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Sildenafil and Outcome of IVF/ICSI Cycles

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ClinicalTrials.gov Identifier: NCT03192709
Recruitment Status : Unknown
Verified April 2017 by Royan Institute.
Recruitment status was:  Recruiting
First Posted : June 20, 2017
Last Update Posted : June 20, 2017
Sponsor:
Collaborator:
Tehran University of Medical Sciences
Information provided by (Responsible Party):
Royan Institute

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Infertility, Female Drug: Sildenafil vaginal suppositories Other: vaginal placebo Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Vaginal Sildenafil on the Outcome of IVF/ICSI Cycles in Patients With Repeated IVF/ICSI Failure: a Pilot Study
Actual Study Start Date : February 2015
Estimated Primary Completion Date : August 2017
Estimated Study Completion Date : September 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: A
Sildenafil vaginal suppositories users
Drug: Sildenafil vaginal suppositories
Sildenafil vaginal suppositories (100 mg/day) from the start of HMG administration day until the day of oocyte retrieval.

Placebo Comparator: B
Daily vaginal placebo users with HMG administration
Other: vaginal placebo
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.

Placebo Comparator: C
Daily vaginal placebo users with HMG administration day until the day of oocyte retrieval.
Other: vaginal placebo
Daily vaginal placebo from the start of HMG administration day until the day of oocyte retrieval.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Implantation rate [ Time Frame: 4-6 weeks ]
    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.

  2. Endometrial thickness [ Time Frame: 1 day ]
    The endometrial thickness is detected by ultrasound examination in hCG day administration.

  3. Endometrial pattern [ Time Frame: Day 14 ]
    Comparing gray scale appearance of the endometrium to that of the adjacent myometrium at Day 14 of previous cycle.

  4. Pulsatility index [ Time Frame: 1 day ]
    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.

  5. Resistance index (RI) [ Time Frame: 1 day ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 38 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Women who had history of PCOS, myomectomy, Asherman's Syndrome and mullerian anomalies

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): NCT03192709


Contacts
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Contact: Nasser Aghdami, MD,PhD (+98)2123562000 ext 516 nasser.aghdami@royaninstitute.org
Contact: Leila Arab, MD (+98)2123562000 ext 414 Leara91@gmail.com

Locations
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Iran, Islamic Republic of
Royan Institute Recruiting
Tehrān, Iran, Islamic Republic of
Contact: Nasser Aghdami, MD,PhD    (+98)2123562000 ext 516    nasser.aghdami@royaninstitute.org   
Contact: Leila Arab, MD    (+98)2123562000 ext 414    Leara91@gmail.com   
Principal Investigator: Nadia Jahangiri, MSc         
Principal Investigator: Maria sadeghi, MSc         
Principal Investigator: Farideh Malekzadeh, MSc         
Sponsors and Collaborators
Royan Institute
Tehran University of Medical Sciences
Investigators
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Study Chair: Hamid Gourabi, PhD Head of Royan Institute
Study Director: Ashraf Moieni, MD Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Principal Investigator: Firoozeh Ahmadi, MD Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Principal Investigator: Fatemeh Zafarani, MSc Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Additional Information:
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Responsible Party: Royan Institute
ClinicalTrials.gov Identifier: NCT03192709     History of Changes
Other Study ID Numbers: Royan-Emb-030
First Posted: June 20, 2017    Key Record Dates
Last Update Posted: June 20, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Royan Institute:
Sildenafil IVF ICI failure

Additional relevant MeSH terms:
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Infertility
Infertility, Female
Genital Diseases, Male
Genital Diseases, Female
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents