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Chronic pelvic pain (CPP), despite its high prevalence, is still relatively poorly understood mechanistically. This study, as part of the Translational Research in Pelvic Pain (TRiPP) project, has used a full quantitative sensory testing (QST) paradigm to profile n = 85 women with and without CPP (endometriosis or bladder pain specifically). We used the foot as a control site and abdomen as the test site. Across 5 diagnostically determined subgroups, we found features which are common across different aetiologies, eg, gain of function in pressure pain threshold (PPT) when assessing responses from the lower abdomen or pelvis (referred pain site). However, disease-specific phenotypes were also identified, eg, greater mechanical allodynia in endometriosis, despite there being large heterogeneities within diagnostic groups. The most common QST sensory phenotype was mechanical hyperalgesia (>50% across all the groups). A "healthy' sensory phenotype was seen in

STUDY QUESTION: Which classification system for endometriosis do clinicians use most frequently, and why? SUMMARY ANSWER: Even with a high uptake of the three existing endometriosis classification systems, most clinicians managing endometriosis would like a new simple surgical descriptive system for endometriosis. WHAT IS KNOWN ALREADY: In the field of endometriosis, several classifications, staging and reporting systems have been developed and published, but there are no data on the uptake of these systems in clinical practice. STUDY DESIGN SIZE DURATION: A survey was designed using the online SurveyMonkey tool consisting of 11 questions concerning three domains-participants background, existing classification systems and intentions with regards to a new classification system for endometriosis. Replies were collected between 15 May and 1 July 2020. PARTICIPANTS/MATERIALS SETTING METHODS: A cross-sectional study was performed to gather data on the current use of endometriosis classification systems, problems encountered and interest in a new simple surgical descriptive system for endometriosis. The particular focus was on the three systems most commonly used: the Revised American Society for Reproductive Medicine (rASRM) classification, the endometriosis fertility index (EFI), and the ENZIAN classification. Data were analysed to detect statistically significant differences among user groups. MAIN RESULTS AND THE ROLE OF CHANCE: The final dataset included the replies of 1178 clinicians, including surgeons, gynaecologists, reproductive endocrinologists, fertility specialists and sonographers, all managing women with endometriosis in their clinical practice. Overall, 75.5% of the professionals indicate that they currently use a classification system for endometriosis. The rASRM classification system was the best known and used system, while the EFI system and ENZIAN system were known by a majority of the professionals but used by only a minority. The lack of clinical relevance was most often selected as a problem with using any system. The vast majority of respondents replied positively to the question on whether they would use a simple surgical descriptive system available for endometriosis, if available. LIMITATIONS REASONS FOR CAUTION: While the total number of respondents was acceptable, some regions/professions were not sufficiently represented to draw conclusions. WIDER IMPLICATIONS OF THE FINDINGS: The findings of the survey suggest that clinicians worldwide are open to using a new classification system for endometriosis that can achieve standardized reporting and is clinically relevant and simple. The findings therefore support future initiatives for the development of a new descriptive system for endometriosis and provide information on user expectations and conditions for universal uptake of such a system. STUDY FUNDING/COMPETING INTERESTS: The meetings and activities of the working group were funded by the American Association of Gynecologic Laparoscopists, European Society for Gynecological Endoscopy, ESHRE and World Endometriosis Society. A.W.H. reports grant funding from the MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring, Charles Wolfson Charitable Trust, Standard Life, and consultancy fees from Roche Diagnostics, AbbVie, Nordic Pharma and Ferring, outside the submitted work. In addition, A.W.H. has a patent Serum biomarker for endometriosis pending. He is Chair of TSC for STOP-OHSS and CERM trials and Chair of RCOG Academic Board 2018-2021. M.A. reports being member of the executive board and vice president of AAGL. N.P.J. reports personal fees from Abbott, Guerbet, Myovant Sciences, Vifor Pharma, Roche Diagnostics outside the submitted work; he is also President of the World Endometriosis Society and chair of the trust board. S.M. reports grants from AbbVie, DoD, NIH and Marriot Family Foundation, honoraria from University British Columbia and WERF, support for speaking at conferences (ESHRE, CanSAGE, Endometriosis UK, UEARS, IFFS, IASP, National Endometriosis Network UK) participation on Advisory Boards from AbbVie and Roche, outside the submitted work. She also discloses having a leadership or fiduciary role in SWHR, WERF, WES, ASRM and ESHRE. C.T. reports grants, consulting and speakers' fees non-financial support and other from Merck SA, non-financial support and other consulting fees from Gedeon Richter and Nordic Pharma, and support for meeting attendance non-financial support from Ferring Pharmaceuticals, outside the submitted work and without private revenue. K.T.Z. reports grants from Bayer Healthcare, MDNA Life Sciences, Volition Rx, and Evotec (Lab282-Partnership programme with Oxford University), non-financial support from AbbVie Ltd, all outside the submitted work; and is a Board member (Secretary) of the World Endometriosis Society and World Endometriosis Research Foundation. J.P. reports personal fees from Hologic, Inc., outside the submitted work; he is also a member of the executive boards of ASRM and SRS. The other authors had nothing to disclose. ispartof: HUMAN REPRODUCTION OPEN vol:2022 issue:1 ispartof: location:England status: published

Endometriosis is a chronic pain condition affecting 1 in 10 women. There is an unmet need for better medical treatments for endometriosis. We spotlight trials of a single preparation combined HRT-GnRH antagonist (Relugolix) by Giudice et al.

Stacey A Missmer,1 Frank F Tu,2 Sanjay K Agarwal,3 Charles Chapron,4 Ahmed M Soliman,5 Stephanie Chiuve,5 Samantha Eichner,5 Idhaliz Flores-Caldera,6 Andrew W Horne,7 Alexandra B Kimball,8 Marc R Laufer,9 Nicholas Leyland,10 Sukhbir S Singh,11 Hugh S Taylor,12 Sawsan As-Sanie13 1Department of Obstetrics, Gynecology, and Reproductive Biology, Michigan State University, Grand Rapids, MI, USA; 2Department of Obstetrics and Gynecology, NorthShore University Health System, Evanston, IL, USA; 3Department of Reproductive Medicine, Center for Endometriosis Research and Treatment, University of California San Diego, La Jolla, CA, USA; 4Department of Gynecology Obstetrics II and Reproductive Medicine, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique – Hôpitaux de Paris, Hôpital Universitaire Paris Centre, Centre Hospitalier Universitaire Cochin, Paris, France; 5AbbVie, Inc., North Chicago, IL, USA; 6Department of Obstetrics and Gynecology, Ponce Health Sciences University – Ponce Research Institute, School of Medicine, Ponce, Puerto Rico; 7Department of Gynaecology and Reproductive Sciences, MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK; 8Harvard Medical Faculty Physicians, Beth Israel Deaconess Medical Center, Boston, MA, USA; 9Department of Obstetrics, Gynecology, and Reproductive Biology, Boston Center for Endometriosis and Boston Children’s Hospital and Brigham and Women’s Hospital, Boston, MA, USA; 10Department of Obstetrics and Gynaecology, McMaster University, Hamilton, Ontario, Canada; 11Department of Obstetrics and Gynaecology, University of Ottawa, and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; 12Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA; 13Department of Obstetrics and Gynecology, University of Michigan Health System, Ann Arbor, MI, USACorrespondence: Stacey A MissmerCollege of Human Medicine, Michigan State University, 15 Michigan Street Northeast, Grand Rapids, MI 49503, USATel +1 616 234 2705Email missmers@msu.eduAbstract: Endometriosis may exert a profound negative influence on the lives of individuals with the disorder, adversely affecting quality of life, participation in daily and social activities, physical and sexual functioning, relationships, educational and work productivity, mental health, and well-being. Over the course of a lifetime, these daily challenges may translate into limitations in achieving life goals such as pursuing or completing educational opportunities; making career choices or advancing in a chosen career; forming stable, fulfilling relationships; or starting a family, all of which ultimately alter one’s life trajectory. The potential for endometriosis to impact the life course is considerable, as symptom onset generally occurs at a time of life (menarche through menopause, adolescence through middle age) when multiple life-changing and trajectory-defining decisions are made. Using a life-course approach, we examine how the known effects of endometriosis on life-domain satisfaction may impact health and well-being across the life course of affected individuals. We provide a quasi-systematic, narrative review of the literature as well as expert opinion on recommendations for clinical management and future research directions.Keywords: endometriosis, health trajectory, life-course impairment

Introduction First-trimester miscarriages are commonly associated with chromosomal abnormality of the embryo (approximately 50% of cases).1 However, 15% of first-trimester and 66% of second-trimester miscarriages are attributed to reproductive tract infections.2 It has been suggested that Chlamydia trachomatis is a causative organism, but its association with miscarriage is inconsistently reported.2-4 This difference of opinion likely reflects the poor performance of major outer membrane protein (MOMP) peptide-based serology assays and the inability of nucleic acid amplification tests (which detect current infection) to detect previous exposure.5 It is now possible to accurately measure lifetime exposure to C trachomatis using an enzyme-linked immunosorbent assay (ELISA) that detects antibodies to the chlamydial plasmid-encoded protein Pgp3.5 This ELISA is more sensitive (73.8%) and specific (97.6%) than commercial ELISAs, including the Medac MOMP-peptide ELISA, or previous serological antibody tests.5 Pgp3 is unique to C trachomatis, eliminating cross-reactivity with antibodies to C pneumoniae infection (a common respiratory pathogen), a major weakness of previous serological tests. The aim of this study was to provide an estimation of the association of previous C trachomatis infection with the risk of spontaneous first-trimester miscarriage. Methods We performed a case-control study, recruiting women with ultrasonography confirming absence of a fetal heart in the first trimester of pregnancy (miscarriage group) and women with normal pregnancies that had progressed into the third trimester (control group) from the same catchment population. Women with a past history of miscarriage were excluded from the control group. Participants were identified from the Pregnancy Support Unit and Delivery Suite at the Royal Infirmary of Edinburgh (a large UK National Health Service teaching hospital). The first study participant was recruited on January 22, 2013, and the last participant was recruited on September 26, 2019. The Scotland A Research Ethics Committee approved this study, and written informed consent was obtained from all participants. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. We anticipated a C trachomatis seroprevalence of 15% in women with miscarriage and 7% in the control group on the basis of literature review3 and pilot work. Our proposed sample size (200 cases and 100 controls) had greater than 95% power, with a level of significance (α) of .05 to estimate a doubling of the C trachomatis–population attributable risk for miscarriage. We collected serum samples and self-taken vulvovaginal swabs taken from 2 to 3 inches within the vagina for C trachomatis nucleic acid amplification testing to detect current infection. Statistical analyses were conducted using GraphPad Prism, version 8.0 (GraphPad). Analysis was by 2-tailed Fisher exact test, and P < .05 indicated significance. Results A total of 251 women (median [95% CI] age, 33 [32-35] years) were included in the miscarriage group, and 118 were included in the control group (median [95% CI] age, 34 [32-35] years). The groups were well balanced for all characteristics measured at baseline (Table). A total of 65 women (25.9%; 95% CI, 20.6%-31.4%) in the miscarriage group and 33 women (28.0%; 95% CI, 19.9%-36.1%) in the control group had positive test results for Pgp3 antibodies, suggesting previous infection with C trachomatis (P = .71). There was no evidence of active C trachomatis infection in either group. More women in the miscarriage group (n = 34 [13.5%; 95% CI, 11.3%-15.7%]) than the control group (n = 2 [1.7%; 95% CI, 0.5%-2.9%]) self-reported past C trachomatis infection (P

Macrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Endometriosis triggers continuous recruitment of monocytes that contribute to LpM and small peritoneal macrophage (SpM) pools. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions. Constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increases the number of lesions. We propose a putative model whereby endometrial macrophages and embryo-derived LpM are ‘pro-endometriosis’, whilst monocyte-derived LpM are ‘anti-endometriosis’. These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.