Research Methods · Measurement and Statistics
Lin T, Allaire C, As-Sanie S, Stratton P, Vincent K, Adamson GD, Arendt-Nielsen L, Bush D, Jansen F, Longpre J, Rombauts L, Shah J, Toussaint A, Hummelshoj L, Missmer SA, Yong PJ, WERF EPHect Physical Examination Working Group
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The World Endometriosis Research Foundation 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, 4 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 underwent multiple rounds of iterations and revisions.
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The EPHect-PE tool provides standardized assessment of physical examination characteristics and pain phenotyping. Data elements involve examination of back and pelvic girdle; abdomen including allodynia and trigger points; vulva including provoked vestibulodynia; pelvic floor muscle tone and tenderness; tenderness on unidigital pelvic examination; presence of pelvic nodularity; uterine size and mobility; presence of adnexal masses; presence of incisional masses; speculum examination; tenderness and allodynia at an extra-pelvic site (e.g., forearm); and recording of anthropometrics.
The EPHect-PE standards will facilitate the standardized documentation of the physical examination, including the assessment and documentation of examination phenotyping of endometriosis-associated pelvic pain.
Rojas HE et al., 2026 · Journal of women's health (2002)
To characterize differences between individuals with and without mid-cycle pain in a registry cohort with endometriosis. Prospective analysis of data from the Endometriosis Pelvic Pain Interdisciplinary Cohort Data Registry (Clinicaltrials.gov #NCT02911090) at a tertiary referral center in Western Canada. Three hundred forty-five individuals aged 18-49 years who: (1) had at least one episode of menstrual bleeding in the last 3 months, (2) attended a baseline initial visit, and (3) subsequently had surgery with histological confirmation of endometriosis between January 2018 and December 2023. Exclusion criteria included (1) previous hysterectomy; (2) hormonal suppressive therapy use in the last 3 months; and (3) missing data on mid-cycle pain, history of hormonal therapy use, or menstrual cycle regularity. N/A. Mid-cycle pain in the last month versus No mid-cycle pain in the last month. Of the 345 participants, 67% (n = 232) reported mid-cycle pain in the last month. Mid-cycle pain in the last month was significantly associated with higher mean Central Sensitization Inventory score (48 ± 17 versus 36 ± 16, p < 0.001) and more months of prior hormonal suppressive therapy use (58 [14-120] versus 26 [0-109], p = 0.012). Abnormal anatomy at the time of surgery (e.g., endometrioma, ovarian adhesions) was not associated with mid-cycle pain in the last month. In this endometriosis cohort at a tertiary referral center, most participants reported mid-cycle pain in the last month, which was associated with central sensitization but was not clearly related to endometriosis anatomical distortion.
Bouchard TP et al., 2026 · Reproductive biomedicine online · Free to read
Do quantitative urinary hormone measurements on the Mira monitor predict and confirm ovulation accurately compared with ultrasound in women with regular menstrual cycles? Do Mira urine hormones correlate with serum hormones? This was a prospective, single-centre, blinded diagnostic accuracy study with 52 women aged 19-44 years with regular cycles (24-38 days) who tracked 153 cycles over 18 months. Daily first-morning urine was tested with the Mira monitor for follicle stimulating hormone (FSH), oestrone-3-glucuronide (E13G), luteinizing hormone (LH) and pregnanediol glucuronide (PDG). Serial transvaginal ultrasounds (890 scans) confirmed the day of ovulation. Serum hormones were measured twice per cycle. The 121 ovulatory cycles from 49 participants with sufficient index test and reference standard data were included in the final analysis. The Mira LH peak day strongly predicted ultrasound-confirmed ovulation (R² = 0.96, P < 0.001; intraclass correlation coefficient = 0.971), with 96% of ovulations occurring within ±1 day. The Mira PDG increase was also strongly associated with ultrasound-confirmed day of ovulation (R² = 0.87, P < 0.001). First-morning urine hormones were significantly associated with serum hormones when collected within 90 min (LH: R² = 0.92; E13G: R² = 0.73; R² = 0.61; R² = 0.75). Anovulatory cycles were identified in 11% of regularly cycling participants. Quantitative urinary hormone monitoring with the Mira monitor provides accurate prediction and confirmation of ovulation, with strong urine-serum associations supporting reduced reliance on serial serum draws in select patients. These findings support clinical adoption of quantitative urinary fertility monitoring.
Balachandran S et al., 2026 · Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To assess the impact of the COVID-19 pandemic on reproductive outcomes in patients with recurrent pregnancy loss (RPL) and the influence of material and social deprivation on these outcomes. This retrospective cohort study included RPL patients seen at a specialized clinic between March 1, 2018, and February 28, 2022. Patients were categorized into two groups based on care period: pre-pandemic (March 1, 2018-February 29, 2020) and pandemic (March 1, 2020-February 28, 2022). Cumulative probabilities of birth were estimated using the cumulative incidence function within a competing risk framework, treating pregnancy loss as a competing event. Fine and Gray regression models calculated sub-distribution hazard ratio (sHR) of birth. 544 patients were included in the study, with 255 in the pre-pandemic group and 289 in the pandemic group. Individuals in the pandemic group were less likely to achieve pregnancy than those in the pre-pandemic group (relative risk = 0.50, 95% confidence interval [CI] 0.39 - 0.66). Among those who conceived, the cumulative probability of live birth was 0.77 in both groups. Relative to individuals residing in high-social deprivation neighborhoods, those living in moderately deprived areas had higher sub-distribution hazards of live birth (adjusted sHR = 1.97, 95% CI 1.25 - 3.10; P = 0.003). Within specialized RPL care and a universal maternity care system, pregnancy rates were lower during the first two years of the COVID-19 pandemic. However, among those who conceived, the probability of achieving a live birth remained similar between the pre-pandemic and pandemic periods.
Bouchard TP et al., 2026 · Reproductive biomedicine online · Free to read
Does formation of the corpus luteum help to identify the day of ovulation on ultrasound when follicular collapse is missed, and how reliable are sonographers versus a review panel in identifying the day of ovulation on ultrasound? Sonographers in a clinic in Canada performed serial endovaginal ultrasound scans (six to eight per cycle) to identify the day of ovulation in regularly cycling women (n = 40) who were followed for one to five cycles (n = 85). The day of ovulation was identified by: (i) identification of the dominant follicle; (ii) disappearance of the dominant follicle; and (iii) identification and dating of the corpus luteum. The main outcome measures were inter-rater reliability between two sonographers, and Bland-Altman agreement between the supervising sonographer and a panel that reviewed each scan to identify the day of ovulation. Of the 85 menstrual cycles reviewed, two cycles did not have sufficient data to date ovulation, one cycle showed an incidental dermoid cyst, and 11 cycles showed anovulatory patterns. This left a total of 71 cycles (84%) for which intra-rater reliability between two sonographers for identifying the day of ovulation was high (intraclass correlation coefficient = 0.99, P < 0.0001), and Bland-Altman agreement showed no significant difference in the estimated day of ovulation between the supervising sonographer and the panel (t = -0.28, P = 0.78). Corpus luteum criteria were necessary to help identify the day of ovulation in 14 of 71 cycles (20%). The estimated day of ovulation can be determined reliably on ultrasound by trained sonographers using collapse of the dominant follicle and formation of the corpus luteum based on six to eight scans per cycle.
Vitonis AF et al., 2014 · Fertil Steril · Free full text on PubMed Central
To harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration. An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. In 2013, two workshops followed by global consultation, bringing together 54 leaders in endometriosis research. None. INTERVENTION(S): Development of a self-administered endometriosis patient questionnaire (EPQ), based on [1] systematic comparison of questionnaires from eight centers that collect data from endometriosis cases (and controls/comparison women) on a medium to large scale (publication on >100 cases); [2] literature evidence; and [3] several global consultation rounds. MAIN OUTCOME MEASURE(S): Standard recommended and minimum required questionnaires to capture detailed clinical and covariate data. RESULT(S): The standard recommended (EPHect EPQ-S) and minimum required (EPHect EPQ-M) questionnaires contain questions on pelvic pain, subfertility and menstrual/reproductive history, hormone/medication use, medical history, and personal information. CONCLUSION(S): The EPQ captures the basic set of patient characteristics and exposures considered by the WERF EPHect Working Group to be most critical for the advancement of endometriosis research, but is also relevant to other female conditions with similar risk factors and/or symptomatology. The instruments will be reviewed based on feedback from investigators, and-after a first review after 1 year-triannually through systematic follow-up surveys. Updated versions will be made available through http://endometriosisfoundation.org/ephect.
Becker CM et al., 2014 · Fertil Steril · Free full text on PubMed Central
To standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition. An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries. Two workshops were conducted in 2013, bringing together 54 clinical, academic, and industry leaders in endometriosis research and management worldwide. PATIENT(S): None. INTERVENTION(S): A postsurgical scoring sheet containing general and gynecological patient and procedural information, extent of disease, the location and type of endometriotic lesion, and any other findings was developed during several rounds of review. Comments and any systematic surgical data collection tools used in the reviewers' centers were incorporated. MAIN OUTCOME MEASURE(S): The development of a standard recommended (SSF) and minimum required (MSF) form to collect data on the surgical phenotype of endometriosis. RESULT(S): SSF and MSF include detailed descriptions of lesions, modes of procedures and sample collection, comorbidities, and potential residual disease at the end of surgery, along with previously published instruments such as the revised American Society for Reproductive Medicine and Endometriosis Fertility Index classification tools for comparison and validation. CONCLUSION(S): This is the first multicenter, international collaboration between academic centers and industry addressing standardization of phenotypic data collection for a specific disease. The Endometriosis Phenome and Biobanking Harmonisation Project SSF and MSF are essential tools to increase our understanding of the pathogenesis of endometriosis by allowing large-scale collaborative research into the condition.
Fassbender A et al., 2014 · Fertil Steril · Free full text on PubMed Central
To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of human tissues relevant to endometriosis. An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. In 2013, two workshops were conducted followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing from around the world. PATIENT(S): None. INTERVENTION(S): Consensus SOPs were based on: 1) systematic comparison of SOPs from 24 global centers collecting tissue samples from women with and without endometriosis on a medium or large scale (publication on >100 cases); 2) literature evidence where available, or consultation with laboratory experts otherwise; and 3) several global consultation rounds. MAIN OUTCOME MEASURE(S): Standard recommended and minimum required SOPs for tissue collection, processing, and storage in endometriosis research. RESULT(S): We developed "recommended standard" and "minimum required" SOPs for the collection, processing, and storage of ectopic and eutopic endometrium, peritoneum, and myometrium, and a biospecimen data collection form necessary for interpretation of sample-derived results. CONCLUSION(S): The EPHect SOPs allow endometriosis research centers to decrease variability in tissue-based results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other gynecologic conditions involving endometrium, myometrium, and peritoneum. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback and through systematic triannual follow-up. Updated versions will be made available at: http://endometriosisfoundation.org/ephect.
Bendifallah S et al., 2023 · NEJM evidence
The discovery of a saliva-based micro–ribonucleic acid (miRNA) signature for endometriosis in 2022 opened up new perspectives for early and noninvasive diagnosis of the disease. The 109-miRNA saliva signature is the product of miRNA biomarkers and artificial intelligence (AI) modeling. We designed a multicenter study to provide external validation of its diagnostic accuracy. We present here an interim analysis. The first 200 patients included in the multicenter prospective ENDOmiRNA Saliva Test study (NCT05244668) were included for interim analysis. The study population comprised women from 18 to 43 years of age with a formal diagnosis of endometriosis or with suspected endometriosis. Epidemiologic, clinical, and saliva sequencing data were collected between November 2021 and March 2022. Genomewide miRNA expression profiling by small RNA sequencing using next-generation sequencing (NGS) was performed, and a random forest algorithm was used to assess the diagnostic accuracy. In this interim analysis of the external validation cohort, with a population prevalence of 79.5%, the 109-miRNA saliva diagnostic signature for endometriosis had a sensitivity of 96.2% (95% confidence interval [CI], 93.7 to 97.3%), specificity of 95.1% (95% CI, 85.2 to 99.1%), positive predictive value of 95.1% (95% CI, 85.2 to 99.1%), negative predictive value of 86.7% (95% CI, 77.6 to 90.3%), positive likelihood ratio of 19.7 (95% CI, 6.3 to 108.8), negative likelihood ratio of 0.04 (95% CI, 0.03 to 0.07), and area under the receiver operating characteristic curve of 0.96 (95% CI, 0.92 to 0.98). The use of NGS and AI in the sequencing and analysis of miRNA provided a saliva-based miRNA signature for endometriosis. Our interim analysis of a prospective multicenter external validation study provides support for its ongoing investigation as a diagnostic tool. (Funded by Ziwig and the Conseil Régional d’Ile de France [Grant EX024087]; ClinicalTrials.gov number, NCT05244668.)
