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Is Metformin Indicated as Primary Ovulation Induction Agent in Women with PCOS? A Systematic Review and Meta-Analysis

Background: A recent meta-analysis has proven that metformin (M) is highly effective for ovulation induction in the clomiphene citrate (CC)-resistant patient. There is uncertainty whether M should be introduced as a primary ovulation induction agent in polycystic ovarian syndrome (PCOS). Methods: We conducted a systematic review and meta-analysis to establish if M is better when given alone or in combination with CC (CC+M) when compared with CC alone. This systematic review studied live birth delivery rate as the primary outcome. Results: We identified 14 prospective trials. Analysis of these results showed a reduction in the live birth rate in the group of patients treated only with M when compared with CC alone (OR = 0.48, 95% CI 0.31–0.73, p = 0.0006). An increase in ovulation (OR = 1.6, 95% CI 1.2–2.1, p = 0.0009) and pregnancy rate (OR = 1.3, 95% CI 1.0–1.6, p = 0.05) with CC+M when compared with CC alone was reported, but no difference was found when live birth rate was analyzed (OR = 1.1, 95% CI 0.8–1.5, p = 0.61). Conclusion: CC alone is superior to M alone regarding live birth rate and ovulation. The combination (CC+M) is superior to CC alone as a primary method for ovulation induction and to achieve pregnancy in PCOS. However, when addressing live birth rate, no statistically significant difference could be demonstrated. Because of the side effects profile and contraindications of M, we believe M should not be indicated as a primary ovulation induction agent in women with PCOS.