Imprinting disorders after assisted reproductive technologies.
To assess the evidence of an increased risk of imprinting diseases in children born after use of assisted reproductive technologies. Imprinting disorders occur when the epigenetic programming during gametogenesis is disturbed, or when this programming is not sufficiently sustained during the process of fertilization and early embryonic development. Ten case or case-reference reports have been published suggesting that compared with reference populations, a higher proportion of children with imprinting diseases were conceived by assisted reproductive technologies. These reports are inconsistent in linking the risk to a specific assisted reproductive technology, and a cytogenetic examination assessing the exact genetic imprinting mechanism was not always provided. Two national systematic follow-up studies on 6052 Danish and 16,280 Swedish in-vitro fertilization children found none and two children with imprinting diseases, respectively. These figures correspond approximately to the expected number of children with imprinting disease from the general population. The evidence of an increased risk of imprinting diseases in children conceived by assisted reproductive technologies is limited. The published case reports, however, call for a systematic multinational long-term follow-up of children born after assisted reproductive technologies.