Adequate growth of the endometrium is crucial for implantation. Accordingly, the pregnancy success rate of patients with a thin endometrium is low. Furthermore, there is a little information about the factors responsible for impaired endometrial growth in patients with a thin endometrium. The researches have revealed that nitric oxide (NO) release can cause relaxation of vascular smooth muscle through a cyclic guanyl monophosphate (cGMP)-mediated pathway. Sildenafil is a type 5-specific Phosphodiesterase inhibitor that augments the vasodilatory effects of NO on vascular smooth muscle by preventing the degradation of cGMP and could improve blood flow and endometrial thickness. This study is designed to evaluate the effect of vaginally administered sildenafil suppositories on IVF/ICSI outcome of infertile patients with repeated IVF/ICSI failures.

The proposal of this study approved by our institutional review boards and institution's ethical committee, and all participants will sign a written consent before enter to study.

The study population will consist of infertile women of <38 years of age with repeated in vitro fertilization/ intra cytoplasmic injection failures. Endometrial parameters including endometrial thickness, endometrial pattern , pulsatility index (PI) and resistance index (RI) will be evaluated with the use of color Doppler ultrasound on the day of hCG administration. Patients will be randomly divided into 3 groups, A, B and C. In the subsequent menstrual cycle, in group A, vaginal sildenafil suppositories (100 mg/day) will be given daily from the start of human menopausal gonadotropin (HMG) administration day until the day of oocyte retrieval. In group B, the women will receive daily vaginal placebo from the start of HMG administration day until 2 days before the human chronic gonadotrophin (hCG) injection day, then will be switched to vaginal sildenafil suppositories (100 mg/day) until the day of oocyte retrieval. In group C, vaginal placebo will be given daily from the start of human menopausal gonadotropin (HMG) administration day until the day of oocyte retrieval.

When the diameter of at least 2 follicles will be reached equal or greater than 18 mm, hCG 10,000 IU will be administered. In all patients, ovarian stimulation will be performed with the conventional GnRh agonist protocol. Endometrial parameters will be measured again on the day of hCG injection. Ovum pick up will be performed 34-36 h after hCG injection and embryos will be transferred 48-72 hours after oocyte retrieval. Pregnancy will be confirmed by assessment of βHCG level 14 days after embryo transfer and ultrasonographic visualization of gestational sac during the 5th week of pregnancy.

Inclusion Criteria:

• Women with normal ovarian reserve and had at least two prior cycle with FSH <10 mIu/ml
• Women with history of two or three prior consecutive failed IVF/ICSI attempts using at least two good quality fresh or frozen-thawed embryos.
• Endometrial thickness on the day of hCG injection was < 9 mm in all prior IVF/ICSI attempts
• Women with normal endometrial appearance in hysteroscopy or hysterosonography or hysterosalpingography

Exclusion Criteria:

• Women who had history of PCOS, myomectomy, Asherman's Syndrome and mullerian anomalies