Case-control study of whether subfertility in men is familial

To test the hypothesis that subfertility in men is familial and to examine the distribution of subfertility within families for consistency with a genetic cause.

Case-control study and segregation analysis.

Two teaching hospitals in Leeds.

Cases (probands) were men with an abnormal sperm count who attended a subfertility clinic and whose partners had no major factor contravening fertility. Controls were fathers of two or more children recruited through vasectomy clinics or a maternity department.

The incidence of involuntary childlessness among brothers with partners and among sisters and second and third degree male relatives. When possible clinical and laboratory details were obtained from involuntarily childless brothers.

Seventeen of the 148 (11.5%) brothers of probands but none of the 169 brothers of controls had sought medical advice for childlessness (P < 0.0005). Four probands had more than one involuntarily childless brother. There were six further brothers whose childlessness was thought to be involuntary bringing the total prevalence of subfertility among brothers of probands to 16%. Segregation analysis was consistent with an autosomal recessive mode of inheritance accounting for 60% of subfertility in men. Seventeen of the 346 (4.9%) uncles of probands and 10 of 420 (2.8%) uncles of controls were reported to be involuntarily childless (P = 0.09), but there was no difference in childlessness among sisters. In three families sperm counts from "affected" brothers confirmed the diagnosis and showed considerable similarities within but not between families.

Subfertility in men has a familial component, and the observations are consistent with an autosomal recessive mode of inheritance in over half the cases. Several different genes are probably involved.