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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

Tracking Information
First Submitted Date  ICMJE April 30, 2017
First Posted Date  ICMJE June 20, 2017
Last Update Posted Date June 20, 2017
Actual Study Start Date  ICMJE February 2015
Estimated Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2017)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2017)
  • 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.
  • Endometrial thickness [ Time Frame: 1 day ]
    The endometrial thickness is detected by ultrasound examination in hCG day administration.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sildenafil and Outcome of IVF/ICSI Cycles
Official Title  ICMJE The Effect of Vaginal Sildenafil on the Outcome of IVF/ICSI Cycles in Patients With Repeated IVF/ICSI Failure: a Pilot Study
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Infertility, Female
Intervention  ICMJE
  • Drug: Sildenafil vaginal suppositories
    Sildenafil vaginal suppositories (100 mg/day) from the start of HMG administration day until the day of oocyte retrieval.
  • 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.
  • Other: vaginal placebo
    Daily vaginal placebo from the start of HMG administration day until the day of oocyte retrieval.
Study Arms  ICMJE
  • Experimental: A
    Sildenafil vaginal suppositories users
    Intervention: Drug: Sildenafil vaginal suppositories
  • Placebo Comparator: B
    Daily vaginal placebo users with HMG administration
    Intervention: Other: vaginal placebo
  • Placebo Comparator: C
    Daily vaginal placebo users with HMG administration day until the day of oocyte retrieval.
    Intervention: Other: vaginal placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 18, 2017)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2017
Estimated Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 16 Years to 38 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Iran, Islamic Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03192709
Other Study ID Numbers  ICMJE Royan-Emb-030
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Royan Institute
Study Sponsor  ICMJE Royan Institute
Collaborators  ICMJE Tehran University of Medical Sciences
Investigators  ICMJE
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.
PRS Account Royan Institute
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP