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Prospective Paired Study on the Effectiveness of MitoGrade

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02673125
Recruitment Status : Unknown
Verified March 2016 by Reprogenetics.
Recruitment status was:  Recruiting
First Posted : February 3, 2016
Last Update Posted : March 15, 2016
Information provided by (Responsible Party):

Brief Summary:

Chromosomal abnormalities are a major cause of pregnancy loss. Preimplantation Genetic Screening (PGS) using Next Generation Sequencing (NGS) allows the effective detection of these abnormalities and improves clinical outcomes. However even the transfer of a chromosomally normal embryo does not guarantee successful implantation. Recent research by Fragouli, et. al. 2015 has demonstrated a strong association between mitochondrial DNA quantities (also known as MitoGradeTM) and implantation outcomes in embryos that are already classified by PGS as chromosomally normal. Investigators have also demonstrated in a clinical study that MitoGradeTM normal and PGS normal embryos have higher chances of implantation than MitoGrade elevated PGS normal embryos. Transferring MitoGrade elevated PGS normal embryos results in less than 10% implantation rates while MitoGrade normal PGS normal embryos resulted in more than 65% implantation rates. The risk of miscarriage after replacing either type is very low (about 8%).

In order to understand the complete effectiveness of the test, investigators are conducting a paired prospective study. This means that investigators will be transferring a MitoGrade normal and a MitoGrade elevated embryo at the same time to see if one implants better than the other. It is expected that patients joining this study will benefit from knowing that at least one embryo is MitoGrade normal PGS normal.

Condition or disease Intervention/treatment Phase
Infertility Genetic: MitoGrade Not Applicable

Detailed Description:

Mitochondria are considered the powerhouses of cells. These membrane-bound organelles play a vital role in embryonic development and are essential for various cellular functions. And unlike other cellular organelles, they contain their own DNA (also known as mitochondrial DNA or mtDNA). Embryonic development is a complex energy-driven process and is thought to be highly dependent on mitochondrial function and mtDNA gene expression. It is believed that amounts of mtDNA remain constant in first three days of preimplantation development. Significant alterations in mtDNA are not initiated until after day 5 when the embryo has undergone the first cellular differentiation into trophectoderm (TE) and inner cell mass. It is possible that mtDNA variation may account chromosomal abnormalities by affecting the accuracy of chromosome segregation.

In addition to describing the relationship between mtDNA expression and clinical outcomes, Reprogenetics and Fragouli et al. (2015) were able to establish a threshold over which no clinical pregnancy was established. These results were further validated in a prospective blinded study and independently validated using Next Generation Sequencing (NGS) analysis. The quantification of mtDNA therefore provides important information in selecting the best embryos for transfer. MitoGradeTM is a real-time polymerase chain reaction (PCR) based method developed to quantify the amount of mitochondrial DNA (mtDNA) present in human preimplantation embryos. It is believed that a chromosomally normal embryo with a MitoGradeTM score lower than the established threshold will have a higher chance of successful implantation in comparison to a similar embryo with a higher MitoGradeTM score.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Prospective Paired Study on the Effectiveness of MitoGrade
Study Start Date : December 2015
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : January 2017

Arm Intervention/treatment
Experimental: Double embryo transfer
Patients with both MitoGrade normal and Mitograde elevated PGS normal embryos will have two embryos replaced- one Mitograde normal and one Mitograde elevated.
Genetic: MitoGrade
MitoGrade refers to the mitochondrial DNA assessment in embryos.

Primary Outcome Measures :
  1. Implantation rates between MitoGrade normal and MitoGrade elevated embryos [ Time Frame: Post natal analysis (9-10 months after replacement) ]
    Using DNA fingerprinting (via cheek swab) to determine which embryo implanted

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

Center criteria:

1. Offered only to those clinics with >20% MitoGrade elevated embryos

Patient criteria:

  1. Persons undergoing IVF and Preimplantation genetic screening (PGS) through Next Generation Sequencing (NGS) will be eligible to be a part of the study.
  2. The study will be limited to those patients who have 4 or more PGS-classified normal embryos
  3. Patients not undergoing PGS will not be included as part of the study.
  4. Patients undergoing PGD (for genetic disorders) plus PGS will be excluded.

Exclusion Criteria:

1. No other specific group of individuals (age, ethnicity, egg donation, etc) will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02673125

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Contact: Krithika Ravichandran, MSc 973-436-5000

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United States, New Jersey
Reprogenetics Recruiting
Livingston, New Jersey, United States, 07039
Contact    973-436-5000   
Principal Investigator: Santiago Munne, Ph.D         
Sponsors and Collaborators
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Study Director: Santiago Munne, PhD Reprogenetics
Publications of Results:
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Responsible Party: Reprogenetics Identifier: NCT02673125    
Other Study ID Numbers: 3.111b
First Posted: February 3, 2016    Key Record Dates
Last Update Posted: March 15, 2016
Last Verified: March 2016
Keywords provided by Reprogenetics:
Preimplantation Genetic Screening
Additional relevant MeSH terms:
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