Abstract To define the exact role of metformin in ovulation induction, it is crucial to distinguish
three different indications: naı¨ve PCOS, CC-resistant PCOS and ART. In naı¨ve PCOS: metformin
as compared to placebo has been shown to improve ovulation rates, but metformin did not exert
significant advantage over CC with respect to cumulative ovulation, pregnancy or live-birth rates.
The combined approach of metformin plus CC is not better than CC or metformin monotherapy in
naı¨ve PCOS. In CC-resistant patients: metformin has no benefit over placebo in ovulation, pregnancy,
and live-birth rates as a single agent, but the combination of metformin and CC significantly
improved ovulation and pregnancy rates when compared with CC alone. However, combined therapy
did not improve the odds of live birth. Metformin pretreatment improves the efficacy of CC in
PCOS patients with CC resistance. In PCOS patients scheduled for ART: metformin addition to
gonadotropins reduces the duration of gonadotropins administration and the doses of gonadotropins
required, and increases the rate of monoovulations, reducing the risk of cancelled cycles. Metformin
co-administration to IVF treatment does not improve pregnancy or live-birth rates but
reduces the risk of OHSS.