Abstract
BACKGROUND: Repeated cryopreservation of embryos in frozen-thawed embryo transfer (FET) has raised concerns regarding its impact on pregnancy outcomes. This study aimed to reveal the association between repeated cryopreservation by vitrification and FET outcomes, and to identify factors influencing these outcomes. METHODS: A single-center retrospective cohort study was conducted, analyzing 13,624 FET cycles (from 2018 to 2022) involving embryos with cryopreservation or repeated cryopreservation. Propensity score matching was employed in this study. The primary outcome was clinical pregnancy rate (CPR) while live birth rate (LBR), miscarriage along with neonatal outcomes were also assessed. Multivariate logistic regression and stratified analyses were used to explore the effect of female age and the quality of embryo on CPR after adjusting for confounders. RESULTS: In total, 321 FET cycles met the inclusion and exclusion criteria were included after matching and divided into re-cryopreservation group (n = 107) and cryopreservation group (n = 214). The re-cryopreservation group showed lower CPR (27.10% vs. 45.33%; aOR, 0.48; 95% CI 0.28-0.84) and LBR (18.69% vs. 38.32%; aOR, 0.35; 95% CI 0.19-0.65), with no differences in miscarriage or biochemical pregnancy rates. Stratified analyses revealed an adverse effect of women aged < 35 years (aOR, 0.40; 95% CI 0.19-0.83) and single-embryo transfers (aOR, 0.51; 95% CI 0.28-0.94) on CPR while transfer of good quality embryos reduced these effects (aOR, 0.55; 95% CI 0.21-1.44). Gestational age, birthweight and congenital anomalies proportion were not significantly different between the two groups. CONCLUSIONS: Repeated cryopreservation was associated with reduced clinical pregnancy and live birth rates, particularly in younger patients. The neonatal outcomes were potentially not affected. Clinicians may consider limiting repeated cryopreservation for women under 35 years and prioritize good-quality embryos for re-vitrification when medically justified. These findings underscored the need for tailored strategies in FET cycles involving re-cryopreserved embryos.