Neither sildenafil nor vaginal estradiol improved endometrial thickness in women with thin endometria after taking oral estradiol in graduating dosages

Abstract

Reduced pregnancy rates (PRs) have been associated with maximum endometrial thickness of ≥8 mm immediately prior to progesterone (P) secretion or supplementation. Some claims have been made that treatment with sildenafil citrate or vaginal estradiol (E2) can improve endometrial thickness in women with poor response to oral E2. The present study randomly assigned women attempting frozen embryo transfer (ET) who failed to attain an 8 mm endometrial thickness following graduating dosages of oral E2 to treatment with oral E2 plus 25 mg 4× per day of sildenafil from day 3 to 9 of cycle (vaginal wash day 10) or oral E2 plus 2 mg 2× per day of vaginal E2 from day 2 to peak thickness. Sixteen patients with a mean number of 1.5 attempted but cancelled frozen ET cycles were selected. The mean endometrial thickness for those cycles following oral E2 treatment was 6.6 mm and was 6.3 mm on cycles immediately prior to the study. Nine patients took sildenafil and the average maximum thickness was 6.4 mm. Seven women randomized to vaginal E2 had a mean endometrial thickness of 7.2 mm. Three of the 9 women first taking sildenafil tried a second cycle with the vaginal E2 regimen and the maximum thickness was 7.3 mm. Six of the 7 women who took vaginal estrogen first tried sildenafil but the maximum thickness attained was 6.8 mm. Frozen ET was attempted in only 6 of the 16 women (4 with sildenafil and 2 with vaginal E2) and only 1 pregnancy (16.6%) was achieved in a woman on the sildenafil treatment. During the same time period the PR at our center for women up to age 45 following frozen ET was 35.0% (n = 513). These data suggest that in general neither the addition of sildenafil therapy nor vaginal E2 improves maximum endometrial thickness. Sildenafil failed to improve the endometrial thickness in 15 of 15 women and vaginal E2 failed in 10 of 10 women. These data do not preclude the possibility that an occasional patient could respond to these treatments. These data are consistent with previous conclusions that thin endometria are associated with a lower PR following ET.