From Embryos to Adults: A DOHaD Perspective on In Vitro Fertilization and Other Assisted Reproductive Technologies

Human in vitro fertilization (IVF) as a treatment for infertility is regarded as one of the most outstanding accomplishments of the 20th century, and its use has grown dramatically since the late 1970s. Although IVF is considered safe and the majority of children appear healthy, reproductive technologies have been viewed with some skepticism since the in vitro environment deviates substantially from that in vivo. This is increasingly significant because the Developmental Origins of Health and Disease (DOHaD) hypothesis has illuminated the sensitivity of an organism to its environment at critical stages during development, including how suboptimal exposures restricted specifically to gamete maturation or the preimplantation period can affect postnatal growth, glucose metabolism, fat deposition, and vascular function. Today, some of the physiological metabolic phenotypes present in animal models of IVF have begun to emerge in human IVF children, but it remains unclear whether or not in vitro embryo manipulation will have lasting health consequences in the offspring. Our expanding knowledge of the DOHaD field is fueling a paradigm shift in how disease susceptibility is viewed across the life course, with particular emphasis on the importance of collecting detailed exposure information, identifying biomarkers of health, and performing longitudinal studies for any medical treatment occurring during a developmentally vulnerable period. As IVF use continues to rise, it will be highly valuable to incorporate DOHaD concepts into the clinical arena and future approaches to public health policy.