Sex chromosome aneuploidies and fertility: 47,XXY, 47,XYY, 47,XXX, and 45,X/47,XXX.

Abstract

The overall incidence of sex chromosome aneuploidies is approximately 1 per 500 live-born infants, but far more common at conception. I shall review the fertility aspects of the sex chromosome trisomies, XXY, XYY, XXX, with special reference to the karyotype 45,X/47,XXX. Each has a "specific" (but variable) phenotype, but may be modified by mosaicism. Although the alterations in the hypothalamic-pituitary-gonadal axis are important (and discussed), the emphasis is on potential fertility. The reproductive axis is often affected in females with the 47,XXX karyotype with diminished ovarian reserve and accelerated loss of ovarian function. Fewer than 5 % of females with the Turner syndrome have the 45,X/47,XXX karyotype. They have taller stature and less severe fertility issues compared to females with the 45,X or other forms of Turner syndrome mosaicism. For the 47,XXY karyotype non-obstructive azoospermia is almost universal with sperm retrieval by micro-testicular sperm extraction possible in slightly fewer than half of the men. Men with the 47,XYY karyotype have normal to large testes and much less testicular dysfunction than those with the 47,XXY karyotype. They do have a slight increase in infertility compared to the reference population, but not nearly so severe as those with 47,XXY karyotype. Assisted reproductive technology, especially micro-TESE has an important role, especially for those with 47,XXY; however, more recent data show promising techniques for the in vitro maturation of spermatogonial stem cells and 3-D organoids in culture. Assisted reproductive technology is more complex for the female, but vitrification of oocytes has shown promising advances.