The origin of abnormalities in recurrent aneuploidy/polyploidy

Recurrent miscarriage due to sporadic chromosomal abnormalities may simply be a consequence of the dramatic increase of trisomic conceptions with incr eased maternal age. However, it is also possible that some couples are at i ncreased risk of abnormalities as a result of gonadal mosaicism, factors af fecting chromosome structure and segregation, increased sperm aneuploidy in the male partner, or accelerated "aging" of the ovaries. We report cytogen etic and molecular findings from 122 spontaneous abortions (SAs) from 54 co uples who were ascertained as having two or more documented aneuploid or po lyploid SAs. The distribution of abnormalities in this group was similar to those from 307 SAs that involved chromosome abnormalities and were diagnos ed at the same center but did not involve documented recurrent aneuploidy/p olyploidy. Although recurrence of the same abnormality was observed in eigh t families, this number was equal to that expected by chance, indicating th at gonadal mosaicism is rarely the explanation for recurrence. The origin o f the abnormality was determined in 37 SAs from 23 of the couples in the st udy. A maternal meiotic origin was involved in 30 trisomies and in 1 triplo id SA; 3 additional maternal trisomies were of possible somatic origin. A p aternal origin was found in the remaining two trisomies and in one triploid SA. In addition, one double trisomy was the consequence of both a maternal and a paternal meiotic error. These results confirm that the etiology of t risomy is predominantly a result of meiotic errors related to increased mat ernal age, regardless of whether the couple has experienced one or multiple aneuploid SAs. Furthermore, this is true even when a second SA involves th e same abnormality. Nonetheless, these data do not exclude some population variability in risk for aneuploidy.