Epigenetic, Environmental, and Sex-Specific Programming of Long-Term Health in ART-Conceived Offspring

Assisted Reproductive Technologies (ART) are non-coital methods of conception widely used to address infertility. These procedures include conventional in vitro fertilization (IVF), intracytoplasmic sperm injection, gamete and embryo cryopreservation, trophectoderm biopsy for preimplantation genetic testing, and newer mitochondrial replacement techniques. Since the first IVF birth in 1978, the global use of ART has increased rapidly, contributing to more than 13 million births worldwide. Although ongoing technological advances have improved safety and increased pregnancy and live-birth rates, ART has also been associated with adverse placental and fetal outcomes, some of which persist into later life and, in certain cases, across generations. The mechanisms underlying these outcomes are not fully understood, but studies suggest that altered epigenetic reprogramming, environmental influences, and sex-specific factors are major contributors. In this review, we examine how long-term health outcomes in ART-conceived offspring are shaped by the interplay of epigenetic mechanisms, environmental influences, and sex-specific responses in both humans and mice.