Rare chromosomal, genetic, and epigenetic-related risks associated with infertility treatment

This article reviews the rarer chromosomal, genetic, and epigenetic-related risks of adverse child outcomes associated with infertility and its treatment. Excess structural chromosomal anomalies have been found in both male and female partners undergoing infertility treatment, and these risk direct transmission to offspring. Microdeletions of the Y-chromosome associated with male infertility have been transmitted to sons following treatment with intracytoplasmic sperm injection. It is thus possible that male offspring of men with infertility could experience fertility problems in adulthood. Infertility treatment for men with cystic fibrosis, or with congenital bilateral absence of the vas deferens in the absence of cystic fibrosis, who have azoospermia is now possible using surgically retrieved sperm. Transmission of known cystic fibrosis mutations can be avoided by testing the female partner prior to treatment and offering pre-implantation genetic diagnosis if she is a carrier. The effect of infertility and its treatment on genomic imprinting is of increasing concern as our understanding of the mechanisms of imprinting in germ cell development and embryogenesis expands. At present, it is far from clear whether there are longstanding effects of infertility per se or of its treatment on the health of adults who were conceived following assisted reproductive technologies, but available data suggest that this should be of concern and long-term follow-up studies are required.