Comparative effectiveness of Sildenafil Citrate and Estradiol Valerate as adjuvants during Clomiphene Citrate-assisted ovarian stimulation cycles in Patients with unexplained infertility: A double-blind randomized controlled trial in Kisangani, DRC

Abstract

Objective This study aimed to assess the effect of sildenafil citrate and estradiol valerate as adjuvant therapy during ovarian stimulation cycles with clomiphene citrate in patients with unexplained infertility to update infertility management guidelines in Kisangani. Method A double-blind, randomized controlled trial was conducted for two years (from October 1, 2021, to October 31, 2023). The population included 148 patients, 74 of whom were on clomiphene citrate + sildenafil citrate (CCSC) regimens and 74 of whom were on clomiphene citrate + estradiol valerate (CCEV) regimens for three months. The primary indicator was the conception rate, with secondary outcomes encompassing endometrial thickness, appearance and vascularity, the number of mature follicles and ovulation rate. Results Perifollicular flow was predominantly high-grade (P = 0.002), and the ovulation rate and clinical pregnancy rate were greater (P = 0.006) in the CCSC group than in the CCEV group. However, biochemical pregnancy rate, endometrial vascularity/thickness, and the number of Graafian follicles were not significantly different. The two groups were comparable in terms of sociodemographic and clinical characteristics. The mean duration of attempting to conceive was 4.39 years versus 4.36 years, and the mean AFC was 11.51 versus 11.46, respectively, in the CCSC versus CCEV groups. Secondary infertility was the most frequent type in each of the two participant assignment groups. Conclusion As an adjuvant, sildenafil increases the rate of clinical pregnancy more than does estradiol in patients with unexplained infertility undergoing ovarian stimulation with clomiphene citrate. However, both sildenafil citrate and estradiol valerate can protect the endometrium from the harmful antiestrogenic effects of clomiphene. Study registration: PACTR 202310849449401 ( Pan African Clinical Trials Registry)