DNA METHYLATION DIFFERENCES BETWEEN CHILDREN CONCEIVED IN VITRO AND IN VIVO ARE ASSOCIATED WITH ART PROCEDURES

Abstract

Epidemiological data indicate that children conceived in vitro have a greater relative risk of low birth-weight, major and minor birth defects, and rare disorders involving imprinted genes, suggesting that epigenetic changes may be associated with assisted reproduction. DNA methylation and gene expression differences have been found in cord blood and placenta comparing children conceived in vitro using assisted reproductive technology (ART) and children conceived in vivo. The source of these differences (the effect of ART versus underlying infertility) has never been identified in humans. In order to determine what fraction of the DNA methylation and gene expression difference is attributable to the ART procedure and what fraction is attributable to underlying infertility, quasi-transcriptome-wide DNA methylation profiles were compared between (1) in vitro ART children of mothers who are infertile as a result of a physical impediment to fertilization (tubal blockage) or children conceived with the aid of donor oocytes as a group (tubal and donor egg group), and (2) children of parent(s) who have idiopathic infertility (infertility group). Both groups were compared to children conceived in vivo. Our data suggest strongly that many of the DNA methylation and gene expression differences observed between the in vitro and in vivo conceptions are associated with some aspect of ART procedure, rather than underlying infertility.