Clinical trial NCT02061228: REFRESH: Receptivity Enhancement by Follicular-phase Renewal After Endometrial ScratcHing
Official title: Endometrial Receptivity Enhancement Through Induced Injury and Repair During Ovarian Stimulation in an Antagonist Down-regulated Cycle
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Infertility
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
First posted: 2014-02-12
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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

Primary outcomes:
measure: Clinical pregnancy rate
timeFrame: 12 weeks
Secondary outcomes:
measure: Live-birth rate
timeFrame: 42 weeks
measure: Complication rate
timeFrame: 42 weeks
measure: Effect on the endometrial histology and expression
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Samuel Santos-Ribeiro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitair Ziekenhuis Brussel
name: Shari Mackens, MD
role: STUDY_CHAIR
affiliation: Universitair Ziekenhuis Brussel
name: Dominic Stoop, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitair Ziekenhuis Brussel
name: Herman Tournaye, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.