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

NCT ID: NCT02061228

Last Updated: 2019-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2018-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Infertility

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Control arm

Women undergoing exogenous gonadotropin ovarian stimulation for ART in an antagonist downregulated cycle.

Group Type NO_INTERVENTION

No interventions assigned to this group

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).

Group Type EXPERIMENTAL

Pipelle de Cornier®

Intervention Type DEVICE

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DEVICE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Samuel Santos-Ribeiro

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Samuel Santos-Ribeiro, MD

Role: PRINCIPAL_INVESTIGATOR

Universitair Ziekenhuis Brussel

Shari Mackens, MD

Role: STUDY_CHAIR

Universitair Ziekenhuis Brussel

Dominic Stoop, PhD

Role: PRINCIPAL_INVESTIGATOR

Universitair Ziekenhuis Brussel

Herman Tournaye, PhD

Role: STUDY_CHAIR

Universitair Ziekenhuis Brussel

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Universitair Ziekenhuis Brussel

Brussels, , Belgium

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Belgium

References

Explore related publications, articles, or registry entries linked to this study.

Mackens S, Santos-Ribeiro S, Racca A, Daneels D, Koch A, Essahib W, Verpoest W, Bourgain C, Van Riet I, Tournaye H, Brosens JJ, Lee YH, Blockeel C, Van de Velde H. The proliferative phase endometrium in IVF/ICSI: an in-cycle molecular analysis predictive of the outcome following fresh embryo transfer. Hum Reprod. 2020 Jan 1;35(1):130-144. doi: 10.1093/humrep/dez218.

Reference Type DERIVED
PMID: 31916571 (View on PubMed)

Santos-Ribeiro S, Mackens S, Tournaye H, Blockeel C, Stoop D. Endometrial receptivity enhancement through induced injury and repair during ovarian stimulation: the Receptivity Enhancement by Follicular-phase Renewal after Endometrial ScratcHing (REFRESH) trial protocol. Hum Reprod Open. 2017 Nov 24;2017(3):hox022. doi: 10.1093/hropen/hox022. eCollection 2017.

Reference Type DERIVED
PMID: 30895236 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2014-000442-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

29012014REFRESH

Identifier Type: -

Identifier Source: org_study_id