Guideline sources The following summarized guidelines for the evaluation and management of endometriosis are prepared by our editorial team based on guidelines from the Society of Obstetricians and Gynaecologists of Canada (SOGC 2023; 2010), the European Society of Human Reproduction and Embryology (ESHRE 2022), and the American College of Obstetricians and Gynecologists (ACOG 2018; 2016; 2010). 1 2 3 4 5 6 Guidelines 1. Screening and diagnosis Clinical presentation: Recognize that: https://web.pathway.md/diseases/recjQIQ99LVWEV83Z 1/9 6/29/23, 4:16 AM Endometriosis Pathway symptoms of endometriosis may vary, but certain hallmark symptoms may be more likely to suggest endometriosis; recognize the atypical presentations A endometriosis can be a chronic, relapsing disorder, which may necessitate a long-term follow-up A adolescent patients with endometriosis are more likely than adult patients to present with acyclic pain B physical examination of adolescent patients with endometriosis will rarely reveal abnormalities, as most will have early-stage disease B endometriosis in adolescent patients is often early-stage and atypical. B Diagnosis: Suspect the diagnosis of endometriosis in patients presenting with the following cyclical and non-cyclical signs and symptoms: dysmenorrhea deep dyspareunia dysuria dyschezia painful rectal bleeding or hematuria shoulder tip pain catamenial pneumothorax cyclical cough/hemoptysis/chest pain cyclical scar swelling and pain fatigue infertility. B 2. Diagnostic investigations History and physical examination: As per ESHRE 2022 guidelines, consider performing a clinical examination, including vaginal examination where appropriate, to identify deep nodules or endometriomas in patients with suspected endometriosis, although the diagnostic accuracy is low. B Elicit a history and perform a physical examination for the evaluation of patients with suspected endometriosis. B Perform a pelvic examination, including rectovaginal examination, when deeply infiltrating endometriosis is suspected. B Diagnostic imaging: As per ESHRE 2022 guidelines: Consider obtaining imaging in patients with suspected endometriosis, even if clinical examination is normal. B Obtain ultrasound or MRI in the diagnostic work-up for endometriosis, recognizing that a negative finding does not exclude endometriosis, particularly superficial peritoneal disease. A https://web.pathway.md/diseases/recjQIQ99LVWEV83Z 2/9 6/29/23, 4:16 AM Endometriosis Pathway As per SOGC 2010 guidelines, obtain imaging assessment for the evaluation of patients with suspected endometriosis. B Laboratory studies: As per ESHRE 2022 guidelines: Do not obtain biomarkers in endometrial, blood, menstrual or uterine fluids for the diagnosis of endometriosis. D Obtain genetic testing in patients with suspected or confirmed endometriosis only within a research setting. As per SOGC 2010 guidelines, do not obtain routine CA-125 testing as part of the diagnostic investigation of endometriosis. D 3. Diagnostic procedures Diagnostic laparoscopy: consider performing laparoscopy for the diagnosis and treatment of suspected endometriosis in patients with negative imaging results or if empirical treatment was unsuccessful or inappropriate. C Biopsy: As per ESHRE 2022 guidelines, perform biopsy to confirm laparoscopic identification of endometriotic lesions, although recognize that negative histology does not entirely rule out the disease. B As per SOGC 2010 guidelines: Consider performing biopsy of endometriosis lesions to confirm the diagnosis and rule out underlying malignancy. B Consider performing excision or sampling of suspected endometriosis lesions and endometriomas to help in confirming the diagnosis and excluding underlying malignancy. C 4. Medical management Hormone therapy: As per ESHRE 2022 guidelines, offer hormone treatment (combined hormonal contraceptives, progestogens, gonadotropin releasing hormone agonists or gonadotropin releasing hormone antagonists) as an option to reduce endometriosis-associated pain. A Show 4 more As per SOGC 2010 guidelines, consider using the following agents as first-line therapy in patients with endometriosis: combined hormonal contraceptives (ideally administered continuously) progestin alone (PO, IM, or subcutaneous). B Show 2 more Gonadotropin-releasing hormone agonists/antagonists: As per ESHRE 2022 guidelines, offer GnRH agonists as second-line therapy, for example if hormonal contraceptives or progestogens have been ineffective B , for endometriosis- https://web.pathway.md/diseases/recjQIQ99LVWEV83Z 3/9 6/29/23, 4:16 AM Endometriosis Pathway associated pain, recognizing that insufficient evidence regarding dosage or duration of treatment. A Show 2 more As per SOGC 2010 guidelines: Consider offering GnRH agonist with add-back hormone therapy, or levonorgestrel- releasing intrauterine system, as second-line therapy in patients with endometriosis. B Combine aGnRH agonist with add-back hormone therapy when initiating the therapy, and consider using the combination for longer-term (> 6 months). A Aromatase inhibitors: offer aromatase inhibitors in patients with endometriosis-associated pain refractory to other medical or surgical treatment. Consider initiating aromatase inhibitors in combination with oral contraceptives, progestogens, gonadotropin releasing hormone agonists or GnRH antagonists. A Analgesics: As per ESHRE 2022 guidelines, consider offering NSAIDs or other analgesics (either alone or in combination with other treatments) to reduce endometriosis-associated pain. C As per SOGC 2010 guidelines, prescribe analgesics ranging from NSAIDs to opioids while awaiting resolution of symptoms from directed medical or surgical treatments for endometriosis. B 5. Nonpharmacologic interventions Alternative and complementary therapies: Discuss non-medical strategies to address quality of life and psychological well-being in patients managing symptoms of endometriosis. B Insufficient evidence to recommend any specific non-medical intervention (Chinese medicine, nutrition, electrotherapy, acupuncture, physiotherapy, exercise, and psychological interventions) to reduce pain or improve quality of life measures in patients with endometriosis. I 6. Therapeutic procedures Hormone-releasing intrauterine device: offer a levonorgestrel-releasing intrauterine system or an etonogestrel-releasing subdermal implant to reduce endometriosis-associated pain in patients with endometriosis. A Fertility preservation: Discuss the pros and cons of fertility preservation with patients with extensive ovarian endometriosis. A Insufficient evidence regarding the true benefit of fertility preservation in patients with endometriosis. I 7. Perioperative care https://web.pathway.md/diseases/recjQIQ99LVWEV83Z 4/9 6/29/23, 4:16 AM Endometriosis Pathway Preoperative hormone therapy: do not offer preoperative hormone therapy to improve the immediate outcome of surgery for pain in patients with endometriosis. D Show 2 more 8. Surgical interventions Indications for surgery: As per ESHRE 2022 guidelines, offer surgery as one of the options to reduce endometriosis- associated pain. A Show 3 more As per SOGC 2010 guidelines, reserve surgical management in patients with endometriosis- related pain for those in whom medical treatment has failed. B Show 3 more Excision of endometrioma: As per SOGC 2023 guidelines: Perform laparoscopic resection of endometrioma if there are concerns about access to the follicles for egg retrieval for IVF. B Counsel patients comprehensively about the risk that endometrioma surgery will diminish ovarian reserve. A As per ESHRE 2022 guidelines, perform cystectomy instead of drainage and coagulation when performing surgery in patients with ovarian endometrioma, as cystectomy reduces recurrence of endometrioma and endometriosis-associated pain. A Show 2 more As per SOGC 2010 guidelines, perform excision of ovarian endometriomas > 3 cm in diameter in patients with pelvic pain, if possible. A Hysterectomy: as per ESHRE 2022 guidelines, consider performing hysterectomy (with or without removal of the ovaries) with removal of all visible endometriosis lesions in patients no longer wishing to conceive and failing to respond to more conservative treatments. Inform patients that hysterectomy will not necessarily cure the symptoms or the disease. C Show 2 more Presacral neurectomy: consider presacral neurectomy as an adjunct to the surgical treatment of patients with endometriosis-related pelvic pain. B 9. Specific circumstances Asymptomatic patients: As per ESHRE 2022 guidelines, inform and counsel patients about any incidental finding of endometriosis. B Show 3 more As per SOGC 2010 guidelines, do not offer any medical or surgical intervention for asymptomatic patients with incidental findings of endometriosis at the time of surgery. D Adolescent patients, diagnosis: https://web.pathway.md/diseases/recjQIQ99LVWEV83Z 5/9 6/29/23, 4:16 AM Endometriosis Pathway As per ESHRE 2022 guidelines, consider suspecting the diagnosis of endometriosis in young patients presenting with (cyclical) absenteeism from school or with use of oral contraceptives for treatment of dysmenorrhea. C Show 8 more As per ACOG 2018 guidelines, recognize that endometriosis is the most common cause of secondary dysmenorrhea in adolescents. E Show 4 more As per SOGC 2010 guidelines, consider offering all available therapies for endometriosis in adolescent patients taking into consideration the age of the patient and the side effect profiles of medications. B Adolescent patients, management: As per ESHRE 2022 guidelines, offer hormonal contraceptives or progestogens (systemically or via levonorgestrel intrauterine system) as first-line hormonal therapy in adolescent patients with severe dysmenorrhea and/or endometriosis-associated pain. Recognize that some progestogens may decrease bone mineral density. A Show 6 more As per ACOG 2018 guidelines, offer NSAIDs as the mainstay of pain relief in adolescent patients with endometriosis. E Show 3 more As per SOGC 2010 guidelines, elicit clear vesicles and red intra-abdominal lesions during laparoscopy in adolescent patients, as endometriosis in adolescent patients is often early- stage and atypical. B Adolescent patients (fertility preservation): Inform adolescent patients with endometriosis of the potential detrimental effect of ovarian endometriosis and surgery on ovarian reserve and future fertility. B Inform adolescent patients about the existing fertility preservation options, although recognize that the true benefit, safety and indications in adolescent patients with endometriosis remain unknown. B Pregnant patients: do not advise patients to become pregnant with the sole purpose of treating endometriosis, as pregnancy does not always lead to improvement of symptoms or reduction of disease progression. D Show 3 more Postmenopausal patients: recognize that endometriosis can still be active/symptomatic after menopause. E Show 7 more Patients with infertility (medical management): do not offer ovarian suppression treatment to improve fertility in infertile patients with endometriosis. D Show 3 more Patients with infertility, operative laparoscopy: As per SOGC 2023 guidelines, consider performing operative laparoscopy in patients with endometriosis and a history of infertility if there are other indications for surgery (such as pain), recognizing that it is not a first-line treatment for endometriosis-associated infertility. https://web.pathway.md/diseases/recjQIQ99LVWEV83Z 6/9 6/29/23, 4:16 AM Endometriosis Pathway Take into consideration the patient's age, duration of infertility, and ovarian reserve for counseling. C As per ESHRE 2022 guidelines, consider performing operative laparoscopy as a treatment option for endometriosis-associated infertility to improve the rate of ongoing pregnancy in patients with rASRM stage I/II endometriosis. C Show 3 more Patients with infertility (assisted reproductive technology): consider offering intrauterine insemination with ovarian stimulation instead of expectant management or intrauterine insemination alone, to increase pregnancy rates in infertile patients with rASRM stage I/II endometriosis. C Show 12 more Patients with extrapelvic endometriosis: recognize the symptoms of extrapelvic endometriosis, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough or nodules which enlarge during menses. B Show 3 more 10. Patient education General counseling: inform patients with endometriosis requesting information on their risk of developing cancer that endometriosis is not associated with a significantly higher risk of cancer overall. Inform that although endometriosis is associated with a higher risk of ovarian, breast, and thyroid cancers in particular, the increase in absolute risk compared with women in the general population is low. A Show 2 more 11. Preventative measures Primary prevention: Consider advising females to follow a healthy lifestyle and diet, with reduced alcohol intake and regular physical activity. C Insufficient evidence to support the usefulness of hormonal contraceptives for the primary prevention of endometriosis. I Prevention of recurrence: perform ovarian cystectomy instead of drainage and electrocoagulation for the secondary prevention of endometriosis-associated dysmenorrhea, dyspareunia, and non-menstrual pelvic pain, when surgery is indicated in patients with an endometrioma. Take into account the risk of reduced ovarian reserve. A Show 3 more 12. Follow-up and surveillance Indications for referral: refer patients with deep endometriosis to a center of expertise. B Follow-up: consider offering follow-up and psychological support in patients with confirmed endometriosis, particularly with deep and ovarian endometriosis, although insufficient evidence https://web.pathway.md/diseases/recjQIQ99LVWEV83Z 7/9 6/29/23, 4:16 AM Endometriosis Pathway regarding the benefit of regular long-term monitoring for early detection of recurrence, complications, or malignancy. C Show 4 more Management of recurrence: consider offering any hormone treatment or surgery for the treatment of recurring pain symptoms in patients with endometriosis. C 13. Quality improvement Management outcomes: as per SOGC 2010 guidelines, recognize that: treatment of endometriosis by excision or ablation reduces pain A excision rather than drainage or fulguration provides better pain relief, a reduced recurrence rate, and a histopathological diagnosis in patients with endometriomas A laparoscopic uterine nerve ablation alone does not offer significant relief of endometriosis- related pain A laparoscopic treatment of minimal or mild endometriosis improves pregnancy rates regardless of the treatment modality A the effect on fertility of surgical treatment of deeply infiltrating endometriosis is controversial B laparoscopic excision of ovarian endometriomas > 3 cm in diameter may improve fertility B if a patient with known endometriosis is to undergo IVF, GnRH agonist suppression with add- back hormone therapy for 3 to 6 months before IVF is associated with an improved pregnancy rate. A Clinical findings Symptoms Past obstetric history Chronic lower abdominal pain Female infertility Dyschezia Recurrent abortion Dysuria Gynecologic exam Fatigue LLQ pain Adnexal mass RLQ pain Uterine bleeding Suprapubic pain Vaginal wall nodules Rectal exam Rectal nodules References 1. ESHRE Endometriosis Guideline Development Group. ESHRE guideline: management of women with endometriosis. ESHRE. 2022 Feb 2. Open https://web.pathway.md/diseases/recjQIQ99LVWEV83Z 8/9 6/29/23, 4:16 AM Endometriosis Pathway 2. Nicholas Leyland, Robert Casper, Philippe Laberge et al. Endometriosis: Diagnosis and Management. J Obstet Gynaecol Can. 2010 Jul;32 7 Suppl 2 S1 32. Open 3. No authors listed. Practice bulletin no. 114 management of endometriosis. Obstet Gynecol. 2010 Jul;116 1 223 236. Open 4. No authors listed. ACOG Committee Opinion No. 760 Dysmenorrhea and Endometriosis in the Adolescent. Obstet Gynecol. 2018 Dec;132 6):e249-e258. Open 5. American College of Obstetricians and Gynecologists Committee on Practice Bulletins Gynecology. Practice Bulletin No. 174 Evaluation and Management of Adnexal Masses. Obstet Gynecol. 2016 Nov;128 5):e210-e226. Open 6. Tarek Motan, Roland Antaki, Jinglan Han et al. Guideline No. 435 Minimally Invasive Surgery in Fertility Therapy. J Obstet Gynaecol Can. 2023 Apr;45 4 273 282.e2. Open 7. Hwang H, Chung YJ, Lee SR et al. Clinical evaluation and management of endometriosis: guideline for Korean patients from Korean Society of Endometriosis. Obstet Gynecol Sci. 2018 Sep;61 5 553 564. Open 8. G A J Dunselman, N Vermeulen, C Becker et al. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014 Mar;29 3 400 12. Open 9. Royal College of Obstetricians and Gynaecologists. The Initial Management of Chronic Pelvic Pain. RCOG. 2012 May. Open https://web.pathway.md/diseases/recjQIQ99LVWEV83Z 9/9