Mitochondrial DNA content as a viability score in human euploid embryos: less is better

Juan, A. Diez; Rubio, Carmen; Marín, Carlos; Martínez, Sebastián; Díaz-Gimeno, Patricia; Riboldi, M.; Al-Asmar, N.; Valbuena, Diana; Simón, Carlos

doi:10.1016/j.fertnstert.2015.07.972

“…Our opinion is that the cf-mtDNA in the embryo spent culture media would inversely mirror the overall embryonic mtDNA content, in line with recent studies suggesting that mtDNA abundance within blastomers may be correlated to aneuploidy, low embryo viability and development [4][5][6]. Undoubtedly, a direct comparison of mtDNA content between embryo and medium would provide a definitive demonstration of this hypothesis.…”

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confidence: 87%

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2021

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On 2013 for the first time, we discovered both cell-free genomic DNA (cf-gDNA) and cellfree mithocondrial DNA (cf-mtDNA) in spent culture media of human cleavage-stage embryos [1]. Analysis of DNA profiles of day 3 spent media demonstrated that cf-mtDNA/cf-gDNA ratio was correlated with embryo quality, and in particular it was significantly associated with degree of embryo fragmentation. Based on our results, the higher cf-mtDNA/cf-gDNA ratio was associated with blastocyst's developmental competence, trophoectoderm quality, and implantation [2]. In a prospective, blinded, multi-centric study we confirmed that the cf-mtDNA/cf-gDNA ratio in day 3 spent culture medium, combined with embryo morphology, improved the prediction upon blastulation compared to morphology alone, without any influence from patient and treatment-related factors [3].

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“…Such a sample size seems far too small to draw any conclusion. The correlation of elevated quantity of mtDNA copy number with a lower embryo viability was subsequently demonstrated by several investigators [ 25 , 26 , 29 ]. However, even though Wang et al [ 29 ] found a statistically significant difference in mtDNA content between implanted and nonimplanted embryos, they considered mtDNA score as independent embryo selection marker by receiver operating characteristic (ROC) curve analysis and found a low predictive value of this parameter in embryo implantation and live birth outcomes.…”

Section: Discussionmentioning

confidence: 88%

“…For that reason, in recent years, several research teams have paid attention to the implication of embryo mtDNA level on reproductive outcome. However, the obtained results are highly conflicting and the utility of mitochondrial score as an embryo selection marker is still unknown [ 23 , 24 , 25 , 26 , 27 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…First of all, we should consider mtDNA score estimation technique. There are several calculation formulas that may influence the obtained findings in different ways [ 23 , 25 , 34 , 36 , 45 ]. Second, technical approaches may also play a crucial role when taking into consideration that even investigators who used the same formula obtained conflicting results.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that elevated levels of mtDNA at the blastocyst stage are associated with aneuploidy and decreased implantation potential for euploid human embryos, and therefore the levels of this genome may reflect embryo viability [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. However, a number of experiments and observations performed by several study groups obtained conflicting results, suggesting no influence of embryo mtDNA copy number on reproductive success [ 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

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Does Trophectoderm Mitochondrial DNA Content Affect Embryo Developmental and Implantation Potential?

Łukaszuk

¹

,

Podolak

²

2022

IJMS

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A retrospective case control study was undertaken at the molecular biology department of a private center for reproductive medicine in order to determine whether any correlation exists between the mitochondrial DNA (mtDNA) content of trophectoderm and embryo developmental potential. A total of 275 couples underwent IVF treatment, producing a total of 716 embryos. The trophectoderm was biopsied from each embryo at the blastocyst stage (day 5 or day 6 post-fertilization) subjected to low-pass next-generation sequencing (NGS), for the purpose of detecting aneuploidy. For each sample, the number of mtDNA reads obtained after analysis using NGS was divided by the number of reads attributable to the nuclear genome. The mtDNA copy number was found to be higher in aneuploid embryos than in those that were euploid (mean mtDNA ratio ± SD: 1.13 ± 1.37 versus 1.45 ± 1.78, p = 0.02) and in day 5 biopsies compared to day 6 biopsies (1.41 ± 1.66 vs. 1.19 ± 1.27, p = 0.001), whereas no statistically significant differences in mtDNA content were seen in relation to embryo morphology (1.58 ± 2.44 vs. 2.19 ± 2.89, p = 0.12), genetic sex (1.27 ± 1.29 vs. 1.27 ± 1.18, p = 0.99), maternal age (1.31 ± 1.41 vs. 1.33 ± 1.29, p = 0.43), or its ability to implant (1.14 ± 0.88 vs. 1.21 ± 1.16, p = 0.39). mtDNA has small potential to serve as an additional, independent biomarker for embryo selection.

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Cell-Free Mitochondrial DNA in Embryo Spent Culture Medium as Biomarker for In- Vitro Fertilization Outcome and its Potential Clinical Use

Scaruffi¹

2021

PRM

0

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On 2013 for the first time, we discovered both cell-free genomic DNA (cf-gDNA) and cellfree mithocondrial DNA (cf-mtDNA) in spent culture media of human cleavage-stage embryos [1]. Analysis of DNA profiles of day 3 spent media demonstrated that cf-mtDNA/cf-gDNA ratio was correlated with embryo quality, and in particular it was significantly associated with degree of embryo fragmentation. Based on our results, the higher cf-mtDNA/cf-gDNA ratio was associated with blastocyst's developmental competence, trophoectoderm quality, and implantation [2]. In a prospective, blinded, multi-centric study we confirmed that the cf-mtDNA/cf-gDNA ratio in day 3 spent culture medium, combined with embryo morphology, improved the prediction upon blastulation compared to morphology alone, without any influence from patient and treatment-related factors [3].

show abstract

Mitochondrial DNA content as a viability score in human euploid embryos: less is better

Cited by 3 publications

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Does Trophectoderm Mitochondrial DNA Content Affect Embryo Developmental and Implantation Potential?

Cell-Free Mitochondrial DNA in Embryo Spent Culture Medium as Biomarker for In- Vitro Fertilization Outcome and its Potential Clinical Use

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