Diminished Ovarian Reserve in Advanced Endometriosis: Prevalence, Clinical Predictors, and Patient Awareness of Fertility Preservation

Background & Objective: Advanced endometriosis is recognized as a potential cause of Diminished Ovarian Reserve (DOR), yet data on its prevalence, predictors, and patient awareness in Central Asia are scarce. The present study was conducted with aim to determine the prevalence of DOR, identify its clinical predictors, and assess awareness of fertility preservation among women with moderate-to-severe endometriosis in Uzbekistan.

& Methods: This cross-sectional analytical study was conducted from March to September 2025 at tertiary care centers in Tashkent, Uzbekistan. The study enrolled 180 women aged 25-38 years with surgically confirmed stage III-IV endometriosis. Ovarian reserve was assessed via serum Anti-Müllerian Hormone (AMH), Antral Follicle Count (AFC), and day-3 Follicle-Stimulating Hormone (FSH). Clinical and sonographic data were collected, and participants completed a validated questionnaire on fertility preservation knowledge and attitudes. Data were analyzed using SPSS software (Version 28.0) and Spearman’s correlation, multivariate linear regression, and Mann-Whitney U tests. P<0.05 was considered significant.

The prevalence of DOR was 33.9% based on AMH (<1.1 ng/mL) and 26.7% based on AFC (<5). The cohort's median AMH was 1.6 ng/mL (IQR: 0.8-2.5) and median AFC was 7 (IQR: 4-11). Significant negative correlations were found between AMH and age (r=-0.42, P<0.001), endometrioma size (r=-0.24, P=0.002), and rASRM stage (r=-0.29, P<0.01). Multivariate analysis identified age (β=-0.11, P3cm (β=-0.65, P=0.001) as independent predictors of lower AMH. Despite the high prevalence of DOR, only 18.3% of participants were aware of oocyte cryopreservation, with high cost (65.6%) and lack of information (47.2%) as major barriers.

A significant proportion of women with advanced endometriosis exhibit DOR, driven primarily by age and large endometriomas. A critical gap exists between clinical risk and patient awareness of fertility preservation. These findings advocate for the routine integration of ovarian reserve testing and early tailored fertility counseling into the standard management protocol for endometriosis.

& Methods: This cross-sectional analytical study was conducted from March to September 2025 at tertiary care centers in Tashkent, Uzbekistan. The study enrolled 180 women aged 25-38 years with surgically confirmed stage III-IV endometriosis. Ovarian reserve was assessed via serum Anti-Müllerian Hormone (AMH), Antral Follicle Count (AFC), and day-3 Follicle-Stimulating Hormone (FSH). Clinical and sonographic data were collected, and participants completed a validated questionnaire on fertility preservation knowledge and attitudes. Data were analyzed using SPSS software (Version 28.0) and Spearman’s correlation, multivariate linear regression, and Mann-Whitney U tests. P<0.05 was considered significant.

The prevalence of DOR was 33.9% based on AMH (<1.1 ng/mL) and 26.7% based on AFC (<5). The cohort's median AMH was 1.6 ng/mL (IQR: 0.8-2.5) and median AFC was 7 (IQR: 4-11). Significant negative correlations were found between AMH and age (r=-0.42, P<0.001), endometrioma size (r=-0.24, P=0.002), and rASRM stage (r=-0.29, P<0.01). Multivariate analysis identified age (β=-0.11, P3cm (β=-0.65, P=0.001) as independent predictors of lower AMH. Despite the high prevalence of DOR, only 18.3% of participants were aware of oocyte cryopreservation, with high cost (65.6%) and lack of information (47.2%) as major barriers.

A significant proportion of women with advanced endometriosis exhibit DOR, driven primarily by age and large endometriomas. A critical gap exists between clinical risk and patient awareness of fertility preservation. These findings advocate for the routine integration of ovarian reserve testing and early tailored fertility counseling into the standard management protocol for endometriosis. Highlights - One-third of women with stage III–IV endometriosis had diminished ovarian reserve based on AMH. - Older age and endometriomas >3 cm independently predicted lower AMH levels. - Fertility preservation awareness was low, highlighting the need for early fertility counseling.

Subjects 1. Gylfason JT, Kristjansson KA, Sverrisdottir G, Jonsdottir K, Rafnsson V, Geirsson RT. Pelvic endometriosis diagnosed in an entire nation over 20 years. Am J Epidemiol. 2010;172(3):237-43. [doi:10.1093/aje/kwq143] 2. Endometriosis and infertility: a committee opinion. Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012;98(3):591-8. [doi:10.1016/j.fertnstert.2012.05.031] 3. 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(4):535-49. [doi:10.1016/j.ogc.2012.10.002] 4. Coccia ME, Nardone L, Rizzello F. Endometriosis and infertility: a long-life approach to preserve reproductive integrity. Int J Environ Res Public Health. 2022;19(10):6162. [doi:10.3390/ijerph19106162] 5. de Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376(9742):730-8. [doi:10.1016/S0140-6736(10)60490-4] 6. Meuleman C, Tomassetti C, D'Hoore A, Van Cleynenbreugel B, Penninckx F, Vergote I, et al. Surgical treatment of deeply infiltrating endometriosis with colorectal involvement. Hum Reprod Update. 2011;17(3):311-26. [doi:10.1093/humupd/dmq057] 7. Clower L, Fleshman T, Geldenhuys WJ, Santanam N. Targeting oxidative stress involved in endometriosis and its pain. Biomolecules. 2022;12(8):1055. [doi:10.3390/biom12081055] 8. Donnez J, Binda MM, Donnez O, Dolmans MM. Oxidative stress in the pelvic cavity and its role in the pathogenesis of endometriosis. Fertil Steril. 2016;106(5):1011-7. [doi:10.1016/j.fertnstert.2016.07.1075] 9. Kitajima M, Dolmans MM, Donnez O, Masuzaki H, Soares M, Donnez J. Enhanced follicular recruitment and atresia in cortex derived from ovaries with endometriomas. Fertil Steril. 2014;101(4):1031-7. [doi:10.1016/j.fertnstert.2013.12.049] 10. Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Crosignani PG. Surgery for endometriosis-associated infertility: a pragmatic approach. Hum Reprod. 2009;24(2):254-69. [doi:10.1093/humrep/den379] 11. Chapron C, Fauconnier A, Vieira M, Barakat H, Dousset B, Pansini V, et al. Anatomical distribution of deeply infiltrating endometriosis: surgical implications and proposition for a classification. Hum Reprod. 2003;18(1):157-61. [doi:10.1093/humrep/deg009] 12. Yu EH, Joo JK. Commentary on the new 2022 European Society of Human Reproduction and Embryology (ESHRE) endometriosis guidelines. Clin Exp Reprod Med. 2022;49(4):219-24. [doi:10.5653/cerm.2022.05603] 13. Keckstein J, Saridogan E, Ulrich UA, Sillem M, Oppelt P, Schweppe KW, et al. The #Enzian classification: a comprehensive non-invasive and surgical description system for endometriosis. Acta Obstet Gynecol Scand. 2021;100(7):1165-75. [doi:10.1111/aogs.14099] 14. Papaleo E, Ottolina J, Viganò P, Brigante C, Marsiglio E, De Michele F, et al. Deep pelvic endometriosis negatively affects ovarian reserve and the number of oocytes retrieved for in vitro fertilization. Acta Obstet Gynecol Scand. 2011;90(8):878-84. [doi:10.1111/j.1600-0412.2011.01161.x] 15. 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. Am J Obstet Gynecol. 2016;215(5):589.e1-589.e6. [doi:10.1016/j.ajog.2016.05.029] 16. Dolmans MM, Martinez-Madrid B, Gadisseux E, Guiot Y, Yuan WY, Torre A, et al. Short-term transplantation of isolated human ovarian follicles and cortical tissue into nude mice. Reproduction. 2007;134(2):253-62. [doi:10.1530/REP-07-0131] 17. Roness H, Gavish Z, Cohen Y, Meirow D. Ovarian follicle burnout: a universal phenomenon? Cell Cycle. 2013;12(20):3245-6. [doi:10.4161/cc.26358] 18. Kalich-Philosoph L, Roness H, Carmely A, Fishel-Bartal M, Ligumsky H, Paglin S, et al. Cyclophosphamide triggers follicle activation and "burnout"; AS101 prevents follicle loss and preserves fertility. Sci Transl Med. 2013;5(185):185ra62. [doi:10.1126/scitranslmed.3005402] 19. Kitazawa H, Numakawa T, Adachi N, Kumamaru E, Tuerxun T, Kudo M, et al. Cyclophosphamide promotes cell survival via activation of intracellular signaling in cultured cortical neurons. Neurosci Lett. 2010;470(2):139-44. [doi:10.1016/j.neulet.2009.12.073] 20. Li J, Kawamura K, Cheng Y, Liu S, Klein C, Liu S, et al. Activation of dormant ovarian follicles to generate mature eggs. Proc Natl Acad Sci U S A. 2010;107(22):10280-4. [doi:10.1073/pnas.1001198107] 21. Coccia ME, Rizzello F, Mariani G, Bulletti C, Palagiano A, Scarselli G. Impact of endometriosis on in vitro fertilization and embryo transfer cycles in young women: a stage-dependent interference. Acta Obstet Gynecol Scand. 2011;90(11):1232-8. [doi:10.1111/j.1600-0412.2011.01247.x] 22. Kitajima M, Khan KN, Harada A, Taniguchi K, Inoue T, Kaneuchi M, et al. Association between ovarian endometrioma and ovarian reserve. Front Biosci (Elite Ed). 2018;10(1):92-102. [doi:10.2741/e810] 23. Lee D, Kim SK, Lee JR, Jee BC. Management of endometriosis-related infertility: considerations and treatment options. Clin Exp Reprod Med. 2020;47(1):1-11. [doi:10.5653/cerm.2019.02971] 24. Somigliana E, Infantino M, Candiani M, Vignali M, Chiodini A, Busacca M, et al. Association rate between deep peritoneal endometriosis and other forms of the disease: pathogenetic implications. Hum Reprod. 2004;19(1):168-71. [doi:10.1093/humrep/deg513] - Receive Date 08 May 2026 - Revise Date 24 July 2026 - Accept Date 27 July 2026 - Publish Date 01 December 2026 | Article View | 272 | | PDF Download | 52 |