Mitochondrial DNA content as a viability indicator in human euploid embryos
1. What is MitoScore?
MitoScore is a mitochondrial biomarker which gives us an indicator of the energy status of an embryo. MitoScore allows us to select those embryos with the greatest probabilities for implantation, therefore more likely to result in a viable pregnancy through IVF/ PGS. The clinical translation of this work is the integration of the mtDNA copy number (MitoScore) to the routine genetic analysis performed in our PGS analysis.
The mitochondrial score “MitoScore” is a value that represents the normalized mtDNA content in euploid embryos and indicates the total mtDNA content in the sample.
Our published studies support the hypothesis that mtDNA copy number in the embryo is not a direct indicator of energetic capability, rather it is an index of energetic stress and thus it can potentially be used to predict their implantation capacity (Diez-Juan A, Rubio C et al. 2015).
Mitochondria and mtDNA
- Mitochondria are structures within cells that play an essential role in energy production.
- Although most DNA is located in chromosomes within the nucleus, mitochondria have their own DNA. This genetic material is known as mitochondrial DNA or mtDNA.
- Mitochondrial DNA content in an embryo is an index of energetic stress, which can be used to predict its implantation potential. Our studies indicate that an increase in the mitochondrial DNA in the embryo is indicative of an insufficient level of energy and a low implantation potential.
2. What is MitoScore useful for?
1) MitoScore will help IVF clinics to select the euploid embryos with higher potential for implantation and therefore increase pregnancy rates for PGS.
2) It provides a mitochondrial score of embryo implantation ability in euploid embryos, to be considered in addition to the routine morphological classification.
3) MitoScore provides this information very soon, since the mitochondrial DNA measurement can be obtained both at day 3 or day 5 of embryonic development.
MitoScore is designed to work using the same sample used for PGS. The embryos do not need to be exposed to any interventions apart from those associated with routine chromosome screening and does not require any additional work in the embryology laboratory. Anyone who needs biopsying their embryos would benefit doing this test.
3. What are the advantages of MitoScore?
1) Increased implantation and pregnancy rates in IVF.
2) Reduction of the number of multiple gestations.
3) Measurement obtained at an early stage: at day 3 or day 5 of embryonic development.
4) Additional information on embryo health by complementing morphological observations.
We have established a means to test the mitochondria DNA levels in embryos, picking out the less efficient ones, thus significantly increasing the chances of evolutive pregnancy. Based on our statistics, initial studies suggest that women might expect a 70-80% pregnancy rate with a single embryo transfer.
1) Can MitoScore be done on day 3 or blastocyst stage (day 5)?
We can perform MitoScore testing on embryos that are biopsied at either day 3 or day 5. A 3 day old embryo has approximately 8 cells, and so only a single cell is removed for a biopsy done at day 3. A 5 day old embryo has a few hundred cells, and so several cells can be safely removed during the biopsy. There are several good reasons to do either a day 3 or a day 5 biopsy. The number of cells that can be safely removed, rates of mosaicism, expertise of the embryologist, and embryo quality are all important factors in deciding when to do embryo biopsy. Patients should discuss with their IVF doctor about the best time to do biopsy.
2) Does MitoScore include mitochondrial diseases?
No, MitoScore only gives a value of relative mitochondrial DNA that is indicative of reduced energetic reserve in early embryos.
3) What is the effectiveness of MitoScore for prediction of implantation potential?
High mtDNA copy number in euploid embryos is indicative of lower embryo viability and implantation. Using the normalized mtDNA content, Mitoscore Ms. Day-3 embryos with MsA had an implantation rate IR of 59% n=51; those with MsB had an IR of 44%; and those with MsC had an IR of 25% n=52.. Day-5 with MsA had an IR of 81%; MsB had an IR of 56% and those with MsD had an IR of 18% n=17.
4) What happens if all my embryos have a high MitoScore?
High MitoScore value indicates a lower implantation potential, however it does not mean none of them will be able to implant. Our recommendation is to transfer the embryo or embyos with lower MitoScore and better morphological grade.