Time to reconsider who the freeze-all approach benefits: a matched cohort analysis of over 9000 embryo transfers

Research question: Is a fresh embryo transfer superior to a frozen embryo transfer after a freeze-all approach in achieving a live birth in IVF cycles?

Design: A retrospective matched analysis of 9923 autologous oocyte retrievals and 9716 embryo transfers performed between 2016 and 2023 at a single UK centre was undertaken. Patients underwent a fresh transfer or the decision was made to freeze all embryos. First embryo transfer outcomes from each cycle were assessed, and a separate analysis was undertaken to assess the hazard ratio of live birth across multiple embryo transfers arising from a single oocyte retrieval, with 1664 cumulative live births after 4202 fresh transfer cycles and 1354 cumulative live births after 2312 freeze-all embryo cycles.

Results: No difference in the odds of live birth was seen when stratifying by age. Among low responders (fewer than six oocytes), fresh and first frozen embryo transfers demonstrated comparable live birth rates [adjusted OR (aOR) 1, 95% CI 0.7–1.5; 26% versus 27%; P = 1]. In high responders (≥16 oocytes) and high-embryo-yield cycles (five embryos or more), higher outcomes were observed in fresh transfers, but the difference was non-significant. Low-embryo-yield cycles (fewer than three embryos) were associated with significantly improved outcomes after a freeze-all approach controlled for embryo quality (aOR 1.6, 95% CI 1.2–2.1; 38% versus 29%; P = 0.02), with potential greater benefit for patients aged ≥38 years. In transfers of suboptimal-grade embryos, the freeze-all approach was associated with a 2-fold increase in the odds of live birth in patients aged <38 years, but this lost significance after correction. Cumulatively, while a higher live birth rate was observed for fresh cycles compared with freeze-all cycles in patients aged <38 years, overall there was no significant difference in the live birth rate per cycle.

Conclusions: A freeze-all approach may improve outcomes in low-embryo-yield cycles and in younger patients with suboptimal-grade embryos, but confirmatory analyses are required.