Publications

Adenomyosis: the missed disease.

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.

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

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.

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).

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

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.

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

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

Microbiome and gynecologic disease

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

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.