What is the effect of sildenafil citrate intake on women undergoing assisted reproduction? A systematic review and meta-analysis of randomized controlled trials

Assisted reproductive technologies (ART) have become a vital option for women facing fertility challenges. One of the potential interventions being explored is the use of sildenafil citrate (SC) to improve clinical outcomes in ART procedures. The aim of this study was to assess the impact of SC on clinical outcomes in women undergoing ART. A comprehensive literature search was conducted using multiple databases, including PubMed, Scopus, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. The search covered studies from inception until April 15, 2023, and identified relevant randomized controlled trials (RCTs) for inclusion in the analysis. The endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). After meticulous analysis, twenty-eight RCTs comprising 3,426 women were included in the study. The results revealed significant findings regarding the impact of SC on clinical pregnancy (CP) rates. Women receiving SC demonstrated a significantly higher probability of CP compared to the control group (n=21 RCTs, RR=1.43; 95% CI: 1.29, 1.59). Additionally, when SC was combined with other medications like clomiphene citrate (CC) or estradiol valerate, it further improved the likelihood of CP compared to these medications alone (RR=1.35, 95% CI: 1.19, 1.53; RR=1.55, 95% CI: 1.08, 2.22, respectively). Furthermore, the study observed that the mean endometrial thickness (ET) was significantly higher in women who received SC compared to the control group, which involved other active interventions or placebo (SMD=0.77, 95% CI: 0.20, 1.34). Particularly, the administration of SC resulted in a notably higher ET level compared to the placebo (SMD: 1.33, 95% CI: 0.15, 2.51). The findings suggest that luteal supplementation of SC can be considered a beneficial approach to enhance ET and improve the CP rate in women undergoing ART.