Diagnosis and Therapy of Endometriosis. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/045, April 2025)

Abstract

Objective The objective of this revised official guideline, published by the German Society for Gynecology and Obstetrics (DGGG) and coordinated in the joint guidelines program of the DGGG, the Austrian Society for Gynecology and Obstetrics (OEGGG), and the Swiss Society for Gynecology and Obstetrics (SGGG), is to provide evidence-based and consensus-based recommendations for the diagnosis, treatment, care, and support of girls and women with confirmed or suspected endometriosis.

Methods This S2k guideline was developed through a structured consensus process involving representative members of various professions (37 professional associations, organizations, and self-help groups) and includes 25 statements and 73 recommendations which are based on a systematic literature review (2019 – 2023) and expert consensus.

Recommendations For the first time, the revised guideline has placed a greater focus on individualized, symptom-oriented diagnosis and treatment that combines hormonal, surgical, and multimodal approaches. A significant innovation is the use of transvaginal ultrasound as the central diagnostic procedure for detecting endometriosis. Therapeutically, primary hormone treatment is now recommended as the first choice approach, with surgical interventions and multimodal approaches supplemented on an individual and symptom-oriented basis.

I  Guideline Information

Guidelines Program of the DGGG, OEGGG and SGGG

For information on the guidelines program, please refer to the end of the guideline.

Citation format

Diagnosis and Therapy of Endometriosis. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/045, April 2025). Geburtsh Frauenheilk 2026; 86: 133–188

Guideline documents

The complete long version in German with a list of the conflicts of interest of all the authors and a slide version of the guideline are available on the homepage of the AWMF: https://register.awmf.org/de/leitlinien/detail/015-045

Guideline authors

See Tables 1 and 2 .

Table 1  Lead and/or coordinating guideline author.

Authors	AWMF professional society
PD Dr. Stefanie Burghaus, MHBA	German Society for Gynecology and Obstetrics [ Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e. V. ] (DGGG)
Dr. Sebastian D. Schäfer	German Society for Gynecological Endocrinology and Reproductive Medicine [ Deutsche Gesellschaft für Gynäkologische Endokrinologie und Fortpflanzungsmedizin ] (DGGEF)
Prof. Dr. Uwe A. Ulrich	Gynecological Endoscopy Working Group [ Arbeitsgemeinschaft Gynäkologische Endoskopie ] (AGE)

Table 2  Contributing guideline authors.

Author Mandate holder	DGGG working group (AG)/ AWMF/non-AWMF professional society/ organization/association
Prof. Dr. Karl-Jürgen Bär	German Society for Psychosomatic Medicine and Medical Psychotherapy [ Deutsche Gesellschaft für Psychosomatische Medizin und Ärztliche Psychotherapie ] (DGPM)
Dr. Julia Bartley	German Society for Reproductive Medicine [ Deutsche Gesellschaft für Reproduktionsmedizin ] (DGRM)
Prof. Dr. Matthias W. Beckmann	Pediatric and Adolescent Gynecology Study Group [ Arbeitsgemeinschaft Kinder und Jugendgynäkologie ]
Dr. Angelika Behrens	German Society for Gastroenterology, Digestive and Metabolic Diseases [ Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten ] (DGVS)
Univ.-Prof. Dr. Katharina Beyer	German Society for General and Visceral Surgery [ Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie ] (DGAV)
Nicole Bianchi	Endo-Help Swiss Endometriosis Association [ Endo-Help Schweizerische Endometriose- Vereinigung ]
Dr. Iris Brandes	German Society for Rehabilitation Sciences [ Deutsche Gesellschaft für Rehabilitationswissenschaften ] (DGRW)
Prof. Christian Brünahl	German College of Psychosomatic Medicine [ Deutsches Kollegium für Psychosomatische Medizin ] (DKPM)
Prof. Dr. Eike- Christian Burandt	German Society of Pathology [ Deutsche Gesellschaft für Pathologie ] Professional Association of German Pathologists [ Bundesverband Deutscher Pathologen ] (BDP)
PD Dr. Stefanie Burghaus	German Society for Gynecology and Obstetrics (DGGG)
Prim. Dr. Radek Chvátal*	Czech Society for Gynaecology and Obstetrics [ Tschechische Gesellschaft für Gynäkologie und Geburtshilfe ]
Dr. Frederic Dietzel	German Roentgen Society [ Deutsche Röntgengesellschaft ] (DRG)
Prof. Dr. Beate Ditzen	German Society for Medical Psychology [ Deutsche Gesellschaft für Medizinische Psychologie ] (DGMP)
MUDr. Jan Drahoňovský*	Czech Society for Gynecology and Obstetrics
PD Dr. Axel Eickhoff	German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS)
Prof. Dr. Joachim Erlenwein	German Society for Anesthesiology and Intensive Care Medicine [ Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin ] (DGAI)
Prof. Dr. Tanja Fehm	Working Group on Gynecologic Cancers [ Arbeitsgemeinschaft für Gynäkologische Onkologie ] (AGO)
Dr. Peter Martin Fehr	Swiss Society for Gynecology and Obstetrics [ Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe ] (SGGG)
Prof. Dr. Ricardo E. Felberbaum	German Society for Reproductive Medicine (DGRM)
Dr. Reinhild Georgieff	Naturopathy, Complementary Medicine, Acupuncture and Environmental Medicine in Gynecology [ Naturheilkunde, Komplementärmedizin, Akupunktur und Umweltmedizin in der Frauenheilkunde ] (NATUM)
Prof. Dr. Dieter Grab	German Society of Ultrasound in Medicine [ Deutsche Gesellschaft für Ultraschall in der Medizin ] (DEGUM)
PD Dr. Donata Grimm-Glang	Kommission IMed der Arbeitsgemeinschaft Gynäkologische Onkologie e. V.
PD Dr. Andreas Hackethal	Gynecological Endoscopy Working Group [ Arbeitsgemeinschaft für Gynäkologische Endoskopie ] (AGE)
Prof. Dr. Katharina Hancke	Association of University Reproductive Medicine Centers [ Arbeitsgemeinschaft Universitärer Reproduktionsmedizinischer Zentren ] (URZ)
Prof. Dr. Winfried Häuser	German Pain Society ( Deutsche Schmerzgesellschaft )
Prof. Dr. Markus Hoopmann	German Society of Ultrasound in Medicine (DEGUM)
PD Dr. Christian Houbois	German Roentgen Society (DRG)
PD Dr. Christian Krautz	German Society for General and Visceral Surgery (DGAV)
Dr. Harald Krentel*	European Endometriosis League [ Europäische Endometriose-Liga] (EEL)
Dr. Klaudija Künzel	Medical Society for the Promotion of Health [ Ärztliche Gesellschaft zur Gesundheitsförderung ] (ÄGGF)
Dr. Simone Linsenbühler	Kommission IMed der Arbeitsgemeinschaft Gynäkologische Onkologie e. V.
Prof. Dr. Gwendolin Manegold-Brauer	Working Group for Ultrasound Diagnosis in Gynecology and Obstetrics [ Arbeitsgemeinschaft für Ultraschalldiagnostik in Gynäkologie und Geburtshilfe ] (ARGUS)
Ines Mayer-Hrusa	Endometriosis Association Austria [ Endometriose-Vereinigung Austria ] (EVA)
Prof. Dr. Sylvia Mechsner	Endometriosis Working Group [ Arbeitsgemeinschaft Endometriose ] (AGEM) Scientific Endometriosis Foundation [ Stiftung Endometriose-Forschung ] (SEF)
Prof. Dr. Harald Meden	Naturopathy, Complementary Medicine, Acupuncture and Environmental Medicine in Gynecology (NATUM)
Prof. Dr. Michael Müller	Swiss Society for Gynecology and Obstetrics (SGGG)
Prof. Dr. Patricia G. Oppelt	Pediatric and Adolescent Gynecology Study Group
Univ.-Prof. Dr. Peter Oppelt, MBA	Austrian Society for Gynecology and Obstetrics [ Österreichische Gesellschaft für Gynäkologie und Geburtshilfe ] (ÖGGG)
Barbara Pasiecznyk	Endometriosis Association Austria (EVA)
Univ.-Prof. Dr. Esther Pogatzki-Zahn	German Pain Society
Prof. Dr. Stefan Renner, MBA*	European Endometriosis League (EEL)
Michelle Röhrig	Endometriosis Association Germany [ Endometriose-Vereinigung Deutschland ] (EVD)
Dr. Daniela Rosenberger	German Society for Anesthesiology and Intensive Care Medicine (DGAI)
Dr. Frank Ruhland	Professional Association of Gynecologists [ Berufsverband der Frauenärzte ] (BVF)
Prof. Dr. Nicole Sänger	German Society for Gynecological Endocrinology and Reproductive Medicine [ Deutsche Gesellschaft für Gynäkologische Endokrinologie und Fortpflanzungsmedizin ] (DGGEF)
Dr. Sebastian D. Schäfer	German Society for Gynecological Endocrinology and Reproductive Medicine (DGGEF)
Jana Schmid	Endo-Help Swiss Endometriosis Association
Prof. Dr. K. W. Schweppe	Scientific Endometriosis Foundation (SEF)
PD Dr. Friederike Siedentopf	German Society for Psychosomatic Gynecology and Obstetrics [ Deutsche Gesellschaft für Psychosomatische Frauenheilkunde und Geburtshilfe ] (DGPFG)
Prof. Dr. Dr. Horia Sirbu	German Society for Thoracic Surgery [ Deutsche Gesellschaft für Thoraxchirurgie ] (DGT)
Dr. Runa Speer	Medical Society for the Promotion of Health (ÄGGF)
Dr. Petra Thorn	German Society for Fertility Counseling [ Deutsche Gesellschaft für Kinderwunschberatung ] (BKiD)
Dr. Denis I. Trufa	German Society for Thoracic Surgery (DGT)
Prof. Dr. Uwe A. Ulrich	Gynecological Endoscopy Working Group (AGE)
Prof. Dr. Frauke von Versen-Höynck	Association of University Reproductive Medicine Centers (URZ)
Dr. Friederike Vogeler	Professional Association of Gynecologists (BVF)
Prof. Dr. Kerstin Weidner	German Society for Psychosomatic Medicine and Medical Psychotherapy (DGPM) German College of Psychosomatic Medicine (DKPM)
Prof. Dr. Tewes Wischmann	German Society for Fertility Counseling (BKiD) German Society for Medical Psychology (DGMP)
Katharina Wittek	Endometriosis Association Germany (EVD)
PD Dr. Monika Wölfler	Austrian Society for Gynecology and Obstetrics (ÖGGG)
Dr. Isabella Zraik	German Society for Urology [ Deutsche Gesellschaft für Urologie ] (DGU)

The following professional societies/working groups/organizations/associations stated that they wished to contribute to the guideline text and participate in the consensus conference and nominated representatives to attend the conference ( Table 2 ).

The guideline was moderated by Dr. Monika Nothacker (AWMF-certified guidelines adviser/moderator).

Abbreviations

AAGL

American Association of Gynecologic Laparoscopists

AFC

antral follicle count

AG

working group [ Arbeitsgemeinschaft ]

AI

aromatase inhibitor(s)

AMH

anti-Müllerian hormone

ART

assisted reproductive technology

ASRM

American Society for Reproductive Medicine

CBT

cognitive behavioral therapy

CI

confidence interval

COC

combined oral contraceptive

COI

conflict of interest

CPR

cumulative pregnancy rate

CT

computed tomography

DIE

deep infiltrating endometriosis

EAOC

endometriosis-associated ovarian carcinoma

ET

fresh embryo transfer

FET

frozen embryo transfer

FSD

female sexual dysfunction

FSFI

female sexual function index

FSH

follicle-stimulating hormone

GnRH

gonadotropin-releasing hormone

ICSI

intracytoplasmic sperm injection

IUI

intrauterine insemination

IVF

in vitro fertilization

LARS

low anterior resection syndrome

LBR

live birth rate

LNG-IUS

levonorgestrel-releasing intrauterine system

MAR

medically assisted reproduction

MBM

mind-body medicine

MRI

magnetic resonance imaging

NIH

National Institutes of Health

NSAIDs

non-steroidal anti-inflammatory drugs

OR

odds ratio

PMR

progressive muscle relaxation

QI

quality indicators

QoL

quality of life

RCT

randomized controlled trial

RR

relative risk

SD

standard deviation

SMD

standardized mean difference

TENS

transcutaneous electrical nerve stimulation

TME

total mesorectal excision

TVS

transvaginal sonography

VEGF

vascular endothelial growth factor  

II  Guideline Application

Purpose and objectives

Women with diagnosed or suspected endometriosis and physicians who treat women with endometriosis must be informed and advised about the diagnosis, therapy, further care, and specific situations of women with endometriosis.

The contents of the guideline must additionally create the foundation for joint therapeutic decisions made by certified endometriosis practices, units and centers. Finally, the defined statements and recommendations must serve as a basis for developing quality indicators.

Targeted areas of care

• Inpatient care

• Outpatient care

• Partial inpatient care

• Prevention

• Screening

• Diagnosis

• Therapy

• Rehabilitation

• Primary specialized medical care

Target user groups/target audience

This guideline is aimed at the following groups of people:

• Gynecologists in private practice

• Hospital-based gynecologists

• Reproductive medicine specialists

• Pathologists

• Urologists

• Abdominal surgery specialists

• Radiologists

• Specialists for psychosomatic disorders and psychologists

• Pain therapists

• Gastroenterologists

• Medical rehabilitation specialists

• Persons with (suspected) endometriosis

• Advocacy groups of gynecologists treating women, children and adolescents (patient and self-help organizations)

Additional target groups (for information purposes) include:

• General practitioners

• Pediatricians

• Nursing staff

• Members of occupational groups involved in the care of patients with (suspected) endometriosis (e.g., stoma nurses)

• Funding agencies

• Health policy decision-makers at federal and federal state levels

Adoption and period of validity

The validity of this guideline was confirmed by the executive boards/representatives of the participating medical professional societies, working groups, organizations, and associations and the boards of the DGGG, SGGG, OEGGG and the DGGG/OEGGG/SGGG Guidelines Commission in March/April 2025 and was thereby approved in its entirety. This guideline is valid from 1 April 2025 through to 31 March 2030. Because of the contents of this guideline, this period of validity is only an estimate. The guideline can be reviewed and updated earlier if urgently necessary. If the guideline still reflects the current state of knowledge, its period of validity can be extended.

III  Methodology

Basic principles

The method used to prepare this guideline was determined by the class to which this guideline was assigned. The AWMF Guidance Manual (version 1.0) has set out the respective rules and requirements for different classes of guidelines. Guidelines are differentiated into lowest (S1), intermediate (S2), and highest (S3) class. The lowest class is defined as consisting of a set of recommendations for action compiled by a non-representative group of experts. In 2004, the S2 class was divided into two subclasses: a systematic evidence-based subclass (S2e) and a structural consensus-based subclass (S2k). The highest S3 class combines both approaches.

This guideline was classified as: S2k

Grading of recommendations

The grading of evidence after a systematic search, selection, evaluation, and synthesis of an evidence base which is then used to grade the recommendations is not envisaged for S2k guidelines. The individual statements and recommendations are only differentiated by syntax, not by symbols (see Table 3 ).

Table 3  Grading of recommendations (based on Lomotan et al., Qual Saf Health Care 2010).

Description of binding character	Expression
Strong recommendation with highly binding character	must/must not
Regular recommendation with moderately binding character	should/should not
Open recommendation with limited binding character	may/may not

Statements

Expositions or explanations of specific facts, circumstances, or problems without any direct recommendations for action included in this guideline are referred to as “statements.” It is not possible to provide any information about the level of evidence for these statements.

Achieving consensus and level of consensus

At structured NIH-type consensus-based conferences (S2k/S3 level), authorized participants attending the session vote on draft statements and recommendations. The process is as follows. A recommendation is presented, its contents are discussed, proposed changes are put forward, and all proposed changes are voted on. If a consensus (> 75% of votes) is not achieved, there is another round of discussions, followed by a repeat vote. Finally, the level of consensus is determined, based on the number of participants (see Table 4 ).

Table 4  Level of consensus based on extent of agreement.

Symbol	Level of consensus	Extent of agreement in percent
+++	Strong consensus	> 95% of participants agree
++	Consensus	> 75 – 95% of participants agree
+	Majority agreement	> 50 – 75% of participants agree
–	No consensus	< 51% of participants agree

Expert consensus

As the term already indicates, this refers to consensus decisions taken which relate specifically to recommendations/statements issued without a prior systematic search of the literature (S2k) or where evidence is lacking (S2e/S3). The term “expert consensus” (EC) used here is synonymous with terms used in other guidelines such as “good clinical practice” (GCP) or “clinical consensus point” (CCP). The strength of the recommendation is graded as previously described in the chapter Grading of recommendations but without the use of symbols; it is only expressed semantically (“must”/“must not” or “should”/“should not” or “may”/“may not”).

IV  Guideline

1  Epidemiology, etiology and pathophysiology, morbidity and manifestations of endometriosis

Epidemiology

Consensus-based statement 1.S1, modified in 2024
Expert consensus	Level of consensus +++
Reference: [1]
It is not possible to estimate the incidence and prevalence of endometriosis because of the methodological differences between existing studies.

Etiology and pathogenesis

Consensus-based statement 1.S2, reviewed in 2024
Expert consensus	Level of consensus +++
Because of the unclear etiology of endometriosis, causal therapy is not possible.

Pain as the leading clinical symptom

Consensus-based statement 1.S3, new in 2024
Expert consensus	Level of consensus +++
The underlying mechanisms of endometriosis-related pain may be nociceptive, neuropathic, nociplastic or a combination of all three.

The International Association of the Study of Pain differentiates between the following pain mechanisms [62]:

• Nociceptive pain: pain from actual or threatened damage to tissue and organs (non-neural tissue) caused by the activation of pain receptors, e.g., by endometrial lesions activating peritoneal nociceptors [63], which is differentiated, depending on the manifestation, into somatic (peritoneum, pelvic wall) and visceral pain (uterus, bladder, intestine).

• Neuropathic pain: pain as a consequence of damage to or a disease of the nervous system, e.g., through the growth of nerve fibers into peritoneal endometriosis lesions [63].

• Nociplastic pain: pain caused by alterations in pain perception although there are no clear signs of actual or potential damage to tissue or of a disorder or lesion of the somatosensory system causing the pain, e.g., persistent lower abdominal pain despite hormone therapy and surgical removal of all endometriosis foci. The extent of nociplastic pain correlates strongly with the intensity of endometriosis pain and associated impairments [64]. High scores for central sensitization are associated with less pain reduction despite surgical removal of endometriosis foci [65].

Consensus-based recommendation 1.E1, new in 2024
Expert consensus	Level of consensus ++
Reference: [66]
The investigation, diagnosis, treatment, and care of patients with endometriosis-related pain must be guided by a biopsychosocial approach to patients.

The biopsychosocial model is an integrative approach to understanding health and illness. It includes three main factors in its approach to patients:

• Biological factors: physical processes such as genetics, inflammation, hormone balance, and nervous system functions affecting disorders.

• Psychological factors: emotions, stress, pain processing, anxieties, and cognitive patterns affecting well-being.

• Social factors: social milieu, working conditions, social norms, support from family and friends.

The longer the duration of pain, the greater the likelihood of pain chronification leading to a chronic pain disorder.

On a physical level this activates peripheral und central sensitization mechanisms. On a psychological level, factors which may lead to chronic pain include psychological distress (negative perceptions of stress, anxiety, helplessness, depression) as well as unfavorable cognition, coping and processing strategies (e.g., catastrophizing, cognitive anxiety avoidance). On a social level, conflicts (e.g., relationship conflicts, conflicts in the family or at work) often have a negative impact on the development of pain (see also Table 8 ). This may lead to a complex clinical picture of chronic pain disorder.

Table 8  Risk factors for pain chronification.

Risk factors for pain chronification
Indications of mental disorders (anxiety, depression, etc.)
Anxious focus on physical processes
Maladaptive response to illness (avoidance/rest)
Unreasonable cognitive pain management (e.g., catastrophizing)
Inappropriate rest and avoidance strategies
Negative social consequences (family/school/workplace)
Conflicts in the family/at school/at work
Recurrent absences from school/workplace
Behavior of family/environment (e.g., incomprehension, overprotection)
Desire for early retirement

Chronification and the related sensitization of the pain processing system could also explain the increased incidence of pain-related comorbidities in women with endometriosis [68, 69].

2  Classification of endometriosis

2.1  Clinical/intraoperative classification of endometriosis

Depending on the location and extent, endometriosis is differentiated clinically/intraoperatively as follows:

• peritoneal endometriosis

• ovarian endometriosis

• deep infiltrating endometriosis (e.g., in the vagina, rectovaginal septum, intestine, bladder and other less common locations such as the abdominal wall, diaphragm, ureter, etc.)

• adenomyosis of the uterus

2.1.1  #Enzian classification

Consensus-based recommendation 2.E2, modified in 2024
Expert consensus	Level of consensus +++
Reference: [81]
The #Enzian classification (version 2021) must be used for every patient with suspected endometriosis to describe diagnostic ultrasound and MRI findings and when reporting intraoperative findings.

The #Enzian classification provides a precise reproducible description of endometriosis in terms of location and severity (similar to the TNM classication in oncology).

It allows information to be compared both in routine clinical practice and between studies. The important advantage of this classification is that it can be used to describe findings obtained with non-invasive diagnostic procedures such as ultrasound [#Enzian(u)] and MRI [#Enzian(m)]. This precise documentation and classification of the severity of endometriosis prior to treatment is used to optimize individual therapeutic planning and for targeted surgical planning, including the duration of surgery, the surgical approach, potential interdisciplinary needs, the instruments required, and the specific detailed information provided to the patient [82 – 84].

2.1.2  rASRM score

Consensus-based recommendation 2.E3, modified in 2024
Expert consensus	Level of consensus +++
Reference: [85]
The rASRM score (version 1996) may be used to compare intraoperatively documented endometriosis reported in previous scientific studies. Documented findings cannot be precisely reproduced with this score.

The rASRM score has only limited informative value as the score only provides a description of the overall situation with no relation to specific organs (similar to the FIGO classification in oncology). This is a significant weakness in international research as it makes it impossible to compare data between studies. An interobserver variability of up to 40% has been reported, which strongly challenges the value of the rASRM score as a reference classification [86].

2.1.3  AAGL classification

Consensus-based recommendation 2.E4, new in 2024
Expert consensus	Level of consensus +++
Reference: [87]
The American Association of Gynecologic Laparoscopists (AAGL) classification may be used for the intraoperative documentation of findings. Exact reproducibility of documented findings is not possible.

In 2021, the American Association of Gynecologic Laparoscopists (AAGL) presented a new score for the documentation of findings [87]. Similar to the ASRM classification, the AAGL score allots points according to the extent and presentation of endometriosis. The points are used to classify endometriosis into one of four stages based on the number of allotted points. The classification therefore provides an overall picture of the severity of disease. The limitations of this classification are similar to those of the rASRM score (see Chapter 2.1.2 rASRM score ). As with the #Enzian classification, findings cannot be exactly reproduced.

2.1.4  Endometriosis Fertility Index

The Endometriosis Fertility Index (EFI) includes macroscopic changes to the adnexa (based on the rASRM score) and medical history criteria [88]. This index also uses a points-based system to ultimately estimate how high the patientʼs chances of getting pregnant within 36 months are.

2.1.5  Categorization of classification systems

Consensus-based statement 2.S4, new in 2024
Expert consensus	Level of consensus +++
Neither the rASRM-Score nor the #Enzian classification record the symptoms pain or sterility. They also do not predict the course of disease.

2.2  Histological classification of endometriosis

Morphological differential diagnosis of endometriosis

Consensus-based statement 2.S5, reviewed in 2024
Expert consensus	Level of consensus +++
Endometriosis refers to the presence of endometrium-like groups of cells consisting of groups of endometrioid glandular cells and/or endometrial stromal cells outside the uterine cavity.

Consensus-based recommendation 2.E5, reviewed in 2024
Expert consensus	Level of consensus +++
The primary histological diagnosis of endometriosis is made by hematoxylin-eosin staining. If the histological diagnosis of macroscopically suspected endometriosis is negative, additional tests (e.g., additional sections, CD 10, or hemosiderin staining) should be carried out.

Endometriosis of the body of the uterus

Consensus-based statement 2.S6, reviewed in 2024
Expert consensus	Level of consensus +++
References: [95 – 97]
Endometriosis of the body of the uterus (clinically: adenomyosis or adenomyosis uteri or internal genital endometriosis) is defined histopathologically as the finding of an endometriosis focus in the myometrium at a distance of 2.5 mm (measured metrically) from the endometrial-myometrial boundary in a medium-sized lens field of view (100 × magnification).

Ovarian endometriosis

Population-related studies have found that the risk of ovarian carcinoma is up to 4 times higher for patients with endometriosis [98, 101]. The majority of these cases or just under two thirds are an endometrioid subtype, followed by clear cell carcinomas (20%); serous and mucinous carcinomas are rare [98, 107, 108]. The histopathological subtype “seromucinous borderline tumor of the ovary” [109] is also associated with ovarian endometriosis [98, 110, 111].

Intestinal endometriosis

Involvement of the intestine has been observed in around 10% of patients with (usually deep infiltrating) endometriosis [121]. Although the spread of endometriosis of the (large) intestine into the submucosa may be detected [122], rectal bleeding is rare and endoscopic biopsies are often not diagnostically useful [121].

Consensus-based recommendation 2.E6, reviewed in 2024
Expert consensus	Level of consensus +++
A statement about resection margins must be included in the histopathological report of bowel specimens resected for deep infiltrating endometriosis with bowel involvement.

Macroscopically, the size of (often tumor-like) intestinal wall changes found in resected bowel specimens [124] and their resection margins must be recorded using the metric system. As 50 – 60% of (rectal) endometriosis lesions are multifocal and around one third are multicentric [122, 126], some authors recommend an endometriosis-free resection margin of 2 cm [126]. It is advisable to embed the intestinal resection margins separately and take representative samples to assess the extent of the lesion in the intestinal wall and evaluate the status and distance to the circumferential (soft tissue) resection margin.

Satellite foci due to secondary reactive changes without thickening of the intestinal wall are observed in 50 – 60% of resected specimens [122, 126]. This should be mentioned in the histopathological report. Pericolic lymph node involvement is rare [124].

2.3  DRG system for endometriosis (ICD-10-GM Version 2025, OPS-2025)

S. P. Renner, S. Burghaus

Endometriosis is classified in the ICD-10-GM Version 2025 as follows ( Table 5 ).

Table 5  ICD-10-GM Version 2025.

ICD 10 Code	Description
N80.0	Endometriosis of uterus includes: adenomyosis uteri
N80.1	Endometriosis of ovary
N80.2	Endometriosis of fallopian tube
N80.3	Endometriosis of pelvic peritoneum
N80.4	Endometriosis of rectovaginal septum and vagina
N80.5	Endometriosis of intestine
N80.6	Endometriosis in cutaneous scar
N80.8	Other endometriosis includes: endometriosis of bladder and ureter, thoracic endometriosis
N80.9	Endometriosis, not specified

The OPS ( Operations- und Prozedurenschlüssel ; this is the official German classification system used to code surgical procedures and medical interventions in hospitals and outpatient units) only lists a few specific codes for the destruction of endometriosis foci. General OPS codes are used for most surgical procedures, e.g., cyst enucleation, peritonectomy or the resection of deep infiltrating endometriosis in specific locations (excision of cutaneous scars, intestinal or vaginal resection).

Consensus-based statement 2.S7, new in 2024
Expert consensus	Level of consensus +++
Because of the complexity of care needed by patients with endometriosis, depending on the specific case, surgical therapy may require admission to hospital for treatment. This is because patientsʼ chronic pain frequently results in the development of acute pain after surgical therapy.

In many cases, the surgical treatment of endometriosis requires admission to hospital, as the complex pain conditions of patients requires special perioperative care. Chronic pain, which is very common with endometriosis, leads to neuroplastic changes to the central nervous system which faciliate increased pain processing and sensitization. This is the key mechanism behind persistent postoperative pain [65]. After surgery, it may lead to a disproportionate pain reaction requiring intensive pain therapy. Admission to hospital makes it possible to carry out structured pain prevention and control using multimodal analgesia concepts, early mobilization, and close monitoring of patients. This not only reduces postoperative pain but also avoids long-term pain chronification and promotes patientsʼ postoperative recovery.

3  Symptoms and diagnosis of endometriosis (diagnostic algorithm)

Consensus-based recommendation 3.E7, modified in 2024
Expert consensus	Level of consensus ++
Source: modified from [140]
Reference: [140]
Leading endometriosis-related symptoms (dysmenorrhea, dysuria, dyschezia, dyspareunia and sterility) and non-specific symptoms such as chronic lower abdominal pain must be recorded when taking patientsʼ gynecological history. The information can be recorded using an endometriosis-specific quesionnaire. The primary gynecological diagnosis must report risk factors for pain chronification and indications of underlying pain mechanisms ( Table 6 ).

Table 6 Standard general and symptom-based gynecological history of cases with (suspected) endometriosis.

General medical history	Symptom-based medical history
Menstrual history	Dysmenorrhea
Gravidity/parity	Lower abdominal pain (cyclical/acyclic)
Prior therapy	Dyschezia/hematochezia
Previous surgery	Dysuria/hematuria
Medications (previous and current)	Dyspareunia
General (internal) medical history	Sterility
Allergies	Fatigue [50, 142]
Body mass index	Cyclical shoulder pain, poss. dyspnea
Family medical history	Cyclical neurogenic pain symptoms in the lower extremities
Social history

Consensus-based recommendation 3.E8, new in 2024
Expert consensus	Level of consensus +++
A structured pain history must be taken when examining patients with endometriosis and/or chronic lower abdominal pain ( Tables 7 and 8 ).

Table 7  Clinical evidence for nociplastic pain mechanisms (central sensitization).

Clinical evidence for nociplastic pain mechanisms (central sensitization)
Constant (acyclic) lower abdominal pain
Several pain locations (head, face, extremities, back)
Functional disorders (temporomandibular dysfunction, irritable stomach, irritable bladder)
General symptoms: increased tendency to fatigue, concentration problems and memory deficits
Increased sensitivity to other stimuli (noise, smell, taste, temperature)

Consensus-based recommendation 3.E9, reviewed in 2024
Expert consensus	Level of consensus +++
A bilateral renal ultrasound scan must be performed if deep infiltrating endometriosis or ovarian endometriosis is suspected.

Kidney damage or renal failure caused by urinary retention is a real risk in 25 – 50% of cases with endometriosis of the ureter. Bilateral renal ultrasound scan may help detect urinary retention at an early stage [144]. Renal ultrasound is recommended when endometriomas and deep infiltrating endometriosis are present, especially if the rectovaginal septum and/or the uterosacral ligaments are involved. Endometriosis foci measuring 3 cm or more on renal ultrasonography provide reliable data for the diagnosis of endometriosis of the ureter [149]. Additional issues are discussed in Chapter 6.7 Endometriosis of bladder and ureter (N80.8) .

Consensus-based recommendation 3.E10, new in 2024
Expert consensus	Level of consensus +++
Imaging with transvaginal sonography should be used as the standard first diagnostic procedure to detect endometriosis and, combined with patient-specific symptoms, should be the starting point for further diagnostic and therapeutic measures. An MRI scan should be additionally carried out as a second-line approach if sonography alone does not provide sufficient information.

Confirmation of suspected endometriosis is only possible after histological confirmation based on tissue specimens. However, obtaining histological evidence of disease is not always useful as this requires surgery in every situation, irrespective of symptoms and findings. As imaging procedures, especially sonography, have developed and improved, a diagnosis of endometriosis – with the exception of peritoneal endometriosis – can be reliably made with sonography or MRI [150, 151].

If imaging findings are unusual, the positive predictive value of transvaginal ultrasound and of MRI for adenomyosis of the uterus, ovarian endometriosis and even deep infiltrating endometriosis is so high that histological confirmation becomes less important [147, 152]. Persistent pain, organ destruction, and assessment of sterility are indications for a surgical diagnostic workup and endometriosis treatment.

An algorithm for symptom-based diagnostic procedures and treatment is shown in Fig. 1 .

Fig. 1.

 Symptom-based diagnostic procedures for patients with (suspected) endometriosis (based on expert consensus, level of consensus +++). * In the event of inadequate symptom control; + Including (* Definition of “inadequate symptom control”: persistent symptoms despite induced amenorrhea after at least three months of hormone therapy or when amenorrhea is not achieved despite treatment attempts using different therapeutic agents). [rerif]

The surgical steps for a diagnostic/therapeutic laparoscopy are shown in Table 9 .

Table 9  Recommendations for diagnostic/therapeutic laparoscopy to diagnose and treat suspected endometriosis.

Mandatory surgical steps for diagnostic/therapeutic laparoscopy (photographic documentation of individual steps recommended)
Patient positioning prior to procedure (see AWMF S2k guideline no. 015/077 Recommendations to avoid positioning-related injuries in surgical gynecology [153])
The initial puncture is usually carried out using a Veress needle in the area of the umbilical fossa; a different point of access may be required depending on the anatomical constellation or prior medical history, the area below the puncture site must be inspected (Injury at entry point? Immediate treatment may be required)
Inspection of the cecum, appendix, ascending colon, right paracolic sulcus, local abdominal wall
Inspection of the right dome of the diaphragm, gallbladder, right lobe of the liver, round ligament of the liver, local abdominal wall
Inspection of the left dome of the diaphragm, left lobe of the liver, stomach, spleen, omentum, transverse colon, local abdominal wall
Inspection of the left paracolic sulcus, descending colon, rectosigmoid colon, omentum, small intestine, local abdominal wall
Patient placed in Trendelenburg position, placement of 1 to 3 trocars depending on the site, usually in the right and left lower abdomen and e.g., 2 cm above the symphysis; placement may vary depending on the site
Inspection of the bladder peritoneum, round ligament, internal inguinal rings
Inspection of the uterus and all uterine surfaces
Inspection of left fallopian tube, anterior and posterior aspect of the left ovary, ovarian fossa, pelvic wall, and left uterosacral ligament, with potential adhesiolysis of rectosigmoidal adhesions
Inspection of right fallopian tube, anterior and posterior aspect of the right ovary, ovarian fossa, pelvic wall, and right uterosacral ligament, with potential adhesiolysis of the cecum, appendix
Inspection of the rectosigmoid colon, rectouterine pouch, sacral promontory

Consensus-based statement 3.S8, reviewed in 2024
Expert consensus	Level of consensus +++
References: [154, 155]
Biomarkers are not suitable to diagnose endometriosis, irrespective of the histopathological diagnosis.

In recent years, resources have increasingly focused on developing a diagnostic test which could be used to diagnose endometriosis. Determination of CA-125 is often done as part of the differential diagnostic workup to diagnose complex ovarian processes. But this this tumor marker lacks specificity for endometriosis [156]. This also applies to tumor marker CA-19-9 [157].

A number of other approaches are being considered in the context of developing a diagnostic test. A panel of six autoimmune biomarkers was defined for the diagnosis of minimal to mild endometriosis (sensitivity ≥ 60% and specificity ≥ 80%) [158]. Serum ICAM-1 has a higher specificity for the diagnosis of endometriosis in the Asian population [159]. Attempts are also being made to identify biomarkers which could establish a correlation with the severity of endometriosis [160]; however, they cannot yet be used in routine practice [154, 155]. Data are available for the determination of miRNA in saliva or blood as a diagnostic test [161, 162].

Consensus-based recommendation 3.E11, new in 2024
Expert consensus	Level of consensus +++
Potential sexual dysfunction should be explored in patients with endometriosis.

It is well established that patients with endometriosis often suffer from deep dyspareunia which has an impact on general sexual function and relationships; this issue is also referred to as female sexual dysfunction (FSD).

4  Basic treatment principles for endometriosis

Endometriosis is a chronic disease which requires long-term planning of therapy. The basis of treatment is conservative forms of therapy, including hormone treatment and/or drug-based options. Surgical interventions are necessary for certain indications. Complementary and multimodal measures also have an important role to play – both in the treatment of secondary myofascial symptoms arising from chronic pain adaptation and in the context of further pain relief and disease management. The choice of therapy is based on a careful risk-benefit analysis which takes potential contraindications into account.

As neither prevention nor causal therapy currently exists for endometriosis, treatment focuses on achieving freedom from symptoms for as long as possible, reducing functional limitiations, preventing damage to organs, and adapting treatment to the patientʼs individual situation to improve her quality of life.

4.1  Hormone therapy

Consensus-based recommendation 4.E12, modified in 2024
Expert consensus	Level of consensus +++
The following first-line substances should be used to treat symptomatic endometriosis-related pain: a suitable progestin (e.g., dienogest), or a GnRH antagonist with oral bioavailability, potentially with add-back therapy (e.g., Relugolix + NETA + E2 or linzagolix with add-back therapy) if preceeded by surgery to diagnose endometriosis.

Consensus-based recommendation 4.E13, modified in 2024
Expert consensus	Level of consensus ++
Second-line therapy may include: A GnRH antagonist with oral bioavailability, potentially with add-back therapy (e.g., relugolix + NETA + E2 or linzagolix with add-back therapy) Combined oral contraceptives Other progestins including progestins for topical application A GnRH agonist, potentially with add-back therapy

Progestins

The primary progestins used for the symptomatic treatment of endometriosis include dienogest, medroxyprogesterone acetate and norethisterone. Progestins available in German-speaking countries which are suitable for long-term use include dienogest, desogestrel and drospirenone. Dydrogesterone may be used cyclically if the woman wishes to become pregnant as it does not inhibit ovulation.

GnRH analogs

Consensus-based recommendation 4.E14, reviewed in 2024
Expert consensus	Level of consensus +++
Treatment with GnRH analogs should be supplemented by add-back treatment with a suitable estrogen-progestin combination. This can minimize the consequences of estrogen deficiency without affecting the therapeutic efficacy of the GnRH analog.

Primary hormone therapy

Consensus-based recommendation 4.E15, new in 2024
Expert consensus	Level of consensus +++
If a patient with endometriosis has already completed two hormone therapies without sufficient improvement of symptoms, she should be reevaluated in a facility specializing in the treatment of patients with endometriosis.

Postoperative hormone therapy

Consensus-based statement 4.S9, reviewed in 2024
Expert consensus	Level of consensus +++
Long-term continuous hormone treatment is effective both for the treatment of endometriosis-related symptoms and for prolonging the recurrence-free interval.

4.2  Pain therapy

Consensus-based recommendation 4.E16, modified in 2024
Expert consensus	Level of consensus +++
Patients with chronic lower abdominal pain should be offered symptom-based pain therapy for the following constellations: Persistent pain-related impairment despite receiving hormone and/or surgical treatment, Hormone therapy is not tolerated and/or is contraindicated, Surgery is contraindicated.

Non-opioid analgesics

Non-steroidal anti-inflammatory drugs

Consensus-based recommendation 4.E17, new in 2024
Expert consensus	Level of consensus +++
Non-steroidal anti-inflammatory drugs should be used as symptomatic pain therapy of nociceptive pain mechanisms.

Consensus-based recommendation 4.E18, new in 2024
Expert consensus	Level of consensus +++
If patients with endometriosis suffer chronic pain, the following substances (listed alphabetically) may be trialed as individualized therapy, depending on the underlying pain mechanism: antidepressants (tricyclical antidepressants) cannabis-based medication gabapentinoids (gabapentin, pregabalin) metamizole, paracetamol serotonin-noradrenaline reuptake inhibitors opioid analgesics

Cannabis-based medication

Cannabis-based medication is not suitable for patients under the age of 25. For a discussion on the responsible use of medicinal cannabis, please refer to the position paper by the ad hoc commission “Cannabis in Medicine” of the German Pain Society [219].

Consensus-based recommendation 4.E19, new in 2024
Expert consensus	Level of consensus ++
Because the substances used for symptomatic pain therapy must be taken over the longer term, every medicinal pain therapy prescribed to patients with endometriosis should be reviewed by professionals from multiple disciplines (e.g., involving an interdisciplinary coordination between specialists for pain medicine and psychotherapists).

In summary, the available treatment options based on the underlying pain mechanisms are listed in Table 10 .

Table 10  Pain medication options for chronic lower abdominal pain*.

Symptom	Option
* Classifications of different classes of medicines for different pain mechanisms based on authorsʼ experience.
Nociceptive pain components , e.g., deep infiltrating endometriosis	Non-opioid analgesics (NSAIDs, metamizole, paracetamol), opioids
Neuropathic pain components	Tricyclical antidepressants (amitriptyline), SNRI (duloxetine), anticonvulsants (pregabalin, gabapentin) and cannabis-based medications (THC, CBD, and combinations)
Nociplastic pain components	Tricyclical antidepressants (amitriptyline), SNRI (duloxetine), anticonvulsants (pregabalin, gabapentin) and cannabis-based medications (THC, CBD, and combinations)

4.3  Surgical treatment

Consensus-based recommendation 4.E20, modified in 2024
Expert consensus	Level of consensus +++
Complete resection should be aimed for in symptomatic patients with deep infiltrating endometriosis if the expected benefits of pain reduction and/or the removal of organ damage outweigh the disadvantages of possible surgery-related organ impairment (e.g., sexuality, bladder and bowel function, sensitivity and motor coordination disorders).

The goal of surgery is to rectify existing symptoms. The aim is to preserve the highest quality of life and carry out surgical procedures which can reduce existing functional disorders or even prevent them from developing. Nerve-sparing dissection must be carried out to avoid the risk of urinary retention when excising deep infiltrating endometriosis [222].

Excision and ablation of endometriosis foci are equivalent methods to treat peritoneal endometriosis; both lead to a significant improvement in endometriosis-related symptoms [223]. The advantage of excision compared to ablation is that excision permits histological confirmation of findings.

Consensus-based recommendation 4.E21, reviewed in 2024
Expert consensus	Level of consensus +++
If symptoms recur after surgical therapy, the first approach should consist of medication before carrying out repeat surgery, unless there are compelling reasons to carry out surgery (e.g., organ destruction).

Cross-sectional and cohort studes were unable to confirm a clear benefit of surgery compared to drug therapy for the treatment of endometriosis-related pain [191].

Consensus-based statement 4.S10, new in 2024
Expert consensus	Level of consensus +++
The standard approach for surgical treatment is minimally invasive surgery.

Laparoscopy is the standard approach for the surgical treatment of endometriosis. After a follow-up of 6 months, access via a single port was found to have no benefit in gynecological surgery compared to conventional laparoscopy [224]. Laparoscopy is associated with significantly shorter operating times, less blood loss, shorter hospital stays, and a shorter incision length compared to laparotomy [225].

4.4  Psychosomatic therapy

Consensus-based statement 4.S11, reviewed in 2024
Expert consensus	Level of consensus +++
Endometriosis may be associated with psychological disorders such as anxiety and depressive disorders.

Consensus-based recommendation 4.E22, reviewed in 2024
Expert consensus	Level of consensus ++
A primary investigation into anxiety and depression should be carried out in patients with endometriosis as part of basic gynecological psychosomatic care.

Screening for increased levels of anxiety and depression is recommended as part of primary gynecological care which also includes basic psychosomatic care. Potentially useful “practical tools” available without licence fees include the patient health questionnaire PHQ-4 and the expanded patient health questionnaires PHQ-9 and GAD7. Especially when treating patients with endometriosis and related pain syndromes it is advisable to agree on appropriate treatment options with pain therapists, psychosomatic medicine specialists and psychotherapists or psychological psychotherapists. Caution is advised when carrying out repeated surgical interventions for pain reduction as chronic pain syndrome is a negative prognostic predictor for the success of endometriosis surgery [228].

Consensus-based recommendation 4.E23, new in 2024
Expert consensus	Level of consensus +++
Psychotherapeutic methods, especially cognitive behavioral therapy and mindfulness-based interventions, may be recommended to patients with heavy psychological burdens and/or physical symptoms.

4.5  Complementary therapies and other treatment options

A few small, prospective, randomized studies have investigated the efficacy of complementary therapy methods in reducing pain in patients with primary dysmenorrhea, although the studies rarely included confirmation of endometriosis. The success of pain reduction was usually similar to that reported for the placebo, comparison, or control group; results for the verum group were seldom better. The numbers of patients and participants included in the studies were usually small. The maximum study periods and follow-up times were 6 to 12 months. The data on fertility is inadequate.

Mind-body medicine

Consensus-based recommendation 4.E24, new in 2024
Expert consensus	Level of consensus ++
Progressive muscle relaxation and self-applied massage of the lower abdomen may be considered as a means of relieving menstrual symptoms.

Physical activity

Consensus-based recommendation 4.E25, new in 2024
Expert consensus	Level of consensus ++
Regular physical activity irrespective of intensity (e.g., aerobic training, yoga or stretching exercises) should be recommended to women to relieve menstrual pain.

Transcutaneous electric nerve stimulation (TENS)

Consensus-based recommendation 4.E26, new in 2024
Expert consensus	Level of consensus ++
TENS and vaginal electrostimulation may be considered to treat chronic endometriosis-related pain.

Physiotherapy

Consensus-based recommendation 4.E27, new in 2024
Expert consensus	Level of consensus +++
Physiotherapy based on individual symptoms should be included in the treatment concept for patients with endometriosis.

Osteopathy

Consensus-based recommendation 4.E28, new in 2024
Expert consensus	Level of consensus ++
Osteopathic treatment may be considered for patients with endometriosis.

Sexual medicine

Consensus-based recommendation 4.E29, new in 2024
Expert consensus	Level of consensus +++
Sexual medical counseling/therapy should be offered to patients with sexual dysfunction.

Sexual medical counseling and therapy may help the patient to understand her pain mechanisms, develop individual coping strategies (guidance about alternative, less painful sexual practices, or the use of assistive devices) and improve communication with their partner. The aim is to improve affected patientsʼ quality of life and ensure a holistic treatment approach [252].

Nutrition

Consensus-based recommendation 4.E30, new in 2024
Expert consensus	Level of consensus +++
A healthy (vitamin-rich and high fiber) diet should be recommended to patients with endometriosis. Patients should not follow special diets if they are not medically indicated (e.g., for food intolerance).

Nutritional supplements ( Table 11 )

Table 11  Dietary supplements to treat dysmenorrhea/endometriosis.

Substance	Dose	Effect
Calcium	1000 mg/d starting on the 15th day of the menstrual cycle and continuing until the start of menstruation for 3 cycles	Significant pain reduction compared to placebo in patients with primary dysmenorrhea [263]
Magnesium citrate	200 mg for 3 cycles Transdermal products (spray) also possible	Significant reduction of pain based on a before/after comparison of patients with dysmenorrhea [262]
Melatonin	20 mg/d for 2 cycles	No effect [265]
Omega-3 fatty acids	300 – 1800 mg/d for 2 – 3 cycles	Significant pain reduction compared to placebo in patients with primary dysmenorrhea [260]
Vitamin D	Up to 50 000 IU/w for 2 – 3 months (recommended dose in cases with Vitamin D deficiency 800 – 1200 IU/d for 6 – 8 weeks followed by review of serum levels)	Significant pain reduction compared to placebo in patients with dysmenorrhea [256, 258]
Vitamin E	200 mg/d for 2 cycles	Significant pain reduction starting from the 2nd menstrual cycle compared to placebo in patients with primary dysmenorrhea [259]
Vitamin combinations/antioxidants	Vitamin E 100 mg/d, Vitamin C100 mg/d, Vitamin D 800 – 1200 mg/d for 6 – 8 weeks	Significant pain reduction of endometriose- and/or dysmenorrhea-related pain compared to placebo with a combination therapy of Vitamin E and C or COC [258]
Zinc sulfate	40 mg/d for 3 cycles	Significant pain reduction after the 2nd menstrual cycle compared to placebo in patients with primary dysmenorrhea [266]
Phytoestrogens	Genistein, resveratrol, isoflavones	No inferences about effectiveness possible

Phytotherapy ( Table 12 )

Table 12  Phytotherapeutics to treat dysmenorrhea/endometriosis.

Substance	Dose	Effect
Damascene rose		No effect [267]
Fennel	120 – 250 mg/d extract or 20 – 30 drops/d of 2% oil for 1 – 3 days over 2 – 3 cycles	Significant pain reduction compared to placebo and equivalent to painkillers in patients with primary dysmenorrhea [268]
Ginger	700 – 1000 mg/d 2 – 5 days	Significant pain reduction compared to placebo and equivalent to painkillers in patients with primary dysmenorrhea [269]
Pine bark	60 mg/d	Limited effect [270]
Curcuma Curcuma + mefenamic acid	500 mg/d 500 mg + 250 mg/d 5 days before and during menstruation	Limited effect [271]
Cinnamon	1200 – 3000 mg/d 3 days	Significant pain reduction compared to placebo in patients with primary dysmenorrhea [272]

Acupuncture

Consensus-based recommendation 4.E31, new in 2024
Expert consensus	Level of consensus ++
Acupuncture treatment (about eight sessions) along with other forms of treatment may be considered to relieve lower abdominal pain and/or menstrual symptoms in women with endometriosis.

4.6  Multimodal therapy for endometriosis

J. Erlenwein, W. Häuser, S. Mechsner

Endometriosis is a complex, multifactorial disease which can affect all areas of a womanʼs life where, in line with the biopsychosocial understanding of the disease, physical, psychological, and social factors come together to determine the burden of disease and level of suffering. A stepped care approach is recommended. Distinct definitions are currently only available for the treatment of chronic pain [289 – 291]. Because the terminology varies, it is important to define the necessary approach step by step. A combination of different therapeutic procedures (e.g., drug therapy and physiotherapy) is referred to as a multimodal approach. Parallel treatment which is not necessarily closely coordinated by different disciplines (e.g., a gynecologist, pain therapist, and physiotherapist) is referred to as multidisciplinary treatment.

In contrast, interdisciplinary multimodal therapy consists of close and systematically coordinated cooperation between different medical specialties and can take the form of systematic team meetings or case conferences. This approach integrates different treatment methods and techniques to address both the physcial and the psychological and social aspects of the disease. The combination of different therapeutic measures is continually coordinated by the specialists involved and patients are offered joint treatment at the same location. The close coordination and integration of professional expertise and different therapeutic approaches aims to achieve the best possible overall result for the patient. Such an approach can only be carried out in specialized centers and/or by a well-balanced team and requires well-defined team and communication structures ( Fig. 2 ).

Fig. 2.

 Multimodal, multidisciplinary, and interdisciplinary treatment of patients with endometriosis. [rerif]

Multimodal treatment methods to treat endometriosis-related pain

Consensus-based recommendation 4.E32, new in 2024
Expert consensus	Level of consensus +++
When a patient with endometriosis has a chronic pain disorder, she should be offered pain treatment as part of interdisciplinary multimodal pain therapy.

Consensus-based recommendation 4.E33, new in 2024
Expert consensus	Level of consensus ++
Reference: [300]
If endometriosis is accompanied by chronic pain, psychotherapeutic methods should be integrated into a multimodal concept.

Psychotherapy for women with unfulfilled wish for children and fertility treatment

Consensus-based recommendation 4.E34, new in 2024
Expert consensus	Level of consensus +++
If a patient with endometriosis has an unfulfilled wish to have a child or if she is currently undergoing fertility treatment, she should be offered psychotherapeutic interventions, especially cognitive-behavioral therapy or mindfulness-based interventions.

Consensus-based recommendation 4.E35, new in 2024
Expert consensus	Level of consensus +++
Reference: [307]
Women suffering with high levels of psychological stress because of their infertility disorder should be offfered psychotherapeutic support as part of standard care.

5  Care structures for patients with suspected or confirmed endometriosis

Consensus-based recommendation 5.E36, reviewed in 2024
Expert consensus	Level of consensus +++
Patients with endometriosis should be treated by an interdisciplinary team. The team should bring together all necessary specialist disciplines in a cross-sectoral network. This can be realized in the context of a care structure with spezialized and/or certified facilities (consultation hours, clinic/medical unit, center).

A definition of treatment standards and care structures must further improve the quality of treatment ( Fig. 3 ).

Fig. 3.

 Consented treatment algorithm by the guideline authors (based on expert consensus, level of consensus +++). [rerif]

6  Diagnosis and therapy of endometriosis according to location

6.1  Adenomyosis uteri (N80.0)

Symptoms

Patients with adenomyosis uteri often present with hypermenorrhea and acyclic bleeding. Other problems may include dysmenorrhea, dyspareunia, and infertility. A key analysis reported that 40 – 50% of affected persons suffer from menorrhagia, 10 – 12% from metrorrhagia, 15 – 30% from dysmenorrhea and 7% from dyspareunia. 30% of patients with adenomyosis uteri have no symptoms [320]. 38 – 64% of patients have isolated adenomyosis uteri, i.e., without other forms of endometriosis [321].

The data suggest an association between adenomyosis uteri and dysmenorrhea in 50 – 93% of cases. A linear correlation between the extent of adenomyosis uteri and dysmenorrhea has also been reported. Suggested causes for the development of pain include the prostaglandin metabolism, the possible presence of nerve fibers in adenomyosis lesions, uterine hyperperistalsis, and increased oxytocin receptor expression.

Diagnosis

Consensus-based recommendation 6.E37, reviewed in 2024
Expert consensus	Level of consensus +++
A diagnosis of suspected adenomyosis uteri can be made with transvaginal ultrasound and/or MRI. Transvaginal sonography must be used for the first-line diagnostic investigation and MRI for a second-line diagnosis. Both methods are equivalent in terms of the validity of their findings.

Sonography

A diagnosis of different forms of adenomyosis uteri may be obtained with transvaginal ultrasound [328]. Different typical ultrasound signs of adenomyosis uteri have been described in the literature, especially by the MUSA (Morphological Uterus Sonographic Assessment) working group ( Table 13 ).

Table 13  Transvaginal ultrasound signs of adenomyosis of the uterus.

Ultrasound signs	Criteria	References
Direct ultrasound signs	myometrial cysts hyperechogenic islands in the myometrium echogenic subendometrial lines and buds	[334], [329, 335]
Indirect ultrasound signs	enlarged spherical uterus asymmetrical myometrial thickness between anterior and posterior wall fan-shaped shadowing translesional vascularization (vessels perpendicular to the uterine cavity/serosa crossing the lesion) question mark sign (retroflexed uterine corpus, fundus faces posterior compartment and cervix is anteverted) irregular junctional zone interrupted junctional zone

Other forms of diagnosis

Consensus-based recommendation 6.E38, reviewed in 2024
Expert consensus	Level of consensus +++
A biopsy should not be carried out because the sensitivity and specificity of a biopsy-based confirmation of adenomyosis uteri is limited.

Therapy of adenomyosis uteri

The choice of drug therapy and/or surgical therapy is influenced by the age of the patient and whether she may wish to have children.

Consensus-based statement 6.S12, modified in 2024
Expert consensus	Level of consensus +++
All established forms of hormone therapy (combined oral contraceptives, progestins, suitable progestin IUD, GnRH agonists, GnRH antagonists) are effective to treat adenomyosis-related symptoms. There is no evidence that one substance class is superior.

Consensus-based recommendation 6.E39, reviewed in 2024
Expert consensus	Level of consensus +++
Interventional treatment options to treat adenomyosis uteri such as high-intensity focused ultrasound (HIFU), uterine artery embolization (UAE), transcervical electroablation, percutaneous microwave ablation (PMWA) must only be used in studies.

Surgical therapy

Consensus-based recommendation 6.E40, reviewed in 2024
Expert consensus	Level of consensus +++
Cystic or focal adenomyosis uteri may be resected to control pain and bleeding.

Consensus-based recommendation 6.E41, modified in 2024
Expert consensus	Level of consensus +++
Hysterectomy may be recommended to treat adenomyosis uteri when family planning has been completed and symptoms could not be sufficiently reduced under conservative treatment.

6.2  Endometriosis of ovary and fallopian tube (N80.1 and N80.2)

Symptoms of ovarian and tubal endometriosis

Typical symptoms of endometriomas are dysmenorrhea, chronic non-menstrual symptoms, and infertility. The symptoms of patients with ovarian or tubal endometriosis do not differ significantly from the symptoms of patients with endometriosis in other locations. The importance of ovarian endometriosis for fertility is higher than for other endometriosis manifestations.

Diagnosis of ovarian and tubal endometriosis

Consensus-based recommendation 6.E42, reviewed in 2024
Expert consensus	Level of consensus +++
Transvaginal sonography must be used to assess the ovaries in cases with confirmed or suspected endometriosis.

Consensus-based recommendation 6.E43, reviewed in 2024
Expert consensus	Level of consensus +++
In cases with suspicious ovarian ultrasound findings, surgery must be performed to obtain histological confirmation of the diagnosis while taking due care to ensure oncological safety.

Consensus-based recommendation 6.E44, reviewed in 2024
Expert consensus	Level of consensus +++
When an endometrioma is diagnosed, the simultaneous presence of deep infiltrating endometriosis must be excluded and renal sonography must be carried out.

Therapy for ovarian and tubal endometriosis

Consensus-based recommendation 6.E45, modified in 2024
Expert consensus	Level of consensus ++
Anti-Müllerian hormone levels must be determined as a marker of ovarian reserve before deciding on the treatment strategy for ovarian endometriosis.

Drug therapy

Consensus-based recommendation 6.E46, modified in 2024
Expert consensus	Level of consensus ++
Long-term systemic progestin therapy may be carried out as prophylaxis against the recurrence of endometriomas, preferably in the form of progestin monotherapy or, if there are no contraindications, using combined hormonal contraceptives.

Drug therapy alone is inadequate to treat ovarian endometriomas over the medium term. The preoperative administration of a GnRH analog or of progestin may reduce the size of the endometrioma [376]. Postoperative administration of GnRH analogs will not compensate for incomplete resection. While some study groups were able to show that the postoperative administration of a hormonal contraceptive can reduce recurrence rates, two other prospective randomized placebo-controlled studies showed low rates of recurrence irrespective of the treatment arm [377, 378]. A meta-analysis was able to show that long-term prophylaxis consisting of continuous intake of ovulation inhibitors over a period of 18 bis 24 months was able to reduce the recurrence rate of ovarian endometriosis [379].

Interventional therapies

Interventional treatment approaches such as HIFU, embolization or transcervical electroablation have no importance for the treatment of ovarian or tubal endometriosis.

Sclerotherapy

There is increasing evidence that sclerotherapy could be an effective treatment option for large endometriomas [380, 381]. Sclerotherapy may be peformed either transvaginally or laparoscopically under ultrasound guidance. To do this, the endometrioma is punctured and the cystic epithelium is sclerosed by applying high percentage ethanol solutions. Detailed descriptions of the different therapeutic procedures and their respective access routes in ten steps are available: Crestani et al. described laparoscopic sclerotherapy [382] and Miguel et al. have described the transvaginal ultrasound-guided technique [383].

A retrospective data analysis reported better IVF outcomes in terms of live birth rates after transvaginal ethanol sclerotherapy [384]. A recent meta-analysis of transvaginal sclerotherapy found that the procedure is effective and can be used safely to treat symptomatic endometriomas and resulted in a lower decrease of AMH levels and comparable or better pregnancy rates compared to laparoscopic cystectomy [380].

Surgical therapy

Impact of surgical procedure on ovarian reserve

Consensus-based statement 6.S13, modified in 2024
Expert consensus	Level of consensus +++
All known surgical procedures performed to treat endometriosis reduce ovarian reserve.

Consensus-based statement 6.S14, reviewed in 2024
Expert consensus	Level of consensus +++
The removal of endometriomas is always associated with a higher risk of premature ovarian insufficiency.

Consensus-based statement 6.S15, reviewed in 2024
Expert consensus	Level of consensus +++
When carrying out surgical primary therapy to treat an endometrioma, complete resection of the endometrioma increases the spontaneous pregnancy rate compared to fenestration of the ovary and is superior to drug therapies in terms of pain reduction and recurrence prevention.

Approach for patients with endometrioma who wish to have children (see also Chapter 7.2 Endometriosis and desire for children )

The following factors support the option of surgically removing an endometrioma [366]:

• patient is symptomatic

• intact ovarian reserve

• endometrioma is unilateral

• suspected presentation of endometrioma is suspicious for ovarian malignancy

The following factors support carrying out primary assisted reproduction [366]:

• patient is oligosymptomatic

• additional causes of sterility are present

• patient is older (> 35 years)

• ovarian reserve is already reduced

• presence of bilateral ovarian endometriomas

• recurrence situation

Concluding remarks

Consensus-based recommendation 6.E47, modified in 2024
Expert consensus	Level of consensus +++
Ovarian function and patient age must be considered when deciding on how to treat endometriomas. Reproductive medical counseling and possibly cryoconservation of oocytes and/or embryos must be offered as fertility-protective measures.

6.3  Endometriosis of pelvic peritoneum/peritoneal endometriosis (N80.3)

Consensus-based recommendation 6.E48, reviewed in 2024
Expert consensus	Level of consensus ++
When symptomatic peritoneal endometriosis is diagnosed intraoperatively, the aim should be complete primary therapy. A planned second-look laparoscopy with or without prior treatment must not be carried out.

Consensus-based statement 6.S16, reviewed in 2024
Expert consensus	Level of consensus +++
Ablation and excision to treat superficial peritoneal endometriosis are equivalent in terms of reducing pain.

Consensus-based statement 6.S17, reviewed in 2024
Expert consensus	Level of consensus ++
The surgical removal of peritoneal endometriosis results in improved fertility and a significant reduction in the intensity of dysmenorrhea. A positive effect following surgical removal of superficial peritoneal endometriosis could not be confirmed for chronic lower abdominal pain, dyschezia, and dyspareunia.

6.4  Endometriosis of rectovaginal septum and vagina (N80.4)

Consensus-based recommendation 6.E49, reviewed in 2024
Expert consensus	Level of consensus ++
Asymptomatic endometriosis of the rectovaginal septum and vagina without currently foreseeable clinically relevant secondary consequences (e.g., urinary retention) should not be treated.

Consensus-based recommendation 6.E50, modified in 2024
Expert consensus	Level of consensus +++
Complete resection should be aimed for when endometriosis of the rectovaginal septum and vagina is symptomatic and symptoms do not improve sufficiently with drug therapy.

6.5  Endometriosis of intestine (N80.5)

Symptoms

Different symptoms such as dyschezia, feeling of abdominal pressure, gas, bloating, tenesmus, bleeding and mucus discharge from the rectum, diarrhea and constipation or altered bowel habits occur in connection with intestinal endometriosis, depending on which sector of bowel is affected. A lack of symptoms does not exclude intestinal disease.

Deep rectal endometriosis is often associated with involvement of the rectovaginal septum or the posterior vaginal fornix, meaning that in addition to dyschezia, patients often also report dyspareunia.

Diagnosis

• Transvaginal sonography is simple to perform and transvaginal sonographic imaging provides important information about DIE including diagnosing deep rectal involvement with a high sensitivity and specificity while minimizing the stress for patients [84, 146, 404, 405].

• Rectal endosonography also provides reliable and simple predictions about the presence of deep rectal infiltration [405, 406].

• MRI has a high sensitivity and specificity for the diagnosis of DIE and provides valuable information [405, 406].

• Colorectoscopy is often performed if rectosigmoid involvement is suspected. However, infiltration of the mucosa is very rare; extensive findings are more likely to provide an external impression (around 26% of patients with rectal endometriosis have stenosis), as negative mucosal findings are common on proctoscopy and are unable to exclude endometriosis affecting the intestinal muscles.

Comparative studies have found that vaginal sonography and magnetic resonance imaging (MRI) are generally equivalent in terms of diagnostic performance [150]. Irrespective of the preoperative diagnosis, the extent of resection is often only finalized during surgery (e.g., in cases with multiple disease foci in the intestine: rectum, sigmoid, cecum). Vaginal sonography is considered the primary diagnostic measure for deep intestinal endometriosis because it is widely available [83, 150, 405, 408] ( Tables 14 and 15 ).

Table 14  Clinical examinations to diagnose deep infiltrating endometriosis.

Examination	Finding
Inspection (double-bladed speculum)	Endometriosis visible in the posterior fornix
Palpation (vaginal, rectal)	Uterus often flexed backward; Tough knotty and painful infiltration of the intestine and rectovaginal septum (retrocervical)
Transvaginal sonography	Imaging of deep rectal involvement (defined as up to 16 cm from the anus)

Table 15  Further examinations to diagnose deep infiltrating endometriosis.

Examination	Finding
Colorectoscopy	External impression Mucosal involvement (rare) Stenosis Mandatory in cases with preoperative rectal bleeding for the differential diagnosis of potential primary intestinal disorders
Magnetic resonance imaging	Intestinal wall involvement, bladder involvement, adenomyosis of the uterus
Rectal endosonography	Intestinal wall involvement
Abdominal sonography	Urinary retention

Consensus-based recommendation 6.E51, reviewed in 2024
Expert consensus	Level of consensus +++
Renal sonography must be performed in patients with intestinal endometriosis receiving conservative treatment or pre- and postoperatively to ensure that clinically silent hydronephrosis is not missed.

Consensus-based recommendation 6.E52, reviewed in 2024
Expert consensus	Level of consensus +++
A differential diagnosis must be made when a patient has hematochezia.

Therapy

Consensus-based recommendation 6.E53, modified in 2024
Expert consensus	Level of consensus ++
An asymptomatic patient with intestinal endometriosis – who does not wish to have children or who is sterile – should not have a surgical intestinal procedure.

The treatment of choice for symptomatic deep infiltrating intestinal endometriosis – after failure, intolerance, or rejection of attempted drug therapy – is resection in healthy tissue [411]. Studies found that resection had an overall positive effect on pain and quality of life [412]. Positive effects with regard to fertility could not be excluded; however, it is important to be aware of the rate of complications if resection is only carried out in an oligosymptomatic or asymptomatic patient because of the patientʼs wish to have children [413].

Consensus-based recommendation 6.E54, modified in 2024
Expert consensus	Level of consensus +++
Treatment of a patient with intestinal endometriosis must be based on an interdisciplinary consensus and performed in a certified facility.

Because DIE of the intestine can expand beyond its original location and affect multiple organs, preoperative counseling and planning and performance of the intervention must be based on an interdisciplinary consensus which includes a specialist for visceral surgery. Preparing the patient for planned deep rectal resection must include informing her that she may require placement of a protective temporary stoma and marking the optimal position for the stoma.

Minimally invasive and robot-assisted resection procedures

Consensus-based recommendation 6.E55, new in 2024
Expert consensus	Level of consensus +++
Unless contraindicated, surgical interventions for intestinal endometriosis should be minimally invasive procedures.

It is well known that laparoscopic procedures can also be safely carried out to treat endometriosis with bowel involvement and that this approach offers benefits over the shorter and longer term: a RCT reported decreased blood loss, a lower rate of postoperative complications, and a better result in terms of fertility when laparoscopic procedures were used compared to open surgery [414]. Better pregnancy rates have also been reported following laparoscopic procedures [415]. Valid data for the assessment of robot-assisted procedures for the surgical treatment of intestinal endometriosis are lacking.

Consensus-based statement 6.S18, new in 2024
Expert consensus	Level of consensus +++
Shaving to treat rectal endometriosis is associated with lower rates of postoperative complications but higher rates of recurrence compared to disc or segmental resection. The currently available data does not permit any recommendation to be made in favor of either method.

The surgical technique used for bowel endometriosis depends on the location of the endometriosis [416]. The benefit of surgical removal must be weighed against surgery-related morbidity, potentially relevant complications (especially: anastomotic leak), and the recurrence rate of endometriosis [412]. Recurrence after bowel resection for DIE occurs in about 14% (5 – 25%) of cases [123, 417].

Rectal endometriosis

The following techniques are used for resection irrespective of the approach used (laparoscopy, laparotomy): shaving (superficial extramucosal excision), disc excision (local full-thickness resection) and segmental resection.

Rectal segmental resection

Resection of the affected bowel segment with creation of an anastomosis is the oldest established procedure for the surgical treatment of rectal endometriosis. The rate of postoperative complications is 22.2% and the respective rates of anastomotic leaks and fistulas are 2% [123].

Low anterior resection syndrome

Bowel function disorders such as incontinence, increased frequency of bowel movements, fractionated and urgent bowel evacuation, and painful defecation are common long-term problems after rectal segmental resection. This symptom complex is known as Low Anterior Resection Syndrome (LARS). The pathophysiology of LARS has not yet been fully elucidated. Suggested significant causes include limited reservoir function, iatrogenic injury to the autonomic nerve plexus, and reduced compliance of the neorectum.

A systematic review compared the different techniques used for segmental resection in terms of preservation of the hypogastric nerves and blood supply by the superior rectal artery in patients with endometriosis. The publication reported that even if the hypogastric nerves were preserved, the mean incidence rate for LARS was 13 ± 16% with 95% confidence interval of 28 – 54 or of 19.5 ± 17% if the superior rectal artery was preserved. This indicates that LARS remains a very relevant problem for rectal resections to treat endometriosis and requires further future studies [422].

Disc excision

Disc excision consists of the full-thickness excision of an affected area of the intestinal wall followed by closure of the defect using either hand sutures or staples. Staples may be placed following transanal introduction of a circular stapler [427]. Because of an initially high rate of R1 resections, the published technique has been modified. Most studies consider unifocal lesions < 3 cm and expansion beyond the muscularis propria an indication for disc excision [416].

Shaving

Shaving is used to describe superficial extramucosal, preferably complete, ablation of endometriosis foci and of fibrotic changes from the intestinal wall – leaving the intestinal lumen intact where possible. The complication rates reported in the literature are lower than those following disc excision and segmental resection [428 – 430].

Intestinal preparation prior to colorectal resection

When considering the preoperative approach prior to colorectal resection, see the recommendations in the POMGAT guideline published in 2023 [440]. It currently recommends combining mechanical preparation with oral antibiotics to prepare the intestine for surgery or, alternatively, using only oral antibiotics for intestinal preparation [440, 441].

6.6  Endometriosis in cutaneous scar (N80.6)

Consensus-based statement 6.S19, reviewed in 2024
Expert consensus	Level of consensus ++
Surgical removal of an endometriosis focus in a cutaneous scar controls symptoms and is the treatment of choice.

6.7  Endometriosis of bladder and ureter (N80.8)

Bladder endometriosis

Symptoms

Patients with bladder endometriosis suffer from unspecific symptoms. The most commonly reported symptoms are suprapubic pain (52%), frequent urination with urinary urgency (41%), and/or dysuria (21%). Hematuria is only reported in around 20% of cases [128, 131]. Because of the incidence of polyuria, dysuria and microhematuria, many patients with bladder endometriosis are often wrongly treated for recurrent urinary tract infections [128].

Diagnosis

If the patientʼs medical history is suspicious for bladder endometriosis, an ultrasound examination with detailed assessment of the bladder wall is indicated. Most endometriosis lesions of the bladder can be visualized very well with ultrasonography. Magnetic resonance imaging is only superior to sonography when visualizing small endometriosis lesions in the bladder (< 1 cm in ∅) [451].

Therapy

Even though isolated cases of drug therapy to treat bladder endometriosis have been reported in the literature [452], in most cases treatment of bladder endometriosis consists of partial cystectomy [128, 453].

Ureteral endometriosis

Symptoms

Ureteral endometriosis is usually unilateral and occurs far more often on the left side than on the right [454]. It is usually located in the lower third of the ureter and generally occurs together with other endometriosis lesions [128, 139, 454].

Consensus-based statement 6.S20, reviewed in 2024
Expert consensus	Level of consensus +++
Endometriosis of the bladder and/or the ureter may have serious consequences, such as urinary retention and potentially the consecutive loss of renal function.

Diagnosis

The possibility of ureteral endometriosis must be considered in cases with clinically palpable endometriosis nodules in the area of the rectovaginal septum, the rectal wall, the parametrium (pelvic wall) or ultrasonographic confirmation of “kissing ovaries.”

Therapy

Nowadays, laparoscopic ureterolysis, potentially with preoperative placement of a double J ureteral catheter, is the method of choice to treat ureteral endometriosis [128, 139, 457]. In most cases, the ureteral stenosis will recover within a few weeks after ureterolysis. In cases where preoperative imaging confirmed ureteral stenosis with dilatation of the ureter and/or the renal pelvis, imaging must be repeated three months postoperatively to confirm the success of treatment. In rare cases, especially in cases with intrinsic endometriosis, a small section of the ureter may be excised and anastomized [457] or ureteral reimplantation may be carried out [458]. In a review of various rather small case series, Berlanda et al. showed that the differences in recurrence rates between the three different surgical techniques are small [459]. It is usually advisable to attempt ureteral decompression without segmental resection or ureteral reimplantation as the first step and only perform ureteral reimplantation if the first attempt is unsuccessful and the ureter or the renal pelvis have not recovered. Nowadays, even if preoperative renal scintigraphy only shows a renal function of < 10%, if there are no other clinical symptoms, the affected kidney is left in situ. Partial recovery of renal function is not uncommon.

6.8  Rare extragenital endometriosis locations, extra-abdominal endometriosis (N80.8)

The clinical term “rare extragenital endometriosis locations and extra-abdominal endometriosis” is mainly used to summarize manifestations of endometriosis in areas such as the umbilicus, vulva, nerve structures, and thorax as well as other extremely rare locations.

Umbilical endometriosis

Consensus-based recommendation 6.E56, reviewed in 2024
Expert consensus	Level of consensus +++
Symptomatic endometriosis of the abdominal wall or umbilicus should be surgically removed.

Inguinal region and canal of Nuck

Primary manifestation of endometriosis in the area of the groin is rare; the nodular changes can occur in connective tissue and also in lymph nodes. Depending on the symptoms, complete surgical resection may be advisable although possible development of a hernia may occur in individual cases [462, 463].

Sacral plexus, sciatic nerve, and obturator nerve

Endometriosis involving pelvic nerve structures can be associated with significant levels of pain and result in a loss of functionality. The anatomical pathology is mainly perineural invasion and actual infiltration of the nerves is extremely rare – even though symptoms may appear to indicate it. Although (laparoscopic) surgical therapy (decompression using neurolysis and excision of findings) may reduce pain, improve motor and sensory symptoms and bladder function, and improve overall quality of life, recovery can take months or even years; in individual cases it is associated with serious complications and must be carried out by very experienced surgeons [464 – 467].

Thoracic endometriosis syndrome (TES)

Catamenial pneumothorax

Consensus-based recommendation 6.E57, modified in 2024
Expert consensus	Level of consensus +++
Conservative drug-based measures should be primarily used to treat thoracic endometriosis. Surgical therapy must be performed if drug treatment is unsuccessful or contraindicated. Nevertheless, primary surgery may be indicated in cases with pronounced, symptomatic, endometriosis-associated pneumothorax (including catamenial pneumothorax).

In the literature, endometriosis of the diaphragm, pleura and lung parenchyma is collectively referred to as Thoracic Endometriosis Syndrome (TES). It also includes the clinical presentation of catamenial pneumothorax. Diagnosis and therapy are carried out together with thoracic surgery specialists.

7  Special endometriosis situations

7.1  Endometriosis in adolescence

Up to two thirds of adult women with surgical confirmation of endometriosis report that their pain symptoms already started in adolescence.

Consensus-based statement 7.S21, reviewed in 2024
Expert consensus	Level of consensus +++
All forms of persistent lower abdominal pain (dysmenorrhea, cyclical and acyclic lower abdominal pain) in adolescence may be symptoms of endometriosis.

Consensus-based recommendation 7.E58, reviewed in 2024
Expert consensus	Level of consensus +++
The primary treatment for suspected endometriosis in adolescence should be conservative drug therapy.

According to the S3 guideline “Hormonal Contraception” (AWMF registry no. 015/015, August 2019) [481], hormonal contraception may help reduce menstrual pain. Hormonal contraceptives are prescribed off-label for the treatment of primary and secondary dysmenorrhea. However, the evidence-based data for both COC and progestin-only preparations is limited.

Because of the extensive clinical experience with these preparations, their ease of use, and the positive additional benefit of COC for adolescent girls, first-line treatment for suspected endometriosis in adolescent girls usually consists of NSAIDs and/or a COC. If symptoms persist despite cyclical adminstration for three months, the preparation may be changed or a long-cycle regimen (off-label use) similar to the therapy prescribed to adult patients should be considered. According to the S3 guideline “Hormonal Contraception” (AWMF registry no. 015/015, August 2019) [481], a long-cycle regimen of a combined hormonal contraceptive offers better results than conventional use to treat menstruation-related complaints (dysmenorrhea, catamenial headache [migraine], intestinal irritation).

Consensus-based recommendation 7.E59, reviewed in 2024
Expert consensus	Level of consensus +++
In cases with treatment-refractory pain in adolescence, laparoscopy should be carried out to determine the cause of symptoms and potentially remove the endometriotic lesion, preferably in the same procedure.

7.2  Endometriosis and the wish to have children

The association between endometriosis and an unfulfilled wish to have children has been known for many years. It is assumed that the prevalence of endometriosis in women with an unfulfilled wish to have children may be up to 50% [485].

Consensus-based recommendation 7.E60, modified in 2024
Expert consensus	Level of consensus +++
Women with endometriosis should be informed about their possibly reduced likelihood of becoming pregnant and the effect of age on fertility.

Effect of hormone therapy

The effect of hormonal ovarian suppression on fertility has been comprehensively investigated and, to date, no positive effect on fertility has been confirmed for the hormonal therapy of endometriosis. This applies to hormone therapy as a stand-alone therapeutic approach, perioperative hormone therapy, and hormone therapy as preparation for assisted reproductive technology (ART).

Effect of surgical therapy

The surgical excision or destruction of endometriosis foci improves fertility in woman with all forms of endometriosis. This was observed when clinical pregnancy rates were compared with placebo [309]. This effect was especially in evidence following the removal of peritoneal endometriosis foci as it was found that removal improved the pregnancy rate and the rate of live births [487, 493, 494]. In general, because of the level of pain, resection of deep infiltrating endometriosis must be carried out irrespective of the patientʼs wish to have children (see Chapter 6.5 Endometriosis of intestine [N80.5] ). Some studies of women with an unfulfilled wish to have children reported that excision of deep infiltrating endometriosis had a beneficial effect on the pregnancy rate [494, 495]. This was confirmed in a recent systematic review and meta-analysis. Although randomized controlled studies were lacking, the analysis found that the probability of becoming pregnant increased by a factor of 1.84 per patient and cycle and the likelihood of giving birth was higher by a factor of 2.22 in the group of affected women who underwent surgical excision of deep infiltrating endometriosis prior to ART. Even partial resection of deep infiltrating endometriosis increased the probability of becoming pregnant by a factor of 1.63 compared to patients who had primary ART. The effect was especially pronounced (higher by a factor of 2.43) in the group of affected women with deep infiltrating endometriosis of the intestine compared to women with deep infiltrating endometriosis in other sites (higher by a factor of 1.55) [496].

Patients with adenomyosis of the uterus who wish to have children

The possibility of additional adenomyosis uteri should be investigated in patients with endometriosis who wish to have children (see Chapter 6.1 Endometriosis of uterus [N80.0] ) as adenomyosis uteri can have a negative effect on fertility. This applies to pregnancy rates, birth rates, and rates of miscarriage, both after spontaneous conception and after ART. There is currently no evidence-based therapy recommendation but different drug-based and surgical options are available which could have a positive effect on patientsʼ fertility [498 – 501].

Patients with endometriomas who wish to have children

Whether the excision of endometriomas increases the chances of becoming pregnant has not yet been clearly established. According to the S2k guideline “Diagnosis and therapy before assisted reproductive treatments” (AWMF registry no. 015/085, February 2019) [494], excision of an endometrioma is not a precondition for the success of IVF. According to a systematic review and meta-analysis, the success rates for conception after excision of an endometrioma prior to starting ART tended to be higher than after primary ART [503]. Every form of endometrioma removal reduces ovarian reserve. Complete cystectomy should not be carried out if the dissection level cannot be identified [504]. It is generally accepted that surgery will significantly reduce ovarian reserve, especially when the procedure targets large endometriomas (> 7 cm) or bilateral endometriomas [390], although a negative effect has also been reported following unilateral surgery [505]. However, if the presence of an endometrioma limits the ability to perform follicular puncture to extract oocytes for planned ART, sclerotherapy may be discussed to reduce the volume of the cyst [506]. If surgical excision of an endometrioma is planned (see also Chapter 6.2 Endometriosis of ovary and fallopian tube [N80.1 and N80.2] ), the indication for surgical excision must also include a discussion with the patient about the potential impact on ovarian reserve [493, 494].

Impact on ovarian reserve

Consensus-based recommendation 7.E61, new in 2024
Expert consensus	Level of consensus ++
Before performing surgical excision of an endometrioma, an objective assessment of ovarian reserve should be carried out using AMH or/and AFC and the advantages and disadvantages of fertility-preserving measures should be discussed preoperatively.

AMH is expressed by ovarian granulosa cells, is not cycle-dependent, and has a high sensitivity. AMH levels are very important predictors of ovarian stimulation before artificial reproductive technology (ART) procedures.

Medically assisted reproduction for women with endometriosis

All patients with endometriosis who currently wish to have a child should be advised about their individual prospects of becoming pregnant and having a child as well as the indications for medically assisted reproduction (MAR).

The data from the review article by Somigliana et al. provides evidence for the safe use of MAR in patients with endometriosis and also reported that IVF treatment did not worsen endometriosis-associated symptoms and did not increase the risk of recurrence [515].

In principle, two forms of MAR are recommended: insemination treatment, preferably combined with hormone therapy, and ART with IVF and/or ICSI.

Intrauterine insemination treatment in patients with endometriosis

A diagnostic workup of the fallopian tubes using hysterosalpingo-contrast sonography or laparoscopic chromopertubation and the known advantages and disadvantages of these procedures must be discussed with every patient prior to insemination treatment in patients with known endometriosis. In principle, a diagnostic workup of the fallopian tubes should always be recommended.

Based on existing data, IUI may be recommended to patients with minimal and mild endometriosis, preferably following ovarian stimulation with FSH. Studies on letrozole in patients with endometriosis are lacking. In cases with severe endometriosis, IUI should be carried out following FSH stimulation but the patient will have to be informed that because only limited data are available, the benefit of therapy is difficult to estimate.

Assisted reproductive therapy in patients with endometriosis

Consensus-based statement 7.S22, new in 2024
Expert consensus	Level of consensus ++
Recent observational studies suggest that women with adenomyosis have higher rates of live births after cryo embryo transfer following previous ovarian function suppression with GnRH analogs.

It is not currently possible to make a definitive recommendation and every decision must be made on a case-by-case basis in consultation with the patient.

As regards the choice of ovarian stimulation protocol (agonist, long agonist, antagonist), a recent systematic review by Kuan et al. evaluating eight studies which included a total of 2700 patients found no significant difference in the CPR or LBR between the agonist and the antagonist protocol.

Finally, it is necessary to clarify whether endometriosis has an impact on embryo quality. Another systematic review and meta-analysis by Dongye et al. which included 22 (observational and cohort) studies reported no significant differences in PN stage numbers, blastocyst development, or high-quality embryos, even for patients with ASRM stages III – IV [532]. But as numerous previous studies have come to controversial conclusions, well-designed RCTS are needed to clarify this issue further.

Fertility preservation with endometriosis

Consensus-based recommendation 7.E62, new in 2024
Expert consensus	Level of consensus ++
Women with endometriosis who wish to have children may be offered primary fertility treatment or fertility protection measures such as oocyte cryopreservation or ovarian cryopreservation after assessing the benefits and risks.

7.3  Endometriosis: pregnancy and birth

Pregnancy

As regards pregnancy , numerous studies have assessed the risk constellation as follows:

• A higher miscarriage rate [537]

• A higher rate of preterm births [538]

• Preterm rupture of membranes [539]

• Preterm placental abruption [540]

• Placenta previa [540]

• Risk of preeclampsia – different opinions [541]

• SHIP – sudden hemoperitoneum in pregnancy (very rare) [542]

• Gestational diabetes [543]

• Pregnancies achieved with the help of reproductive medicine because of endometriosis have higher rates of placenta previa and preterm placental abruption [544].

• When endometriosis coexists with adenomyosis uteri, the risk of preterm birth is additionally paired with the risk of intrauterine deficiency (small for gestational age, SGA) [545].

• A higher rate of intrauterine fetal death (IUFD) [543]

Birth

The impact of endometriosis on the birth process is still controversially discussed. There are individual case reports in the literature about complications associated with giving birth but these studies do not yet provide a clear picture [401, 547].

Individual reports about issues with delivery/birth are therefore briefly listed below:

• Rectal perforation during birth in patients with deep infiltrating endometriosis of the rectovaginal septum [547].

• Birth injuries following spontaneous delivery did not occur more often after excision of endometriosis in #Enzian A/B/C compartments [548].

Women with known endometriosis may have questions about the optimal procedure to follow if they wish to have children. The following three question are often asked in this context and the answers are intended to help with decision-making:

1. Must deep infiltrating endometriosis of the intestine be excised prior to any pregnancy?

• The rate of spontaneous births is higher for patients in whom deep infiltrating endometriosis of the intestine was not resected prior to pregnancy [549].

• Intraoperative and postoperative complications occurred more often during cesarean section in patients with deep infiltrating endometriosis of the intestine which had not been surgically removed [549].

2. Do women who underwent partial surgical excision of deep infiltrating endometriosis have a higher risk during pregnancy and birth?

Yes, the following risks have been reported:

• preterm birth [401]

• placenta previa [401]

• preterm placental abruption [401]

• gestational hypertension [401]

• peripartum hysterectomy [401]

3. How must patients with or without surgically excised endometriosis be advised about giving birth?

Consensus-based statement 7.S23, reviewed in 2024
Expert consensus	Level of consensus +++
Excised or existing deep infiltrating endometriosis is not a contraindication for spontaneous delivery.

Consensus-based recommendation 7.E63, reviewed in 2024
Expert consensus	Level of consensus +++
It is not possible to recommend a specific delivery mode (i.e., spontaneous delivery versus cesarean section) for women with existing or excised rectal endometriosis.

Consensus-based statement 7.S24, reviewed in 2024
Expert consensus	Level of consensus +++
Previous surgical therapy of deep infiltrating endometriosis in the area of the sigmoid colon, appendix/cecum, ileum, or colon is not an indication for primary cesarean section.

Consensus-based recommendation 7.E64, new in 2024
Expert consensus	Level of consensus +++
Because of the higher rate of secondary cesarean sections, patients with existing or excised deep infiltrating endometriosis should give birth in hospital.

7.4  Endometriosis and malignancy

Endometriosis and risk of malignant cancer

Patients with endometriosis do not generally have a higher risk of developing a malignancy [551, 552]. However epidemiological studies have reported a 1.3 to 1.9 times higher risk of developing ovarian carcinoma [551 – 554] (see Chapter Endometriosis and ovarian carcinoma ). Moreover, there are also some indications that postmenopausal patients may have a 1.3 to 1.6 higher risk of endometrial cancer [555]. This association was mainly found for patients with adenomyosis uteri [101, 556, 557]. However, these observations have not been confirmed in other meta-analyses [552, 553, 558].

Endometriosis and ovarian carcinoma

Malignant tumors may develop from endometriosis lesions. This does not apply to all endometriosis locations and forms. Ovarian carcinomas are more common while non-gonadal endometriosis-associated malignancies are much rarer.

Most published studies on endometriosis-associated ovarian carcinoma (EAOC) classify the risk of patients with endometriosis developing cancer as moderately increased (RR, SIR or OR: 1.3 – 1.9) [551, 552, 559, 560]. However, women with endometriomas have a significantly higher risk of developing ovarian carcinoma (SIR = 8.95).

Pathology of endometriosis-associated carcinomas

Consensus-based recommendation 7.E65, reviewed in 2024
Expert consensus	Level of consensus +++
The terminology and morphological diagnosis used for endometriosis-associated carcinomas must be based on the WHO classification applicable at the time.

Consequences for counseling and therapy

Consensus-based recommendation 7.E66, reviewed in 2024
Expert consensus	Level of consensus +++
The surgical treatment concept for premenopausal patients with endometriosis should not be influenced by the slightly higher risk of ovarian carcinoma.

In principle, based on epidemiological data, the risk of developing ovarian carcinoma is higher for patients with endometriosis. But because the risk of ovarian cancer is only slightly higher and starts from an already low lifetime risk of 1.3%, the overall risk of developing disease is very low. Endometriosis can therefore not be termed a premalignant lesion. Routine screening for ovarian cancer using vaginal ultrasound or regular measurement of CA-125 is not indicated, also because screening is ineffective [552].

7.5  Endometriosis and association with other disorders

Consensus-based statement 7.S25, reviewed in 2024
Expert consensus	Level of consensus +++
Endometriosis may be associated with other chronic pain syndromes (e.g., irritable bowel syndrome, bladder pain syndrome, fibromyalgia syndrome).

Consensus-based recommendation 7.E67, reviewed in 2024
Expert consensus	Level of consensus +++
Patients with endometriosis and chronic lower abdominal pain must be examined for other chronic pain syndromes.

An examination to determine the presence of other chronic pain syndromes may be carried out in a number of ways:

• By discussing a pain drawing completed by the patient as part of a pain questionnaire (see Chapter 3 Symptoms and Diagnosis of Endometriosis [diagnostic algorithm] ).

• By asking questions: Do you often have a headache, back pain, pain in your arms and legs?

• The patient can complete a questionnaire about gastrointestinal and urological complaints (practical assessment tool: “Visceral and urogenital pain” module of the German Pain Society)

Consensus-based recommendation 7.E68, reviewed in 2024
Expert consensus	Level of consensus +++
When carrying out a gynecological examination, attention should be paid to increased local (e.g., myofascial trigger points) and generalized (increased tenderness on palpation in other areas of the body) sensitivity to pain as an indication of central sensitization to pain.

Consensus-based recommendation 7.E69, reviewed in 2024
Expert consensus	Level of consensus +++
When treating patients with endometriosis and related pain syndromes, treatment options should be coordinated with pain therapists and psychotherapists.

Useful practical tools

• Patient health questionnaire: Physical Symptoms (PHQ-15)

• Patient health questionnaire: Screening Tool for Anxiety and Depression (PHQ-4)

Or the expanded version:

• Patient health questionnaire: Depression (PHQ-9) and GAD-7

8  Rehabilitation, rehab aftercare and self-help

Rehabilitation, follow-up treatment

Consensus-based recommendation 8.E70, reviewed in 2024
Expert consensus	Level of consensus +++
Rehabilitation/follow-up treatment for women with endometriosis should be provided in a rehabilitation clinic certified to treat this disease.* * Addendum for Austria and Switzerland: no inpatient treatment concepts for rehabilitation/follow-up care exist.

Rehab follow-up care

Consensus-based recommendation 8.E71, modified in 2024
Expert consensus	Level of consensus +++
Reference: [596]
Women with endometriosis must be directed to services provided by the funders of medical care, inpatient (in this context: follow-up care) and outpatient care services and to rehab follow-up care.* * Addendum for Austria and Switzerland: no inpatient treatment concepts for rehabilitation/follow-up care exist. Patients should be directed to outpatient services where available.

Self-help

Consensus-based recommendation 8.E72, reviewed in 2024
Expert consensus	Level of consensus +++
References: [597, 598]
Patients should be informed about available self-help options to help them cope with the physical and psychological problems which may affect women with endometriosis.

Consensus-based recommendation 8.E73, modified in 2024
Expert consensus	Level of consensus ++
References: [597, 598]
Women with endometriosis should be encouraged and supported to attend information sessions on endometriosis. The continued development of structured training courses should be supported.

All references are included in the long German-language version of the guideline.