Implications of epigenetics and genomic imprinting in assisted reproductive technologies

There have been several reports of an increased risk of genomic imprinting disorders associated with assisted reproductive technology (ART). However, the connection between imprinting defects and ART is tenuous. In this review, this putative association is investigated in detail, with emphasis on particular steps of the ART process, and which of these may be prone to induction of imprinting errors due to synchrony with major imprinting events during gametogenesis, fertilization, and early embryonic development. While contributions from in vitro manipulation of gametes and embryos cannot be ruled out, it appears that superovulation and/or the condition of infertility, itself, may be largely responsible for the increased risk of genomic imprinting disorders observed with ART births. However, two significant shortcomings of all of these studies preclude rigorous exploration of this issue: the lack of large, longitudinal studies on specific cohorts of ART-conceived children, and questions surrounding the primary generation of expression and epigenetic data from oocytes and embryos. Future directions for study are proposed, along with a preview of what may be in store as the art of ART advances.