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

Study Overview
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Brief Summary
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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.

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

Conditions
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IVF, Embryo Loss, Miscarriage, Recurrent

Intervention / Treatment
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* Drug: EmbryoGlue®, Vitrolife
* Drug: Conventional Transfer


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group: EmbryoGlue<br>Embryo transfer with EmbryoGlue® | Drug: EmbryoGlue®, Vitrolife<br>* 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.<br>|
| Active Comparator: Control group<br>Conventional embryo transfer | Drug: Conventional Transfer<br>* The control arm is the conventional embryo transfer without Embryo glue medium<br>|

What is the study measuring?
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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 |