Duration of progesterone exposure before frozen embryo transfer impacts live birth rates following single vitrified-thawed day 6 blastocyst transfer: a multicenter cohort study

TL;DR

Extending progesterone exposure to six days before frozen embryo transfer improves live birth rates compared to five days when using day 6 blastocysts.

Contribution

Demonstrates that a six-day progesterone protocol before frozen embryo transfer increases live birth rates for day 6 blastocysts.

Findings

Six days of progesterone priming before FET significantly increased live birth rates compared to five days.

Biochemical and clinical pregnancy rates were also higher with six days of progesterone exposure.

No significant differences in miscarriage rates or neonatal outcomes were observed between the groups.

Abstract

Does administering progesterone for 6 days prior to frozen embryo transfer (FET) improve live birth rate (LBR) compared to 5 days of progesterone exposure when transferring blastocysts expanded on Day 6 (D6)?

This multicenter retrospective cohort study included 1,639 single FET cycles using D6 blastocysts under hormone replacement therapy (HRT) between January 2018 and December 2023. Cycles were stratified by duration of progesterone priming: 6 days (P6 group, n = 1,122) or 5 days (P5 group, n = 517). The primary outcome was LBR; secondary outcomes included biochemical and clinical pregnancy rates, miscarriage rate, and neonatal outcomes (birth weight and gestational age at delivery). Generalized estimating equation (GEE) regression models were used to adjust for potential confounders. Subgroup analyses by PGT status and sensitivity analyses restricted to first FET cycles or good-quality blastocysts were also conducted.

The P6 group demonstrated a significantly higher LBR than the P5 group (33.87% [380/1,122] vs. 24.95% [129/517]; P < 0.001). After multivariable adjustment, the P6 regimen remained independently associated with increased LBR (adjusted odds ratio [aOR] 1.72; 95% CI 1.32–2.19; P < 0.001). Biochemical pregnancy (51.96% vs. 37.72%; aOR 2.10; 95% CI 1.64–2.62) and clinical pregnancy rates (46.52% vs. 33.66%; aOR 1.94; 95% CI 1.50–2.47) were also significantly higher with 6 days of progesterone priming. No significant differences were observed in miscarriage rates or neonatal outcomes between groups. Sensitivity analyses including restriction to first FET cycles, good-quality blastocysts, or stratification by blastocyst ploidy status did not alter the primary findings.

Extending progesterone exposure to 6 days before FET is associated with a significantly higher live birth rate compared with a 5-day protocol in transfers of vitrified–thawed Day 6 blastocysts. These findings warrant confirmation in prospective, large-scale randomized controlled trials.

Not applicable

The online version contains supplementary material available at 10.1186/s40834-026-00425-3.

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