Hyaluronan-enriched Medium and Euploid Blastocyst Transfers

Study Overview
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Brief Summary
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It has been proposed that enriching transfer media with hyaluronan (EmbryoGlue medium) improves pregnancy outcomes compared with media containing lower concentrations of this molecule. However, none of previous studies included preimplantation genetic testing for aneuploidy (PGT-A) embryos. In order to investigate the impact of this hyaluronan-enriched on pregnancy outcomes, it is essential to evaluate its efficacy on euploid-only embryo transfers. The aim of the present study is to evaluate whether a short period of exposure of euploid blastocysts to EmbryoGlue prior to and during transfer positively impact on pregnancy outcomes of frozen embryo transfer (FET) cycles.

Detailed Description
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The study period will be determined by the completion of the predetermined sample size, with two interim analyses planned when 35% (n=274) and 70% (n=548) of the target sample size is achieved to calculate conditional power. If conditional power is estimated to be lower than 15% at first interim analysis or lower than 30% in the second interim analysis, the trial will be stopped due to futility. The study will be performed in Abu Dhabi-Fertility clinic. During the period of this prospective study, euploid blastocysts of enough quality that have been biopsied only on Day-5 for PGT-A, will be warmed for single blastocyst transfer. The patient´s endometrial preparation protocol for FET will be restricted to HRT only. The study will be double-blinded (blinded to patient and doctor performing transfer).

Official Title
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Impact of Hyaluronan-enriched Medium on Pregnancy Outcomes Following Euploid Blastocyst Transfers

Conditions
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Infertility, Implantation Rate, Clinical Pregnancy Rate, Live Birth Rate, Blastocysts, FET

Intervention / Treatment
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* Drug: EmbryoGlue Medium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All frozen embryo transfer (FET) cycles with euploid blastocysts biopsied and vitrified on Day 5 after PGT-A. Rank of randomization based on embryo quality. Only hormonal replacement theraphy (HRT) cycle regimen. Women aged 18 years to 46 years. Having at least 1 chromosomally normal vitrified blastocyst(s) on Day 5 available for transfer. All sperm samples. BMI between 18 and 35. Exclusion Criteria: FET cycles with preimplantation genetic testing for monogenic disorders (PGT-M) and for structural rearrangements (PGT-SR). FET cycles with mosaic / aneuploid blastocysts. FET cycles with unknown outcome. FET cycles with Day 6 or Day 7 biopsied blastocysts. FET with patients' endometrium preparation with treatments other than HRT. FET where PGT-A was performed for gender selection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 46 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
Interventional Model Description: Randomization will be stratified according to the in-house embryo prognosis classification. Our internal data shows top quality embryos have 65% ongoing pregnancy rate and good quality embryos have 55% ongoing pregnancy rate. We assume a 20% relative increase over the baseline with the intervention which corresponds to 78% and 66% ongoing pregnancy rates for top and good quality euploid embryos, respectively. Total sample size requires in each group corresponds to 295 and 488 transfers of top and good quality embryos for a total of 783. Two interim analyses are planned when 35% (n=274) and 70% (n=548) of the target sample size is achieved to calculate conditional power. If conditional power is estimated to be lower than 15% at first interim analysis or lower than 30% in the second interim analysis, the trial will be stopped due to futility.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Blastocysts exposed to normal media (NEG)<br>Blastocysts exposed to routine-in use medium No intervention | |
| Active Comparator: Blastocysts exposed to EmbryoGlue (EG)<br>Blastocysts exposed to EmbryoGlue | Drug: EmbryoGlue Medium<br>* Embryos will be exposed to hyaluronic-enriched media (EmbryoGlue) before and during embryo transfer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth rate (LBR) | Defined as the delivery if a live infant born after 24 completed weeks of gestation | 41 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| human chorionic gonadotropin (hCG) positiveness | hCG pregnancy test checks human chorionic gonadotropin (HCG) levels in the blood. | 10-12 days after embryo transfer | 
| Clinical pregnancy rate | ultrasonographic sac visible at 5 gestational weeks | 6 weeks | 
| Clinical miscarriage rate | spontaneous loss of a clinical pregnancy before 24 weeks of gestation | 24 weeks | 
| Ongoing pregnancy rate after 12 weeks | viable pregnancy with gestational age more than 12 weeks | 13 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HRT, PGT-A, Next-generation sequencing (NGS), Miscarriage rate, single embryo transfer (SET), EmbryoGlue, BMI, Embryo quality, Hyaluronan-enriched medium, Transfer medium