Genetics and genetic diagnosis. Non-reproductive heritable disorders in infertile couples and their first degree relatives

The genetic safety of intracytoplasmic sperm injection (ICSI) remains a matter of continuing debate. One source of concern is the limited knowledge about the general genetic constitution and background of patients who need sophisticated reproductive technology to procreate. It has been postulated that such individuals could be carriers of genetic lesions that might result in an increased prevalence of heritable disorders among their offspring. To investigate this issue, we determined the frequency of potentially heritable non-reproductive diseases in 621 infertile couples and their first degree relatives. A total of 1302 fertile couples who underwent genetic counselling prior to prenatal diagnosis served as controls. The infertile patients had a slightly higher prevalence of potentially heritable non-reproductive disorders (`significant genetic risk factors') than the controls (1.9 versus 0.9%; P = 0.015). In contrast, such diseases were less prevalent in their families than in the fertile couples' families. Our data do not support the hypothesis that their familial genetic background predisposes children born after ICSI to malformations or other non-reproductive genetic diseases.