Systematic review and Meta-analysis of the impact of the re-freezing and re- biopsy embryos on reproductive outcomes in patients undergoing freeze-thaw embryo transfer.

Abstract

Importance: During FET cycles in IVF/ICSI patients (including PGT patients), transfer of embryos that have been thawed may be abandoned for medical or personal reasons, resulting in the need to refreeze embryos. Typically, embryos from patients undergoing preimplantation genetic testing (PGT) are cryopreserved after biopsy, pending test results. However, in the absence of a clear result, another biopsy is required and the embryo is frozen again to await the results for future use.

Objective: To explore whether refreezing and re-biopsy affect reproductive outcomes DATA SOURCES: Computer search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, CBM, CNKI, WanFang Data, and VIP databases and searched until May, 2023.

Study selection and synthesis: STATA/MP software was utilized for conducting data analysis. Dichotomous outcome data were pooled to calculate odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). Continuous outcome data were combined using an inverse variance model to determine the mean difference (MD) between the two groups. Random-effects and fixed-effects meta-analysis models were employed to assess heterogeneity. Subgroup analysis was conducted based on different freezing methods and various embryo types.

Main outcomes: The primary outcome measure was the live birthrate, with secondary indicators including clinical pregnancy rate, implantation rate, miscarriage rate, ectopic pregnancy, preterm delivery, average birth weight of neonates, and neonatal malformation.

Results: This study included 19 retrospective studies with a total of 11,024 FET cycles. Across the FET cycles, re-cryopreservation, compared to once-cryopreservation demonstrated reduced live birthrates (OR=0.79; 95% CI: 0.60 to 0.92; I²=21.7%, P=0.000), reduced clinical pregnancy rates (OR=0.74; 95% CI: 0.60 to 0.92, I²=56.9%, P=0.006), and increased miscarriage rates (OR=1.27; 95% CI: 1.03 to 1.55, I²=37.1%, P=0.024). Pregnancy outcomes following re-biopsies, revealing significantly lower live birth rates after re-biopsies compared with single biopsy (OR = 0.65; 95%CI: 0.45 to 0.94, I²=43.5%; P=0.024). Similarly, re-biopsies were associated with reduced clinical pregnancy rates (OR = 0.75; 95%CI: 0.54 to 1.03, I²=29.6%) and increased miscarriage rates (OR= 1.54; 95%CI: 0.89 to 2.66, I²=13.0%) compared to single-biopsy.

Conclusion and relevance: Re-frozen embryos compared to once-frozen embryos suggests a decrease in live birth rates and clinical pregnancy rates, coupled with an increase in miscarriage rates, with negligible influence on neonatal outcomes. Similarly, re-biopsy yields comparable results, leading to a reduction in live birth rates.