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

Dı́ez-Juan, Antonio; Rubio, Carmen; Marín, Carlos; Martínez, Sebastián; Al‐Asmar, Nasser; Riboldi, M.; Díaz-Gimeno, Patricia; Valbuena, Diana; Simón, Carlos

doi:10.1016/j.fertnstert.2015.05.022

Cited by 203 publications

(195 citation statements)

References 23 publications

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“…In human embryos, recent studies have investigated amounts of mtDNA, generally describing a correlation of high mtDNA lev (4)(5)(6). Conditions that deviate from the steady state such as aneuploidy, advanced maternal age, or chemically induced-stress tend to associate with higher mtDNA content.…”

Section: Introductionmentioning

confidence: 99%

“…Conditions that deviate from the steady state such as aneuploidy, advanced maternal age, or chemically induced-stress tend to associate with higher mtDNA content. Of clinical relevance, such reports suggested that embryos with mtDNA levels above the norm showed significantly poor frequency of pregnancy when transferred (4,5).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, in the case of euploid embryos being chosen for transfer, sub-optimal intrinsic or environmental factors could elicit higher levels of mtDNA. Consequently, mtDNA content has been proposed as a biomarker for embryo viability (4,5).…”

Section: Introductionmentioning

confidence: 99%

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Accurate Quantitation of Mitochondrial DNA Reveals Uniform Levels in Human Blastocysts Irrespective of Ploidy, Age, or Implantation Potential

Victor

Brake

Tyndall

et al. 2017

Obstetrical &Amp; Gynecological Survey

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Main Outcome Measure(s): For each sample the mtDNA value was divided by the nuclear DNA (nDNA) value and the result was further subjected to mathematical analysis tailored to the genetic makeup of the source embryo.Result(s): On average the mathematical correction factor changed the conventionally determined mtDNA score of a given blastocyst via NGS by 1.43% +/-1.59% (N=1396), with maximal adjustments of 17.42%, and via qPCR by 1.33% +/-8.08% (N=150), with maximal adjustments of 50.00%. Levels of mtDNA in euploid and aneuploid embryos showed a statistically insignificant difference by NGS (euploids N=775, aneuploids N=621) and by qPCR (euploids N=100, aneuploids N=50). Blastocysts derived from younger or older patients had comparable mtDNA levels by NGS ( N=874 age group N=514) and by qPCR ( N age group N=58). Viable blastocysts did not contain significantly different mtDNA levels compared to unviable blastocysts when analyzed by NGS (implanted N=101, nonimplanted N=140) and by qPCR (implanted N=49, non-implanted N=51). Conclusion(s):We recommend implementation of the correction factor calculation to laboratories evaluating mtDNA levels in embryos by NGS or qPCR. When applied to our in-house data, the calculation reveals that overall levels of mtDNA are largely equal between blastocysts stratified by ploidy, age, or implantation potential.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Accurate Quantitation of Mitochondrial DNA Reveals Uniform Levels in Human Blastocysts Irrespective of Ploidy, Age, or Implantation Potential

Victor

Brake

Tyndall

et al. 2017

Obstetrical &Amp; Gynecological Survey

View full text Add to dashboard Cite

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“…They concluded that further RCTs are needed to examine the role of ICSI versus IVF for men with high DNA fragmentation. Simon et al, (2015) looked at 8068 treatment cycles where DNA damage was measured using all four assays and found a modest but statistically significant association of DNA damage with CPR following IVF and/or ICSI. They found that the data varied depending on the assay used.…”

Section: Sperm Dna Fragmentationmentioning

confidence: 99%

“…In 2015, two papers were published reporting an association between higher mtDNA level and lower implantation potential in blastocysts (Diez-Juan et al, 2015;Fragouli et al, 2015), pointing to disturbed energy provision and metabolic stress in embryos with a higher mtDNA content. While the paper of Diez-Juan et al focused on euploid, transferred blastocysts, the other report also showed a relationship between aneuploidy of the blastocyst and a higher mtDNA load.…”

Section: Mitochondrial Dna Load Measurementmentioning

confidence: 99%

Adjuncts in the IVF laboratory: where is the evidence for ‘add-on’ interventions?

et al. 2017

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Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or 'add-ons' that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high quality evidence that the procedure is safe and effective. Only then should the technique be considered as 'routine' and only when applied to the similar patient population as those studied in the RCT. Even then, further paediatric and long-term follow up studies will need to be undertaken to examine the long-term safety of the procedure. Alarmingly, there are currently numerous examples where adjunct treatments are used in the absence of evidence-based medicine and often at an additional fee. In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic. In this paper, we discuss some of the adjunct treatments currently being offered globally in IVF laboratories including embryo glue and adherence compounds, sperm DNA fragmentation, time lapse imaging, preimplantation genetic screening, mitochondria DNA load measurement and assisted hatching and examine the evidence for their safety and efficacy in increasing LBRs. We conclude that robust studies are needed to confirm the safety and efficacy of any adjunct treatment or test before they are offered routinely to IVF patients.

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The role of mitochondria in the female germline: Implications to fertility and inheritance of mitochondrial diseases

Chiaratti

Garcia

Carvalho

et al. 2018

Cell Biology International

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Mitochondria play a fundamental role during development of the female germline. They are fragmented, round, and small. Despite these characteristics suggesting that they are inactive, there is accumulating evidence that mitochondrial dysfunctions are a major cause of infertility and generation of aneuploidies in humans. In addition, mitochondria and their own genomes (mitochondrial DNA-mtDNA) may become damaged with time, which might be one reason why aging leads to infertility. As a result, mitochondria have been proposed as an important target for evaluating oocyte and embryo quality, and developing treatments for female infertility. On the other hand, mutations in mtDNA may cause mitochondrial dysfunctions, leading to severe diseases that affect 1 in 4,300 people. Moreover, very low levels of mutated mtDNA seem to be present in every person worldwide. These may increase with time and associate with late-onset degenerative diseases such as Parkinson disease, Alzheimer disease, and common cancers. Mutations in mtDNA are transmitted down the maternal lineage, following a poorly understood pattern of inheritance. Recent findings have indicated existence in the female germline of a purifying filter against deleterious mtDNA variants. Although the underlying mechanism of this filter is largely unknown, it has been suggested to rely on autophagic degradation of dysfunctional mitochondria or selective replication/transmission of non-deleterious variants. Thus, understanding the mechanisms regulating mitochondrial inheritance is important both to improve diagnosis and develop therapeutic tools for preventing transmission of mtDNA-encoded diseases.

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

Abstract: An increased amount of mtDNA in euploid embryos is related to poor implantation potential and may be indicative of reduced metabolic fuel during oocyte maturation. We are implementing Ms in our preimplantation genetic screening platform to prospectively analyze its clinical relevance.

Cited by 203 publications

References 23 publications

Accurate Quantitation of Mitochondrial DNA Reveals Uniform Levels in Human Blastocysts Irrespective of Ploidy, Age, or Implantation Potential

Accurate Quantitation of Mitochondrial DNA Reveals Uniform Levels in Human Blastocysts Irrespective of Ploidy, Age, or Implantation Potential

Adjuncts in the IVF laboratory: where is the evidence for ‘add-on’ interventions?

The role of mitochondria in the female germline: Implications to fertility and inheritance of mitochondrial diseases

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