This study will evaluate the efficacy of the anti-estrogens, clomiphene citrate (CC) and tamoxifen (TX), in the treatment of oligospermic male infertility. This protocol seeks to establish and/or reaffirm; 1) the efficacy of CC and TX in improving sperm number, morphology, and motility; 2) usefulness of the sperm penetration assay (SPA) and the bovine mucus penetration test (BMPT) as means of directly assessing potential improvement in the functional capacity of sperm in response to CC or TX: 3) comparative pregnancy rates in female cohorts of oligospermic males treated with CC, TX or placebo; 4) guidelines for the screening and selection of oligospermic males who are most likely to respond to drug therapy; 5) guidelines for the early prediction of subsequent response to drug therapy in oligospermic males. Male subjects and their female partners will undergo complete infertility evaluations. For couples in whom the primary factor for infertility appears to be normogonadotropic oligospermia (mean sperm density 5-20 million/ml with total sperm count less than 60 million per ejaculate on the basis of 2 or more semen specimens), anti-estrogen therapy that will be offered to men satisfying uniform screening criteria. This protocol employs a modified double-blind design with a parallel, placebo-controlled format. From those men qualifying and giving informed consent, three groups will be randomly selected in a double-blind fashion. Group 1 (n=10) will receive placebo for 9 months. Group 2 (n=30) will receive an initial 3 months of placebo, followed by 6 months of CC 50 mg/day. Group 3 (n=30) will receive placebo for 3 months, followed by TX 20 mg/day for 6 months. All groups will conclude their 12 month observation period with a 3 month drug-free interval. Artificial insemination with husband sperm (AIH) will be performed 2 or 3 times in the periovulatory period for the 12 month study interval. The response to placebo or active drug will be assessed at 3 month intervals utilizing direct measures of sperm functional capacity (SPA, BMPT), semen analysis (count, motility, morphology), endocrine parameters (FSH, testosterone) and pregnancy rates.

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Vanderbilt University Medical Center
Schools of Medicine
United States
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