A Cross-Sectional Analysis of Live Birth Rates in Day 5 Fresh Versus Vitrified Single Blastocyst Transfer Cycles

Abstract

Background: The use of frozen embryo transfers (FETs) in assisted reproduction has increased worldwide. Proponents of FETs suggest that controlled ovarian hyperstimulation (COH) in a fresh transfer impairs endometrial-embryo synchronicity, however there has been conflicting evidence on live birth rate (LBR) and clinical pregnancy rate (CPR) outcomes. Aim: To compare LBRs and CPRs between single autologous day 5 fresh versus vitrified blastocyst transfer cycles, in order to investigate the impact of COH on embryo-endometrium asynchrony. Method: A large cross-sectional analysis of 6,002 embryo transfers (ETs), comprising of 3774 fresh and 2228 FET cycles from 2016-2019. Inclusion criteria: first two stimulation cycles, single ET, and no pre-implantation genetic testing for aneuploidy (PGT-A). Multivariate analysis performed, also sub-group analysis for high-responders (>20 oocytes collected). Results: Univariate analysis showed no absolute difference in LBR (28.3% vs 27.4%, p=0.43) and CPR (32.2% vs 30.9%, p=0.30), however multivariate analysis demonstrated significantly lower LBR (OR 0.864, p<0.05, 95% CI 0.749-0.997) and CPR (OR 0.852, p<0.05, 95% CI 0.742-0.979) in FET compared to fresh ETs. Younger patient age, previous IVF pregnancy, advanced blastocyst expansion, higher trophectoderm quality and lower cumulative number of ETs all improved the odds of both LBR and CPR (p<0.001). Conventional IVF, rather than ICSI, improved CPR (p<0.05) but not LBR (p=0.138). BMI affected neither LBR (p=0.492) nor CPR (p=0.359). In sub-group multivariate analysis of high-responders, no significant difference in LBR (p=0.439) or CPR (p=0.450) noted. Conclusion: This study demonstrates a relative higher LBR and CPR for fresh ETs compared to FETs, in multivariate analysis. Having a FET decreased the odds of LBR by nearly 14% compared to fresh ET, when adjusted for confounders. Our results suggest that universal freeze-all strategy, without appropriate indication, may lead to suboptimal outcomes. In high-responders, freeze-all cycles may be beneficial, as adjusted outcomes appear to be similar.