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

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

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.

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Author information

Authors and Affiliations

  1. Infertility Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via M. Fanti, 6, 20122, Milan, Italy

    Andrea Busnelli, Alessio Paffoni & Edgardo Somigliana

  2. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    Andrea Busnelli, Luca Persani, Luigi Fedele & Edgardo Somigliana

  3. Department of Obstetrics and Gynaecology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Debora Lattuada & Luigi Fedele

  4. Division of Endocrine and Metabolic Diseases, San Luca Hospital, IRCCS Istituto Auxologico Italiano, Milan, Italy

    Raffaella Rossetti & Luca Persani

Authors
  1. Andrea Busnelli
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  2. Debora Lattuada
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  3. Raffaella Rossetti
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  4. Alessio Paffoni
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  5. Luca Persani
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  6. Luigi Fedele
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  7. Edgardo Somigliana
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Corresponding author

Correspondence to Andrea Busnelli.

Ethics declarations

The study was accepted by the local Institutional Review Board. All recruited patients provided a written informed consent to participate.

Conflict of interest

A.B., D.L., R.R., A.P., L.P., L.F., and E.S., according to Italian laws, filed a patent application for mitochondrial DNA quantification in peripheral blood and for its use as non-invasive biomarker for female subfertility. E.S. handled grants of research from Ferring and Merck-Serono.

Additional information

Andrea Busnelli and Debora Lattuada should be regarded as joint first authors.

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Busnelli, A., Lattuada, D., Rossetti, R. et al. Mitochondrial DNA copy number in peripheral blood: a potential non-invasive biomarker for female subfertility. J Assist Reprod Genet 35, 1987–1994 (2018). https://doi.org/10.1007/s10815-018-1291-5

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  • DOI: https://doi.org/10.1007/s10815-018-1291-5

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