Sildenafil citrate as an adjuvant to clomiphene citrate for ovulation induction in polycystic ovary syndrome: crossover randomized controlled trial

Introduction
To evaluate sildenafil citrate as an adjuvant to clomiphene citrate (CC) for ovulation induction (OI) in women with polycystic ovary syndrome (PCOS).

Material and methods
A total of 595 infertile PCOS women were randomly assigned into either a clomiphene/sildenafil (C/S) group or a CC group. Transvaginal (TVS)-Doppler studies were done for participants when the dominant follicle reach 16 mm, to measure the resistance index, pulsatility index, and maximum velocity of sub-endometrial, uterine, and ovarian vessels. Participants were examined using TVS on the 21st day of the cycle to detect ovulation or, after a positive pregnancy test, for documentation of pregnancy. Participants with negative pregnancy tests were given 2 months’ rest without OI, followed by crossover of OI medication between the 2 studied groups. The crossover results were assessed by TVS, TVS-Doppler, and pregnancy test.

Results
The endometrial thickness was significantly higher among the C/S than the CC group during the first 3 months (9.6 ± 1.2 vs. 8.7 ± 1.0 mm, respectively, p = 0.003) and after crossover of OI (9.1 ± 1.3 vs. 8.2 ± 1.0 mm, respectively, p = 0.007).The chemical and clinical pregnancy rates were significantly higher among the C/S compared to the CC group (39.8% and 36.6% vs. 25% and 18.98%, respectively) (p = 0.01 and 0.001, respectively) during the first 3 months and after crossover of OI (36.6% and 33.1% vs. 23.8% and 20.6%, respectively) (p = 0.02 and 0.01, respectively).

Conclusions
SC as an adjuvant to CC for OI in PCOS women increases the chemical and clinical pregnancy rates. It also improves the endometrial thickness and ovulation rate through improved endometrial and ovarian Doppler indices.