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

IVF Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04283435
• Other study ID #: PROTOCOL 500
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: September 1, 2021
• Est. completion date: March 1, 2022

Study information

• Verified date: August 2021
• Source: Cairo University
• Contact: Eman Elkattan, MD
• Phone: 01212529213
• Email: emyelkattan[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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) .

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: March 1, 2022
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Endometrial Receptivity
• IVF

Intervention

Drug:
• Sildenafil Citrate
Sildenafil Citrate 50 mg tablets taken from the first day of the cycle till the day we start progesterone (we stop 3 days before embryo transfer)

Other:
• Placebo
Placebo tablet (multivitamins),Pregnacare vitamins (Vitabiotics,UK)

Drug:
• Estradiol Valerate
Estradiol valerate tablets 2mg every 8 hours daily starting from the fist day of the cycle till 12th day of the menstrual cycle.

Locations

Country	Name	City	State
Egypt	Cairo University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Pregnancy rate		2 weeks after embryo transfer
Secondary	endometrial thickness		at the time of embryo transfer
Secondary	Endometrial volume		at the time of embryo transfer
Secondary	Uterine artery doppler indices		at the time of embryo transfer
Secondary	3D endometrial and subendometrial vascular indices(VI,FI.VFI)		at the time of embryo transfer