The effects of assisted reproduction technologies on metabolic health and disease†

The increasing prevalence of metabolic diseases places a substantial burden on human health throughout the world. It is believed that predisposition to metabolic disease starts early in life, a period of great susceptibility to epigenetic reprogramming due to environmental insults. Assisted reproductive technologies (ART), i.e., treatments for infertility, may affect embryo development, resulting in multiple adverse health outcomes in postnatal life. The most frequently observed alteration in ART pregnancies is impaired placental nutrient transfer. Moreover, consequent intrauterine growth restriction and low birth weight followed by catch-up growth can all predict future obesity, insulin resistance, and chronic metabolic diseases. In this review, we have focused on evidence of adverse metabolic alterations associated with ART, which can contribute to the development of chronic adult-onset diseases, such as metabolic syndrome, type 2 diabetes, and cardiovascular disease. Due to high phenotypic plasticity, ART pregnancies can produce both offspring with adverse health outcomes, as well as healthy individuals. We further discuss the sex-specific and age-dependent metabolic alterations reflected in ART offspring, and how the degree of interference of a given ART procedure (from mild to more severe manipulation of the egg) affects the occurrence and degree of offspring alterations. Over the last few years, studies have reported signs of cardiometabolic alterations in ART offspring that are detectable at a young age but that do not appear to constitute a high risk of disease and morbidity per se. These abnormal phenotypes could be early indicators of the development of chronic diseases, including metabolic syndrome, in adulthood. The early detection of metabolic alterations could contribute to preventing the onset of disease in adulthood. Such early interventions may counteract the risk factors and improve the long-term health of the individual.