Endometrial ThicknessNCT03301233
Effect Sildenafil and Estradiiol Valerate on Endometrial Thickness in Infertile Women
A study testing estradiol valerate and sildenafil in people with Endometrial Thickness, run by Ain Shams University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 35 years, women only
- Conditions the study is for
- Endometrial Thickness
- What is being tested?
- estradiol valerate and sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Nov 2017to 30 Jul 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 35 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Patients having ovulatory infertility.
- Age: 20-35 years old.
- BMI less than 30 kg/m2
Who cannot join
- 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).
- Women who have any tubal factor that relates to infertility (e.g., tubal adhesion or previous ectopic pregnancy).
- Women who have contraindication for estrogen treatment (e.g., history of stroke, DVT and Benign liver disease).
- Women who have male factor for infertility (e.g., azoospermia, teratospermia).
Trial locations and contacts
1 site in 1 country.
About this study
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
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 .
Read the 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.
- Conditions
- Endometrial Thickness
- Being tested
- estradiol valerate and sildenafil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
estradiol valerate and sildenafilDrug
Also called cycloprogenova and silden
(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).
| Study group | Role | What they receive |
|---|---|---|
| estradiol valerate | Active comparator | 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). Receives: Drug: estradiol valerate and sildenafil |
| estradiol valerate and sildenafil | Experimental | 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). Receives: Drug: estradiol valerate and sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
endometrial line thickness
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.
Measured: 9 days
Secondary outcomes (2)
positive pregnancy test
Serum B-HCG
Measured: 14 days after triggering of ovulation
sub endometrial blood flow
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.
Measured: 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2017
- Study start1 Nov 2017
- Primary completion1 Jul 2018
- Study completion30 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial ThicknessStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hayam Fathy Mohammad, Ain Shams University
- Investigators
- Hayam F Mohammad, MD, Principal investigator, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03301233
- Sponsor's protocol ID
- 2
- Status last verified
- Aug 2018
- First submitted
- 24 Sep 2017
- Last updated
- 14 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03301233
- Acronym / sponsor ID
- 2
- Conditions
- Endometrial Thickness
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 1 Jul 2018 (actual)
- Study completion
- 30 Jul 2018 (actual)
- First posted
- 4 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| estradiol valerate | Active comparator | Drug: estradiol valerate and sildenafiloral 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). |
| estradiol valerate and sildenafil | Experimental | Drug: estradiol valerate and sildenafiloral 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). |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Patients having ovulatory infertility.
- Age: 20-35 years old.
- BMI less than 30 kg/m2
Key exclusion criteria (4 listed)
- 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).
- Women who have any tubal factor that relates to infertility (e.g., tubal adhesion or previous ectopic pregnancy).
- Women who have contraindication for estrogen treatment (e.g., history of stroke, DVT and Benign liver disease).
- Women who have male factor for infertility (e.g., azoospermia, teratospermia).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| estradiol valerate and sildenafilAlso: cycloprogenova and silden(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). | Drug | estradiol valerate, estradiol valerate and sildenafil |
Primary outcome
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.
2 secondary outcomes
positive pregnancy test
Time frame: 14 days after triggering of ovulation
sub endometrial blood flow
Time frame: 9 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2018.
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Asymptomatic Women With Thick Endometrium: Hysteroscopic and Histopathological Report
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Effect of Tadalafil on Endometrial Thickness and Frozen Embryo Transfer Outcomes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hayam F Mohammad, MD principal investigator
Ain Shams University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing estradiol valerate and sildenafil in people with Endometrial Thickness, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
endometrial line thickness (time frame: 9 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2018.