Insights gained from a cleavage-stage embryo freeze-all policy in in vitro maturation cycles

Cycles of in vitro maturation (IVM) of oocytes show asynchrony between embryo development and endometrial receptivity. Hence, elective embryo vitrification/warming (V/W) for embryo transfer (FET) is routinely performed. However, clinical outcomes after IVM are lower compared to conventional ovarian stimulation, mainly due to lower embryo quality. Vitrification at cleavage stage, rather than blastocyst stage, is used to optimize embryo utilization while maintaining acceptable pregnancy rates. The aim of this study is to ascertain the vulnerability to V/W of IVM-derived cleavage-stage embryos and to identify characteristics that predict pregnancy.

In this single-center retrospective cohort study, 442 day-3 IVM-derived embryos from PCOS patients were investigated. Cell survival upon warming, cell cycle progression during overnight culture and clinical outcome in 425 FET cycles were analyzed.

From 442 V/W embryos, 85% were fully intact. Cell loss reduced the cell cycle progression after overnight culture of V/W embryos (p = 0.047) and tended to lower clinical pregnancy rates (16% vs 23%, p = 0.22) compared to intact embryos. Better fresh embryo quality was associated with enhanced cell cycle resumption after overnight culture (p < 0.0001). Cell cycle resumption was required for pregnancy to occur. Additionally, the extent of cell cycle progression (OR = 0.439, CI = 0.24-0.78, p < 0.001) and the number of available top-quality embryos (OR = 0.174, CI = 0.04-0.32, p = 0.01) were indicative for success.

A clinical pregnancy rate of 23% per FET with V/W IVM-derived cleavage-stage embryo was obtained with cell cycle resumption after overnight culture as dominant predictive factor.