InfertilityNCT02673125
Prospective Paired Study on the Effectiveness of MitoGrade
A study testing MitoGrade in people with Infertility, run by Reprogenetics at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Infertility
- What is being tested?
- MitoGrade
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to Jan 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Center criteria:
- 1. Offered only to those clinics with >20% MitoGrade elevated embryos
- Patient criteria:
- Persons undergoing IVF and Preimplantation genetic screening (PGS) through Next Generation Sequencing (NGS) will be eligible to be a part of the study.
- The study will be limited to those patients who have 4 or more PGS-classified normal embryos
- Patients not undergoing PGS will not be included as part of the study.
- Patients undergoing PGD (for genetic disorders) plus PGS will be excluded.
Who cannot join
- 1. No other specific group of individuals (age, ethnicity, egg donation, etc) will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Reprogenetics
Livingston, New Jersey, 07039
973-436-5000, research@reprogenetics.com
Santiago Munne, Ph.D
About this study
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.
Read the 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.
- Conditions
- Infertility
- Being tested
- MitoGrade
- Keywords
- Preimplantation Genetic Screening
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MitoGradeGenetic
MitoGrade refers to the mitochondrial DNA assessment in embryos.
| Study group | Role | What they receive |
|---|---|---|
| Double embryo transfer | Experimental | Patients with both MitoGrade normal and Mitograde elevated PGS normal embryos will have two embryos replaced- one Mitograde normal and one Mitograde elevated. Receives: Genetic: MitoGrade |
What is being measured
The primary outcome is the main question the study is designed to answer.
Implantation rates between MitoGrade normal and MitoGrade elevated embryos
Using DNA fingerprinting (via cheek swab) to determine which embryo implanted
Measured: Post natal analysis (9-10 months after replacement)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2016 (estimated)
- Study startDec 2015
- Primary completionDec 2016 (estimated)
- Study completionJan 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Reprogenetics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Santiago Munne, PhD, Study director, Reprogenetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02673125
- Sponsor's protocol ID
- 3.111b
- Status last verified
- Mar 2016
- First submitted
- 1 Feb 2016
- Last updated
- 15 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Fragouli E, Spath K, Alfarawati S, Kaper F, Craig A, Michel CE, Kokocinski F, Cohen J, Munne S, Wells D. Altered levels of mitochondrial DNA are associated with female age, aneuploidy, and provide an independent measure of embryonic implantation potential. PLoS Genet. 2015 Jun 3;11(6):e1005241. doi: 10.1371/journal.pgen.1005241. eCollection 2015 Jun.
PubMed 26039092
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Paired Study on the Effectiveness of MitoGrade
- ClinicalTrials.gov ID
- NCT02673125
- Acronym / sponsor ID
- 3.111b
- Conditions
- Infertility
- Keywords
- Preimplantation Genetic Screening
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- ReprogeneticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2015
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Jan 2017 (estimated)
- First posted
- 3 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Double embryo transfer | Experimental | Genetic: MitoGradePatients with both MitoGrade normal and Mitograde elevated PGS normal embryos will have two embryos replaced- one Mitograde normal and one Mitograde elevated. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1. Offered only to those clinics with >20% MitoGrade elevated embryos
- Persons undergoing IVF and Preimplantation genetic screening (PGS) through Next Generation Sequencing (NGS) will be eligible to be a part of the study.
- The study will be limited to those patients who have 4 or more PGS-classified normal embryos
- Patients not undergoing PGS will not be included as part of the study.
- Patients undergoing PGD (for genetic disorders) plus PGS will be excluded.
Key exclusion criteria (1 listed)
- 1. No other specific group of individuals (age, ethnicity, egg donation, etc) will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MitoGradeMitoGrade refers to the mitochondrial DNA assessment in embryos. | Genetic | Double embryo transfer |
Primary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2016.
- Results publication: PubMed 26039092Fragouli E, Spath K, Alfarawati S, Kaper F, Craig A, Michel CE, Kokocinski F, Cohen J, Munne S, Wells D. Altered levels of mitochondrial DNA are associated with female age, aneuploidy, and provide an independent measure of embryonic implantation potential. PLoS Genet. 2015 Jun 3;11(6):e1005241. doi: 10.1371/journal.pgen.1005241. eCollection 2015 Jun.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Santiago Munne, PhD study director
Reprogenetics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MitoGrade in people with Infertility, run by Reprogenetics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Krithika Ravichandran, MSc (973-436-5000, research@reprogenetics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Implantation rates between MitoGrade normal and MitoGrade elevated embryos (time frame: Post natal analysis (9-10 months after replacement)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02673125, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2016.