Accurate quantitation of mitochondrial DNA reveals uniform levels in human blastocysts irrespective of ploidy, age, or implantation potential

Victor, Andrea; Brake, Alan; Tyndall, Jack C.; Griffin, Darren K.; Zouves, Christo; Barnes, Frank L.; Viotti, Manuel

doi:10.1016/j.fertnstert.2016.09.028

Cited by 127 publications

(119 citation statements)

References 29 publications

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“…However, in this study we did not observe any correlation between maternal age (24-46 years) at the time of oocyte retrieval and mtDNA levels in trophectodermal cells of blastocyst. Similar to our findings, other studies also failed to report any correlation between maternal age with mtDNA levels in the blastocysts (de Los Santos et al, 2018; Diez-Juan et al, 2015; Klimczak et al, 2018; Victor et al, 2017). Together the results indicate, maternal age does not contribute to alterations in mtDNA levels in the blastocysts.…”

Section: Discussionsupporting

confidence: 92%

“…Interestingly, in another study, embryos with monosomies showed higher mtDNA levels as compared to embryos trisomies (de Los Santos et al, 2018). Whereas, some studies fail to show any association between chromosomal status of the blastocyst and mtDNA levels (Qui et al, 2018; Victor et.al., 2017). The association of mtDNA levels and the ploidy status of the blastocyst require further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…al., 2017). In another study the authors argued that the differences in mtDNA content could arise out of differences in genomic DNA content, and hence a normalization factor was used, which led to the conclusion that the levels of mtDNA are near identical between blastocysts stratified by ploidy, maternal age, or implantation potential (Victor et.al., 2017). Another study by Qui and group failed to establish any correlation between mtDNA, embryo quality and clinical outcomes (Qui et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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No association of mitochondrial DNA levels in trophectodermal cells with the developmental competence of the blastocyst and pregnancy outcomes

Ritu

Veerasigamani

Ashraf

et al. 2019

Preprint

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17Study question 18 Can mitochondrial DNA (mtDNA) levels in trophectodermal cells of the blastocyst predict the 19 blastocyst quality, ploidy status, implantation rate and clinical outcomes? 20 Summary answer 21 mtDNA levels in trophectodermal cells of the blastocyst do not associate with the blastocyst 22 quality, ploidy status, implantation potential and clinical outcomes, but can differentiate between 23 aneuploid and euploid blastocysts.24 What we already know 25 mtDNA levels in the trophectodermal cells have been suggested to be associated with blastocyst 26 morphology, ploidy and implantation rates, and has been proposed as biomarker to access 27 blastocyst quality and predict clinical outcomes. However, discrepancies exist if mtDNA levels 28 could serve as a marker for the same.29 Study design and duration 30

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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No association of mitochondrial DNA levels in trophectodermal cells with the developmental competence of the blastocyst and pregnancy outcomes

Ritu

Veerasigamani

Ashraf

et al. 2019

Preprint

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“…While these data support the conclusion that mtDNA may serve as a useful biomarker of reproductive potential, multiple questions still remain with regards to the clinical applicability of this technology. In addition, another group recently reported the lack of predictive value of mtDNA for reproductive potential using a modified methodology that improved normalization strategies (Victor et al ., 2016). …”

Section: Introductionmentioning

confidence: 99%

Levels of trophectoderm mitochondrial DNA do not predict the reproductive potential of sibling embryos

Treff

Zhan²,

Tao³

et al. 2017

Human Reproduction

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STUDY QUESTIONWhat is the predictive value of trophectoderm mitochondrial DNA (mtDNA) quantity for blastocyst reproductive potential?SUMMARY ANSWERThis study demonstrates that, within a given cohort, mtDNA quantitation does not distinguish between embryos that implant and embryos that do not implant after double embryo transfer (DET).WHAT IS ALREADY KNOWNAn association between implantation failure and increased quantities of mtDNA has been observed in two studies but not in a third.STUDY DESIGN, SIZE AND DURATIONA total of 187 patients (nine who received donor oocytes) with DET of one male and one female euploid blastocyst were included in this retrospective study, with 69 singleton deliveries providing the primary dataset to evaluate the predictive value of mtDNA for reproductive potential between January 2010 and July 2016.PARTICIPANTS/MATERIALS, SETTING AND METHODMtDNA was quantified in cell lines to validate the quantitative PCR assay on limited quantities of starting material and then applied to 374 blastocyst biopsies. Pregnancies resulting in a singleton outcome were analyzed and newborn gender was utilized as a means to identify the implanted embryo. MtDNA quantity was then compared between implanted and non-implanted embryos in order to define the predictive value of mtDNA content for reproductive potential in this subset of patients.MAIN RESULTS AND THE ROLE OF CHANCEAn initial comparison of mtDNA levels between all successful and unsuccessful embryos revealed no significant differences. In order to control for patient-specific variables, gender was subsequently used to identify the implanted embryo in DETs resulting in a singleton (n = 69). No systematic difference in relative mtDNA quantity was detected between implanted and non-implanted embryos.LIMITATIONS, REASONS FOR CAUTIONThis study was conducted at a single center and did not evaluate the entire cohort of embryos from each patient to evaluate cohort specific variation in mtDNA quantity. Although the largest of its kind so far, the sample size of DETs leading to a singleton was relatively small.WIDER IMPLICATIONS OF THE FINDINGSThese data highlight the importance of control over patient-specific variables when evaluating candidate biomarkers of reproductive potential. All current available data suggest that mtDNA quantification needs further study before its clinical use to augment embryo selection.STUDY FUNDING/COMPETING INTERESTSThe authors have no potential conflict of interest to declare. No external funding was obtained for this study.TRIAL REGISTRATION NUMBERNot applicable.

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“…According to the "quiet embryo" hypothesis, under ideal circumstances, embryos are in low metabolic activity, which suggests that a viable embryo has a relatively lower metabolism, whereas those under stress and of reduced developmental potential, tend to be metabolically more active (Ravichandran et al, 2017). Elevated mtDNA levels and by extension increased adenosine triphosphate (ATP) production could be a compensatory mechanism providing distressed embryos with more chemical energy to overcome adverse conditions (Victor et al, 2017). MtDNA replicates since the primordial germ cell stage and the MII oocyte fixes its mtDNA composition before fertilization (St. John, 2014).…”

Section: Discussionmentioning

confidence: 99%

Embryo quality, and not chromosome nondiploidy, affects mitochondrial DNA content in mouse blastocysts

Jing

et al. 2018

Journal Cellular Physiology

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It has been shown recently that there is premature mitochondria biosynthesis in blastocysts from older women whose egg or embryo quality is poor and that aneuploid blastocysts also have a high number of mitochondrial DNA (mtDNA) copies. Whether nondiploidy/aneuploidy or reduced egg or embryo quality causes premature mitochondrial biosynthesis is not known. This study constructed haploid, diploid, triploid, and tetraploid blastocysts by parthenogenetic activation, intracytoplasmic sperm injection with one or two sperm heads, blastomere electrofusion, respectively, and generated reduced cytoplasm quality embryos from diabetic mouse and in vitro fertilization of aged oocytes, and examined whether nondiploidy or reduced cytoplasm quality causes premature mitochondrial biosynthesis. MtDNA numbers of each blastocyst from different models were tested by absolute quantitative real‐time polymerase chain reaction. It was found that mtDNA content in preimplantation embryos was not associated with their chromosome ploidy, while mtDNA copy numbers in embryos with suboptimal quality were increased. Therefore, it might be the reduced cytoplasmic quality, and not chromosome nondiploidy, that causes premature mitochondria biosynthesis in blastocysts.

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Accurate quantitation of mitochondrial DNA reveals uniform levels in human blastocysts irrespective of ploidy, age, or implantation potential

Cited by 127 publications

References 29 publications

No association of mitochondrial DNA levels in trophectodermal cells with the developmental competence of the blastocyst and pregnancy outcomes

No association of mitochondrial DNA levels in trophectodermal cells with the developmental competence of the blastocyst and pregnancy outcomes

Levels of trophectoderm mitochondrial DNA do not predict the reproductive potential of sibling embryos

Embryo quality, and not chromosome nondiploidy, affects mitochondrial DNA content in mouse blastocysts

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