DeAngelis Anthony M, Martini Anne E, Owen Carter M
Reproductive Biology and Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Colorado Center for Reproductive Medicine Northern Virginia, Vienna, Virginia.
Semin Reprod Med. 2018 May;36(3-04):221-232. doi: 10.1055/s-0038-1675780. Epub 2019 Mar 13.
Assisted reproductive technology (ART) is responsible for 1.7% of births in the United States annually. Despite a large number of studies promoting the efficacy and safety of these practices, there have been reports of imprinting disorders occurring at higher frequencies in children born through ART. Driven by findings in animal studies, it has been postulated that various ART procedures employed at critical points in embryonic development may predispose the genomic imprinting process to errors. Alterations in DNA methylation patterns at imprinting control centers have been reported by some studies to occur more frequently in children with imprinting disorders conceived by ART compared with spontaneous conception, though these findings are not consistently demonstrated and controversy has surrounded the strength of these associations. The rarity of imprinting disorders with a reliance of studies on disease registry cohorts, wide variations in ART protocols, and a lack of proper control groups limit the ability to substantiate associations between imprinting disorders and ART. Large, prospective cohort studies with a focus on molecular etiologies of these conditions are needed to discern whether a true association exists. Based on current evidence, the absolute risk of imprinting disorders after ART is low and screening for imprinting disorders in children conceived by ART is not warranted.
辅助生殖技术（ART）在美国每年的出生人口中占1.7%。尽管有大量研究宣传这些技术的有效性和安全性，但有报道称，通过ART出生的儿童中，印记紊乱的发生率更高。受动物研究结果的驱动，有人推测在胚胎发育的关键阶段采用的各种ART程序可能会使基因组印记过程更容易出现错误。一些研究报告称，与自然受孕相比，通过ART受孕且患有印记紊乱的儿童中，印记控制中心的DNA甲基化模式改变更为频繁，不过这些发现并未得到一致证实，而且这些关联的强度也一直存在争议。印记紊乱罕见，研究依赖疾病登记队列，ART方案差异很大，且缺乏合适的对照组，这些都限制了证实印记紊乱与ART之间关联的能力。需要开展大型前瞻性队列研究，重点关注这些疾病的分子病因，以确定是否真的存在关联。根据目前的证据，ART后发生印记紊乱的绝对风险较低，因此没有必要对通过ART受孕的儿童进行印记紊乱筛查。
