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

NCT04283435 | Unknown Phase 1

• 1 other identifier: PROTOCOL 500
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

IVF; Endometrial Receptivity

Outcome Measures

Primary Outcomes (1)

• Clinical Pregnancy rate

  2 weeks after embryo transfer

Secondary Outcomes (4)

• endometrial thickness

  at the time of embryo transfer

• Endometrial volume

  at the time of embryo transfer

• Uterine artery doppler indices

  at the time of embryo transfer

• 3D endometrial and subendometrial vascular indices(VI,FI.VFI)

  at the time of embryo transfer

Study Arms (2)

estradiol valerate + placebo

PLACEBO COMPARATOR

preparation of the endometrium with Estradiol valerate 2mg/day (every 8 hours)(white tablets of cycloprogenova) .from the first day of the cycle till 12th day and we add placebo from the first day of the cycle till the day of start progesterone (we stop 3 days before embryo transfer).

Other: Placebo; Drug: Estradiol Valerate

estradiol valerate + Sildenafil citrate

EXPERIMENTAL

We add Sildenfil citrate 50 mg daily from the first day of the period till the day of starting the progesterone. and stop 3 days before the embryo transfer.

Drug: Sildenafil Citrate; Drug: Estradiol Valerate

Interventions

Sildenafil Citrate DRUG

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)

estradiol valerate + Sildenafil citrate

Placebo OTHER

Placebo tablet (multivitamins),Pregnacare vitamins (Vitabiotics,UK)

Also known as: Pregnacare vitamins (Vitabiotics,UK)

estradiol valerate + placebo

Estradiol Valerate DRUG

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

estradiol valerate + Sildenafil citrate; estradiol valerate + placebo

Eligibility Criteria

• Age: 25 Years - 40 Years
• Gender Eligibility Details: Females undergoing IVF
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Cairo University

Cairo, Egypt

Location

MeSH Terms

Interventions

Sildenafil Citrate; Estradiol

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Eman Elkattan, MD

CONTACT

01212529213; emyelkattan@gmail.com

wafaa Ramadan, MD

CONTACT

01019944328

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: One hundred envelopes will be numbered serially and in each envelope the corresponding letter which denotes the allocated group will be put according to randomization table. When the first patient arrives, the first envelope will be opened and the patient will be allocated according to the letter inside.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: February 25, 2020
• Study Start: September 1, 2021
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: August 20, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)