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

• EmbryoGlue®, Vitrolife (Drug): 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.
• Conventional Transfer (Drug): The control arm is the conventional embryo transfer without Embryo glue medium

Primary outcomes

• Live birth [9 months after embryo transfer]: live birth per randomized subject.

Secondary outcomes

• positive hCG [11 days (± 2 days) after embryo transfer.]: cumulative positive hCG rate confirmed by blood sample
• ongoing pregnancy rate [between 6 and 8 weeks of gestation]: cumulative ongoing pregnancy rate per randomized subject, confirmed by ultrasound

Sex: Female, ages: 18 Years to 40 Years, accepts healthy volunteers

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

• Dominic Stoop, MD, Principal investigator, University Hospital, Ghent