Effect of Sildenafil in Endometrial Ripening with Induction of Ovulation by Clomiphene Citrate in Polycystic Ovarian Syndrome; Double Blinded; Randomized Controlled Trial

Back ground: World Health Organization (WHO) defines infertility as a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. Worldwide, 8 to 12 percent of couples experience fertility problems. Causes of infertility in women were as follows: menstrual disorders (disorders of cycle length and flow) 62.6%, diseases (obesity, thyroid diseases, diabetes) 58.7%, impaired ovulation (hormonal disorders, oligoovulation and anovulation) 50.3%, uterine causes 16.7%, tubal factor 15.4%, and cervical causes 7.9%. In the male factor fertility there was semen abnormalities (44.6%), genetic factors (29.8%), anti-spermatogenesis agents (11%), and vascular disorders (17.2%). Aim of the Study: The purpose of this study is to evaluate the effect of sildenafil in endometrial ripening with induction of ovulation by clomiphene citrate in polycystic ovarian syndrome. Patients and methods: It is a randomized controlled trial on 65 infertile women with polycystic ovarian syndrome; patients were randomly divided into two equal groups. In control group, 31 patients were given oral sildenafil, one tablet every 12 hrs. From 2nd day of the cycle till 12th day and clomiphene citrate, one tablet every 12 hours, for 5 days from 3rd day of the menstrual cycle. In study group, 34 patients were given oral placebo, one tablet every 12 hrs. From 2nd day of the cycle till 12th day and clomiphene citrate, one tablet every 12 hours, for 5 days from 3rd day of the menstrual cycle. A transvaginal ultrasound was performed to evaluated the endometrial thickness before and after treatment, the follicularometeric was measured on day 11 and day13. Uterine artery Doppler was then measured. Qualitative serum B-hCG level was checked 14 days after ovulation to assess clinical pregnancy rate. Design: Prospective, Double blinded randomized controlled trial. Setting: Obstetrics & Gynecology outpatient clinic, Ain Shams University Hospital. Study duration: 3 months. Results: The present study was a double-blind, randomized, controlled study that was conducted on 65 women with PCOS who underwent induction of ovulation by Clomiphene citrate in outpatient clinic of Ain Shams University hospital. Conclusion: Our systematic review and meta-analysis showed that follicular 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. Future high-quality RCT with large sample size to evaluate the sildenafil citrate effect in women undergoing assisted reproduction are needed. Future RCTs should focus on type of processing, stage of embryo, embryo quality, dosage, time of administration, type of control group, in order to identify the groups of patients who would benefit the most from this intervention and the most appropriate dosage, time, and type of sildenafil citrate which would have the most positive effect and the less possible side effects.