Meiotic errors in oocytes of young and advanced maternal age women: the U-curve of fertility

Italy is currently one of the countries most affected by declining birth rates, a negative trend mainly determined by several socio-economic factors that lead women to postpone pregnancy. The use of in vitro fertilization techniques cannot counteract the natural decline in fertility that accompanies advancing maternal age. This decline is associated with an increase in chromosomal aneuploidy in oocytes that, if fertilized, could result in aneuploid embryos that are often miscarried. Here, we discuss the “molecular clock hypothesis” proposed by Hoffmann’s lab, which suggests a U-shaped trend of female fertility. The high rates of chromosomal aneuploidy observed at the two “ends of the curve” may represent an evolutionary mechanism of protection that exists to balance the risks associated with pregnancy. This hypothesis lays the foundations for debating the idea that very young women are free from the risk of aneuploidy, and also suggests the existence of a safety mechanism that “protects” against possibly complicated pregnancies both after the age of 40 years and in very young women. The U-shape hypothesis described in humans will be discussed in a comparison with the fertility trends of other mammalian species. KEY WORDS: Fertility, aneuploidy, advanced maternal age, IVF