Effect Sildenafil and Estradiiol Valerate on Endometrial Thickness in Infertile Women

Not Applicable

Completed

• Conditions: Endometrial Thickness
• Interventions: Drug: estradiol valerate and sildenafil

• Registration Number: NCT03301233
• Lead Sponsor: Ain Shams University

Brief Summary

The endometrium is a dynamic tissue that responds to changing hormonal signals throughout the cycle. The changes in the endometrial composition are expressed in alteration in gene expression, micro architectural morphological changes as well as in protein and hormone secretion. These factors combine together to construct the "window of implantation" a short period of time during the luteal phase in which the endometrium is receptive.

Thin endometrium is associated with a low pregnancy rate. Endometrial thickness 7 mm in the pre-ovulatory phase is widely accepted to be cut-off of thin endometrium.

for that the aim of this study is to compare the effect of sildenafil-estrogen combination to estrogen alone on endometrium thickness in infertile women. Half of the patients will receive estrogen ( estradiol valerate ) and the other half will receive combination of sildenafil-estrogen .

Detailed Description

Being a hormone dependent tissue, the endometrium proliferates in response to estrogen, which further induces the production of progesterone receptors. As a result, infertile patients who demonstrated thin endometrium, were offered estradiol (E2) remedies, in an attempt to improve endometrial proliferation. Most of the studies regarding E2 treatment in patients with thin endometrium dealt with frozen-thawed embryo transfer cycles. Moreover, while there are several routes and duration of administration of E2, including per Os, transdermal, Intramuscular and vaginal, no compelling advantage for one protocol for endometrial preparation over another, with regard to pregnancy rates, has been established.

Sildenafil acts as a type 5-specific phosphodiesterase inhibitor hence augments the vasodilatory effects of nitric oxide by preventing the degradation of cGMP. Nitric oxide (NO) relaxes vascular smooth muscle through a cGMP-mediated pathway and NO synthase isoforms have been identified in the uterus. A decade ago, Sher and Fisch studied the effect of vaginal sildenafil on the endometrial thickness of infertile patients with poor endometrial development, who underwent IVF treatment. They have demonstrated improved uterine artery blood flow and endometrial growth, with higher implantation and ongoing pregnancy rates following vaginal sildenafil administration.

Study Timeline

• Study First Submitted: 2017-09-24
• Study First Submitted QC: 2017-09-28
• Study First Posted: 2017-10-04
• Study Start: 2017-11-01
• Primary Completion: 2018-07-01
• Study Completion: 2018-07-30
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-13
• Last Update Posted: 2018-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 90

Inclusion Criteria

1. Patients having ovulatory infertility.
2. Age: 20-35 years old.
3. BMI less than 30 kg/m2

Exclusion Criteria

1. Women who have any congenital uterine anomaly (e.g., unicornuate uterus or infantile uterus) or acquired deformities of the uterine cavity that interfere with embryo implantation (as Asherman Syndrome).
2. Women who have any tubal factor that relates to infertility (e.g., tubal adhesion or previous ectopic pregnancy).
3. Women who have contraindication for estrogen treatment (e.g., history of stroke, DVT and Benign liver disease).
4. Women who have male factor for infertility (e.g., azoospermia, teratospermia).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
estradiol valerate and sildenafil	estradiol valerate and sildenafil	oral estradiol valerate (Cyclo-Progynova ® 2mg, white tablets, BAYER Schering Pharma), one tablet every 12 hour from 2nd day of the cycle + sildenafil (silden® 25 mg, E.I.P.I.CO.) every 8 hour from 2nd day of the cycle till the day of trigger of ovulation).
estradiol valerate	estradiol valerate and sildenafil	oral estradiol valerate (Cyclo-Progynova ® 2mg, white tablets, BAYER Schering Pharma). One tablet every 12 hour from 2nd day of the cycle till the day of trigger of ovulation).

Primary Outcome Measures

Name	Time	Method
endometrial line thickness	9 days	The thickness of the endometrium will be measured (maximum distance between each myometrial/endometrial interface through the longitudinal axis of the uterus) using two dimensional transvaginal ultrasound.

Secondary Outcome Measures

Name	Time	Method
positive pregnancy test	14 days after triggering of ovulation	Serum B-HCG
sub endometrial blood flow	9 days	Using two dimensional (2D) transvaginal Doppler, flow velocity wave forms will be obtained from the ascending main branch of the uterine artery on the right and left side of the cervix before it enters the uterus.

Trial Locations

Locations (1)

Ain Shams University; 🇪🇬 Cairo, Egypt