Comprehensive review of the latest evidence available on endometriosis and subfertility

Alina Shirazi; Saira Azhar; Tokunbo Adeoye; Humna Mian Faiz Rasul; Seema Bagtharia; Jitendra Jadhav

doi:10.18203/2320-1770.ijrcog20250548

Authors

Alina Shirazi Department of Obstetrics and Gynaecology, Basildon Hospital, South and Mid-Essex Foundation Trust, Basildon, Essex, UK
Saira Azhar Department of Obstetrics and Gynaecology, Peterbrough Hospital, UK
Tokunbo Adeoye Department of Obstetrics and Gynaecology, Basildon Hospital, South and Mid-Essex Foundation Trust, Basildon, Essex, UK
Humna Mian Faiz Rasul Department of Obstetrics and Gynaecology, Bedford Hospital, Bedfordshire Hospitals NHS, UK
Seema Bagtharia Department of Obstetrics and Gynaecology, Basildon Hospital, South and Mid-Essex Foundation Trust, Basildon, Essex, UK
Jitendra Jadhav Department of Obstetrics and Gynaecology, Basildon Hospital, South and Mid-Essex Foundation Trust, Basildon, Essex, UK

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20250548

Keywords:

Assisted reproductive technology cycles, Anti-Müllerian hormone levels, Deep endometriosis, Endometriosis fertility index, Follicular stimulating hormone, Ovarian tissue cryopreservation, Pouch of douglas

Abstract

Endometriosis is a chronic inflammatory condition affecting women of reproductive age group, often resulting in subfertility and chronic pelvic pain. The multifactorial nature of endometriosis-associated infertility is influenced by a complex interplay of genetic, hormonal, menstrual, inflammatory and immunological factors, which together define the phenotypic presentation of the disease. These factors complicate natural conception and impact the success of Assisted Reproductive Technology (ART) cycles. While medical management, typically contraceptive, offers symptomatic relief, it may not address the underlying issues that impede natural conception. Surgical intervention, particularly for ovarian endometriosis, has the potential to enhance spontaneous conception rates but also carries the risk of reducing ovarian reserve. This presents a dilemma in fertility preservation, especially when considering assisted reproductive technologies (ART). The current evidence on the efficacy of surgery in improving ART outcomes remains inconclusive, underscoring the need for an individualized and holistic approach in treatment planning. Such an approach is crucial in optimizing reproductive outcomes for women with endometriosis. A systematic search of the literature was conducted to gather the latest evidence on endometriosis and subfertility. Databases searched included PubMed, Scopus, Web of Science and Cochrane Library. While excising endometriomas may help restore pelvic anatomy and increase spontaneous pregnancy rates, there is also a substantial risk of reducing ovarian reserve due to damage caused during the procedure. In particular, cystectomy has been associated with a significant reduction in anti-Müllerian hormone (AMH) levels, a key marker of ovarian reserve.

Metrics

Metrics Loading ...

References

Morris G, Lilly C, Jefferys A, O'Donovan O, Akande V. Endometriosis and subfertility. J Obstetr Gynaecol. 2024;26:32-43. DOI: https://doi.org/10.1111/tog.12911

Meuleman C, Vandenabeele B, Fieuws S, Spiessens C, Timmerman D, D'Hooghe T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril. 2009;92(1):68-74. DOI: https://doi.org/10.1016/j.fertnstert.2008.04.056

Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382(13):1244-56. DOI: https://doi.org/10.1056/NEJMra1810764

Ryan IP, Tseng JF, Schriock ED, Khorram O, Landers DV, Taylor RN. Interleukin-8 concentrations are elevated in peritoneal fluid of women with endometriosis. Fertil Steril. 1995;63(4):929-32. DOI: https://doi.org/10.1016/S0015-0282(16)57506-2

American Society for Reproductive Medicine (1997). Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67(5):817-21. DOI: https://doi.org/10.1016/S0015-0282(97)81391-X

Hill CJ, Fakhreldin M, Maclean A, Dobson L, Nancarrow L, Bradfield A, et al. Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications. J Clin Med. 2020;9(6):1905. DOI: https://doi.org/10.3390/jcm9061905

De Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376(9742):730-8. DOI: https://doi.org/10.1016/S0140-6736(10)60490-4

Practice Committee of the American Society for Reproductive Medicine. Fertility evaluation of infertile women: a committee opinion. Fertil Steril. 2021;116(5):1255-65.

Skorupskaite K, Hardy M, Bhandari H, Yasmin E, Saab W, Seshadri S. Evidence based management of patients with endometriosis undergoing assisted conception: British fertility society policy and practice recommendations. Hum Fertil (Camb). 2024;27(1):2288634. DOI: https://doi.org/10.1080/14647273.2023.2288634

Practice Committee of the American Society for Reproductive Medicine. Fertility evaluation of infertile women: a committee opinion. Fertil Steril. 2021;116(5):1255-65.

Guerriero S, Condous G, van den Bosch T, Valentin L, Leone FPG, Van Schoubroeck D, et al. Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group. Ultrasound Obstet Gynecol. 2016;48(3):318-32. DOI: https://doi.org/10.1002/uog.15955

Johnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS, et al. World Endometriosis Society consensus on the classification of endometriosis. Hum Reprod. 2017;32(2):315-24. DOI: https://doi.org/10.1093/humrep/dew293

Tomassetti C, D’Hooghe T. Endometriosis and infertility: Insights into the causal link and management strategies. Best Pract Res Clin Obstetr Gynaecol. 2018;51:25-33. DOI: https://doi.org/10.1016/j.bpobgyn.2018.06.002

Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM, Vandekerckhove P. Ovulation suppression for endometriosis. Cochrane Database Syst Rev. 2007;2007(3):CD000155. DOI: https://doi.org/10.1002/14651858.CD000155.pub2

ESHRE. ESHRE Guideline Endometriosis, 2022. Available at: https://www.eshre.eu/guideline/endometriosis. Accessed on 31 January 2025.

Bosteels J, Weyers S, Mathieu C, Mol BW, D’Hooghe T. The effectiveness of reproductive surgery in the treatment of female infertility: facts, views and vision. Facts Views Vis Obgyn. 2010;2(4):232-52.

Adamson GD, Pasta DJ. Surgical treatment of endometriosis-associated infertility: Meta-analysis compared with survival analysis. Am J Obstet Gynecol. 1994;171(6):1488-504. DOI: https://doi.org/10.1016/0002-9378(94)90392-1

Bafort C, Beebeejaun Y, Tomassetti C, Bosteels J, Duffy JM. Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev. 2020;10(10):CD011031. DOI: https://doi.org/10.1002/14651858.CD011031.pub3

Somigliana E, Benaglia L, Vigano P, Candiani M, Vercellini P, Fedele L. Surgical measures for endometriosis-related infertility: a plea for research. Placenta. 2011:32(3):238-42. DOI: https://doi.org/10.1016/j.placenta.2011.06.011

Raffi F, Metwally M, Amer S. The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2012;97(9):3146-54. DOI: https://doi.org/10.1210/jc.2012-1558

Hart RJ, Hickey M, Maouris P, Buckett W. Excisional surgery versus ablative surgery for ovarian endometriomata. Cochrane Database Syst Rev. 2008:(2):CD004992. DOI: https://doi.org/10.1002/14651858.CD004992.pub3

Mircea O, Puscasiu L, Resch B, Lucas J, Collinet P, von Theobald P, et al. Fertility outcomes after ablation using plasma energy versus cystectomy in infertile women with ovarian endometrioma: a multicentric comparative study. J Minim Invasive Gynecol. 2016;23(7):1138-45. DOI: https://doi.org/10.1016/j.jmig.2016.08.818

Carmona F, Martinez-Zamora MA, Rabanal A, Martínez-Román S, Balasch J. Ovarian cystectomy versus laser vaporization in the treatment of ovarian endometriomas: a randomized clinical trial with a five-year follow-up. Fertil Steril. 2011;96(1):251-4. DOI: https://doi.org/10.1016/j.fertnstert.2011.04.068

Alborzi S, Keramati P, Younesi M, Samsami A, Dadras N. The impact of laparoscopic cystectomy on ovarian reserve in patients with unilateral and bilateral endometriomas. Fertil Steril. 2014;101(2):427-34. DOI: https://doi.org/10.1016/j.fertnstert.2013.10.019

Nickkho-Amiry M, Savant R, Majumder K, Edi-O'sagie E, Akhtar M. The effect of surgical management of endometrioma on the IVF/ICSI outcomes when compared with no treatment? A systematic review and meta-analysis. Arch Gynecol Obstet. 2018;297(4):1043-57. DOI: https://doi.org/10.1007/s00404-017-4640-1

Şükür YE, Özmen B, Yakıştıran B, Atabekoğlu CS, Berker B, Aytaç R, et al. Endometrioma surgery is associated with increased risk of subsequent assisted reproductive technology cycle cancellation; a retrospective cohort study. J Obstet Gynaecol. 2021;41(2):259-62. DOI: https://doi.org/10.1080/01443615.2020.1754366

Broer SL, Dólleman M, Opmeer BC, Fauser BC, Mol BW, Broekmans FJ. AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Hum Reprod Update. 2011;17(1):46-54. DOI: https://doi.org/10.1093/humupd/dmq034

Ersahin AA, Arpaci H, Ersahin SS, Celik N, Acet M. AFC vs. AMH: prediction of ovarian response in women with endometrioma undergoing controlled ovarian stimulation. Eur Rev Med Pharmacol Sci. 2017;21(10):2499-503.

Pacchiarotti A, Iaconianni P, Caporali S, Vitillo M, Meledandri M, Monaco G, et al. Severe endometriosis: low value of AMH did not affect oocyte quality and pregnancy outcome in IVF patients. Eur Rev Med Pharmacol Sci. 2020;24(22):11488-95.

Georgiou EX, Melo P, Baker PE, Sallam HN, Arici A, Garcia-Velasco JA, et al. Long-term GnRH agonist therapy before in vitro fertilisation (IVF) for improving fertility outcomes in women with endometriosis. Cochrane Database Syst Rev. 2019;9(11):13240. DOI: https://doi.org/10.1002/14651858.CD013240.pub2

de Ziegler D, Gayet V, Aubriot FX, Fauque P, Streuli I, Wolf JP, et al. Use of oral contraceptives in women with endometriosis before assisted reproduction treatment improves outcomes. Fertil Steril. 2010;94(7):2796-9. DOI: https://doi.org/10.1016/j.fertnstert.2010.05.056

Barra F, Laganà AS, Scala C, Garzon S, Ghezzi F, Ferrero S. Pretreatment with dienogest in women with endometriosis undergoing IVF after a previous failed cycle. Reprod Biomed Online. 2020;41(5):859-68. DOI: https://doi.org/10.1016/j.rbmo.2020.07.022

Gazzo I, Moffa F, Ferrero S. Fertility preservation in women with endometriosis: Oocyte cryopreservation and other techniques. Best Pract Res Clin Obstetr Gynaecol. 2024;95:102503. DOI: https://doi.org/10.1016/j.bpobgyn.2024.102503

Cobo A, Giles J, Paolelli S, Pellicer A, Remohí J, García-Velasco JA. Oocyte vitrification for fertility preservation in women with endometriosis: an observational study. Fertil Steril. 2020;113(4):836-44. DOI: https://doi.org/10.1016/j.fertnstert.2019.11.017

Harzif AK, Pratama G, Maidarti M, Prameswari N, Shadrina A, Mutia K, et al. Ovarian cortex freezing as a method of fertility preservation in endometriosis: A case report. Ann Med Surg (Lond). 2022:74:103222.

Carrillo L, Seidman DS, Cittadini E, Meirow D. The role of fertility preservation in patients with endometriosis’, J Assist Reprod Genet. 2016;33(3):317-23. DOI: https://doi.org/10.1007/s10815-016-0646-z

Donnez J, Squifflet J, Dolmans MM, Martinez-Madrid B, Jadoul P, Van Langendonckt A. Orthotopic transplantation of fresh ovarian cortex: a report of two cases. Fertil Steril. 2005;84(4):1018. DOI: https://doi.org/10.1016/j.fertnstert.2005.06.011

Oktay K, Oktem O. Ovarian cryopreservation and transplantation for fertility preservation for medical indications: report of an ongoing experience. Fertil Steril. 2010;93(3):762-8. DOI: https://doi.org/10.1016/j.fertnstert.2008.10.006

Harzif AK, Pratama G, Maidarti M, Prameswari N, Shadrina A, Mutia K, et al. Ovarian cortex freezing as a method of fertility preservation in endometriosis: a case report. Ann Med Surg (Lond). 2022;74:103222. DOI: https://doi.org/10.1016/j.amsu.2021.103222