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Assisted Reproductive Technology: Cautionary Signs

17 August 2004: Every day we are directed to proceed slowly by a variety of cautionary signs. Recently, a series of articles suggest that we may also need to proceed with greater caution when employing assisted reproductive technologies (ARTs). These studies show that children conceived with ART have lower birth weights, and a higher incidence of juvenile tumors (Schieve et al., Obstet. Gynecol. 103: 1154-1163, 2004; Gosden et al., Lancet 361: 1975-1977, 2003). They also have an increased frequency of Beckwith-Weidemann and Angelman syndromes because of imprinting defects rarely seen in children conceived naturally (Niemitz and Feinberg, Am. J. Hum. Genet. 74: 599-609, 2004; Gosden et al., Lancet 361: 1975-1977, 2003). Genomic imprinting is a phenomenon in which an autosomal gene is expressed from only one copy in a parent-of-origin dependent manner (Murphy and Jirtle, BioEssays 25: 577-588, 2003). Moreover, imprinting deregulation in animal models increases the incidence of developmental and behavioral disorders (Murphy and Jirtle, BioEssays 25: 577-588, 2003).

Although the incidence of Beckwith-Wiedemann and Angelman syndromes in children conceived with ART is above normal, its frequency is still relatively low (Gibson, Obstet. Gynecol. 103: 1142-1143, 2004). Nevertheless, there is mounting concern that environmentally-induced epigenetic modifications of the genome in early development could result in a much greater spectrum of complications than presently appreciated (Maher et al., Hum. Reprod. 18: 2508-2511, 2003). For example, maternal dietary-induced epigenetic modifications early in mouse development can result in increased susceptibility to adult chronic diseases including cancer, obesity, and diabetes (Waterland and Jirtle, Mol. Cell. Biol. 23: 5293-5300, 2003). The Dutch famine studies provide evidence that humans may also respond in a similar manner to dietary perturbations while in utero (Barker, Med. Health Care. Philos. 4: 31-35, 2001). Therefore, it is important to determine if the increased reproductive complications observed with the use of ART are a direct consequence of the procedures employed, and/or occur because of the inherent fertility problems that first brought the patients to the clinic (Marques et al., Lancet 363: 1700-1702, 2004).