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

Capsule:
Higher mitochondrial DNA content in euploid human embryos is related to poor implantation potential and may be indicative of reduced metabolic fuel during oocyte maturation.

Authors:
Antonio Diez-Juan, Ph.D., Carmen Rubio, Ph.D., Carlos Marin, B.Sc., Sebastian Martinez, B.Sc., Nasser Al-Asmar, M.Sc., Marcia Riboldi, Ph.D., Patricia Díaz-Gimeno, Ph.D., Diana Valbuena, M.D., Ph.D., Carlos Simón, M.D., Ph.D.

Volume 104, Issue 3, Pages 534-541

Abstract:

Objective:
To investigate the clinical relevance of mitochondrial DNA (mtDNA) content as a viability score in human euploid embryos.

Design:
Retrospective analysis of mtDNA content of transferred euploid embryos.

Setting:
Reproductive genetics laboratory.

Patient(s):
Single-embryo transfer in 270 patients who underwent preimplantation genetic screening (205 day-3 blastomere biopsies, and 65 day-5 trophectoderm biopsies), and 10 patients with double-embryo transfer (male-female).

Intervention(s):
None.

Main Outcome Measure(s):
Normalized mtDNA content versus nuclear DNA (nDNA) from transferred euploid embryos.

Result(s):
A high mtDNA copy number in euploid embryos is indicative of lower embryo viability and implantation. Using the normalized mtDNA content, we created the mitochondrial score or Mitoscore (Ms). Day-3 embryos with <34 (MsA) had an implantation rate (IR) of 59% (n = 51); those with 34–52 (MsB) had an IR of 44% (n = 52); those with 52–97 (MsC) had an IR of 42% (n = 50); and those with >97 (MsD) had an IR of 25% (n = 52). Embryos with Ms >160 (n = 22) never implanted. Day-5 embryos with <18.19 (MsA) had an IR of 81%; those with 18.19–24.15 (MsB) had an IR of 50% (n = 16); those with 24.15–50.58 (MsC) had an IR of 62% (n = 16); and those with levels >50.58 (MsD) had an IR of 18% (n = 17). Embryos with levels >60 (n = 7) never implanted.

Conclusion(s):
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.

  • Jason M. Franasiak

    Congratulations on a very interesting manuscript. In terms of the differences in implanted vs. non-implanted, is it possible that, given SET, that this is due to variations or confounding factors between patients? In future studies as this is implemented is there any thought to a paired embryo transfer to see if it predicts between embryos in a single cohort? May not be feasible study design given transfer order restrictions but may be informative. Many thanks.

    • Antonio Diez-Juan

      Thanks Jason, we are going to start a RCT and confounding factors is something that we are trying to solve as far as possible. DET would be very informative and although as you say transfer order could be also a confounding factor it can give us some more clues about the usefulness of this marker.

      Thanks again

      • Jason M. Franasiak

        Many thanks for your reply, I look forward to your data!

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