Clomiphene citrate for male infertility: A systematic review and meta-analysis

Male infertility is a prevalent and worldwide problem with various difficulties in treatment. Clomiphene citrate is a selective estrogen receptor modulator and may improve semen quality by stimulating hormone synthesis and spermatogenesis. There is lack of evidence on the efficacy of clomiphene citrate as therapy for male infertility.

Therefore, a systematic review and meta-analysis was performed to assess the efficacy of clomiphene citrate on sperm quality in infertile men.

A search was conducted in the PubMed, EMBASE and Cochrane databases for effectiveness in infertile males treated with clomiphene citrate. Both intervention and observational studies were included. Primary outcome measures were semen parameters (concentration, motility and morphology). Secondary outcomes included hormonal evaluation, pregnancy rate and side effects. Studies were included for meta-analysis if they provided absolute numbers for outcomes before and during treatment with appropriate SD or SE.

Total 1799 studies were identified during the search, 18 studies remained for qualitative analysis (n = 731) and 15 studies for meta-analysis (n = 566). Study populations ranged between 11 and 140 participants. Sperm concentration was higher during treatment, with a mean difference 8.38 × 10⁶ /ml (95% confidence interval: 5.17-11.59; p < 0.00001; I²  = 87%). Total sperm motility was higher during treatment, with a mean difference of 8.14% (95% confidence interval: 3.83-12.45; p < 0.00001; I²  = 76%). There was no difference in sperm morphology before and during treatment. Total testosterone, follicle-stimulating hormone, luteinizing hormone and estradiol were higher during clomiphene citrate treatment. During follow-up, no serious adverse effects occurred. In 10 studies, pregnancy rate was reported and yielded a mean of 17% during clomiphene citrate treatment (range: 0%-40%).

Clomiphene citrate increased sperm concentration and motility and could be considered as a safe therapy for improving sperm parameters in infertile males.