The Effect of Vaginal Sildenafil on The Outcome of Assisted Reproductive Technology Cycles in Patients with Repeated Implantation Failures: A Randomized Placebo-Controlled Trial

The aim of this study was to investigate the effects of vaginal sildenafil on the outcome of patients with at least two times of unsuccessful IVF / ICSI.

Method and Material(s): A total of 66 infertile women aged ≤ 38 years, with a history of normal ovarian reserve, two prior consecutive failed IVF/ICSI attempts, hCG day endometrial thickness <7 mm in all prior IVF/ICSI cycles, normal endometrial appearance in hysteroscopy or hysterosonography or hysterosalpingography were studied. The conventional GnRH protocol was used for ovarian stimulation. The patients were randomly divided into three groups: vaginal sildenafil (100 mg/daily), a combination of placebo (vaginal supp.) and vaginal Sildenafil (100 mg/daily), and placebo alone (vaginal sup.). All patients underwent color Doppler ultrasound (day 14 previous cycle) to investigate any abnormality in uterus and adnexa, and endometrial parameters including thickness, echo pattern, uterine artery resistance and pulsatility indices were recorded pre- and post-treatment. The primary outcome measures were implantation, chemical and clinical pregnancy rates. For data analysis, SPSS version 20 software was used. In all tests, the significance level was considered less than 0.05.

There was no significant difference between three groups in endometrial thickness on hCG injection day. The chemical and clinical pregnancy in women who received sildenafil (alone or in combination with placebo) showed a two-fold increase in comparison to those who just used placebo. This increase was clinically meaningful, but according to sample size, it was statistically non-significant. The results of our study showed that the implantation is also higher in women who received placebo + sildenafil compared than those in two other groups. Abortion rate was not statistically significant among the groups.

It seems that vaginal sildenafil may, conceivably, improve chemical and clinical pregnancy rates in repeated IVF failure patients. Further randomized clinical trials using oral or vaginal sildenafil with higher sample size are recommended.