{"paper_id":"68d02e9d-3eef-40b3-af30-20de011193ed","body_text":"Abstract\n!\nIntroduction: Endometriosis is a heterogeneous\ndisease characterized by a range of different pre-\nsentations. It is usually diagnosed when patients\npresent with pain and/or infertility, but it has also\nbeen diagnosed in asymptomatic patients. Be-\ncause of the different diagnostic approaches and\ndiverse therapies, time to diagnosis can vary con-\nsiderably and the definitive diagnosis may be de-\nlayed, with some cases not being diagnosed for\nseveral years. Endometriosis patients have many\nunmet needs. A systematic registration and fol-\nlow-up of endometriosis patients could be useful\nto obtain an insight into the course of the disease.\nThe validation of biomarkers could contribute to\nthe development of diagnostic and predictive\ntests which could help select patients for surgical\nassessment earlier and offer better predictions\nabout patients who might benefit from medical,\nsurgical or other interventions. The aim is also to\nobtain a better understanding of the etiology,\npathogenesis and progression of the disease.\nMaterial and Methods: To do this, an online mul-\nticenter documentation system was introduced to\nfacilitate the establishment of a prospective mul-\nticenter case-control study, the IEEP (Internation-\nal Endometriosis Evaluation Program) study. We\nreport here on the first 696 patients with endo-\nmetriosis included in the program between June\n2013 and June 2015.\nResults: A documentation system was created,\nand the structure and course of the study were\nmapped out with regard to data collection and\nthe collection of biomaterials.\nConclusion: The documentation system permits\nthe history and clinical data of patients with en-\ndometriosis to be recorded. The IEEP combines\nZusammenfassung\n!\nEinleitung: Das Erkrankungsbild der Endometri-\nose ist sehr heterogen. Die Diagnosestellung er-\nfolgt häufig im Zusammenhang mit Schmerzen\nund/oder Sterilität. Es können aber auch keine Be-\nschwerden vorhanden sein. Dies führt dazu, dass\ndie Zeit bis zur definitiven Diagnose aufgrund\nverschiedener Diagnostik- und Behandlungs-\nansätze unterschiedlich lang sein kann und die\nDiagnose teilweise hierdurch verzögert wird. Die\nValidierung von Biomarkern könnte zur Entwick-\nlung eines diagnostischen und prädiktiven Tests\nbeitragen, um besser beurteilen zu können, ob\nund von welcher Therapie eine Patientin pro-\nfitiert.\nMaterial und Methoden: Um diese Fragestellun-\ngen zu beantworten, wurde multizentrisch ein\nonlinebasiertes Dokumentationssystem einge-\nführt, das zur Implementierung einer prospekti-\nven multizentrischen Fall-Kontroll-Studie, der\nIEEP (International Endometriosis Evaluation Pro-\ngram)-Studie, beiträgt. Im Zeitraum von Juni 2013\nbis Juni 2015 wurden die anamnestischen und\nklinischen Daten von 696 Patientinnen erfasst.\nErgebnisse: Durch die Implementierung konnten\nder Ablauf und die Strukturierung der Studie, ins-\nbesondere die Datenerhebung und die Biomateri-\nalsammlung, etabliert werden.\nSchlussfolgerung: In dem Dokumentationssys-\ntem ist es möglich, anamnestische und klinische\nDaten von Patientinnen mit Endometriose so zu\ndokumentieren, um sowohl in Kombination mit\nBiomaterialien wissenschaftliche Fragestellungen\nim Rahmen der IEEP-Studie zu beantworten, als\nauch Daten zu Zertifizierungszwecken zu erhe-\nben.\n* These two authors have contributed equally to this paper.\nThe International Endometriosis Evaluation Program\n(IEEP Study) – A Systematic Study for Physicians,\nResearchers and Patients\nDas internationale Endometriose-Evaluations-Programm (IEEP-Studie) –\neine systematische Studie für Kliniker, Forscher und Patientinnen\nAuthors S. Burghaus 1*, T. Fehm 4*, P. A. Fasching 1, 8,S .B l u m1, S. K. Renner 1,F .B a i e r1, T. Brodkorb 1, C. Fahlbusch 1,\nS. Findeklee 1, L. Häberle 2, K. Heusinger 1, T. Hildebrandt 1,J .L e r m a n n1, O. Strahl 1, G. Tchartchian 3, B. Bojahr 3,\nA. Porn 4, M. Fleisch 5, S. Reicke 6, T. Füger 6, C.-P. Hartung 7, J. Hackl 1, M. W. Beckmann 1, S. P. Renner 1\nAffiliations The affiliations are listed at the end of the article.\nKey words\nl\" endometriosis\nl\" biomarker\nl\" epidemiology\nl\" diagnostics\nl\" case control study\nSchlüsselwörter\nl\" Endometriose\nl\" Biomarker\nl\" Epidemiologie\nl\" Diagnostik\nl\" Fallkontrollstudie\nreceived 11. 2. 2016\nrevised 18. 4. 2016\naccepted 18. 4. 2016\nBibliography\nDOI http://dx.doi.org/\n10.1055/s-0042-106895\nGeburtsh Frauenheilk 2016; 76:\n875–881 © Georg Thieme\nVerlag KG Stuttgart · New York ·\nISSN 0016‑5751\nCorrespondence\nDr. Stefanie Burghaus\nFrauenklinik\nUniversitätsklinikum Erlangen\nFriedrich Alexander Universität\nErlangen-Nürnberg\nComprehensive Cancer Center\nErlangen-EMN\nUniversitäts-Endometriose-\nzentrum Franken, Stufe III\nUniversitätsstraße 21–23\n91054 Erlangen\nGermany\nStefanie.Burghaus@\nuk-erlangen.de\n875\nBurghaus S et al. The International Endometriosis … Geburtsh Frauenheilk 2016; 76: 875 –881\nDeutsche Version unter:\nhttp://dx.doi.org/\n10.1055/s-0042-106895\nOriginal Article\n\n\nIntroduction\n!\nA range of different clinical symptoms can signal the presence of\nendometriosis, some of which may overlap. In one group of\nwomen, the presence of endometriosis is associated with pain.\nIn another group of women, endometriosis presents as infertility.\nIn a further group of women, endometriosis is an incidental find-\ning and the women experience no or few clinical symptoms. The\nheterogeneity of the symptoms may lead to a significant delay in\ndiagnosing the disease [1].\nSurgical removal of endometriosis and systemic drug treatment\ncan reduce or even eliminate the pain experienced by some of\nthe women with the disease [2]. Some studies have reported a\npositive impact on fertility rates [2]. However, the interplay of\nfactors which result in some women finding relief in therapy\nwhile other women experience no alleviation are still not en-\ntirely understood.\nResearch into endometriosis is currently moving in completely\ndifferent directions. While some investigations are focusing on\ndiagnostic tests which could identify the disease in most affected\nwomen as early as possible, other studies are attempting to iden-\ntify those women in whom no intervention should be performed,\neither because the intervention will not help or because the af-\nfected women do not require treatment.\nFollowing the publication of the human genome in 2001, molec-\nular analysis methods have evolved rapidly and contributed to\nthe development of many therapies and diagnostic tests for other\ndiseases. There have also been significant improvements in data\nprocessing, allowing data to be usefully deployed in studies col-\nlecting epidemiological data. However, these efforts have not yet\nprogressed very far with regard to endometriosis.\nWe report here on the introduction of an online documentation\nsystem which will be the basis for the IEEP (International Endo-\nmetriosis Evaluation Program) study, a program which aims to\ninvestigate relevant clinical and molecular issues in an interna-\ntional research concept and which will additionally collect data\nfor certification purposes.\nMaterial and Methods\n!\nIn the period from June 2013 and June 2015, endometriosis was\ndiagnosed and treated in a total of 696 patients attending one of\nthe 5 participating hospitals and surgical outpatient facilities.\nThe data of these patients was recorded in an online documenta-\ntion system.\nThe clinical information of patients was obtained from their pa-\ntient records. These records include information on the patient ʼs\nhistory and medical treatment, including information on the sur-\ngical intervention, the histological findings, and any further\ntreatment. All patients for whom the clinical data were complete\nwere included in the analysis.\nAt the time of data collection patients were differentiated and\nclassified into one of two groups. Patients categorized into the\nPrevalent Endometriosis group had already been diagnosed pre-\nviously at operation; in these patients endometriosis had either\nrecurred or was still present. Patients classified into the Inciden-\ntal Endometriosis group had just been newly diagnosed with dis-\nease.\nDatabase design\nDocumentation of the patients ʼ history and clinical data was\ndone using an Oracle-based database with an electronic case re-\nport form (eCRF). The database meets all the requirements of a\nclinical study system. Data collection is based on appointments\nwith healthcare professionals; the database can document ad-\nverse events and serious adverse events and will permit audits\nto be carried out. The eCRF collects data on 23 variables at regis-\ntration and data on at least 41 variables are collected when doc-\numenting the patient ʼs medical history. In addition, at least 22\nendometriosis-specific variables are recorded; if the patient\nundergoes surgery for endometriosis, data on a further 18 vari-\nables are recorded. This allows the type of endometriosis diag-\nnosis to be differentiated very precisely, with the data showing\nwhether the diagnosis was made clinically or surgically and\nwhether the patient has superficial, deep infiltrating endome-\ntriosis, and/or adenomyosis. Information on 10 variables is col-\nlected at follow-up. Data monitoring is done using a professional\nquery verification process and a source data verification process.\nDocumentation in an online database system\nfor therapists and patients\nThe online documentation system for this multicenter study can\nbe accessed with a standard browser. Users do not require instal-\nlation of a separate program. Access to the documentation sys-\ntem is obtained and controlled by entering a username and a\npassword. The access to various tools is controlled by internal\nuse rights.\nCertification of endometriosis centers\nSince 2006 medical facilities have been certified by the German\nStiftung Endometriose-Forschung (SEF), the European Endome-\ntriosis League and the Endometriose Vereinigung Deutschland\ne. V. with the long-term goal of improving the quality of medical\ntreatment of, the research into, and the teaching on endometrio-\nsis [3]. Essential prerequisites for certification as an endometrio-\nsis center is diagnosing and treating endometriosis in accordance\nwith the guideline, cooperating with self-help groups and – in\nparticular – the documentation of (anonymized) patient-specific\ndata and data from patient follow-ups [4]. The latter information\nis queried in an annual report which also includes information on\nwhether patients with endometriosis are treated in hospital or\non an outpatient basis and whether they receive conservative\ntreatment or undergo surgery. The IEEP study network and the\ncollected data are used to compile the annual report.\nthis information with biomaterials and uses it for scientific stud-\nies. The recorded data can also be used to evaluate clinical quality\ncontrol measures such as the certification parameters used by\nthe EEL (European Endometriosis League) to assess certified en-\ndometriosis centers.\n876\nBurghaus S et al. The International Endometriosis … Geburtsh Frauenheilk 2016; 76: 875 –881\nGebFra Science\n\n\nResults\n!\nThe data on patients ʼ medical history recorded in the database\nare summarized in l\" Table 1 . Patients are differentiated accord-\ning to whether they have incidental or prevalent endometriosis.\nDifferent times to diagnosis\nWhen the documentation system was set up, the time of diagno-\nsis was discussed and it became clear that the circumstances that\nlead to a diagnosis of endometriosis differ widely. The patient\nmay present with a clinical suspicion of endometriosis; she may\nalready be suffering from endometriosis or have undergone a\nprevious operation; or, endometriosis may be diagnosed as an in-\ncidental finding during surgery performed for reasons uncon-\nnected to endometriosis. This combination of different possibil-\nities results in different diagnostic pathways ( l\n\" Fig. 1) which\nneed to be taken into account when processing the data.\nThe symptoms which lead to a diagnosis of endometriosis can be\nvery heterogeneous. Patients may present with pain or infertility\nor both. Other patients may experience no symptoms with the\ndiagnosis of endometriosis made as an incidental finding at sur-\ngery. To take account of patients ʼ individual needs and to ensure\nthat, as far as possible, all patients with endometriosis are in-\ncluded in the IEEP study, it was necessary to form different study\ncohorts ( l\n\" Fig. 2) as this will subsequently allow individual pre-\ndictions to be made.\nTable 1 Clinical variables which could play a role in the pathogenesis and prognosis of endometriosis or allow a prediction to be made with regard to the ther-\napeutic efficacy of different therapies.\nPatient characteristics Prevalent group (n = 202) Incidental group (n = 494) Total (n = 696)\nAge (years) at documentation Mean = 34.4\nSD = 7.9\nn = 202\nMean = 34.3\nSD = 7.9\nn = 494\nMean = 34.3\nSD = 7.9\nn = 696\nAge (years) at first diagnosis Mean = 29.7\nSD = 6.9\nn = 202\nMean = 34.4\nSD = 7.8\nn = 494\nMean = 33.0\nSD = 7.8\nn = 696\nAge at menarche (years) Mean = 12.6\nSD = 1.4\nn = 191\nMean = 13.0\nSD = 1.5\nn = 463\nMean = 12.9\nSD = 1.5\nn = 654\n≤ 11 41 (21.5 %) 73 (15.8 %) 114 (17.4 %)\n12 57 (29.8 %) 89 (19.2 %) 146 (22.3 %)\n13 43 (22.5 %) 135 (29.2 %) 178 (27.2 %)\n14 32 (16.8 %) 100 (21.6 %) 132 (20.2 %)\n≥ 15 18 (9.4 %) 66 (14.3 %) 84 (12.8 %)\nMenstrual cycle length (days) Mean = 29.2\nSD = 7.0\nn = 108\nMean = 28.1\nSD = 5.8\nn = 273\nMean = 28.3\nSD = 6.1\nn = 381\n≤ 27 38 (35.2 %) 93 (34.1 %) 131 (34.4 %)\n28 31 (28.7 %) 97 (35.5 %) 128 (33.6 %)\n≥ 29 39 (36.1 %) 83 (30.4 %) 122 (32.0 %)\nDuration of menstrual bleeding (days) Mean = 5.8\nSD = 2.1\nn = 124\nMean = 5.5\nSD = 2.0\nn = 360\nMean = 5.6\nSD = 2.0\nn = 484\n≤ 4 24 (19.4 %) 93 (25.8 %) 117 (24.2 %)\n5 37 (29.8 %) 135 (37.5 %) 172 (35.5 %)\n≥ 6 63 (50.8 %) 132 (36.7 %) 195 (40.3 %)\nPregnancies (number) Total 202 (100 %) 493 (100 %) 695 (100 %)\n0 110 (54.5 %) 296 (60.0 %) 406 (58.4 %)\n1 43 (21.3 %) 91 (18.5 %) 134 (19.3 %)\n2 31 (15.3 %) 65 (13.2 %) 96 (13.8 %)\n≥ 3 18 (8.9 %) 41 (8.3 %) 59 (8.5 %)\nLive births (number) Total 92 (100 %) 197 (100 %) 289 (100 %)\n0 17 (18.5 %) 48 (24.4 %) 65 (22.5 %)\n1 38 (41.3 %) 73 (37.1 %) 111 (38.4 %)\n2 30 (32.6 %) 60 (30.5 %) 90 (31.1 %)\n≥ 3 7 (7.6 %) 16 (8.1 %) 23 (8.0 %)\nAbortions (number) Total 92 (100 %) 197 (100 %) 289 (100 %)\n0 77 (83.7 %) 158 (80.2 %) 235 (81.3 %)\n≥ 1 15 (16.3 %) 39 (19.8 %) 54 (18.7 %)\nOral contraceptive intake (ever and currently) Total 156 (100 %) 242 (100 %) 398 (100 %)\nYes 151 (96.8 %) 228 (94.2 %) 379 (95.2 %)\nNo 5 (3.2 %) 14 (5.8 %) 19 (4.8 %)\nBody mass index (kg/m\n2) Total 200 (100 %) 482 (100 %) 682 (100 %)\n< 18.5 8 (4.0 %) 19 (3.9 %) 26 (4.0 %)\n18.5 to < 25 120 (60.0 %) 319 (66.2 %) 425 (64.4 %)\n25 to < 30 44 (22.0 %) 88 (18.3 %) 127 (19.4 %)\n≥ 30 28 (14.0 %) 56 (11.6 %) 81 (12.3 %)\n877\nBurghaus S et al. The International Endometriosis … Geburtsh Frauenheilk 2016; 76: 875 –881\nOriginal Article\n\n\nCollection of biomaterials\nThe collection of biomaterials will play a central role in the IEEP\nstudy network. The collected biomaterials will be used to carry\nout high-quality patient-relevant analyses and will be combined\nwith clinical information to validate a diagnostic and predictive\ntest (l\n\" Fig. 3). The aim is to find a predictive and diagnostic test\nwhich will predict the response to therapy as well as a predictive\ntest which will predict the response to therapy over the course of\ndisease after endometriosis has been diagnosed.\nThe procedure and process of collecting biomaterial was estab-\nlished with the introduction of the documentation system at the\nGynecology Department of Erlangen University Hospital. Collec-\ntion of biomaterials includes both material obtained at the first\ndiagnosis of endometriosis and any biomaterials collected when\nAsymptomatic\nSymptomatic\nInclusion in the study\nIncidental diagnosis at surgery\nSurgical diagnosis/treatment\nClinical diagnosis\nLead time\nClinical diagnosis\nSurgical diagnosis/treatment\nChange of conservative therapy\nConservative therapy\nSurgical diagnosis/treatment\nSurgical diagnosis/treatment\nConservative therapy\nConservative therapySurgical diagnosis\nSurgical diagnosis/treatment\nChange of conservative therapy\nFig. 1 Different scenarios until a diagnosis of endometriosis is made: in asymptomatic patients the diagnosis of endometriosis may be an incidental findin ga t\nsurgery. But even symptomatic patients may be diagnosed with endometriosis in a number of different ways, through surgery or clinically.\nFollow-up with regard to diagnosis of endometriosis/pregnancy\nFollow-up with regard to\ndiagnosis of endometrio-\nsis/recurrence/pregnancy\nEndometriosis\nyes\nOP for other reasons\nOP because of infertility\nOP because of pain\nEndometriosis\nno\nEndometriosis\nyesCohort 2:\nPlanned surgery\nCohort 3:\nControl cohort\nCohort 1:\nPrevalent endometriosis\nEndometriosis\nno\nEndometriosis\nyes\nEndometriosis\nno\nFig. 2 Overview of the study cohorts of the IEEP study (OP: surgery).\n878\nBurghaus S et al. The International Endometriosis … Geburtsh Frauenheilk 2016; 76: 875 –881\nGebFra Science\n\n\npatients experience recurrence or a worsening of symptoms\n(l\" Fig. 4).\nDiscussion\n!\nWe report here on the introduction of an online documentation\nsystem for patients with endometriosis which is being used to es-\ntablish the structures and processes of the prospective multicen-\nter IEEP (International Endometriosis Evaluation Program) study.\nThe aim is to validate a diagnostic and predictive test which will\nmeet the different needs of patients.\nThe latency period between the first occurrence of endometrio-\nsis-specific symptoms and the diagnosis of endometriosis has\nbeen reported to be as much as 11 years [1]. A sensitive and spe-\ncific non-invasive diagnostic test to diagnose endometriosis\ncould lead to an earlier diagnosis of the disease. The advantage\nwould be that no invasive diagnostics (i.e. surgery) would be re-\nquired and the earlier time of diagnosis could prevent disease\nprogression during the latency period. Although laparoscopy is\ngenerally considered to be a safe intervention with minimal risks\nand a low morbidity compared to laparotomy, complications can\nnevertheless occur, depending on the type of surgical interven-\ntion [5].\nTo validate a diagnostic and predictive test it is first necessary to\nidentify patients who have been diagnosed with endometriosis.\nThe most certain means of diagnosing endometriosis is by histo-\nlogical examination during surgical workup. But clinical exami-\nnation and a review of the patient ʼs medical history can also pro-\nvide information which points to endometriosis. Depending on\nwhen the patient is diagnosed with endometriosis, this can lead\nto a number of different scenarios which data management must\ntake into account.\nIn addition to a diagnostic test to diagnose endometriosis, a pre-\ndictive test could offer help when making decisions such as\nwhether surgical and/or drug therapy would be beneficial or\nwhether the patient does not require therapy. A prospective ob-\nservation of patients with endometriosis is necessary to validate\nany predictive test. For this it is important to create different\nstudy cohorts which will take account of the individual needs of\npatients.\nLower abdominal pain is one of the main symptoms of patients\nwith endometriosis. Endometriosis is diagnosed in around one\nthird of patients who undergo surgery for chronic lower abdom-\ninal pain [6]. As described in the guideline, a workup of charac-\nteristic symptoms must be done to establish or exclude a diagno-\nsis of endometriosis, with the workup consisting of either lapa-\nroscopy or carefully calculated drug therapy [7]. With regard to\ndisease progression, there are only limited data on the risks asso-\nciated with repeat abdominal surgery or on increased pain in pa-\ntients with endometriosis, as high or low pain levels have been\nfound not to be correlated with the extent of disease [8]. There\nare also only a few studies on the efficacy of postoperative drug\ntherapies (GnRH analogues, combined oral contraceptives or\nplacebo) [9, 10]. In one study, only 6.6 % of patients with deep in-\nfiltrating endometriosis and chronic pelvic pain who underwent\nsurgery experienced recurrence, defined as a suspicious finding\non rectovaginal examination, sigmoidoscopy or laparoscopy after\n94 months [11].\nThe IEEP study aims to identify a cohort of patients and their clin-\nical data and biomarkers, who were diagnosed with endometrio-\nsis after presenting with recurrent pain.\nThis cohort of patients with pain will be followed up prospec-\ntively with regard to the rate of recurrence, with recurrence de-\nfined as a worsening of symptoms or repeat abdominal surgery,\nand the impact of various therapies will be evaluated in order to\nmake predictions regarding various therapies.\nEndometriosis is diagnosed during laparoscopy in a quarter of\npatients with infertility [12]. The association between endome-\ntriosis and infertility remains unclear, although various etiologies\nhave been proposed and discussed [13]. Anatomical changes of\nthe adnexa are accepted to be a potential cause. Other etiologies\nNo\ntherapy\nEndometriosis\nyes\nEndometriosis\nyes\nEndometriosis\nno\nEndometriosis\nno\nPredictive test 2\n()together with OP material\nPredictive test 2\n(together with OP material)\nDiagnostic test\nnegative\nDiagnostic test\npositive\nDiagnostic testPredictive test 1\n(together with diagnostic test)\nNo\ntherapy\nOP\nbest\nOP\nbest\nOP+MedTh\nbest\nOP+MedTh\nbest\nMedTh\nbest\nMedTh\nbest\nFig. 3 Opportunities to implement a diagnostic or predictive test (OP: surgery, MedTh: drug therapy).\n879\nBurghaus S et al. The International Endometriosis … Geburtsh Frauenheilk 2016; 76: 875 –881\nOriginal Article\n\n\ninclude changes to the immunological milieu for implantation or\naffecting sperm motility, uterotubal transport disorders, and dis-\norders of oocyte maturation [14, 15]. Published pregnancy rates\nfor patients with endometriosis range from 24 to 54 %, but these\nfigures may be an overestimation as some patients did not at-\ntempt spontaneous pregnancy prior to surgery for endometriosis\n[16].\nThe IEEP study aims to contribute to validating a diagnostic and\npredictive test in patients with endometriosis and infertility, so\nas to be able to advise patients about the therapeutic approach\nand offer individualized therapy. Moreover, the study may result\nin a better understanding of the possible common etiology of en-\ndometriosis and infertility and allow the evaluation of pregnancy\nrates in a large patient population.\nNo correlation has been found between severity of symptoms\nand the extent of endometriotic lesions [17]. Endometriosis is di-\nagnosed as an incidental finding in 5–25 % of patients who under-\ngo laparoscopic surgery for other reasons, such as tubal ligation\n[12, 18, 19]. In 2009, a multicenter study confirmed that the prev-\nalence of adenomyosis is the same in women with uterine fi-\nbroids, endometriosis, pelvic pain or abnormal uterine bleeding\nand those who had none of the above-mentioned disorders [20].\nIn the IEEP study the cohort with incidental diagnosed endome-\ntriosis will serve as a comparative cohort to the two other cohorts\nof patients with pain and patients with infertility and contribute\nto the validation of a diagnostic and predictive test as well as\nfinding an answer to the question whether these asymptomatic\npatients benefit from therapy or not.\nIt is important to ensure that the number of patients wrongly\nidentified by the diagnostic test as negative for disease is as low\nas possible, as this will otherwise result in a continued delay in\ndiagnosis and reduce the patients ʼ quality of life. It is also impor-\ntant not to wrongly identify patients as positive for disease to\navoid overtreatment and the wrong therapy.\nThe aim must therefore be to ensure the highest possible validity\nof a diagnostic or predictive test. This could be achieved by add-\ning the patients ʼ clinical data to the obtained biomarkers [21].\nOne of the most important advantages of validated biomarkers\nwill be that they can be used to diagnose endometriosis and\nmonitor disease quickly, cost-effectively and non-invasively. Pos-\nsible biomarkers include peripheral biomarkers in blood, such as\ngrowth factors, hormones, proteolytic enzymes, glycoproteins,\nsoluble adhesion molecules, immunological cell changes, auto-\nantibodies, miRNA, circulating cell-free DNA, and cytokines [22],\nand tissue obtained during surgery.\nIn the context of the IEEP study, biomarkers and clinical data will\nbe collected and recorded on inclusion into the study and at\nevery recurrence or worsening of symptoms.\nThe goal of this collaboration between centers is to process the\ninformation obtained in such a way that differences in the treat-\nObservation/therapy\nInclusion into the study possible at any time\nBiomaterial at inclusion into\nthe study, including FFPE Biomaterial\nClinical dataClinical data Clinical data Clinical data\nBiomaterial Biomaterial\nFirst diagnosis of\nendometriosis\nControl group First diagnosis of\nendometriosis/pregnancy\n1st recurrence/\npregnancy\n2nd recurrence/\npregnancy\n3rd recurrence/\npregnancy\nObservation/therapy Observation/therapy\nSurvey of quality of life/patient questionnaires every 3 months\nObservation/therapyObservation\n…………\nFig. 4 Overview of the IEEP study: inclusion into the study for cases and\ncontrols at any time, thereby collection of biomaterial and clinical data and\nelevation of recurrence of endometriosis, pregnancies and optionally first di-\nagnosis of endometriosis in the control group (FFPE: formalin-fixed, paraffin-\nembedded tissue).\n880\nBurghaus S et al. The International Endometriosis … Geburtsh Frauenheilk 2016; 76: 875 –881\nGebFra Science\n\n\nment provided by the participating centers are made visible,\nprompting a debate about these differences. Patients can contrib-\nute to the evaluation by completing specific questionnaires and\nthe information obtained can be shared with the patients. In the\ncurrent age of information, data collection and documentation\nshould not only be used to collect data for studies but also deliver\na direct and immediate benefit for the patients, as well as for the\nparticipating centers.\nConclusion\n!\nThere is little information available which could help predict the\ncourse of endometriotic disease or the course of therapy and the\nresponse to different therapies. Treatment center networks, re-\nsearch networks and study networks need to focus and combine\ntheir resources to ensure that patients receive the best treatment\navailable and need to cooperate to develop individualized treat-\nment concepts. Working in the interest of patients with endome-\ntriosis, these are the goals the IEEP study network has set itself.\nConflict of Interest\n!\nThe authors declare no conflicts of interest.\nAffiliations\n1 Department of Gynecology and Obstetrics, Erlangen University Hospital,\nFriedrich Alexander University of Erlangen –Nuremberg, Comprehensive\nCancer Center Erlangen-EMN, Erlangen, Germany\n2 Biostatistics Unit, Department of Gynecology and Obstetrics, Erlangen\nUniversity Hospital, Comprehensive Cancer Center Erlangen-EMN, Erlangen,\nGermany\n3 Certified Centre for Endometriosis at the MIC Klinik, Berlin, Germany\n4 Department of Obstetrics and Gynecology, University of Duesseldorf,\nDuesseldorf, Germany\n5 HELIOS University Hospital Wuppertal, Wuppertal, Germany\n6 MIC Centre, Women Health Clinic Dr. Geisenhofer, Munich, Germany\n7 Rems-Murr-Klinik, Schorndorf, Germany\n8 Division of Hematology and Oncology, Department of Medicine,\nDavid Geffen School of Medicine, University of California at Los Angeles,\nLos Angeles, CA, USA\nReferences\n1 Hudelist G, Fritzer N, Thomas A et al. 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