Background: Aromatase inhibitors (AIs) have been used to treat male infertility for decades. However, due to the lack of large-scale randomized controlled studies and basic research, the efficacy and safety of AIs in the treatment of male infertility remain controversial. Therefore, it is necessary to conduct an evidence-based preliminary evaluation of the existing clinical trials of AIs in the treatment of male infertility. Method: A comprehensive literature search was performed in the PubMed, Embase, Cochrane, CNKI, VIP, CBM, and Wanfang databases through August 2021 for all studies. We conducted a systematic review with a meta-analysis of all available studies reporting sperm conventional parameters, gonadotropin and testosterone levels, and/or the pregnancy rate.Results: A total of 10 studies involving 666 patients were included. Letrozole (LE) or anastrozole (AZ) administration significantly increased sperm concentration, total sperm count, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) levels, and the testosterone-to-estradiol ratio (T/E2), but E2 levels were significantly reduced compared with baseline values. Compared with the control group, which included selective estrogen receptor modulators (SEMRs) or human chorionic gonadotropin (HCG), LE, or AZ did not have any significant effect on sperm concentration, motility, and morphology, except that AIs had less effect on sperm motility than the control group (weighted mean difference [WMD]: −2.55; 95% CI: −4.11 to −1.00; p = 0.001). Conclusion:AIs may be effective in the treatment of male infertility. For infertile male patients planning assisted reproduction, discontinuation of AIs for 2-7 days prior to sperm retrieval may increase the success rate of fertilization. Further studies with larger sample sizes are needed to validate these findings.

Background: Letrozole (LE) or anastrozole (AZ) is clinically beneficial in male infertility patients with a low testosterone-estradiol ratio (T/E2). Many scholars believe it has the potential to become one of the effective drugs to treat male infertility. But some relevant research results are different or even the opposite. Study Question: The purpose of this report is to evaluate the efficacy and safety of letrozole or anastrozole in the treatment of specific male infertility patients. Data Sources: We performed a comprehensive literature search using PubMed, Embase, Cochrane, CNKI, VIP, CBM, and Wanfang Date through August 2021 for all studies.Study Design: We conducted a systematic review with meta- analysis of the all available literature reporting sperm conventional parameters, gonadotropin and testosterone levels, and/or the pregnancy rate. Results: The total of 10 studies involving 280 patients were included. LE or AZ administration increased significantly sperm concentration, total sperm count, and serum luteinizing hormone, follicle-stimulating hormone, testosterone levels and T / E2 compared with baseline values, but E2 levels were significantly reduced. In contrast, LE or AZ did not have any significant effect on sperm concentration and motility and pregnancy rate, but improved total sperm count, sperm morphology, compared to the control group, which included studies done with Selective estrogen receptor modulators (SEMR) or testosterone undecanoate (TU). Conclusion: LE or AZ may be effective in the treatment of low T / E2 male infertility, perhaps better than other anti-estrogen or exogenous testosterone supplementation. In addition, we should pay special attention to the changes of E2 during treatment.