Publications

[Chronic inflammatory rheumatic diseases and female fertility].

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.

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.

The endocrine aspects of endometriosis.

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.

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

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.

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.

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

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.

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.

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.