Mouse Offspring Conceived by In Vitro Fertilization Exhibit Accelerated Reproductive Aging Through Early Ovarian Failure

In vitro fertilization (IVF) is an assisted reproductive technology that has enabled millions of births. Although considered safe, emerging evidence suggests that IVF may have long-term health adverse outcomes in offspring, though its impact on female reproduction, especially on reproductive aging is largely unknown. Here, we use a mouse model to investigate how IVF influences female reproductive and transgenerational health outcomes. We assessed IVF-conceived fetal (E18.5) and adult (12-week and 39-week) female offspring, identifying alterations in ovarian-to-body weight ratios, ovarian morphology, serum sex hormone levels, and transcriptomic and DNA methylation profiles in ovaries, oocytes, and cumulus cells, consistent with biomarkers of accelerated reproductive aging. The offspring of IVF females and wild-type males exhibited altered fetal-to-placental weight ratios, placental morphology, and dysregulated placental gene expression. At 12-weeks-of-age, offspring showed increased body weight, disrupted lipid and glucose metabolism, and transcriptomic and epigenetic changes in liver and reproductive organs. Our results highlight the need for deeper mechanistic understanding of assisted reproduction’s long-term and multigenerational impacts on female reproductive health.