Interdisciplinary S2k Guidelines for the Diagnosis and Treatment of Endometriosis: Short Version - AWMF Registry No. 015-045, August 2013

DOI http://dx.doi.org/ 10.1055/s-0033-1350810 Geburtsh Frauenheilk 2013; 73: 890–898 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0016‑5751 Correspondence Prof. Dr. Uwe Ulrich Department of Obstetrics and Gynecology Martin Luther Hospital Caspar-Theyss-Straße 27–31 14193 Berlin [email protected] DGGG-Leitliniensekretariat Prof. Dr. med. Matthias W. Beckmann, DGGG-Leitlinienbeauftragter Frauenklinik Universitätsklinikum Erlangen Universitätsstraße 21–23 91054 Erlangen Tel.: 0 91 31-85-3 35 07/4 40 63 Fax: 0 91 31-85-3 39 51 890 Ulrich U et al. Interdisciplinary S2k Guidelines … Geburtsh Frauenheilk 2013; 73: 890 –898 GebFra Science 1.6 Responsibilities 1.6.1 Task Force Group for these guidelines Directing author Expert panel (Task Force Group Endometriosis Guidelines) Official representatives of the professional associations that have consented 1.6.2 Consulting Monika Nothacker, M. D., Berlin, Germany (Association of the Scientific Medical Societies of Germany (Arbeitsgemeinschaft der wissenschaftlichen medizinischen Fachgesellschaften). 1.7 Abbreviations used in this paper AFS American Fertility Society AGE Arbeitsgemeinschaft Gynäkologische Endoskopie der DGGG (Working Group Gynecologic Endoscopy DGGG) AGO Arbeitsgemeinschaft Gynäkologische Onkologie der DGGG und der Deutschen Krebsgesellschaft (Working Group Gynecologic Oncology of the DGGG and the Ger- man Cancer Society) CT computed tomography DGGG Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (German Society for Obstetrics and Gynecology) DIE deep infiltrating endometriosis EEL Europäische Endometriose Liga (European Endometrio- sis League) ENZIAN name of a hotel in Weissensee, Carinthia (Austria) where the classification of DIE was first established by an SEF expert group in 2002 GnRHa gonadotropin-releasing hormone analog HRT hormone replacement therapy ICSI intracytoplasmatic sperm injection IUD intrauterine device IUI intrauterine Insemination IVF in-vitro fertilization MRI magnetic resonance imaging OC oral contraceptive (orales, hormonelles Antikonzepti- vum) OEGGG Österreichische Gesellschaft für Gynäkologie und Ge- burtshilfe (Austrian Society for Obstetrics and Gynecol- ogy) rASRM (revised) American Society for Reproductive Medicine (-classification) SEF Stiftung Endometrioseforschung (Endometriosis Re- search Foundation) Name Place Prof. Uwe Ulrich, M. D. Berlin, Germany Name Place Olaf Buchweitz, M. D. Hamburg, Germany Radek Chvatal, M. D. Znaim, Czech Republic Prof. Rudy-Leon De Wilde, M. D. Oldenburg, Germany Prof. Andreas D. Ebert, M. D., Ph.D. Berlin, Germany Bruno Engl, M. D. Bruneck, South Tyrol Ingo von Leffern, M. D. Hamburg, Germany Prof. Robert Greb, M. D. Dortmund, Germany Gülden Halis, M. D. Berlin, Germany Dietmar Haas, M. D. Linz, Austria Prof. Jürgen Hucke, M. D. Wuppertal, Germany Prof. Jörg Keckstein, M. D. Villach, Austria Prof. Michel Müller, M. D. Berne, Switzerland Prof. Peter Oppelt, M. D. Linz, Austria Stefan P . Renner, M. D. Erlangen, Germany Martin Sillem, M. D. Mannheim, Germany Prof. Karl-Werner Schweppe, M. D. Westerstede, Germany Wolfgang Stummvoll†, M. D. Linz, Austria Prof. Hans-Rudolf Tinneberg, M. D. Gießen, Germany Frank Tuttlies, M. D. Villach, Austria Prof. Uwe Ulrich, M. D. Berlin, Germany Prof. Ludwig Wildt, M. D. Innsbruck, Austria Professional association Name Place German Society for Obstetrics and Gynecology Prof. Ludwig Kiesel, M. D. Münster, Germany Prof. Hans-Rudolf Tinneberg, M. D. Giessen, Germany German Society for General and Visceral Surgery Prof. Jan Langrehr, M. D. Berlin, Germany German Society for Urology Prof. Jürgen Geschwend, M. D. Munich, Germany German Society for Gynecologic Endocrinology and Reproductive Medicine (Working Group of the DGGG) Prof. Ludwig Kiesel, M. D. Münster, Germany Working Group Gynecologic Endoscopy (AGE/DGGG) Prof. Uwe Ulrich, M. D. Berlin, Germany Working Group Gynecologic Oncology (AGO/DGGG) Prof. Uwe Ulrich, M. D. Berlin, Germany German Society for Psychosomatic Obstetrics and Gynecology Friederike Siedentopf, M. D. Berlin, Germany Swiss Society for Obstetrics and Gynecology Prof. Michel Müller, M. D. Berne, Switzerland Austrian Society for Obstetrics and Gynecology Prof. Jörg Keckstein, M. D. Villach, Austria Prof. Peter Oppelt, M. D. Linz, Austria Wolfgang Stummvoll†, M. D. Linz, Austria Prof. Ludwig Wildt, M. D. Innsbruck, Austria Czech Society for Obstetrics and Gynecology Radek Chvatal, M. D. Znaim, Chech Republic Eduard Kucera, M. D. Prague, Czech Republic Endometriosis Research Foundation (SEF) Prof. Karl-Werner Schweppe, M. D. Westerstede, Germany European Endometriosis League (EEL) Prof. Hans-Rudolf Tinneberg, M. D. Gießen, Germany Stefan P. Renner, M. D. Erlangen, Germany Endometriosis Association Germany (self-help) Dr. Heike Matuszewski Berlin, Germany Endometriosis Association Austria (self-help) Katrin Steinberger Vienna, Austria 891 Ulrich U et al. Interdisciplinary S2k Guidelines … Geburtsh Frauenheilk 2013; 73: 890 –898 Guideline 2 Special Notes While a company ʼs brand name, or a registered trade mark, re- spectively, are not necessarily given in the present paper, it must not be presumed that such name or mark was free. As medical science is a rapidly developing field, informations and recommendations given in these guidelines do represent the state-of-the-art knowledge as it stands at the time of submission of the paper. Utmost care has been taken by the expert panel to extract that knowledge from the scientific literature as well as their personal experience. Having said that, the user remains fully liable for all applications based upon recommendations giv- en in the present paper. The reader ʼs attention is drawn to the fact that oral contracep- tives (OCs) and intrauterine levonorgestrel-releasing systems are not specifically approved in Germany for the treatment of en- dometriosis. Thus, their therapeutic application for the treat- ment of endometriosis is made off label. Finally, this work is fully protected. Any use that infringes the law on copyright without written permission by the editors, authors, and copyright holders, respectively, is prohibited and considered a criminal offense. No part of these guidelines may be reproduced in any form without the written permission of the editors and au- thors. This applies to photocopies, translations, microfilms, and to the storage, use and processing on electronic media, intranets and the internet. 3 Introduction and General Comments 3.1 Definition and epidemiology Statements: a. Endometriosis – one of the most common gynecologic diseases – is defined as the occurence of endometrium-like cell forma- tions outside the uterine cavity. b. The cardinal symptom is chronic pelvic pain. Infertility is com- mon. There are about 20 000 hospital admissions per year for endome- triosis in Germany (Haas et al. 2012). Pathologically and histolog- ically, endometriosis is a benign disease. However, infiltrative growth into adjacent organs is possible requiring extensive surgi- cal procedures. 3.2 Etiology, pathology, and staging Statement: Etiology and pathogenesis of endometriosis are not fully under- stood. Therefore, a causal therapy is not known to date. Recommendation: All staging systems known to date have their limitations. In order to ensure the international comparability of data, the use of the rASRM staging system – and in cases of deep infiltrating endo- metriosis the additional use of the ENZIAN classification – is rec- ommended. Endometriosis and malignancy Statements: a. In rare cases, malignancy – usually ovarian cancer – may arise from endometriosis. b. Aside from this, the association of other, non-gynecologic ma- lignancies with endometriosis has been described in the litera- ture. The clinical significance of this observation is not under- stood. 4 Diagnosis and Treatment of Endometriosis Statements: a. Indications for endoscopic diagnosis and treatment of endo- metriosis are as follows: " Chronic pelvic pain, " Destruction of organs, and/or " Infertility. b. For control of symptoms, the surgical removal of endometriotic lesions is considered as “gold standard” (Abbott et al. 2004, De- guara et al. 2012, Garry 2004). Recommendations: In general, the diagnosis of endometriosis is to be established his- tologically. Hence, diagnostic laparoscopy is essential for the di- agnostic work-up (Walter et al. 2001). 4.1 General comments Some affected women have no symptoms. Also, there is no corre- lation between stage of the disease and grade of symptoms. Asymptomatic endometriosis in a woman without infertility is no indication of surgical or other medical interventions (excep- tion: endometriosis-related hydronephrosis). Almost every woman with symptomatic endometriosis suffers from dysmen- orrhea. If this cardinal symptom is lacking, other differential diag- noses are to be considered (see Guidelines for Chronic Pelvic Pain in Women, AWMF Registry No. 016 – 001, Sillem u. Teichmann 2003, Siedentopf et al. 2009). 4.2 Peritoneal endometriosis Statements: a. The diagnosis of peritoneal endometriosis is made laparoscop- ically. b. Treatment of choice is the laparoscopic removal of the im- plants. Recommendation: Following hormonal suppression of the ovarian function, endo- metriotic implants may undergo regression. For the reduction of endometriosis-associated symptoms, progestins, OCs, or GnRH analogs may be used in order to induce therapeutic amenorrhea (Abou-Setta et al. Cochrane Review 2013, Brown et al. Cochrane Review 2012, Allen et al. Cochrane Review 2009). 4.3 Ovarian endometriosis (endometriomas) Statement: The diagnosis of ovarian endometriomas is primarily made by transvaginal ultrasound. Recommendations: a. For primary treatment of ovarian endometriomas, the cyst wall should be removed surgically. Fenestration alone is con- sidered insufficient. b. Endocrine drug treatment alone is neither effective in elimi- nating an ovarian endometrioma (and, consequently, to re- place its surgical removal) – nor in compensating for incom- plete surgical removal. Therefore, it is not recommended. 892 Ulrich U et al. Interdisciplinary S2k Guidelines … Geburtsh Frauenheilk 2013; 73: 890 –898 GebFra Science Differential diagnosis In ovarian endometriomas, often a typical echogenic pattern is found (Hudelist et al. 2009b). However, there are also sonograph- ically complex ovarian masses with heterogeneous appearance making it sometimes difficult to differentiate between functional ovarian cysts on the one side and dermoid cysts, kystomas, or ovarian malignant neoplasms on the other side. If a laparoscopic approach is scheduled in unclear ovarian findings, the DGGG S1 Guidelines for Laparoscopic Surgery of Ovarian Tumors apply (AWMF Registry No. 015 – 003). Any unclear ovarian mass must be clarified histologically. As the CA-125 level in endometriosis patients is consistently ele- vated, its assessment is not recommended routinely. The same applies to the serum level of human epididymal protein (HE4, Lenhard et al. 2011, Zheng and Gao 2012). 4.4 Deep infiltrating endometriosis Statements: a. Deep infiltrating endometriosis (DIE) is defined as involve- ment of the rectovaginal septum, vaginal fornix, retroperito- neum (pelvic side wall, parametrium), bowel, ureters, and uri- nary bladder. b. The primary diagnosis of DIE is made clinically with rectovagi- nal palpation, inspection with divided specula, vaginal ultra- sound, and transabdominal ultrasound of the kidneys being mandatory. Recommendations: a. For treatment, complete resection of DIE should be performed. Nonetheless, compromises must be made as preservation of fertility often is imperative. Considering that the disease is be- nign and potentially relevant complications may occur, the ex- tent of resection should be thoroughly discussed and agreed upon with the patient. b. Treatment of DIE should be carried out in specialized centers with a multidisciplinary approach (Ebert et al. 2013). c. If patients with DIE are to be managed conservatively – as well as pre- and postoperatively – sonographic examination of the kidneys is mandatory in order to avoid overlooking silent hy- dronephrosis. DIE-associated hydronephrosis is an absolute in- dication of appropriate diagnosis and treatment. Hormone replacement therapy in patients with endometriosis Premenopausal patients who have undergone hysterectomy be- cause of endometriosis – proper indication provided – should re- ceive a combined estrogen-progestin HRT. In postmenopause, in view of the fact that there is a potential risk of malignancy (see paragraph on endometriosis-associated malignancy), combined estrogen-progestin HRT – or tibolone – is recommended as well (Moen et al. 2010, Soliman and Hillard 2006). Nonetheless, the problem of breast cancer risk has to be balanced against that – and an individual decision made together with the patient (see also S3 Guidelines for HRT in the peri- and postmenopause, AWMF Registry No. 015– 062). 4.5 Adenomyosis Statement: The diagnosis of adenomyosis is primarily established clinically by vaginal ultrasonography and/or MRI. Most often, it is only the histological result after hysterectomy that is proving. Recommendations: a. Given completion of family planning and presence of respec- tive symptoms, hysterectomy can be recommended. b. If the patient opts for preservation of the uterus, a therapeutic amenorrhea may be induced, or a progestin-releasing IUD in- serted (Garcia and Isaacson 2011). 5 Endometriosis and Infertility Statements: a. While a causal relationship has not been resolved yet, endome- triosis and infertility are often associated. b. For the treatment of women with both endometriosis and in- fertility, appropriate skills and experience in infertility surgery, as well as cooperation with centers for reproductive medicine are required. Recommendations: a. In women with both infertility and endometriosis, the im- plants should be surgically removed for the improvement of fertility. b. In cases of recurrence, assisted reproductive technologies are superior to repeated surgery in terms of pregnancy rate. In re- peat operations for ovarian endometriosis, the surgery-related reduction of ovarian reserve is to be considered. c. Postoperative treatment with GnRH analogs was ineffective in improving spontaneous pregnancy rates and is, therefore, not recommended. d. Any drug treatment for endmetriosis alone does not improve fertility and should not be applied from a reproductive-medi- cine perspective. 6 Psychosomatic Aspects Recommendation: Psychosomatic aspects in the treatment of patients with endo- metriosis should be considered and integrated early on. 7 Complementary and Integrative Treatment Approaches No statements, no recommendations. 8 Rehabilitation, Follow-up, and Self-help Statement: After extensive surgery – especially for deep infiltrating endome- triosis, after repeat endometriosis operations, or in patients with chronic pain, there often is a need for rehabilitation. Recommendation: This need mentioned should be assessed, and measures of reha- bilitation, or after-care, respectively, be initiated. 893 Ulrich U et al. Interdisciplinary S2k Guidelines … Geburtsh Frauenheilk 2013; 73: 890 –898 Guideline Affiliations 1 Klinik für Gynäkologie und Geburtshilfe, Martin-Luther-Krankenhaus, Berlin 2 Tagesklinik Altonaer Straße, Hamburg 3 Kinderwunschzentrum Dortmund, Dortmund 4 Abteilung für Gynäkologie und Geburtshilfe, Landeskrankenhaus, Villach 5 Klinik für Gynäkologie und Geburtshilfe, Albertinen-Krankenhaus, Hamburg 6 Abteilung für Gynäkologie und Geburtshilfe, Landesfrauen- und Kinderklinik, Linz 7 Frauenklinik, Universitätsklinikum Erlangen, Erlangen 8 Praxisklinik am Rosengarten, Mannheim 9 vormals Abteilung für Gynäkologie, Krankenhaus der Barmherzigen Schwestern, Linz 10 Endometriosezentrum Ammerland, Westerstede

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