Live birth outcomes after cleavage-stage (day 3) versus blastocyst-stage (day 5) embryo transfer in IVF/ICSI cycles: a systematic review

Background: The optimal timing of embryo transfer in IVF/ICSI is controversial. Although blastocyst transfer improve fresh-cycle success through embryo selection, its effect on cumulative live birth rate (CLBR) is uncertain. In this study we aimed to compare live birth outcomes after Day 3 cleavage-stage versus Day 5 blastocyst-stage embryo transfer in IVF/ICSI cycles. Methods: A PRISMA-guided systematic review was conducted using PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Eligible studies included women undergoing fresh or frozen-thawed IVF/ICSI cycles comparing Day 5/6 blastocyst transfer with Day 2/3 cleavage-stage transfer. Results: Seven studies were included. In women with a good prognosis blastocyst transfer was associated with higher live birth rates in fresh cycles. Recent large studies showed no significant difference in CLBR between blastocyst and cleavage-stage policies. In women with four or fewer zygotes, blastocyst transfer provided no advantage, while cleavage-stage quality is a predictive of success among transferred blastocysts. Conclusion: Blastocyst transfer benefit good-prognosis patients, but it does not improve cumulative live birth outcomes in IVF/ICSI populations. Embryo transfer timing should be individualized, with cleavage-stage transfer favored in patients with low embryo yield to reduce cycle cancellation risk.