Fixed Versus Flexible GnRH Antagonist Initiation in Women with Suboptimal Ovarian Response Undergoing IVF/ICSI: A Retrospective Cohort Study
4 affiliations
- 1Department of Obstetrics and Gynecology, Clinical Hospital Sveti Duh, 10000 Zagreb, Croatia
- 2Polyclinic Hormona Split, 21000 Split, Croatia
- 3School of Medicine and Faculty of Health Sciences, University of Split, 21000 Split, Croatia
- 4Department of Obstetrics and Gynecology, Clinical Hospital Center Zagreb, 10000 Zagreb, Croatia
Abstract
Background: Suboptimal ovarian responders are a clinically important subgroup of patients treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Although their ovarian reserve is usually normal, fewer oocytes than expected are retrieved after controlled ovarian stimulation. Whether the timing of gonadotropin-releasing hormone (GnRH) antagonist initiation affects their reproductive outcomes is unknown. Objective: The objective of this study was to compare reproductive outcomes between fixed and flexible GnRH antagonist protocols in women with suboptimal ovarian response undergoing IVF/ICSI treatment. Methods: This retrospective single-center cohort study included 419 women treated with GnRH antagonist protocol between January 2019 and February 2020. After applying the exclusion criteria, 322 women undergoing IVF/ICSI with a GnRH antagonist protocol were eligible for analysis. Of these, 98 women with normal ovarian reserve and a suboptimal ovarian response (4–9 oocytes retrieved) were included, of whom 89 had a fresh embryo transfer (fixed protocol, n = 41; flexible protocol, n = 48). The primary outcome was live birth rate. Secondary outcomes included ovarian stimulation characteristics, embryo transfer strategy and pregnancy outcomes. Outcomes were analysed per embryo transfer and per oocyte retrieval, and factors associated with live birth were explored with Firth’s penalised logistic regression. Results: Baseline characteristics, including age, AMH, duration of infertility and number of previous IVF attempts, were comparable between groups. Antagonist initiation was later in the flexible group (median day 8 vs. 7), and more embryos were transferred in the fixed group (median 2 vs. 1). The numbers of retrieved and metaphase II oocytes did not differ. Live birth rate per transfer was higher with the fixed protocol (13/41, 31.7% vs. 6/48, 12.5%; p = 0.038), whereas positive β-hCG (43.9% vs. 27.1%; p = 0.12) and clinical pregnancy (41.5% vs. 22.9%; p = 0.071) did not differ significantly; results per oocyte retrieval were similar (live birth 29.5% vs. 11.1%; p = 0.038). In Firth regression, the crude OR for live birth with flexible vs. fixed initiation was 0.32 (95% CI 0.11–0.89); estimates were similar after adjustment for age and previous IVF attempts, whereas the confidence interval crossed 1 once the number of transferred embryos was added to the model (OR 0.36, 95% CI 0.11–1.04). Conclusions: In this small retrospective cohort of women with suboptimal ovarian response, live births were more frequent after fixed than after flexible GnRH antagonist initiation. In view of the small number of events, possible confounding by indication and differences in transfer strategy, this finding is hypothesis-generating and should be tested in a randomised trial.
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BibTeX
@article{medic2026fixed,
title = {{Fixed Versus Flexible GnRH Antagonist Initiation in Women with Suboptimal Ovarian Response Undergoing IVF/ICSI: A Retrospective Cohort Study}},
author = {Nina Medić and Damir Roje and Marina Šprem Goldštajn},
journal = {Journal of Clinical Medicine},
year = {2026},
month = nov,
doi = {10.3390/jcm15218497},
url = {https://www.mdpi.com/2077-0383/15/21/8497},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Fixed Versus Flexible GnRH Antagonist Initiation in Women with Suboptimal Ovarian Response Undergoing IVF/ICSI: A Retrospective Cohort Study
AU - Nina Medić
AU - Damir Roje
AU - Marina Šprem Goldštajn
PY - 2026
DA - 2026/11/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15218497
UR - https://www.mdpi.com/2077-0383/15/21/8497
AB - Background: Suboptimal ovarian responders are a clinically important subgroup of patients treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Although their ovarian reserve is usually normal, fewer oocytes than expected are retrieved after controlled ovarian stimulation. Whether the timing of gonadotropin-releasing hormone (GnRH) antagonist initiation affects their reproductive outcomes is unknown. Objective: The objective of this study was to compare reproductive outcomes between fixed and flexible GnRH antagonist protocols in women with suboptimal ovarian response undergoing IVF/ICSI treatment. Methods: This retrospective single-center cohort study included 419 women treated with GnRH antagonist protocol between January 2019 and February 2020. After applying the exclusion criteria, 322 women undergoing IVF/ICSI with a GnRH antagonist protocol were eligible for analysis. Of these, 98 women with normal ovarian reserve and a suboptimal ovarian response (4–9 oocytes retrieved) were included, of whom 89 had a fresh embryo transfer (fixed protocol, n = 41; flexible protocol, n = 48). The primary outcome was live birth rate. Secondary outcomes included ovarian stimulation characteristics, embryo transfer strategy and pregnancy outcomes. Outcomes were analysed per embryo transfer and per oocyte retrieval, and factors associated with live birth were explored with Firth’s penalised logistic regression. Results: Baseline characteristics, including age, AMH, duration of infertility and number of previous IVF attempts, were comparable between groups. Antagonist initiation was later in the flexible group (median day 8 vs. 7), and more embryos were transferred in the fixed group (median 2 vs. 1). The numbers of retrieved and metaphase II oocytes did not differ. Live birth rate per transfer was higher with the fixed protocol (13/41, 31.7% vs. 6/48, 12.5%; p = 0.038), whereas positive β-hCG (43.9% vs. 27.1%; p = 0.12) and clinical pregnancy (41.5% vs. 22.9%; p = 0.071) did not differ significantly; results per oocyte retrieval were similar (live birth 29.5% vs. 11.1%; p = 0.038). In Firth regression, the crude OR for live birth with flexible vs. fixed initiation was 0.32 (95% CI 0.11–0.89); estimates were similar after adjustment for age and previous IVF attempts, whereas the confidence interval crossed 1 once the number of transferred embryos was added to the model (OR 0.36, 95% CI 0.11–1.04). Conclusions: In this small retrospective cohort of women with suboptimal ovarian response, live births were more frequent after fixed than after flexible GnRH antagonist initiation. In view of the small number of events, possible confounding by indication and differences in transfer strategy, this finding is hypothesis-generating and should be tested in a randomised trial.
SN - 2077-0383
ER -