Assisted Reproductive Technology and Epigenetics

Abstract

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.

<p>Comparative Pharmacokinetics, Bioequivalence and Safety Study of Two Recombinant Human Chorionic Gonadotropin Injections in Healthy Chinese Subjects</p>

“…Assisted Reproductive Technology (ART) refers to the technology of using medical assistance for treating infertility, including in vitro fertilization-embryo transfer (IVF-ET), intracytoplasmic sperm injection (ICSI), embryo culture, and embryo cryopreservation. 1 Controlled ovarian hyperstimulation (COH) is the first stage of IVF-ET technology which requires the administration of gonadotropins such as gonadotropin-releasing hormone agonists (GnRHa), recombinant follicle-stimulating hormone (r-FSH) and human chorionic gonadotropin (hCG) to induce the maturation of a large number of follicles. 2 hCG, a heterodimer glycoprotein composed of αand βsubunits secreted by placental trophoblast cells, acts like a superagonist of luteinizing hormone (LH).…”

Bilateral Retinoblastoma Presenting in an in vitro Fertilization Infant with Retinopathy of Prematurity

“…Our case represents the second case of RB occurring with ROP in an infant conceived by IVF [ 5 ], raising the possibility that IVF may predispose to RB; indeed, IVF has been suggested to cause epigenetic abnormalities in offspring that predispose to various diseases [ 7 , 16 ]. Although the literature is sparse, there is some evidence to suggest that IVF increases the risk of RB [ 17 , 18 ], although several studies have failed to find this association, including in large population-based studies [ 19 , 20 ].…”

Epigenetic Mechanisms of ART-Related Imprinting Disorders: Lessons From iPSC and Mouse Models

“…The prevalence of BWS in naturally conceived children is estimated to range from 1 in 13,700 to 1 in 287,000 live births [15]. Conversely in ART populations it has been demonstrated to be as high as 1 in 1126 live births in one USA-based study [16], although varying results have been described in other countries, with some reporting no association between ART and BWS [17].…”