PERSPECTIVE: Cryopreservation of Human Oocytes and the 'Carryover' Effect on Early Embryo Development

Worldwide women are increasingly facing the issue of delayed child-bearing and fertility decline. Oocyte cryopreservation provides an option for fertility preservation, especially for women with diseases and other special needs to conceive babies later. In this review we examine the effect of oocyte cryopreservation on early development of human embryos. Databases (Medline, PubMed and Web of Science) were searched for relevant clinical studies published between 1999 and 2020. A total of 27 studies on oocyte cryopreservation and embryo development were identified, and data in those studies are retrieved for meta-analysis on the outcomes of oocyte survival, fertilization and early embryo development. In comparison to the slow freezing technique, vitrification yields significantly better oocyte survival (84.7% ± 0.6% vs 58.0% ± 0.5%), and subsequently higher rates of fertilization (65.5% ± 0.9% vs 40.0% ± 0.6%), cleavage (58.8% ± 0.9% vs 34.6% ± 0.8%), as well as embryo implantation (5.9% ± 0.3% vs 2.9% ± 0.2%). This analysis reveals a negative 'carryover' effect of oocyte cryopreservation on early development of embryos after oocyte fertilization (i.e., cleavage and implantation). This 'carryover' effect is greater for slowly-frozen oocytes than for vitrified oocytes, and may represent subtle functional or molecular alterations that are not severe enough to affect cell survival and fertilization, but sufficient to impair later development. The nature of the 'carryover' effect is unknown. Hypothermia, membrane ion channels, bioenergy metabolism and epigenetic modifications are likely involved. In conclusion, oocyte cryopreservation can negatively affect early development of human embryos. Future studies should go beyond oocyte survival and look further into the effects on epigenetic changes.