{"paper_id":"e2d5d445-8979-43a2-bdc0-ead3b88cc86a","body_text":"The Guideline is Supported by the\nFollowing Professional Associations\nand Organizations:\n\" German Society for Obstetrics and Gynecology\n(Deutsche Gesellschaft für Gynäkologie und\nGeburtshilfe e. V., DGGG)\n\" Gynecological Endoscopy Study Group (Ar-\nbeitsgemeinschaft für Gynäkologische Endo-\nskopie, AGE)\n\" Gynecological Oncology Study Group (Ar-\nbeitsgemeinschaft für Gynäkologische Onko-\nlogie e. V., AGO)\n\" German Society for Gynecological Endocri-\nnology and Reproductive Medicine (Deut-\nsche Gesellschaft für Gynäkologische Endo-\nkrinologie und Fortpflanzungsmedizin e. V.)\n\" German Society for Psychosomatic Obstetrics\nand Gynecology (Deutsche Gesellschaft für Psy-\nchosomatische Frauenheilkunde und Geburt-\nshilfe, DGPFG)\n\" German Society for General and Visceral Sur-\ngery (Deutsche Gesellschaft für Allgemein-\nund Viszeralchirurgie e. V., DGAV)\n\" German Society for Urology (Deutsche Gesell-\nschaft für Urologie e. V.)\n\" Austrian Society for Obstetrics and Gynecology\n(Österreichische Gesellschaft für Gynäkologie\nund Geburtshilfe e. V., ÖGGG)\n\" Swiss Society for Obstetrics and Gynecology\n(Schweizerische Gesellschaft für Gynäkologie\nund Geburtshilfe, SGGG)\n\" Czech Society for Obstetrics and Gynecology\n\" Endometriosis Research Foundation (Stiftung\nEndometriose-Forschung, SEF)\n\" European Endometriosis League (EEL)\n\" Endometriosis Association of Germany (Endo-\nmetriose-Vereinigung Deutschland e. V.)\n\" Endometriosis Association of Austria (Endome-\ntriose-Vereinigung Austria)\nProject Management and Lead Author:\nProf. Dr. U. Ulrich, Berlin\nTask Force Members:\nDr. O. Buchweitz, Hamburg (Germany)\nDr. R. Chvatal, Znaim (Czech Republic)\nProf. Dr. R.-L. De Wilde, Oldenburg (Germany)\nProf. Dr. Dr. Dr. A. D. Ebert, Berlin (Germany)\nDr. B. Engl, Bruneck (South Tyrol)\nDr. I. von Leffern, Hamburg (Germany)\nProf. Dr. R. Greb, Dortmund (Germany)\nDr. D. Haas, Linz (Austria)\nDr. G. Halis, Berlin (Germany)\nAbstract\n!\nIn this guideline, recommendations and stan-\ndards for optimum diagnosis and treatment of en-\ndometriosis are presented. They are based on the\nanalysis of the available scientific evidence as\npublished in prospective randomized and retro-\nspective studies as well as in systematic reviews.\nThe guideline working group consisted of experts\nfrom Austria, Germany, Switzerland, and the\nCzech Republic.\nZusammenfassung\n!\nMit dieser Leitlinie werden Empfehlungen und\nStandards für eine optimale Diagnostik und The-\nrapie der Endometriose vorgestellt. Sie basieren\nauf einer Analyse prospektiv-randomisierter und\nretrospektiver Studien sowie systematischer\nÜbersichten. Die Arbeitsgruppe bestand aus Ex-\nperten aus Deutschland, Österreich, der Schweiz\nund Tschechien.\nNational German Guideline (S2k): Guideline for\nthe Diagnosis and Treatment of Endometriosis\nLong Version – AWMF Registry No. 015-045\nLeitlinie für die Diagnostik und Therapie der Endometriose\nLangversion – AWMF-Register-Nr. 015-045\nAuthors U. Ulrich 1, O. Buchweitz 2,R .G r e b3, J. Keckstein 4, I. von Leffern 5, P. Oppelt6, S. P. Renner 7, M. Sillem 8, W. Stummvoll 9,\nR.-L. De Wilde 10, K.-W. Schweppe 11, for the German and Austrian Societies for Obstetrics and Gynecology\nAffiliations The affiliations are listed at the end of the article.\nKey words\nl\" endometriosis\nl\" laparoscopy\nl\" reproductive medicine\nl\" health care\nSchlüsselwörter\nl\" Endometriose\nl\" Laparoskopie\nl\" Reproduktionsmedizin\nl\" Gesundheitswesen\nBibliography\nDOI http://dx.doi.org/\n10.1055/s-0034-1383187\nGeburtsh Frauenheilk 2014; 74:\n1104–1118 © Georg Thieme\nVerlag KG Stuttgart · New York ·\nISSN 0016‑5751\nCorrespondence\nProf. Dr. U. Ulrich\nDepartment of Obstetrics\nand Gynecology\nMartin Luther Hospital\nCaspar-Theyß-Straße 27–31\n14193 Berlin\nu.ulrich@mlk-berlin.de\nDGGG-Leitliniensekretariat\nProf. Dr. med.\nMatthias W. Beckmann,\nDGGG-Leitlinienbeauftragter\nFrauenklinik\nUniversitätsklinikum Erlangen\nUniversitätsstraße 21–23\n91054 Erlangen\nTel.: 0 91 31-85-3 35 07/4 40 63\nFax: 0 91 31-85-3 39 51\n1104\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGebFra Science\n\n\nProf. Dr. J. Hucke, Wuppertal (Germany)\nProf. Dr. J. Keckstein, Villach (Austria)\nProf. Dr. M. Müller, Bern (Switzerland)\nProf. Dr. P. Oppelt, Linz (Austria)\nDr. S. P. Renner, Erlangen (Germany)\nDr. M. Sillem, Mannheim (Germany)\nProf. Dr. K.-W. Schweppe, Westerstede (Germany)\nDr. W. Stummvoll †, Linz (Austria)\nProf. Dr. H.-R. Tinneberg, Gießen (Germany)\nDr. F. Tuttlies, Villach (Austria)\nProf. Dr. U. Ulrich, Berlin (Germany)\nProf. Dr. L. Wildt,Innsbruck (Austria)\n1 Background\nIn this guideline, a standard is recommended for the diagnosis\nand treatment of endometriosis on the basis of the previously\npublished scientific knowledge and of the experience of the au-\nthors. Doctors providing care for patients with endometriosis\nrepresent the target group for this guideline.\nThe recommendations are based on an analysis of the scientific\nliterature (PubMed, MEDLINE search, Cochrane Library),\nalthough only a limited number of prospective, randomized stud-\nies are available on the diagnosis and treatment of endometriosis.\nThe recommendations and publications of the following profes-\nsional associations were also taken into consideration:\n\" Endometriosis Research Foundation (http://www.endome-\ntriose-sef.de)\n\" The Royal College of Obstetricians and Gynaecologists Clinical\nGreen-Top Guidelines for the Investigation and Management\nof Endometriosis (http://www.rcog.org.uk/)\n\" ESHRE Guideline for the Diagnosis and Treatment of Endome-\ntriosis (http://www.eshre.eu)\n\" The American College of Obstetrics and Gynecology Commit-\ntee on Practice Bulletins (http://www.acog.org/)\n\" awmf.de [86]\n2 Introduction\n2.1 Definition and epidemiology\nCore statements:\na. Endometriosis is defined as the presence of endometrium-like\ngroups of cells outside the uterine cavity.\nb. The cardinal symptom is pelvic pain, and infertility is common.\nEndometriosis is one of the most common gynecological dis-\neases. It occurs predominantly after sexual maturity has been\nreached and is considered to be estrogen-dependent. In one\nstudy, adolescents in the 10- to 15-year-old age group repre-\nsented 0.05 % and in the 15- to 20-year-old age group 1.93 % of\nall women with endometriosis. Postmenopausal women ac-\ncounted for 2.55 % of the cases [78]. Endometriosis is a cause of\nsignificant morbidity [5, 68, 172].\nReliable information on frequency is lacking, and there are signif-\nicant fluctuations in the prevalence rates quoted in the literature.\nIt is estimated that approx. 40 000 new cases occur in Germany\neach year. Around 20 000 women are admitted for hospital treat-\nment for endometriosis each year in Germany [78]. The economic\nimpact is considerable in terms of medical cost and reduced work\nproductivity. Despite this, the disease is under-represented in\nclinical and basic scientific research [168].\nThe dilemma of endometriosis is caused partly by the long inter-\nval between the appearance of the first symptoms and the cor-\nrect diagnosis – 10 years on average in Austria and Germany\n[91] – and partly by the repeated operations in chronic forms of\nthe disease.\nAlthough endometriosis is a histopathologically benign disease,\nit can spread to other organs as a result of infiltrative growth\nand require extensive surgery [189].\n2.2 Etiology, pathology and staging\nCore statement:\nThe etiology and pathogenesis of endometriosis are still not fully\nunderstood. There is, therefore, no known causal treatment at\npresent.\nRecommendation:\nAll known staging systems have their limitations. For the purpose\nof international comparability, the rASRM staging system should\nbe used, with the addition of the ENZIAN classification in deep\ninfiltrating endometriosis.\nVarious theories on the etiology and pathology of endometriosis\nhave been presented in the literature: implantation theory [164,\n165], celomic metaplasia theory [126], archimetra or “tissue in-\njury and repair ” concept [113, 114].\nThe most widely used classification is that of the American Soci-\nety for Reproductive Medicine (the “rASRM score ”, [11]). This\nrASRM score shows only a weak correlation with the cardinal\nsymptoms of pain and infertility [72, 194]. The description of ret-\nroperitoneal and deep infiltrating growth forms is also inad-\nequate with this system. The Endometriosis Research Foundation\nhas attempted to overcome this shortcoming by creating an ap-\npropriate classification – the ENZIAN classification [77, 79, 80,\n157, 186]. Like the rASRM score, the ENZIAN classification is also\nmorphologically descriptive. At present, no data exist showing\nwhether the ENZIAN classification correlates with symptoms\nsuch as pain and infertility. The traditional division into external\nand internal genital endometriosis and extragenital endometrio-\nsis [9] has proven useful in routine clinical practice; it takes into\naccount the concept of a single disease entity.\nIn decreasing order of frequency, the following are involved: pel-\nvic peritoneum, ovaries, uterosacral ligaments, rectovaginal sep-\ntum/vaginal fornix, and extragenital sites (e.g., rectosigmoid co-\nlon and urinary bladder).\nThe incidence of involvement of the uterus (adenomyosis) and\ntubes is not entirely clear. The diaphragmatic peritoneum [137,\n155], the vermiform appendix [71] and the umbilicus [197] are\nrare but typical extragenital sites. Endometriosis also occurs in\nsurgical scars following hysterectomy, cesarean section, episioto-\nmy, and perineal lacerations [19, 62, 144, 167]. It is debated that\nthis may be caused by the mechanical transfer of endometrial\nparticles. Manifestations in the spleen, lungs, kidneys, brain or\nskeleton are rare.\nPatient information – Causes of endometriosis\nThe causes of the development of endometriosis have not yet been scientifi-\ncally proven. No causal treatment options are, therefore, available at present\nwhich might enable endometriosis to be eliminated completely or cured.\nThere is also no treatment available that prevents endometriosis from devel-\noping in the first place.\n1105\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGuideline\n\n\nEndometriosis and malignancy\nCore statements:\na. In very rare cases, malignancy may arise from endometriosis –\nusually ovarian cancer.\nb. An association with the occurrence of other, non-gynecological\nmalignancies can also be found in the literature. The clinical\nsignificance of this observation is unclear.\nRisk of malignant diseases in women with endometriosis\nEven though there is no statistically detectable increase in the\nrisk of cancer for women with endometriosis in general [122,\n181], an association has been described between the existence\nof endometriosis and certain malignancies such as endocrine tu-\nmors, ovarian cancer, renal cell carcinoma, brain tumors, malig-\nnant melanoma, non-Hodgkin lymphomas and breast cancer\n[28, 82, 122, 136, 139, 148, 198]. The standardized incidence ratio\n(SIR) is stated as, for example, 1.38 for endocrine tumors, 1.37\nfor ovarian cancer and 1.08 for breast cancer [122]. The SIR might\nbe even higher in women with primary infertility, endometriosis\nand one of the aforementioned malignancies [27]. The validity of\nthese data and their clinical significance are unclear.\nEndometriosis-associated malignancies Malignant tumors\nmay arise from endometriosis. Ovarian cancer accounts for\naround 80 % and extragonadal tumors for 20 % of these cases\n[187, 199], with the positive correlation persisting even if it was\nmany years previously that the woman had the endometriosis\n[148]. Endometriosis is considered to be a risk factor that can ac-\ncelerate the development of ovarian cancer by 5 years [12]. Ac-\ncording to one study, the overall risk is approx. 2.5 % [190]. Histo-\nlogically, the tumors are mainly of the endometrioid (OR 3.05) or\nclear cell (OR 2.04) type, although a correlation has been found\nrecently between endometriosis and well differentiated (G1) se-\nrous carcinomas (OR 2.11) [148]. The association between poorly\ndifferentiated (high-grade) serous and mucinous ovarian carci-\nnomas or borderline ovarian tumors is not statistically significant\n[148]. Other histologic entities occur (endometrial stromal sarco-\nma, mixed tumors, etc.) [200]. Furthermore, an ovarian endome-\ntrioma diameter of ≥ 9 cm, a postmenopausal situation [106] and\na hyperestrogenic state [206] are reported to be independent risk\nfactors (single center data). In the Swedish Hospital Discharge\nRegistry of 2004, the presence of endometrial cysts in women be-\ntween 10 and 29 years of age was defined as an additional risk\nfactor for the subsequent development of ovarian cancer [25].\nOvulation inhibitors, births, tubal sterilization or hysterectomy\nmight reduce the risk, on the other hand [128]. Extragonadal en-\ndometriosis-associated carcinomas have virtually been described\nin almost all tissues in which endometriosis occurs [121].\nSummary On the basis of the described incidence rates and\nrisk factors, the possibility of endometriosis-associated malig-\nnant disease should be included in considerations relating to dif-\nferential diagnosis, and patients should be informed about this\naccordingly. At the same time, it is important to exercise pru-\ndence and to keep a sense of proportion when confronting endo-\nmetriosis patients with these statements.\nPatient information – Endometriosis and malignancy\nEven if women with endometriosis are not generally at increased risk of\nmalignant disease, some malignant diseases may occur more frequently\nthan in women who do not have endometriosis.\nThe work-up for and treatment of endometriosis should, therefore, take this\nfact and the individual situation of the woman concerned into account.\nSpecific additional investigations may thus be required in individual cases.\n3 Diagnosis and Treatment of Endometriosis\nCore statements:\na. Indications for endoscopic diagnosis and treatment in endo-\nmetriosis are as follows:\n\" Pain\n\" Organ destruction, and/or\n\" Infertility\nb. Surgical removal of the lesions is considered the “gold stan-\ndard” for symptom control [1, 50, 67].\nRecommendation:\nIn general, the diagnosis of endometriosis is to be established his-\ntologically. Hence, laparoscopy is essential for the diagnostic\nwork-up [202].\n3.1 General remarks\nSome of the women affected are asymptomatic. Furthermore, the\ndisease stage does not correlate with the severity of the symp-\ntoms [70, 161]. The determination of CA-125 levels is not helpful\neither for diagnosis or follow-up and is not recommended (see\nsection 3.3.1, [131]). In some cases, it is difficult to prove whether\na causal relationship actually exists between endometriosis and\ncertain symptoms. Asymptomatic endometriosis in a patient\nwho does not wish to become pregnant is not generally an indi-\ncation for surgical or medical intervention. There are exceptions\nto this, e.g., endometriosis-induced ureteral stenosis with hydro-\nnephrosis (absolute indication). Almost all women with sympto-\nmatic endometriosis suffer from dysmenorrhea. If this cardinal\nsymptom is absent, other causes of pelvic pain must be consid-\nered in the differential diagnosis [173, 174].\nFor the sake of clarity, the different forms of endometriosis are\ndiscussed separately. Nevertheless, they are often combined\n[188].\nPatient information – General notes on diagnosis and treatment\nIn the presence of suspected endometriosis, a histologic assessment should\nbe performed. As a general rule, laparoscopy is necessary for this.\nPersistent pain, desire to conceive and/or functional impairment of an af-\nfected organ (e.g. ovaries, bowel or ureter) are reasons for the surgical and/\nor pharmacological treatment of endometriosis. Conversely, it follows that a\nwoman who has endometriosis but does not have any symptoms, does not\nwish to conceive and does not exhibit any organ damage, does not need to\nbe treated, although it is always important to consider the patient ʼs indi-\nvidual situation.\n3.2 Peritoneal endometriosis\nCore statements:\na. Peritoneal endometriosis is diagnosed laparoscopically.\nb. The treatment of choice is laparoscopic removal of the im-\nplants.\nRecommendation:\nFollowing medical suppression of the ovarian function, endo-\nmetriotic implants may undergo regression. To reduce endome-\ntriosis-associated symptoms, progestins, oral contraceptives or\nGnRH analogs can be used in order to induce therapeutic amen-\norrhea.\n1106\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGebFra Science\n\n\n3.2.1 Morphology and symptoms\nIn peritoneal endometriosis, a distinction is made between red,\nwhite and black lesions [11] and/or between pigmented and\nnon-pigmented (atypical) lesions [95, 138]. The red and non-pig-\nmented lesions are seen as early manifestations of endometriosis.\nThey are considered to be particularly active. In terms of response\nto hormone therapy, peritoneal endometriosis appears to differ\nfrom ovarian and deep infiltrating endometriosis [138]. It is not\nknown, however, whether the different forms of peritoneal en-\ndometriosis behave differently in relation to pain, fertility and\ncourse of the disease [75]. Patients with pronounced symptoms\nprior to surgery are at higher risk of recurrence than patients\nwho do not feel much pain [156]. The lifetime risk of endometrio-\nsis recurrence depends on the age at initial diagnosis and is 1.75-\nfold higher for 20- to 29-year-old than for 30- to 39-year-old pa-\ntients [171]. Early diagnosis of endometriosis, including in ado-\nlescent girls, might be of significance in terms of the subsequent\ncourse of the disease and the maintenance of fertility [4, 204].\n3.2.2 Diagnosis\nFollowing a detailed past medical history-taking and vaginal/rec-\ntal examination, the key measure for diagnosing peritoneal endo-\nmetriosis is laparoscopy with histologic confirmation [67]. Trans-\nvaginal ultrasonography or MRI are equally irrelevant to the de-\ntection of peritoneal implants, although the former serves to rule\nout ovarian endometriosis [132], and the latter may provide ad-\nditional information where deep infiltrating endometriosis is\npresent at the same time [105].\n3.2.3 Treatment\nSurgical treatment Laparoscopic removal of the lesions is the\nprimary therapeutic objective. This has been shown to reduce the\npain [93]. Whether the methods available (coagulation, vaporiza-\ntion, excision) are equivalent is unclear [81]. Additional LUNA\n(laparoscopic uterine nerve ablation) does not lead to any im-\nprovement in outcome in patients with minimal to moderate en-\ndometriosis who have pain [196]. It has not been proven whether\npostoperative pharmacological suppression of ovarian function is\nsuccessful in improving the effect of surgery or maintaining it for\nlonger [64].\nOne option for reducing persistent pain after surgery is the inser-\ntion of a levonorgestrel-releasing IUD [2].\nPrimary medical treatment Suppression of ovarian function\nproduces regressive changes in endometriotic implants. A reduc-\ntion in endometriosis-associated symptoms can be achieved\nequally with progestins, oral contraceptives (continuous) or\nGnRH analogs [29, 73, 211], while GnRH analogs were more effec-\ntive for dysmenorrhea and dyspareunia in some studies. Differ-\nences exist in terms of the adverse effect profiles and costs, how-\never [30, 47, 84, 193]. In two current, prospective and randomized\nstudies, continuous oral administration of a progestin (dieno-\ngest) has been shown to have the same efficacy as a GnRH analog\nin endometriosis-associated pain, while dienogest offered advan-\ntages for the patient in terms of clinical tolerability [74, 180].\nLong-term data show a sustained clinical effect continuing be-\nyond the period of administration [151].\nWhen administered over a more prolonged period of time, GnRH\nanalogs should be administered concomitantly with appropriate\nprotective add-back medication because of the potential effects\nof estrogen deficiency. The duration of treatment with GnRH\nanalogs is 6 months in patients with pain. Although a 3-month\ntreatment period is just as effective, it is associated with a shorter\nrecurrence-free interval [83]. No data are available on the benefit\nof extended GnRH ‑a therapy. According to the findings of one\nprospective study, treatment with dienogest as maintenance\ntherapy after GnRH ‑a was effective in maintaining the GnRH ‑a-\ninduced effect for at least 12 months [103]. Although non-steroi-\ndal and other anti-inflammatory drugs are used frequently in\nroutine clinical practice, there is no evidence at present that they\nhave a positive influence on the specific symptoms associated\nwith endometriosis [10].\n3.3 Ovarian endometriomas\nCore statement:\nThe diagnosis of ovarian endometriomas is primarily made by\ntransvaginal ultrasound.\nRecommendations:\na. For primary treatment of ovarian endometriomas, the cyst\nwall should be removed surgically. Fenestration alone is insuf-\nficient.\nb. Hormonal drug treatment alone is neither effective in elimi-\nnating an ovarian endometrioma and thus to replace its surgi-\ncal removal, nor in compensating for incomplete surgical re-\nmoval. Therefore, it is not recommended.\n3.3.1 Diagnosis\nIn 20 – 50 % of all women with endometriosis, the ovaries are af-\nfected [89]. The preoperative work-up is based on the clinical ex-\namination and transvaginal ultrasound, with ovarian endome-\ntrioma often exhibiting a typical echo texture [88]. However,\nsonographically complex ovarian masses with a heterogeneous\nappearance are also found, which makes it difficult to distinguish\nbetween functional cysts on the one hand and dermoid cysts,\ncystomas or ovarian cancer on the other in individual cases\n[109] (l\n\" Table 1). In the case of planned laparoscopic procedures\nin the presence of unclear ovarian findings, reference is made to\nthe relevant S1 Guideline of the German Society for Obstetrics\nand Gynecology (Guideline: laparoscopic surgery for ovarian tu-\nmors, AWMF no. 015-003). Any unclear ovarian mass should be\nevaluated histologically.\nIf there is pain, additional deep infiltrating endometriosis is\nprobably present [40] which must be taken into consideration\nduring the clinical examination.\nTable 1 Ultrasound appearance of ovarian endometrioma in premenopausal\nwomen (modified according to [88, 191]).\nAppearance: heterogeneous\nSize: up to 15 cm\nBorders: smooth\nWall thickness: increased\nEchogenicity: not anechogenic (hypo- to hyperechogenic)\nInternal echoes: fine, uniformly distributed\nFurther features: one or more compartments\nuni- or bilateral\nThe same characteristics are associated\nwith a higher risk of malignancy in\npostmenopausal women.\n1107\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGuideline\n\n\nDetermination of tumor markers The CA-125 value is often\nassessed in the differential diagnostic work-up of complex ovar-\nian masses. As the CA-125 value is commonly elevated in endo-\nmetriosis patients, however, it is of no relevance in terms of the\ndifferential diagnosis (Guideline: laparoscopic surgery for ovar-\nian tumors, AWMF no. 015-003). It is not sufficiently specific.\nTherefore, its determination for the evaluation of suspected en-\ndometriosis is not recommended in the clinical routine. In the\ncourse of the disease (e.g., in a suspected recurrence), the clinical\nsituation is the decisive factor rather than the CA-125 level. The\nsame applies at present to serum levels of human epididymis se-\ncretory protein 4 (HE4) [112, 207].\n3.3.2 Treatment\nThe most effective treatment for ovarian endometriomas is their\nsurgical removal. The method of choice for this is surgical lapa-\nroscopy [32]. According to a meta-analysis, ovary-sparing remov-\nal (extraction) of the cyst wall is superior overall to thermal de-\nstruction using a high-frequency current, laser vaporization or\nargon plasma coagulation in terms of pain symptoms and recur-\nrence and pregnancy rates [76]. Whether this recommendation\nshould apply only to endometriomas with a diameter of > 4 cm\nis a moot point [85, 100]. The problem of the potential loss of oo-\ncytes following the excision of recurrent endometriomas in infer-\ntility patients resulting in the procedure not being performed\nprior to assisted reproduction (but therefore also in no histologic\nconfirmation being obtained) in the case of smaller endometrio-\nmas, will be examined later in detail in section 4.3. The experi-\nence of the surgeon may have an influence on this oocyte loss\n[205].\nThe opening and drainage of the cyst capsule of the endometrio-\nma cannot be recommended as a surgical procedure alone be-\ncause 80 % of patients receiving this treatment suffer a recurrence\nwithin six months [7, 162]. This high recurrence rate cannot be\nreduced by subsequent treatment with GnRH analogs [192].\nMedical (hormonal) treatment for ovarian endometriomas alone\nis not sufficient and is not recommended. Pre-operative adminis-\ntration of GnRH analogs may lead to a decrease in the size of the\nendometrioma. Whether this results in surgical benefits or a re-\nduction in recurrence rates is the subject of controversy in the lit-\nerature [53, 134]. Postoperative GnRH analogs do not compen-\nsate for incomplete surgery [33]. While some working groups\nhave been able to show that postoperative administration of a\nhormonal contraceptive resulted in a reduction in the recurrence\nrate [135, 169, 182], two other prospective, randomized, placebo-\ncontrolled trials showed low recurrence rates irrespective of the\ntreatment arm [8, 170].\nPatient information – Ovarian endometriosis\nAn endometriotic ovarian cyst should be removed completely by means\nof laparoscopy.\nHormonal treatment alone is not sufficient.\n3.4 Deep infiltrating endometriosis\nCore statements:\na. Deep infiltrating endometriosis (DIE) is defined as the involve-\nment of the rectovaginal septum, the vaginal fornix, the retro-\nperitoneum (pelvic side wall, parametrium), the bowel, ureter,\nand urinary bladder.\nb. The primary diagnosis is made clinically with rectovaginal pal-\npation, inspection with divided specula, transvaginal ultra-\nsound and transabdominal ultrasound of the kidneys being\nmandatory.\nRecommendations:\na. For treatment, complete resection should be performed. None-\ntheless, compromises must be made as preservation of fertility\noften is imperative.\nThe extent of the resection should be decided in close agree-\nment with the patient against the background of benign dis-\nease and possible relevant complications.\nb. The treatment of DIE should take place in dedicated specialist\ncenters on the basis of an interdisciplinary approach.\nc. In the case of conservatively managed patients and before and\nafter surgery, kidney ultrasound is mandatory in order to avoid\noverlooking clinically silent hydronephrosis. Hydronephrosis\nassociated with DIE is an absolute indication of appropriate\ndiagnosis and treatment.\n3.4.1 Symptoms\nDIE refers to the forms which manifest in the rectovaginal sep-\ntum, in the vaginal fornix, in the retroperitoneum (pelvic side\nwalls, parametrium) and in the bowel, ureter and urinary blad-\nder. In the case of ureteral endometriosis, a distinction is made\nbetween the intrinsic (infiltration of the ureter itself; rare) and\nextrinsic (external compression) subtypes. The way in which the\naforementioned structures are involved may be very complex\n[189].\nThe symptoms depend on the site. In the case of bowel involve-\nment, various intestinal symptoms occur, including dyschezia,\nfeeling of pressure, flatulence, tenesmus, blood and mucus in the\nstool, diarrhea and constipation, and altered bowel habits. The ab-\nsence of symptoms does not rule out bowel involvement. Endo-\nmetriosis of the bladder can cause voiding difficulties and hema-\nturia. Ureteral endometriosis can lead to hydronephrosis. Endo-\nmetriosis-induced back-up of urine develops slowly and is, there-\nfore, usually clinically silent [177]. Dyspareunia is typically caused\nby alteration of the pelvic plexus [154]. Although most patients\nwith DIE complain of a variety of bowel symptoms, it has not been\npossible so far to reproduce any sensitive anorectal dysfunction\nby means of manometry in studies on this subject [118].\nRectovaginal septum involvement is most common, followed by\ninvolvement of the rectum, the sigmoid colon, the cecum and\nthe vermiform appendix, the bladder and ureters and, much\nmore rarely, the ileum while multiple sites involvement is possi-\nble.\n3.4.2 Diagnosis\nA clinical diagnosis of suspected disease is made initially on the\nbasis of the patient ʼs history, which is often indicative, and on\nvaginal and rectal palpation, followed by an investigation-based\ndiagnosis by means of transvaginal ultrasound. Various investiga-\ntions have been found to be useful in connection with the subse-\nquent work-up (l\n\" Tables 2 and 3):\n1108\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGebFra Science\n\n\nProctosigmoidoscopy is used very frequently in the presence of\nsuspected rectosigmoid involvement. However, infiltration of\nthe mucosa is extremely rare. In the presence of extensive dis-\nease, an external impression is rather to be expected – around\n26 % of patients with rectal endometriosis exhibit stenosis [161],\nso a negative proctoscopic mucosal finding is the rule, and by no\nmeans excludes involvement of the muscularis. The importance\nof proctoscopy thus lies in the evaluation of other causes of rectal\nbleeding as part of the differential diagnosis. MRI exhibits a high\nsensitivity for the diagnosis of DIE and provides useful informa-\ntion [18]. Transrectal endoscopic ultrasound provides a reliable\nand simple means of predicting the presence of deep rectal infil-\ntration [18]. Transvaginal ultrasound also provides a straightfor-\nward means of DIE visualization, including the diagnosis of deep\nrectal involvement with a high level of sensitivity and specificity\ncombined with minimal patient discomfort [87, 90]. In a compar-\native study, the aforementioned methods were found to be equiv-\nalent overall in terms of diagnostic effectiveness, although MRI\nhad the highest sensitivity in some cases [18]; in another study,\ntransvaginal ultrasonography was favored [3]. Regardless of the\npre-operative diagnosis, the extent of the resection is often not\ndecided until during the operation (e.g. multiple intestinal foci:\nrectum, sigmoid colon, cecum).\n3.4.3 Treatment\nThe treatment of choice for symptomatic deep infiltrating endo-\nmetriosis is resection, leaving a free margin on all sides [42, 61,\n98, 125, 127, 153]. In many studies, a positive effect on pain, over-\nall quality of life and fertility has been demonstrated [17]. Vari-\nous methods are available for this: vaginal resection, laparoscopy,\nlaparoscopically assisted vaginal surgery, laparotomy. In the\npresence of infiltration-related manifestations of endometriosis\n(rectosigmoid colon, bladder, ureter), the pre-operative counsel-\ning for and planning and performance of the intervention should\nbe carried out on the basis of interdisciplinary consensus (includ-\ning Visceral Surgery and/or Urology, depending on the situation).\nIf hydronephrosis is present (i.e., an absolute indication of treat-\nment), it is vital to refer the patient to a urologist who will carry\nout an assessment of renal function and decide whether, how,\nand to what extent treatment should be carried out [117]. If there\nis a desire to conceive, the need to preserve the uterus and ova-\nries often results in incomplete resection of the endometriosis.\nThe benefits of the resection are to be confronted with the mor-\nbidity associated with surgery [31, 36, 45, 154] as well as the re-\ncurrence rate of endometriosis. Recurrences after bowel resec-\ntion for DIE occur in about 14 % of cases (5 – 25 %, see [49, 124]).\nComplications, some of which can be severe (anastomotic leaks),\nmust be anticipated during surgery and in the immediate post-\noperative period in approx. 5 – 14 % of cases. This applies espe-\ncially to segmental rectal resection (associated with an incidence\nof up to 24 %, see [108, 127, 147, 150, 160]), which is why some re-\nsearch teams warn against segmental rectal resection for benign\nendometriotic disease and recommend the mucosa-sparing\n“shaving” technique or full-thickness resection of the wall with-\nout in-continuity resection [54, 69]. The long-term consequences\n– some of which being irreversible – must always be weighed\nagainst the desired positive effect of the operation. Besides fistula\nand rectal dysfunction [13], bladder atony – sometimes associ-\nated with the need for permanent self-catheterization by the pa-\ntient – is of particular clinical relevance [15, 160]. This is caused\nby surgical alteration of the hypogastric plexus (splanchnic\nnerves) which is unavoidable in some cases. The risk of postoper-\native bladder atony with self-catheterization was stated as 29 % in\none study; the risk was associated with simultaneous partial col-\npectomy [210]. Whether nerve-sparing surgical techniques can\nprevent such urological complications is under investigation [37,\n97]. A particular situation also arises when complex colorectal\nand urological procedures are performed in one session – in\nthese cases, it is important to consider whether it would not be\nbetter to adopt a two-step approach [159].\nOwing to the complexity of the procedures, surgical treatment of\nDIE should be carried out in centers with relevant experience\n[56]. Asymptomatic findings should always be monitored with\nthe inclusion of renal ultrasound, and do not necessarily require\nsurgery in the absence of progression. Spontaneous bowel perfo-\nration and ileus are extremely rare [51]. Because of the risk of\nthese occurring, however (e.g., including during pregnancy with\nconsiderable maternal and fetal consequences in some cases), the\npros and cons of a deliberate decision not to operate should also\nbe discussed in detail. This gives rise to the dilemma that both\nsurgery for deep rectovaginal endometriosis and leaving it in situ\nmay possibly result in a higher risk of spontaneous perforation/\nvulnerability during pregnancy and delivery (posterior vaginal\nfornix rupture), which is attributed to decidualization during\npregnancy [24, 41, 152]. Against this background, the primary\nmethod of delivery (spontaneous delivery versus cesarean sec-\ntion) is a subject which should definitely be broached with the\npatient and considered carefully (expert opinion, Weissensee\nmeeting of the Endometriosis Research Foundation, 2013). Con-\nclusion: Possible surgical and non-surgical alternatives for DIE\nmust always be explained in both directions (documentation).\nTable 2 Clinical investigations for the work-up of deep infiltrating endome-\ntriosis.\nInvestigation Evidence provided\nInspection (double-\nbladed speculum)\nVisible endometriosis in the posterior fornix\nPalpation (always\nincluding rectal)\nUterus often retroverted; dense, nodular,\ntender infiltration of the rectovaginal septum\n(retrocervical)\nTransvaginal\nultrasound\nChanges in the uterus in the presence of concur-\nrent adenomyosis and information about possible\novarian endometriomas, good visualization of\ndeep rectal involvement\nRenal ultrasound Be alert to back-up of urine (parametrial,\npelvic wall and ureteral endometriosis)\nTable 3 Optional investigations for the evaluation of deep infiltrating endo-\nmetriosis.\nInvestigation Evidence provided\nProctosigmoidoscopy External impression, mucosal\ninvolvement (rare), differential\ndiagnosis of primary bowel disease\nMagnetic resonance imaging Involvement of the bowel wall,\nthe bladder; adenomyosis?\nTransrectal endoscopic ultrasound Involvement of the bowel wall?\nContrast enema Bowel involvement in higher sections\nIntravenous pyelogram\nor computed tomography\nUreteral stenosis, hydronephrosis\nCystoscopy Bladder involvement\n1109\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGuideline\n\n\nThe benefit of pre- or postoperative GnRH analog therapy for\ndeep infiltrating endometriosis is not proven [33, 64], and, there-\nfore, cannot generally be recommended. Medical hormonal ther-\napy will be given, however, if the patient wishes to avoid surgery\nor if there are postoperative symptoms. An effect can only be ex-\npected during therapy, and long-term treatment is therefore nec-\nessary. Progestin monotherapy, a monophasic continuous oral\ncontraceptive or GnRH analogs (with add-back therapy) for the\ninduction of therapeutic amenorrhea are options. Another possi-\nble alternative to surgery is the insertion of a levonorgestrel-re-\nleasing IUD under which pain relief and a reduction in rectovagi-\nnal endometriosis size have been observed [59].\nEstrogen and progestogen replacement therapy in endome-\ntriosis Premenopausal patients following hysterectomy for\nendometriosis receive combined estrogen and progestin replace-\nment therapy if indicated. In postmenopausal women, estrogen\nand progestogen combinations or tibolone are also recom-\nmended following hysterectomy in view of the fact that there is\na risk of recurrence and malignancy (see section entitled “Endo-\nmetriosis-associated malignancies ”) [129, 175]. The problem of\nthe risk of breast cancer must nevertheless be weighed against\nthis and discussed with the patient so that an individual decision\ncan be made (AWMF ‑S3 Guideline: Hormone replacement ther-\napy in peri- and postmenopausal women, AWMF Registry no.\n015-062, 2009).\nPatient information – Deep infiltrating endometriosis\nWhere endometriosis involves the vagina, bowel, bladder and ureters,\ncomplete surgical removal of the lesions is the best treatment at present.\nExtensive surgery is often needed for this, which requires good cooperation\nbetween gynecologists, surgeons and urologists and should be performed\nin a dedicated specialist unit.\nBefore surgery for deep infiltrating endometriosis, the risks and benefits\nmust always be weighed up carefully, because even extensive surgery with\ncomplete removal of the endometriosis cannot guarantee the desired pain\nrelief which is the aim of surgery.\n3.5 Uterine adenomyosis\nCore statement:\nThe diagnosis of adenomyosis is primarily established clinically,\nby vaginal ultrasound and/or MRI; confirmation is usually pro-\nvided only by the histological findings based on the hysterectomy\nspecimen.\nRecommendations:\na. Given completion of family planning and presence of respec-\ntive symptoms, hysterectomy can be recommended.\nb. If the patients opts for preservation of the uterus, therapeutic\namenorrhea may be induced or a progestin-releasing IUD in-\nserted.\n3.5.1 Symptoms\nAdenomyosis is defined as the infiltration of the myometrium by\nendometriosis. The main symptoms are painful, heavy and acy-\nclic bleeding together with infertility [65].\n3.5.2 Diagnosis\nIn clinically suspected cases, the following investigations have\nproved effective (l\n\" Table 4):\nTransvaginal ultrasound is of greatest significance in day-to-day\npractice with approx. 65 – 70 % sensitivity and 95 – 98 % specificity\n[89, 123]. MRI, with high sensitivity and specificity for the diag-\nnosis of adenomyosis, is also suitable and useful in individual\ncases [38, 101, 104, 149].\nAlthough desirable, there is no suitable routine method for the\nhistologic confirmation of adenomyosis. Various groups have\nworked on biopsy methods, while only positive results are ex-\nploitable. It cannot be used to rule out the disease (e.g. [99]).\nThe definitive diagnosis, therefore, is ultimately based on the hys-\nterectomy specimen in most cases. Adenomyosis can occur in iso-\nlation or together with various forms of endometriosis. DIE is\noften associated with adenomyosis [110].\n3.5.3 Treatment\nIf the patient ʼs family planning is complete, hysterectomy repre-\nsents the most effective treatment [65]. The decision regarding\nwhich method to be used for this (vaginal, abdominal, laparo-\nscopically assisted vaginal, total laparoscopic, laparoscopic supra-\ncervical) is left to the discretion of patient and surgeon. Vaginal\nhysterectomy on its own without simultaneous laparoscopy rules\nout the possibility of peritoneal implant removal, however, and\nshould therefore be the exception. Laparoscopic supracervical\nhysterectomy (LASH) appears to be suitable for this indication\nwith careful reference to the S1 Guideline of the German Society\nfor Obstetrics and Gynecology (AWMF no. 015-064) as the cervix\nis involved only in extremely rare cases [14, 166]. Irrespective of\nthis general recommendation of hysterectomy, consideration\nmust still be given to the potentially negative consequences of\nhysterectomy in women with chronic pelvic pain (AWMF Guide-\nline of the German Society for Psychosomatic Obstetrics and\nGynecology, AWMF no. 016-001).\nThe benefit of uterus-preserving surgical treatment for patients\nwishing to conceive or desiring organ preservation in focal forms\nof adenomyosis is not demonstrated by studies. If this is at-\ntempted in individual cases (e.g. encouraging results by [142]),\nan MRI scan or preoperative administration of a GnRH analog\nmay be useful for planning the operation [133, 143, 149]. The risk\nof uterine rupture during pregnancy or childbirth, especially if\nTable 4 Work-up for adenomyosis.\nMeasure/\ninvestigation\nFinding\nPast medical history Dysmenorrhea (including with neurodystonia),\nhypermenorrhea\nClinical examination Occasionally tender, enlarged uterus (bimanual,\nrectovaginal palpation)\nTransvaginal\nultrasound\nPoorly demarcated heterogeneous areas, cystic\nintramural changes in some cases, areas of variable\nechogenicity, irregular halo effect, discrepancy\nbetween anterior and posterior wall\nMRI Changes in the zonal anatomy of the uterus,\nIrregular junctional zones on T1- and T2-weighted\nimages, areas of low signal intensity and subendo-\nmetrial foci of high signal intensity, anterior-poste-\nrior wall asymmetry as a sign of muscle hyperplasia\n1110\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGebFra Science\n\n\nlarger myometrial defects arise, should be taken into account in\nthe subsequent management of the patient [149, 201].\nThe use of interventional radiology procedures for the treatment\nof adenomyosis, such as embolization [26] and MRI-guided fo-\ncused ultrasound ablation [63], hitherto, should be limited to\nstudies.\nProgestogins, oral contraceptives and progestin-releasing intra-\nuterine systems are used as an alternative to hysterectomy [58].\nThe therapeutic effect is based on the induction of amenorrhea.\nContraceptives (monophasic products) and progestins should be\ntaken continuously [44, 195].\n4 Endometriosis and Infertility\nCore statements:\na. While a causal relationship has not been resolved yet, endome-\ntriosis and infertility are frequently associated.\nb. For the treatment of women with both endometriosis and in-\nfertility, appropriate skills and experience in infertility surgery\nas well as cooperation with centers for reproductive medicine\nare required.\nRecommendations:\na. In women with endometriosis who wish to conceive, implants\nshould be removed surgically to improve fertility.\nb. In cases of recurrence, assisted reproductive technologies are\nsuperior to repeat surgical interventions in terms of the preg-\nnancy rate. In repeat operations for ovarian endometriosis, the\nsurgery-related potential reduction in ovarian reserve is to be\nconsidered.\nc. Postoperative treatment with GnRH analogs has not been ef-\nfective in improving the spontaneous pregnancy rate in infer-\ntility patients and is, therefore, not recommended.\nd. Any drug treatment of endometriosis alone does not improve\nfertility and should not be applied from a reproductive medi-\ncine perspective.\n4.1 Pathophysiology of infertility associated\nwith endometriosis\nInfertility and endometriosis are often associated, although it is\nnot clear whether there is a causal relationship. Mechanical alter-\nation of the adnexa is unequivocally accepted as the cause of in-\nfertility. However, whether the endometriosis creates an immu-\nnologically “hostile” environment for implantation or whether it\nleads to impairment of sperm transport, Fallopian tube mobility\nand oocyte maturation is unclear [102]. Nevertheless, results\nfrom egg donation programs indicate that oocyte and early em-\nbryonic development may be impaired in women with endome-\ntriosis [66].\n4.2 Medical and surgical treatment\nMedical treatment alone\nIn the presence of rASRM stage I and II endometriosis, no im-\nprovement in fertility was shown in a meta-analysis of 16 ran-\ndomized and controlled studies following medical treatment\n(GnRH analogs, progestins) compared with placebo or a wait-\nand-see approach [92].\nSurgical treatment\na) Minimal and mild endometriosis (in accordance with\nrASRM) Two randomized, controlled studies on the effect of\nsurgical removal (coagulation/excision) of endometriotic lesions\nin patients with infertility and AFS stage I and II endometriosis\nhave been identified: Marcoux et al. [119] and Parazzini et al.\n[146]. Marcoux et al. randomized a total of 341 patients (average\nage: 30.5 years, average duration of infertility: 31 months) intra-\noperatively. Over a follow-up period of 36 weeks, 30.7 % of the pa-\ntients in the group who underwent excision of the endometriosis\n(50 out of 179) became pregnant compared with 17.7 % (29 out of\n169; cumulative incidence ratio 1.7; 95 % CI 1.2 – 2.6) in the group\nwho underwent diagnostic laparoscopy alone. The birth rate was\nnot given. Parazzini et al. [146] intraoperatively randomized 101\npatients with ASF stage I and II endometriosis who had experi-\nenced infertility for 38 months on average. During the follow-up\nperiod of at least one year, 12 patients in the excision group (12\nout of 54 = 22.2 %) and 13 in the diagnostic laparoscopy group (13\nout of 47 = 27.6 %) became pregnant. No statistically significant\ndifference was found between the results, including in terms of\nbirth rate of n = 10 in each group. In a meta-analysis based on\nthese two studies, Jacobson et al. [94] came up with a positive\noverall result with respect to a benefit of excision in terms of an\nimproved pregnancy rate, although the magnitude of the effect\nwas uncertain (odds ratio 1.66; 95 % CI 1.09 – 2.51). The confi-\ndence interval shows the possible variability in the actual effect\nin the presence of non-parallel results for the two studies.\nIn a retrospective cohort study (n = 661) of patients with AFS\nstage I and II endometriosis undergoing IVF, a 10.7 % increase in\nthe first IVF cycle pregnancy rate (29.4 % compared with 40.1 %,\np = 0.004) and a 6.9 % increase in the birth rate (p = 0.04; [140])\nwas found in those patients (n = 399) whose endometriotic le-\nsions were excised before IVF.\nb) Deep infiltrating endometriosis No controlled, random-\nized studies are available for deep infiltrating endometriosis in-\ncluding bowel involvement in which the primary objective was\nto compare surgical against non-surgical treatment in terms of\nthe pregnancy and birth rates. Some non-randomized studies\nshow that excision of DIE may improve the spontaneous and\nIVF-induced pregnancy rate [23, 39, 46, 69, 98, 115, 179].\nIn deep infiltrating endometriosis with bowel involvement, a\nprospective cohort study showed a significantly higher IVF-in-\nduced pregnancy rate when complete surgical removal was per-\nformed before [23]. Another prospective cohort study showed a\nhigher pregnancy rate in patients with bowel endometriosis\nwho underwent segmental rectosigmoid resection compared to\nleaving the bowel endometriosis in place (28.3 % compared with\n20 % p-value not specified; [179]). In another study in pregnant\nwomen with DIE who wished to conceive, spontaneous pregnan-\ncies were observed only after laparoscopy compared with open\nsurgery [46]. The outcome of a case-control study, on the other\nhand, indicated that radical, retroperitoneal excision of DIE did\nnot confer any additional benefit in terms of reproductive func-\ntion (and was associated with a significantly higher complication\nrate) compared with removal of intraperitoneal lesions alone\n[55].\nIn patients with endometriotic cysts, endometrioma excision is\nsuperior to fenestration and coagulation in terms of the sponta-\nneous pregnancy rate [7, 76]. Preoperative medical treatment\ndoes not improve the outcome [53, 76].\n1111\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGuideline\n\n\nPostsurgical medical treatment\nPostsurgical treatment with GnRH analogs did not produce an\nimprovement in the spontaneous pregnancy rate in infertility pa-\ntients and is, therefore, not recommended [33, 92].\n4.3 Assisted reproduction\nIntrauterine insemination (IUI)\nIn the presence of minimal and mild endometriosis, IUI leads to\nan improvement in the pregnancy rate, while some studies have\nshown a benefit of ovulation induction compared with spontane-\nous cycles prior to IUI in terms of the pregnancy [48] and live-\nbirth rate [185]. In one study, in contrast to the initial hypothesis,\nthe cumulative endometriosis recurrence rate after 21 months\nwas significantly higher following stimulation for IUI cycles than\nfollowing controlled ovarian hyperstimulation for IVF [52].\nIn vitro fertilization (IVF) and intracytoplasmic\nsperm injection (ICSI)\nData from national treatment registries and current retrospec-\ntive analyses show similar pregnancy rates following IVF in endo-\nmetriosis patients compared with patients with tubal factor in-\nfertility [141]. Thus, conflicting results in a previous review could\nnot be confirmed [16].\nThe effect of ovarian endometriomas on the outcome of IVF is un-\nclear. Systematic reviews have shown that surgical treatment for\nendometriomas is not a prerequisite for success of IVF (i.e. with\nregard to pregnancy rates) [22, 184]. On the other hand, it makes\nneedle insertion easier and reduces the risk of infection. Consid-\neration must also be given to the (very rare) possibility of ovarian\ncancer arising from endometriosis [120, 130]. The question of\nwhether doing without surgery in patients who are desperate to\nconceive in view of the ovarian reserve potentially being compro-\nmised by the ablation [43] arises in the presence of bilateral and\nrecurrent endometriomas in particular [34, 176]. The individual\ndecision, based on these considerations, not to operate or re-op-\nerate (and thus to do without a histologic analysis or complete\nexcision of the endometriosis as is desirable) but with the risk of\nrelevant ovarian disease being overlooked, is a difficult one and\nshould be made only in consultation with the patient, taking into\naccount existing symptoms, safety concerns and differential diag-\nnostic considerations [34]. If loss of ovarian function is imminent,\nsome authors have considered cryopreservation of oocytes fol-\nlowing ovarian stimulation or of ovarian tissue as an option for\nvery young women not wishing to conceive at the present time\n[57].\nIn cases of recurrence of extensive endometriosis, assisted repro-\nduction is superior to repeat surgical treatment in terms of the\npregnancy rate [145]. Considerations regarding whether to oper-\nate yet again or to attempt assisted reproductive techniques\nwithout intervention should take into account the tubal status,\nduration of infertility, the patient ʼs age, the extent of the endo-\nmetriosis and the endometriosis-induced symptoms not associ-\nated with infertility, along with the patientʼs wishes [6]. Although\nthe possibility of endometriosis exacerbation during stimulation\nfor IVF should be considered this has not been demonstrated in\ncontrolled studies [20, 21]; nevertheless, the cumulative rate of\nendometriosis recurrence was 7 % for IVF cycles after 21 months\nin one study [52]. As a general rule, the more extensive the endo-\nmetriosis and the older the patient, the earlier assisted reproduc-\ntion should be recommended [107]. Nevertheless, younger pa-\ntients with endometriosis who wish to conceive should also def-\ninitely be made aware of this option. According to a systematic\nCochrane review, ultra-long GnRH analog therapy after surgical\ntreatment and (3 – 6 months) prior to IVF/ICSI leads to signifi-\ncantly higher pregnancy rates in rASRM stage III and IV endome-\ntriosis [158, 163].\nPatient information – Infertility and endometriosis\nThe surgical removal of endometriotic lesions is generally recommended in\nwomen who wish to conceive. It has been shown that an improvement in\nfertility can be achieved with surgery alone if the Fallopian tubes were intact\nand the sperm analysis normal. The treatment of these patients should be\nleft in expert hands.\nIf endometriosis recurs (particularly after several operations), in vitro fertil-\nization is a better way to achieve pregnancy than undergoing surgery again.\n5 Psychosomatic Aspects\nRecommendation:\nPsychosomatic aspects in the treatment of patients with endo-\nmetriosis should be considered and integrated early on.\nEven if the evidence suggests that the pain a woman is suffering is\ncaused by the presence of endometriosis, this does not rule out\nemotional conflict or psychosocial stress as co-factors. Generally\nspeaking, chronic pelvic pain is accompanied by a considerable\nloss of quality of life and is frequently associated with a somato-\nform pain disorder (Guideline: Chronic pelvic pain in women,\nAWMF Registry no. 016-001). A desire to conceive and dysfunc-\ntional sick-role behavior (e.g. avoidance of physical activity),\nwhich can have an exacerbating effect on pain, leading to a vi-\ncious circle, may be additional psychological stress factors in en-\ndometriosis.\nThe integration of psychosomatic approaches to treatment for\npatients with chronic pelvic pain against a background of endo-\nmetriosis (as an adjunct to surgical and medical measures) may,\non the other hand, improve the patients ʼ quality of life and their\nhandling of the chronic pelvic pain and thus have a positive influ-\nence on treatment outcomes [50, 173]. The integration of sex\ncounseling into psychological support is also important.\nMany authors are now calling for multidisciplinary approaches to\ntreatment when it comes to dealing with chronic pelvic pain [35,\n116, 178, 203]. Causes other than endometriosis should also al-\nways be considered in the differential diagnosis of chronic pelvic\npain [173, 174].\nIn addition, there are some epidemiological studies that suggest\nan association between endometriosis and other chronic pain\nconditions such as migraine and chronic irritable bowel syn-\ndrome [111, 183].\n6 Complementary and Integrative Approaches\nto Treatment\nCore statement:\nOwing to the lack of controlled, randomized studies to date on\ncomplementary and integrative approaches to the treatment of\nendometriosis, no recommendations can be made.\nWomen with chronic recurrent endometriosis and correspond-\ning symptoms may obtain relief of symptoms and an improve-\n1112\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGebFra Science\n\n\nment in quality of life from the use of complementary therapies\n[208]. In particular, these include the methods of acupuncture\nand Chinese medicine, classical homeopathy, herbal medicine,\nphysiotherapy, etc. This should always be preceded by appropri-\nate clinical screening for potential organ changes (endometrio-\nmas, hydronephrosis).\nAlthough results from larger scale, randomized and controlled\nstudies are not yet available, initial investigations clearly point\nto acupuncture [209] and Chinese herbal medicine having an ef-\nfect on endometriosis-induced pain [60].\n7 Rehabilitation, Follow-up and Self-help\nCore statement:\nAfter extensive surgical interventions (particularly for deep infil-\ntrating endometriosis), repeat surgery for endometriosis, or in\npatients with chronic pain, there is often a need for rehabilita-\ntion.\nRecommendation:\nThis need should be assessed and rehabilitation measures or fol-\nlow-up treatment initiated.\nAll efforts in the area of rehabilitation are focused on the restora-\ntion of physical, mental and social well-being. Coping with a dis-\nease that frequently follows a chronic course and is sometimes\nassociated with unavoidable limitations and pain is also an im-\nportant aspect, however. In Germany, specialist centers exist that\nhave considerable experience in the rehabilitation of endome-\ntriosis patients.\nFollow-up should be based on symptoms, with the focus being on\nthe patient ʼs quality of life. All doctors should be aware of the\nlimitations of the treatment options – particularly in cases where\nthe endometriosis keeps recurring.\nSelf-help options exist to assist women with endometriosis in\ncoping with the physical and mental problems they face. The in-\ndependent endometriosis associations in Germany and Austria,\nthe members of which are sufferers themselves, represent the in-\nterests of women with endometriosis. Besides free advice, they\ncan provide addresses of self-help groups, rehabilitation centers\nand specialist doctors.\nPatient information – Rehabilitation and aftercare\nFollowing extensive surgery for endometriosis, additional follow-on treat-\nment is also helpful.\nThe medical treatment of endometriosis has its limitations. Even after\ncareful surgery in the hands of an expert, many patients continue to suffer\nfrom chronic pain – even if all the endometriosis was removed successfully.\nAnd not all women wishing to conceive will manage to become pregnant.\nIn order to cope with the physical and mental problems that women with\nendometriosis can face, patients should be informed about the opportuni-\nties for self-help. The independent endometriosis associations in Germany\nand Austria, the members of which are sufferers themselves, represent the\ninterests of women with endometriosis. Besides free advice, they can pro-\nvide addresses of self-help groups, rehabilitation centers and specialist doc-\ntors in the different regions.\n8 Summary\nEndometriosis is one of the most common gynecological dis-\neases. Women affected may suffer a considerable loss of quality\nof life [96]. Besides the individual health problem, the economic\nimpact caused by the high level of morbidity, reduced work pro-\nductivity and repeated therapeutic interventions should also be\nconsidered.\nThe etiology and pathogenesis are unclear. There is no known\ncausal therapy. Laparoscopic removal is considered to be the sur-\ngical “gold standard”. Because the patients affected often wish to\nconceive and organ preservation is a top priority, radical surgery\nmust often be limited. A patient with asymptomatic endometrio-\nsis who does not wish to conceive does not generally need to be\ntreated (exception: hydronephrosis).\nCareful patient selection and good interdisciplinary cooperation\nare prerequisites for surgical therapy in cases of endometriotic\ninfiltration of the bowel, urinary bladder and/or ureter. The ex-\ntent of surgery must always be weighed up against the morbidity\nassociated with surgery and the unavoidable tendency to recur.\nCounseling regarding alternatives to surgery (medical treatment)\nmust be documented as carefully as any decision by the patient\nnot to undergo surgery (despite a clear indication).\nWhile pre-operative medical treatment is not recommended\nwith the products available at present, postoperative administra-\ntion may prolong the recurrence-free interval in cases of perito-\nneal endometriosis. Various medical options for the treatment of\npain symptoms can be considered as an alternative to the surgical\napproach or in the event of problems with recurrence, with pro-\ngestins, monophasic oral contraceptives and GnRH analogs (with\nconcomitant add-back medication to eliminate hypo-estrogenic\nside effects) having similar efficacy with different adverse effect\nprofiles. Progestin-releasing intrauterine systems are another\noption.\nHormone therapy alone does not result in an improvement in fer-\ntility in endometriosis. Surgical removal of the endometriosis\nand the associated sequelae increased the spontaneous preg-\nnancy rate in some studies. In the presence of severe endome-\ntriosis with destruction of organs (i.e. tubes and ovaries), assisted\nreproduction may be a better option, although surgery before-\nhand may increase the associated pregnancy rate. There are other\nreasons (pain, disease unrelated to pregnancy) for which such\nsurgical correction should be considered in individual cases be-\nfore planned assisted reproduction.\nAlmost all patients with endometriosis require medication for\npain relief in the course of their disease. Depending on the cir-\ncumstances, professional pain therapy should be provided, with\npsychosomatic support where necessary.\n9 Important Internet Addresses\nhttp://www.dggg.de\nhttp://www.oeggg.at\nhttp://www.sggg.ch\nhttp://leitlinien.net (http://www.awmf.de)\nhttp://www.AGEndoskopie.de\nhttp://www.endometriose-sef.de\nhttp://www.endometriose-liga.eu\nhttp://www.endometriose-vereinigung.de\nhttp://www.eva-info.at\n1113\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGuideline\n\n\nThe validity of the guideline has been approved by the Board of\nthe DGGG [German Society for Gynecology and Obstetrics] and\nthe DGGG Guidelines Commission in August 2013. The guideline\nwill remain valid until September, 2016.\nTo cite as: National German Guideline (S2K). Guideline for Diag-\nnosis and Treatment of Endometriosis, AWMF Registry No. 015-\n045. Geburtsh Frauenheilk 2014; 74: 1104 – 1118\nAffiliations\n1 Department of Obstetrics and Gynecology, Martin Luther Hospital, Berlin\n2 Gynecological Outpatient Surgery Altonaer Straße, Hamburg\n3 Center for Reproductive Medicine, Dortmund\n4 Department of Obstetrics and Gynecology, Provincial Hospital, Villach\n5 Department of Obstetrics and Gynecology, Albertinen Hospital, Hamburg\n6 Department of Obstetrics and Gynecology, Provincial Women ʼs\nand Childrenʼs Hospital, Linz\n7 Department of Obstetrics and Gynecology, University of Erlangen\nSchool of Medicine\n8 Gynecological Practice and Clinic Rosengarten, Mannheim\n9 Departement of Gynecology, Hospital of the Sisters of Mercy, Linz\n10 Department of Obstetrics, Gynecology, and Gynecologic Oncology,\nPius Hospital Oldenburg, University of Oldenburg School of Medicine\n11 Endometriosis Center Ammerland, Ammerland Clinic, Westerstede\n10 References\n1 Abbott J, Hawe J, Hunter D et al. 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Eur J Obstet Gynecol Reprod Biol 2010;\n152: 172– 175\n206 Zanetta GM, Webb MJ, Li H et al. Hyperestrogenism: a relevant risk\nfactor for the development of cancer from endometriosis. Gynecol\nOncol 2000; 79: 18 – 22\n207 Zheng H, Gao Y. Serum HE4 as a useful biomarker in discriminating\novarian cancer from benign pelvic disease. Int J Gynecol Cancer\n2012; 22: 1000 – 1005\n208 Zhu X, Proctor M, Bensoussan A et al. Chinese herbal medicine for pri-\nmary dysmenorrhoea. Cochrane Database Syst Rev 2008; 16:\nCD005288\n209 Zhu X, Hamilton KD, McNicol ED. Acupuncture for pain in endometrio-\nsis. Cochrane Database Syst Rev 2011; 9: CD007864\n210 Zilberman S, Ballester M, Touboul C et al. Partial colpectomy is a risk\nfactor for urologic complications of colorectal resection for endome-\ntriosis. J Minim Invasive Gynecol 2013; 20: 49 – 55\n211 Zupi E, Marconi D, Sbracia M et al. Add-back therapy in the treatment\nof endometriosis-associated pain. Fertil Steril 2004; 82: 1303 – 1308\nNote\nOral contraceptives and levonorgestrel-releasing intrauterine\nsystems are not approved for the treatment of endometriosis in\nGermany. They can, therefore, only be used on an off-label basis.\n1118\nUlrich U et al. National German Guideline … Geburtsh Frauenheilk 2014; 74: 1104 –1118\nGebFra Science","source_license":"CC0","license_restricted":false}