What is the underlying cause of aneuploidy associated with increasing maternal age? Is it associated with elevated levels of gonadotropins?

Aneuploidy is the most common chromosomal abnormality and also is the leading cause of early fetal loss and serious mental retardations. Except for the advanced maternal age, there is no clearly established factor for the development of aneuploidy. On the other hand, advanced maternal age is well characterized with elevated gonadotropin levels due to the decreased ovarian reserve. Such high level gonadotropins are also seen physiologically in the adolescent period. Both age groups may have an increased risk for having a baby with chromosomal abnormality. On the other hand, high doses of gonadotropins are widely used in artificial reproductive technologies (ART). Low pregnancy and high abortion rates in ART practices may be explained by higher incidence of chromosomal abnormalities in the unfertilized oocytes maturated by high dose gonadotropins. Gonadotropins are also found to induce congenital malformations and chromosomal abnormalities in some animal studies. From this point of view, we hypothesized that gonadotropins might have a role in the development of aneuploidy. If this hypothesis is true, basal serum FSH levels may be used as a screening test in preconceptional period for assessment of the aneuploidy risk in low risk population. Furthermore, new ART protocols using low dose gonadotropins should be developed in order to improve pregnancy outcomes and possibly to prevent aneuploidy.