Endometrial Effects of Sildenafil in Frozen-Thawed Cycles in Women With Thin Endometrium

Effect of Sildenafil on Uterine and Endometrial Vasculature in Women With Thin Endometrium Having Frozen-Thawed IVF Cycles

Management of Thin endometrium in IVF is challenging. Thin endometrium is often defined as <7 mm or < 8 mm on the day of Human Gonadotropin administration(Bu and Sun, 2015; Wu et al., 2014).

Its incidence is 1-2.5% in most studies ( AlGhamdi et al.,2008).

Endometrial thickness and endometrial vascularity is closely linked to endometrial receptivity.Improving endometrial receptivity is a predictor of the success in IVF.

Many medications have been tried to improve endometrial thickness as Aspirin,sildenafil citrate,luteal estradiol and Granulocyte colony stimulating factor.

Nitric oxide (NO) is a key signaling molecule involved in the vasodilator response of smooth muscle cells. NO activates the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway within smooth muscle cells to promote smooth muscle cell relaxation. Sildenafil citrate inhibits phosphodiesterase 5 (PDE5) maintaining activation of cGMP and PKG and maximizing the effect of existing NO, thus facilitating smooth muscle cell relaxation. The potent vasodilator action of sildenafil has led researchers to evaluate sildenafil as a treatment in assisted reproduction where low uterine blood flow is perceived to be a contributor to implantation failure (Fairouzabadi et al.2013).

The investigators aim at this study to investigate the role of sildenafil citrate on endometrial and subendometrial vasculature in women with thin endometrium undergoing Frozen-Thawed IVF cycles.

This is a Randomised-controlled trial .The investigators recruited 100 women who are known to have thin endometrium in previous IVF cycles (failed/cancelled cycles).

They are randomised into group A (50 women) : preparation of the endometrium with Estradiol valerate 2mg/day (every 8 hours)(white tablets of cycloprogenova,Payer,Germany) from the first day of the cycle till 12th day and The investigators add placebo from the first day of the cycle till the day of starting progesterone (It will be stopped 3 days before embryo transfer).Group B (50 women): The investigators add Sildenafil citrate (Viagra,pfizer,United states) to the estradiol valerate. Sildenafil 50 mg will be used daily from the first day of the cycle till the day of starting progesterone (It will be stopped 3 days before embryo transfer). The embryos will be transferred depending on their age on day 3 or day 5.

At the transfer date ,the investigators will assess the endometrial thickness, endometrial volume, uterine artery doppler indices (RI,PI) as well as 3D endometrial vascular indices (VI,FI,VFI) .

Inclusion Criteria:

• Women (25 -40 years) undergoing IVF frozen-Thawed cycles and known to have good quality embryos.
• previous thin endometrium (< 8mm on at least 3 previous cycles) with normal Hysteroscopy findings

Exclusion Criteria:

• women less than 25 years old or more than 40 years old.
• abnormal hysteroscopic findings.
• women with congenital uterine anomalies.
• History of previous uterine surgery
• Any contraindication to Sildenafil as Previous history of cardiac disease or stroke.