{"paper_id":"671b820c-25dd-4611-a812-5f0a0ffd0bfb","body_text":"Standards Used by a Clinical and Scientific Endometriosis Center\nfor the Diagnosis and Therapy of Patients with Endometriosis\nStandards für die Diagnostik und Therapie von Patientinnen\nmit Endometriose an einem klinis chen und wissenschaftlichen\nEndometriosezentrum\nAuthors\nStefanie Burghaus 1, Thomas Hildebrandt 1, Christine Fahlbusch 1, Katharina Heusinger 1, Sophia Antoniadis 1,J o h a n n e s\nLermann 2,J a n i n aH a c k l1,L o t h a rH ä b e r l e3, Stefan P. Renner 4, Peter A. Fasching 1,M a t t h i a sW .B e c k m a n n1, Simon Blum 1\nAffiliations\n1 Frauenklinik, Universitätsklinikum Erlangen, Universitäts-\nEndometriosezentrum Franken (UEF), Erlangen, Germany\n2 Klinik für Gynäkologie und Geburtshilfe, Klinikum\nBayreuth, Bayreuth, Germany\n3 Abteilung für Biostatistik, Frauenklinik, Universitäts-\nklinikum Erlangen, Erlangen, Germany\n4 Frauenklinik, Klinikum Sindelfingen-Böblingen, Böblingen,\nGermany\nKey words\nendometriosis, sterility, lower abdominal pain, diagnostic\nSchlüsselwörter\nEndometriose, Unfruchtbarkeit, Unterleibsschmerzen,\nDiagnostik\nreceived 26. 8. 2018\nrevised 30. 10. 2018\naccepted 4. 12. 2018\nBibliography\nDOI https://doi.org/10.1055/a-0813-4411\nPublished online 28. 2. 2019 | Geburtsh Frauenheilk 2019; 79:\n487–497 © Georg Thieme Verlag KG Stuttgart · New York |\nISSN 0016 ‑5751\nCorrespondence\nDr. Stefanie Burghaus\nFrauenklinik, Universitätsklinikum Erlangen\nUniversitätsstraße 21 –23, 91054 Erlangen, Germany\nStefanie.Burghaus@uk-erlangen.de\nDeutsche Version unter:\nhttps://doi.org/10.1055/a-0813-4411\nSupporting Information:\nhttps://doi.org/10.1055/a-0813-4411\nABSTRACT\nEndometriosis is one of the most common benign gynecolog-\nical diseases. The extremely heterogeneous complex of symp-\ntoms complicates the diagnosis and treatment of this disease.\nIn most patients, there is a latency period of several years be-\ntween the first occurrence of symptoms and the definitive di-\nagnosis. This paper aims (1) to evaluate standards for the di-\nagnosis and treatment of patients with (symptoms suspicious\nfor) endometriosis in terms of feasibility, and (2) to assess the\npotential use of data collected by a certified clinical and scien-\ntific endometriosis center to answer scientific questions. Stan-\ndards for outpatient consultations were developed for a spe-\ncial endometriosis outpatient clinic. Between January 2014\nand December 2017, a total of 1715 outpatients with a suspi-\ncion of endometriosis presented to this special endometriosis\noutpatient clinic; the diagnosis and treatment of patients was\ncarried out in accordance with the developed standards. Data\nof this patient cohort obtained from patient records created\nduring outpatient consultations and from a questionnaire re-\ncorded in an Oracle-based database was analyzed. The patient\ncohort was also compared with another patient cohort who\nhad attended different outpatient clinics and had been diag-\nnosed intraoperatively with endometriosis. 41.8 % of patients\nexamined during special outpatient consultations had surgery\nfor suspicion or recurrence of endometriosis. Endometriosis\nwas confirmed in 81.5 % of cases. Pain symptoms were the\nmain indication for surgery in 70.1 % of cases compared to\n45.1 % of cases in the comparison group. The structured ap-\nproach used in the special endometriosis outpatient clinic is\na key aspect of the care provided by the certified clinical and\nscientific endometriosis center. It ensures that patients are di-\nagnosed and treated in accordance with guideline recommen-\ndations, that diagnosis and treatment comply with certifica-\ntion requirements, and that the collected data can be used\nto answer scientific questions.\nGebFra Science | Original Article\n487Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497\nPublished online: 2019-02-28\n\nIntroduction\nEndometriosis is associated with a range of different clinical symp-\ntoms. The tentative diagnosis may be based on menstrual cycle-\nrelated pain, chronic pain or infertility, and the definitive diagnosis\nis then confirmed by diagnostic laparoscopy. However, endome-\ntriosis may also be diagnosed as an incidental finding in asymp-\ntomatic patients. Around 25 –30 % of women between the ages\nof 25 and 35 years are affected by this disease [1, 2]. The preva-\nlence of endometriosis among sterile women is even higher, with\na reported incidence of up to 50 % [3 – 5 ] .A c c o r d i n gt od a t af r o m\nthe German Federal Statistical Office, 27 113 patients with endo-\nmetriosis were hospitalized in Germany in 2016 and had conserva-\ntive or surgical treatment. Because of the very heterogeneous\npresentation of the disease, it is assumed that the number of pa-\ntients with non-surgically diagnosed endometriosis is significantly\nhigher [6].\nAlthough gynecological research is becoming incr easingly\naware of endometriosis, it is still assumed that the average latency\nperiod between the first appearance of symptoms and the defini-\ntive diagnosis is around 10 years [7]. This delay does not just put\npatients under considerable psychological strain and reduces their\nquality of life, it also leads to higher healthcare costs due to fre-\nquent visits to different physicians and unnecessary or futile diag-\nnostic and therapeutic procedures and limits patients ʼ capacity to\nwork [8 – 11]. Establishing a consistent structure for special endo-\nmetriosis outpatient clinics is necessary to enable treating physi-\ncians to make comparable, efficient and specific diagnoses and\npromptly prescribe the appropriate therapeutic measures.\nTo improve the quality of medical care, research, and teaching,\na certification process for endometriosis centers was introduced\nby the Stiftung Endometriose-Forschung (SEF), the European En-\ndometriosis League and the self-help group Endometriose Vereini-\ngung Deutschland e. V. in 2006 [12]. It uses a phased approach\nand defines the requisite criteria for certification. According to\nthe criteria, diagnosis and treatment must be carried out in ac-\ncordance with appropriate guidelines, the center must work to-\ngether with self-help groups, the patient ʼs medical history must\nbe recorded, and the center must compile an annual report. The\nstandards differentiate between\n1. gynecological practices,\n2. centers of reproductive medicine,\n3. rehabilitation clinics,\n4. centers with only one surgeon specialized in treating endome-\ntriosis, and\n5. hospitals and surgical day clinics, which can be certified as clin-\nical or clinical and scientific endometriosis centers.\nPatients have also taken note of this new certification process. In a\nmulticenter study, 2500 patients were asked what they knew\nabout certified centers, and 43.8 % of respondents reported that\nthey had deliberately contacted a certified center to obtain a diag-\nnosis and treatment [13].\nThis study aimed to evaluate the feasibility of the standards de-\nveloped for certified clinical and scientific endometriosis centers\nto diagnose and treat patients with (symptoms suspicious for) en-\ndometriosis and analyzed a patient cohort diagnosed with endo-\nmetriosis to determine whether additional scientific questions\nneed to be asked. A model for the organizational structure of spe-\ncial endometriosis outpatient clinics and for the necessary diag-\nnostic and therapeutic procedures is presented here, and aims to\ndefine professional clinical standards.\nPatients and Methods\nIn 2006, a standardized special endometriosis outpatient clinic\nwas set up in the Gynecology Department of the University Hospi-\ntal of Erlangen and certified as a highest-level endometriosis cen-\nter. Outpatient clinics are held twice a week; they are staffed by\nspecialists who have additional qualifications/have undergone ad-\nvanced training in endometriosis. Patients present to the clinic\nafter a referral by their gynecologist or on their own initiative after\nZUSAMMENFASSUNG\nEndometriose zählt zu den häufigsten gutartigen gynäkologi-\nschen Erkrankungen. Ein sehr heterogener Symptomkomplex\nerschwert die Diagnose und die Therapie der Erkrankung.\nMeist besteht eine mehrjährige Latenz zwischen dem erstmali-\ngen Auftreten von Symptomen und der Diagnosestellung. Ziel\nder vorliegenden Arbeit sind (1) die Überprüfung von definier-\nten Standards für die Diagnostik und die Therapie von Patien-\ntinnen mit (Verdacht auf) Endometriose auf ihre Umsetzbarkeit\nund (2) eine mögliche Nutzung dieses zur Beantwortung von\nwissenschaftlichen Fragestellungen als Grundlage im zertifi-\nzierten klinischen und wissenschaftlichen Endometriosezen-\ntrum. In der Spezialambulanz für Endometriose wurde ein Stan-\ndard für die Durchführung dieser Sprechstunde entwickelt. Im\nRahmen dieser Spezialambulanz erfolgten 1715 ambulante Pa-\ntientenvorstellungen von Januar 2014 bis Dezember 2017, we-\ngen der (Verdachts-)Diagnose Endometriose, die nach diesem\nStandard diagnostiziert und behandelt wurden. Anhand der\nDokumentation der Patientinnenakte und des Fragebogens in\neiner Oracle-basierten Datenbank wurde eine Analyse des aus\ndieser Sprechstunde hervorgehenden Patientenkollektivs\ndurchgeführt. Zudem wurde ein Vergleich mit dem Patientin-\nnenkollektiv durchgeführt, das sich in anderen Spezialambu-\nlanzen vorgestellt hat und bei dem intraoperativ ebenfalls En-\ndometriose diagnostiziert wurde. 41,8 % der Patientinnen aus\ndieser Sprechstunde wurden bei Verdacht auf Endometriose\noder dem Rezidiv einer Endometriose operiert. Eine Endomet-\nriose konnte bei 81,5 % bestätigt werden. Die Schmerzsympto-\nmatik war in 70,1 % die Hauptindikation für die Operation, im\nVergleichskollektiv war diese 45,1 %. Die vorgestellte Struktu-\nrierung einer Spezialambulanz für Endometriose als zentraler\nBestandteil eines zertifizierten klinischen und wissenschaftli-\nchen Endometriosezentrums ermöglicht eine leitliniengerech-\nte Diagnostik und Therapie der Patientinnen mit Endometriose,\ndie Erfüllung der Zertifizierungsvoraussetzungen und das Be-\nantworten von wissenschaftlichen Fragestellungen.\n488 Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497\nGebFra Science | Original Article\n\n\nthey have researched the options themselves. A diagnostic and\ntherapeutic approach was developed, based on the most impor-\ntant symptoms of disease. The feasibility of the approach was ret-\nrospectively evaluated in this feasibility study.\nStandards for special outpatient endometriosis clinics\nwithin certified endometriosis centers\nBefore the patient first presents to her physician, she is given a\ncase-history questionnaire to complete which contains detailed\nquestions about her general medical and gynecological history.\nThe patient is additionally given a specific questionnaire with\nquestions which focus on typical endometriosis-related com-\nplaints. In addition to the case-history questionnaire, the patient\nis given a further questionnaire with questions which aim to an-\nswer a number of scientific questions. During the subsequent in-\ndepth talk with the treating physician, the patient ʼs individual an-\nswers are discussed and amplified. The patient ʼs history of symp-\ntoms is recorded, with a special focus on symptoms typical for en-\ndometriosis (\n▶ Fig. 1). Particular importance is attached to the\npatientʼs report on the extent of pain she experiences, which she\nrates using a numeric analog scale with values between 1 and 10.\nAfter the completed questionnaires have been handed in, the\nfirst diagnostic procedure consists of a general gynecological ex-\namination and ultrasound (\n▶ Fig. 2). Ultrasound by itself is not\nenough to make a diagnosis of endometriosis or exclude it. How-\never, ultrasound can be used to detect the presence of ovarian en-\ndometrial cysts (also known as an endometrioma), assess the con-\ndition of the uterus including indications for adenomyosis, detect\nadhesions in the inner genital region, and evaluate uterine motil-\nity status and any thickening of the intestinal wall in cases where\nthe intestines are also affected [14 – 16]. Renal ultrasound should\nbe carried out in addition to gynecological ultrasound to exclude\nasymptomatic hydronephrosis caused by deep infiltrating endo-\nmetriosis affecting the ureters.\nSymptom-based diagnostic procedures are carried out to in-\nvestigate endometriotic symptoms (\n▶ Fig. 3). Clinical examina-\ntions are of only limited use to diagnose deep infiltrating endome-\ntriosis. For certain clinical conditions such as deep infiltrating en-\ndometriosis of the ureter with hydronephrosis, magnetic reso-\nnance imaging is required to determine the extent of disease.\nMagnetic resonance imaging (MRI) and transvaginal ultrasound\nare equivalent in terms of making a diagnosis. However, MRI is\nmore sensitive for detecting endometriotic foci in the vagina and\nuterosacral ligaments [17]. When patients present with chronic\npain of the lower abdomen, close cooperation with a gastroenter-\nologist is recommended to investigate and exclude other possible\ncauses such as food intolerances, chronic inflammatory bowel dis-\nMedical history\nGeneral medical history: Symptom-based\nmedical history:Menstrual history\nDysmenorrheaGravidity/parity\nLower abdominal painPrevious therapies\nDyschezia/\nhematochezia\nPrevious operations\nDysuria/hematuria\nMedication\n(previous and current)\nDyspareuniaAdditional diagnoses\nSterilityAllergies\nAsymptomaticBody mass index\nFamilial history\nSocial history\n▶ Fig. 1 Standards for taking the general and symptomatic gyne-\ncological history of patients with endometriosis or symptoms sus-\npicious for endometriosis.\nBasic diagnostic procedures\nInspection/speculum examination Bimanual vaginal rectal\npalpation\nand Vaginal ultrasound\nRenal ultrasound\nGenitals/vagina\nPosterior vaginal fornix Uterus\nBil. uterosacral lig.\nBil. adnexa\nParametria\nPouch of Douglas\nRectovaginal septum\nUterus (signs of adenomyosis)\nOvaries\nIntestines\nBladder\n▶ Fig. 2 Standards for basic diagnostic procedures for patients with (symptoms suspicious for) endometriosis. Bil. = bilateral.\n489Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497\n\n\nease or irritable bowel syndrome and to obtain a differential diag-\nnosis.\nThe third and last step of the treatment algorithm consists of\ndeveloping an individual, guideline-based and, where necessary,\ninterdisciplinary treatment concept for the respective patient\n(\n▶ Fig. 4). The treatment of endometriosis rests on two pillars:\nsurgery and conservative management [18 – 20]. The choice of\nt h e r a p yi sg u i d e db yt h ep a t i e n tʼs symptoms and the patient ʼs\nreasons for presenting to the outpatient clinic and by the time\nand type of diagnosis, i.e. whether it is a primary diagnosis or\nwhether the patient is presenting with recurrence. The definitive\ndiagnosis can only be obtained by histological examination. Surgi-\ncal removal of endometriotic foci is the gold standard to control\nsymptoms [20 – 22]. When considering whether excision of endo-\nmetrioma is indicated, the decision to opt for surgery must also\ntake the subsequent reduction in ovarian reserve after repeat sur-\ngical excisions into account. Other indications for endoscopic\ntherapy of recurrent endometriosis are pain resistant to therapy\nand organ destruction. If the patient ʼs main focus is not on the\npain but on her wish to have children, then, depending on the pa-\ntientʼs age and ovarian reserve, after a primary diagnosis of endo-\nmetriosis, the recommended approach in most cases is surgery to\nremove the endometriotic foci followed by a visit to a clinic for re-\nproductive medicine. If the patient has rASRM stage I or II endo-\nmetriosis, then ablation or excision of endometriotic foci can im-\nprove fertility [23]. A patient- and goal-oriented approach is es-\nsential to find an individual solution for the patient [24]. It is worth\nassessing whether the patient should participate in a study to help\nestablish new therapeutic concepts [25, 26].\nMedical hormone therapy should be prescribed postopera-\ntively as prophylaxis and long-term therapy to prevent the recur-\nrence of endometriosis [18, 27]. Treatment options include pro-\ngestogen therapies, oral contraceptives (off-label use) and GnRH\nanalogs [18].\nPresentation to an outpatient pain clinic can be an additional\ntherapeutic option for patients with persistent postoperative pain\n[28]. Other postoperative therapeutic options include physiother-\napy, nutrition counselling and rehabilitation as well as individual\ntherapeutic approaches such as osteopathy and traditional Chi-\nnese medicine (TCM). In addition to surgical and medical thera-\npies, the interdisciplinary concept also includes the integration of\npsychosomatic therapies for patients with chronic lower abdomi-\nnal pain and sterility.\nA multidisciplinary approach is useful for patients with chronic\nlower abdominal pain [29, 30]. The quality of life of affected pa-\ntients and their ability to cope with chronic pain on a day-to-day\nbasis can be significantly improved by the integration of psycho-\nsomatic care into their care plan, and this can ultimately also have\na positive impact on treatment results [22, 31].\nA follow-up examination at the special endometriosis outpa-\ntient clinic or by the patient ʼs regular gynecologist should be\nagreed upon with the patient to monitor the outcome of treat-\nment.\nDescriptive analysis of treated patients\nThis study analyzed patients with (symptoms suspicious for) en-\ndometriosis who presented to the special endometriosis outpa-\ntient clinic of the University Endometriosis Center Franken (UEF)\nbetween January 1, 2014 and December 31, 2016. Patients from\nthis patient population who had surgery between January 1, 2014\nand December 31, 2017 were selected for further analysis. The\nselected time period was extended by a further year to include\nthose patients whose visit to the outpatient clinic resulted in an\nindication for surgery. Only patients who were operated in the\nSymptom-based diagnostic procedures\n(Diagnostic) laparoscopy\nDysmenorrhea Dysuria Dyspareunia Dyschezia Sterility\nMRI if applicable Cystoscopy in pa-\ntients with chronic\nmicrohematuria\nand/or ultrasound-\nbased suspicion of\nbladder infiltration\nif applicable\nMRI\nColoscopy/\nrectoscopy to\nexclude differ-\nential diagnosis\nif applicable\nMRI if applicable\nPresentation to\nGastroenterology\nDept. to obtain\ndifferential diag-\nnosis, e.g. food\nintolerances\nHysteroscopy\nChromo-\npertubation\n▶ Fig. 3 Symptom-based diagnosis of patients with (symptoms suspicious for) endometriosis. MRI = magnetic resonance imaging.\n490 Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497\nGebFra Science | Original Article\n\n\nGynecology Department of Erlangen University Hospital were in-\ncluded.\nPatients in whom endometrial disease was detected during\nsurgery carried out between January 1, 2014 and December 31,\n2017 were also included in the study. These patients had present-\ned to other medical facilities such as polyclinics, private medical\nconsultations, preoperative outpatient clinics or special outpa-\ntient clinics for gynecological endocrinology and reproductive\nmedicine for lower abdominal pain of unknown origin or sterility.\nPatient data consisting of the patient ʼs medical history and\nclinical and surgical data were recorded in an Oracle-based IEEP\n(International Endometriosis Evaluation Program) database. The\nIEEP database is a multicenter online documentation system\nwhich has been used since January 1, 2014 to record the medical\nhistory and clinical data of patients with endometriosis in Ger-\nmany. By June 2018, the data of more than 8000 female patients\ntreated in different centers all over Germany had been recorded in\nthe database. Patients ʼ medical history and clinical examination\nfindings are recorded using an electronic case report form (eCRF).\nIn addition, every patient completes a questionnaire which pro-\nvides data for various scientific questions (Supplement). This is\nuseful as it contributes to developing and improving established\nstandards and provides data for current research projects [32].\nBased on the IEEP database, a sub-analysis was done of pa-\ntients presenting to the special endometriosis outpatient clinic\nand to other outpatient clinics. The analysis included age at initial\noperation, age at menarche, cycle length, duration of menstrual\nflow, body mass index (BMI), use of oral contraceptives (at any\ntime and currently), incidental or prevalent endometriosis,\nwhether surgery was indicated, surgical procedure (minimally in-\nvasive/open surgery/intraoperative change of surgical procedure\n(from minimally invasive to open surgery), ASRM classification,\ndeep infiltrating endometriosis, histological diagnosis, and\nwhether a hysterectomy was carried out.\nTherapy\nSuspicion of\nendometriosis\nRecurrent\nendometriosis\nSurgical:\nLaparoscopy to con-\nfirm diagnosis and\nexcise endometriotic\nf o c i ;i fn e c e s s a r y ,i n -\nterdisciplinary proce-\ndure together with\nsurgeon/urologist\nSurgical:\nPoss. re-laparoscopy\n(laparotomy) if organ\ndamage is present\n(e.g., hydronephrosis)\na n dt h e r ei sas u s p i -\ncion of deep infiltrat-\ning endometriosis;\nif necessary, interdis-\nciplinary procedure\ntogether with sur-\ngeon/urologist\nIndividual symptom-based therapy and hormone therapy after\nexcluding organ damage (e.g., hydronephrosis), no diagnostic signs\nof deep infiltrating endometriosis (except uterine adenomyosis) and\nthe exclusion of an endometrioma\nHormone therapy (progestogen therapy, off-label use of oral\ncontraceptives, GnRH analogs)/prophylaxis against recurrence\nPostoperative hormone therapy as prophylaxis against recurrence\nor reproductive medicine if the patient wishes to have a child\nPostoperative hormone therapy as prophylaxis against recurrence or\nreproductive medicine if the patient wishes to have a child\nPain therapy (multimodal)\nPain therapy (multimodal)\nPsychosomatic support\nPsychosomatic support\nPhysiotherapy\nPhysiotherapy\nNutritional counseling\nNutritional counseling\nRehabilitation\nRehabilitation\nSexual counseling\nSexual counseling\nOsteopathy\nOsteopathy\nTCM/acupuncture\nTCM/acupuncture\nAlternative/integrative therapies:\nAlternative/integrative therapies:\nConservative:\nConservative:\n▶ Fig. 4 Treatment algorithm: interdisciplinary care of patients with (symptoms suspicious for) endometriosis.\n491Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497\n\n\nResults\nA total of 1245 patients with (symptoms suspicious for) endome-\ntriosis presented to the special endometriosis outpatient clinic be-\ntween January 1, 2014 and December 31, 2016, with a total of\n1715 visits to the outpatient clinic ( ▶ Fig. 5 a). 520 of these pa-\ntients underwent surgery in the period between January 1, 2014\nand December 31, 2017. Endometriosis was additionally diag-\nnosed during surgery in a further 1375 patients in the period be-\ntween January 1, 2014 and December 31, 2017. The patient co-\nhort of operated patients from the special endometriosis out-\npatient clinic and from other outpatient clinics is described in\n▶ Table 1 . All patients were treated in accordance with the diag-\nnostic and therapeutic concept established by the UEF.\nIndications for surgery\nThis study evaluated the patients attending the special endome-\ntriosis outpatient clinic who required surgery. More than one third\nof patients (41.8 %; n = 520) who presented to the special endo-\nmetriosis outpatient clinic between 2014 and 2016 subsequently\nunderwent surgery between 2014 and 2017 because of sus-\npected endometriosis or recurrence of endometriosis (\n▶ Fig. 5 a).\nEndometriosis was confirmed intraoperatively in 424 (81.5 %) of\nthe 520 patients during 478 operations.\nThe main indication for surgery was pain (70.1 %; n = 302). Pri-\nmary or secondary sterility was cited as the indication for surgery\nin 22.3 % (n = 96) of patients. Only 7.7 % (n = 33) of patients were\noperated on for other reasons such as suspicious ovarian findings.\nThe number of re-operations in this period, i.e. the number of pa-\ntients who underwent more than one operation, was 47 (9.8 %).\nSome of the repeat operations were carried out for recurrence of\nendometriosis. In other cases, repeat surgery was done because\nextensive intestinal endometriosis was found intraoperatively,\nand this finding required an interdisciplinary follow-up procedure\nwith partial intestinal resection.\nPatient cohorts from other special outpatient clinics\nBetween 2014 and 2017, 1853 operations were carried out at the\nGynecology Department in 1744 patients with an intraoperative\ndiagnosis of endometriosis. This results in a difference of 1320 pa-\ntients who had surgery but did not present to the special endome-\ntriosis outpatient clinic preoperatively (\n▶ Fig. 5 b). This cohort,\nwhich amounts to 75.7 % of operated patients, consists of patients\nwith an incidental finding of endometriosis during surgery for oth-\nSpecial endometriosis\noutpatient clinic\nn = 1245\nV = 1715\nConservative\nn = 725 Yes\nn = 424\nO = 478\nPain\nO = 302\nIndications\nfor surgery\nDiagnosis of\nendometriosis\nDiagnosis of\nendometriosis\nSterility\nO=9 6\nOther\nO=3 3\nNot specified\nO=4 7\na\nb\nPain\nO = 573\nIndications\nfor surgery\nSterility\nO = 362\nOther\nO = 336\nNot specified\nO = 104\nConservative\nn=N .E . Yes\nn = 1320\nO = 1375\nSurgery\nn = 520\nO = 580 No\nn=9 6\nO = 102\nSurgery\nn=N .E .\nNo\nn=N .E .\nOther outpatient clinics:\nPolyclinic\nPrivate consultation\nDirect referral to pre-\noperative outpatient clinic\nSpecial outpatient clinic\nfor reproductive medicine\nn=N .E .\n▶ Fig. 5 Description of patients who underwent surgery or were treated conservatively from a the special endometriosis outpatient clinic, and\nb other outpatient clinics. n = number of patients, V = number of outpatient visits; O = number of surgeries, N. E. = not evaluable.\n492 Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497\nGebFra Science | Original Article\n\n\ner causes and patients who presented to other medical facilities\nsuch as special outpatient clinics for reproductive medicine, pri-\nvate consultations, polyclinics or directly to the preoperative out-\npatient clinic because of sterility or lower abdominal pain.\nWhen evaluating the main indication for surgery, it turned out\nthat pain was mentioned significantly less often (45.1%). Sterility\n(28.5 %) and other reasons (26.4 %) were the other main indica-\ntions for surgery and almost as important as pain.\nThe percentage of procedures performed laparoscopically\n(96.9 %), the percentage of histological confirmations of endome-\ntriosis (90.0 %) and the extent of endometriosis classified using\nthe rASRM score were comparable with the percentages of the\npatients from the endometriosis outpatient clinic.\nSurgical procedure and intraoperative findings\nThe overwhelming majority of surgical operations were carried\nout as laparoscopic procedures (95.9 %), although in ten cases\nthe procedure had to change intraoperatively from laparoscopic\nsurgery to laparotomy. Six of these ten operations were carried\nout as interdisciplinary procedures, and the reason for switching\nprocedures was partial intestinal resection carried out in coopera-\ntion with another surgeon. In two cases, secondary laparotomy\nwas performed for myoma enucleation and to remove a large\nmyomatous uterus, respectively. The final two operations were\ncarried out together with a urologist, with one patient under-\ngoing nephrectomy and one patient undergoing ureteric implan-\ntation for endometriosis.\n63.1 % of cases had rASRM stage I –II disease. Histological con-\nfirmation was obtained in 93.7 % of operations (\n▶ Table 2 ). Of the\npatients where no histological evaluation was carried out intra-\noperatively, 19 patients had an adenomatous uterus and hysterec-\ntomy was not carried out. Only two cases had macroscopic suspi-\ncion of endometriosis which was not confirmed histologically. The\nremaining cases where no histological investigation was carried\nout were two-stage surgeries. In these cases, extensive disease\nwith deep infiltrating endometriosis was found during the first op-\neration. The decision was then taken to discontinue surgery and\nto perform a second subsequent operation, during which the di-\nagnosis was confirmed and partial intestinal resection or partial\nureteric resection was carried out. Hysterectomy was carried out\nin 10.6 % of recorded cases.\nPostoperative course\nAfter surgery, every patient was given a doctor ʼs letter with writ-\nten therapeutic recommendations. The recommendations in-\ncluded the proposed time of the postoperative follow-up exami-\nnations and, depending on the case, recommendations for medi-\ncations to control symptoms and to prevent recurrence, or further\nprocedures to be followed in cases with primary or secondary ste-\nrility. It was recommended that patients wishing to have children\nshould attend a special outpatient clinic for reproductive medi-\n▶ Table 1 Characteristics of patients with a diagnosis of endometriosis who underwent surgery.\nParameter Special endometriosis\noutpatient clinic\nOther outpatient clinics Total\nn=4 2 4 n=1 3 2 0 n=1 7 4 4\nAge at first surgery (years) 32.9 (7.8, 399)* 34.9 (8.3, 1242)* 34.4 (8.2, 1642)*\nAge at menarche (years) 12.9 (1.5, 398)* 13.0 (1.5, 1179)* 12.9 (1.5, 1577)*\nCycle length at initial presentation (days) 28.7 (7.4, 229)* 28.0 (5.3, 686)* 28.2 (5.9, 915)*\nDuration of menstrual flow at initial presentation\n(days)\n5.4 (1.6, 279)* 5.4 (1.9, 896)* 5.4 (1.8, 1175)*\nBody mass index at initial presentation (kg/m\n2) 24.1 (5.0, 327)* 24.3 (5.1, 1060)* 24.3 (5.1, 1384)*\nUse of oral contraceptives (ever) at the time\nof the initial presentation\n417 (100%) 1300 (100%) 1717 (100 %)\n▪ yes 246 (59.0 %) 476 (36.6 %) 722 (42.1 %)\n▪ no 6( 1 . 4 % ) 4 9( 3 . 8% ) 5 5( 3 . 2% )\n▪ unknown 165 (39.6 %) 775 (59.6 %) 940 (54.7 %)\nUse of oral contraceptives (currently) at the time\nof initial presentation\n418 (100%) 1301 (100%) 1719 (100 %)\n▪ yes 140 (33.5 %) 305 (23.4 %) 445 (25.9 %)\n▪ no 272 (65.1 %) 951 (73.1 %) 1223 (71.0 %)\n▪ unknown 6( 1 . 4 % ) 4 5( 3 . 5% ) 5 1( 3 . 0% )\nPrevalent/incidental endometriosis\nat initial presentation\n390 (100%) 1218 (100%) 1608 (100 %)\n▪ prevalent 224 (57.4 %) 194 (15.9 %) 418 (26.0 %)\n▪ incidental 166 (42.6 %) 1024 (84.1 %) 1250 (74.0 %)\n* Mean value (standard deviation, number of patients)\n493Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497\n\n\ncine. Postoperative follow-up examinations were carried out ei-\nther at the Gynecology Department or by doctors in private prac-\ntice. 16.0 % (n = 68) of patients from the special endometriosis\noutpatient clinic with confirmation of endometriosis who had\nundergone surgery returned to our clinic within one year for a\n(postoperative) follow-up examination. Most of these patients\nhad undergone an interdisciplinary procedure in cooperation with\na surgeon and urologist and required specific follow-up examina-\ntions.\nDiscussion\nStandards for the process to be used by a special endometriosis\noutpatient clinic were developed at a certified clinical and scien-\ntific endometriosis center. These standards cover the specific clin-\nical steps required to obtain a diagnosis, decide on the appropri-\nate therapy and collect data for scientific purposes. The standards\nare based on the international recommendation of the S2k guide-\nline “Diagnosis and Therapy of Endometriosis ” [20] and the Euro-\npean Society of Human Reproduction and Embryology [33]. A re-\nview of the literature showed that no comparable standardized\napproach for special endometriosis outpatient clinics has been\npublished to date. There have been a number of international at-\ntempts to standardize the management of endometriosis and to\ncompare national therapy recommendations. Every patient with\nendometriosis should be able to access diagnostic procedures\nand treatment tailored to her needs in certified specialist centers\n[34]. Careful detailed investigation of the patient ʼsm e d i c a lh i s -\ntory can provide important information about the location of en-\ndometriotic foci which, taken together with the findings obtained\nduring non-invasive diagnostic procedures, can confirm the suspi-\ncion of endometriosis [35, 36]. The patient ʼsm e d i c a lh i s t o r yt o -\n▶ Table 2 Description of surgical approach used.\nParameter Special endometriosis\noutpatient clinic\nOther outpatient clinics Total\nO=4 7 8 O=1 3 7 5 O=1 8 5 3\nIndications for surgery 431 (100%) 1271 (100%) 1702 (100 %)\n▪ pain 302 (70.07 %) 573 (45.1 %) 875 (51.4 %)\n▪ sterility 96 (22.27 %) 362 (28.5 %) 458 (26.9 %)\n▪ other 33 (7.66 %) 336 (26.4 %) 369 (21.7 %)\nSurgical approach 441 (100%) 1273 (100%) 1714 (100 %)\n▪ minimally invasive 423 (95.9 %) 1233 (96.9 %) 1656 (96.6 %)\n▪ laparotomy 4( 0 . 9 % ) 1 6( 1 . 3% ) 2 0( 1 . 1% )\n▪ change of procedure intraoperatively 10 (2.3 %) 16 (1.3 %) 26 (1.5 %)\n▪ other 4 (0.9 %) 7 (0.5 %) 11 (0.6 %)\n▪ unknown 0( 0 . 0 % ) 1( 0 . 1 % ) 1( 0 . 1 % )\nrASRM 404 (100%) 1195 (100%) 1599 (100 %)\n▪ stage 0 21 (5.2 %) 80 (6.7 %) 101 (6.3 %)\n▪ stage I 143 (35.4 %) 564 (47.2 %) 707 (44.2 %)\n▪ stage II 93 (23.0 %) 210 (17.6 %) 303 (18.9 %)\n▪ stage III 53 (13.1 %) 146 (12.2 %) 199 (12.4 %)\n▪ stage IV 82 (20.3 %) 132 (11.0 %) 214 (13.4 %)\n▪ unknown 12 (3.0 %) 63 (5.3 %) 75 (4.7 %)\nDeep infiltrating endometriosis 442 (100%) 1275 (100%) 1717 (100 %)\n▪ yes 327 (74.0 %) 779 (61.1 %) 1106 (64.4 %)\n▪ no 112 (25.3 %) 471 (36.9 %) 583 (34.0 %)\n▪ unknown 3( 0 . 7 % ) 2 5( 2 . 0% ) 2 8( 1 . 6% )\nHistological confirmation 442 (100%) 1275 (100%) 1717 (100 %)\n▪ yes 414 (93.7 %) 1147 (90.0 %) 1561 (90.9 %)\n▪ no 28 (6.3 %) 125 (9.8%) 153 (8.9 %)\n▪ unknown 0( 0 . 0 % ) 3( 0 . 2 % ) 3( 0 . 2 % )\nHysterectomy 445 (100%) 1279 (100%) 1724 (100 %)\n▪ yes 47 (10.6 %) 153 (12.0 %) 200 (11.6 %)\n▪ no 398 (89.4 %) 1126 (88.0 %) 1524 (88.4 %)\nO = number of operations; rASRM = classification of the American Society for Reproductive Medicine\n494 Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497\nGebFra Science | Original Article\n\n\ngether with a gynecological examination have a combined sensi-\ntivity of around 80 % for diagnosing endometriosis, although only\nhistological examination can provide the definitive confirmation\nof the diagnosis.\nThere is a symptom-based prognostic model which can be\nused to improve the selection of patients requiring surgery. The\nselection accuracy for patients who had surgery with histological\nconfirmation of endometriosis was higher for patients with rASRM\nstages III and IV. By comparison, the predictive accuracy was\nmuch poorer for lower-stage endometriosis (stage I and II) [37].\nIn our study, endometriosis was confirmed in more than 80 % of\npatients who underwent surgery. The extent of pain is not directly\ncorrelated with the location and extent of endometriosis [38, 39].\nOur data were unable to confirm an increase in rASRM scores for\npatients with significant clinical symptoms (data not shown).\nSome specialist societies support primary conservative medi-\ncal treatment for women with mild to moderate lower abdominal\npain who have regular ultrasound examinations [33, 40]. Howev-\ner, there are no data which have shown that this approach is supe-\nrior, and this approach should therefore only be agreed upon with\npatients on an individual basis.\nA review of the indications for surgery provides information\nabout the patient cohort presenting to the special endometriosis\noutpatient clinic. Non-specific lower abdominal pain was associ-\nated with endometriosis in up to half of all cases [35]. Our results\nshowed that 70.1 % of surgical procedures performed in patients\nfrom the special endometriosis outpatient clinic and 45.1 % of op-\nerations carried out in patients from other outpatient clinics were\nperformed because of pain. The low number of patients with ste-\nrility presenting to the special endometriosis outpatient clinic can\nbe explained by the fact that patients with sterility usually first\npresented to the special outpatient clinic for gynecological endo-\ncrinology and reproductive medicine at the University Center for\nReproduction Franken (UEF) and did not initially present to the en-\ndometriosis center. In the patient cohort from other outpatient\nclinics, the relatively low number of patients where pain was the\nmain indication for surgery was because, in the majority of these\npatients, surgery was indicated for other findings such as myo-\nmatous uterus, ovarian cysts or sterility.\nSurgical procedures to diagnose and alleviate endometriosis\nplay a very important role. In terms of diagnosing endometriosis,\nno imaging procedures used to date offer results which are as ac-\ncurate as surgery [41], meaning that surgical procedures remain\nthe gold standard for diagnosing endometriosis. However, be-\ncause of the possible negative consequences of this invasive ap-\nproach such as adhesions, loss of functional ovarian tissue or dam-\nage to internal organs, it is important that in cases with recurrent\nendometriosis the recommendation for surgery is based on strict\nand restrictive criteria [24, 42]. If stage rASRM I/II resectable en-\ndometriosis is found during surgical investigation for endometrio-\nsis, complete excision of endometriotic tissue should be done dur-\ning the same procedure. Cases with rASRM stage III/IV endome-\ntriosis require an individual approach according to the main ther-\napy goals agreed upon with the patient prior to surgery (pain re-\nlief vs. pregnancy). During the surgical removal of endometriotic\ntissue in a patient with ovarian endometriosis it is important to\nconsider the best way of preserving ovarian reserve in the long\nterm, particularly when treating patients who wish to have chil-\ndren.\nWomen below the age of 30 are reported to have a higher risk\nfor repeat surgery for endometriosis [43]. The success of therapy\nin terms of improving pain symptoms is higher for the first opera-\ntion compared to subsequent operations. Abboth et al. reported a\ndecrease in pain symptoms of 83 % in the first 6 months compared\nto 53 % after subsequent operations [21]. Experienced surgeons,\nguideline-based recommendations for follow-up treatment, and\nthe integration of interdisciplinary therapy concepts should re-\nduce the rate of re-operations, although the well-known, dis-\nease-specific rate of recurrence reported for endometriosis must\nbe taken into account [44]. Even after carrying out complete exci-\nsion of endometriotic foci, recurrence rates of between 10 % and\n55 % within the first 12 months after surgery have been reported\n[45].\nTo be able to deal appropriately with the above-mentioned cir-\ncumstances, it is proposed that patients with a history of disease\nshould be cared for in endometriosis centers. This is also reflected\nby our figures. After presenting to the special endometriosis out-\npatient clinic, excisional surgery was carried out 49.2 % of all pa-\ntients. These patients were already known to have endometriosis,\nand surgery was performed because of therapy-resistant pain.\nThe majority of patients presenting to the special endometriosis\noutpatient clinic had already been treated previously for endome-\ntriosis, and this was also reflected in the percentage of patients\ntaking oral contraceptives (59.1 %). By comparison, 89.9% of pa-\ntients from other outpatient clinics did not have a previous surgi-\ncal confirmation of endometriosis, and the percentage of them\ntaking oral contraceptives as therapy was significantly lower\n(36.6 %). The quality criteria for surgery for patients from the spe-\ncial endometriosis outpatient clinic did not differ from that for pa-\ntients from other outpatient clinics.\n96.6 % of procedures were carried out as minimally invasive\nprocedures. Magnification provides better visualization of the\nperitoneum, making it easier to detect and excise endometriotic\nfoci. The intraoperative histological confirmation of the suspected\ndiagnosis was high (90.9 %). The majority of cases where surgical\nprocedures did not provide histological confirmation of the sus-\npected diagnosis had uterine adenomyosis. Nor routine proce-\ndure has been established to confirm uterine adenomyosis, mak-\ning it difficult to confirm adenomyosis surgically. A large percent-\nage of cases in this patient population had deep infiltrating endo-\nmetriosis, the majority of whom had uterine adenomyosis.\nWhen a center becomes a certified endometriosis center, its\nquality criteria must also include postoperative follow-up. At\npresent, 16.0 % of patients who have a surgical procedure for en-\ndometriosis return to our clinic for their postoperative follow-up.\nNon-hospital-based gynecologists who cooperate with the endo-\nmetriosis center by providing follow-up care for operated patients\nreceive written therapy recommendations, thereby completing\nthe postoperative care network. All operated patients who have\nno wish to have children and no contraindications should be of-\nfered prophylactic therapy against recurrence to reduce the recur-\nrence of typical endometriosis-related complaints and prevent\nthe development of endometrioma [18, 46]. Patients who booked\nappointments with non-hospital-based gynecologists who are\n495Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497\n\n\npart of the care network were not included in this data evaluation,\nwhich may explain the low number of postoperative follow-up ex-\naminations carried out by the center.\nThis study aimed to present the standards for the process fol-\nlowed by a special endometriosis outpatient clinic and to evaluate\na specific patient cohort. The study has both strengths and weak-\nnesses. Setting up a special outpatient clinic and the correspond-\ning data analysis is associated with higher costs for personnel and\ndocumentation and a greater ex penditure of time and requires\nadditional resources in terms of more personnel. However, the\nmajority of patients who received an intraoperative diagnosis of\nendometriosis previously presented to other outpatient clinics.\nDiagnosis and treatment at these other outpatient clinics are in\naccordance with the same accepted standards, but because of\nthe inconsistency with which outpatient visits are coded, the data\nof patients who present to those outpatient clinics with a suspi-\ncion of endometriosis or recurrence of endometriosis and are\nmanaged conservatively or for whom the suspected endometrio-\nsis was not confirmed intraoperatively cannot be evaluated. More-\nover, the data does not yet show whether the patient presented to\nthe outpatient clinic at the recommendation of her gynecologist,\nof an outpatient endometriosis clinic or on her own initiative. If\nthis information were available, it could be used to develop a tar-\ngeted process to attract more patients to the endometriosis out-\npatient clinic and focus more attention on the topic of endome-\ntriosis.\nThe strengths of the study include the high number of treated\npatients and the fact that use of a scientific questionnaire made it\npossible to analyze the characteristics of operated patients. The\nclinicʼs structure represents a marketing tool to recruit patients\nto the center and maintain a long-term relationship with patients.\nThe standards for the special endometriosis outpatient clinic\npublished here are also relevant for routine gynecological prac-\ntice. They ensure that the choice of therapy is patient-centered\nand goal-oriented. This was demonstrated by the high level of\nsensitivity for the indications for surgery. The concept presented\nin this study should serve as an example and can be implemented\nor adapted by other endometriosis centers according to their in-\nfrastructure. As the recommendations for a standardized therapy\nalgorithm for women with endometriosis are, in some cases, still\ninconsistent, the algorithm presented here aimed to fill this gap.\nAttending an outpatient clinic encourages a relationship of trust\nand creates a bond between the patient and the clinic where she\nis treated. Patients benefit from undergoing surgery at a certified\ncenter for endometriosis which follows standardized processes,\nwith patients profiting from the clinical and scientific expertise\nand the quality-assured transparent structures and processes cre-\nated during certification.\nConflict of Interest\nThe authors declare that they have no conflict of interest.\nReferences\n[1] Saha R, Kuja-Halkola R, Tornvall P et al. Reproductive and Lifestyle Fac-\ntors Associated with Endometriosis in a Large Cross-Sectional Population\nSample. J Womens Health (Larchmt) 2017; 26: 152 –158\n[2] Sar ıdoğ an E. Adolescent endometriosis. Eur J Obstet Gynecol Reprod Biol\n2017; 209: 46 –49\n[3] Mahmood TA, Templeton A. Prevalence and genesis of endometriosis.\nHum Reprod 1991; 6: 544 –549\n[4] Witz CA, Burns WN. Endometriosis and infertility: is there a cause and\neffect relationship? Gynecol Obstet Invest 2002; 53 (Suppl. 1): 2 –11\n[5] Viganò P, Parazzini F, Somigliana E et al. Endometriosis: epidemiology\nand aetiological factors. Best Pract Res Clin Obstet Gynaecol 2004; 18:\n177–200\n[6] Buck Louis GM, Hediger ML, Peterson CM et al.; ENDO Study Working\nGroup. Incidence of endometriosis by study population and diagnostic\nmethod: the ENDO study. Fertil Steril 2011; 96: 360 –365\n[7] Hudelist G, Fritzer N, Thomas A et al. Diagnostic delay for endometriosis\nin Austria and Germany: causes and possible consequences. Hum Re-\nprod 2012; 27: 3412 –3416\n[8] Simoens S, Hummelshoj L, D ʼHooghe T. Endometriosis: cost estimates\nand methodological perspective. Hum Reprod Update 2007; 13: 395 –\n404\n[9] Nnoaham KE, Hummelshoj L, Webster P et al.; World Endometriosis Re-\nsearch Foundation Global Study of Women ʼs Health consortium. Impact\nof endometriosis on quality of life and work productivity: a multicenter\nstudy across ten countries. Fertil Steril 2011; 96: 366 –373.e8\n[10] Simoens S, Dunselman G, Dirksen C et al. The burden of endometriosis:\ncosts and quality of life of women with endometriosis and treated in re-\nferral centres. H um Reprod 2012; 27: 1292 –1299\n[11] Soliman AM, Surrey E, Bonafede M et al. Real-World Evaluation of Direct\nand Indirect Economic Burden Among Endometriosis Patients in the\nUnited States. Adv Ther 2018; 35: 408 –423\n[12] Ebert AD, Ulrich U, Keckstein J et al.; Endometriosis Research Founda-\ntion, and the European Endometriosis League. Implementation of certi-\nfied endometriosis centers: 5-year experience in German-speaking Eu-\nrope. Gynecol Obstet Invest 2013; 76: 4 –9\n[13] Thiel FC, Scharl A, Hildebrandt T et al. Financing of certified centers: a\nwillingness-to-pay analysis. Arch Gynecol Obstet 2013; 287: 495 –509\n[14] Hudelist G, Fritzer N, Staettner S et al. Uterine sliding sign: a simple\nsonographic predictor for presence of deep infiltrating endometriosis\nof the rectum. Ultrasound Obstet Gynecol 2013; 41: 692 –695\n[15] Exacoustos C, Manganaro L, Zupi E. Imaging for the evaluation of endo-\nmetriosis and adenomyosis. Best Pract Res Clin Obstet Gynaecol 2014;\n28: 655 –681\n[16] Van den Bosch T, Dueholm M, Leone FP et al. Terms, definitions and\nmeasurements to desc ribe sonog raphic features of myometrium and\nuterine masses: a consensus opinion from the Morphological Uterus\nSonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol\n2015; 46: 284 –298\n[17] Bazot M, Lafont C, Rouzier R et al. Diagnostic accuracy of physical exami-\nnation, transvaginal sonography, rectal endoscopic sonography, and\nmagnetic resonance imaging to diagnose deep infiltrating endometrio-\nsis. Fertil Steril 2009; 92: 1825 –1833\n[18] Lermann J, Hackl J, Burghaus S et al. Die medikamentöse Therapie der\nPatientin mit Endometriose. Frauenheilkunde up2date 2017; 11: 27 –41\n[19] Renner SP, Lermann J, Burghaus S et al. Die operative Therapie der Endo-\nmetriose. Frauenheilkunde up2date 2016; 10: 311 –330\n[20] Ulrich U, Buchweitz O, Greb R et al.; German and Austrian Societies for\nObstetrics and Gynecology. National German Guideline (S2k): Guideline\nfor the Diagnosis and Treatment of Endometriosis: Long Version – AWMF\nRegistry No. 015-045. Geburtsh Frauenheilk 2014; 74: 1104 –1118\n496 Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497\nGebFra Science | Original Article\n\n\n[21] Abbott J, Hawe J, Hunter D et al. Laparoscopic excision of endometriosis:\na randomized, placebo-controlled trial. Fertil Steril 2004; 82: 878 –884\n[22] Deguara CS, Pepas L, Davis C. Does minimally invasive surgery for endo-\nmetriosis improve pelvic symptoms and quality of life? Curr Opin Obstet\nGynecol 2012; 24: 241 –244\n[23] Jacobson TZ, Duffy JM, Barlow D et al. Laparoscopic surgery for subfertil-\nity associated with endometriosis. Cochrane Database Syst Rev 2010;\n(1): CD001398\n[24] Singh SS, Suen MW. Surgery for endometriosis: beyond medical thera-\npies. Fertil Steril 2017; 107: 549 –554\n[25] Barra F, Ferrero S. mTor Inhibitors for the Treatment of Endometriosis.\nGeburtsh Frauenheilk 2018; 78: 283 –284\n[26] Kacan T, Yildiz C, Baloglu Kacan S et al. Everolimus as an mTOR Inhibitor\nSuppresses Endometriotic Implants: an Experimental Rat Study. Ge-\nburtsh Frauenheilk 2017; 77: 66 –72\n[27] Petraglia F, Hornung D, Seitz C et al. Reduced pelvic pain in women with\nendometriosis: efficacy of long-term dienogest treatment. Arch Gynecol\nObstet 2012; 285: 167 –173\n[28] Oladosu FA, Tu FF, Hellman KM. Nonsteroidal antiinflammatory drug re-\nsistance in dysmenorrhea: epidemiology, causes, and treatment. Am\nJ Obstet Gynecol 2018; 218: 390 –400\n[29] Butrick CW. Chronic pelvic pain: how many surgeries are enough? Clin\nObstet Gynecol 2007; 50: 412 –424\n[30] Lovrincevic M. Chronic pelvic pain in women of childbearing age. Curr\nOpin Anaesthesiol 2003; 16: 275 –280\n[31] Siedentopf F, Tariverdian N, Rücke M et al. Immune status, psychosocial\ndistress and reduced quality of life in infertile patients with endometrio-\nsis. Am J Reprod Immunol 2008; 60: 449 –461\n[32] Burghaus S, Fehm T, Fasching PA et al. The International Endometriosis\nEvaluation Program (IEEP Study) – A Systematic Study for Physicians, Re-\nsearchers and Patients. Geburtsh Frauenheilk 2016; 76: 875 –881\n[33] Dunselman GA, Vermeulen N, Becker C et al.; European Society of Hu-\nman Reproduction and Embryology. ESHRE guideline: management of\nwomen with endometrios is. Hum Reprod 2014; 29: 400 –412\n[34] Johnson NP , Hummelshoj L. Consensus on current management of en-\ndometriosis. Hum Reprod 2013; 28: 1552 –1568\n[35] Fauconnier A, Chapron C. Endometriosis and pelvic pain: epidemiologi-\ncal evidence of the relationship and implications. Hum Reprod Update\n2005; 11: 595 –606\n[36] Vercellini P, Giudice LC, Evers JL et al. Reducing low-value care in endo-\nmetriosis between limited evidence and unresolved issues: a proposal.\nHum Reprod 2015; 30: 1996 –2004\n[37] Nnoaham KE, Hummelshoj L, Kennedy SH et al.; World Endometriosis\nResearch Foundation Women ʼs Health Symptom Survey Consortium.\nDeveloping symptom-based predictive models of endometriosis as a\nclinical screening tool: results from a multicenter study. Fertil Steril\n2012; 98: 692 –701.e5\n[38] Vercellini P, Trespidi L, De Giorgi O et al. Endometriosis and pelvic pain:\nrelation to disease stage and localization. Fertil Steril 1996; 65: 299 –304\n[39] Renner SP, Boosz AS, Burghaus S et al. Visual pain mapping in endome-\ntriosis. Arch Gynecol Obstet 2012; 286: 687 –693\n[40] Practice Committee of the American Society for Reproductive Medicine.\nTreatment of pelvic pain associated with endometriosis: a committee\nopinion. Fertil Steril 20 14; 101: 927 –935\n[41] Nisenblat V, Bossuyt PM, Farquhar C et al. Imaging modalities for the\nnon-invasive diagnosis of endometr iosis. Cochrane Database Syst Rev\n2016; (2): CD009591\n[42] Janssen EB, Rijkers AC, Hoppenbrouwers K et al. Prevalence of endome-\ntriosis diagnosed by laparoscopy in adolescents with dysmenorrhea or\nchronic pelvic pain: a systematic review. Hum Reprod Update 2013; 19:\n570–\n582\n[43] Shakiba K, Bena JF, McGill KM et al. Surgical treatment of endometriosis:\na 7-year follow-up on the requirement for further surgery. Obstet Gyne-\ncol 2008; 111: 1285 –1292\n[44] Renner SP , Rix S, Boosz A et al. Preoperative pain and recurrence risk in\npatients with peritoneal endometriosis. Gynecol Endocrinol 2010; 26:\n230–235\n[45] Vercellini P, Somigliana E, Viganò P et al. The effect of second-line sur-\ngery on reproductive performance of women with recurrent endome-\ntriosis: a systematic review. Acta Obstet Gynecol Scand 2009; 88:\n1074–1082\n[46] Zorbas KA, Economopoulos KP, Vlahos NF. Continuous versus cyclic oral\ncontraceptives for the treatment of endometriosis: a systematic review.\nArch Gynecol Obstet 2015; 292: 37 –43\n497Burghaus S et al. Standards Used by … Geburtsh Frauenheilk 2019; 79: 487 –497","source_license":"CC0","license_restricted":false}