Objective: The widespread classic PCOS treatment algorithm, consisting of 6-12 cycles of clomiphene followed by shifting to gonadotropins in case of failure to conceive, doesn't really address the cause of failure to conceive despite documented ovulation. Sildenafil citrate improves uterine blood flow, enhances endometrial development and modulates endometrial receptivity. Hence, this study monitored the ovarian response, endometrial development and subendometrial Doppler changes in PCOS women with previous clomiphene citrate failure following the use of adjuvant sildenafil citrate instead of shifting to gonadotropins.  Patients and Methods: A double-blinded randomized controlled trial was conducted in Ain-Shams University Women's Hospital on 850 PCOS women with clomiphene failure. Those were randomized to clomiphene therapy, either with adjuvant placebo or sildenafil citrate (25 mg orally 6 hourly), starting from the 6th day till the end of the cycle.
Folliculometry, every other day, started on the 10th day of the cycle. When ≥1 follicle reached a size ≥18mm, transvaginal ultrasound assessment of the endometrium and uterine/subendometrial Doppler was done. The resulting pregnancy rates were recorded.  Results: The sildenafil group developed higher endometrial thickness (10.6±1.3 versus 9.4±1.5; p<0.001), a higher percentage of women with trilaminar endometrium (78.35% versus 59.76%; p<0.001) was found while the lower percentage was found with subendometrial and uterine artery Doppler indices (p<0.001 for all). It also developed higher pregnancy rates (43.7% versus 34.5%, p=0.006; NNT=10.8, 95% CI: 6.36 – 37.84).
Conclusion: Sildenafil adjuvant therapy significantly increased pregnancy rates, improved endometrial development in terms of endometrial thickness and pattern as well as uterine and subendometrial blood flow.