World Endometriosis Research Foundation Research Articles

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?

Cyprus Women\u2019s Health Research (COHERE) initiative: determining the relative burden of women\u2019s health conditions and related co-morbidities in an Eastern Mediterranean population

There is lack of population level data on prevalence and distribution of common benign women’s health conditions such as endometriosis, uterine fibroids, polycystic ovary syndrome from the Eastern Mediterranean region despite their significant consequences on quality of life. In particular, there is complete absence of any health statistics from Northern Cyprus, which is an emerging region in Europe. The Cyprus Women’s Health Research (COHERE) Initiative is the first large-scale cross-sectional study in the region, aiming to determine the relative burden of benign women’s health conditions and related co-morbidities in women living in Northern Cyprus. The COHERE Initiative is a cross-sectional study aiming to recruit 8000 women aged 18–55 years and residing for at least the past 5 years in Northern Cyprus. The study is composed of two main steps: (1) Baseline recruitment, including (i) completion of a detailed health questionnaire, which is an expanded version of the World Endometriosis Research Foundation (WERF) Endometriosis Phenome Harmonisation Project (EPHect) standardised questionnaire, including questions on demographics, menstrual history, hormone use, pregnancy, pain (pelvic pain, bladder and bowel pain, migraine), medical history, family history of illnesses, medication use, life-style factors in relation to a wide range of reproductive and endocrine conditions, resource use (ii) measurement of weight, height, waist/hip circumference and blood pressure, (iii) collection of saliva samples for genotyping. (2) Gynaecology clinic follow up, including a pelvic ultrasound scan (USS). There is also a follow-up food frequency questionnaire (FFQ) targeted to all women taking part in the baseline recruitment with an aim to collect more detailed data on dietary habits. The COHERE Initiative will generate prevalence rates for conditions, define the clinical profiles for women’s health conditions, and estimate the economic burden of these conditions in Northern Cyprus. The results will also provide insights into the current status of health-care among women living in a currently under-investigated region. The genetic findings will inform future gene mapping studies for investigation of the heritable component of conditions in this population/region. Moreover, the results will be compared with other centres collecting data using EPHect tools globally and will help determine population differences and similarities in disease patterns and clinical profiles. The COHERE Initiative will serve as a resource to conduct hypothesis-driven follow-up studies investigating effect of the ‘Mediterranean life-style’ as well as genetic factors on common benign women’s health conditions that maybe specific to Eastern Mediterranean populations.

The Impact of Endometriosis on Quality of Life in Adolescents

PurposeWhile endometriosis is recognized to have a high patient burden for adults, the level of morbidity it causes for adolescents has been understudied, and may be minimized by clinicians. The purpose of this study was to determine whether endometriosis has a significant impact on quality of life (QOL) for adolescents and young adults. MethodsFive hundred and sixty-seven participants (360 cases and 207 controls) aged <25 years old who are enrolled in the Women's Health Study: From Adolescence to Adulthood longitudinal study were included in this analysis. Participants were enrolled from medical clinics and the communities surrounding Boston, MA. Participants completed an expanded World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project standard clinical questionnaire that included the Short Form-36 (SF-36), a widely used measure of health-related QOL. We calculated SF-36 physical component summary and mental component summary scores, as well as eight subscale scores. On the SF-36, lower scores reflect greater impairment. ResultsAdolescents with endometriosis had significantly lower physical component summary (mean [standard deviation]: 43.4 [11.1] vs. 53.8 [7.6], p < .0001) and mental component summary (43.3 [12.3] vs. 46.3 [10.8], p = .008) scores compared to controls, as well as lower scores on all eight subscales. More cases than controls reported mental health diagnoses, pain medication use, and avoidance of exercise during menstruation. Among cases, earlier age at menarche, more severe pelvic pain, and longer duration of diagnostic delay were associated with poorer QOL. ConclusionsEndometriosis is associated with significantly worse reports of QOL for adolescents and young women with endometriosis compared to unaffected peers. Earlier menarche was associated with poorer physical health-related QOL among cases, whereas severe pelvic pain was associated with both poorer physical and mental health-related QOL among cases. Impairment in QOL is not limited to adults with endometriosis, but affects younger patients as well.

Creating Solutions in Endometriosis: Global Collaboration through the World Endometriosis Research Foundation:

Endometriosis affects an estimated 176 million women worldwide during the prime years of their lives. Yet many clinical questions remain unanswered, treatment failures are common, and there is litt...

Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs adulthood

Endometriosis symptoms often start at a young age, and the time between symptom onset and endometriosis diagnosis can be several years. It is not clear whether the symptoms that are experienced by adolescents differ from adults. Better understanding may shorten the often lengthy delay in diagnosis. The purpose of the study was to further elucidate the symptom presentation of adolescents as compared with adults to determine whether differences existed, based on age at surgical diagnosis that could impact time to diagnosis. This investigation was a cross-sectional study at enrollment within a longitudinal cohort of adolescents and women with endometriosis. The population-based cohort was recruited from 2 tertiary care centers and the surrounding communities. Participants included adolescents (diagnosed at ≤18 years old; n=295) and adults (diagnosed at >18 years old; n=107) with surgically confirmed endometriosis who were enrolled into The Women's Health Study: From Adolescence to Adulthood. Participants completed an expanded version of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project standard clinical questionnaire that included items regarding menstrual history, associated symptoms, and pain. Chi-square or Fisher's exact tests were applied to categoric data; Wilcoxon rank sum tests were applied to continuous data. Most participants (90%) experienced moderate-severe menstrual pain. On average, 3 doctors were seen before diagnosis, regardless of age at presentation (range, 0-25 years). Time from symptoms to diagnosis averaged 2 years for adolescents and 5 years for adults (P<.001). More adolescents (50%) than adults (33%) reported pain starting at menarche (P=.002) and nausea accompanying pain (69% vs 53%; P=.01). Noncyclic, general pelvic pain was prevalent. One-half of the participants reported relief of their general pelvic pain after a bowel movement. Pain interfered with work/school, daily activities, exercise, and sleep to a moderate-extreme degree; difficulties were similar by age at diagnosis. Pelvic pain was severe and noncyclic and negatively impacted quality of life. At our tertiary care centers, symptoms of endometriosis did not differ between women surgically diagnosed during adolescence compared with those diagnosed as adults. Adolescents had more nausea and symptom onset at menarche. Multi-year delays in diagnosis were common. Clinicians should be aware of these alternate symptom patterns and include endometriosis in their differential diagnosis for both adolescent and young adult women who experience noncyclic pelvic pain and nausea.

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.

Industry is not the dark side, but an essential partner to make progress in reproductive health.

For the last 20 years, Thomas D'Hooghe has been coordinator of the Leuven University Fertility Center at Leuven University Hospitals, Belgium, one of the largest teaching hospitals in Europe. Since 1995, he has also been Professor of Reproductive Medicine and Biology at KU Leuven (University of Leuven) and Adjunct Professor at Yale University, USA. Since 1 October 2015, he has been the Vice President and Head of Global Medical Affairs Fertility at Merck's headquarters in Darmstadt, Germany. He has published nearly 300 papers in internationally peer-reviewed journals and has contributed to reproductive health serving major international organizations such as the WHO, the European Society of Human Reproduction and Embryology, the Society of Reproductive Investigation and the World Endometriosis Research Foundation.

Quality of life outcomes in women with endometriosis are highly influenced by recruitment strategies.

To what extent are outcome measures in endometriosis-related quality of life studies influenced by the setting in which patient recruitment is performed? Quality of life outcomes in women with endometriosis are highly influenced by recruitment strategies. Most studies on quality of life in women with endometriosis are conducted in tertiary care centres or patient associations. It is conceivable that the setting in which patient recruitment is performed influences the quality of life results. This has not been investigated before. Retrospective questionnaire based cohort study (part of the World Endometriosis Research Foundation (WERF) EndoCost study). The investigated women were recruited in three settings: a tertiary care centre for endometriosis (n = 135); five secondary care centres (n = 63); an endometriosis patient association (n = 291). The secondary and tertiary care population included women with a laparoscopic and/or histological diagnosis of endometriosis. The patient association population consisted of women with a self-reported diagnosis of surgically confirmed endometriosis. The populations did not differ in terms of age, co-morbidities and education level. Delay of diagnosis was the longest in the patient association (median 7 years) (tertiary care 2 years; secondary care 1.5 years) (P < 0.001). The tertiary care population reported more laparotomies (64%) than the other populations (secondary care 43%; patient association 47%) (P = 0.002). Affected job was least prevalent in the secondary care setting (35%) (patient association 64%; tertiary care 56%) (P < 0.001). Affected relationships were most prevalent in the patient association setting (52%) (tertiary care 38%; secondary care 22%) (P < 0.001). Chronic pain was least prevalent in patients in secondary care (44%) (tertiary care 65%; patient association 61%) (P = 0.009). Substantial differences in quality of life were detected between secondary care (median physical component 50.4, mental component 49.6); tertiary care (physical component 46.2, mental component 46.2) and the patient association (physical component 45.0, mental component 44.6) (P < 0.001, P = 0.018). The response rate was relatively low (35%). Analysis of the hospital populations revealed that non-responders and responders did not differ with respect to age or revised American Fertility Society classification, indicating that the non-responder bias is limited. However, other factors, such as social and marital status or symptomatology, might be different for non-responders. Missing values were analysed as if the symptom was not present. Missing values never exceeded 10%, except for one value. Therefore, it can be expected that the effect of missing data on the outcome is negligible. Twenty-five patients belonged to more than one category. A sensitivity analysis showed that the influence of assigning patients to another category was limited. Outcomes regarding quality of life are highly influenced by recruitment strategy. None of the groups appeared to be a representative selection of the total population of women with endometriosis. An alternative strategy for creating a representative population for cost and quality of life studies is probably to recruit women who live in a specific geographic area rather than women that visit a specific hospital or are a member of a patient association. The WERF EndoCost study was funded by the World Endometriosis Research Foundation. The sponsors did not have a role in the design and conduct of this study: collection, management, analysis, interpretation of the data; preparation, review, approval of the manuscript. L.H. is the chief executive and T.M.D. was a board member of WERF at the time of funding. T.M.D holds the Merck-Serono Chair and the Ferring Chair in Reproductive Medicine in Leuven, Belgium and has served as consultant for Merck-Serono, Schering-Plough, Astellas, and Arresto. Not applicable.

Minimally invasive surgery when treating endometriosis has a positive effect on health and on quality of work life of affected women.

What is the effect of the minimally invasive surgical treatment of endometriosis on health and on quality of work life (e.g. working performance) of affected women? Absence from work, performance loss and the general negative impact of endometriosis on the job are reduced significantly by the laparoscopic surgery. The benefits of surgery overall and of the laparoscopic method in particular for treating endometriosis have been described before. However, previous studies focus on medical benchmarks without including the patient's perspective in a quantitative manner. A retrospective questionnaire-based survey covering 211 women with endometriosis and a history of specific laparoscopic surgery in a Swiss university hospital, tertiary care center. Data were returned anonymously and were collected from the beginning of 2012 until March 2013. Women diagnosed with endometriosis and with at least one specific laparoscopic surgery in the past were enrolled in the study. The study investigated the effect of the minimally invasive surgery on health and on quality of work life of affected women. Questions used were obtained from the World Endometriosis Research Foundation (WERF) Global Study on Women's Health (GSWH) instrument. The questionnaire was shortened and adapted for the purpose of the present study. Of the 587 women invited to participate in the study, 232 (232/587 = 40%) returned the questionnaires. Twenty-one questionnaires were excluded due to incomplete data and 211 sets (211/587 = 36%) were included in the study. Our data show that 62% (n = 130) of the study population declared endometriosis as influencing the job during the period prior to surgery, compared with 28% after surgery (P < 0.001). The mean (maximal) absence from work due to endometriosis was reduced from 2.0 (4.9) to 0.5 (1.4) hours per week (P < 0.001). The mean (maximal) loss in working performance after the surgery averaged out at 5.7% (12.6%) compared with 17.5% (30.5%) before this treatment (P < 0.001). The mediocre response rate of the study weakens the representativeness of the investigated population. Considering the anonymous setting a non-responder investigation was not performed. A bias due to selection, information and negativity effects within a retrospective survey cannot be excluded, although study-sensitive questions were provided in multiple ways. The absence of a control group (sham group; e.g. patients undergoing specific diagnostic laparoscopy without treatment) is a further limitation of the study. Our study shows that indicated minimally invasive surgery has a clear positive effect on the wellbeing and working performance of women suffering from moderate to severe endometriosis. Furthermore, national net savings in indirect costs with the present number of surgeries is estimated to be €10.7 million per year. In an idealized setting (i.e. without any diagnosis delay) this figure could be more than doubled. The study was performed on behalf of the University Hospital of Bern (Inselspital) as one of the leading Swiss tertiary care centers. The authors do not declare any competing interests.

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.

The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey

To what extent do the management of endometriosis and the symptoms that remain after treatment affect the quality of life in women with the disease? Many women with endometriosis had impaired quality of life and continued to suffer from endometriosis-associated symptoms even though their endometriosis has been managed in tertiary care centres. The existing literature indicates that quality of life and work productivity is reduced in women with endometriosis. However, most studies have small sample sizes, are treatment related or examine newly diagnosed patients only. A cross-sectional questionnaire-based survey among 931 women with endometriosis treated in 12 tertiary care centres in 10 countries. Women diagnosed with endometriosis who had at least one contact related to endometriosis-associated symptoms during 2008 with a participating centre were enrolled into the study. The study investigated the effect of endometriosis on education, work and social wellbeing, endometriosis-associated symptoms and health-related quality of life, by using questions obtained from the World Endometriosis Research Foundation (WERF) GSWH instrument (designed and validated for the WERF Global Study on Women's Health) and the Short Form 36 version 2 (SF-36v2). Of 3216 women invited to participate in the study, 1450 (45%) provided informed consent and out of these, 931 (931/3216 = 29%) returned the questionnaires. Endometriosis had affected work in 51% of the women and affected relationships in 50% of the women at some time during their life. Dysmenorrhoea was reported by 59%, dyspareunia by 56% and chronic pelvic pain by 60% of women. Quality of life was decreased in all eight dimensions of the SF-36v2 compared with norm-based scores from a general US population (all P < 0.01). Multivariate regression analysis showed that number of co-morbidities, chronic pain and dyspareunia had an independent negative effect on both the physical and mental component of the SF-36v2. The fact that women were enrolled in tertiary care centres could lead to a possible over-representation of women with moderate-to-severe endometriosis, because the participating centres typically treat more complex and referred cases of endometriosis. The response rate was relatively low. Since there was no Institute Review Board approval to do a non-responder investigation on basic characteristics, some uncertainty remains regarding the representativeness of the investigated population. This international multicentre survey represents a large group of women with endometriosis, in all phases of the disease, which increases the generalizability of the data. Women still suffer from frequent symptoms, despite tertiary care management, in particular chronic pain and dyspareunia. As a result their quality of life is significantly decreased. A patient-centred approach with extensive collaboration across disciplines, such as pain specialists, psychologists, sexologists and social workers, may be a valuable strategy to improve the long-term care of women with endometriosis. The WERF EndoCost study is funded by the World Endometriosis Research Foundation (WERF) through grants received from Bayer Schering Pharma AG, Takeda Italia Farmaceutici SpA, Pfizer Ltd and the European Society of Human Reproduction and Embryology. The sponsors did not have a role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. L.H. is the chief executive and T.D. was a board member of WERF at the time of funding. T.D. holds the Merck-Serono Chair in Reproductive Medicine and Surgery, and the Ferring Chair in Reproductive Medicine at the Katholieke Universiteit Leuven in Belgium and has served as consultant/research collaborator for Merck-Serono, Schering-Plough, Astellas and Arresto.

Creating Solutions in Endometriosis: Global Collaboration through the World Endometriosis Research Foundation

Endometriosis affects an estimated 176 million women worldwide during the prime years of their lives. Yet many clinical questions remain unanswered, treatment failures are common, and there is little investment in investigating disease mechanisms. The World Endometriosis Research Foundation (WERF) has been created to provide a global platform where resources and intelligence are pooled to enable international collaboration in order to find answers so that treatments for endometriosis can be improved and prevention can become reality in future generations of women. WERF is now working with 30 centres in 19 countries conducting prospective studies investigating the impact of endometriosis, disease predictability, and personal and societal cost. (Journal of Endometriosis 2010; 2: 3–6)