Systematic review and meta-analysis of the impact of the refreezing and rebiopsy embryos on reproductive outcomes in patients undergoing freeze-thaw embryo transfer.

Abstract

Importance: During frozen-thawed embryo transfer (FET) cycles in in vitro fertilization/intracytoplasmic sperm injection patients (including preimplantation genetic testing 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 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 rebiopsy 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 used 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 between the two groups. Random-effects and fixed-effects meta-analysis models were employed to assess heterogeneity. Subgroup analysis was conducted on the basis of different freezing methods and various embryo types.

Main outcomes: The primary outcome measure was the live birth rate (LBR), with secondary indicators including clinical pregnancy rate (CPR), implantation rate, miscarriage rate (MR), ectopic pregnancy, preterm delivery, mean 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, recryopreservation, compared with once-cryopreservation, demonstrated reduced LBRs (OR, 0.79; 95% CI, 0.60 -0.92; I² = 21.7%), reduced CPRs (OR, 0.74; 95% CI, 0.60 -0.92; I² = 56.9%), and increased MRs (OR, 1.27; 95% CI, 1.03 -1.55; I² = 37.1%). Pregnancy outcomes after rebiopsies, revealing significantly lower LBRs after rebiopsies than after single biopsy (OR, 0.65; 95% CI, 0.45 -0.94; I² = 43.5%). Similarly, rebiopsies were associated with reduced CPRs (OR, 0.75; 95% CI, 0.54 -1.03; I² = 29.6%) and increased MRs (OR, 1.54; 95% CI, 0.89 -2.66; I² = 13.0%) compared with single biopsy.

Conclusion and relevance: Refrozen embryos compared with once-frozen embryos suggest a decrease in the LBRs and CPRs, coupled with an increase in the MRs, with negligible influence on neonatal outcomes. Similarly, rebiopsy yields comparable results, leading to a reduction in the LBRs.