Assisted reproductive technology (ART), which in its broadest sense encompasses all fertility treatments, has revolutionized reproductive medicine and dramatically changed the lives of many people. Nevertheless, recent reports of an increased incidence of Angelman syndrome following IVF raised the possibility that ART might bring about epigenetic changes in the early embryo and lead to birth defects. Now, in a collaborative study of families with Beckwith–Wiedemann syndrome (BWS), which also involves epigenetic modifications, DeBaun, Feinberg and colleagues show that it, too, might become more frequent following ART. In addition, in a letter to the Editor, Ørstavik and colleagues report another case of Angelman syndrome following ICSI (intracytoplasmic sperm injection), a technique used to treat male infertility.

BWS, which is characterized by overgrowth and neoplasia, results from the loss of imprinting of a few specific loci, including LIT1 and H19 . Previous reports of an association between epigenetic disorders and ART, together with the similarity between the BWS phenotype and the large offspring syndrome — previously reported in cloned mammals — led DeBaun et al. to investigate the possibility of an association between ART and BWS incidence. Extending their existing study of BWS, which involved a registry of families with this syndrome, the authors designed a questionnaire to assess the method of conception for children with BWS. They found that six out of seven children with BWS were concieved as a result of IVF. The incidence of ART was 4.6% among those who participated in the study, compared with 0.76% in the general US population, leading De Baun et al. to suggest that the incidence of BWS increases at least sixfold after ART treatment, compared with the general population.

Given the previous reports of Angelman syndrome in association with ART and the observation that five out of the six BWS cases were associated with classic BWS imprinting alterations, the authors believe that sufficient evidence now exists to suspect that some aspect of ART might interfere with imprinting either in the gametes or in the early embryo. So far, nothing is known about how this might occur, but one thing is certain — ART does not imitate life.