Publications

Authors' Reply.

Clinical signs and diagnosis of fibroids from adolescence to menopause.

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

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.

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.

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.

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

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.

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.

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.

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

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.