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REFRESH: Receptivity Enhancement by Follicular-phase Renewal After Endometrial ScratcHing (REFRESH)

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ClinicalTrials.gov Identifier: NCT02061228
Recruitment Status : Active, not recruiting
First Posted : February 12, 2014
Last Update Posted : May 4, 2018
Sponsor:
Information provided by (Responsible Party):
Samuel Santos-Ribeiro, Universitair Ziekenhuis Brussel

Brief Summary:
A randomised controlled open-label clinical trial to assess the effect of artificially induced endometrial injury and repair during ovarian stimulation on the clinical pregnancy rate of an antagonist downregulated in-vitro fertilisation cycle

Condition or disease Intervention/treatment Phase
Infertility Device: Pipelle de Cornier® Not Applicable

Detailed Description:

Ovarian stimulation, ultrasound and hormonal monitoring, ovulation induction, oocyte retrieval, embryology procedure, IVF and luteal support will be according to how they are normally performed in our centre.

All women included will undergo artificial ovarian stimulation with gonadotropin-releasing hormone (GnRH) antagonist downregulation with daily injections of either ganirelix or cetrorelix. Treating physicians will opt on which exogenous gonadotropins should be used according to the patient's profile and preference and can include either recombinant follicle stimulating hormone (FSH) or highly purified urinary human menopausal gonadotropin (HP-HMG). Ovarian stimulation will commence after it is confirmed that the patient is not pregnant and has basal levels of oestradiol, progesterone, FSH and luteinizing hormone (LH). The stimulation will be monitored simultaneously by pelvic ultrasound and hormonal analysis (oestradiol, progesterone), starting on day 6 of stimulation and then every 1 to 3 days, according to the individual endocrine profile and follicular development.

Final oocyte maturation will be triggered with either 5000/10000 IU of human menopausal human chorionic gonadotropin (hCG) or 150 IU of recombinant hCG when more than 2 follicles of ≥17 mm are present. Oocyte retrieval will be performed 36 hours after hCG administration under either local anaesthesia with analgesic premedication or general anaesthesia, according to patient preference.

IVF or IVF/intracytoplasmatic sperm injection (ICSI) will be performed, using the specimen of sperm made available by the male progenitor on the day of oocyte retrieval. According to embryo quality, embryo transfer to the uterine cavity will be performed on either the 3rd or 5th day of development under ultrasound guidance whenever possible. Following embryo transfer, luteal support will be provided with vaginally administered progesterone 200 mg tid.

For clarity, cycle cancelation is defined as any interruption of the ART process that occurs before fresh embryo transfer. Cycle cancelation will occur a) upon patient request, b) if inadequate follicular development occurs, c) if no embryo is available for transfer.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Endometrial Receptivity Enhancement Through Induced Injury and Repair During Ovarian Stimulation in an Antagonist Down-regulated Cycle
Study Start Date : March 2014
Actual Primary Completion Date : February 26, 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Infertility

Arm Intervention/treatment
No Intervention: Control arm
Women undergoing exogenous gonadotropin ovarian stimulation for ART in an antagonist downregulated cycle.
Experimental: Induced endometrial injury arm
Women undergoing exogenous gonadotropin ovarian stimulation for ART in an antagonist downregulated cycle. Additionally, they will undergo an endometrial biopsy on the 6th day of ovarian stimulation using a Pipelle de Cornier® (CCD International, Paris, France).
Device: Pipelle de Cornier®
Women in the intervention group will undergo an endometrial biopsy on the 6th day of ovarian stimulation using a Pipelle de Cornier® (CCD International, Paris, France). This class I individually and sterile-packaged medical device, complies with Directive 93/42/European Economic Community (EEC) and is routinely used in our centre for endometrial sampling. It is comprised of a flexible disposable polypropylene suction cannula with an outer diameter of 3.1 mm and a 2.4 mm diameter opening on the distal end, on one side of the cannula. An inner plunger creates a vacuum essential for the blind endometrial biopsy. After the introduction of the Pipelle into the uterine cavity, it will be rotated 360 degrees and moved up and down four times after withdrawing the piston.




Primary Outcome Measures :
  1. Clinical pregnancy rate [ Time Frame: 12 weeks ]
    Sample size calculation was based on the adequate sample which would simultaneously 1) allow two safety-check interim analyses (at one-third and two-thirds of recruitment) and 2) have an 80% power to detect an increase of 15% in clinical pregnancy rate (from 32% to 47%) in the intervention group [using a two-side Fisher-exact test with a significance level (alfa) of 0.05]. Using a 1:1 randomisation ratio, each group would require approximately 180 patients, adding up to a total of 360 patients required for the trial.


Secondary Outcome Measures :
  1. Live-birth rate [ Time Frame: 42 weeks ]
    Delivery of at least one live born

  2. Complication rate [ Time Frame: 42 weeks ]
    Pain during biopsy, failed biospy and occurance of a premature delivery (<37 weeks) and low birth weight delivery (<2500 g)

  3. Effect on the endometrial histology and expression [ Time Frame: 2 weeks ]
    Histology and RNA expression analysis of collected samples



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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Fresh IVF/ICSI cycle
  • Antagonist down-regulation
  • Signed informed consent

Exclusion Criteria:

  • Other known reasons for impaired implantation (i.e. hydrosalpinx, fibroid distorting the endometrial cavity, Asherman's syndrome, thrombophilia or endometrial tuberculosis)
  • Oocyte donation acceptors
  • Frozen egg transfers
  • Embryos planned to undergo preimplantation genetic diagnosis (PGD)
  • BMI >35 or <18
  • Women already recruited for another trial on medically assisted procreation during the same cycle
  • Women who have previously enrolled in the trial
  • Those unable to comprehend the investigational nature of the proposed study

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): NCT02061228


Locations
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Belgium
Universitair Ziekenhuis Brussel
Brussels, Belgium
Sponsors and Collaborators
Universitair Ziekenhuis Brussel
Investigators
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Principal Investigator: Samuel Santos-Ribeiro, MD Universitair Ziekenhuis Brussel
Study Chair: Shari Mackens, MD Universitair Ziekenhuis Brussel
Principal Investigator: Dominic Stoop, PhD Universitair Ziekenhuis Brussel
Study Chair: Herman Tournaye, PhD Universitair Ziekenhuis Brussel

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Responsible Party: Samuel Santos-Ribeiro, MD, Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier: NCT02061228     History of Changes
Other Study ID Numbers: 29012014REFRESH
2014-000442-29 ( EudraCT Number )
First Posted: February 12, 2014    Key Record Dates
Last Update Posted: May 4, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
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Infertility
Genital Diseases, Male
Genital Diseases, Female