Study for the Evaluation of MitoScore Marker in the Diagnosis of Embryo Viability in Euploids Embryos

Study Overview
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Brief Summary
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The number of copies of mitochondrial genes (mtDNA or MitoScore) is related to the energy supply of the embryo, which can affect its ability to implant in the maternal uterus. The objective of this study is to analyse the potential of MitoScore before embryo transfer as a marker to identify and select the embryo with greater capacity of implantation. First of all, chromosomally normal embryos will be selected and mtDNA copies will be quantified. Finally, embryos with less copies of mtDNA will be considered for embryo transfer.

Detailed Description
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The number of mitochondrial DNA copies (mtDNA) of a chromosomally normal embryo is related to a state of energy, which affects the ability of the embryo to implant in the maternal uterus. There is a decrease in the rate of implantation in euploid embryos containing a high number of mtDNA copies. It is known that after a certain number of mtDNA copies implantation is disrupted even in euploid embryos. The main purpose of this study is to evaluate the possible relationship between the mtDNA content contained in developing embryos and the result of implantation in order to evaluate the potential of such relationship as a diagnostic tool. The number of mtDNA copies present in chromosomally normal embryos will be quantified. Subsequently, the transfer of euploid embryos after the randomization will be using either routine morphological or MitoScore criteria. Study population: women undergoing either IVF or egg donation that go through preimplantation genetic screening (PGS) for different indications, either in day 5/6 or day 3. This is a triple blinded, randomized, prospective, clinical study where patients with embryos analyzed by PGS in blastocyst stage or day 3 and mitochondrial analysis with day 5/6 transfer, with deferred cycle for those analyzed in day 5/6 and fresh embryo transfer for those analyzed in day 3, will be randomized into two groups: GROUP A: Embryo selection for transfer will be based initially on chromosomal normality and secondly on embryo morphology criteria (specific for IVF lab). GROUP B: Embryo selection for transfer will be based initially on chromosomal normality and secondly on the MitoScore value, trying to transfer normal embryos containing the lowest number of mitochondrial DNA copies.

Official Title
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Randomized Multi-centric Prospective Study for the Evaluation of MitoScore Marker in the Diagnosis of Embryo Viability in Euploids Embryos.

Conditions
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Infertility

Intervention / Treatment
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* Other: Transfer according to morphological criteria
* Other: Transfer according to the MitoScore results


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PGS cycles for different indications Maternal age: ≤40 years old (FIV/ICSI patients) Maternal age: <50 years old (OVODON patients) Spermatocyte concentration: > 2 million of spermatocyte/ml Single embryo transfer -≥ 8 oocytes MII Number of Antral Follicules (AFC: ≥10 MII) Exclusion Criteria: Detection in the moment of inclusion or previous diagnosis of congenital uterine malformations. Patients with embryo sex selection for those countries in which it is allowed.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Embryo selection for transfer will be based initially on chromosomally normal embryos and secondly on embryo morphology criteria (specific of IVF lab, as standard practice). | Other: Transfer according to morphological criteria<br>* Embryos will be analyzed by PGS and mitochondrial score on day 3 or day 5/6 biopsy and transferred on day 5/6, according to morphological criteria (control group).<br>|
| Experimental: MitoScore<br>Embryo selection for transfer will be based initially on chromosomal normality and secondly on the MitoScore value, trying to transfer chromosomally normal embryos which contain the lowest number of mitochondrial DNA copies. | Other: Transfer according to the MitoScore results<br>* Embryos will be analyzed by PGS and mitochondrial score on day 3 or day 5/6 biopsy and transferred on day 5/6, according to the MitoScore results (experimental group).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate |  | 20 days | 
| Pregnancy rate |  | 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Miscarriage rate |  | 9 months | 
| Ongoing pregnancy rate |  | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Embryo Implantation, Mitochondrial genes, Mitochondrial DNA, MitoScore, Embryo selection, Embryo viability, Embryo biomarker, Diagnosis of embryo viability in euploids embryos