Metformin + clomiphene citrate vs. clomiphene alone for PCOS infertility

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Created On: 26/11/2025

This systematic review and meta-analysis sought to compare the therapeutic efficacy of clomiphene citrate + metformin versus clomiphene citrate alone in the management of primary infertility among women with polycystic ovarian syndrome (PCOS).

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Key take away

The combination of metformin and clomiphene citrate outperforms clomiphene alone in improving fertility among women with PCOS.

Background

Method

An extensive literature search was carried out in PubMed, SCOPUS, and Google Scholar databases for English-language randomized controlled trials (RCTs). Eligible studies included women aged 15–35 years, of any ethnicity, diagnosed with PCOS based on established diagnostic criteria, presenting with primary infertility, and treated with either clomiphene citrate plus metformin or clomiphene citrate alone/placebo.

A total of 1,737 women were analyzed. Metformin was administered at doses of 500–850 mg twice or thrice daily, while clomiphene citrate was given at 50–100 mg once daily. The primary endpoint was treatment efficacy, defined by improvement in fertility outcomes.

Result

The database search identified 1,251 studies, of which 4 RCTs met the inclusion criteria. The combination therapy portrayed a remarkably higher fertility improvement rate compared with clomiphene citrate alone or placebo (Odds ratio = 1.5; p = 0.0004; I² = 49%; n = 1,737), as shown in Table 1:

Conclusion

Combination therapy with metformin and clomiphene citrate markedly boosted fertility outcomes compared with clomiphene citrate monotherapy or placebo in women with PCOS-related primary infertility. Further high-quality, large-scale trials are need to corroborate these findings and elucidate the long-term safety and tolerability profiles of the combined regimen.