpingectomy. Among the 375 patients who underwent this operation between January 1983 and December 1993, there were 145 patients who desired pregnancy and whose contralateral tube was not obstructed. The overall rate of intrauterine pregnancy (IUP) was 50.3%, with an EP rate of 15.2%. These results were analysed according to the patients’ past history together with the condition of the contralateral tube at the time of the laparoscopy. We defined two groups. Group 1 included patients who had no previous history of tubal surgery and whose contralateral tube was normal. Group 2 comprised those patients who had a previous history of tubal surgery and/or those whose tube was pathological, but not obstructed. Postoperative fertility of the patients in group 1 was significantly higher than that of the patients in group 2, with IUP rates of 75 and 36.6% respectively (P < 0.001), and a risk of EP recurrence of 9.6 and 18.3% respectively. In group 1, the actuarial IUP rate at 24 months was significantly higher than that for the patients in group 2 (66.7 versus 36.9%; P < 0.001). The patient’s past history and the condition of the contralateral tube were the two major factors related to fertility outcome after laparoscopic salpingectomy for EP. In patients with no past history of tubal surgery or infertility and whose contralateral tube was normal, the fertility results after laparoscopic salpingectomy appeared comparable to those observed after conservative laparoscopic treatment.

Laparoscopic myomectomy today. A good technique when correctly indicated.

Wed, 01 May 1996 00:00:00 +0000

Treatment of adnexal torsion using operative laparoscopy.

Wed, 01 May 1996 00:00:00 +0000

The aim of this work was to clarify the value and application of operative laparoscopic treatment for adnexal torsion. We included in our study all patients (n = 27) who presented with an intra-operative diagnosis of torsion of the adnexa between January 1989 and May 1995. A total of 28 adnexal torsions were treated. Treatment was carried out by laparoscopic surgery in 75% of cases (21 torsions): in one-half of the cases (14 torsions) it was possible to achieve conservative laparoscopic treatment. The nature of the lesions and the experience of the surgeons are two factors which closely govern the outcome of surgical treatment. For those patients presenting a benign pathology, laparoscopic surgery was used to treat 84% of cases in the series. All the patients presenting a benign pathology and operated upon since 1993 have received laparoscopic surgical treatment. No major complications (peritonitis, thrombotic emboli, coagulation problems) were observed after conservative laparoscopic surgery. These results demonstrate that, provided the surgeons are sufficiently experienced, treatment by conservative laparoscopic surgery for adnexal torsion is both safe and reliable. In the years to come more work must be done to assess the vitality of the adnexa so that as many patients as possible can benefit from conservative treatment.

Laparoscopic treatment of deep endometriosis located on the uterosacral ligaments.

Mon, 01 Apr 1996 00:00:00 +0000

The goal of this study was to assess the efficiency of laparoscopic surgical treatment of pain for patients presenting deep endometriosis located on the uterosacral ligaments. To this end we analysed a continuous series of 21 patients treated by laparoscopic surgery between January 1993 and June 1994. In all these cases treatment consisted of resection of all the uterosacral ligament(s) presenting deep endometriotic lesions together with exercise of all other endometriotic lesions. No complications were observed per- or postoperatively. The results were assessed for all the patients with a minimum follow-up of one year. The efficiency of the treatment varied according to the symptoms. Patients who presented dysmenorrhoea (19 cases) improved in 84.2% of cases (16 patients). Out of the 17 patients who presented deep dyspareunia, improvement was evident for 94.1% of cases (16 patients). The chronic pelvic pain suffered improved in seven out of nine cases (77.7%). Patients who benefited from an improvement rated it excellent or satisfactory in over 80% of cases. These results demonstrate that, provided the surgeon is highly skilled in laparoscopy, laparoscopic surgery is efficient for the treatment of patients presenting painful symptoms related to deep endometriotic implants located on the uterosacral ligaments.

Fertility after laparoscopic myomectomy of large intramural myomas: preliminary results.

Fri, 01 Mar 1996 00:00:00 +0000

Fertility outcome following laparoscopic myomectomy was evaluated. A prospective clinical study was carried out between October 1990 and October 1993 in 21 infertile patients who underwent laparoscopic myomectomy for a myoma measuring > or = 5 cm in diameter. The overall rate of intrauterine pregnancy was 33.3% (seven patients). Out of 12 patients with infertility factors associated with uterine myomas, three (25.0%) became pregnant, whereas four (44.4%) out of nine patients with no other associated infertility factor became pregnant. No uterine rupture was observed. Out of the seven pregnancies, four were spontaneous and began within 1 year of the operation. The other three were achieved after in-vitro fertilization in patients with associated infertility factors. In the four patients who gave birth by Caesarean section, no adhesions were found on the myomectomy scar. From these preliminary results, laparoscopic surgery for myomas seems to offer comparable results with those obtained by laparotomy.

Uterine fibroids: place and modalities of laparoscopic treatment.

Fri, 01 Mar 1996 00:00:00 +0000

Only fibroids which give rise to symptoms resistant to properly conducted medical treatment and/or complicated myomas require surgical treatment. The possibility offered by the new surgical approaches enables myomectomies to be now carried out via laparoscopy. We report our technique of laparoscopic myomectomy performed since 1989. Monopolar coagulation is used for the uterine incision, after myomectomy, myometrium and serosa are sutured. Myomas are removed through the suprapubic puncture site after fragmentation of large myomas, through a colpotomy or using the morcellator. Our results enable us to say that, although it is a difficult technique, laparoscopic myomectomy is a safe and reliable technique even for large intramural myomas.

[Radical laparoscopic surgery of ectopic pregnancy: results from a continuous series of 383 interventions].

Thu, 01 Feb 1996 00:00:00 +0000

From January 1983 to December 1993, 375 patients underwent laparoscopic salpingectomy. Six complications (1.5 %) were observed. Among 145 patients with a patent contralateral tube who desired pregnancy, 73 had an intrauterine pregnancy (50.3 %) and 22 had ectopic pregnancy (15.2 %). These results are discussed according to the contralateral tube status and gynecologic past history.

[Genital bilharziasis and female infertility. Review of the literature and three case reports].

Mon, 01 Jan 1996 00:00:00 +0000

Genital schistosomiasis is an uncommon disease. Its responsibility in female infertility is controversial. We reported 3 cases of pelvic schistosomiasis and we debate about the pathogenic contribution of the bilharziosis in sterility.

[Uterine fibroma. Diagnosis, development, treatment].

Mon, 01 Jan 1996 00:00:00 +0000

[Complete hysterectomy for benign pathology and laparoscopy: respective indications of laparoscopic preparation and an exclusively laparoscopic approach].

Fri, 01 Dec 1995 00:00:00 +0000

According to whether uterine artery treatment takes place vaginally or laparoscopically, laparoscopy for hysterectomy can be considered according to two modalities: laparoscopically assisted vaginal hysterectomy (LAVH) and total laparoscopic hysterectomy (TLH). The indications for laparoscopy are defined by the limits and/or contraindications of the vaginal route. LAVH is indicated in the following situations: pelvic pain syndrome where diagnosis and treatment can be made at the same time as hysterectomy; minimal endometriosis; past surgical history favouring adhesions formation; necessity to perform an oophorectomy; existence of an ovarian pathology. The elective indications for TLH are the severe pelvic adhesions, deep endometriosis and especially a limited vaginal accessibility associating with a narrow vagina and a fixed or non prolapsed uterus. Laparoscopy thus allows to reduce the number of laparotomies. When on overage three quarters of the hysterectomies (excluding cases of uterogenital prolapse) were up till now performed abdominally, laparoscopy could reduce this rate to approximately 10%.

[Laparoscopic tubal sterilization reversal: a technic using a single stitch].

Fri, 01 Dec 1995 00:00:00 +0000

We report our laparoscopic technique of tubal sterilization reversal. We perform a simple and atraumatic technique with a single point. After preparation and approximation of the two tubal segments, the anastomosis consists of one single suture placed at the -‘12 o’clock-’ site of the antimesenteric border. The feasibility, the advantages and the preliminary results are presented.

Laparoscopic myomectomy and myolysis.

Fri, 01 Dec 1995 00:00:00 +0000

The indications for operative laparoscopy have increased greatly over the past decades as its many advantages over laparotomy have become recognized. Laparoscopic myomectomy as a technique is now clearly described. A monopolar hook is used for the uterine incision. After atraumatic enucleation of the myoma, myometrium and serosa are usually sutured particularly if the incision is deep or more than 2 cm long. Myomas can be removed by posterior colpotomy. However, the development of an electrical cutting device permits an easier and quicker removal of the myoma through the suprapubic puncture site. Only complicated myomas and/or those which give rise to persistent symptoms despite properly prescribed medical treatment, together with those which grow rapidly, require surgery. In our experience of ablation of myomas measuring 5 cm and over the results were satisfactory in all 71 patients with more than one year of follow-up. In two cases (2.7%) we were obliged to convert to laparotomy. We were confronted with no serious per-operative or post-operative complications. These satisfactory results must not mask the fact that the technique is lengthy and difficult and should be carried out by experienced surgeons thoroughly familiar with endoscopic sutures. Under these conditions, laparoscopic myomectomy is possible, for large myomas (5 cm and over) even if they are located completely intramurally. However, there are limits and it is preferable to use laparotomy for myomas measuring over 10 cm and for multiple myomectomy (over 3). Finally, the risk of causing adhesions and the quality of the uterine suture need to be assessed in the near future.

[Hydrosalpinx and sterility: indications for salpingectomy].

Wed, 01 Nov 1995 00:00:00 +0000

[Total hysterectomy for benign pathologies: why is laparoscopy of value?].

Wed, 01 Nov 1995 00:00:00 +0000

The majority of the hysterectomies are performed by laparotomy. With laparoscopic surgery it will be possible to perform only 10 to 20 per cent of the hysterectomies by the abdominal route. Even if laparoscopic hysterectomy is a feasible technique, all the hysterectomies should not be performed by the endoscopic route. Laparoscopic surgery is in no case an alternative to vaginal surgery. Laparoscopic surgery is not indicated for hysterectomy if the operation is feasible quickly and under good conditions via the vaginal route. Laparoscopic surgery is only indicated when vaginal surgery is difficult and/or contra-indicated. In these situations, laparoscopic surgery can be performed according two different modalities: laparoscopically assisted vaginal hysterectomy and total hysterectomy completely performed by laparoscopy.

History of infertility.

Fri, 01 Sep 1995 00:00:00 +0000

Infertility has always been a constant preoccupation. The problems it raises today on medical, social, ethical, political and religious levels bear witness to this emphasis, but also to how complicated infertility is to deal with and understand. This study not only examines the history of infertility and the treatments applied but also the repercussions for infertile women socially. As we look through history, we find that the attitudes of physicians have often reflected the role of the woman and her image in society.

Complications of gynecologic laparoscopic surgery.

Tue, 01 Aug 1995 00:00:00 +0000

The growing impact of laparoscopic surgery must not make us underestimate the existence of complications, some of them severe, with medical-legal implications. Several surveys and case reports of complications following modern gynecologic laparoscopic surgery, some reporting laparoscopic management of visceral injuries, have been published recently. The complication rate depends on the complexity of the surgical procedure; serious complications still arise during performance of laparoscopy. Patients must be informed of the hazards of so-called ‘minimally’ invasive surgery.

Uterine rupture during pregnancy after laparoscopic myomectomy.

Thu, 01 Jun 1995 00:00:00 +0000

A 31 year old patient presenting with primary infertility underwent an operative laparoscopy for the treatment of bilateral hydrosalpinges, during which a myomectomy was also performed. The uterus was repaired using interrupted sutures. At follow-up laparoscopy seven weeks later, a uterine fistula was diagnosed and was oversewn using a single ‘figure of eight’ suture. One year later the patient became pregnant through in-vitro fertilization. At 34 weeks gestation, she required an emergency laparotomy for acute abdominal pain and the presence of fetal bradycardia. The operative findings revealed a uterine rupture at the site of the previous myomectomy scar. This was then enlarged with a scalpel and a live baby was delivered. The uterus was repaired in two layers. The postoperative period for both mother and baby was satisfactory. This complication raises the problem of the quality of uterine repair following laparoscopic myomectomy, together with the question of how to prevent this type of life-threatening situation.

Sterilization reversal: fertility results.

Mon, 01 May 1995 00:00:00 +0000

Fertility outcome following sterilization reversal by laparotomy was evaluated. We studied all sterilization reversals performed between January 1978 and December 1991; a total of 226 women were treated. Tubal anastomosis was performed according to the rules for microsurgery. The microsurgical technique comprised two main phases: preparation of the healthy tube segments and the anastomosis carried out on two layers. It was possible to study the subsequent fertility of 206 patients in all, as 20 patients were lost to follow-up (8.8%). Cumulative pregnancy rates were evaluated by life-table analysis. The overall intrauterine pregnancy rate, including births and miscarriages, was 69.9% (144 patients) after 2 years. The cumulative intrauterine pregnancy rate was 62% at 18 months. Analysis of the fertility results demonstrated that age was the most significant predictive factor. The cumulative intrauterine pregnancy rate at 2 years was 83.5% (61 cases) for patients < or = 33 years, 70% (35 cases) for patients aged 34-36 years, 62.5% (30 cases) for patients aged 37-39 years, and 51.4% (18 cases) for patients aged > or = 40 years. Even for patients aged approximately 40 years, microsurgical repermeabilization can be retained as the first choice rather than in-vitro fertilization. PIP: At Cochin-Port Royal Hospital in Paris, France, gynecologic surgeons used laparotomy to perform microsurgical sterilization reversal on 226 patients aged 6-41 during January 1978-December 1991. 20 women were lost to follow-up. The researchers used life-table analysis to examine cumulative pregnancy rates. The mean interval between sterilization and sterilization reversal was 6.15 years. The surgeons first prepared the healthy tube segments and then performed anastomosis on two layers. At 18 months and 2 years post-reversal, the overall intrauterine pregnancy rates (births and miscarriages) stood at 62% and 69.9%, respectively. The average time between sterilization reversal and intrauterine pregnancy was 9.6 months. At 2 years, there were 4 ectopic pregnancies (2%). Even though women who had undergone bilateral sterilization reversal were more likely to become pregnant and to become pregnant more quickly than those who had undergone unilateral sterilization (73% vs. 56.4% and 8.8 vs. 12.2 months), the differences were insignificant. The type of anastomosis (e.g., isthmic-isthmic or isthmic-ampullary) had no bearing on fertility, as long as the tubes were at least 3 cm in length. The intrauterine pregnancy rates decreased with age (p = 0.01) (at 2 years post-reversal: 83.5% for age 33 or younger; 70% for age 34-36; 62.5% for age 37-39; and 51.4% for age 40 or older). Age was the most significant predictive factor of return to fertility. The findings show that microsurgical repermeabilization can remain the first choice rather than in-vitro fertilization for sterilized women wishing to bear a child, even women around age 40.

Laparoscopic hysterectomy.

Sat, 04 Mar 1995 00:00:00 +0000

Lancet. 1995 Mar 4;345(8949):593. Laparoscopic hysterectomy. Chapron C, Dubuisson JB.

[Trophoblast graft on the omentum. Failure of conservative celioscopic treatment of extra-uterine pregnancy].

Sat, 11 Feb 1995 00:00:00 +0000

Presse Med. 1995 Feb 11;24(6):327. [Trophoblast graft on the omentum. Failure of conservative celioscopic treatment of extra-uterine pregnancy]. Chapron C, Decoret E, Morice P, Capella S, Dubuisson JB.

[Laparoscopic salpingostomies: analysis of results].

Wed, 01 Feb 1995 00:00:00 +0000

One hundred and twenty three infertile women were treated by laparoscopic salpingostomy. The intra-uterine pregnancy rate is 30.4%. The mucosal status seems to be the principal prognostic factor.

Laparoscopic management of asymmetric Mayer-Rokitansky-Kuster-Hauser syndrome.

Wed, 01 Feb 1995 00:00:00 +0000

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a partial or complete absence (agenesis) of the uterus with an absent or hypoplastic vagina. Until now, the recommended treatment, when resection of a rudimentary horn was indicated, was laparotomy. We report a case of MRKH syndrome in which the patient benefited from laparoscopic surgery for bilateral resection of rudimentary horns. Laparoscopy is not only useful for diagnosis of uterine malformations but can also be valuable for any treatment required for this type of malformation, this being carried out during the same operative procedure, thus avoiding laparotomy for the patient. The creation of an artificial vagina is performed during a second operation.

Bladder injuries during total laparoscopic hysterectomy: diagnosis, management, and prevention.

Sun, 01 Jan 1995 00:00:00 +0000

Based on a series of 150 total hysterectomies carried out via laparoscopy between January 1993 and December 1994, we observed 2 bladder complications: 1 bladder injury and 1 vesicovaginal fistula. These two accidents form the basis of discussion on the risk factors for these complications, their diagnosis, treatment, and prevention.

Classification of endometriosis. The need for modification.

Thu, 01 Dec 1994 00:00:00 +0000

[Techniques and indications for using an endoscopic sac in the management of ovarian cysts].

Tue, 01 Nov 1994 00:00:00 +0000

Total laparoscopic hysterectomy: preliminary results.

Tue, 01 Nov 1994 00:00:00 +0000

Total hysterectomy carried out entirely via laparoscopy benefited 31 patients. In all cases the operation was carried out using conventional, re-usable instruments (grasping forceps, laparoscopic scissors, bipolar coagulation). The mean duration of the operation was 171 min. No serious peri- or post-operative complications were encountered and no transfusion was required. The mean drop in haemoglobin was 1.3 g/100 ml and the average length of hospital stay was 4 days. In one case (3.26%) we converted to laparotomy because a lateral myoma made it impossible to achieve haemostasis of the uterine pedicle under suitably safe conditions. These results confirm that total hysterectomy via laparoscopy is a safe, feasible and reproducible technique. Future work will establish the exact place and methods for laparoscopic surgery for hysterectomy; it can be suggested, however, that laparoscopic surgery is only indicated when vaginal hysterectomy is contra-indicated or impossible. So, laparoscopic hysterectomy constitutes an alternative to laparotomy rather than to vaginal hysterectomy. The combination of an immobile uterus and poor vaginal accessibility is the prime indication for total hysterectomy via laparoscopy.

Laparoscopic myomectomy. Operative procedure and results.

Fri, 30 Sep 1994 00:00:00 +0000

Myomectomy was performed by laparoscopy in 102 patients, according to a precise technique using the monopolar hook for the uterine incision and intraperitoneal sutures. Myomas were mostly removed through the suprapubic puncture site after fragmentation or by colpotomy. Conversion to laparotomy during the laparoscopic procedure was necessary in 2 cases. No complications were observed. A second-look laparoscopy was performed in 17 cases. Postoperative adhesions were noted in 2 cases. In our experience, operative laparoscopy has several advantages over laparotomy and the risk of complications is low in selected cases.

Treatment of ovarian dermoid cysts. Place and modalities of operative laparoscopy.

Thu, 01 Sep 1994 00:00:00 +0000

The purpose of this study was to discuss the place and the specific modalities of laparoscopic surgery in the management of ovarian dermoid cysts. This retrospective and noncomparative study was carried out in 65 patients who presented dermoid ovarian cyst between January 1986 and December 1990 in our institution. The surgical treatment was performed purely by laparoscopy in 86.2% of the cases (56 patients). The modalities of laparoscopic surgery were as follows: ovariectomy (8 cases; 14.3%), transparietal cystectomy (4 cases; 7.1%) and intraperitoneal cystectomy (44 cases; 78.6%). In 15 cases (15/44 = 34%) the intraperitoneal cystectomy was carried out without opening the cyst and the intact cyst was extracted using an endoscopic impermeable sack. We observed no cases of chemical peritonitis. The risk of recurrence after conservative treatment is 4% (two patients) and out of the ten patients for whom a second-look laparoscopy was performed only two (20%) presented adhesions. Laparoscopic treatment of dermoid ovarian cysts is feasible, safe, and effective. The treatment can be conservative in over 80% of the cases. The specific risk of chemical peritonitis can be countered by a change in the cystectomy technique. The use of an impermeable laparoscopic sack permits extraction of the cyst without any peritoneal contamination.

Treatment and causes of female infertility.

Sat, 30 Jul 1994 00:00:00 +0000

Lancet. 1994 Jul 30;344(8918):333-4. doi: 10.1016/s0140-6736(94)91372-2. Treatment and causes of female infertility. Chapron C, Dubuisson JB, Chavet X, Morice P.

[Recurrent spontaneous early abortions].

Fri, 01 Jul 1994 00:00:00 +0000

Laparoscopic hysterectomy: it is not such an expensive surgical procedure.

Fri, 01 Apr 1994 00:00:00 +0000

Am J Obstet Gynecol. 1994 Apr;170(4):1210-1. doi: 10.1016/s0002-9378(94)70127-x. Laparoscopic hysterectomy: it is not such an expensive surgical procedure. Chapron C, Dubuisson JB, Aubert V.

Pregnancy after laparoscopic partial cystectomy for bladder endometriosis.

Fri, 01 Apr 1994 00:00:00 +0000

We report a case of partial laparoscopic cystectomy in a 31-year-old infertile patient presenting vesical endometriosis. This patient had suffered severe dysmenorrhoea for 10 years previously together with repeated episodes of urinary infection, mostly occurring during the menstrual period. A diagnostic laparoscopy performed in another centre diagnosed a stage IV endometriosis. Gonadotrophin-releasing hormone agonists were prescribed for 9 months. After failure of this treatment, the patient came to consult us. A solid mass in the left supratrigone was detected by pelvic ultrasonography and confirmed by cystoscopy. Transurethral resection was carried out. A recurrence of the symptoms 9 months later prompted operative laparoscopy under cystoscopic control. This confirmed recurrence of a 3.5 cm endometriotic nodule. Laparoscopic partial cystectomy was performed using the monopolar electrode. The bladder was then sutured via laparoscopy. No complications occurred. No postoperative treatment was given. Second-look cystoscopy 2 months later revealed that healing was perfect. Eight months later, the patient is well and has a normal intra-uterine pregnancy.

Laparoscopic salpingostomy: fertility results according to the tubal mucosal appearance.

Tue, 01 Feb 1994 00:00:00 +0000

Prognostic factors for fertility outcome following laparoscopic salpingostomy were evaluated. We studied all distal tuboplasties performed between May 1986 and June 1991. Ninety infertile women were treated. Tuboplasty was carried out bilaterally except when one tube was absent or when bifocal lesions were present. Salpingostomy was performed using either scissors and thermocoagulation for eversion, or the CO2 laser. Cumulative pregnancy rates were evaluated by life-table analysis, according to the tubal classification and the mucosal status. The 18 months estimated cumulative pregnancy rate with normal delivery was 28.7%. Pregnancy rates were significantly higher in patients classified in grades I and II versus grade III and IV (severely damaged tubes) according to the distal tubal scoring system, and in patients with normal or lightly atrophic mucosa versus alveolar or absent mucosa. Operative laparoscopy is effective for treatment of hydrosalpinges. Fertility outcome is related to the tubal damage. Our results demonstrate that the prognosis value of the mucosal status seems to be as predictive as the distal tubal scoring system.

Failure of laparoscopic treatment for peritoneal trophoblastic implants.

Sat, 01 Jan 1994 00:00:00 +0000

We report on two cases of peritoneal trophoblastic tissue implants, one after salpingostomy, and one after salpingectomy for ectopic pregnancy. During each secondary laparoscopy, simple excision of implants with laparoscopic biopsy forceps resulted in persistent elevated beta-human chorionic gonadotrophin (beta-HCG) levels. Methotrexate therapy was used. Removal of all trophoblastic tissues present and avoidance of trophoblastic spillage during the laparoscopic procedure should prevent such an uncommon complication.

[Cysts of the adnexa. The role of endoscopy].

Wed, 01 Dec 1993 00:00:00 +0000

[Laparoscopic myomectomy. 102 cases].

Wed, 01 Dec 1993 00:00:00 +0000

Myomectomy was performed by laparoscopy in 102 patients, according to a precise technique using the monopolar hook for the uterine incision and intraperitoneal sutures. Myomes were mostly removed through the suprapubic puncture site after fragmentation or by colpotomy. A laparotomy during the laparoscopic procedures was necessary in 2 cases. No complications were observed. A second-look laparoscopy or a cesarean section was performed in 24 cases. Post-operative adhesions were noted in 3 cases. In our experience, operative laparoscopy has several advantages over laparotomy and the risks of complications is low in selected cases.

Complications of gynecologic laparoscopic surgery--a French multicenter collaborative study.

Thu, 06 May 1993 00:00:00 +0000

N Engl J Med. 1993 May 6;328(18):1355. doi: 10.1056/NEJM199305063281817. Complications of gynecologic laparoscopic surgery–a French multicenter collaborative study. Querleu D, Chapron C, Chevallier L, Bruhat MA.

Laparoscopic management of tubal ectopic pregnancy.

Thu, 01 Apr 1993 00:00:00 +0000

As with laparotomy, laparoscopic treatment of ectopic pregnancy (EP) can be either conservative or radical. After conservative laparoscopic treatment by salpingotomy the risk of failure (between 4 and 6%) is comparable with that observed after similar treatment by laparotomy. The fertility results after laparoscopic treatment of EP are comparable if not better than those observed after similar treatment by laparotomy. These two reasons, together with the considerable advantages of endoscopy over laparotomy, mean that today laparoscopic treatment is without question the best surgical treatment for EP. The prognosis for post-EP fertility is unrelated to the characteristics of the EP (size, rupture, location). The post-EP fertility depends mainly on the patient’s previous history. We have established the Therapeutic Scoring System for EP by assessing the different factors affecting future fertility and multivariable analysis. This score allowed us to choose the most suitable treatment to preserve fertility and reduce the risk of recurrence between conservative laparoscopic treatment, laparoscopic salpingectomy with or without contralateral tubal sterilization.

[The benefits and risks of laparoscopic surgery].

Mon, 01 Feb 1993 00:00:00 +0000

The advantages of laparoscopic surgery in comparison to those of conventional surgery are mainly due to the very low rates of postoperative infections and adhesions and due to the aesthetic nature of this type of surgery. Endoscopy enables a thorough search of lesions which can then be treated in a more conservative manner. The short hospital stay and rapid postoperative recovery are two key advantages of endoscopic surgery. Complications at endoscopic surgery mainly occur if the safety measures are not strictly followed, due to improper choice and use of instruments (eg. old instruments), an antecedent laparotomy and also depend upon the type of surgery performed. It should be noted that the introduction of the trocar is not a simple affair, that non-recognition of complications is not infrequent and that the incidence of complications is directly proportional to the experience of the operator.

[Place of celiosurgery in cancer of the cervix uteri].

Fri, 01 Jan 1993 00:00:00 +0000

Laparoscopic hysterectomy. A preliminary study.

Fri, 01 Jan 1993 00:00:00 +0000

Thirty-three patients were selected for laparoscopic hysterectomy and operated on in the Department of Obstetrics, Gynecology and Reproductive Medicine of Clermont-Ferrand University Hospital. Surgical techniques included blunt dissection with scissors and bipolar coagulation to achieve hemostasis. A case was considered successful when all the uterine vessels were treated by laparoscopy. Twenty-four cases were completed laparoscopically (72.7%). None of these patients had postoperative bleeding; 22 had an uneventful postoperative recovery. Nine procedures were converted to laparotomy (27.3%), five because of a difficult or unsatisfactory hemostasis. We conclude that in selected cases, a total hysterectomy can be performed safely by experienced laparoscopists. Further technological progress is necessary to make this procedure more acceptable. Its value as compared to the others will have to be demonstrated.

Treatment of recurrent ectopic pregnancy.

Thu, 01 Oct 1992 00:00:00 +0000

Fertil Steril. 1992 Oct;58(4):859-60. doi: 10.1016/s0015-0282(16)55347-3. Treatment of recurrent ectopic pregnancy. Chapron C, Pouly JL, Manhès H, Mage G, Canis M, Wattiez A, Bruhat MA.

Second-look laparoscopy after laparoscopic cystectomy of large ovarian endometriomas.

Tue, 01 Sep 1992 00:00:00 +0000

Forty-two patients who underwent a second-look laparoscopy after a unilateral or bilateral intraperitoneal cystectomy for treatment of an ovarian endometrioma of greater than 3 cm were included. At second-look laparoscopy, 92.4% of the adnexae treated for a large endometrioma had no deep ovarian endometriosis. Adhesion de novo formation occurred in 21% of the treated adnexae and in 17% of the contralateral adnexae. Complete or partial recurrence of dense adhesions occurred in 82% of the cases. Laparoscopic cystectomy is effective in treating large endometriomas. However, operative difficulties may be encountered, explaining persistent endometriomas and postoperative adhesions.

Results of conservative laparoscopic treatment of isthmic ectopic pregnancies: a 26 case study.

Sun, 01 Mar 1992 00:00:00 +0000

Twenty-six ectopic pregnancies located strictly within the isthmus were treated surgically using conservative laparoscopic techniques. In each and every case, the Triton monopolar electrode was used to perform salpingostomy which was followed by aspiration of the trophoblast. This therapeutic approach is very reliable since only one failure was observed (3.9%), requiring a further operation during which salpingectomy was carried out by laparoscopy. It was possible to evaluate subsequent fertility for 11 patients, seven of whom (63.6%) obtained an intrauterine pregnancy and only one patient (9.1%) had a recurrence. This highly satisfactory prognosis is perfectly comparable with that obtained with treatment via laparotomy with segmental resection of the isthmic portion of the tube and immediate or delayed anastomosis. These very encouraging results mean that conservative laparoscopic treatment presents an advantageous alternative to classic surgical treatment for isthmic ectopic pregnancies, in that the patients are spared a laparotomy.

[Surgical celioscopy in gynecology].

Sat, 30 Nov 1991 00:00:00 +0000

Presse Med. 1991 Nov 30;20(41):2081-3. [Surgical celioscopy in gynecology]. Bruhat MA, Mage G, Chapron C, Pouly JL, Manhes H, Canis M, Wattiez A.

[Celioscopic hysterectomy. Technical improvements].

Sat, 23 Nov 1991 00:00:00 +0000

Presse Med. 1991 Nov 23;20(39):1950. [Celioscopic hysterectomy. Technical improvements]. Mage G, Chapron C, Wattiez A, Canis M, Pouly JL, Bruhat MA.

Laparoscopic treatment of ectopic pregnancies: a one hundred cases study.

Tue, 08 Oct 1991 00:00:00 +0000

From June 1987 to December 1989, 100 ectopic pregnancies (93 patients) were operated on by laparoscopy. The different techniques included salpingostomy, salpingectomy and tubal expression. There were no intra-operative complications or unwanted laparotomy. Only one patient (1%), on the fourth post-operative day, underwent a laparotomy due to an occlusive syndrome. Six failures (9.5%), in cases of conservative treatment were observed including three (16.6%) after tubal expression. The length of operation and hospitalization is similar with regard to the different endoscopic procedures, and shorter than those observed after treatment by laparotomy. These results confirm that laparoscopic treatment of ectopic pregnancies is not only reliable but also significantly less expensive than treatment by means of classical surgery.

Multifactorial analysis of fertility after conservative laparoscopic treatment of ectopic pregnancy in a series of 223 patients.

Sun, 01 Sep 1991 00:00:00 +0000

OBJECTIVES: To lay down the criteria to clearly define whether conservative or radical laparoscopic treatment should be adopted in cases of ectopic pregnancies (EP). DESIGN: Retrospective, noncomparative. SETTING: At the University Hospital of Clermont Ferrand and the La Pergola Clinic at Vichy from July 1974 to December 1987. PATIENTS: This study was carried out in 223 patients who had been treated laparoscopically for EP and who desired future childbearing and who were not lost to follow-up. MAIN OUTCOME MEASURES: The measures chosen to achieve the objective included age, parity, size of hematosalpinx, volume of hemoperitoneum, tubal rupture, location, intrauterine device, ipsilateral and contralateral adhesions, and patient’s previous history of salpingitis, EP, solitary tube, and tubal infertility. RESULTS: The general intrauterine pregnancy rate was 67% (149 patients) and the recurrence rate 12% (27 patients). The results according to the studied factors demonstrated that age, parity, and the type of the EP have no influence on the postectopic fertility. The history of the patient, ipsilateral adhesions, or contralateral tubal status significantly reduce the future fertility prognosis and risk of recurrence. CONCLUSIONS: From a multivariable analysis, the authors propose a scoring system to choose the most suitable treatment to preserve fertility and to reduce the risk of recurrence ranging from laparoscopic conservative treatment to laparoscopic salpingectomy with contralateral sterilization.

Present day endoscopic surgery in gynecology.

Tue, 20 Aug 1991 00:00:00 +0000

The last ten years have been characterized by a tremendous change in laparoscopy. Initially used exclusively for diagnosis, laparoscopy is now a surgical method in its own right and plays a strategic role. Long-term evaluation of results for various pathologies (such as ectopic pregnancy and tubo-peritoneal sterility) means that just one laparoscopic procedure can be used for diagnosis, selection of the best therapeutic approach and also for treatment in those cases where laparoscopy is the optimum choice. Other more recent indications (including hysterectomy, lymphadenectomy etc.) which are now possible thanks to recent technological developments (such as clips and mechanical sutures) need long-term analysis of their results.

Advanced heterotopic pregnancy after in-vitro fertilization and embryo transfer, with survival of both the babies and the mother.

Thu, 01 Aug 1991 00:00:00 +0000

A combination of an extra-uterine and an intra-uterine pregnancy is defined as heterotopic pregnancy. An infertile patient, pregnant at her fourth in-vitro fertilization/embryo transfer attempt, was diagnosed at 21 weeks’ gestation as having simultaneous abdominal and intra-uterine pregnancy. Expectant management under strict hospitalization was proposed and accepted by the couple, fetal assessment was by serial ultrasound evaluation of growth and amniotic fluid volume and by non-stress tests. Planned operative delivery was accomplished at 34 weeks’ gestation. Both the mother and infants are alive and well.

Subsequent fertility for patients presenting with an ectopic pregnancy and having an intra-uterine device in situ.

Thu, 01 Aug 1991 00:00:00 +0000

Of 503 ectopic pregnancies (EP) dealt with surgically using conservative laparoscopic techniques, 153 (30.4%) occurred in patients with an intra-uterine device (IUD) in situ. Examination of the characteristics of the EP revealed that the fimbrial location was more frequent among patients with an IUD whereas a significantly higher proportion were located in the isthmus in the group of patients without an IUD. Whereas the condition of the tubal wall did not differ according to the presence or absence of an IUD, adhesions and obstructed or non-existent contralateral tubes were significantly less frequent among patients with an IUD in situ. Two hundred and twenty three patients desired pregnancy, 30 of whom had an IUD in situ when the EP was diagnosed. The subsequent fertility for these 30 patients with an IUD was shown by rates for intrauterine pregnancy (IUP), recurrent EP and infertility of 96.7, 3.3 and 0% respectively. These results were significantly better than those for women who had no IUD, the figures for this group being 59, 13.4 and 27.4%, respectively. The favourable prognosis was due solely to the fact that women with an IUD had far fewer negative antecedents and that the EP probably occurred due to impaired ciliary action which is reversible when the IUD is removed.

Treatment of tubal pregnancy.

Thu, 01 Aug 1991 00:00:00 +0000

Fertil Steril. 1991 Aug;56(2):374-5. doi: 10.1016/s0015-0282(16)54507-5. Treatment of tubal pregnancy. Chapron C, Pouly JL, Manhes H, Mage G, Canis M, Wattiez A, Bruhat MA.

[Fertility after ectopic pregnancy. III. The prognostic role of antecedents].

Sat, 01 Jun 1991 00:00:00 +0000

Contracept Fertil Sex (Paris). 1991 Jun;19(6):453-9. [Fertility after ectopic pregnancy. III. The prognostic role of antecedents]. Pouly JL, Chapron C, Mage G, Canis M, Wattiez A, Manhes H, Bruhat MA. PIP: Fertility after conservative laparoscopic treatment for ectopic pregnancy (EP) was studies in 223 patients based on the existence of either past EP, salpingitis, having a single tube, or sterility. These factors impact significantly on fertility rate. The global fertility rate is statistically much higher for patients who do not fit into any of these categories (group a-101 patients) compared to patients with 1 or more criteria (group B-122 patients). For each group, the compared intrauterine pregnancy rate is 90% (91 cases) for group A and 42.6% (52 cases) for group B (p001). The compared ectopic recurrence rate is 5% (5 cases) in group A and 18% (22 cases) in group B (0.001p0.01). The rate of sterility was only 5% (5 cases) in group A as compared to 39.4% (48 cases) in group b (p0.001). Moreover, the fertility rate for patients with 1 or more of the above mentioned criteria is significantly much lower that that of patients without any of the factors examined. This is a significant difference when intrauterine rate, ectopic recurrence rate, and sterility rate are each examined separately. A positive past history for these criteria also affects cumulative intrauterine pregnancy (IUP) rate. For all patients, cumulative IUP rate is 54.60% at 2 years. For patients in group A, this rate increased up to 75.70%. For patients with 1 of these factors, the cumulative IUP rate is only between 12.90% and 25.50%. Finally, these factors delay the onset of subsequent intrauterine pregnancy. Globally, 70% of all IUP occurred with 2 years after the conservative laparoscopic treatment for EP. This rate is 83.20% for patients without any of these factors and 50% for those with at least 1 factor. (author’s modified)

[Fertility after ectopic pregnancy. IV. Proposition for a therapeutic score and a strategy for surgical treatment for ectopic pregnancy].

Sat, 01 Jun 1991 00:00:00 +0000

Contracept Fertil Sex (Paris). 1991 Jun;19(6):461-7. [Fertility after ectopic pregnancy. IV. Proposition for a therapeutic score and a strategy for surgical treatment for ectopic pregnancy]. Pouly JL, Chapron C, Mage G, Canis M, Wattiez A, Manhes H, Bruhat MA. PIP: A series to extrauterine pregnancies treated with conservative laparoscopic techniques was the basis for an evaluation of the subsequent fertility of 223 women. Treatment for extrauterine pregnancy should be based on a proven and reproducible technique that does not expose the patient to a significant risk f complications or failure in the hands of a well trained surgeon. The treatment should preserve the fertility of patients desiring later pregnancy if possible while controlling the risk of recurrence. No operative complications justifying laparotomy were observed in the author’s series of 321 cases, and their failure rate of 4.8% was not significantly different from that reported after conservative treatment by laparotomy. Subsequent fertility, explored in terms of intrauterine pregnancy, recurrence of ectopic pregnancy and sterility, or in cumulative intrauterine pregnancy rates, was comparable or superior to that of the principle series treated by laparotomy, whether radical or conservative and using or not using microsurgical techniques. In appears that, in the absence of the few rare contraindications, the most satisfactory surgical treatment of extrauterine pregnancy at present is laparoscopic. The possibility of intrauterine pregnancy should be kept in mind in choosing between radical and conservative laparoscopic treatment. The authors found in their series of 223 patients desiring subsequent pregnancy that factors significantly affecting the fertility prognosis included the presence of adhesions on the tube, the condition of the contralateral tube, and a history of salpingitis. Neither age, parity, nor the characteristics of the extrauterine pregnancy significantly affected the possibility of pregnancy. A treatment score was created based on the results of a multiple regression analysis that assessed the fertility impact of 8 risk factors. A coefficient of 2 was assigned to a history of ectopic pregnancy or tubal microsurgery or to presence of a single tube. A coefficient of 1 was assigned to each additional ectopic pregnancy after the 1st, to a history of laparoscopic adhesiolysis, to homolateral and contralateral adhesions, and to a history of salpingitis. A score of 6 or over indicated that the patient’s hopes of subsequent pregnancy would be maximized by radical laparoscopic treatment and sterilization of the contralateral tube to avoid recurrence, and attempts at in vitro fertilization. Patients with a score of 5 had approximately equal chances of recurrence or intrauterine pregnancy after conservative laparoscopic treatment. But radical treatment would greatly reduce chances of recurrence and increase chances of normal pregnancy. Patients with a score of 4 or less had much greater chances of normal pregnancy than of recurrence after conservative laparoscopic treatment. Women desiring pregnancy who failed to conceive within 2 years should be referred for in vitro fertilization.

[Lobular carcinoma in situ of the breast].

Thu, 01 Mar 1990 00:00:00 +0000

The diagnosis of the lobular carcinoma in situ (LCIS), whose frequency is estimated to range from 0.8 to 3.8 p. cent of breast cancers on the whole, is exclusively anatomopathological since it does not have any specific clinical and/or radiological characteristics. After describing the two main differential diagnoses, the various possible treatments are studied, bearing in mind that the therapeutic strategy must take into account the three characteristics which are typical of LCIS: multicentricity, bilaterality and the possible occurrence of an invasive cancer.

[Nutritional evaluation after serious head injury].

Sun, 01 May 1988 00:00:00 +0000

Agressologie. 1988 May;29(6):413-8. [Nutritional evaluation after serious head injury]. Millet A, Roquefeuil B, Geniez C, Chapron C, Aznar M, Pratlong F, Bellet H.

[Incidence of normovolemic hemodilution in subjects with acute brain disease and in conscious subjects].

Sun, 01 Mar 1987 00:00:00 +0000

Agressologie. 1987 Mar;28(3):333-4. [Incidence of normovolemic hemodilution in subjects with acute brain disease and in conscious subjects]. Boularan A, Buxeda M, Duboin MP, Blanchet P, Chapron C, Wagner X, Roquefeuil B.

[Bone dedifferentiation ion during healing of amputated digits of mice, and study of its control].

Mon, 29 Sep 1980 00:00:00 +0000

C R Seances Acad Sci D. 1980 Sep 29;291(4):429-31. [Bone dedifferentiation ion during healing of amputated digits of mice, and study of its control]. Al Samarrae N, Chapron C. Processus of bone dedifferentiation have been shown in Mouse after amputation of the end of digits. Their meaning and their control have been searched for. Chemical sclerosis experiments on blood-vessels and ligature of the superficial femoral artery allowed to show they depended on the blood flow in the limb.

Relationship of sulfamethazine disposition kinetics to acetylator phenotype in man. A preliminary study.

Thu, 01 Jul 1976 00:00:00 +0000

J Clin Pharmacol. 1976 Jul;16(7):338-44. doi: 10.1002/j.1552-4604.1976.tb01530.x. Relationship of sulfamethazine disposition kinetics to acetylator phenotype in man. A preliminary study. Chapron CJ, Blum MR. The relationship between sulfamethazine disposition kinetics and acetylation phenotype was studied in man. Sulfamethazine pharmacokinetic parameters were determined after the administration of the drug as an oral suspension. When the half-life, acetylation rate constant, or per cent available dose excreted in the urine as acetylsulfamethazine of each subject was plotted on frequency distribution histograms, bimodal distribution patterns were observed. However, when acetylation clearance values were plotted in the same manner, an apparent trimodal pattern was seen. The failure to identify the presumed homozygous rapid acetylator using the commonly employed indices of drug metabolism, i.e., half-life, metabolic rate constant, or per cent of the dose metabolized, was attributed to a significant increase in the apparent volume of distribution of this genotype, as well as the low renal clearance of sulfamethazine found in all genotypes. This preliminary study points out the value of using metabolic clearance as an index of drug metabolizing capacity and suggests its application to further pharmacogenetic studies.

[Evidence for the role of an apical cap glycoprotein in amphibian regeneration: cytochemical and autoradiographic electron-microscopic studies (author's transl)].

Thu, 01 Aug 1974 00:00:00 +0000

J Embryol Exp Morphol. 1974 Aug;32(1):133-45. [Evidence for the role of an apical cap glycoprotein in amphibian regeneration: cytochemical and autoradiographic electron-microscopic studies (author’s transl)]. Chapron C.

[Effect of cyclic AMP and 5'AMP on meiosis and early development of Eisenia foetida ova].

Mon, 29 Jul 1974 00:00:00 +0000

C R Acad Hebd Seances Acad Sci D. 1974 Jul 29;279(5):433-5. [Effect of cyclic AMP and 5’AMP on meiosis and early development of Eisenia foetida ova]. Chapron C, Davant N, André F.

[Study of the origin and differentiation of the pharynx during regeneration in Eisenia foetida (Annelida)].

Tue, 01 Jun 1971 00:00:00 +0000

J Embryol Exp Morphol. 1971 Jun;25(3):439-55. [Study of the origin and differentiation of the pharynx during regeneration in Eisenia foetida (Annelida)]. Chapron C.

[Relations between the morphogenetic events of regeneration and the synthesis of ribonucleic acids and proteins. Study in Eisenia foetida (Oligochaeta)].

Mon, 08 Feb 1971 00:00:00 +0000

C R Acad Hebd Seances Acad Sci D. 1971 Feb 8;272(6):859-62. [Relations between the morphogenetic events of regeneration and the synthesis of ribonucleic acids and proteins. Study in Eisenia foetida (Oligochaeta)]. Chapron C.

[Histological and infrastructural study in the lombrician Eisenia foetida, of regression of the genital system during cephalic regeneration].

Wed, 01 Apr 1970 00:00:00 +0000

Arch Anat Microsc Morphol Exp. 1970 Apr-Jun;59(2):113-23. [Histological and infrastructural study in the lombrician Eisenia foetida, of regression of the genital system during cephalic regeneration]. Chapron C.

[Study in the oligochaetous Eisenia foetida of morphallaxis phenomena which are demonstrated in the previous digestive duct during cephalic regeneration].

Mon, 09 Mar 1970 00:00:00 +0000

C R Acad Hebd Seances Acad Sci D. 1970 Mar 9;270(10):1362-4. [Study in the oligochaetous Eisenia foetida of morphallaxis phenomena which are demonstrated in the previous digestive duct during cephalic regeneration]. Chapron C.

[Infrasturctural differentiation of the epidermis and the nervous system during cephalic regeneration of the lumbricid, Eisenia foetida unicolor].

Mon, 16 Feb 1970 00:00:00 +0000

C R Acad Hebd Seances Acad Sci D. 1970 Feb 16;270(7):973-6. [Infrasturctural differentiation of the epidermis and the nervous system during cephalic regeneration of the lumbricid, Eisenia foetida unicolor]. Chapron C.

[Structural analysis of the esophagus and pharynx of Eisenia foetida (Oligochaeta, Lumbricidae)].

Mon, 05 Jan 1970 00:00:00 +0000

C R Acad Hebd Seances Acad Sci D. 1970 Jan 5;270(1):112-5. [Structural analysis of the esophagus and pharynx of Eisenia foetida (Oligochaeta, Lumbricidae)]. Chapron C.