The Effects of Sildenafil Citrate on the Success Rate of Ovulation Induction Using Clomiphene: A Randomized Controlled Trial

Abstract

Appropriate embryonic development, coincident with a receptive endometrium, which occurs during the mid-luteal phase of the menstrual cycle, is very important for successful embryo implantation. Implantation is a complex process controlled by number of molecules as hormones, growth factor and cytokines, but the initial steps give the opposition and attachment of the blastocyst to the epithelial layer of the endometrium. Several reports have shown correlation between thin endometrium and low implantation rates .The commonly expected minimal endometrium thickness at the end of follicular phase associated with conception is 7 mm). Endometrial growth is a hormone dependent process requiring appropriate uterine blood flow. Thin endometrium may be due to high blood flow impedance of uterine radial arteries: the lower extremity of the uterine arteries Different vasodilating agents have been proposed to thicken endometrium and to favor uterine relaxation such as: sildenafil, glyceryltrinitrate, nifedipine, nimodipine, pentoxyfylline and isosorbide monohydrate. Sildenafil is aphosphodiestrase-5-specific inhibitor that increases the vasodilatory effects of nitric oxide on vascular smooth muscle by preventing the degradation of cGMP so its vaginal administration could lead to an improvement of uterine blood flow. Clomiphene citrate is considered the treatment of choice in anovulatory women with polycystic ovary disease. It is efficient as an oral ovulation induction drug, with low cost, minimal side effects and low incidence of complications, but many studies showed that it causes retardation of endometrial growth during the proliferative phase and delayed endometrial development based on textural patterns. It also causes reduction in glandular density and an increase in the number of vacuolated cells, so using sildenafil may be effective on prevent or overcoming the effect of CC on endometrial thinning. This prospective randomized controlled clinical trial study aimed to evaluate the efficacy of sildenafil citrate on the clinical pregnancy rate in 210 women With PCO undergoing induction of ovulation using clomiphene citrate that were recruited to two groups in two steps: First step: A) Group I (Sildenafil plus clomiphene citrate group): Patients received 25 mg of sildenafil citrate (sildin 25mg , EIPICO pharma company) 6 hourly orally (day 6 to the end of the cycle), and 100 mg/day of clomiphene citrate (clomid 50mg, SANOFI company ) once orally (day 2 to 6) by the patient. B) Group II (clomiphene citrate placebo group ): Patients received clomiphene 100mg/day (clomid 50mg, SANOFI company) once orally (day 2 to 6) with placebo (oral pills of same size, shape and color of sildenafil /daily) by the patient. The first step protocol is used for 3 consecutive cycles then we waited for one cycle for washing of body medication.