Clustering of male infertility in the families of couples treated with intracytoplasmic sperm injection

Intracytoplasmic sperm injection (ICSI) is an effective treatment modality for male factor infertility, but it could promote the transgenerational tra nsmission of genetic defects causing gametogenic failure. Cytogenetic and m olecular techniques permit the diagnosis of some infertility-causing geneti c aberrations, but many more probably evade detection with currently availa ble technology. The analysis of the recurrence pattern of infertility in in fertile couples' families could define the importance of heritable factors in the pathogenesis of human infertility, We have subjected 621 consecutive infertile couples treated with ICSI in a single institution to a comprehen sive genetic workup including documentation of the family history, karyotyp ing and various DNA tests, In all, 1302 fertile couples served as controls. Of the infertile couples 6.4% were shown to have a fertility problem with a definite genetic basis. Male, but not female fertility problems displayed a distinct pattern of familial aggregation. In addition, the infertile cou ples had fewer siblings than the fertile controls, a finding compatible wit h suboptimal fertility already among the infertile couples' parents. In sum mary, our data indicate that male factor infertility should be considered a potentially heritable condition. The recurrence risk for infertility in th e offspring of couples treated with ICSI might be substantial.