Empirical therapy of the male with clomiphene in couples with unexplained infertility

Unexplained infertility may be secondary to a cryptic male or female factor. Although most often empirical therapy of the female partner may be attempted, clomiphene has been claimed, after uncontrolled studies, to improve fertility in men with subnormal spermograms. We chose to determine if clomiphene therapy of the male would improve fertility in couples with unexplained infertility despite normal-appearing semen parameters. One hundred husbands were randomized to treatment with clomiphene citrate, 25 mg daily for 25 days with 5 days' rest each month, if their social security numbers ended in an even number or ascorbic acid, 500 mg daily, if ending in an odd number. All female infertility factors had to be meticulously corrected for at least eight cycles for inclusion in the study, along with a minimum of 1 1/2 years' duration of infertility. Within 8 months, 29 of 50 couples (58%) with clomiphene therapy of the male achieved a pregnancy, but only 8 of 50 (16%) with ascorbic acid treatment of the male. There were no appreciable changes in sperm counts, motility, or morphology after either treatment, nor were there any significant differences in semen parameters in those conceiving versus those who did not. Further, improved fertility could not be accounted for by improvement in the hamster ova penetration test. Possibly, clomiphene improves some quality of the sperm that is defective but not measurable by standard androgenologic methods, or it improves some aspect of the seminal plasma. Perhaps, though, the results might be better explained on a psychogenic basis, i.e., clomiphene is a "better" placebo than ascorbic acid.(ABSTRACT TRUNCATED AT 250 WORDS)