Impact of male factor infertility on offspring health and development

Monitoring the safety of intracytoplasmic sperm injection (ICSI) has been impeded by uncertainties regarding the extent to which offspring health is influenced by paternal characteristics linked to male infertility or the processes that ICSI treatment entails. Few studies examining long-term health and developmental outcomes in children conceived with ICSI have considered the influence of paternal infertility adequately. In the available literature, large population-based studies suggest underlying male factors, and the severity of male factor infertility, increase the risk of mental retardation and autism in offspring, as does the ICSI procedure itself, but these findings have not been replicated consistently. Robust evidence of the influence of male factors on other health outcomes is lacking, with many studies limited by sample size. Nevertheless, emerging evidence suggests children conceived with ICSI have increased adiposity, particularly girls. Further, young men conceived with ICSI may have impaired spermatogenesis; the mechanisms underlying this remain unclear, with inconclusive evidence of inheritance of Y chromosome microdeletions. The current inconsistent and often sparse literature concerning the long-term health of children conceived with ICSI, and the specific influence of male infertility factors, underscore the need for concerted monitoring of children conceived with this technique across the lifespan. With the rapid expansion of use of ICSI for non-male factors, sufficiently large studies that compare outcomes between groups conceived with this technique for male factors versus non-male factors will provide critical evidence to elucidate the intergenerational impact of male infertility.