Effect of nitric oxide donors on uterine and sub-endometrial blood flow in patients with unexplained infertility: a randomized controlled trial

Abstract

Background: Impaired sub-endometrial perfusion might reduce endometrial receptivity and possibly contribute to unexplained infertility. A favorable effect on sub-endometrial blood flow has been demonstrated with nitric oxide. Methods: This randomized controlled trial evaluated the effect of nitroglycerine on uterine and sub-endometrial blood flow in women with unexplained infertility. Sixty women were randomized into 2 equal groups. The study group received 5mg nitroglycerine patch daily from day 2 of the cycle till the evaluation day and the control group received no treatment. Independent of the study arms, 30 parous women were included as the fertile group. Six to eight days after detecting luteinizing hormone surge, women were assessed for endometrial thickness, uterine artery blood flow with color Doppler and sub-endometrial blood flow with three-dimensional power Doppler. Results: Compared to fertile women, cases with unexplained infertility (control group) had a significantly thinner endometrium, higher uterine artery Doppler indices and lower sub-endometrial blood flow. Women who received nitroglycerin showed a significant improvement in sub-endometrial blood flow while uterine artery blood flow did not show a significant difference; however, the values were also comparable to fertile women. In addition, no effect on endometrial thickness was found with nitroglycerin treatment. Nitroglycerin treatment side effects were headache, blurring of vision and hypotension. These adverse effects were not significant compared to controls. Conclusions: In women with unexplained infertility, nitroglycerin significantly improved the sub-endometrial blood flow but did not affect the endometrial thickness.