Adverse effect of clomiphene citrate on sperm morphology

The beneficial effect of clomiphene citrate (CC) in treating male infertility is controversial. To evaluate the effects of CC on sperm morphology using strict criteria, the semen analyses of 74 men were evaluated at intervals ranging from 1 to 18 months of treatment. Seventy patients receiving no medication were used as control. The patients in each category were divided into three subgroups: A (1-3 months), B (4-6 months), and C (greater than 6 months). In the control group, there were no significant differences in percentages or total normal forms between baseline and repeat semen analysis at any interval. Treatment with CC for 1-3 months did not adversely affect percentages of normal forms. Treatment for greater than 3 months caused a highly significant decrease in percentage of normal forms. Three months of CC caused no change in the absolute number of morphologically normal sperm, but longer periods (greater than 6 months) were associated with a significant decrease. There was significant deterioration of sperm function as measured by percentage of normal forms in patients treated with CC for 4-18 months. The physiological clinical significance remains to be investigated.