Comparative effectiveness of luteal phase support strategies in natural cycle frozen-thawed embryo transfer: a systematic review and network meta-analysis

Luteal phase support (LPS) may improve pregnancy outcomes in natural cycle frozen-thawed embryo transfer (NC-FET), though the comparative effectiveness of different regimens remains uncertain. This network meta-analysis (NMA) was conducted as an exploratory synthesis.

A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted through March 2026. We performed pairwise meta-analyses using Review Manager 5.3 and exploratory network meta-analyses with Stata 14.0. We assessed certainty of evidence using the CINeMA framework.

Twenty studies (8 RCTs, 12 retrospective studies) were included. Pairwise meta-analyses suggested LPS was associated with improved clinical pregnancy rate (CPR) and live birth rate (LBR) compared with no LPS, with no apparent increase in miscarriage rate (MR). The RCT-only NMA could not be performed because the network was disconnected, with no closed loops among the 8 RCTs, reflecting the current lack of head-to-head randomized evidence for LPS regimen selection in NC-FET. In the exploratory full-network analysis, VP + triptorelin + hCG showed a relatively high surface under the cumulative ranking curve (SUCRA) for CPR, and VP + triptorelin for LBR.

LPS was associated with improved pregnancy outcomes in NC-FET. The RCT-only network was too sparse to support valid rankings. While VP + triptorelin ( ± hCG) showed relatively high SUCRA values for CPR and LBR, the very low certainty of evidence precludes definitive conclusions.