Extended embryo culture has brought many benefits to ART (assisted reproduction technologies). However, it is difficult to establish a culture system that mimics physiological conditions completely, and there is concern that artificial conditions could affect human development. Epigenetic modifications, such as DNA methylation, alter gene functions without mutations of gene sequences and are essential mechanisms for normal human development. For example, aberrant DNA methylation patterns (epimutations) actually cause some congenital anomaly syndromes. Since DNA methylation is a reversible chemical modification, it has been shown experimentally that epimutations can be introduced into embryos by environmental conditions. Several reports have suggested that ART may lead to epimutations in children and cause developmental defects. Detailed epidemic and biological studies of the relations among all these events are necessary.