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

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 97 (MsD) had an IR of 25% (n = 52). Embryos with Ms >160 (n = 22) never implanted. Day-5 embryos with 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.