World Endometriosis Research Foundation Research Articles

World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: V. Physical examination standards in endometriosis research

The World Endometriosis Research Foundation (WERF) established the Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) to create standardized documentation tools (with common data elements) to facilitate the comparison and combination of data across different research sites and studies. In 2014, four data research standards were published: clinician-reported surgical data, patient-reported clinical data, and fluid and tissue biospecimen collection. Our current objective is to create an EPHect standard for the clinician-reported physical examination (EPHect-PE) for research studies. An international consortium involving 26 clinical and academic experts and patient partners from 11 countries representing 25 institutions and organizations. Two virtual workshops, followed by the development of the physical examination standards that underwent multiple rounds of iterations and revisions. N/A MAIN OUTCOME MEASURE(S): N/A RESULT(S): The EPHect physical examination (EPHect-PE) tool provides standardised assessment of physical examination characteristics and pain phenotyping. Data elements involve examination of a) back and pelvic girdle; b) abdomen including allodynia and trigger points; c) vulva including provoked vestibulodynia; d) pelvic floor muscle tone and tenderness; e) tenderness on unidigital pelvic exam; f) presence of pelvic nodularity; g) uterine size and mobility; h) presence of adnexal masses; i) presence of incisional masses; j) speculum examination; k) tenderness and allodynia at an extra-pelvic site (e.g. forearm); and l) recording of anthropometrics. The EPHect physical examination standards (EPHect-PE) will facilitate the standardised documentation of the physical examination, including the assessment and documentation of examination phenotyping of endometriosis-associated pelvic pain.

Plasma proteins and persistent post-surgical pelvic pain among adolescents and young adults with endometriosis

Non-invasive biomarkers that predict surgical treatment response would inform personalized treatments and provide insight into potential biological pathways underlying endometriosis-associated pain and symptom progression. Thus, we evaluated plasma proteins in relation to persistence of pelvic pain following laparoscopic surgery in predominantly adolescents and young adults with endometriosis using a multiplex aptamer-based proteomics biomarker discovery platform. We conducted a prospective analysis including 142 participants with laparoscopically- confirmed endometriosis from the Women's Health Study: From Adolescence to Adulthood (A2A) observational longitudinal cohort with study enrollment from 2012-2018. Biologic samples and patient data were collected with modified World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (EPHect) tools. In blood collected before laparoscopic ablation or excision of endometriosis, we simultaneously measured 1,305 plasma protein levels including markers for immunity, angiogenesis and inflammation using SomaScan. Worsening or persistent post-surgical pelvic pain was defined as having newly developed, persistent (i.e., stable), or worsening severity, frequency, or persistent life-interference of dysmenorrhea or acyclic pelvic pain at one-year post-surgery compared to pre-surgery. We calculated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression adjusted for age, body mass index, and fasting status and hormone use at blood draw. We applied Ingenuity Pathway Analysis and STRING analysis to identify pathophysiologic pathways and protein interactions. Median age at blood draw was 17 years (interquartile range 15-19), and most participants were white race (90%). All had superficial peritoneal lesions only and were treated by excision or ablation. One-year post-surgery, pelvic pain worsened or persisted for 76 (54%) of these participants with endometriosis, while pelvic pain improved for 66 (46%). We identified 83 proteins associated with worsening or persistent pelvic pain one-year post-surgery (nominal p<0.05). Compared to those with improved pelvic pain one year post-surgery, those with worsening or persistent pelvic pain had higher plasma levels of CD63 antigen (OR=2.98, 95% CI:1.44-6.19) and CD47 (OR=2.68, 95%CI=1.28-5.61), but lower levels of Sonic Hedgehog protein (SHH; OR=0.55, 95%CI=0.36-0.84) in pre-surgical blood. Pathways related to cell migration were upregulated and pathways related to angiogenesis were downregulated in those with worsening/persistent post-surgical pelvic pain compared to those with improved pain. When we examined change in proteins levels from pre- to post-surgery and its subsequent risk of worsening/persistent post-surgical pain at one-year follow-up, we observed increasing levels of SHH from pre- to post-surgery was associated with four-fold increase in risk of post-surgical pain (OR quartile 4 vs. 1=3.86, 1.04-14.33). Using an aptamer-based proteomics platform, we identified plasma proteins and pathways associated with worsening or persistent pelvic pain post-surgical treatment of endometriosis among adolescents and young adults that may aid in risk stratification of individuals with endometriosis.

Visualized peritoneal fluid variation in adolescents and young adults with endometriosis: is there more to it?

Peritoneal fluid is a medium for endometriosis-associated biomarker discovery from which the local peritoneal environment and pathophysiologic pathways are often inferred. Therefore, we evaluated the associations between peritoneal fluid color and volume at time of endometriosis-related laparoscopic surgery with patient characteristics, endometriosis type and lesion location in adolescents and young adults with endometriosis. We conducted a cross-sectional analysis among 545 patients undergoing surgery for endometriosis who enrolled in the Women's Health Study: from Adolescence to Adulthood cohort study. Patient characteristics, surgically visualized endometriosis phenotypes, and gross characteristics of peritoneal fluid were collected in compliance with World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (EPHect) tools. Chi-square or Fisher's exact tests were applied to test for differences across categories. Most of the patients were adolescents or young adults (86% age <25 years) of white race (89%), with only superficial peritoneal lesions and rASRM stage = I/II observed at surgery (both 95%). We observed variation in peritoneal fluid color across different menstrual cycle phases at time of surgery (p = 0.006). Among those who were cycling at time of surgery, endometriosis patients with red peritoneal fluid were most likely to be in the proliferative phase (49%) compared to the secretory phase (27%), while those with yellow or orange peritoneal fluid were most likely to be in the secretory phase (57% and 86% respectively). Yellow color was significantly less common in those taking combined oral contraceptives but much more common with progesterone only formulation exposure (p = 0.002). Peritoneal fluid volume did not differ by cycle phase but was more likely to be low (≤6 ml) for those exposed to hormones at time of surgery (p = 0.01). Those with acyclic pelvic pain were less likely to have red peritoneal fluid (p = 0.001) but had greater volume (p = 0.02) compared to those without. Our findings highlight the importance of accounting for menstrual cycle phase and hormonal exposures when designing research using peritoneal fluid samples and inferring from biomarker results intended to advance our understanding of endometriosis and associated symptom pathophysiology.

Gender inequality and utilization of ART: an international cross-sectional and longitudinal analysis.

What is the association between a country's level of gender equality and access to ART, as measured through ART utilization? ART utilization is associated with a country's level of gender equality even after controlling for the level of development. Although gender equality is recognized as an important determinant of population health, its association with fertility care, a highly gendered condition, has not been explored. A longitudinal cross-national analysis of ART utilization in 69 countries during 2002-2014 was carried out. The Gender Inequality Index (GII), Human Development Index (HDI), and their component indicators were modelled against ART utilization using univariate regression models as well as mixed-effects regression methods (adjusted for country, time, and economic/human development) with multiple imputation to account for missing data. ART utilization is associated with the GII. In an HDI-adjusted analysis, a one standard deviation decrease in the GII (towards greater equality) is associated with a 59% increase in ART utilization. Gross national income per capita, the maternal mortality ratio, and female parliamentary representation were the index components most predictive of ART utilization. Only ART was used rather than all infertility treatments (including less costly and non-invasive treatments such as ovulation induction). This was a country-level analysis and the results cannot be generalized to smaller groups. Not all modelled variables were available for each country across 2002-2014. Access to fertility care is central to women's sexual and reproductive health, to women's rights, and to human rights. As gender equality improves, so does access to ART. This relation is likely to be reinforcing and bi-directional, with progress towards global, equitable access to fertility care also improving women's status and participation in societies. External funding was not provided for this study. G.D.A. declares consulting fees from Labcorp and CooperSurgical. G.D.A. is the founder and CEO of Advanced Reproductive Care, Inc., as well as the Chair of the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) and the World Endometriosis Research Foundation, both of which are unpaid roles. G.M.C. is an ICMART Board Representative, which is an unpaid role, and no payments are received from ICMART to UNSW, Sydney, or to G.M.C. to undertake this study. O.F., S.D., F.Z.-H., and E.K. report no conflicts of interest. N/A.

Utilization of healthcare prior to endometriosis diagnosis: a Danish case-control study.

Do women with endometriosis have higher utilization of primary and secondary healthcare prior to diagnosis compared to women without endometriosis? Women with a hospital-based diagnosis of endometriosis had an overall higher utilization of both primary and secondary healthcare in all 10 years prior to diagnosis. Endometriosis is associated with a diagnostic delay, but only a few studies have investigated the potential consequences of this delay with regard to the utilization of healthcare. To the best of our knowledge, no study has investigated it in a period corresponding to the estimated diagnostic delay. This national Danish registry-based case-control study included 129 696 women. Cases were women with a first-time hospital-based diagnosis of endometriosis between 1 January 2000 and 31 December 2017. We identified 21 616 cases using density sampling. Each case was matched on age at the date of diagnosis (index date) to five women without diagnosed endometriosis (n = 108 080). The utilization of healthcare was assessed for the 10 years before the index. Cases had significantly higher use of healthcare in all 10 years preceding the index. The mean number of yearly contacts with the GP was 9.99 for cases and 7.85 for controls, with an adjusted incidence rate ratio of 1.28 (1.27; 1.29). For hospital contacts, the association increased slightly in the first 9 years and was most profound in the last year preceding index when the adjusted incidence rate ratio was 2.26 (95% CI 2.28; 2.31). We were not able to include women with an endometriosis diagnosis from the general practitioner or private gynaecologist. Therefore, our results are only applicable to hospital-based diagnoses of endometriosis. We do not have information on the specific reasons for contacting the healthcare providers and we can therefore only speculate that the higher utilization of healthcare among cases was related to endometriosis. This study is in agreement with the other known studies on the subject. Future studies should include specific reasons for contacting the healthcare system and thereby identify any specific contact patterns for women with endometriosis. With this knowledge, healthcare professionals could be better at relating certain healthcare seeking behaviour to endometriosis earlier and thereby reduce the time from onset of symptoms to diagnosis. This study is supported by grants from the project 'Finding Endometriosis using Machine Learning' (FEMaLe/101017562), which has received funding from The European Union's Horizon 2020 research and innovation program and Helsefonden (21-B-0141). K.Z. report grants from Bayer AG, Roche Inc. and Volition, royalties from Oxford-Bayer scientific collaboration in gynaecological therapies, non-financial collaboration with the World Endometriosis Society and World Endometriosis Research Foundation and is a Wellbeing of Women research advisory committee member. All this is outside the submitted work. The other authors have no conflict of interest to declare. N/A.

P-318 Epidemiologic analysis of endometriosis awareness in Turkey

Abstract Study question What is the prevalence of endometriosis in Turkey, and what are the impacts of endometriosis-related symptoms on social, occupational, medical, and daily life activities? Summary answer Endometriosis is a debilitating disease that affects 18% of Turkish women of reproductive age. Social, occupational, and psychological functioning are all negatively impacted. What is known already Endometriosis is a chronic, inflammatory disease. It affects about 6–10 percent of women worldwide. It can alter the quality of life, mental health, relationships, and sexuality of the carriers. The delay in the diagnosis of endometriosis causes a loss of workforce, a decrease in productivity, and, most importantly, excessive finances. Previous studies from developed countries show endometriosis carriers have lower annual incomes and higher short or long-term workforce loss. Due to the difficulty of diagnosing most cases, the actual incidence of endometriosis in the population, including in developed countries, is unknown. Study design, size, duration This study used a web-based survey to identify the prevalence of symptoms and endometriosis-diagnosed women. For this purpose, the World Endometriosis Research Foundation (WERF) EndoCost tool was utilized and altered by the Turkish demographic and healthcare background. Between September 15, 2022, and November 2022, the survey was accessible. In this process, 16304 surveys were completed, with 15673 being counted. Participants/materials, setting, methods The survey's applicants were reached through social media platforms (Facebook and Instagram), which included social media accounts of influencers with followers from all over the country, reports of authors and women's support organizations, countywide student clubs of universities, and nurses working on family medicine in all parts of the country delivering to regions of responsibility. The ethical committee approval have been taken from an university hospital ethical commission (E-10840098-772.02-4247). Main results and the role of chance Our study showed that the prevalence of endometriosis in developing countries was not insignificant. This survey had 15673 participants, and 2880 (18.3%) were diagnosed with endometriosis. There was a significant difference in the impact of endometriosis-related symptoms on social, occupational, medical, and daily life between the participants with endometriosis and the non-endometriosis participants. The percentage of participants with endometriosis (1.3%) who reported quitting work/school due to pain was statistically higher than the non-endometriosis population (0.6%) (P = 0.001). Also, 21.2% of endometriosis participants reported feeling socially isolated related to their condition (P = 0.001). One thousand one hundred fifty-two individuals with endometriosis reported work/school difficulties (28.3%), and 224 respondents could not attend class/work due to endometriosis-related symptoms (7.4%). In addition, most respondents with endometriosis (46.0%) reported problems in a personal relationship, and interestingly, according to 1820 (63.2%) participants with endometriosis, people did not believe their pain or symptoms. There is also this to consider: our data shows that the average number of physician visits before diagnosis was four. Limitations, reasons for caution The study is limited by self-reported patient responses that were not confirmed by medical records or other complementary data. Wider implications of the findings Our findings can be used to increase awareness of the prevalence and challenges of endometriosis carriers, which may help develop future prevention programs. Since most participants with endometriosis experience financial difficulties due to their treatment, health policies can be designed to improve this issue. Trial registration number not applicable

Establishing the Australian National Endometriosis Clinical and Scientific Trials (NECST) Registry: A protocol paper.

Endometriosis is a common yet under-recognised chronic inflammatory disease, affecting 176 million women, trans and gender diverse people globally. The National Endometriosis Clinical and Scientific Trials (NECST) Registry is a new clinical registry, collecting and tracking diagnostic and treatment data, and patient-reported outcomes on people with endometriosis. The registry is a research priority action item from the 2018 National Action Plan for Endometriosis and aims to provide, large-scale, national and longitudinal population-based data on endometriosis. Working groups (consisting of patients with endometriosis, clinicians and researchers) developing the NECST Registry data dictionary and data collection platform started in 2019. Our data dictionary was developed based on existing and validated questionnaires, tools, meta-data and data cubes - World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonisation Project (EPHect), endometriosis CORE outcomes set, patient-reported outcome measures, the International Statistical Classification of Diseases-10th Revision Australian Modification diagnosis codes, and Australian Government datasets: Australian Institute for Health and Welfare (for sociodemographic data), Medicare Benefits Schedule (MBS; for medical procedures) and the Pharmaceutical Benefits Scheme (PBS; for medical therapies). The resulting NECST Registry is an online, secure cloud-based database; prospectively collecting minimum core clinical and health data across eight patient and clinician modules and longitudinal data tracking disease life course. The NECST Registry has ethics approval (HREC/62508/MonH-2020) and is registered on the Australian New Zealand Clinical Trials Registry (ACTRN12622000987763).

Epidemiology of Endometriosis Awareness in Turkey.

Endometriosis is a chronic painful disease that affects the daily quality of life of individuals. Estimated rates show one in 10 women has endometriosis, although the actual prevalence is unknown. In this study, the impact of endometriosis prevalence and symptoms on women's lives in Turkey was questioned through a web-based questionnaire. We utilized a version of the World Endometriosis Research Foundation (WERF) EndoCost tool, which was sent to applicants via social media. Data from women aged 18-50 years were analyzed. The results of 15,673 participants have been analyzed, and 2880 (18.3%) participants had endometriosis. Respondents with endometriosis reported urinary, neurological, and gastrointestinal disorders at statistically higher rates when compared to individuals without endometriosis diagnosis (54.2%, 84.5%, and 89.9% vs. 37.2%, 75.5%, and 81.1%, respectively; p = 0.001). Most respondents with endometriosis (80.1%) reported persistent fatigue and 21.2% of endometriosis participants reported feeling socially isolated related to their condition (p = 0.001). Of the participants with endometriosis,63.2% mentioned that people did not believe their pain or symptoms and 77.9% experienced financial difficulties due to the cost of therapy. Of the participants with endometriosis, 46.0% reported that they had problems in their personal relationships, 28.3% had difficulties at work/school, and 7.4% were unable to attend class/work due to endometriosis-related symptoms. Endometriosis is a chronic, underestimated disease that affects 18% of Turkish women of reproductive age. There is a need for guidelines to inform healthcare providers, population professionals, and patients. Societies and governmental health authorities must work together to resolve this public health issue.

Danish translation, cross-cultural adaptation, and electronic migration of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project Endometriosis Patient Questionnaire.

This study aims to translate and cross-culturally adapt the standard version of the World Endometriosis Research Foundation (WERF) EPHect Endometriosis Patient Questionnaire (EPQ) into Danish and to ensure equivalence of a Danish electronic version. The translation, cultural adaption, and electronic migration followed recommendations from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the Critical Path Institute. Ten women with endometriosis were enrolled for cognitive debriefing of the paper version (pEPQ) after translation and back translation. The questionnaire was then migrated into an electronic version (eEPQ) and subsequently tested for usability and measurement equivalence by five women with endometriosis. Cross-cultural alterations were needed for medical terms, response options for ethnicity, the educational system, and measurement units. Thirteen questions were altered after back translation, while 21 underwent minor changes after cognitive debriefing. After testing the eEPQ, 13 questions were altered. Questions tested for measurement equivalence across the two modes of administration were found comparable. The median time-to-complete the pEPQ and eEPQ was 62 min (range: 29-110) and 63 min (range: 31-88), respectively. General comments included the questionnaire being relevant but long and repetitive. We find the the Danish pEPQ and eEPQ similar and comparable to the original English instrument. However, attention must be drawn to questions regarding measurement units, ethnicity, and educational systems before cross-country comparison. The Danish pEPQ and eEPQ are suitable for obtaining subjective data on women with endometriosis.

‘Guess who’? An Italian multicentric study on pigmentation traits prevalence in endometriosis localizations

ObjectivesPrevious evidence seems to support the more common presence of certain pigmentation types in women with endometriosis. The aim of this study was to assess the association of certain somatic phenotypes with specific localizations of the disease. The genetic makeup of those somatic traits may will help in better define the disease pathogenesis. Study designMulticentric, retrospective study of women aged 18 to 45 with histologically confirmed endometriosis. 575 patients were recruited at eleven different Italian endometriosis clinics from March 2015 to January 2021. Data regarding clinical and surgical features were recorded following the self-administered endometriosis patient questionnaire and the surgical standard of reports approved by the World Endometriosis Research Foundation (WERF). Pigmentation types/somatic phenotypes frequencies among endometriosis localizations were reported. A logistic regression analysis was performed to determine somatic types independently associated with disease’ localizations. ResultsHaving green eyes increased by ∼4 folds (OR 3.7; 95% CI: 1.42–9.61; p = 0.007) the risk of having a ureteral nodule, whereas brown/black eyes decreased this risk (OR 0.34; 95% CI: 0.13–0.87; p = 0.025). Consistently, the combination of green eyes and blonde/light brown hairs increased the odds of ureteral endometriosis by more than 5 folds (OR 5.40; 95%CI: 2.02–14.49; p = 0.001), even after correction for anthropometric confounders (aOR 5.85; 95% CI: 2.13–16.09; p < 0.001). ConclusionsThe association between endometriosis and pigmentary traits has been herein confirmed, with the novel finding of the possible predisposition of ureteral endometriosis in patients with green eyes and blonde/light brown hairs. Further investigation on the genetic makeup of somatic traits may provide new inroads also into the molecular aspects of endometriosis leading to a better understanding of this complex disease.

Pregnancy and SARS-CoV-2: an opportunity to systematically study the complexity of maternal health

Pregnancy and SARS-CoV-2: an opportunity to systematically study the complexity of maternal health

Endometriosis classification systems: an international survey to map current knowledge and uptake.

STUDY QUESTIONWhich classification system for endometriosis do clinicians use most frequently, and why?SUMMARY ANSWEREven 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 ALREADYIn 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, DURATIONA 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, METHODSA 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 CHANCEThe 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 CAUTIONWhile the total number of respondents was acceptable, some regions/professions were not sufficiently represented to draw conclusions.WIDER IMPLICATIONS OF THE FINDINGSThe 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 INTEREST(S)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.

An international terminology for endometriosis, 2021.

STUDY QUESTIONCan a set of terms and definitions be prepared on endometriosis that would be the basis for standardization in disease description, classification and research?SUMMARY ANSWERThe current paper outlines a list of 49 terms and definitions in the field of endometriosis.WHAT IS KNOWN ALREADYDifferent classification systems have been developed for endometriosis, using different definitions for the disease, the different subtypes, symptoms and treatments. In addition, an International Glossary on Infertility and Fertility Care was published in 2017 by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) in collaboration with other organisations.STUDY DESIGN, SIZE, DURATIONAn international working group convened over the development of a classification or descriptive system for endometriosis. As a basis for such a system, a terminology for endometriosis was considered a condition sine qua non. The working group listed a number of terms relevant to be included in the terminology, documented currently used and published definitions, and discussed and adapted them until consensus was reached within the working group. Following stakeholder review, further terms were added, and definitions further clarified.PARTICIPANTS/MATERIALS, SETTING, METHODSAlthough definitions were collected through published literature, the final set of terms and definitions is to be considered consensus-based. After finalization of the first draft, the members of the international societies and other stakeholders were consulted for feedback and comments, which led to further adaptations.MAIN RESULTS AND THE ROLE OF CHANCEA list of 49 terms and definitions in the field of endometriosis is presented, including a definition for endometriosis and its subtypes, different locations, interventions, symptoms and outcomes. Endometriosis is defined as a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process.LIMITATIONS, REASONS FOR CAUTIONFuture research may require further refinement of the presented definitions.WIDER IMPLICATIONS OF THE FINDINGSThe application of the defined terms aims to facilitate harmonization in endometriosis research and clinical practice.STUDY FUNDING/COMPETING INTEREST(S)The meetings and activities of the working group were funded by the American Association of Gynecologic Laparoscopists, European Society for Gynecological Endoscopy, European Society of Human Reproduction and Embryology and World Endometriosis Society. A.W.H. reports grant funding from the MRC, NIHR, CSO, Wellbeing of Women, Roche Diagnostics, Astra Zeneca, Ferring, Charles Wolfson Charitable Trust, Standard Life, 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. 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 and personal fees from AbbVie, and personal fees from Roche outside the submitted work. C.T. reports grants, non-financial support and other from Merck SA, non-financial support and other from Gedeon Richter, 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, Roche Diagnostics Inc, Volition Rx, outside the submitted work; she is also a Board member (Secretary) of the World Endometriosis Society and World Endometriosis Research Foundation, Research Advisory Board member of Wellbeing of Women, UK (research charity), and Chair, Research Directions Working Group, World Endometriosis Society. 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.TRIAL REGISTRATION NUMBERN/A.

Endometriosis classification, staging and reporting systems: a review on the road to a universally accepted endometriosis classification.

STUDY QUESTIONWhich endometriosis classification, staging and reporting systems have been published and validated for use in clinical practice?SUMMARY ANSWEROf the 22 endometriosis classification, staging and reporting systems identified in this historical overview, only a few have been evaluated, in 46 studies, for the purpose for which they were developed.WHAT IS KNOWN ALREADYIn the field of endometriosis, several classification, staging and reporting systems have been developed.PARTICIPANTS/MATERIALS, SETTING, METHODSA systematic PUBMED literature search was performed. Data were extracted and summarized.MAIN RESULTS AND THE ROLE OF CHANCETwenty-two endometriosis classification, staging and reporting systems have been published between 1973 and 2021, each developed for specific, and different, purposes. There still is no international agreement on how to describe the disease. Studies evaluating the different systems are summarized showing a discrepancy between the intended and the evaluated purpose, and a general lack of validation data confirming a correlation with pain symptoms or quality of life for any of the current systems. A few studies confirm the value of the ENZIAN system for surgical description of deep endometriosis. With regards to infertility, the endometriosis fertility index has been confirmed valid for its intended purpose.LARGE SCALE DATANA.LIMITATIONS, REASONS FOR CAUTIONThe literature search was limited to PUBMED. Unpublished classification, staging or reporting systems, or those published in books were not considered.WIDER IMPLICATIONS OF THE FINDINGSIt can be concluded that there is no international agreement on how to describe endometriosis or how to classify it, and that most classification/staging systems show no or very little correlation with patient outcomes. This overview of existing systems is a first step in working toward a universally accepted endometriosis classification.STUDY FUNDING/COMPETING INTEREST(S)The meetings and activities of the working group were funded by the American Association of Gynecologic Laparoscopists, European Society for Gynecological Endoscopy, European Society of Human Reproduction and Embryology and World Endometriosis Society. A.W.H. reports grant funding from the MRC, NIHR, CSO, Wellbeing of Women, Roche Diagnostics, Astra Zeneca, Ferring, Charles Wolfson Charitable Trust, Standard Life, 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. 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 and personal fees from AbbVie, and personal fees from Roche outside the submitted work. C.T. reports grants, non-financial support and other from Merck SA, non-financial support and other from Gedeon Richter, 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, Roche Diagnostics Inc, Volition Rx, outside the submitted work; she is also a Board member (Secretary) of the World Endometriosis Society and World Endometriosis Research Foundation, Research Advisory Board member of Wellbeing of Women, UK (research charity), and Chair, Research Directions Working Group, World Endometriosis Society. The other authors had nothing to disclose.TRIAL REGISTRATION NUMBERNA.

Impact of Endometriosis in Women of Arab Ancestry on: Health-Related Quality of Life, Work Productivity, and Diagnostic Delay.

Introduction: Endometriosis has a negative effect on health-related quality of life (HRQoL), wellbeing and daily functioning. Endometriosis is an under-researched condition within non-western populations. Cultural representations are needed to understand the relative roles of societal norms, traditional factors, and religious sensitivities on the impact of endometriosis on HRQoL in various populations. In particular, there is a lack of emphasis placed in understanding the association of HRQoL on endometriosis in Arab women.Method: In this prospective case-control study, 2,610 Arab ancestry women in the United Arab Emirates were recruited to investigate the impact of endometriosis on HRQoL, diagnostic delay, psychological co-morbidities, work productivity, and physical activity. Participants completed the following standardized, validated questionnaires: Short Form-36 version 2 questionnaire, the World Endometriosis Research Foundation EPHect minimum clinical questionnaire version, and Work Productivity and Activity Impairment questionnaire. Translations to the Arabic language, validated using the forward-backward translation method, of the questionnaires were utilized.Results: HRQoL scores were significantly impaired in women with endometriosis, as demonstrated in the Physical Composite Scores and Mental Composite Scores in the symptomatic control group (p = 0.001; p = 0.003, respectively) and the asymptomatic control group (p < 0.001; p < 0.001, respectively). Susceptibility and severity of multiple pain syndromes and infertility in women with endometriosis was the main indicator of lower HRQoL. Anxiety (p = 0.007) and depression (p = 0.005) were significantly associated with endometriosis, in comparison to symptomatic controls. The average diagnostic delay was 11.61 years, however single women experience 15.81 years of diagnosis delay, with approximately 18% (n = 15) of the single women experiencing more than a 20-year delay in diagnosis. The intensity of physical activity was not associated with endometriosis, when compared to symptomatic (p = 0.405) or asymptomatic controls (p = 0.144).Conclusion: For the first time, we provide evidence from a combined hospital, clinic, and population-based study that Arab women with endometriosis experience significant impacts on HRQoL, substantial diagnostic delay after the onset of symptoms, significant association to psychological disorders (anxiety and depression), and a negative impact on work productivity. Future research must focus on understanding the personal and culturally centered beliefs of Arab women to ensure a positive HRQoL trajectory by improving diagnosis and management strategies.

Ibero-American Endometriosis Patient Phenome: Demographics, Obstetric-Gynecologic Traits, and Symptomatology.

Background: An international collaborative study was conducted to determine the demographic and clinical profiles of Hispanic/Latinx endometriosis patients from Latin America and Spain using the Minimal Clinical Questionnaire developed by the World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonization Project (EPHect).Methods: This is a cross-sectional study to collect self-reported data on demographics, lifestyle, and endometriosis symptoms of Hispanic/Latinx endometriosis patients from April 2019 to February 2020. The EPHect Minimal Clinical Questionnaire (EPQ-M) was translated into Spanish. Comprehension and length of the translated survey were assessed by Spanish-speaking women. An electronic link was distributed via social media of endometriosis patient associations from 11 Latin American countries and Spain. Descriptive statistics (frequency, means and SD, percentages, and proportions) and correlations were conducted using SPSSv26.Results: The questionnaire was completed by 1,378 participants from 23 countries; 94.6% had self-reported diagnosis of endometriosis. Diagnostic delay was 6.6 years. Most participants had higher education, private health insurance, and were employed. The most common symptoms were back/leg pain (85.4%) and fatigue (80.7%). The mean number of children was 1.5; 34.4% had miscarriages; the mean length of infertility was 3.7 years; 47.2% reported pregnancy complications. The most common hormone treatment was oral contraceptives (47.0%). The most common comorbidities were migraines (24.1%), polycystic ovary syndrome (PCOS) (22.2%), and irritable bowel syndrome (21.1%). Most participants (97.0%) experienced pelvic pain during menses; for 78.7%, pain was severe; 86.4% reported dyspareunia. The mean age of dysmenorrhea onset was 16.2 years (SD ± 6.1). Hormone treatments were underutilized, while impact was substantial. Pain catastrophizing scores were significantly correlated with pain intensity (p < 0.001).Conclusion: This is the first comprehensive effort to generate a clinical–demographic profile of Hispanic/Latinx endometriosis patients. Differences in clinical presentation compared to other cohorts included higher prevalence and severity of dysmenorrhea and dyspareunia and high levels of pain catastrophizing. Though future studies are needed to dissect the impact of race and ethnicity on pain and impact, this profile is the first step to facilitate the recognition of risk factors and diagnostic features and promote improved clinical management of this patient population. The EPHect questionnaire is an efficient tool to capture data to allow comparisons across ethnicities and geographic regions and tackle disparities in endometriosis research.

Translation and Cultural Validation of the WERF EPHect Endometriosis Patient Questionnaire into Canadian French.

To produce a culturally validated Canadian French version of the Standard EPHect Endometriosis Patient Questionnaire (EPQ-S) from the World Endometriosis Research Foundation (WERF). We studied 17 premenopausal women who were seen for pelvic pain symptoms or suspicion of endometriosis at the gynaecology clinic of the CHU de Québec - Université Laval (Québec City, Canada). Participants completed the French language version of the questionnaire at their first visit, and the validation took place about 1 week later. All 22 of the invited women agreed to participate, of whom 17 were reached for the validation. The mean age of participants was 38.9 years, and 15 (88%) had a confirmed diagnosis of endometriosis. Fourteen participants (82%) found the questionnaire clear and relevant. The average length of time to complete the questionnaire was 36.25 ± 10.8 minutes. The validation process resulted in the addition of lines at the end of each section to allow space for specific comments and some clarifications with respect to timelines. This study validated a Canadian French version of the EPHect questionnaire. With such validation studies, differences in language and culture will no longer be a barrier to large national and international studies on endometriosis, leading to high-quality research and breakthroughs for millions of individuals living with this disease.

Protocol for the Cultural Translation and Adaptation of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project Endometriosis Participant Questionnaire (EPHect)

Endometriosis affects 10% of women worldwide and is one of the most common causes of chronic pelvic pain and infertility. However, causal mechanisms of this disease remain unknown due to its heterogeneous presentation. In order to successfully study its phenotypic variation, large sample sizes are needed. Pooling of data across sites is not always feasible given the large variation in the complexity and quality of the data collected. The World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonization Project (EPHect) have developed an endometriosis participant questionnaire (EPQ) to harmonize non-surgical clinical participant characteristic data relevant to endometriosis research, allowing for large-scale collaborations in English-speaking populations. Although the WERF EPHect EPQs have been translated into different languages, no study has examined the cross-cultural translation and adaptation for content and face validity. In order to investigate this, we followed the standard guidelines for cross-cultural adaptation and translation of the minimum version of the EPQ (EPQ-M) using 40 patients who underwent laparoscopic surgery in Turkey and 40 women in Northern Cyprus, aged between 18 and 55. We assessed the consistency by using cognitive testing and found the EPHect EPQ-M to be comprehensive, informative, and feasible in these two Turkish-speaking populations. The translated and adapted questionnaire was found to be epidemiologically robust, taking around 30–60 min to complete; furthermore, participants reported a similar understanding of the questions, showing that common perspectives were explored. Results from the cognitive testing process led to minor additions to some items such as further descriptive and/or visuals in order to clarify medical terminology. This paper illustrates the first successful cross-cultural translation and adaptation of the EPHect EPQ-M and should act as a tool to allow for further studies that wish to use this questionnaire in different languages. Standardized tools like this should be adopted by researchers worldwide to facilitate collaboration and aid in the design and conduction of global studies to ultimately help those affected by endometriosis and its associated symptoms.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

Clinical and Demographic Profile of Women With Endometriosis From Iberoamerica [12B

INTRODUCTION: This study was conducted to determine for the first time the demographic and clinical profile of women with endometriosis of Hispanic/Latina background, a patient population not well represented in databases and cohort studies. In order to gather standardized, comparable data we used the Clinical Questionnaire developed by the Endometriosis Phenome project (EPhect) of the World Endometriosis Research Foundation (WERF). METHODS: A cross-sectional anonymous study was conducted using the Spanish translation of the questionnaire. A REDCap-based link was distributed via social media to women with endometriosis in collaboration with Patient Associations. Data was analyzed using SPSS. RESULTS: Women (1,296) from 22 countries of South America, Central America, the Caribbean, Spain and US participated. Patients reported on education (43.5% had a degree), race (49.8% were white), and work (78.5%). Mean age was 33.7 years old (y/o; range 15–66); at menarche was 12 y/o; at pain onset was 16.2 y/o. Many reported having regular menstrual cycles (70.4%), and profuse menstrual bleeding (47.9%). Most (78.9%) patients reported severe pelvic pain (mean VAS 7.7). Most (82.9%) reported dyspareunia (mean VAS 6.3). Mean number of children was 1.52; 40.3% reported infertility/abortion; only 27.6% sought infertility treatment. The mean length of infertility was 0.52 years (range 0.08–8 years). Quality of life was negatively impacted in household chores (64.8%), sleep (58.7%), and exercise/sports (56.4%). CONCLUSION: Hispanic/Latina women with endometriosis present with severe symptoms and substantial quality of life impact. The EPhect questionnaire is a valuable tool to capture data and allow comparisons across ethnicities and geographic regions.