Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF.
Endometrial growth is thought to depend on uterine artery blood flow and the importance of endometrial development on in-vitro fertilization (IVF) outcome has been previously reported. Nitric oxide (NO) relaxes vascular smooth muscle through a cGMP-mediated pathway and NO synthase isoforms have been identified in the uterus. Sildenafil citrate (Viagra), a type 5-specific phosphodiesterase inhibitor, augments the vasodilatory effects of NO by preventing the degradation of cGMP. In this preliminary report we describe the use of vaginal sildenafil to improve uterine artery blood flow and sonographic endometrial appearance in four patients with prior failed assisted reproductive cycles due to poor endometrial response. The uterine artery pulsatility index (PI) was measured in a mock cycle after pituitary down-regulation with Lupron. The PI was decreased after 7 days of sildenafil (indicating increased blood flow) and returned to baseline following treatment with placebo. The combination of sildenafil and oestradiol valerate improved blood flow and endometrial thickness in all patients. These findings were reproduced in an ensuing gonadotrophin-stimulated cycle. Three of the four patients conceived. Although greater numbers of patients and randomized evaluation are needed to validate this treatment, vaginal sildenafil may be effective for improving uterine artery blood flow and endometrial development in IVF patients with prior poor endometrial response.
Sher
G
G
Sher Institute for Reproductive Medicine, 3121 S. Maryland Parkway, Suite 300, Las Vegas, Nevada 89109, USA.
Fisch
J D
JD
D000282:Administration, Intravaginal; D001158:Arteries / Q000187:drug effects; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000378:metabolism; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011247:Pregnancy; D011673:Pulsatile Flow / Q000187:drug effects; D011687:Purines; D012646:Self Administration; D000068677:Sildenafil Citrate; D013450:Sulfones; D014463:Ultrasonography; D014599:Uterus / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D004958:Estradiol; D000068677:Sildenafil Citrate; D006152:Cyclic GMP