Outcomes of Single Blastocyst Transfer Versus Double Cleavage-Stage Embryo Transfer in Young Women with Recurrent Implantation Failure: A Secondary Analysis of a Multicenter Randomized Trial.

Objectives: Although blastocyst transfer may improve embryo selection and early pregnancy outcomes, its impact on live birth in women with recurrent implantation failure (RIF) remains uncertain. This study compared reproductive and perinatal outcomes between single blastocyst transfer (SBT) and double cleavage-stage embryo transfer (DET) among women younger than 38 years with RIF. Methods: Secondary observational analysis of a multicenter, randomized, double-blind, placebo-controlled clinical trial conducted across eight academic fertility centers in China. In the original trial, patients with RIF under 38 years of age were enrolled and randomized to receive either prednisone or placebo. For the present analysis, a total of 582 patients were categorized according to the embryo transfer strategy. The SBT-versus-DET comparison was not randomized, and the two strategies differed in both embryo developmental stage and number of embryos transferred. Results: No statistically significant difference in live birth rate was observed between the SBT and DET groups (41.8% vs. 38.4%; p = 0.471), despite a higher biochemical pregnancy rate in the SBT group (59.9% vs. 45.7%, p = 0.003). Pregnancy loss was more frequent in the SBT group than in the DET group (30.2% vs. 15.9%; p = 0.018), particularly biochemical pregnancy loss (15.5% vs. 5.8%; p = 0.036), whereas twin live birth was less frequent (0.7% vs. 9.9%; p < 0.001). After adjustment, no significant difference in live birth rate was observed between DET and SBT (adjusted OR 1.04, 95% CI 0.68-1.57). In addition, Day 5 SBT showed a higher live birth rate than Day 6 SBT, whereas pregnancy loss rates were similar between Day 5 and Day 6 SBT cycles. Other exploratory sensitivity and stratified analyses showed broadly consistent findings. Conclusions: Although SBT is generally preferred in clinical practice, our study found no statistically significant difference in live birth rates between SBT and DET among women younger than 38 years with RIF. Given that pregnancy loss was observed more frequently in the SBT group, whereas twin live births were less frequent, our findings support individualized counseling rather than uniform use of either transfer strategy. However, given the non-randomized nature of this comparison, these findings should be interpreted with caution.