Prospective Paired Study on the Effectiveness of MitoGrade
| Status: | Recruiting |
|---|---|
| Conditions: | Infertility |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | December 2015 |
| End Date: | January 2017 |
| Contact: | Krithika Ravichandran, MSc |
| Email: | research@reprogenetics.com |
| Phone: | 973-436-5000 |
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.
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.
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.
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.
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.
We found this trial at
1
site
Livingston, New Jersey 07039
Principal Investigator: Santiago Munne, Ph.D
Phone: 973-436-5000
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