Effect of sildenafil citrate in women undergoing assisted reproduction: a meta-analysis based on randomized controlled trials

Abstract

Background to evaluate whether the sildenafil citrate in women undergoing assisted reproduction ameliorate the clinical outcomes. Methods We performed a comprehensive literature search for published randomized controlled trials (RCT) in Medline, Embase, Scopus, Web of Science and Cochrane Central Register of Controlled Trials from inception to 25 Jun 2020. Literature screening, selection of relevant studies, assessment risk of bias and data extraction was conducted independently by two reviewers. We combined study data using the random-effects model. Results Sixteen trials including 1,589 women (771 cases and 818 controls) were included in meta-analysis. Pooling results from five trials, which compared clinical pregnancy between sildenafil citrate and placebo, showed a significantly higher probability of clinical pregnancy in sildenafil citrate group (RR: 1.57, 95% CI: 1.05, 2.36, I2 = 0%). The probability of clinical pregnancy was significantly higher in women who received the combination of sildenafil citrate and clomiphene citrate compared with clomiphene citrate alone (RR: 1.31, 95% CI: 1.12, 1.53, I2 = 0%). Following the intervention, clinical pregnancy significantly increased in women who received the combination of estradiol valerate and sildenafil citrate compared to estradiol valerate (RR: 1.59, 95% CI: 1.05, 2.43, I2 = 0%). Following the intervention, endometrial thickness (ET) increased in women who received sildenafil citrate compared to women who received placebo (SMD: 1.32, 95% CI: 0.30, 2.34, I2 = 92.41%). The mean of ET was significantly higher in women who received the combination of sildenafil citrate and clomiphene citrate compared to women who received clomiphene citrate (SMD: 0.92, 95% CI: 0.49, 1.36). Conclusion Our systematic review and meta-analysis showed that luteal supplementation of sildenafil citrate (oral or vaginal), alone or adjuvant therapy can be used for improving the EM and clinical pregnancy rate in women undergoing assisted reproduction. However, given the methodological limitations the current evidence does not support its use in clinical practice yet.