Comparison of the Efficacy of Oral Elagolix Versus Leuprolide Depot: Optimizing Natural Conception in Women with Endometrioma

Introduction Endometrioma, even when asymptomatic, may adversely affect reproductive outcomes by interfering with folliculogenesis, oocyte quality and the pelvic microenvironment. Suppression of endometriotic activity with gonadotropin-releasing hormone (GnRH) analogue has been utilized to improve the likelihood of spontaneous conception. Recently, oral GnRH antagonists such as Elagolix have emerged as less invasive alternatives to injectable depot medications. This study aims to compare the efficacy of oral Elagolix versus intramuscular Leuprolide Depot in facilitating spontaneous conception, reducing endometrioma size, alleviating symptoms and improving patient compliance.

A retrospective cohort study was conducted on 100 women with both asymptomatic and symptomatic ovarian endometriomas (< 3 cm), patent fallopian tubes and partners with normal semen parameters. Group A (n = 50) received oral Elagolix 200 mg twice daily for 3 months, while Group B (n = 50) received Leuprolide Depot 3.75 mg monthly for the same duration. Patients were monitored monthly and followed for 12-months post-treatment for spontaneous conception, symptom relief, cyst size reduction and compliance. Primary outcome was defined as spontaneous conception rate within 12 months of treatment cessation. Secondary outcomes involved patient compliance (treatment adherence), symptom improvement (notably dysmenorrhea) and reduction in endometrioma size on transvaginal sonography.

Baseline demographics and reproductive characteristics were comparable between the Elagolix and leuprolide groups. Spontaneous conception occurred in 36% of the Elagolix group compared to 12.5% in the Leuprolide group (p = 0.028). Compliance was 100% in the Elagolix group, while 20% of patients in the Leuprolide group were lost to follow-up. Both treatments resulted in symptomatic relief and cyst size reduction; however, Elagolix demonstrated more pronounced benefits in both domains. Additionally, patients in the Elagolix group reported earlier return of regular menstrual cycles (2.85 months vs 4.23 months in leuprolide arm), which may have contributed to the higher conception rates observed. The greater ease of administration and reduced need for clinical visits likely played a key role in enhancing adherence among Elagolix users.

Oral Elagolix is superior to Leuprolide Depot in enhancing spontaneous conception rates, reducing endometrioma size, relieving symptoms and ensuring better treatment adherence. Given its ease of administration and quicker return to ovulatory function, Elagolix may be the preferred option in fertility-focused management of asymptomatic endometriomas. Similar content being viewed by others Change history 10 June 2026 The original version of this article was revised: to update the spelling Elagolix.

Taylor HS, Giudice LC, Lessey BA, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med. 2017;377(6):28–40. Paoletti AM, Neri M, Pilloni M, et al. Pharmacokinetics of GnRH agonists and antagonists in endometriosis. Res Gate Preprint. 2025;25(5):23–6. Mikuš M, ŠpremGoldštajn M, Laganà AS, et al. Medical options for endometriosis-related pelvic pain: A review. Pharmaceuticals (Basel). 2023;16(9):1315–20. Perricos A, Wenzl R. Efficacy of elagolix in endometriosis treatment. Expert Opin Pharmacother. 2017;18(11):1093–101. Yan H, Shi J, Li X, et al. GnRH antagonists for endometriosis pain: Systematic review. Fertil Steril. 2022;118(4):632–44. Soliman AM, Poulos C, Tekin S, et al. Patient preferences for elagolix versus leuprolide. Expert Rev Pharmacoecon Outcomes Res. 2021;21(3):299–310. Ng J, Archer DF, Chwalisz K, et al. Ovulation suppression by elagolix. J Clin Endocrinol Metab. 2020;105(3):821–32. Barretta M, Vignali M, La Marca A, et al. Oral GnRH antagonists in gynecology. Expert Opin Drug Metab Toxicol. 2025;12(3):125–30. Rzewuska AM, Żybowska M. GnRH antagonists: a new hope. J Clin Med. 2023;12(3):1008–12. Wang ST, Johnson SJ, Mitchell D, et al. Cost-effectiveness of elagolix versus leuprolide. J Comp Eff Res. 2019;8(4):263–72. Merhi Z. Elagolix for ovulation suppression in in vitro fertilization: is it time to switch from the painful costly injectables? F&S Reports. 2024;5(4):350–1. Kou L, Huang C, Xiao D, et al. Pharmacologic interventions for endometriosis-related pain: a systematic review and meta-analysis. Obstet Gynecol. 2025;146(2):e23–35. Funding No external funds have been received for this article. Author information Authors and Affiliations Contributions Ashish Kale and Ashwini Kale were the primary investigators who were involved in patient interaction, data collection and analysis. Avir Sarkar did the data analysis. Avir Sarkar, Amiya Das and Suman Sandeep Samal helped in writing the manuscript. Corresponding author Ethics declarations Conflict of interest None declared. Ethics Approval Institutional Ethics Committee approval has been obtained prior to the initiation of this study (BSMC/Aca/19/24). Informed consent Not applicable as a retrospective study and data analysis. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Ashish Kale: Director, Ashakiran Hospital and ASHA IVF Centre; Ashwini Kale: Director, Ashakiran Hospital and ASHA IVF Centre; Avir Sarkar: Assistant Professor, Department of Obstetrics and Gynaecology, AIIMS Kalyani; Amiya Das: Senior Resident, Department of Obstetrics and Gynaecology, AIIMS Kalyani; Suman Sandeep Samal: Junior Resident, Department of Obstetrics and Gynaecology, AIIMS Kalyani. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Kale, A., Kale, A., Sarkar, A. et al. Comparison of the Efficacy of Oral Elagolix Versus Leuprolide Depot: Optimizing Natural Conception in Women with Endometrioma. J Obstet Gynecol India (2026). https://doi.org/10.1007/s13224-025-02328-w Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s13224-025-02328-w