Rapid ReviewRare congenital disorders, imprinted genes, and assisted reproductive technology
Section snippets
Safety of assisted reproductive technologies
Most studies of children conceived in vitro have shown a negligible or only a slight excess risk of major and minor birth defects.2, 3 By contrast, in Western Australia the risk of one or more major birth defects in babies conceived by ARTs was twice the expected rate (8·6% for intra-cytoplasmic sperm injection [ICSI] and 9·0% for in-vitro fertilisation [IVF], vs 4·2%).4 In a simultaneous report from the USA, the incidence of low birthweight for singleton pregnancies at full term among babies
Imprinted genes in development
About 50 genes are differentially expressed according to their origin in either the oocyte or spermatozoon. These imprinted genes have roles in growth and development as well as in tumour suppression (eg, retinoblastoma has been reported by Dutch investigators to be more frequent among ART children than normal).17 By definition, at imprinted loci, only one allele is active (maternal or paternal) and the inactive one is epigenetically marked by histone modification, cytosine methylation, or both.
New reproductive technologies
ARTs are constantly evolving to improve pregnancy success rates, to reduce the incidence of multiple pregnancy, and to increase treatment options for patients. Changes in the drugs used are less likely to have a harmful effect on development than the maturation and manipulation of gametes and embryos in vitro. Immature spermatozoa are collected from the genital tract or testis of oligospermic men for ICSI, but the paternal imprinting process seems to be complete by this stage. Since the primary
Conclusions
The epidemiological evidence associating Beckwith-Wiedemann syndrome or Angelman syndrome with ART procedures is still tentative and does not yet establish a causal link. The absolute risks are small and unlikely to deter would-be parents from using the technology. Nonetheless, the implementation of ARTs during a critical period for formation and maintenance of epigenetic information in gametes and early embryos, as well as the evidence of culture artifacts in animals, requires further
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