Perinatal outcomes of frozen-thawed embryo transfer following blastocyst-stage embryo transfer compared to those of cleavage-stage embryo transfer: analysis of 9408 singleton newborns using propensity score analysis

Objective: Regarding frozen-thawed embryo transfer (FET), there is limited consensus on whether extending embryo culture from the cleavage stage to the blastocyst stage affects perinatal outcomes. This study aimed to compare perinatal outcomes of singletons between blastocyst-stage embryo transfer (BT) and cleavage-stage embryo transfer (CT) in FET.Methods: A total of 9408 FET cycles that met the inclusion criteria were included in this retrospective cohort study between 2019 and 2022. Blastocyst-stage embryo transfers were performed in the BT group, and cleavage-stage embryo transfers were performed in the CT group. Multivariate logistic regression analyses were performed, as well as propensity score matching (PSM) to adjust for confounders.Results: After PSM, a higher risk of pre-term birth (PTB; odds ratio [OR]: 1.23, 95% confidence interval [CI]: 1.00-1.50,P = 0.048) and being large for gestational age (LGA;OR: 1.16, 95%CI: 1.00-1.35,P = 0.050) was observed in the BT group compared to that in the CT group. After stratified PSM, in the subgroup under 35 years of age, only an increased risk of LGA was observed in the BT group compared to the CT group. Perinatal outcomes in the double-embryo transfer subgroup were similar to those in the unstratified group. However, in the subgroup beyond 35 years of age and the single embryo transfer subgroup, perinatal outcomes were not statistically different between the BT and CT groups (P >0.05).Conclusions: In FET, prolonged embryo culture to the blastocyst stage increased the risk of PTB and LGA in single fetuses. However, stratified analysis based on age and the number of transferred embryos yielded different results, necessitating further mechanistic studies.