Familial clustering of impaired spermatogenesis: no evidence for a common genetic inheritance pattern

BACKGROUND: The aetiology of impaired spermatogenesis is unknown in the majority of cases. Evidence of a contribution of genetic factors is still scarce. Therefore, the aim of our study was to assess whether male factor subfertility due to impaired spermatogenesis has a familial component and to test different genetic models of inheritance. METHODS: Cases were all men with severe idiopathic impaired spermatogenesis attending our fertility clinic from January 1998 until December 2001. Controls were all men with normozoospermia attending our fertility clinic in the same period. Family data were collected from the medical records and by additional interviews of the probands. If subfertility of a first-degree relative was mentioned, permission was sought to contact the affected family member in order to obtain all medical information available, including the results of semen analyses. RESULTS: In total, 160 patients and 285 controls were included in the analysis. Family size and number of brothers and sisters were equally distributed in both groups. In the patient group, 1.63% of the brothers who had tried to father a child were mentioned to be subfertile compared to 5.8% in the control group [odds ratio 3.18 (95% confidence interval 1.59-6.37)]. The subfertility among the brothers in the patient group was more often due to reduced semen parameters compared to the control group. The data did not fit with frequent autosomal dominant or recessive segregation. CONCLUSION: Male factor subfertility due to impaired spermatogenesis appears to cluster in families. Our data suggests that heritable genetic factors play a role in a limited number of cases. Impaired spermatogenesis is not caused by a common genetic defect, but is most likely a complex disease in which several different factors play a role.