Evidence - Diagnostic laparoscopy endometriosis treatment

Endometriosis is a chronic, benign, and estrogen-dependent condition where endometrial glandular tissue and stroma grow outside the uterine cavity. These ectopic endometriosis lesions are most commonly found in the pelvic area but can also affect other body regions such as the intestines, diaphragm, or pleural cavity.

Although endometriosis is a non-malignant condition, the displaced tissue can trigger an inflammatory response, leading to severe pain, adhesions, and infertility. The most common symptoms are dysmenorrhea (painful menstruation), dyspareunia (pain during intercourse), chronic pelvic pain, and fertility issues. The severity of symptoms varies greatly—while some affected individuals have few symptoms, the condition can lead to significant impairments in quality of life for others.

Endometriosis affects women in all hormonal life stages, including premenarchal, reproductive, and postmenopausal periods. As it is hormone-dependent, the condition may remain inactive during pregnancy or under hormonal therapies but can flare up again after discontinuing therapy.

The exact cause of endometriosis is not yet fully understood, but hormonal, immunological, and genetic factors play a role. Despite its high prevalence, diagnosis is often delayed because the symptoms are nonspecific and not always directly associated with the condition.

Locations of endometriosis in decreasing frequency

1. Pelvic peritoneum – most common location, affects the peritoneum of the pelvis.
2. Ovaries (endometriomas / chocolate cysts) – often associated with adhesions.
3. Uterosacral ligaments (pelvic ligaments) – deep infiltrating endometriosis often occurs here.
4. Rectovaginal septum / posterior vaginal fornix – can lead to pain during intercourse (dyspareunia) and bowel movements (dyschezia).
5. Rectosigmoid (bowel endometriosis) – commonly affected in deep infiltrating endometriosis.
6. Bladder and ureters (ureteral endometriosis) – can lead to urinary obstruction and kidney damage.
7. Uterus (adenomyosis) – endometriosis within the uterine wall, causes heavy bleeding.
8. Fallopian tubes (tubal endometriosis) – can lead to tubal occlusions and infertility.
9. Diaphragm (diaphragmatic endometriosis) – rare, but can lead to cyclic shoulder pain.
10. Extragenital endometriosis (e.g., appendix, navel, skin scars, thorax, lung, brain) – very rare, but possible.

Reference:

1. Ulrich U, Buchweitz O, Greb R et al (2014) German and Austrian Societies for Obstetrics and Gynecology. National German Guideline (S2k): Guideline for the Diagnosis and Treatment of Endometriosis: Long Version – AWMF Registry No. 015–045. Geburtshilfe Frauenheilk 74:1104–1118

The basic principle of hormonal treatment is to suppress estrogen production to prevent the growth of ectopic endometrium.

First-line Therapy

Progestins, e.g., Dienogest

• Inhibit the growth of endometriosis lesions through decidualization and atrophy.
• Long-term pain reduction with continuous intake.
• Fewer side effects than other hormonal preparations.
• Examples: Dienogest, Norethisterone acetate, Medroxyprogesterone acetate.

Second-line Therapy

Combined Oral Contraceptives

• Reduction of dysmenorrhea and chronic pelvic pain.
• Most effective with continuous intake (long cycle) without pill break.
• Off-label use, but clinical evidence of effectiveness is available.

GnRH Analogues (with Add-Back Therapy)

• Block estrogen production at the pituitary level.
• Significant pain reduction and inhibition of endometriosis.
• High rate of side effects (hot flushes, osteoporosis, loss of libido).
• Use is usually limited to 3–6 months, longer use only with add-back therapy to avoid estrogen deficiency symptoms.

GnRH Antagonists (Elagolix, Relugolix Combination Therapy)

• Relugolix is approved in Germany in combination with Estradiol and Norethisterone acetate (Ryeqo®).
• Elagolix was approved in the USA in 2018 but is not primarily recommended in Europe.
• Directly effective, no initial hormone fluctuations compared to GnRH analogues.
• Less pronounced side effects than GnRH analogues due to accompanying add-back therapy.
• Reduction of dysmenorrhea and chronic pelvic pain confirmed in clinical studies.

Intrauterine Devices (IUD) with Levonorgestrel

• Direct effect on the endometrium through local hormone release.
• Especially suitable for long-term therapy in adenomyosis.

Aromatase Inhibitors

• Inhibit local estrogen production in endometriosis tissue.
• Due to strong side effects (osteoporosis, muscle pain), only recommended in studies for therapy-resistant endometriosis.

Reference:

1. Nagandla K, Idris N, Nalliah S, Sreeramareddy CT, George SRK, Kanagasabai S. Hormonal treatment for uterine adenomyosis. Cochrane Database of Systematic Reviews 2014, DOI: 10.1002/14651858.CD011372
2. Ferrero S, Barra F, Leone Roberti Maggiore U. Current and Emerging Therapeutics for the Management of Endometriosis. Drugs 2018, DOI: 10.1007/s40265-018-0928-0: 1‐18
3. Takaesu Y, Nishi H, Kojima J, Sasaki T, Nagamitsu Y, Kato R, Isaka K. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. The journal of obstetrics and gynaecology research 2016; 42: 1152-1158
4. Strowitzki T, Faustmann T, Gerlinger C, Schumacher U, Ahlers C, Seitz C. Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program. Int J Womens Health 2015; 7: 393-401
5. Lee KH, Jung YW, Song SY, Kang BH, Yang JB, Ko YB, Lee M, Han HY, Yoo HJ. Comparison of the efficacy of diegnogest and levonorgestrel-releasing intrauterine system after laparoscopic surgery for endometriosis. Journal of obstetrics and gynaecology research 2018, DOI: 10.1111/jog.13703
6. Brown J, Farquhar C. Endometriosis: an overview of Cochrane Reviews. The Cochrane database of systematic reviews 2014, DOI: 10.1002/14651858.CD009590.pub2: Cd009590
7. Houda MR, Grant NH. Gonadotrophin antagonists for pain associated with endometriosis. Cochrane Database of Systematic Reviews 2014, DOI: 10.1002/14651858.CD011446
8. Wu D, Hu M, Hong L, Hong S, Ding W, Min J, Fang G, Guo W. Clinical efficacy of add-back therapy in treatment of endometriosis: a meta-analysis. Archives of gynecology and obstetrics 2014; 290: 513-523
9. Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, Surrey E, Johnson NP, Watts NB, et al. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. New England journal of medicine 2017; 377: 28‐40
10. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2) Giudice, Linda C et al. The Lancet, Volume 399, Issue 10343, 2267 - 2279
11. Harada T, Osuga Y, Suzuki Y, Fujisawa M, Fukui M, Kitawaki J. Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain compared with leuprorelin in Japanese women: a phase 3, randomized, double-blind, noninferiority study. Fertil Steril. 2022 Mar;117(3):583-592. doi: 10.1016/j.fertnstert.2021.11.013. Epub 2021 Dec 8. PMID: 34895700.
12. Harada T, Osuga Y, Suzuki Y, Fujisawa M, Fukui M, Kitawaki J. Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain compared with leuprorelin in Japanese women: a phase 3, randomized, double-blind, noninferiority study. Fertil Steril. 2022 Mar;117(3):583-592. doi: 10.1016/j.fertnstert.2021.11.013. Epub 2021 Dec 8. PMID: 34895700.

Laparoscopy (abdominal endoscopy) is considered the preferred surgical method for treating endometriosis, as it offers less strain on the patient, shorter recovery times, and better cosmetic results compared to open surgery (laparotomy).

• Removal of endometriosis lesions (peritonectomy): The affected tissue areas of the peritoneum are specifically excised to completely remove the lesions.
• Adhesiolysis: Adhesions between organs such as the uterus, ovaries, intestines, or bladder can arise from endometriosis and lead to pain or functional impairments. These adhesions are surgically released to restore normal organ mobility.
• Ureterolysis: If endometriosis tissue compresses or invades the ureter, the ureter is carefully exposed to ensure normal ureteral function.
• Bowel or bladder resections: If endometriosis has invaded the bowel wall or bladder wall, partial resections may be necessary to relieve the affected organs.
• Adhesion prophylaxis: After the removal of endometriosis lesions, an adhesion barrier such as 4DryField® is often applied to prevent postoperative adhesions.
• Fertility optimization: If the patient desires to have children, the surgery can be planned to maximize the preservation of fertility.

Bowel endometriosis:

• Shaving technique: Removal of endometriosis lesions without completely transecting the bowel wall.
• Segmental resection: If endometriosis has deeply invaded the bowel wall, a partial resection may be necessary.
• Protective stoma: In rare cases, a temporary artificial bowel outlet may be required to support healing.

Bladder endometriosis:

• Small lesions can be removed via transurethral resection.
• Deeper infiltrations require a partial cystectomy (removal of part of the bladder wall).

Ureteral endometriosis:

• If the ureter is compressed by endometriosis, a ureterolysis (exposure of the ureter) can be performed.
• In severe cases, ureteral reimplantation may be necessary if the ureter is significantly affected.

Endometriosis of the ovary and tube:

• Endometriomas (chocolate cysts) can reduce ovarian reserve, so the gentlest method should be chosen, and the anti-Müllerian hormone should be determined as a marker of ovarian reserve.
• Cystectomy (complete removal of the cyst wall) is superior to fenestration as it reduces the risk of recurrence.
• Hemostasis should be performed using sutures and not bipolar coagulation.
• In bilateral endometriomas, the fertility prognosis is poorer, so cryopreservation of oocytes should be considered.
• Tubal endometriosis can lead to tubal occlusions, making spontaneous pregnancy difficult. In these cases, IVF may be required.

Thoracic endometriosis:

• Can lead to catamenial pneumothorax (air accumulation in the chest cavity during menstruation).
• Interdisciplinary collaboration with thoracic surgeons is necessary.

Reference:

1. Riley KA, Benton AS, Deimling TA, Kunselman AR, Harkins GJ. Surgical Excision Versus Ablation for Superficial Endometriosis-Associated Pain: a Randomized Controlled Trial. Journal of minimally invasive gynecology 2018; (no pagination)
2. Exacoustos C, Zupi E, Piccione E. Ultrasound Imaging for Ovarian and Deep Infiltrating Endometriosis. Seminars in reproductive medicine 2017; 35: 5-24
3. Goodman LR, Goldberg JM, Flyckt RL, Gupta M, Harwalker J, Falcone T. Effect of surgery on ovarian reserve in women with endometriomas, endometriosis and controls. American journal of obstetrics and gynecology 2016; 215: 589.e581‐589.e586
4. Zhang CH, Wu L, Li PQ. Clinical study of the impact on ovarian reserve by different hemostasis methods in laparoscopic cystectomy for ovarian endometrioma. Taiwanese journal of obstetrics & gynecology 2016; 55: 507-511
5. Iwase A, Nakamura T, Nakahara T, Goto M, Kikkawa F. Assessment of ovarian reserve using anti-Mullerian hormone levels in benign gynecologic conditions and surgical interventions: a systematic narrative review. Reproductive biology and endocrinology : RB&E 2014; 12: 125
6. Giampaolino P, Della Corte L, Saccone G, Vitagliano A, Bifulco G, Calagna G, Carugno J, Di Spiezio Sardo A. Role of Ovarian Suspension in Preventing Postsurgical Ovarian Adhesions in Patients with Stage III-IV Pelvic Endometriosis: A Systematic Review. Journal of minimally invasive gynecology 2019; 26: 53-62
7. Angioni S, Pontis A, Dessole M, Surico D, De Cicco Nardone C, Melis I. Pain control and quality of life after laparoscopic en-block resection of deep infiltrating endometriosis (DIE) vs. incomplete surgical treatment with or without GnRHa administration after surgery. Archives of gynecology and obstetrics 2015; 291: 363-370
8. Mabrouk M, Ferrini G, Montanari G, Di Donato N, Raimondo D, Stanghellini V, Corinaldesi R, Seracchioli R. Does colorectal endometriosis alter intestinal functions? A prospective manometric and questionnaire-based study. Fertility and sterility 2012; 97: 652-656
9. Minelli L, Fanfani F, Fagotti A, Ruffo G, Ceccaroni M, Mereu L, Landi S, Pomini P, Scambia G. Laparoscopic colorectal resection for bowel endometriosis: feasibility, complications, and clinical outcome. Archives of surgery 2009; 144: 234-239; discussion 239
10. Afors K, Centini G, Fernandes R, Murtada R, Zupi E, Akladios C, Wattiez A. Segmental and Discoid Resection are Preferential to Bowel Shaving for Medium-Term Symptomatic Relief in Patients With Bowel Endometriosis. Journal of minimally invasive gynecology 2016; 23: 1123-1129
11. Roman H, Moatassim-Drissa S, Marty N, Milles M, Vallee A, Desnyder E, Stochino Loi E, Abo C. Rectal shaving for deep endometriosis infiltrating the rectum: a 5-year continuous retrospective series. Fertility and sterility 2016; 106: 1438-1445 e1432
12. Knabben L, Imboden S, Fellmann B, Nirgianakis K, Kuhn A, Mueller MD. Urinary tract endometriosis in patients with deep infiltrating endometriosis: prevalence, symptoms, management, and proposal for a new clinical classification. Fertility and sterility 2015; 103: 147-152
13. Angioni S, Nappi L, Pontis A, Sedda F, Luisi S, Mais V, Melis GB. Dienogest. A possible conservative approach in bladder endometriosis. Results of a pilot study. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 2015; 31: 406-408
14. Mereu L, Gagliardi ML, Clarizia R, Mainardi P, Landi S, Minelli L. Laparoscopic management of ureteral endometriosis in case of moderate-severe hydroureteronephrosis. Fertility and sterility 2010; 93: 46-51
15. Ceccaroni M, Ceccarello M, Caleffi G, Clarizia R, Scarperi S, Pastorello M, Molinari A, Ruffo G, Cavalleri S. Total Laparoscopic Ureteroneocystostomy for Ureteral Endometriosis: A Single-Center Experience of 160 Consecutive Patients. Journal of minimally invasive gynecology 2019; 26: 78-86
16. Nezhat C, Lindheim SR, Backhus L, Vu M, Vang N, Nezhat A, Nezhat C. Thoracic Endometriosis Syndrome: A Review of Diagnosis and Management. JSLS : Journal of the Society of Laparoendoscopic Surgeons 2019; 23

In addition to conventional medicine, there are supportive measures that can improve the well-being of patients.

Pain Therapy

• NSAIDs (Ibuprofen, Naproxen, Diclofenac) for acute pain management.
• Opioids for severe pain conditions, but only for a limited time.
• Neuromodulators (Gabapentin, Amitriptyline) for chronic pain.

Physical Therapy & Osteopathy

• Pelvic floor relaxation to alleviate myofascial tension.
• Manual therapy for adhesions and scar tissue binding.

Nutritional Medical Measures

• Anti-inflammatory diet with omega-3 fatty acids and antioxidants can help.
• Reducing sugar, dairy products, and gluten can alleviate symptoms.

Psychological Support & Pain Management

• Chronic pain often leads to anxiety and depression.
• Psychotherapy and cognitive behavioral therapy can support disease management.

Traditional & Complementary Medicine

• Acupuncture and TCM have positive effects on pain reduction.
• Meditation, yoga, and mindfulness training can reduce stress.

Reference:

1. Marjoribanks J, Ayeleke RO, Farquhar C, Proctor M. Nonsteroidal anti‐inflammatory drugs for dysmenorrhea. Cochrane Database of Systematic Reviews 2015, DOI: 10.1002/14651858.CD001751.pub3
2. Feng X, Wang X. Comparison of the efficacy and safety of non-steroidal anti-inflammatory drugs for patients with primary dysmenorrhea: A network meta-analysis. Molecular pain 2018; 14: 1744806918770320
3. Sharghi M, Mansurkhani SM, Larky DA, Kooti W, Niksefat M, Firoozbakht M, Behzadifar M, Azami M, Servatyari K, Jouybari L. An update and systematic review on the treatment of primary dysmenorrhea. JBRA assisted reproduction 2018, DOI: 10.5935/1518-0557.20180083
4. Iacovides S, Baker FC, Avidon I. The 24-h progression of menstrual pain in women with primary dysmenorrhea when given diclofenac potassium: a randomized, double-blinded, placebo-controlled crossover study. Archives of gynecology and obstetrics 2014; 289: 993-1002
5. Engel CC, Jr., Walker EA, Engel AL, Bullis J, Armstrong A. A randomized, double-blind crossover trial of sertraline in women with chronic pelvic pain. Journal of psychosomatic research 1998; 44: 203-207
6. Chen LC, Hsu JW, Huang KL, Bai YM, Su TP, Li CT, Yang AC, Chang WH, Chen TJ, Tsai SJ, Chen MH. Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study. Journal of affective disorders 2016; 190: 282-285
7. Lagana AS, La Rosa VL, Rapisarda AMC, Valenti G, Sapia F, Chiofalo B, Rossetti D, Ban Frangez H, Vrtacnik Bokal E, Vitale SG. Anxiety and depression in patients with endometriosis: impact and management challenges. Int J Womens Health 2017; 9: 323-330
8. Meissner K, Schweizer-Arau A, Limmer A, Preibisch C, Popovici RM, Lange I, De Oriol B, Beissner F. Psychotherapy with Somatosensory Stimulation for Endometriosis-Associated Pain: A Randomized Controlled Trial. Obstetrics and gynecology 2016; 128: 1134‐1142
9. Abd-El-Maeboud KHI, Kortam M, Ali MS, Ibrahim MI, Mohamed R. A preliminary pilot randomized crossover study of uzara (Xysmalobium undulatum) versus ibuprofen in the treatment of primary dysmenorrhea. PloS one 2014; 9
10. Anjum A, Sultana A. A randomized comparative study of herbal decoction of Cassia fistula Linn pod's pericarp and Myristica fragrans Houtt arils vs. mefenamic acid in spasmodic dysmenorrhea. Journal of complementary and integrative medicine 2018; (no pagination)
11. Miao EY, Miao MYM, Kildea DG, Lao YW. Effects of electroacupuncture and electroacupuncture plus Tao Hong Si Wu Wan in treating primary dysmenorrhea. JAMS journal of acupuncture and meridian studies 2014; 7: 6‐14
12. Hong GY, Shin BC, Park SN, Gu YH, Kim NG, Park KJ, Kim SY, Shin YI. Randomized controlled trial of the efficacy and safety of self-adhesive low-level light therapy in women with primary dysmenorrhea. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 2016; 133: 37-42
13. Armour M, Dahlen HG, Smith CA. More Than Needles: the Importance of Explanations and Self-Care Advice in Treating Primary Dysmenorrhea with Acupuncture. Evidence-based complementary and alternative medicine 2016; 2016
14. Fallah F, Mirfeizi M. How is the quality and quantity of primary dysmenorrhea affected by physical exercises? A study among Iranian students. International journal of women's health and reproduction sciences 2018; 6: 60‐66
15. Molins-Cubero S, Rodríguez-Blanco C, Oliva-Pascual-Vaca A, Heredia-Rizo AM, Boscá-Gandía JJ, Ricard F. Changes in pain perception after pelvis manipulation in women with primary dysmenorrhea: a randomized controlled trial. Pain medicine (Malden, Mass) 2014; 15: 1455‐1463

Endometriosis is one of the most common gynecological diseases and can significantly impair women's fertility. It is estimated that up to 50% of women with infertility issues suffer from some form of endometriosis. The disease can reduce the likelihood of pregnancy through anatomical changes, inflammatory reactions, and hormonal imbalances. Nevertheless, there are various treatment options that can enable conception.

Endometriosis can affect fertility in various ways:

Mechanical impairment of reproductive organs:

• Adhesions and scarring can lead to fallopian tube blockages, preventing the fertilization of the egg.
• Ovaries can be damaged by endometriomas (chocolate cysts), reducing the egg reserve.

Hormonal and inflammatory changes:

• Overproduction of prostaglandins, metalloproteinases, and cytokines leads to a chronic inflammatory reaction in the abdominal cavity, which can impair egg quality and embryo implantation.
• Endometriosis can disrupt ovulation and lead to insufficient maturation of eggs.

Impairment of sperm and embryo quality:

• The inflammatory environment can negatively affect sperm motility and viability.
• The altered endometrial lining can make embryo implantation more difficult.

Pain during intercourse (dyspareunia):

• Many women with endometriosis avoid intercourse due to severe pain, reducing the chances of natural conception.

Adenomyosis and desire for children

• Women with endometriosis and adenomyosis have an increased miscarriage rate, lower pregnancy rates, and higher risks of complications during pregnancy.
• Hormonal pretreatments (e.g., GnRH analogs or progestins) can improve pregnancy chances.
• Surgical removal is possible but only recommended in severe cases.

Surgical therapy to improve fertility

A laparoscopic treatment of endometriosis can increase pregnancy chances, especially in women with mild to moderate endometriosis (Stage I-II according to rASRM).

Peritoneal endometriosis

• Surgical removal of peritoneal endometriosis lesions has led to improved pregnancy rates in studies.
• The surgery should only be performed if there is a clear indication to improve fertility.

Deep infiltrating endometriosis

• Surgery for deep infiltrating endometriosis can be beneficial, but the results for fertility are not conclusive.
• The decision should be weighed individually, especially if there is involvement of the bowel, bladder, or ureter.

Ovarian endometriosis (endometriomas)

• Surgical removal of endometriomas should be done cautiously as it can affect ovarian reserves.
• In certain cases, preoperative hormone therapy can reduce cyst volume before surgery.
• If assisted reproduction (IVF/ICSI) is planned, it should be carefully considered whether surgery is necessary.

If spontaneous pregnancy does not occur despite therapy, assisted reproduction (ART) can be considered.

Intrauterine insemination (IUI):

• Can be used in mild endometriosis without fallopian tube involvement.
• However, the success prospects are limited.

In vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI):

• Preferred in severe endometriosis, fallopian tube blockages, or significantly reduced egg reserve.
• Pregnancy rates are lower in advanced endometriosis, yet IVF can be a realistic option.
• Before IVF, hormone therapy to improve egg quality can be considered.

Egg or embryo cryopreservation:

• If ovarian surgery is necessary, precautionary egg retrieval (social freezing) should be considered.

Reference: 

1. Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am 2012; 39: 535-549
2. Practice Committee of the American Society for Reproductive M. Endometriosis and infertility: a committee opinion. Fertility and sterility 2012; 98: 591-598
3. Johnson NP, Hummelshoj L, World Endometriosis Society Montpellier C. Consensus on current management of endometriosis. Human reproduction (Oxford, England) 2013; 28: 1552-1568
4. Diagnostic and therapy before assisted reproductive treatments. Guideline of the DGGG, OEGGG and SGGG (S2K-Level, AWMF Registry No. 015/085, 02/2019). http://www.awmf.org/leitlinien/detail/ll/015-085.html)
5. Tal R, Seifer DB. Ovarian reserve testing: a user's guide. American journal of obstetrics and gynecology 2017; 217: 129-140