![]() A relatively modest rate of chromosome errors (1.7-4.2%) affects a large proportion of oocytes (23.6-53.5% fig. Both the slope from the mid-point (25.3 years) towards the younger oocytes, as well as upwards towards AMAs, contributed to the fit (χ 2-of-deviance, p<0.05 pseudo- R 2=0.137). Maternal age was the only significant factor that affected aneuploidy and the best-fit model was provided by a quadratic equation, suggestive of a U-curve of aneuploidy (χ 2-of-deviance, p<0.001 pseudo- R 2 oocyte=0.10, pseudo- R 2 chromosome=0.12 fig. S2-S7 table S2, S3, S5) and aneuploidy rates were not affected by maturation method ( in vivo or in vitro) ( 8, 9), cohort, or technology ( fig. Meiotic progression was similar between immature oocytes from the two cohorts ( fig. The age range overlapped with oocytes (mature and immature) from women receiving gonadotrophin-stimulation in IVF clinics (20-43 years), allowing us to validate findings in two independent patient cohorts ( fig. We obtained small antral follicles directly from ovarian tissue of unstimulated girls and women prior to chemotherapy for blood disorders and a range of cancers, excluding ovarian cancer (ages 9.1-38.8 years fig. To address this, we used two sources of oocytes to determine aneuploidy rates that span females aged 9 to 43 years ( fig. S1B) ( 6, 7), we speculated that meiotic error rates throughout the entire reproductive lifespan may shape natural fertility. Since chromosome errors in female meiosis cause substantial pregnancy loss due to aneuploid conceptions in women of advanced maternal age ( fig. ![]() ![]() However, the mechanism(s) that shapes the fertility curve are unclear. Reduced fertility towards both ends of the inverse U-curve in humans is assumed to depend on selective forces that balance risks and evolutionary fitness associated with childbearing ( 2– 5). The curve differs substantially from chimpanzees, where fertility rates remain steady throughout their reproductive lifespan ( fig S1A) ( 1). ![]() Natural fertility in humans follows an inverse U-curve, where teenagers (≥13) and women of advancing maternal age (AMA, mid 30s and above) show reduced rates ( 1). ![]()
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