REFRESH: Receptivity Enhancement by Follicular-phase Renewal After Endometrial ScratcHing (REFRESH)
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|ClinicalTrials.gov Identifier: NCT02061228|
Recruitment Status : Terminated (Safety concerns, apparent futility and protracted recruitment)
First Posted : February 12, 2014
Last Update Posted : December 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Infertility||Device: Pipelle de Cornier®||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Completion Date :||September 30, 2018|
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.
- 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.
- Live-birth rate [ Time Frame: 42 weeks ]Delivery of at least one live born
- 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)
- Effect on the endometrial histology and expression [ Time Frame: 2 weeks ]Histology and RNA expression analysis of collected samples
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
|Universitair Ziekenhuis Brussel|
|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|