Preventive therapeutic options for postoperative recurrence of ovarian endometrioma: gonadotropin-releasing hormone agonist with or without levonorgestrel intrauterine system insertion

Purpose Here, we compared endometrioma recurrence rates in patients who have undergone a laparoscopic cystectomy and treated with a gonadotropin-releasing hormone agonist (GnRHa) alone or a GnRHa combined with a levonogestrel intrauterine system (LND-IUS).

We enrolled endometrioma patients who underwent laparoscopic cyst enucleation and divided them into two groups according to postoperative management: GnRHa alone and GnRHa in combination with LND-IUS. We compared preoperative history, perioperative parameters, postoperative endometrioma recurrence, and symptoms between these two groups.

A total of 320 patients were included in the final analysis. With a median 84.6 months of follow-up, we detected significant differences between the two groups with respect to age at surgery (31.6 ± 4.8 vs. 37.6 ± 4.2 years, χ2 = 1.978, p < 0.001), gravida (0 vs. 2, χ2 = 4.391, p < 0.001), parity (0 vs. 1, χ2 = 0.035, p < 0.001), body mass index (21.0 ± 2.5 vs. 21.9 ± 2.4, χ2 = 0.0096, p = 0.009), r-AFS score (48 vs. 64, χ2 = 4.888, p = 0.001), and operation time (60 vs. 75 min, χ2 = 9.119, p = 0.003). Patients treated with both GnRHa and LND-IUS achieved significantly less endometrioma recurrence (23.6 vs. 11.5%, χ2 = 5.202, p = 0.023) and higher rates of pain remission (92.1 vs. 100%, χ2 = 6.511, p = 0.011), while those with GnRHa alone suffered more recurrent and painful symptoms (χ2 = 9.280, p = 0.026). Multivariate analysis using a Cox regression demonstrated that combined GnRHa and LNG-IUS treatment correlated with a decreased endometrioma recurrence rate after laparoscopic cystectomy (RR 0.369, 95% CI 0.182–0.749, p = 0.006).

Combination treatment of GnRHa and LNG-IUS exhibited superior pain relief and recurrence prevention among endometrioma patients after fertility-sparing surgery. Thus, combination treatment is a preferable long-term option for patients without intent for pregnancy in the near future. Similar content being viewed by others Code availability Not applicable. All the authors gave final approval of the version to be published.

Hickey M, Ballard K, Farquhar C (2014) Endometriosis. BMJ 348:g1752. https://doi.org/10.1136/bmj.g1752 Shim JY, Laufer MR (2019) Adolescent endometriosis: an update. J Pediatr Adolesc Gynecol. https://doi.org/10.1016/j.jpag.2019.11.011 Seo JW, Lee DY, Yoon BK, Choi D (2017) The age-related recurrence of endometrioma after conservative surgery. Eur J Obstet Gynecol Reprod Biol. https://doi.org/10.1016/j.ejogrb.2016.11.015 Dunselman GA, Vermeulen N, Becker C, Calhaz-Jorge C, D’Hooghe T, De Bie B et al (2014) ESHRE guideline: management of women with endometriosis. Hum Reprod. https://doi.org/10.1093/humrep/det457 Ferrero S, Evangelisti G, Barra F (2018) Current and emerging treatment options for endometriosis. Exp Opin Pharmacother 19(10):1109–1125. https://doi.org/10.1080/14656566.2018.1494154 Geoffron S, Cohen J, Sauvan M, Legendre G, Wattier JM, Darai E et al (2018) 2018 Endometriosis medical treatment: hormonal treatment for the management of pain and endometriotic lesions recurrence CNGOF–HAS endometriosis guidelines. Gynecol Obstet Fertil Senol. 46(3):231–247. https://doi.org/10.1016/j.gofs.2018.02.011 Brown J, Pan A, Hart R (2010) Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev 8(12):CD0008475 Petta CA, Ferriani RA, Abrao MS, Hassan D, Silva RE, Podgaec S, Bahamondes L et al (2005) Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod 20(7):1993–1998 Deng S, Lang J-h, Leng J, Liu Z-f, Liu Z, Sun D-w, Zhu L (2006) Effects of levonorgestrel-releasing intrauterine system on pain and recurrence associated with endometriosis and adenomyosis. Zhonghua Fu Chan Ke Za Zhi. 41(10):664–668 Brown J, Farquhar C (2015) An overview of treatments for endometriosis. JAMA 313(3):296–297 Kyoung MK, Chon SJ, Lee JH, Yun BH, Cho S et al (2018) Postoperative levonorgestrel-releasing intrauterine system insertion after gonadotropin-releasing hormone agonist treatment for preventing endometriotic cyst recurrence: a prospective observational study. Reprod Sci 25(1):39–43 Yj C, Tf H, Bs H, Hw T, Yh C, Ph W (2017) Postoperative maintenance levonorgestrel-releasing intrauterine system and endometrioma recurrence: a randomized controlled study. Am J Obstet Gynecol 216(6):15 Jeon SJ, Lee JI, Lee M, Kim HS, Kim JW, Park NH et al (2017) Endometrial polyp surveillance in premenopausal breast cancer patients using tamoxifen. Obstet Gynecol Sci 60(1):26–31. https://doi.org/10.5468/ogs.2017.60.1.26 Gallagher JS, Missmer SA, Hornstein MD, Laufer MR, Gordon CM, DiVasta AD (2018) Long-term effects of gonadotropin-releasing hormone agonists and add-back in adolescent endometriosis. J Pediatr Adolesc Gynecol 31(4):376–381. https://doi.org/10.1016/j.jpag.2018.03.004 Jee BC, Lee JY, Suh CS, Kim SH, Choi YM, Moon SY (2009) Impact of GnRH agonist treatment on recurrence of ovarian endometriomas after conservative laparoscopic surgery. Fertil Steril 91(1):40–45. https://doi.org/10.1016/j.fertnstert.2007.11.027 Yang XH, Ji F, AiLi A, TuerXun H, He Y, Ding Y (2014) Effects of laparoscopic ovarian endometriosis cystectomy combined with postoperative GnRH-a therapy on ovarian reserve, pregnancy, and outcome recurrence. Clin Exp Obstet Gynecol 41(3):272–275 Lee DY, Bae DS, Yoon BK, Choi D (2010) Post-operative cyclic oral contraceptive use after gonadotrophin-releasing hormone agonist treatment effectively prevents endometrioma recurrence. Hum Reprod. 25(12):3050–3054. https://doi.org/10.1093/humrep/deq279 Sun TT, Chen SK, Li XY, Zhang JJ, Dai Y, Shi JH et al (2020) Fertility outcomes after laparoscopic cystectomy in infertile patients with stage III–IV endometriosis: a cohort with 6–10 years of follow-up. Adv Ther. https://doi.org/10.1007/s12325-020-01299-w Porpora MG, Pallante D, Ferro A, Crisafi B, Bellati F, Benedetti PP (2010) Pain and ovarian endometrioma recurrence after laparoscopic treatment of endometriosis: a long-term prospective study. Fertil Steril. 93(3):716–721. https://doi.org/10.1016/j.fertnstert.2008.10.018 Tobiume T, Kotani Y, Takaya H, Nakai H, Tsuji I, Suzuki A et al (2016) Determinant factors of postoperative recurrence of endometriosis: difference between endometrioma and pain. Eur J Obstet Gynecol Reprod Biol. 205:54–59. https://doi.org/10.1016/j.ejogrb.2016.07.516 Yucel N, Baskent E, Karamustafaoglu Balci B, Goynumer G (2018) The levonorgestrel-releasing intrauterine system is associated with a reduction in dysmenorrhoea and dyspareunia, a decrease in CA 125 levels, and an increase in quality of life in women with suspected endometriosis. Aust N Z J Obstet Gynaecol 58(5):560–563. https://doi.org/10.1111/ajo.12773 Vercellini P, Vigano P, Somigliana E (2005) The role of the levonorgestrel-releasing intrauterine device in the management of symptomatic endometriosis. Curr Opin Obstet Gynecol 17(4):359–365 Abou-Setta AM, Houston B, Al-Inany HG, Farquhar C (2013) Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery. Cochrane Database Syst Rev. 1:CD005072. https://doi.org/10.1002/14651858.CD005072.pub3 Chen YJ, Hsu TF, Huang BS, Tsai HW, Chang YH, Wang PH (2017) Postoperative maintenance levonorgestrel-releasing intrauterine system and endometrioma recurrence: a randomized controlled study. Am J Obstet Gynecol. 216(6):582e1-582e9. https://doi.org/10.1016/j.ajog.2017.02.008 Kim MK, Chon SJ, Lee JH, Yun BH, Cho S, Choi YS et al (2018) Postoperative levonorgestrel-releasing intrauterine system insertion after gonadotropin-releasing hormone agonist treatment for preventing endometriotic cyst recurrence: a prospective observational study. Reprod Sci 25(1):39–43. https://doi.org/10.1177/1933719117718274

We appreciate the staff for their arduous work maintaining the medical records used in the study and the National Natural Science Foundation of China for the project (no. 81501237). Funding This work was supported by the National Natural Science Foundation of China (no. 81501237). Author information Authors and Affiliations Contributions S-YZ and X-YL contributed to protocol development, data analysis, and manuscript writing. Y-SW and JZ collected the data. Z-YG and YD performed data management. S-ZJ analyzed the data. J-HS contributed to data collection or management and data analysis. J-HL is the responsible surgeon. Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of interest. Ethical approval This study was approved by the Ethics Committee of Peking Union Medical College Hospital (IRB No. SK730). Informed consent This research study was conducted retrospectively according to medical record data obtained during hospitalization. We consulted extensively with the IRB of Peking Union Medical College Hospital (PUMCH) who determined that our study did not require informed consent. Consent to participate Not applicable. Consent for publication Not applicable. Availability of data and material The dataset supporting this article is included within the article, and additional data are available from the corresponding author upon request. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Zhu, SY., Wu, YS., Gu, ZY. et al. Preventive therapeutic options for postoperative recurrence of ovarian endometrioma: gonadotropin-releasing hormone agonist with or without levonorgestrel intrauterine system insertion. Arch Gynecol Obstet 303, 533–539 (2021). https://doi.org/10.1007/s00404-020-05843-5 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00404-020-05843-5