Nature Medicine, Published online: 14 September 2026; doi:10.1038/s41591-026-04676-0 Whole-genome sequencing of 7,851 parent–offspring families enabled the identification of parent-of-origin and post-zygotic de novo mutations that were associated with distinct procedures of assisted reproductive technology (ART), independently of parental age at conception. Increased paternal mutational burden statistically mediates the effects of advanced parental age and ART on gestational duration and other birth outcomes.