BackgroundPolycystic ovary syndrome is one of the most frequent endocrinological problems causing infertility in women worldwide. The main problem in these women is hyperandrogenism and/or chronic oligo/anovulation, which leads to infertility. In this systematic review and meta-analysis, we aimed to investigate the efficacy of a relatively new drug for ovulation induction, letrozole, by comparing it to the first line of treatment for ovulation induction, clomiphene citrate.MethodsA literary search was conducted in three databases and included randomized clinical trials comparing letrozole and clomiphene citrate for ovulation induction for women with polycystic ovary syndrome. The diagnosis of polycystic ovary syndrome was determined according to the Rotterdam criteria. We pooled data using a random-effects model.ResultsOur search provided a total of 1,994 articles, of which we included 25 studies. In the letrozole group, endometrial thickness was significantly higher (Mean Difference=1.70, Confidence Interval: 0.55-2.86; Heterogeinity: I2=97%, p-value=0.008); odds for ovulation (Odds Ratio=1.8, Confidence Interval: 1.21-2.69; Heterogeinity: I2=51%, p-value=0.010) and pregnancy (Odds Ratio=1.96, Confidence Interval: 1.37-2.81; Heterogeinity: I2=32%, p- value=0.002) were significantly higher; the resistance index of subendometrial arteries was significantly lower (Mean Difference=-0.15, Confidence Interval: -0.27- -0.04; Heterogeneity: I2=92%, p-value=0.030).ConclusionWomen with polycystic ovary syndrome treated with letrozole for ovulation induction had higher ovulation and pregnancy rates, their endometrium became thicker, the resistance index of subendometrial arteries was lower. The lower resistance index of the subendometrial arteries can improve intrauterine circulation, which may provide better circumstances for embryo implantation and development.