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Comparative Study
. 2025 Nov:314:114682.
doi: 10.1016/j.ejogrb.2025.114682. Epub 2025 Sep 1.

A retrospective comparison of live birth rate in freeze-all cycles between progestin-primed ovarian stimulation with dydrogesterone and GnRH antagonist protocols

Tien Khac Le  1 , Toan Duong Pham  2 , Xuyen Thi-Ha Le  3 , Nguyen-Tuong Ho  4 , Ho Long Le  3 , Tuong Manh Ho  4 , Lan Ngoc Vuong  5
Affiliations
Comparative Study

A retrospective comparison of live birth rate in freeze-all cycles between progestin-primed ovarian stimulation with dydrogesterone and GnRH antagonist protocols

Tien Khac Le et al. Eur J Obstet Gynecol Reprod Biol. 2025 Nov.

Abstract

Research question: Does progestin-primed ovarian stimulation (PPOS) using dydrogesterone yield a live birth rate comparable with the gonadotrophin-releasing hormone (GnRH) antagonist protocol in in-vitro fertilization (IVF) freeze-all cycles?

Design: This retrospective cohort study, conducted at a tertiary hospital from June 2022 to January 2024, included 1045 women aged 18-40 years undergoing IVF/intracytoplasmic sperm injection with freeze-all indications. Participants were assigned to receive PPOS-dydrogesterone (n = 482) or GnRH antagonist (n = 563), followed by frozen embryo transfer (FET). The primary outcome was the live birth rate after the first FET cycle.

Results: The live birth rate after the first FET cycle were comparable between the PPOS-dydrogesterone (35.1 %) and GnRH antagonist (40.3 %) groups (p = 0.092), showing no significant difference. The PPOS-dydrogesterone group experienced a longer stimulation period [mean ± standard deviation (SD) 8.4 ± 2.0 vs 8.0 ± 2.0 days; p = 0.002] and a higher gonadotrophin dosage (mean ± SD 2622.2 ± 818.8 vs 2413.4 ± 663.4 IU; p < 0.001) than the GnRH antagonist group, but produced more blastocysts (mean ± SD 6.3 ± 3.9 vs 5.6 ± 3.5; p = 0.013). Multivariate analysis showed that age [adjusted odds ratio (aOR) 0.96, 95 % confidence interval (CI) 0.93-0.99; p = 0.006] and anti-Müllerian hormone concentration (aOR 1.05, 95 % CI 1.01-1.10; p = 0.011) were key predictors of live birth, overshadowing protocol effects (aOR 1.27, 95 % CI 0.98-1.67; p = 0.076).

Conclusion: The PPOS-dydrogesterone protocol has a similar live birth rate to the GnRH antagonist protocol in IVF freeze-all cycles, with added benefits in blastocyst yield despite higher stimulation demands. Patient factors, rather than protocol choice, primarily drive outcomes, positioning the PPOS-dydrogesterone protocol as an effective alternative to the GnRH antagonist protocol.

Keywords: Dydrogesterone; Frozen embryo transfer; GnRH antagonist; In-vitro fertilization; Progesterone-primed ovarian stimulation.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LNV has received grant, speaker, and conference fees from Merck Sharp and Dohme, and grant, speaker, conference, and scientific board fees from Ferring. TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; TKL, XTHL, TNH, HLL, and TDP have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work.

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