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Effect Sildenafil and Estradiiol Valerate on Endometrial Thickness in Infertile Women

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ClinicalTrials.gov Identifier: NCT03301233
Recruitment Status : Completed
First Posted : October 4, 2017
Last Update Posted : August 14, 2018
Sponsor:
Information provided by (Responsible Party):
Hayam Fathy Mohammad, 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 .


Condition or disease Intervention/treatment Phase
Endometrial Thickness Drug: estradiol valerate and sildenafil Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: Ninety opaque envelopes will be numbered serially and in each envelope the corresponding letter which denotes the allocated group will be put according to randomization table. Then all envelopes will be closed and put in one box. When the first patient arrives, the first envelope will be opened and the patient will be allocated according to the letter inside.
Primary Purpose: Diagnostic
Official Title: The Effect of Estradiol Valerate With and Without Oral Sildenafil on Endometrial Thickness and Pregnancy Rates in Infertile Women: A R.C.T
Actual Study Start Date : November 1, 2017
Actual Primary Completion Date : July 1, 2018
Actual Study Completion Date : July 30, 2018


Arm Intervention/treatment
Active Comparator: estradiol valerate
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).
Drug: estradiol valerate and sildenafil
(45 women will receive clomiphene citrate (clomid 50mg ®, Sanofi aventis) 2 tab. single dose orally from the 2nd day of the cycle for 5 days with 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, E.I.P.I.CO.) every 8 hour from 2nd day of the cycle till the day of trigger of ovulation).
Other Name: cycloprogenova and silden

Experimental: 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).
Drug: estradiol valerate and sildenafil
(45 women will receive clomiphene citrate (clomid 50mg ®, Sanofi aventis) 2 tab. single dose orally from the 2nd day of the cycle for 5 days with 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, E.I.P.I.CO.) every 8 hour from 2nd day of the cycle till the day of trigger of ovulation).
Other Name: cycloprogenova and silden




Primary Outcome Measures :
  1. endometrial line thickness [ Time Frame: 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 :
  1. positive pregnancy test [ Time Frame: 14 days after triggering of ovulation ]
    Serum B-HCG

  2. sub endometrial blood flow [ Time Frame: 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.



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Ages Eligible for Study:   20 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03301233


Locations
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Egypt
Ain Shams University
Cairo, Egypt
Sponsors and Collaborators
Ain Shams University
Investigators
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Principal Investigator: Hayam F Mohammad, MD Ain Shams University

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Responsible Party: Hayam Fathy Mohammad, Assistant Professor of Obstetrics and Gynecology , Ain Shams University, Ain Shams University
ClinicalTrials.gov Identifier: NCT03301233     History of Changes
Other Study ID Numbers: 2
First Posted: October 4, 2017    Key Record Dates
Last Update Posted: August 14, 2018
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol
Polyestradiol phosphate
Infertility
Genital Diseases, Male
Genital Diseases, Female
Sildenafil Citrate
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents