Imprinting and assisted reproductive technology
1Section of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham School of Medicine, Edgbaston, Birmingham B15 2TT, UK and 2West Midlands Regional Genetics Service, Birmingham Women's Hospital, Edgbaston, Birmingham B15 T2G, UK
* To whom correspondence should be addressed at: Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, The Medical School, Edgbaston, Birmingham B15 2TT, UK. Tel: +44 216272741; Fax: +44 216272618; Email: e.r.maher{at}bham.ac.uk
Received January 7, 2005; Revised February 9, 2005; Accepted February 17, 2005
In the past 25 years, the frequency of assisted reproductive technology (ART) births has increased rapidly to account for 1–2% of all births in many developed countries. ART procedures such as in vitro fertilization and intracytoplasmic sperm injection are generally considered to be safe, but recent studies suggest a small excess of birth defects and low-birth weight in ART children. In addition, several clinical studies have reported an increased frequency of ART conceptions among children with Beckwith–Wiedemann syndrome or Angelman syndrome caused by an imprinting defect. Although these studies require further confirmation, they are consistent with animal studies reporting disordered expression and epigenetic changes in imprinted genes following in vitro embryo culture. The absolute risk of an imprinting disorder after ART appears to be very small, but further data are required to determine whether the association between ART and human imprinting disorders reflects the effect of embryo culture (or some other aspect of ART) and/or a common mechanism for infertility and imprinting disorders. Retinoblastoma and neurodevelopmental defects have been only tentatively linked to ART, but in view of the role of epigenetic processes in the regulation of gene expression in development and cancer, further research is required into long-term health outcomes for ART children and the epigenetic consequences of ART protocols.
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