Sildenafil increased the Applebaum score and pregnancy rate in patients with unexplained infertility: a double-blind randomized controlled trial

Abstract

Abstract Introduction: Ovarian stimulation with clomiphene is often associated with low pregnancy rates despite high ovulation rates in patients. Several approaches have been proposed to improve the results of clomiphene induction cycles, including the adjuvant use of sildenafil and estradiol. However, the efficacy of these adjuvants has been assessed in the majority of studies by measuring endometrial thickness, yet some evidence has reported a lack of correlation between endometrial thickness and clinical pregnancy rate. Our study therefore aims to compare the effects of sildenafil on the biophysical profile of the uterus (Applebaum score) and pregnancy rate, in comparison with valerate estradiol, among patients with unexplained infertility undergoing clomiphene induction cycles. Methods: This was a double-blinded, randomized controlled trial that compared two ovarian stimulation protocols in patients with unexplained infertility. Eligible patients who consented to this study were randomly assigned to one of two groups: clomiphene + sildenafil or clomiphene + estradiol valerate. The outcomes measured were clinical pregnancy rates and Applebaum scores. Results: The mean Applebaum scores of patients in the sildenafil group were significantly higher than those in the estradiol group (P=0.000). The rate of biochemical pregnancy was comparable and not significantly different between both randomization groups (P=0.385). However, the clinical pregnancy rate was significantly higher in the sildenafil group, at 28.92% versus 20.83% in the control group (P=0.04). Conclusion: As compared to estradiol valerate, the addition of sildenafil as an adjuvant during clomiphene ovulation induction cycles is associated with a high rate of clinical pregnancy and a good Applebaum score in patients with unexplained infertility. Study registration: Registry: Pan African Clinical Trials Registry Trial n°: PACTR 202310849449401 Date of registration: October 12, 2023.