Chromosome errors in human eggs shape natural fertility over reproductive life span

TLDR

Chromosome errors (aneuploidy) cause a high rate of human conceptions to fail, leading to pregnancy loss and congenital disorders. Aneuploidy in human oocytes follows a U‑shaped age curve, with whole‑chromosome nondisjunction driving high rates in young girls and centromeric/cohesion loss limiting fertility in older women, explaining the natural fertility curve.

Abstract

Chromosome errors, or aneuploidy, affect an exceptionally high number of human conceptions, causing pregnancy loss and congenital disorders. Here, we have followed chromosome segregation in human oocytes from females aged 9 to 43 years and report that aneuploidy follows a U-curve. Specific segregation error types show different age dependencies, providing a quantitative explanation for the U-curve. Whole-chromosome nondisjunction events are preferentially associated with increased aneuploidy in young girls, whereas centromeric and more extensive cohesion loss limit fertility as women age. Our findings suggest that chromosomal errors originating in oocytes determine the curve of natural fertility in humans.