title: Mitochondrial DNA content as a viability score in human euploid embryos: less is better.
abstract: OBJECTIVE
  To investigate the clinical relevance of mitochondrial DNA (mtDNA) content as a viability score in human euploid embryos.
  
  
  METHODS
  Retrospective analysis of mtDNA content of transferred euploid embryos.
  
  
  METHODS
  Reproductive genetics laboratory.
  
  
  METHODS
  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).
  
  
  METHODS
  None.
  
  
  METHODS
  Normalized mtDNA content versus nuclear DNA (nDNA) from transferred euploid embryos.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Igenomix Europe, Valencia, Spain. Electronic address: antonio.diez@igenomix.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Diez-Juan
authors.affiliation: Igenomix Europe, Valencia, Spain; Igenomix USA, Miami, Florida.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rubio
authors.affiliation: Igenomix Europe, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Marin
authors.affiliation: Igenomix Europe, Valencia, Spain.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Martinez
authors.affiliation: Igenomix USA, Miami, Florida.
authors.forename: Nasser
authors.initials: N
authors.lastname: Al-Asmar
authors.affiliation: Igenomix Brasil, São Paulo, Brazil.
authors.forename: Marcia
authors.initials: M
authors.lastname: Riboldi
authors.affiliation: Fundación Instituto Valenciano de Infertilidad (FIVI), Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Díaz-Gimeno
authors.affiliation: Igenomix Europe, Valencia, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Valbuena
authors.affiliation: Igenomix Europe, Valencia, Spain; Igenomix USA, Miami, Florida; Igenomix Brasil, São Paulo, Brazil; Fundación Instituto Valenciano de Infertilidad (FIVI), Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
mesh_terms: D001755:Blastocyst / Q000737:chemistry* / Q000473:pathology; D002470:Cell Survival; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000032:analysis*; D046149:Embryo Culture Techniques; D010064:Embryo Implantation; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects; D005819:Genetic Markers; D006801:Humans; D008297:Male; D011003:Ploidies; D011247:Pregnancy; D018873:Pregnancy Rate; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers
keywords: Energy; human embryo; implantation; mitochondrial DNA; prediction