GnRH Agonist Versus GNRH Antagonist in IVF: A Comparison of Ovarian Hyperstimulation Syndrome in Infertile Females
DOI:
https://doi.org/10.36283/ziun-pjmd15-2/017Keywords:
Fertilization, Gonadotrophins, InfertilityAbstract
Background: Gonadotropin-releasing hormone (GnRH) antagonists and agonists are a major part of in vitro fertilization as they control ovulation and egg development. But there are conflicting results regarding the effectiveness of GnRH agonists and antagonists and the development of OHSS in the literature. This study was conducted to compare the frequency of ovarian hyperstimulation syndrome in infertile females with GnRH agonists versus GnRH antagonists seeking in vitro fertilization.
Methods: A prospective cohort study was conducted at the Obstetrics and Gynecology Department of Hameed Latif Hospital, Lahore, from 4th January 2024 to 4th January 2025. A total of 60 infertile women aged 20-40 years referred for the first IVF/ ICSI were selected for the study, using non-probability, consecutive sampling. Patients in Group A were 30 women administered 500 µg GnRH agonist (Buserelin) subcutaneously every day since the 21st day of the menstrual cycle. Patients in Group B were 30 women administered 0.25 mg GnRH antagonist (Cetrotide) subcutaneously. An estradiol >3000 pg/ml in more than three follicles at 3 months and 6 months was described as OHSS, which was managed by standard procedure. Data analysis was done by SPSS version 25.
Results: The frequency of primary infertility patients in Group A was 16 (53.3%), and secondary infertility was 14(46.7%). The frequency of primary infertility patients in Group B was 19(63.3%), and secondary infertility was 11(36.7%). The mean number of mature follicles of patients in Group A was 14.4±1.27 (1-35). The mean number of mature follicles of patients in Group B was 13.6±1.24 (2-27). The mean E2 level in patients of Group A was 3261.8±134.7 (Range: 1008-4215), and the mean E2 level in patients of Group B was 3500±167.4 (Range: 1000-4890). The frequency of patients with ovarian hyperstimulation syndrome in Group A was 2 (6.7%) and in Group B was 8 (26.7%).
Conclusion: GnRH agonist is more effective than GnRH antagonist in terms of frequency of ovarian hyperstimulation syndrome in infertile women seeking in vitro fertilization.
References
1. Papamentzelopoulou M, Stavros S, Mavrogianni D, Kalantzis C, et al. Meta-analysis of GnRH-antagonists versus GnRH-agonists in poor responder protocols. Arch Gynecol Obstet. 2021 Aug; 304(2): 547–557. https://doi.org/10.1007/s00404-020-05954-z
2. Zhu J, Xing W, Li T, Lin H, et al. GnRH antagonist protocol versus GnRH agonist long protocol: a retrospective cohort study on clinical outcomes and maternal-neonatal safety. FrontEndocrinol. 2022 Jun.13:875779. https://doi.org/10.3389/fendo.2022.875779
3. Tesarik J. Benefits and risks of agonist triggering strategies. Front Endocrinol. 2024 Dec.1538412.https://doi.org/10.3389/fendo.2024.1538412
4. Freedland SJ, Abrahamsson P-A. Androgen deprivation therapy and side effects: are GnRH antagonists safer? Asian J Androl. 2021 Jan.23(1):3-10. DOI: 10.4103/aja.aja_22_20
5. Mashaly A, Abo Ali A, ElKassar Y. Comparison between Agonist & Antagonist Risks and Outcome. JReprod MedEmbryol. 2024 July.1(2):118-33. DOI: 10.21608/jrme.2024.265325.1008
6. Elsebaee MF, Mesbah Y, Ismail KS, El Menayyer A, et al. Incidence of ovarian hyperstimulation Syndrome among patients with polycystic ovarian syndrome undergoing IVF/ICSI. Egypt J FertilSteril. 2025 Jan.29(1):41-56. DOI: 10.21608/egyfs.2025.409768
7. Xu B, Geerts D, Yuan J, Wang M, et al. A modified flexible GnRH antagonist protocol using antagonist early cessation and a gonadotropin step-down approach improves live birth rates in fresh cycles: a randomized controlled trial. Human Reprod. 2024 Sep.39(9):1969-78. https://doi.org/10.1093/humrep/deae145
8. Yang R, Guan Y, Perrot V, Ma J, et al. Comparison of the long-acting GnRH agonist follicular protocol with the GnRH antagonist protocol in women undergoing in vitro fertilization: a systematic review and meta-analysis. Adv Ther. 2021 May; 38(5): 2027–2037 (2021). https://doi.org/10.1007/s12325-020-01612-7
9. Kadoura S, Alhalabi M, Nattouf AH. Conventional GnRH antagonist protocols versus long GnRH agonist protocol in IVF/ICSI cycles of polycystic ovary syndrome women: a systematic review and meta-analysis. Sci rep. 2022 Mar;12(1):4456.https://doi.org/10.1038/s41598-022-08400-z
10. Liu C, Tian T, Lou Y, Li J, et al. Live birth rate of gonadotropin-releasing hormone antagonist versus luteal phase gonadotropin-releasing hormone agonist protocol in IVF/ICSI: a systematic review and meta-analysis. Expert Rev MolMed. 2024 Jan.26:e2. doi: 10.1017/erm.2023.25.
11. Saeed AM. Efficacy of Gonadotropin Releasing Hormone Antagonist (GnRHant) in Treatment of Severe Ovarian Hyperstimulation Syndrome (OHSS): a Randomized Controlled Trial. Al-Azhar Int Med J. 2025 Dec;2025(12):43-7.DOI: 10.21608/aimj.2026.418196.2824
12. Lai J, Lu J, Wu X, Chen X. Gonadotrophin-releasing hormone antagonist regimen versus agonist regimen among normal ovarian responders: a systematic review and meta-analysis. Afric JReprod Health. 2026 Mar;30(6).
13. Slifirski O, Rozen G, Medwin C, Nassar N, Polyakov A. Severe Ovarian Hyperstimulation Syndrome (OHSS) After Gonadotrophin Releasing Hormone Agonist (GnRHa) Triggering. Aus New Zea J Obstet Gynaecol. 2026 Feb;66(1):e70072.https://doi.org/10.1111/ajo.70072
14. Fernández-Sánchez M, Fatemi H, García-Velasco J, Heiser P, et al. Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in “freeze-all” approach. GynecolEndocrinol. 2023 Dec.39(1):2205952. https://doi.org/10.1080/09513590.2023.2205952
15. Yang R, Guan Y, Perrot V, Ma J, et al. Comparison of the long-acting GnRH agonist follicular protocol with the GnRH antagonist protocol in women undergoing in vitro fertilization: a systematic review and meta-analysis. AdvTher. 2021 May.38:2027-37. doi: 10.1007/s12325-020-01612-7.
16. Kuan KK, Omoseni S, Tello JA. Comparing ART outcomes in women with endometriosis after GnRH agonist versus GnRH antagonist ovarian stimulation: a systematic review. Ther Adv Endocrinol Metab. 2023 July.14:20420188231173325. doi: 10.1177/20420188231173325.
17. Elmahdy M, Elsharkawy S. GnRH-Agonist Trigger versus Human Chorionic Gonadotrophin (HCG) Trigger in Cases of Controlled Ovarian Stimulation; Randomized Controlled Trial. Open J ObstetrGynecol. 2021.11(11):1452-60. DOI: 10.4236/ojog.2021.1111135
18. Ni Y-H, Zhang H-L, Jiang W-W. Analysis and prediction of risk factors of ovarian hyperstimulation caused by Long-acting GnRH agonist protocol in follicular phase. Eur Rev Med Pharmacol Sci. 2022 May.26(9). doi: 10.3389/fendo.2022.837880.
19. Kalafat E, Turkgeldi E, Yıldız S, Dizdar M, et al. Outcomes of a GnRH agonist trigger following a GnRH antagonist or flexible progestin-primed ovarian stimulation cycle. Frontendocrinol. 2022 May.13:837880. doi: 10.3389/fendo.2022.837880.
20. Geng Y, Xun Y, Hu S, Lai Q, et al. GnRH antagonist versus follicular-phase single-dose GnRH agonist protocol in patients of normal ovarian responses during controlled ovarian stimulation. GynecolEndocrinol. 2019 Apr.35(4):309-13. DOI: 10.1080/09513590.2018.1528221
21. Zhang Y, Liu L, Qin J, Huang H, et al. Evaluation of GnRH antagonist pretreatment before ovarian stimulation in a GnRH antagonist protocol in normal ovulatory women undergoing IVF/ICSI: a randomized controlled trial. ReprodBioEndocrinol. 2021 Oct.19:1-10. doi: 10.1186/s12958-021-00836-8.
22. Mills G, Dahan MH. Gonadotropin releasing hormone (GnRH) antagonist administration to decrease the risk of ovarian hyperstimulation syndrome in GNRH agonist cycles triggered with human chorionic gonadotropin. ArchGynecolObstet. 2022 Nov.306(5):1731-7. doi: 10.1007/s00404-022-06717-8.
23. Jiang Y, Cui C, Guo J, Wang T, et al. A prediction model for high ovarian response in the GnRH antagonist protocol. FrontEndocrinol. 2023 Nov.14:1238092. doi: 10.3389/fendo.2023.1238092
24. Inoue D, Sakakibara Y, Ishida C, Kondo M, et al. Risk factors for empty follicle syndrome in assisted reproductive technology with gonadotropin‐releasing hormone agonist trigger. Reprod Med Bio. 2023 Dec.22(1):e12553. doi: 10.1002/rmb2.12553.
25. Ranit H, Shmuel H, Ahlad A, Shirley G, et al. Is there a preferred time interval between gonadotropin-releasing hormone (GnRH) agonist trigger and oocyte retrieval in GnRH antagonist cycles? A retrospective cohort of planned fertility preservation cycles. JAssist ReprodGene. 2024 Mar.41(6):1531-8.doi: 10.1007/s10815-024-03083-z
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