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Abstract STUDY QUESTION How should endometriosis be diagnosed and managed based on the best available evidence from published literature? SUMMARY ANSWER The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer. WHAT IS KNOWN ALREADY Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organized after finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE This guideline aims to help clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected. LIMITATIONS, REASONS FOR CAUTION The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payments. C.M.B. reports grants from Bayer Healthcare and the European Commission; Participation on a Data Safety Monitoring Board or Advisory Board with ObsEva (Data Safety Monitoring Group) and Myovant (Scientific Advisory Group). A.B. reports grants from FEMaLE executive board member and European Commission Horizon 2020 grant; consulting fees from Ethicon Endo Surgery, Medtronic; honoraria for lectures from Ethicon; and support for meeting attendance from Gedeon Richter; A.H. reports grants from MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring; Consulting fees from Roche Diagnostics, Nordic Pharma, Chugai and Benevolent Al Bio Limited all paid to the institution; a pending patent on Serum endometriosis biomarker; he is also Chair of TSC for STOP-OHSS and CERM trials. O.H. reports consulting fees and speaker’s fees from Gedeon Richter and Bayer AG; support for attending meetings from Gedeon-Richter, and leadership roles at the Finnish Society for Obstetrics and Gynecology and the Nordic federation of the societies of obstetrics and gynecology. L.K. reports consulting fees from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; honoraria for lectures from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; support for attending meetings from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; he also has a leadership role in the German Society of Gynecological Endocrinology (DGGEF). M.K. reports grants from French Foundation for Medical Research (FRM), Australian Ministry of Health, Medical Research Future Fund and French National Cancer Institute; support for meeting attendance from European Society for Gynaecological Endoscopy (ESGE), European Congress on Endometriosis (EEC) and ESHRE; She is an advisory Board Member, FEMaLe Project (Finding Endometriosis Using Machine Learning), Scientific Committee Chair for the French Foundation for Research on Endometriosis and Scientific Committee Chair for the ComPaRe-Endometriosis cohort. A.N. reports grants from Merck SA and Ferring; speaker fees from Merck SA and Ferring; support for meeting attendance from Merck SA; Participation on a Data Safety Monitoring Board or Advisory Board with Nordic Pharma and Merck SA; she also is a board member of medical advisory board, Endometriosis Society, the Netherlands (patients advocacy group) and an executive board member of the World Endometriosis Society. E.S. reports grants from National Institute for Health Research UK, Rosetrees Trust, Barts and the London Charity; Royalties from De Gruyter (book editor); consulting fees from Hologic; speakers fees from Hologic, Johnson & Johnson, Medtronic, Intuitive, Olympus and Karl Storz; Participation in the Medicines for Women’s Health Expert Advisory Group with Medicines and Healthcare Products Regulatory Agency (MHRA); he is also Ambassador for the World Endometriosis Society. C.T. reports grants from Merck SA; Consulting fees from Gedeon Richter, Nordic Pharma and Merck SA; speaker fees from Merck SA, all paid to the institution; and support for meeting attendance from Ferring, Gedeon Richter and Merck SA. The other authors have no conflicts of interest to declare. DISCLAIMER This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (Full disclaimer available at www.eshre.eu/guidelines.).

During the menopausal transition, which begins four to six years before cessation of menses, middle-aged women experience a progressive change in ovarian activity and a physiologic deterioration of hypothalamic-pituitary-ovarian axis function associated with fluctuating hormone levels. During this transition, women can suffer symptoms related to menopause (such as hot flushes, sleep disturbance, mood changes, memory complaints and vaginal dryness). Neurological symptoms such as sleep disturbance, “brain fog” and mood changes are a major complaint of women transitioning menopause, with a significant impact on their quality of life, productivity and physical health. In this paper, we consider the associations between menopausal stage and/or hormone levels and sleep problems, mood and reduced cognitive performance. The role of estrogen and menopause hormone therapy (MHT) in cognitive function, sleep and mood are also discussed.

Sexual and reproductive issues are essential elements of well-being in cisgenders as well as for the transgender population. Gender-affirming hormonal treatments (GAHTs) aim to induce phenotypical changes congruent with the desired gender and subsequent reduction of gender dysphoria. While genital surgical procedures including hysterectomy and/or adenectomy cause permanent loss of ability to conceive, GAHT may induce a varying degree of reversible loss of fertility. For these reasons, transgender men and women need to be counseled concerning contraceptive options and potential effects of treatment on reproductive function before initiating GAHT. The literature reports that sexual activity with genital involvement is performed by less than half of transgender persons who have been sexually active with a partner in the past. Testosterone (T) is the most commonly used compound in transmen and usually leads to amenorrhea within 1–12 months from first administration, however cessation of menses does not mean anovulation. Some studies report cases of unintended pregnancies among transgender men under masculinizing therapy, therefore T treatment cannot be considered a contraceptive option. Currently available contraceptive options have pros and cons in transmen and scarce literature exists on their use. The effects of GAHT on fertility in transwomen are even less well known. Prolonged estrogen exposure induces sperm suppression and morphological changes of the spermatozoa, however the degree of resulting pregnancy protection is unclear. Further research to inform the contraceptive counseling in this population is mandatory.

The aim of this review is to provide an overview of genitourinary health in peri- and postmenopause, particularly of vulvovaginal atrophy (VVA), which is part of genitourinary syndrome (GSM). This condition has a high prevalence among post-menopausal women and negatively affects a woman’s quality of life. Epidemiology, signs, symptoms, diagnostic criteria of VVA and target treatments for restoring vaginal health are discussed in light of the most recent literature. Issues related to this condition in menopausal women are under-diagnosed, lack objective diagnostic criteria, and consequently under-treated. Over the years, many treatments have been developed but their long-term effectiveness and safety have yet to be clearly defined. Patients are often dissatisfied and stop treatment, suggesting the need for a more personalized and tailored approach to achieve better compliance and thereby effectiveness. The aim of this paper is to provide an overview of the most recent literature on VVA in order to help the gynecologist in the management of this condition.

BackgroundIn the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP).ObjectiveTo define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis.MethodsElectronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05.ResultsSeven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026).ConclusionCTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

IntroductionSeveral studies have assessed the histological co-existence of endometrial carcinoma (EC) and adenomyosis. However, the significance of this association is still unclear.ObjectiveTo assess the prevalence of adenomyosis in women with EC for a better understanding of the association between the two diseases.Materials and methodsA systematic review and meta-analysis was performed by searching electronics databases from their inception to March 2020, for all studies that allowed extraction of data about prevalence of adenomyosis in EC patients. Adenomyosis prevalence was calculated for each included study and as pooled estimate, with 95% confidence interval (CI). ResultsEight retrospective cohort studies assessing 5573 EC patients were included in our analysis. Of total, 1322 were patients with adenomyosis, and 4251 were patients without adenomyosis. Pooled prevalence of adenomyosis in EC patients was 22.6% (95% CI 12.7–37.1%).ConclusionAdenomyosis prevalence in EC patients was not different from that reported for other gynecological conditions. The supposed association between the two diseases appears unsupported.

IntroductionSurgical repair of pelvic organ prolapse is one of the most frequent gynecological procedures, and its frequency is expected to increase as the population is gradually aging. Mesh use in urogynecological surgery should be limited because of important and life-treating complications. Sacral mesh-less and lateral procedures have been described as safe and effective to treat apical compartment prolapse. In this video, we describe a new laparoscopic mesh-less cervicopexy in women with symptomatic uterovaginal prolapse who did not desire uterine preservation.MethodsEleven women with symptomatic uterovaginal prolapse [stage 2 or higher according to the Pelvic Organ Prolapse Quantitative (POP-Q) classification system] underwent laparoscopic mesh-less cervicopexy to the sacrum and transverse fascia between May 2018 and June 2019. We performed application of the right uterosacral ligament starting from the sacrum and two semicontinous sutures including the transverse fascia, round ligament, prevescical peritoneum, pubocervical fascia and cervix that were subsequently knotted.ResultsAt 6-month follow-up, the objective success rate for apical prolapse (POP-Q score C > −1) was 90.9% (10/11 women). Only one woman presented stage 3 apical prolapse recurrence with vaginal buldge.ConclusionLaparoscopic mesh-less cervicopexy for uterovaginal prolapse seems to be a feasible surgical technique at 6-month follow-up.

Background Malignant epithelioid neoplasm with ACTB-GLI1 fusion are considered different from the more common pericytic lesions, such myopericytoma, because they have a spectrum of different genetic abnormalities. They appear to pursue a benign clinical course in young adults, although in sporadic cases lymph node metastasis were described. The categorization of this new type of tumor may also lead to new therapeutic strategies, because they might be sensitive to SHH pathway inhibitors. Case presentation The case involves a 72-years-old multiparous woman who accessed our department after an incidental finding of a right adnexal mass of 43 mm with contrast-enhancement on a control computed tomography scan made for suspected diverticulitis. Our intervention was a detailed ultrasound description of the suspected neoplasm; a diagnostic laparoscopy and the contextual laparotomic removal of abdominal mass; its histological and immunohistochemical analysis. Our main outcome measure is the definition and future recognition of new pathologic entity called malignant epithelioid neoplasm with ACTB-GLI1 fusion. Conclusions We described for the first time the ultrasound characteristic of this type of lesion using standardized terminology and we believe that it may be the first step to improve the acknowledgement of this novel pathologic entity defined as malignant epithelioid neoplasm with GLI-1 fusions.

This feasibility study explores the potential of salivary microRNAs (miRNAs) as non-invasive biomarkers for diagnosing endometriosis and assessing treatment response. Almost one-third of patients with endometriosis do not respond to the standard progestin treatment due to various mechanisms of progesterone resistance. MiRNAs, recognized for their stability in body fluids and role in gene regulation, may offer new diagnostic and prognostic opportunities as they are involved in the pathogenic pathways of endometriosis and progesterone resistance. We sequenced salivary miRNAs in three cohorts of patients: control women without endometriosis and patients with endometriosis who responded and did not respond to standard progestin treatment. This aims to identify the differential miRNA expression profiles associated with therapeutic response to dienogest. The preliminary results demonstrate the feasibility of miRNA sequencing from saliva and reveal distinct miRNA profiles between responders, non-responders, and controls. Key miRNAs, including mir-3168, the mir-200a family, and mir-93-5p, emerged as potential biomarkers, showing significant differential expression linked to both endometriosis presence and treatment response. Further validation of these findings in larger cohorts could pave the way for miRNA-based diagnostic and prognostic tools, potentially reducing diagnostic delays and personalizing treatment approaches for endometriosis patients, also with new target therapies.

Introduction Long-acting reversible contraceptives (LARCs) are increasingly gaining popularity due to their high efficacy and ease of use compared to short-acting reversible contraceptives (SARCs). Among available LARCs, the etonogestrel (ENG) subdermal implant represents a particularly effective contraceptive method. However, many patients request early removal of the device due to the persistence of unfavourable bleeding patterns. Methods We developed a short, multiple-choice ad hoc questionnaire distributed online from October 2024 to March 2025 to investigate the attitude of Italian gynaecologists towards medical treatment of unfavourable bleeding in women using the ENG-releasing implant. A total of 141 physicians responded reporting their first- and second-line treatments for patients with and without a contraindication to combined oral contraceptives (COC). We discuss the results of our survey in the light of the existing literature, through a systematic review including studies evaluating medical treatments in ENG implant users experiencing troublesome bleeding. Results and conclusion The results of our survey and the review of the literature highlight the diverse, sparse, and sometimes confused approaches to unfavourable bleeding in ENG implant users. In our survey, up to 19% of practitioners indicated they would not know what to do in different case scenarios. In order to help gynaecologists gain greater confidence in managing this symptom, large randomised controlled trials (RCTs) with long-term follow-up on which clinical guidelines and standardized training programs can be based, are needed.