Biobanking Harmonisation Project 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.

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).

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.

P-313 The Cyprus women’s health research (COHERE) initiative: estimating the prevalence, symptomatology, associated risk factors and economic burden of endometriosis in an Eastern Mediterranean population

Abstract Study question In this previous undescribed population of women, what is the prevalence of endometriosis and associated symptomatology, and how are women affected? Summary answer Prevalence of endometriosis was 5.4% (95%CI; 4.9%-5.9%). Cases suffered from worse physical health, higher use of pain medication and decreased productivity at work. What is known already There is a lack of population level data on prevalence and distribution of women’s health conditions, such as endometriosis, from the Eastern Mediterranean region, despite their known negative effects on quality of life. In addition, there is a complete absence of any health statistics from Northern Cyprus, an emerging region in Europe. Most current endometriosis research comes from Western populations and is not generalisable to non-Western populations due to differences in culture, lifestyle, and care seeking patterns. Therefore, it is important to investigate endometriosis in a variety of settings. Study design, size, duration The COHERE Initiative is a cross-sectional, population-based study that recruited 7,646 women between the ages 18-55 residing in Northern Cyprus between January 31st 2018, and January 31st 2020. Recruitment took place face-to-face (90%) and online (10%). Participants completed an expanded version of the WERF Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) questionnaire, consisting of previously validated measurement instruments, such as the Short-Form-36-version-2 questionnaire (SF-36v2) and the Work Productivity and Impairment Questionnaire: General Health (WPAI:GH). Participants/materials, setting, methods Endometriosis cases were defined using a combination of self-reported and pelvic ultrasound data. Controls were women without endometriosis. Chi-square, Fisher’s exact test, Student’s t-test, linear regression, and multivariable logistic regression were used for data analysis. The significance level was set at p < 0.05. Main results and the role of chance Endometriosis prevalence was 5.4% (95%CI; 4.9%-5.9%;n=410). The mean age women with endometriosis reported to first experience related-symptoms was 25.9-years, despite average age of first menstrual-pain occurring at 16.2-years. Average age of first gynaecologist visit was 21.0-years and endometriosis diagnostic-delay was 1.5-years. Physical health-related-quality-of-life was lower in women with endometriosis compared to those without (48.4 vs 50.2, p = 0.001). Cases had a higher mean percentage of activity impairment (25.8% vs 22.5%, p = 0.03) and reduced effectiveness whilst working (23.4% vs 19.5%, p = 0.006) than controls. Hormone-use was higher in women with endometriosis compared to controls for heavy-bleeding (5.9% vs 1.4%, p < 0.001), irregular periods (14.4% vs 7.2%, p < 0.001) and pelvic-pain (9.3% vs 1.7%, p < 0.001), though overall hormone use was low at 24.1%. Iron and vitamin-D deficiency were the most reported co-morbidities, and these proportions were significantly different from women without endometriosis (38.8% vs 28.3%, 23.9% vs 17.0% respectively, p < 0.001). Migraine headaches were more frequent in women with endometriosis than in those without (19.8% vs 13.2%, p < 0.001). Women with endometriosis were more likely to have ever used drugs for pain relief (77.1% vs 60.5%, p < 0.001). Further analysis will include estimation of economic burden of endometriosis and investigation into Mediterranean-specific factors including sun-exposure and dietary-habits. Limitations, reasons for caution Given the cross-sectional nature of this study, causality cannot be inferred. The majority of endometriosis cases are self-reported which is not as reliable as hospital diagnosis/surgeries and laparoscopy is not available in Northern Cyprus. However, research has shown that women self-report endometriosis diagnoses with reasonable accuracy (>70%). Wider implications of the findings This is the first study that has estimated prevalence of endometriosis in the region and provided insight into the current-status of healthcare. It has highlighted gaps in the public’s general knowledge of common gynaecological conditions. The results form the basis for targeted follow-up-studies and promotes evidence-based reproductive-medicine in the Eastern-Mediterranean-region. Trial registration number Not applicable

1974 Is the World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonisation Project (EPHECT) Questionnaire a Good Triaging Tool for Women with Ovarian and Posterior Compartment Endometriosis?

Study Objective We aim to demonstrate whether the WERF EPHect Questionnaire can be used as a triaging tool to determine which women, based upon symptoms, are more likely to have ovarian and posterior compartment endometriosis on ultrasound. Design Prospective observational study (July 2018 to March 2019). Setting The WERF EPHect Questionnaires were emailed to women with possible endometriosis booked in for a 'deep endometriosis' (DE) ultrasound at two specialized ultrasound centers. Patients or Participants Women with a history of pelvic pain, dysmenorrhoea, dyspareunia and dyschezia were included. Interventions The DE ultrasounds were performed by advanced sonologists as per the IDEA consensus opinion. A subsection of the questionnaire focusing on bowel symptoms (during menses and in the preceding 3 months) was compared to DE ultrasound findings. Logistic regression analysis was performed to assess the correlation between online responses and ultrasound findings. Measurements and Main Results 217 women were emailed the online questionnaire; 136/217 (62%) responded prior to their DE ultrasound. The ultrasound prevalence of ovarian endometriomas, rectal DE and complete pouch of Douglas (POD) obliteration on ultrasound were 24%, 18% and 18%, respectively. There was no significant difference in the prevalence of disease in the respondents versus non-respondents (47%/47% posterior compartment, 31%/24% ovarian, respectively (p-value Conclusion When the WERF EPHect Questionnaire is applied, bowel symptoms have the potential to be utilized as a triaging tool to determine which women require DE ultrasounds. A structured international symptomatology survey may be able to better target the utility of the DE ultrasound.

EP31.01: Is the World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) questionnaire a good triaging tool for women with ovarian and posterior compartment endometriosis?

EP31.01: Is the World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) questionnaire a good triaging tool for women with ovarian and posterior compartment endometriosis?

How feasible and practical is it to introduce the Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) standard surgical form into clinical practice?

Background: The Endometriosis Phenome and Biobanking Harmonisation Project has been set up to facilitate and advance global endometriosis research. Aim: To test the feasibility and practicality of using the Endometriosis Phenome and Biobanking Harmonisation Project standard surgical form in routine clinical practice. Materials and methods: Standard surgical form was filled out using a web-based application for 225 consecutive women who underwent surgery for suspected or known endometriosis. Results: Median age was 37 years. Half (49.8%) of the women had a previous surgical diagnosis of endometriosis. Endometriosis was found in 91.5% of patients in this cohort. Median operative time was 101 min. Operative photographs substantially assisted completion of the standard surgical form post-operatively. The median time required to fill out the questionnaire was 8 min (range, 2–17 min). This was mostly dependent on the severity and distribution of endometriosis lesions. The standard surgical form is very comprehensive and has the advantage of including both the American Society of Reproductive Medicine classification and the Endometriosis Fertility Index; however, characterisation of deep endometriosis is insufficient for some women. In addition, some sections such as the descriptive endometriosis table (section IX) remain subjective. Conclusion: Using the Endometriosis Phenome and Biobanking Harmonisation Project standard surgical form to collect research data is feasible, especially when using an electronic database entry tool. It is also practically manageable, although the time taken is more than originally estimated by the Endometriosis Phenome and Biobanking Harmonisation Project standard surgical form authors. Even though some sections of the standard surgical form may be subjective, it is comprehensive and we would recommend its adoption into routine clinical practice for endometriosis research.

EPHect – the Endometriosis Phenome (and Biobanking) Harmonisation Project – may be very helpful for clinicians and the women they are treating

This article acts as a summary of the recently published papers by the World Endometriosis Research Foundation aiming to set up the Endometriosis Phenome and Biobanking Harmonisation Project. The objective of this project is to standardise recording of patient history and characteristics, recording of surgical procedure and extent of disease as well as collection, processing and storage of specimens and consequently create a reliable resource for research into endometriosis.

World Endometriosis Society consensus on the classification of endometriosis.

What is the global consensus on the classification of endometriosis that considers the views of women with endometriosis? We have produced an international consensus statement on the classification of endometriosis through systematic appraisal of evidence and a consensus process that included representatives of national and international, medical and non-medical societies, patient organizations, and companies with an interest in endometriosis. Classification systems of endometriosis, developed by several professional organizations, traditionally have been based on lesion appearance, pelvic adhesions, and anatomic location of disease. One system predicts fertility outcome and none predicts pelvic pain, response to medications, disease recurrence, risks for associated disorders, quality of life measures, and other endpoints important to women and health care providers for guiding appropriate therapeutic options and prognosis. A consensus meeting, in conjunction with pre- and post-meeting processes, was undertaken. A consensus meeting was held on 30 April 2014 in conjunction with the World Endometriosis Society's 12th World Congress on Endometriosis. Rigorous pre- and post-meeting processes, involving 55 representatives of 29 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement. A total of 28 consensus statements were made. Of all, 10 statements had unanimous consensus, however none of the statements was made without expression of a caveat about the strength of the statement or the statement itself. Two statements did not achieve majority consensus. The statements covered women's priorities, aspects of classification, impact of low resources, as well as all the major classification systems for endometriosis. Until better classification systems are developed, we propose a classification toolbox (that includes the revised American Society for Reproductive Medicine and, where appropriate, the Enzian and Endometriosis Fertility Index staging systems), that may be used by all surgeons in each case of surgery undertaken for women with endometriosis. We also propose wider use of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project surgical and clinical data collection tools for research to improve classification of endometriosis in the future, of particular relevance when surgery is not undertaken. This consensus process differed from that of formal guideline development, although based on the same available evidence. A different group of international experts from those participating in this process may have yielded subtly different consensus statements. This is the first time that a large, global, consortium-representing 29 major stake-holding organizations, from 19 countries - has convened to systematically evaluate the best available evidence on the classification of endometriosis and reach consensus. In addition to 21 international medical organizations and companies, representatives from eight national endometriosis organizations were involved, including lay support groups, thus generating and including input from women who suffer from endometriosis in an endeavour to keep uppermost the goal of optimizing quality of life for women with endometriosis. The World Endometriosis Society convened and hosted the consensus meeting. Financial support for participants to attend the meeting was provided by the organizations that they represented. There was no other specific funding for this consensus process. Mauricio Abrao is an advisor to Bayer Pharma, and a consultant to AbbVie and AstraZeneca; G David Adamson is the Owner of Advanced Reproductive Care Inc and Ziva and a consultant to Bayer Pharma, Ferring, and AbbVie; Deborah Bush has received travel grants from Fisher & Paykel Healthcare and Bayer Pharmaceuticals; Linda Giudice is a consultant to AbbVie, Juniper Pharmaceutical, and NextGen Jane, holds research grant from the NIH, is site PI on a clinical trial sponsored by Bayer, and is a shareholder in Merck and Pfizer; Lone Hummelshoj is an unpaid consultant to AbbVie; Neil Johnson has received conference expenses from Bayer Pharma, Merck-Serono, and MSD, research funding from AbbVie, and is a consultant to Vifor Pharma and Guerbet; Jörg Keckstein has received a travel grant from AbbVie; Ludwig Kiesel is a consultant to Bayer Pharma, AbbVie, AstraZeneca, Gedeon Richter, and Shionogi, and holds a research grant from Bayer Pharma; Luk Rombauts is an advisor to MSD, Merck Serono, and Ferring, and a shareholder in Monash IVF. The following have declared that they have nothing to disclose: Kathy Sharpe Timms; Rulla Tamimi; Hugh Taylor. N/A.

Beyond Endometriosis Genome-Wide Association Study: From Genomics to Phenomics to the Patient.

Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remains unknown. Genome-wide association studies (GWAS) to date have identified 12 single nucleotide polymorphisms at 10 independent genetic loci associated with endometriosis. Most of these were more strongly associated with revised American Fertility Society stage III/IV, rather than stage I/II. The loci are almost all located in intergenic regions that are known to play a role in the regulation of expression of target genes yet to be identified. To identify the target genes and pathways perturbed by the implicated variants, studies are required involving functional genomic annotation of the surrounding chromosomal regions, in terms of transcription factor binding, epigenetic modification (e.g., DNA methylation and histone modification) sites, as well as their correlation with RNA transcription. These studies need to be conducted in tissue types relevant to endometriosis-in particular, endometrium. In addition, to allow biologically and clinically relevant interpretation of molecular profiling data, they need to be combined and correlated with detailed, systematically collected phenotypic information (surgical and clinical). The WERF Endometriosis Phenome and Biobanking Harmonisation Project is a global standardization initiative that has produced consensus data and sample collection protocols for endometriosis research. These now pave the way for collaborative studies integrating phenomic with genomic data, to identify informative subtypes of endometriosis that will enhance understanding of the pathogenic mechanisms of the disease and discovery of novel, targeted treatments.

Introduction: New tools for enhancing collaborative endometriosis research

This issue of Fertility and Sterility contains four articles by the World Endometriosis Research Foundation whose present objective is global standardization of the collection of phenotypic data and biological samples, designated as the Endometriosis Phenome and Biobanking Harmonisation Project. The aim is to facilitate large-scale international, multicenter trials that are robust, and will result in biomarker and treatment targets to advance research in endometriosis.