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Objective: Clomiphene citrate (CC) has some negative effects on the endometrium. We evaluated the effect of concomitant administration of oral sildenafil and estrogen on endometrial thickness (ET), pattern and pregnancy rates in CC stimulated cycles in infertile women diagnosed as unexplained infertility.  Aim of the Work: Compare the effect of sildenafil‌-estrogen combination to estrogen alone on endometrium thickness in infertile women.  Materials and methods: It is a randomized controlled trial on 90 infertile women with unexplained infertility; patients were randomly divided into two equal groups. In control group, 45 patients were given ovulation induction with CC 100mg/d from 2nd to 6th day of cycle and oral estradiol valerate 2mg 12 hourly from 2nd day of the cycle till the day of trigger of ovulation. In study group, 45 patients were given ovulation induction with CC100mg/d from 2nd to 6th day of cycle, estradiol valerate 2mg 12 hourly plus oral sildenafil citrate 25mg every 8 h from 2nd day of the cycle till the day of hCG trigger. A transvaginal ultrasound was performed on day 10 to assess follicular growth until the detection of at least one dominant follicle ≥18 mm. At that time, the endometrium was evaluated as regards both endometrial thickness and pattern. Uterine artery resistive index (RI) was then measured. Qualitative serum B-hCG level was checked 14 days after ovulation to assess chemical pregnancy rate.  Results: Mean endometrial thickness at the time of hCG trigger was 9.8 mm in study group and 8.42 mm in control group (p value <0.001). 88.9% patients given sildenafil had trilaminar endometrium whereas 29% patients without sildenafil had trilaminar endometrial pattern (p value = 0.006). Mean uterine artery resistive index (RI) after adding sildenafil was non-significantly lower among study group than among control group; the values were 0.66 and 0.72, respectively (P= 0.078). Pregnancy rates in study group and control group were 17.8% and 11.1%, respectively.  Conclusion: Sildenafil‌-estrogen combination has a potent effect on improving the endometrium (thickness and pattern) in patients undergoing induction of ovulation by clomiphene citrate. This improvement in endometrial development has a weak positive feedback on pregnancy rate.

The effect of estradiol valerate with and without oral sildenafil on endometrial thickness and pregnancy rates in infertile women: A R.C.T