ESHRE guideline: endometriosis

Abstract

STUDY QUESTION How should endometriosis be diagnosed and managed, based on the best available evidence from published literature? SUMMARY ANSWER The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer. WHAT IS KNOWN ALREADY Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organised after finalisation of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE This guideline aims to help clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments, and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected. LIMITATIONS, REASONS FOR CAUTION The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payments. CMB reports grants from Bayer Healthcare and the European Commission; Participation on a Data Safety Monitoring Board or Advisory Board with ObsEva (Data Safety Monitoring Group) and Myovant (Scientific Advisory Group). AB reports grants from FEMaLE executive board member and European Commission Horizon 2020 grant; consulting fees from Ethicon Endo Surgery, Medtronic; honoraria for lectures from Ethicon; and support for meeting attendance from Gedeon Richter; AH reports grants from MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring; Consulting fees from Roche Diagnostics, Nordic Pharma, Chugai and Benevolent Al Bio Limited all paid to the institution; a pending patent on Serum endometriosis biomarker; he is also Chair of TSC for STOP-OHSS and CERM trials. OH reports consulting fees and speaker’s fees from Gedeon Richter and Bayer AG; support for attending meetings from Gedeon-Richter, and leadership roles at the Finnish Society for Obstetrics and Gynecology and the Nordic federation of the societies of obstetrics and gynecology. LK reports consulting fees from Gedeon Richter, AstraZeneca, Novartis, Dr. KADE/Besins, Palleos Healthcare, Roche, Mithra; honoraria for lectures from Gedeon Richter, AstraZeneca, Novartis, Dr. KADE/Besins, Palleos Healthcare, Roche, Mithra; support for attending meetings from Gedeon Richter, AstraZeneca, Novartis, Dr. KADE/Besins, Palleos Healthcare, Roche, Mithra; he also has a leadership role in the German Society of Gynecological Endocrinology (DGGEF). MK reports grants from French Foundation for Medical Research (FRM), Australian Ministry of Health, Medical Research Future Fund, and French National Cancer Institute; support for meeting attendance from European Society for Gynaecological Endoscopy (ESGE), European Congress on Endometriosis (EEC) and ESHRE; She is an advisory Board Member, FEMaLe Project (Finding Endometriosis Using Machine Learning), Scientific Committee Chair for the French Foundation for Research on Endometriosis and Scientific Committee Chair for the ComPaRe-Endometriosis cohort. AN reports grants from Merck SA and Ferring; speaker fees from Merck SA and Ferring; support for meeting attendance from Merck SA; Participation on a Data Safety Monitoring Board or Advisory Board with Nordic Pharma and Merck SA; she also is a board member of medical advisory board, Endometriosis Society, the Netherlands (patients advocacy group) and an executive board member World Endometriosis Society. ES reports grants from National Institute for Health Research UK, Rosetrees Trust, Barts and the London Charity; Royalties from De Gruyter (book editor); consulting fees from Hologic; speakers fees from Hologic, Johnson & Johnson, Medtronic, Intuitive, Olympus and Karl Storz; Participation in the Medicines for Women’s Health Expert Advisory Group with Medicines and Healthcare Products Regulatory Agency (MHRA); he is also Ambassador for the World Endometriosis Society. CT reports grants from Merck SA; Consulting fees from Gedeon Richter, Nordic Pharma and Merck SA; speaker fees from Merck SA, all paid to the institution; and support for meeting attendance from Ferring, Gedeon Richter, Merck SA. The other authors have no conflicts of interest to declare.

Genomic Evidence Supports the Recognition of Endometriosis as an Inflammatory Systemic Disease and Reveals Disease-Specific Therapeutic Potentials of Targeting Neutrophil Degranulation

“…These proof-of-concept targets in endometriosis were all at the top 1% prioritized gene list, including: MAPK8 (9 th ), MAPK10 (46 th ), and MAPK9 (47 th ) targeted by bentamapimod, a JNK inhibitor; ESR1 (19 th ) targeted by estradiol, an estrogen receptor (ER) alpha agonist; ESR2 (99 th ) targeted by prinaberel, an ER beta agonist; AR (26 th ) targeted by danazol, an androgen receptor (AR) agonist, and cyproterone acetate, an AR antagonist; NR3C1 (53 th ) targeted by cyproterone acetate and mifepristone, two glucocorticoid receptor antagonists; NGF (91 th ) targeted by tanezumab, a beta-nerve growth factor inhibitor; PGR (116 th ) targeted by selective progesterone receptor modulators (SPRMs); and TNF (136 th ) targeted by infliximab, a TNF-alpha inhibitor. According to the latest ESHIR guideline ( 62 ), SPRMs such as medroxyprogesterone acetate and levonorgestrel are highly recommended to reduce endometriosis-associated pain, and norethindrone acetate (alongside GnRH) highly recommended to prevent bone loss and hypoestrogenic symptom, but no longer recommended for danazol. Figure 3C also provides a summary of the predictors used and their relative importance (informativeness).…”

ATR-IR Spectroscopy Application to Diagnostic Screening of Advanced Endometriosis

“…However, the current ESHRE guideline (2022) does not support this recommendation anymore, and now, laparoscopy is recommended only for patients with negative imaging results and/or where empirical treatment was unsuccessful or inappropriate. However, members of the Endometriosis Guideline Core Group emphasize that there is still an urgent need for more research to gain more clarity on the most appropriate diagnostics, including laboratory diagnostics [ 4 ]. Therefore, there is a great need for a broadly understood, noninvasive diagnosis of endometriosis.…”

T2*-Weighted Imaging Performance in the Detection of Deep Endometriosis among Readers with Different Experience: Comparison with Conventional MRI Sequences

“…Laparoscopy has been conventionally considered the gold standard for diagnosing endometriosis. However, recent guidelines redefined this indication, underlying that imaging methods have achieved high diagnostic accuracy and recommending invasive diagnostic procedures only in patients with negative imaging findings and/or where empirical treatment was unsuccessful [ 7 ].…”