Time to re-evaluate ART protocols in the light of advances in knowledge about methylation and epigenetics: an opinion paper.

DNA methylation is a biochemical process that modifies gene expression without changing the underlying DNA sequence, and this represents the molecular basis for imprinting and epigenetics. Recent reports have revealed alterations in DNA methylation profiles in the placenta of babies born from assisted reproductive technologies (ART). This supports several previous observations that suggested an increase in the prevalence of imprinting diseases following ART treatment, and also fits our observations regarding the metabolism and requirements of early human embryos. Human embryo culture media (HECM) are currently formulated according to requirements based on the mouse embryo model, and in fact need to pass the Mouse Embryo Assay test in order to be accepted by the relevant authorities, despite the fact that physiological (especially the time necessary to reach genomic activation) and biochemical requirements of mouse and human embryos are quite different. This commentary aims to explain some of the discrepancies, and emphasize why human embryo metabolism tells us that the composition of HECM, as well as the role of the MEA as a unique model, should be re-evaluated.