Comparative effectiveness of luteal phase support strategies in natural cycle frozen-thawed embryo transfer: a systematic review and network meta-analysis.
Luteal phase support may improve pregnancy outcomes in natural cycle frozen-thawed embryo transfer, but the evidence is not strong enough to make definitive recommendations.
Where it sits
this study against the rest of the triptorelin corpusSummary and findings
This study evaluated the effectiveness of luteal phase support (LPS) strategies in natural cycle frozen-thawed embryo transfer (NC-FET). It included data from twenty studies, with a focus on clinical pregnancy rates (CPR) and live birth rates (LBR). The findings suggest LPS may improve outcomes compared to no LPS, but definitive conclusions are limited by the quality of evidence.
Abstract
<h4>Aim</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.
Background
This paper addresses the clinical question of how different luteal phase support (LPS) strategies affect pregnancy outcomes in natural cycle frozen-thawed embryo transfer (NC-FET). Previous studies have indicated that LPS may improve outcomes, but the comparative effectiveness of various regimens remains unclear. This systematic review and network meta-analysis aim to synthesize existing evidence to inform clinical practice.
Methods
A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted through March 2026. The analysis included 20 studies, comprising 8 randomized controlled trials (RCTs) and 12 retrospective studies. Pairwise meta-analyses and exploratory network meta-analyses were performed using Review Manager 5.3 and Stata 14.0, respectively.
Results
The analysis suggested that LPS was associated with improved clinical pregnancy rates and live birth rates compared to no LPS, with no significant increase in miscarriage rates. However, the RCT-only network was disconnected, limiting the ability to perform valid rankings among LPS regimens. In the exploratory full-network analysis, VP + triptorelin + hCG showed a relatively high surface under the cumulative ranking curve (SUCRA) for clinical pregnancy rate.
Interpretation
The findings suggest a potential benefit of LPS in improving pregnancy outcomes, but the low certainty of evidence and disconnected RCT network limit the strength of these conclusions. The effect sizes observed may not be clinically meaningful given the uncertainty. Practitioners should be cautious in interpreting these results due to the methodological limitations and the lack of robust head-to-head evidence.
Key findings
- LPS associated with improved clinical pregnancy rate (CPR) and live birth rate (LBR) compared with no LPS.
- No apparent increase in miscarriage rate (MR) with LPS.
- RCT-only network was disconnected, preventing valid rankings among LPS regimens.
- VP + triptorelin + hCG showed relatively high surface under the cumulative ranking curve (SUCRA) for CPR.
- VP + triptorelin showed relatively high SUCRA values for LBR.
- Very low certainty of evidence precludes definitive conclusions.
Limitations
- Low certainty of evidence.
- RCT-only network was disconnected.
- Includes retrospective studies.
- No closed loops among RCTs.
- Exploratory analysis with limited definitive conclusions.