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Semin Reprod Med 2009; 27(5): 417-428
DOI: 10.1055/s-0029-1237430
Published in 2009 by Thieme Medical Publishers

Imprinting Disorders and Assisted Reproductive Technology

Carter M. Owen1 , 2 , James H. Segars1
  • 1Reproductive Biology and Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
  • 2Clinical Research Training Program, National Institutes of Health, Clinical Center, Bethesda, Maryland
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Publication History

Publication Date:
26 August 2009 (online)

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ABSTRACT

Worldwide use of assisted reproductive technology (ART) accounts for an estimated 1 to 3% of births. Since 2002, a series of reports have suggested an increased risk of imprinting disorders (Beckwith-Wiedemann syndrome and Angelman syndrome) in children conceived by ART. Definitive conclusions are difficult to substantiate due to the rarity of imprinting disorders and the variability in ART protocols. Despite these limitations, there is biological plausibility for alteration in nongenomic inheritance caused by ART. Animal studies have shown that ART procedures can alter normal imprinting, specifically DNA methylation patterns. Collectively, studies suggest an association between ART and loss of maternal methylation. More recent reports examined a possible association between ART and global hypomethylation of DNA. Three other imprinting disorders (Silver-Russell syndrome, maternal hypomethylation syndrome, and retinoblastoma) have also been implicated, but there is insufficient evidence to establish an association of these syndromes with ART. Based on current evidence, the absolute risk of imprinting disorders after ART remains small and does not warrant routine screening. Large prospective studies are needed to better understand the risks associated with imprinting disorders, imprinting defects, and ART.

KEYWORDS

Assisted reproductive technology - ART - imprinting disorders - nongenomic inheritance - loss of maternal methylation - DNA methylation - BWS - AS

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James H SegarsJr. M.D. 

Building 10, CRC, Room 1E-3140

10 Center Drive, MSC 1109, Bethesda, MD 20892-1109

Email: segarsj@mail.nih.gov

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