Assessing the epigenetic risks of assisted reproductive technologies: a way forward.

Since the birth of the first baby conceived by in vitro fertilization (IVF), assisted reproductive technologies (ART) have been constantly evolving to accomodate needs of a growing number of infertile couples. Rapidly developing ART procedures are directly applied for human infertility treatment without prior long-term safety evaluation. Although the majority of ART babies are healthy at birth, a comprehensive assessment of the long-term risks associated with ART is still lacking. An increased risk of epigenetic errors has been associated with the use of ART, which may contribute to the onset of civilization disease later in adolescence/adulthood and/or in subsequent generations. Therefore, our investigations should not focus on (or be limited to) the occurrence of a few very rare imprinting disorders in ART children, which might be associated with parental age and/or the use of ART, but on the possibly increased disease susceptibilities later in life and their potential transmission to the subsequent generations. Retrospective studies do not offer exhaustive information on long-term consequences of ART. Animal models are useful tools to study long-term effects including transgenerational ones and the epigenetic risk of a given ART procedure, which could then be translated to the human context. The final goal is the establishment of common guidelines for assessing the epigenetic risk of ART in humans, which will contribute to two key objectives of the Horizon2020 programme, i.e. to improve our understanding of the causes and mechanisms underlying health and disease, and to improve our ability to monitor health and prevent/manage disease.