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Endometriosis is a common finding among women with infertility, and women who are diagnosed with endometriosis are almost twice as likely to experience infertility. Mechanisms by which endometriosis causes infertility remain poorly understood. In this review, we evaluate the current literature on the impact of endometriosis on oocyte and embryo quality. The presence of endometriosis evidently reduces ovarian reserve, oocyte quality, and embryo quality; however, this does not appear to translate to a clear clinical impact. Analysis of data from large assisted reproduction technology registries has shown that women with endometriosis have a lower oocyte yield but no reduction in reproductive outcomes. There is a need for future studies in the form of well-designed randomized controlled trials to further evaluate the role of surgical and medical treatment options in women with endometriosis undergoing assisted conception.

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.).

In vitro fertilization (IVF) is an established option for the management of infertility in patients with endometriosis, though there remains ongoing debate around the extent to which endometriosis may compromise IVF treatment success, in which fertilization and preimplantation embryo development occur outside the pelvis. Whether endometriosis impacts oocyte and embryo quality and/or endometrial receptivity remains central to this debate. Here, we review the current literature relating to the impact of endometriosis on IVF outcomes and management strategies to consider when performing IVF treatment.

Introduction Ultrasound assessment of superficial endometriosis (SE) is difficult, and it is still mainly diagnosed via surgery. We hypothesized that a thickening of the subperitoneal layer of tissue overlying the anterior pouch of Douglas (POD), labeled the “White line sign” (WLS), could indicate the presence of SE. The aim of the study was to investigate the association between the WLS and the finding of endometriosis at histology. Material and Methods This prospective diagnostic accuracy study included 100 premenopausal women with chronic pelvic pain who underwent transvaginal ultrasound (TVS) by a single expert operator and subsequent laparoscopy by a specialist surgeon between January 2021 and January 2023. To assess intra‐ and inter‐observer reproducibility of the WLS, 36 consecutive ultrasound scans were recorded and re‐evaluated 6 months later by the first operator and an independent, second operator, both blinded to the original and each other's findings. Outcomes of interest were the diagnostic accuracy of the WLS for predicting the presence of SE and deep endometriosis (DE) at histopathology, and the reproducibility of the WLS at TVS. The former was assessed by calculating specificity, sensitivity, and accuracy, and the latter by determining proportions of agreement and Cohen's kappa coefficient (κ), respectively. Results The WLS had high specificity [100% (95% CI, 2.5–100%)], but low sensitivity and accuracy for the detection of SE [30.6% (95% CI, 20.2–42.5%) and 31.5% (95% CI, 21.1–43.4%)], respectively. The WLS was highly sensitive, specific, and accurate for the identification of DE [79.7% (95% CI, 67.8–88.7%), 100% (95% CI, 66.4–100%), and 82.2% (95% CI, 71.5–90.2%)], respectively. The WLS was reproducible, demonstrated by good inter‐ and intra‐rater agreement and reliability for its diagnosis on TVS [proportions of agreement 0.86 (95% CI, 0.69–0.95) and 0.83 (95% CI, 0.66–0.93), κ 0.72 (95% CI 0.49–0.94) and 0.64 (95% CI, 0.38–0.89)], respectively. Conclusions Our study demonstrated that the WLS could be a valuable soft marker of both SE and DE. This is particularly useful in cases where no other or only subtle signs of endometriosis are present on scan. The “White line sign” represents thickening of the subperitoneal tissue overlying the anterior pouch of Douglas on transvaginal ultrasound. It demonstrated high specificity for detecting superficial endometriosis and high specificity, sensitivity, and accuracy for deep endometriosis. It was also reproducible and could be a useful soft ultrasound marker of endometriosis.

IntroductionBowel symptoms often accompany pelvic pain in patients with endometriosis and adenomyosis, however the pathophysiology of these symptoms is unclear. The aim of this study is to determine the nature of gut physiological dysfunction in patients with endometriosis and compare this to patients with no abnormality and presumed functional causes for their symptoms.MethodsPatients were recruited at the point of referral to our tertiary endometriosis centre for pelvic pain. Inclusion criteria: aged 18–50 years, the presence of bowel symptoms, and no known bowel disease. Participants completed symptom questionnaires (0–10 numeric rating scale, IBS-SSS, PACSYM, HADS, VSI) and underwent a bowel transit (Sitz marker) test, high resolution anorectal manometry (HRAM) with electrosensation, and MRI proctogram. They also underwent an abdomino-pelvic MRI scan to detect endometriosis lesions and other pathology. Patients with and without pathology on MRI were compared using Fischer’s and Mann-Whitney-U tests.ResultsA total of 101 patients were recruited, of whom 95 underwent a bowel transit study, 74 underwent HRAM, and 82 underwent MRI. Mean age was 32.5 years (SD:7.2) and BMI was 26.8 (SD:7.9). Their distribution of endometriosis is shown in figure 1.Patients with endometriosis or adenomyosis on MRI had a particular symptom phenotype:Worse chronic dyschaezia (mean 3.8 vs 2.3, p=0.026)Less fluctuation in nausea with the menstrual cycle (1.0/10 vs 2.9/10, p=0.016).In terms of physiology, patients with endometriosis or adenomyosis on MRI:were more likely to have slow bowel transit than those without (38.3% vs 15.6%, p=0.043)constipation scores correlated with bowel transit time (rho=0.316, p=0.031)had lower rates of defaecatory dyssynergia (22.5% vs 54.5%, p=0.023)often had rectal hypersensitivity to distension, but at a similar prevalence to those without disease on MRI (36.6% vs 26.9%, p=0.439)In particular, patients with deep rectovaginal endometriosis had significantly lower threshold to electrical stimulation compared to those with no disease (12.9 vs 20.2 milliAmps, p=0.017).ConclusionsDifferent pathophysiological mechanisms underlie bowel symptoms in patients with adenomyosis or endometriosis on MRI disease compared to those with presumed functional origins of their symptoms – in particular the former seem to have slow gut transit with a hypersensate rectum and non-dyssynergic evacuation. This suggests that abdomino-pelvic MRI should be used to quantify endometriosis burden in female patients with pain and bowel symptoms, as this has implications for the management of patients with proven endometriosis.Abstract P381 Figure 1Subgroups in study population.

AbstractObjectivesTo evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain.DesignThe PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial.Setting34 UK hospitals.Participants405 women of reproductive age undergoing conservative surgery for endometriosis.InterventionsParticipants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill.Main outcome measuresThe primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment).Results405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference −0.8, 95% confidence interval −5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00).ConclusionsPostoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some.Trial registrationISRCTN registry ISRCTN97865475.

STUDY QUESTIONHow should surgery for endometriosis be performed?SUMMARY ANSWERThis document provides recommendations covering technical aspects of different methods of surgery for deep endometriosis in women of reproductive age.WHAT IS KNOWN ALREADYEndometriosis is highly prevalent and often associated with severe symptoms. Yet compared to equally prevalent conditions, it is poorly understood and a challenge to manage. Previously published guidelines have provided recommendations for (surgical) treatment of deep endometriosis, based on the best available evidence, but without technical information and details on how to best perform such treatment in order to be effective and safe.STUDY DESIGN, SIZE, DURATIONA working group of the European Society for Gynaecological Endoscopy (ESGE), ESHRE and the World Endometriosis Society (WES) collaborated on writing recommendations on the practical aspects of surgery for treatment of deep endometriosis.PARTICIPANTS/MATERIALS, SETTING, METHODSThis document focused on surgery for deep endometriosis and is complementary to a previous document in this series focusing on endometrioma surgery.MAIN RESULTS AND THE ROLE OF CHANCEThe document presents general recommendations for surgery for deep endometriosis, starting from preoperative assessments and first steps of surgery. Different approaches for surgical treatment are discussed and are respective of location and extent of disease; uterosacral ligaments and rectovaginal septum with or without involvement of the rectum, urinary tract or extrapelvic endometriosis. In addition, recommendations are provided on the treatment of frozen pelvis and on hysterectomy as a treatment for deep endometriosis.LIMITATIONS, REASONS FOR CAUTIONOwing to the limited evidence available, recommendations are mostly based on clinical expertise. Where available, references of relevant studies were added.WIDER IMPLICATIONS OF THE FINDINGSThese recommendations complement previous guidelines on management of endometriosis and the recommendations for surgical treatment of ovarian endometrioma.STUDY FUNDING/COMPETING INTEREST(S)The meetings of the working group were funded by ESGE, ESHRE and WES. Dr Roman reports personal fees from ETHICON, PLASMASURGICAL, OLYMPUS and NORDIC PHARMA, outside the submitted work; Dr Becker reports grants from Bayer AG, Volition Rx, MDNA Life Sciences and Roche Diagnostics Inc. and other relationships or activities from AbbVie Inc., and Myriad Inc, during the conduct of the study; Dr Tomassetti reports non-financial support from ESHRE, during the conduct of the study; and non-financial support and other were from Lumenis, Gedeon-Richter, Ferring Pharmaceuticals and Merck SA, outside the submitted work. The other authors had nothing to disclose.TRIAL REGISTRATION NUMBERna

BackgroundAcceptance of the role of the fallopian tube in ‘ovarian’ carcinogenesis and the detrimental sequelae of surgical menopause in premenopausal women following risk-reducing salpingo-oophorectomy (RRSO) has resulted in risk-reducing early-salpingectomy with delayed oophorectomy (RRESDO) being proposed as an attractive alternative risk-reducing strategy in women who decline/delay oophorectomy. We present the results of a qualitative study evaluating the decision-making process among BRCA carriers considering prophylactic surgeries (RRSO/RRESDO) as part of the multicentre PROTECTOR trial (ISRCTN:25173360).MethodsIn-depth semistructured 1:1 interviews conducted using a predeveloped topic-guide (development informed by literature review and expert consultation) until informational saturation reached. Wording and sequencing of questions were left open with probes used to elicit additional information. All interviews were audio-recorded, transcribed verbatim, transcripts analysed using an inductive theoretical framework and data managed using NVIVO-v12.ResultsInformational saturation was reached following 24 interviews. Seven interconnected themes integral to surgical decision making were identified: fertility/menopause/cancer risk reduction/surgical choices/surgical complications/sequence of ovarian-and-breast prophylactic surgeries/support/satisfaction. Women for whom maximising ovarian cancer risk reduction was relatively more important than early menopause/quality-of-life preferred RRSO, whereas those more concerned about detrimental impact of menopause chose RRESDO. Women managed in specialist familial cancer clinic settings compared with non-specialist settings felt they received better quality care, improved hormone replacement therapy access and were more satisfied.ConclusionMultiple contextual factors (medical, physical, psychological, social) influence timing of risk-reducing surgeries. RRESDO offers women delaying/declining premenopausal oophorectomy, particularly those concerned about menopausal effects, a degree of ovarian cancer risk reduction while avoiding early menopause. Care of high-risk women should be centralised to centres with specialist familial gynaecological cancer risk management services to provide a better-quality, streamlined, holistic multidisciplinary approach.

BackgroundRisk-reducing salpingo-oophorectomy is the 'gold standard' for preventing tubo-ovarian cancer in women at increased risk. However, when performed in pre-menopausal women, it results in premature menopause and associated detrimental health consequences. This, together with acceptance of the central role of the fallopian tube in etiopathogenesis of high-grade serous carcinoma, by far the most common type of tubo-ovarian cancer, has led to risk-reducing early salpingectomy with delayed oophorectomy being proposed as a two-step surgical alternative for pre-menopausal women declining/delaying oophorectomy.Primary ObjectiveTo evaluate the impact on sexual function of risk-reducing early salpingectomy, within a two-step, risk-reducing, early salpingectomy with delayed oophorectomy tubo-ovarian cancer prevention strategy in pre-menopausal women at increased risk of tubo-ovarian cancer.Study HypothesisRisk-reducing early salpingectomy is non-inferior for sexual and endocrine function compared with controls; risk-reducing early salpingectomy is superior for sexual/endocrine function, non-inferior for quality-of-life, and equivalent in satisfaction to the standard risk-reducing salpingo-oophorectomy.Trial DesignMulti-center, observational cohort trial with three arms: risk-reducing early salpingectomy with delayed oophorectomy; risk-reducing salpingo-oophorectomy; controls (no surgery). Consenting individuals undergo an ultrasound, serum CA125, and follicle-stimulating hormone measurements and provide information on medical history, family history, quality-of-life, sexual function, cancer worry, psychological well-being, and satisfaction/regret. Follow-up by questionnaire takes place annually for 3 years. Women receiving risk-reducing early salpingectomy can undergo delayed oophorectomy at a later date of their choosing, or definitely by the menopause.Major Inclusion/Exclusion CriteriaInclusion criteria: pre-menopausal; aged >30 years; at increased risk of tubo-ovarian cancer (mutation carriers or on the basis of a strong family history); completed their family (for surgical arms). Exclusion criteria: post-menopausal; previous bilateral salpingectomy or bilateral oophorectomy; pregnancy; previous tubal/ovarian/peritoneal malignancy; <12 months after cancer treatment; clinical suspicion of tubal/ovarian cancer at baseline.Primary EndpointSexual function measured by validated questionnaires.Sample Size1000 (333 per arm).Estimated Dates for Completing Accrual and Presenting ResultsIt is estimated recruitment will be completed by 2023 and results published by 2027.Trial Registration NumberISRCTN registry: 25 173 360 (https://doi.org/10.1186/ISRCTN25173360).

Uterocutaneous fistula is an extremely rare clinical condition that may be caused by postoperative or postpartum complications, such as infection or inflammation. Although fibroids and myomectomy are common clinical entities among women of reproductive age, there are very few postmyomectomy uterocutaneous fistula cases in the literature. This article presents the first reported case of a succesful pregnancy and live birth following treatment of a postmyomectomy uterocutaneous fistula. After laparoscopic adhesiolysis, a minilaparotomy was performed to excise the fistula tract completely from both the abdominal wall and the uterus. The uterine wall defect was repaired in multiple layers. The patient had a good recovery after surgery, and the uterocutaneous fistula resolved completely. Due to obliteration of both tubal ostia, the patient was referred for in vitro fertilisation treatment. She conceived after the third frozen embryo transfer procedure and gave birth to a 4.4 kg baby at full term by caesarean section.