The Use of High Concentration Hyaluronic Acid (HA) Transfer Medium in Repeated Implantation Failure (RIF) Patients (RIFLE)

This is a pilot study with the aim to investigate the beneficial effect of bicarbonate buffered medium containing hyaluronan and recombinant human albumin (EmbryoGlue®, Vitrolife) in patients with documented repeated implantation failure on live birth per randomized subject as primary endpoint.

Study Overview

• Status: Recruiting
• Conditions: Miscarriage, Recurrent; IVF; Embryo Loss
• Intervention / Treatment: Drug: EmbryoGlue®, Vitrolife; Drug: Conventional Transfer

• Study Type: Interventional
• Enrollment (Estimated): 178
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • UZ Ghent
    • Contact: Dominic Stoop; Phone Number: 09/332.16.99; Email: dominic.stoop@uzgent.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• The trial only includes women with a clinical indication for ART with a history of RIF defined as the absence of implantation after two consecutive cycles of IVF, ICSI or frozen embryo replacement cycles where the cumulative number of transferred embryos was no less than four for cleavage-stage embryos and no less than two for blastocysts, with all embryos being of good quality and of appropriate developmental stage.

Furthermore, other specific 'RIF' investigations were performed and treated if necessary:

• Normal hysteroscopy
• Normal karyotype of both parents
• Coagulation screening (Antitrombine II deficiency, Factor VIII augmentation, APC resistance, Factor V + Factor II augmentation, Protein S and C deficiency an homocysteine augmentation)
• Auto-immune screening (Lupus anticoagulant, Rheumatoid Factor, Anti-nuclear antibodies, Anti-cardiolipine antibodies and Glycoprotein-1-antibodies)

Exclusion Criteria:

• • Simultaneous participation in another clinical study

  • Untreated and uncontrolled thyroid dysfunction
  • Tumors of the ovary, breast, uterus, pituitary or hypothalamus
  • Abnormal (not menstrual) vaginal bleeding without a known/diagnosed cause
  • Ovarian cysts or enlarged ovaries
  • Malformations of the reproductive organs
  • Moderate or severe hepatic impairment
  • Current use of oral contraceptives, anti-psychotics, anti-epileptics or chemotherapy
  • Patients who undergo preimplantation genetic testing (PGT), fertility preservation or oocyte donation
  • Couples needing TESE/MESA material

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group: EmbryoGlue; Embryo transfer with EmbryoGlue®	Drug: EmbryoGlue®, Vitrolife; The intervention under study is the application of EmbryoGlue®, a class III medical device (CE Marked). EmbryoGlue® is a bicarbonate buffered medium containing recombinant human albumin, hyaluronan and gentamicin as an antibacterial agent.
Active Comparator: Control group; Conventional embryo transfer	Drug: Conventional Transfer; The control arm is the conventional embryo transfer without Embryo glue medium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth	live birth per randomized subject.	9 months after embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
positive hCG	cumulative positive hCG rate confirmed by blood sample	11 days (± 2 days) after embryo transfer.
ongoing pregnancy rate	cumulative ongoing pregnancy rate per randomized subject, confirmed by ultrasound	between 6 and 8 weeks of gestation

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Dominic Stoop, MD, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Death; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Abortion, Spontaneous; Abortion, Habitual; Embryo Loss
• Other Study ID Numbers: BC-08429

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No