Mitochondrial DNA copy number in peripheral blood: a potential non-invasive biomarker for female subfertility

Andrea Busnelli, Debora Lattuada, Raffaella Rossetti, Alessio Paffoni, Luca Persani, Luigi Fedele, Edgardo Somigliana

Research output: Contribution to journalArticlepeer-review


PURPOSE: Low mitochondrial DNA (mtDNA) content in oocytes and in cumulus cells is an indicator of poor oocyte quality. Moreover, initial evidence showed a correlation between mtDNA content in cumulus cells and mtDNA copy number in peripheral blood cells. On these bases, we deemed of interest investigating the correlation between mtDNA copy number in peripheral blood and natural fecundity.

METHODS: This is a nested case-control study drawn from a prospective cohort of pregnant women referred for routine first trimester screening for aneuploidies (from 11 + 0 to 12 + 6 weeks of gestation) between January 2012 and March 2013 at the "Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico" of Milan, Italy. Cases were subfertile women who attempted to become pregnant for 12-24 months. Controls were the two subsequently age-matched women who became pregnant in less than 1 year. MtDNA was quantified using real-time PCR and normalized to nuclear DNA.

RESULTS: One hundred and four subfertile women and 208 controls were selected. The median (IQR) mtDNA copy number was 95 (73-124) and 145 (106-198), respectively (p < 0.001). The area under the ROC curve was 0.73 (95% CI 0.67-0.79) (p < 0.001). The Youden index was 105 mtDNA copy number. The crude OR for subfertility in women with mtDNA copy number below this threshold was 5.72 (95% CI 3.43-9.55). The accuracy of mtDNA copy number assessment in peripheral blood progressively decreased with increasing female age.

CONCLUSIONS: Low mtDNA copy number in peripheral blood is associated with an increased risk of subfertility and may represent a biomarker of natural fecundity.

Original languageEnglish
Pages (from-to)1987-1994
Number of pages8
JournalJournal of Assisted Reproduction and Genetics
Issue number11
Publication statusPublished - Nov 2018


  • Adult
  • Biomarkers/blood
  • Case-Control Studies
  • DNA Copy Number Variations
  • DNA, Mitochondrial/genetics
  • Female
  • Humans
  • Infertility, Female/blood
  • Mitochondria/genetics
  • Prospective Studies
  • ROC Curve


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