Assisted reproductive technologies particularly the induction of ovulation, oocytes in vitro maturation, and prolonged embryo culture require in vitro manipulation of gamete and embryos at critical times of their maturation and development. In consequence, they may interfere with epigenetic reprogramming and affect particularly demethylation and remethylation of imprinted genes. To evaluate such a risk, we have determined the methylation profile of KvDMR1, the region that regulates KCNQ1OT1 imprinted gene, in human oocytes retrieved from stimulated or unstimulated cycles, at different phases of their maturation in vivo or in vitro. Our results show that the timing of establishment of the methylation profile of KvDMR1 covers the maturation phase of oocyte growth, in vivo and in vitro, and that hyperstimulation likely recruits young follicles epigenetically immature. Analysis of the methylation profile of H19DMR (DMR of IGF2/H19) in atypical ICSI embryos and corresponding sperm suggests that imprinting disorders are not responsible of embryo developmental failure prior the blastocyst stage.
