Somjate Manipalviratn1, Alan DeCherney, James Segars. 1. Reproductive Biology and Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract
OBJECTIVE: To review currently available literature on the association between imprinting disorders (Beckwith-Wiedemann syndrome [BWS], Angelman syndrome [AS] and retinoblastoma) and assisted reproductive technology (ART) in humans. DESIGN: Publications related to imprinting/epigenetic disorders including BWS, AS, and retinoblastoma with ART, as well as articles publishing outcome of ART, including IVF and ICSI from July 1978 to February 2008, were identified using PubMed, Medline, and EMBASE. RESULT(S): Considerable evidence in animal studies has demonstrated alteration in gene imprinting of embryos cultured in vitro. Publications from Europe, the United States, and Australia have suggested an association between ART and BWS. Importantly, more than 90% of children with BWS that were born after ART had imprinting defects, compared with 40%-50% of children with BWS and conceived without ART. Moreover, there have been other reports suggesting an association between AS and ART. The majority of children with AS born after ART had an imprinting defect as the underlying etiology, specifically loss of methylation of the maternal allele. There was a single report suggesting an increased incidence of retinoblastoma in children conceived with ART. CONCLUSION(S): Because the absolute incidence of imprinting disorders is small (<1:12,000 births), routine screening for imprinting disorders in children conceived by ART is not recommended. Additional large cohort studies of children born after ART are needed to determine whether there is a genuine association between ART and imprinting disorders.
OBJECTIVE: To review currently available literature on the association between imprinting disorders (Beckwith-Wiedemann syndrome [BWS], Angelman syndrome [AS] and retinoblastoma) and assisted reproductive technology (ART) in humans. DESIGN: Publications related to imprinting/epigenetic disorders including BWS, AS, and retinoblastoma with ART, as well as articles publishing outcome of ART, including IVF and ICSI from July 1978 to February 2008, were identified using PubMed, Medline, and EMBASE. RESULT(S): Considerable evidence in animal studies has demonstrated alteration in gene imprinting of embryos cultured in vitro. Publications from Europe, the United States, and Australia have suggested an association between ART and BWS. Importantly, more than 90% of children with BWS that were born after ART had imprinting defects, compared with 40%-50% of children with BWS and conceived without ART. Moreover, there have been other reports suggesting an association between AS and ART. The majority of children with AS born after ART had an imprinting defect as the underlying etiology, specifically loss of methylation of the maternal allele. There was a single report suggesting an increased incidence of retinoblastoma in children conceived with ART. CONCLUSION(S): Because the absolute incidence of imprinting disorders is small (<1:12,000 births), routine screening for imprinting disorders in children conceived by ART is not recommended. Additional large cohort studies of children born after ART are needed to determine whether there is a genuine association between ART and imprinting disorders.
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