Birth defects and possible imprinting defects after assisted conception
Purpose: Recent studies of pregnancy outcome after assisted conception have reported an increased risk of genomic imprinting defects and specific urogenital and other malformations. Experimental studies in mice and other species have shown how epigenetic factors such as embryo culture media may alter DNA methylation in the early embryo and increase the risk of imprinting defects.
Methods: This study aimed to evaluate the occurrence of these birth defects notified by IVF units to a population-based register of pregnancy outcomes and birth defects.
Results: Among almost 29,000 births and terminations of pregnancy after assisted conception in Australia and New Zealand, major malformations were notified in 2.5 per cent. As well as higher rates of neural tube defects, exomphalos, tracheo-oesophageal fistula and imperforate anus, there were 2 cases of Beckwith-Wiedemann syndrome, 4 cases of Prader-Willi syndrome, and 2 cases of Russell-Silver syndrome, probably an excess number of the latter two defects. Other possible genomic imprinting defects and genetic diseases included: congenital adrenal hyperplasia (2), myotonic dystrophy (2), ocular albinism (3 cases, including identical twins), Cornelia de Lange syndrome (1), Klippel-Trenauny-Weber syndrome (1), partial androgen sensitivity (1), and osteogenesis imperfecta (3). There were also 4 cases of cloacal-bladder exstrophy-epispadias complex, when only 1 case was expected.
Conclusions: While detailed information about specific exposures of treated women and their embryos is often lacking, there is mounting evidence that some uncommon genomic imprinting defects are more likely after assisted conception. Until more studies of adequate sample size are conducted, the specific risks of birth defects after assisted conception will remain uncertain. The results of molecular genetic studies are needed to assess the likelihood of causal associations.