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

Modified natural cycle frozen embryo transfer (mNC-FET) using an exogenous human chorionic gonadotrophin (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 meta-analysis was the impact of progesterone LPS on the live birth rate (LBR). Secondary outcomes included clinical pregnancy rate (CPR) and pregnancy loss rate (PLR). A systematic literature search identified eight eligible studies, of which seven [three randomized controlled trials (RCT) and four retrospective cohort studies] were included in the meta-analysis, comprising 3896 cycles. Five studies, including the three RCT, found no benefit of progesterone LPS in mNC-FET. Using study-reported OR and adjusted OR (aOR), the meta-analysis showed no difference in LBR between progesterone LPS and no LPS (OR 1.15, 95% CI 0.98-1.36; aOR 1.07, 95% CI 0.64-1.79). CPR 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). PLR 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. It remains to be determined whether certain subgroups require an individualized approach.