Safety issues in assisted reproduction technology. From theory to reality--just what are the data telling us about ICSI offspring health and future fertility and should we be concerned?

Concerns about the effects of ICSI on offspring health and fertility include the rate of chromosomal anomalies, cystic fibrosis (CF) gene mutations associated with congenital bilateral absence of the vas deferens (CBAVD) and Y-chromosome microdeletions. The evidence in favour of screening for these in the presence of azoospermia or severe oligozoospermia is beyond debate. Concerns requiring further investigation include the effects of ICSI on imprinted genes and genes involved in DNA replication error repair. There is evidence of an increased risk of low birth weight, cerebral palsy and major birth defects following assisted reproductive technologies (ART), including ICSI, although the causes remain unknown. Given the large studies required to investigate these questions, particularly for rarer genetic conditions, we may simply have to accept that we may not know for many years if there are increased risks associated with ICSI. It would be prudent, however, to acknowledge this as a possibility and counsel patients accordingly. In terms of certainty of outcome and magnitude of impact the single most important health effect of ART for the offspring remains the iatrogenic multiple pregnancy rate. A reduction of iatrogenic multiples is the single most important and achievable means of preventing cerebral palsy currently available. Once achieved, the occurrence of rare genetic conditions will assume greater importance.