Effectiveness of Clomiphene Citrate for Improving Sperm Concentration: A Literature Review and Meta-Analysis

Abstract

Demographic data regarding male infertility suggest an increase in prevalence. This is an entity with multifactorial etiology, hormonal causes are often encountered. Although treatment with clomiphene was advocated to stimulate gametogenesis, it is still used off-label. We aimed to evaluate data from literature related to the effect of clomiphene as a single therapy, on the improvement of sperm count in infertile patients. Out of the 4,017 results of the search, only eight articles have been selected. The selected studies have been published between 1983 and 2020, and have included a total of 616 patients. From data reported, the treatment with clomiphene lead to a significant improvement of sperm concentration compared with placebo or with the level before starting the therapy (p<0.00001). Out of the 616 patients, in 369 (59.90%) cases improved sperm concentration was reported. In our meta-analysis, the selected studies had a high heterogeneity (I² = 97%). Nevertheless, clomiphene is not an ideal treatment, paroxysmal effects have been reported. Our findings encourage the use of clomiphene on male infertility, although the potential side effects should be clearly explained to patients.

Keywords: clomiphene; male infertility; meta-analysis; sperm count; srems.

Figure 1. PRISMA flowchart of the study selection

Figure 2. Forest plot of the treatment outcome

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Figure 3. Risk of bias graph