IVFPhase 1NCT04283435
Endometrial Effects of Sildenafil in Frozen-Thawed Cycles in Women With Thin Endometrium
A Phase 1 study testing Sildenafil Citrate and Estradiol Valerate in people with IVF and Endometrial Receptivity, run by Cairo University at 1 site in Egypt.
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). Read more about this study
- Who is it for?
- Ages 25 to 40 years, women only
- Conditions the study is for
- IVF, Endometrial Receptivity
- What is being tested?
- Sildenafil Citrate and Estradiol Valerate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Sep 2021to 1 Mar 2022
- Phase
- Phase 1
- 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 25 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
wafaa Ramadan, MD contact
About this study
Official title: Effect of Sildenafil on Uterine and Endometrial Vasculature in Women With Thin Endometrium Having Frozen-Thawed IVF Cycles
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).
Read more
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.
Read the detailed 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) .
- Conditions
- IVF, Endometrial Receptivity
- Being tested
- Sildenafil Citrate, Placebo, Estradiol Valerate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil CitrateDrug
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)
PlaceboOther
Also called Pregnacare vitamins (Vitabiotics,UK)
Placebo tablet (multivitamins),Pregnacare vitamins (Vitabiotics,UK)
Estradiol ValerateDrug
Estradiol valerate tablets 2mg every 8 hours daily starting from the fist day of the cycle till 12th day of the menstrual cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Drug: Sildenafil Citrate; Drug: Estradiol Valerate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Pregnancy rate
Measured: 2 weeks after embryo transfer
Secondary outcomes (4)
endometrial thickness
Measured: at the time of embryo transfer
Endometrial volume
Measured: at the time of embryo transfer
Uterine artery doppler indices
Measured: at the time of embryo transfer
3D endometrial and subendometrial vascular indices(VI,FI.VFI)
Measured: at the time of embryo transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2020
- Study start1 Sep 2021 (estimated)
- Primary completion1 Mar 2022 (estimated)
- Study completion1 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for IVFStudies of the same condition, open and under way.
- More trials run by Cairo 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eman Elkattan, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04283435
- Sponsor's protocol ID
- PROTOCOL 500
- Status last verified
- Aug 2021
- First submitted
- 18 Feb 2020
- Last updated
- 20 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Sildenafil on Uterine and Endometrial Vasculature in Women With Thin Endometrium Having Frozen-Thawed IVF Cycles
- ClinicalTrials.gov ID
- NCT04283435
- Acronym / sponsor ID
- PROTOCOL 500
- Conditions
- IVF, Endometrial Receptivity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 1 Sep 2021 (estimated)
- Primary completion
- 1 Mar 2022 (estimated)
- Study completion
- 1 Mar 2022 (estimated)
- First posted
- 25 Feb 2020 (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.
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.
Detailed 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) .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| estradiol valerate + placebo | Placebo comparator | Other: Placebo, Drug: Estradiol Valeratepreparation 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). |
| estradiol valerate + Sildenafil citrate | Experimental | Drug: Sildenafil Citrate, Drug: Estradiol ValerateWe 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. |
Who may qualify
- Ages
- 25 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
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 |
|---|---|---|
| Sildenafil CitrateSildenafil 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) | Drug | estradiol valerate + Sildenafil citrate |
| PlaceboAlso: Pregnacare vitamins (Vitabiotics,UK)Placebo tablet (multivitamins),Pregnacare vitamins (Vitabiotics,UK) | Other | estradiol valerate + placebo |
| Estradiol ValerateEstradiol valerate tablets 2mg every 8 hours daily starting from the fist day of the cycle till 12th day of the menstrual cycle. | Drug | estradiol valerate + Sildenafil citrate, estradiol valerate + placebo |
Primary outcome
Clinical Pregnancy rate
Time frame: 2 weeks after embryo transfer
4 secondary outcomes
endometrial thickness
Time frame: at the time of embryo transfer
Endometrial volume
Time frame: at the time of embryo transfer
Uterine artery doppler indices
Time frame: at the time of embryo transfer
3D endometrial and subendometrial vascular indices(VI,FI.VFI)
Time frame: at the time of embryo transfer
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2021.
- Individual participant dataSharing planned: No
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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.
wafaa Ramadan, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sildenafil Citrate and Estradiol Valerate in people with IVF and Endometrial Receptivity, run by Cairo 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 2 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 20 Aug 2021. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eman Elkattan, MD (01212529213, emyelkattan@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Pregnancy rate (time frame: 2 weeks after embryo transfer). 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 20 Aug 2021.