Adding sildenafil vaginal gel to clomiphene citrate in infertile women with prior clomiphene citrate failure due to thin endometrium: a prospective self-controlled clinical trial.

We aimed to investigate the effect of adding sildenafil vaginal gel to clomiphene citrate (CC) in infertile women with prior CC failure.

METHODS: This is a self- controlled clinical trial. Women with CC failure (in prior 5 cycles) and thin endometrium were recruited (N = 42). In their 6th (CC only) cycle, women continued on CC 100 mg/ day for 5 days, and had measurement of endometrial thickness and Doppler assessment of uterine arteries on day of HCG administration. In the 7th cycle, women (N = 36) were given usual dose of CC supplemented with sildenafil vaginal gel (5 gm, containing 50 mg sildenafil) twice daily from cycle day 8 to day of HCG administration. Endometrial thickness and uterine artery Doppler were measured on the day of HCG injection.

RESULTS: In the 7th (CC + sildenafil vaginal gel) cycle, endometrial thickness was significantly higher than in the 6th (CC only) cycle (9.3 mm +/- 3.1mm versus 6.6 mm +/- 1.4 mm, respectively, P = < 0.001). Uterine artery pulsatility index dropped from 2.4 +/- 0.8 in 6th cycle to 1.6 +/- 1.3 in 7th cycle (P = 0.002). Clinical pregnancy rate increased but numbers were too small (only 3 pregnancies).

CONCLUSION: Sildenafil vaginal gel significantly increased endometrial thickness and uterine blood flow, and may improve pregnancy rate in patients with CC failure due to thin endometrium. Mucoadhesive vaginal gel formulation allowed shorter duration of sildenafil application, and less frequent daily dosing.