What does this research mean for the field?

Progesterone luteal phase support does not improve live birth rates, clinical pregnancy rates, or pregnancy loss rates in modified natural cycle frozen embryo transfer. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This review assesses the effectiveness of progesterone luteal phase support during modified natural cycle frozen embryo transfer.

April 25, 2026Open Access

Luteal phase progesterone support in modified natural cycle frozen embryo transfer: a systematic review and meta-analysis

Key Points

This review assesses the effectiveness of progesterone luteal phase support during modified natural cycle frozen embryo transfer.
Systematic literature search identified eight eligible studies, seven included in meta-analysis.
Studies included three randomized controlled trials and four retrospective cohort studies.
Analysis comprised a total of 3,896 cycles.
Meta-analysis showed no difference in live birth rate between progesterone LPS and no LPS (OR 1.15, 95% CI 0.98-1.36).
Clinical pregnancy rate increased with LPS in crude analysis (OR 1.21, 95% CI 1.04-1.40), but not in adjusted analysis (aOR 1.15, 95% CI 0.87-1.51).
Pregnancy loss rate was similar between LPS and no LPS (OR 0.98, 95% CI 0.70-1.38).

Abstract

A modified natural cycle frozen embryo transfer (mNC-FET) using exogenous human chorionic gonadotropin (hCG) trigger is a widely used endometrial preparation protocol.The need for luteal phase support (LPS) in mNC-FET remains uncertain.The primary outcome of this systematic review and metaanalysis was the impact of progesterone LPS on live birth rates.Secondary outcomes included clinical pregnancy and pregnancy loss rates.A systematic literature search identified eight eligible studies, of which seven (three randomised controlled trials (RCT) and four retrospective cohort studies) were included in the meta-analysis, comprising 3,896 cycles.Five studies, including the three RCTs, found no benefit of progesterone LPS in mNC-FET.Using study-reported odds ratios (OR) and adjusted odds ratios (aOR), the meta-analysis showed no difference in live birth rate between progesterone LPS and no LPS (OR 1.15, 95% CI 0.98-1.36;aOR 1.07, 95% CI 0.64-1.79).Clinical pregnancy rate increased with LPS in the crude analysis (OR 1.21, 95% CI 1.04-1.40),but not in the adjusted analysis (aOR 1.15, 95% CI 0.87-1.51).Pregnancy loss rate was similar between LPS and no LPS (OR 0.98, 95% CI 0.70-1.38).These results do not support a general benefit of progesterone LPS in mNC-FET.Whether certain subgroups require an individualised approach remains to be determined.

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