Infertility, FemalePhase 1/2NCT03192709
Sildenafil and Outcome of IVF/ICSI Cycles
A Phase 1/2 study testing Sildenafil vaginal suppositories in people with Infertility, Female, run by Royan Institute at 1 site in Iran.
Trial summary
Adequate growth of the endometrium is crucial for implantation. Accordingly, the pregnancy success rate of patients with a thin endometrium is low. Furthermore, there is a little information about the factors responsible for impaired endometrial growth in patients with a thin endometrium. Read more about this study
- Who is it for?
- Ages 16 to 38 years, women only
- Conditions the study is for
- Infertility, Female
- What is being tested?
- Sildenafil vaginal suppositories
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteIran
- Study dates
- Feb 2015to Sep 2017
- Phase
- Phase 1/2
- 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 16 to 38 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Women with normal ovarian reserve and had at least two prior cycle with FSH <10 mIu/ml
- Women with history of two or three prior consecutive failed IVF/ICSI attempts using at least two good quality fresh or frozen-thawed embryos.
- Endometrial thickness on the day of hCG injection was < 9 mm in all prior IVF/ICSI attempts
- Women with normal endometrial appearance in hysteroscopy or hysterosonography or hysterosalpingography
Who cannot join
- Women who had history of PCOS, myomectomy, Asherman's Syndrome and mullerian anomalies
Trial locations and contacts
1 site in 1 country.
Iran1 site, 1 recruiting
- Recruiting
Royan Institute
Tehrān
Nasser Aghdami, MD,PhD, (+98)2123562000 ext. 516, nasser.aghdami@royaninstitute.org
Leila Arab, MD, (+98)2123562000 ext. 414, Leara91@gmail.com
About this study
Official title: The Effect of Vaginal Sildenafil on the Outcome of IVF/ICSI Cycles in Patients With Repeated IVF/ICSI Failure: a Pilot Study
Adequate growth of the endometrium is crucial for implantation. Accordingly, the pregnancy success rate of patients with a thin endometrium is low. Furthermore, there is a little information about the factors responsible for impaired endometrial growth in patients with a thin endometrium. The researches have revealed that nitric oxide (NO) release can cause relaxation of vascular smooth muscle through a cyclic guanyl monophosphate (cGMP)-mediated pathway. Sildenafil is a type 5-specific Phosphodiesterase inhibitor that augments the vasodilatory effects of NO on vascular smooth muscle by preventing the degradation of cGMP and could improve blood flow and endometrial thickness. This study is designed to evaluate the effect of vaginally administered sildenafil suppositories on IVF/ICSI outcome of infertile patients with repeated IVF/ICSI failures.
Read the detailed description
The proposal of this study approved by our institutional review boards and institution's ethical committee, and all participants will sign a written consent before enter to study.
The study population will consist of infertile women of <38 years of age with repeated in vitro fertilization/ intra cytoplasmic injection failures. Endometrial parameters including endometrial thickness, endometrial pattern , pulsatility index (PI) and resistance index (RI) will be evaluated with the use of color Doppler ultrasound on the day of hCG administration. Patients will be randomly divided into 3 groups, A, B and C. In the subsequent menstrual cycle, in group A, vaginal sildenafil suppositories (100 mg/day) will be given daily from the start of human menopausal gonadotropin (HMG) administration day until the day of oocyte retrieval. In group B, the women will receive daily vaginal placebo from the start of HMG administration day until 2 days before the human chronic gonadotrophin (hCG) injection day, then will be switched to vaginal sildenafil suppositories (100 mg/day) until the day of oocyte retrieval. In group C, vaginal placebo will be given daily from the start of human menopausal gonadotropin (HMG) administration day until the day of oocyte retrieval.
When the diameter of at least 2 follicles will be reached equal or greater than 18 mm, hCG 10,000 IU will be administered. In all patients, ovarian stimulation will be performed with the conventional GnRh agonist protocol. Endometrial parameters will be measured again on the day of hCG injection. Ovum pick up will be performed 34-36 h after hCG injection and embryos will be transferred 48-72 hours after oocyte retrieval. Pregnancy will be confirmed by assessment of βHCG level 14 days after embryo transfer and ultrasonographic visualization of gestational sac during the 5th week of pregnancy.
- Conditions
- Infertility, Female
- Being tested
- Sildenafil vaginal suppositories, vaginal placebo
- Keywords
- Sildenafil IVF ICI failure
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sildenafil vaginal suppositoriesDrug
Sildenafil vaginal suppositories (100 mg/day) from the start of HMG administration day until the day of oocyte retrieval.
vaginal placeboOther
Daily vaginal placebo from the start of HMG administration day until 2 days before the hCG injection day, then will be switched to vaginal sildenafil suppositories (100 mg/day) until the day of oocyte retrieval.
vaginal placeboOther
Daily vaginal placebo from the start of HMG administration day until the day of oocyte retrieval.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Sildenafil vaginal suppositories users Receives: Drug: Sildenafil vaginal suppositories |
| B | Placebo comparator | Daily vaginal placebo users with HMG administration Receives: Other: vaginal placebo |
| C | Placebo comparator | Daily vaginal placebo users with HMG administration day until the day of oocyte retrieval. Receives: Other: vaginal placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Pregnancy rate
Evaluation the Clinical Pregnancy rate after using Sildenafil vaginal suppositories (100 mg/day) from the start of HMG administration day until the day of oocyte retrieval. It is detected by a positive ß-hCG test result and ultrasonographic visualization of at least one gestational sac
Measured: 4-6 weeks after embryos transfer
Secondary outcomes (5)
Implantation rate
The implantation rate is defined as number of gestational sacs per transferred embryo. It Is detected by a positive ß-hCG test result and ultrasonographic visualization of at least one gestational sac 4-6 weeks after embryos transfer.
Measured: 4-6 weeks
Endometrial thickness
The endometrial thickness is detected by ultrasound examination in hCG day administration.
Measured: 1 day
Endometrial pattern
Comparing gray scale appearance of the endometrium to that of the adjacent myometrium at Day 14 of previous cycle.
Measured: Day 14
Pulsatility index
The variability in flow between the systole and the diastole; this measure was calculated by dividing the difference between the peak systolic and end-diastolic frequencies by the time-average of the maximum frequency shift.This is measured at hCG administration day.
Measured: 1 day
Resistance index (RI)
The RI is defined as a ratio of the difference between the maximum and minimum flow velocity to maximum flow velocity.This is measured at hCG administration day.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2017
- Study startFeb 2015
- Primary completionAug 2017 (estimated)
- Study completionSep 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infertility, FemaleStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royan Institute
- Sponsor type
- Other government
- Collaborators
- Tehran University of Medical Sciences
- Responsible party
- Sponsor
- Investigators
- Hamid Gourabi, PhD, Study chair, Head of Royan InstituteAshraf Moieni, MD, Study director, Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.Firoozeh Ahmadi, MD, Principal investigator, Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.Fatemeh Zafarani, MSc, Principal investigator, Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03192709
- Sponsor's protocol ID
- Royan-Emb-030
- Status last verified
- Apr 2017
- First submitted
- 30 Apr 2017
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Moini A, Zafarani F, Jahangiri N, Jahanian Sadatmahalleh SH, Sadeghi M, Chehrazi M, Ahmadi F. The Effect of Vaginal Sildenafil on The Outcome of Assisted Reproductive Technology Cycles in Patients with Repeated Implantation Failures: A Randomized Placebo-Controlled Trial. Int J Fertil Steril. 2020 Jan;13(4):289-295. doi: 10.22074/ijfs.2020.5681. Epub 2019 Nov 11.
PubMed 31710189
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Vaginal Sildenafil on the Outcome of IVF/ICSI Cycles in Patients With Repeated IVF/ICSI Failure: a Pilot Study
- ClinicalTrials.gov ID
- NCT03192709
- Acronym / sponsor ID
- Royan-Emb-030
- Conditions
- Infertility, Female
- Keywords
- Sildenafil IVF ICI failure
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Royan InstituteOther government
- Collaborators
- Tehran University of Medical Sciences
- Study start
- Feb 2015 (actual)
- Primary completion
- Aug 2017 (estimated)
- Study completion
- Sep 2017 (estimated)
- First posted
- 20 Jun 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.
Adequate growth of the endometrium is crucial for implantation. Accordingly, the pregnancy success rate of patients with a thin endometrium is low. Furthermore, there is a little information about the factors responsible for impaired endometrial growth in patients with a thin endometrium. The researches have revealed that nitric oxide (NO) release can cause relaxation of vascular smooth muscle through a cyclic guanyl monophosphate (cGMP)-mediated pathway. Sildenafil is a type 5-specific Phosphodiesterase inhibitor that augments the vasodilatory effects of NO on vascular smooth muscle by preventing the degradation of cGMP and could improve blood flow and endometrial thickness. This study is designed to evaluate the effect of vaginally administered sildenafil suppositories on IVF/ICSI outcome of infertile patients with repeated IVF/ICSI failures.
Detailed description
The proposal of this study approved by our institutional review boards and institution's ethical committee, and all participants will sign a written consent before enter to study.
The study population will consist of infertile women of <38 years of age with repeated in vitro fertilization/ intra cytoplasmic injection failures. Endometrial parameters including endometrial thickness, endometrial pattern , pulsatility index (PI) and resistance index (RI) will be evaluated with the use of color Doppler ultrasound on the day of hCG administration. Patients will be randomly divided into 3 groups, A, B and C. In the subsequent menstrual cycle, in group A, vaginal sildenafil suppositories (100 mg/day) will be given daily from the start of human menopausal gonadotropin (HMG) administration day until the day of oocyte retrieval. In group B, the women will receive daily vaginal placebo from the start of HMG administration day until 2 days before the human chronic gonadotrophin (hCG) injection day, then will be switched to vaginal sildenafil suppositories (100 mg/day) until the day of oocyte retrieval. In group C, vaginal placebo will be given daily from the start of human menopausal gonadotropin (HMG) administration day until the day of oocyte retrieval.
When the diameter of at least 2 follicles will be reached equal or greater than 18 mm, hCG 10,000 IU will be administered. In all patients, ovarian stimulation will be performed with the conventional GnRh agonist protocol. Endometrial parameters will be measured again on the day of hCG injection. Ovum pick up will be performed 34-36 h after hCG injection and embryos will be transferred 48-72 hours after oocyte retrieval. Pregnancy will be confirmed by assessment of βHCG level 14 days after embryo transfer and ultrasonographic visualization of gestational sac during the 5th week of pregnancy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Sildenafil vaginal suppositoriesSildenafil vaginal suppositories users |
| B | Placebo comparator | Other: vaginal placeboDaily vaginal placebo users with HMG administration |
| C | Placebo comparator | Other: vaginal placeboDaily vaginal placebo users with HMG administration day until the day of oocyte retrieval. |
Who may qualify
- Ages
- 16 to 38 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Women with normal ovarian reserve and had at least two prior cycle with FSH <10 mIu/ml
- Women with history of two or three prior consecutive failed IVF/ICSI attempts using at least two good quality fresh or frozen-thawed embryos.
- Endometrial thickness on the day of hCG injection was < 9 mm in all prior IVF/ICSI attempts
- Women with normal endometrial appearance in hysteroscopy or hysterosonography or hysterosalpingography
Key exclusion criteria (1 listed)
- Women who had history of PCOS, myomectomy, Asherman's Syndrome and mullerian anomalies
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 vaginal suppositoriesSildenafil vaginal suppositories (100 mg/day) from the start of HMG administration day until the day of oocyte retrieval. | Drug | A |
| vaginal placeboDaily vaginal placebo from the start of HMG administration day until 2 days before the hCG injection day, then will be switched to vaginal sildenafil suppositories (100 mg/day) until the day of oocyte retrieval. | Other | B |
| vaginal placeboDaily vaginal placebo from the start of HMG administration day until the day of oocyte retrieval. | Other | C |
Primary outcome
Clinical Pregnancy rate
Time frame: 4-6 weeks after embryos transfer
Evaluation the Clinical Pregnancy rate after using Sildenafil vaginal suppositories (100 mg/day) from the start of HMG administration day until the day of oocyte retrieval. It is detected by a positive ß-hCG test result and ultrasonographic visualization of at least one gestational sac
5 secondary outcomes
Implantation rate
Time frame: 4-6 weeks
Endometrial thickness
Time frame: 1 day
Endometrial pattern
Time frame: Day 14
Pulsatility index
Time frame: 1 day
Resistance index (RI)
Time frame: 1 day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Derived from this study: PubMed 31710189Moini A, Zafarani F, Jahangiri N, Jahanian Sadatmahalleh SH, Sadeghi M, Chehrazi M, Ahmadi F. The Effect of Vaginal Sildenafil on The Outcome of Assisted Reproductive Technology Cycles in Patients with Repeated Implantation Failures: A Randomized Placebo-Controlled Trial. Int J Fertil Steril. 2020 Jan;13(4):289-295. doi: 10.22074/ijfs.2020.5681. Epub 2019 Nov 11.
- Related InfoLink provided by the sponsor.
- 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.
Hamid Gourabi, PhD study chair
Head of Royan Institute
Ashraf Moieni, MD study director
Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Firoozeh Ahmadi, MD principal investigator
Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sildenafil vaginal suppositories in people with Infertility, Female, run by Royan Institute at 1 site in Iran.
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 4 inclusion and 1 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 Jun 2017. 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 Iran. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Nasser Aghdami, MD,PhD ((+98)2123562000 ext. 516, nasser.aghdami@royaninstitute.org), 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: 4-6 weeks after embryos transfer). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03192709, which also lists 1 linked publication.
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 Jun 2017.