The appropriate upper age limit for semen donors: a review of the genetic effects of paternal age.

There is little evidence to support a correlation between increased paternal age and the incidence of chromosome anomalies. Though a few early studies demonstrated an increased risk of Down syndrome with advanced paternal age, especially after the age of 55, numerous later studies failed to confirm any paternal age effect. Among structural chromosome anomalies, only the inherited reciprocal translocations were found to be more common among children of older fathers. Chromosome analysis of semen donors would rule out this problem. There is evidence, however, that the incidence of serious nonchromosomal birth defects, especially those arising from new autosomal mutations, increases with paternal age. Risk estimates have been established for increased paternal age and contribution to new dominant mutations. The established association between increased paternal age and new autosomal mutations and the fact that most of the disorders associated with such mutations cannot be prenatally diagnosed may be important in establishing the upper age limit for semen donors. Recommendations from the literature are interpreted to advise men to have their children before age 40. This suggestion would obviously benefit immediate offspring and perhaps successive generations as well. The limit of 35 years set by AATB standards, therefore, is in harmony with such benefit, but may be too stringent in eliminating potential donors. Accordingly, the Reproductive Council of the AATB has initiated steps to modify its standards to the age limit of 40.