Predictors of optimal ovarian response in GnRH antagonist ovarian stimulation protocol
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20251987Keywords:
Antral follicle count, Assisted reproductive technology, Controlled ovarian stimulation, Follicle-stimulating hormone, Gonadotropin-releasing hormone antagonist protocol, Ovarian response, Predictive biomarkersAbstract
Background: The outcome of assisted reproductive technology (ART) is significantly influenced by the ovarian response to controlled ovarian stimulation (COS). Identifying robust and reliable predictors of ovarian response is essential for tailoring individualized treatment strategies and optimizing reproductive success. This study aims to investigate clinical, hormonal, and stimulation-related variables that influence ovarian response among women undergoing ART and to identify significant predictors for both hyper-response and hypo-response patterns.
Methods: A retrospective cohort analysis was conducted involving 278 women who underwent COS under a gonadotropin-releasing hormone (GnRH) antagonist protocol. Based on ovarian responsiveness, participants were categorized into three groups: high responders (n=56), normal responders (n=151), and low responders (n=71). Demographic data, hormonal markers (including Anti-Müllerian hormone [AMH], antral follicle count [AFC], follicle-stimulating hormone [FSH], and luteinizing hormone [LH]), stimulation characteristics, and infertility etiologies were systematically analyzed. Statistical comparisons utilized t-tests and chi-square tests, while logistic regression identified independent predictive parameters. A p-value of less than 0.05 was considered statistically significant.
Results: Higher AFC and AMH levels, younger age, and lower baseline FSH levels were significantly correlated with high ovarian response. In contrast, women with low AMH, high FSH, reduced AFC, and prolonged stimulation duration tended to demonstrate poor ovarian responsiveness. Notably, polycystic ovary syndrome (PCOS) was more frequent in high responders, while diminished ovarian reserve (DOR) predominated in low responders. Multivariate logistic regression identified AMH and AFC as the most significant independent predictors of ovarian response.
Conclusions: Age, AMH, AFC, and baseline FSH are critical determinants of ovarian response in ART cycles. Incorporating these biomarkers into pre-treatment evaluation facilitates the customization of stimulation protocols, thereby enhancing oocyte yield and improving overall clinical outcomes. Personalized treatment planning grounded in these predictors holds promise for advancing ART success.
Metrics
References
Van Rooij IA, Broekmans FJ, Hunault CC, Scheffer GJ, Eijkemans MJ, de Jong FH, et al. Use of ovarian reserve tests for the prediction of ongoing pregnancy in couples with unexplained or mild male infertility. Reprod Biomed Online. 2006;12(2):182-90. DOI: https://doi.org/10.1016/S1472-6483(10)60859-0
Butts SF, Seifer DB. Racial and ethnic differences in reproductive potential across the life cycle. Fertil Steril. 2010;93(3):681-90. DOI: https://doi.org/10.1016/j.fertnstert.2009.10.047
Toftager M, Bogstad J, Løssl K, Prætorius L, Zedeler A, Bryndorf T, et al. Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols. Hum Reprod. 2017;32(3):556-67. DOI: https://doi.org/10.1093/humrep/dew358
Lainas TG, Sfontouris IA, Zorzovilis IZ, Petsas GK, Lainas GT, Alexopoulou E, et al. Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomized controlled trial. Hum Reprod. 2010;25(3):683-9. DOI: https://doi.org/10.1093/humrep/dep436
Shrestha D, La X, Feng HL. Comparison of different stimulation protocols used in in vitro fertilization: a review. Ann Transl Med. 2015;3(10):137.
Toftager M, Sylvest R, Schmidt L, Bogstad J, Løssl K, Prætorius L, et al. Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols. Fertil Steril. 2018;109(1):154-64. DOI: https://doi.org/10.1016/j.fertnstert.2017.09.020
Depalo R, Trerotoli P, Chincoli A, Vacca MP, Lamanna G, Cicinelli E. Endogenous luteinizing hormone concentration and IVF outcome during ovarian stimulation in fixed versus flexible GnRH antagonist protocols: an RCT. Int J Reprod Biomed. 2018;16(3):175-82. DOI: https://doi.org/10.29252/ijrm.16.3.175
La Marca A, Sunkara SK. Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice. Hum Reprod Update. 2014;20(1):124-40. DOI: https://doi.org/10.1093/humupd/dmt037
Fabregues F, González-Foruria I, Peñarrubia J, Carmona F. Ovarian response is associated with anogenital distance in patients undergoing controlled ovarian stimulation for IVF. Hum Reprod. 2018;33(9):1696-704. DOI: https://doi.org/10.1093/humrep/dey244
Grisendi V, La Marca A. Individualization of controlled ovarian stimulation in vitro fertilization using ovarian reserve markers. Minerva Ginecol. 2017;69(3):250-8. DOI: https://doi.org/10.23736/S0026-4784.17.04044-8
Aghssa MM, Tarafdari AM, Tehraninejad ES, Ezzati M, Bagheri M, Panahi Z, et al. Optimal cutoff value of basal anti-Müllerian hormone in Iranian infertile women for prediction of ovarian hyperstimulation syndrome and poor response to stimulation. Reprod Health. 2015;12:85. DOI: https://doi.org/10.1186/s12978-015-0053-4
Jiang W, Zheng B, Liao X, Chen X, Zhu S, Li R, et al. Analysis of relative factors and prediction model for optimal ovarian response with gonadotropin-releasing hormone antagonist protocol. Front Endocrinol (Lausanne). 2022;13:1030201. DOI: https://doi.org/10.3389/fendo.2022.1030201
Jiang Y, Cui C, Guo J, Wang T, Zhang C. A prediction model for high ovarian response in the GnRH antagonist protocol. Front Endocrinol (Lausanne). 2023;13:1238092. DOI: https://doi.org/10.3389/fendo.2023.1238092
Zhao S, Xu H, Wu X, Xia L, Li J, Zhang D, et al. The serum follicle stimulating hormone-to-luteinizing hormone ratios can predict assisted reproductive technology outcomes in women undergoing gonadotropin releasing hormone antagonist protocol. Front Endocrinol (Lausanne). 2023;14:1093954. DOI: https://doi.org/10.3389/fendo.2023.1093954
Li Q, Zhou X, Ye B, Tang M, Zhu Y. Ovarian response determines the luteinizing hormone suppression threshold for patients following the gonadotrophin releasing hormone antagonist protocol: a retrospective cohort study. Heliyon. 2023;9(6):e23933. DOI: https://doi.org/10.1016/j.heliyon.2023.e23933
Arms JM. Prediction of ovarian response using the automated Elecsys anti-Müllerian hormone assay in gonadotrophin-releasing hormone antagonist cycles. Reprod Biomed Online. 2023;46(2):295-301. DOI: https://doi.org/10.1016/j.rbmo.2022.10.012
Xu Z, Lin Q, Liang Z, Li S, Wu Y, Fu Y, et al. Optimising luteinising hormone levels on trigger day for improved ovarian response and pregnancy outcomes in gonadotropin-releasing hormone antagonist protocols: a retrospective cohort study. BJOG. 2025;132(3):522-31. DOI: https://doi.org/10.1111/1471-0528.18064
Andersen AN, Witjes H, Gordon K, Mannaerts B. Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment. Hum Reprod. 2011;26(12):3413-23. DOI: https://doi.org/10.1093/humrep/der318
Oehninger S, Nelson SM, Verweij P, Stegmann BJ. Predictive factors for ovarian response in a corifollitropin alfa/GnRH antagonist protocol for controlled ovarian stimulation. Hum Reprod. 2013;28:343-44.
El-Shorbagy SH. Comparison of the predictive value of antral follicle count, anti-Müllerian hormone and follicle-stimulating hormone in women following GnRH-antagonist protocol for intracytoplasmic sperm injection. Open J Obstet Gynecol. 2017;7(4):432-46. DOI: https://doi.org/10.4236/ojog.2017.74045
Broekmans FJ, Verweij PJ, Eijkemans MJ, Mannaerts BM, Witjes H. Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2014;29(8):1688-97. DOI: https://doi.org/10.1093/humrep/deu090
Downloads
Published
How to Cite
Issue
Section
