ObjectiveTo standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition.DesignAn international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries.SettingTwo 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.

Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor b, with up to 20% being estrogen receptor a positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1edifferentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brainderived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. Endometriosis affects 10% of reproductive age women and is associated with persistent pelvic pain. 1 It is defined by the presence of endometrial-like tissue (lesions) found outside the uterus, most commonly on the peritoneum. The mechanisms underlying endometriosis-associated pain are poorly understood, but it has been postulated that estrogen-dependent neuroinflammation may be involved. 2 Notably, the presence of endometrial tissue fragments on the peritoneum elicits an immune response, including recruitment of macrophages, 3 blood vessels, and nerve fibers into the resultant lesions. 4,5 Within the lesions, CD68 þ macrophages have been detected in close association with nerve fibers. 6 Studies investigating macrophage activation and recruitment have revealed that endometriosis-associated macrophages exhibit a phenotype consistent with the alternative end of the macrophage activation spectrum. 7,8 In a mouse model of endometriosis that included cell transfer of polarized macrophages, Bacci et al 7 reported that mice injected with proinflammatory macrophages [macrophage (interferon g)] developed microscopic lesions, but those injected with alternatively activated macrophages [macrophage (IL-4)] developed larger lesions with a well-developed vasculature. Our studies in a mouse model of endometriosis have revealed that macrophages resident in peritoneal lesions can originate from both the peritoneum and the endometrium. 9

ObjectiveTo harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of fluid biospecimens relevant to endometriosis.DesignAn international collaboration involving 34 clinical/academic centers and 3 industry collaborators from 16 countries on 5 continents.SettingIn 2013, 2 workshops were conducted, followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing worldwide.Patient(s)None.Intervention(s)Consensus SOPs were based on: [1] systematic comparison of SOPs from 18 global centers collecting fluid samples from women with and without endometriosis on a medium/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 biofluid collection, processing, and storage in endometriosis research.Result(s)We developed recommended standard and minimum required SOPs for the collection, processing, and storage of plasma, serum, saliva, urine, endometrial/peritoneal fluid, and menstrual effluent, and a biospecimen data-collection form necessary for interpretation of sample-derived results.Conclusion(s)The Endometriosis Phenome and Biobanking Harmonisation Project SOPs allow endometriosis research centers to decrease variability in biofluid sample results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other female conditions involving biofluid samples subject to cyclic reproductive influences. 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 tri-annual follow-up. Updated versions will be made available at: endometriosisfoundation.org/ephect.