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Mol Hum Reprod. 2014 Dec;20(12):1238-46. doi: 10.1093/molehr/gau086. Epub 2014 Sep 17.

Mitochondrial DNA in Day 3 embryo culture medium is a novel, non-invasive biomarker of blastocyst potential and implantation outcome.

Author information

1
UOS Physiopathology of Human Reproduction, IRCCS AOU San Martino-IST, Largo R. Benzi, 10, 16132 Genoa, Italy.
2
Department of Economics and Business Studies, University of Genoa, Genoa, Italy.
3
UOS Physiopathology of Human Reproduction, IRCCS AOU San Martino-IST, Largo R. Benzi, 10, 16132 Genoa, Italy University of Genoa, Genoa, Italy.
4
UOS Physiopathology of Human Reproduction, IRCCS AOU San Martino-IST, Largo R. Benzi, 10, 16132 Genoa, Italy paola.scaruffi@hsanmartino.it.

Abstract

In assisted reproduction technology, embryo competence is routinely evaluated on morphological criteria. Over the last decade, efforts in improving non-invasive embryo assessment have looked into the secretome of embryos. Human embryos release genomic DNA (gDNA) and mitochondrial DNA (mtDNA) into the culture medium, and the mtDNA/gDNA ratio is significantly correlated with embryo fragmentation. Here, we investigate whether mtDNA/gDNA ratio in embryo spent medium is correlated with blastulation potential and implantation. The mtDNA/gDNA ratio was assessed in 699 Day 3 culture media by quantitative polymerase chain reaction (qPCR) to investigate its correlation with embryo morphology, blastocyst development and implantation. A logistic regression model evaluated whether mtDNA/gDNA ratio in the secretome may improve the prediction of blastulation. We found that embryos that successfully developed into blastocysts exhibited a significantly higher mtDNA/gDNA ratio in the culture medium compared with those that arrest (P = 0.0251), and mtDNA/gDNA, combined with morphological grading, has the potential to predict blastulation better than morphology alone (P = 0.02). Moreover, mtDNA/gDNA ratio was higher in the media from good-quality embryos that reached the full blastocyst stage on Day 5 compared with those that developed more slowly (P < 0.0001). With respect to blastocyst morphology, higher trophectoderm quality was associated with a higher mtDNA/gDNA ratio in the culture medium. Finally, a high mtDNA/gDNA ratio in spent medium was associated with successful implantation outcome (P = 0.0452) of good-quality embryos. In summary, the mtDNA/gDNA ratio in the Day 3 embryo secretome, in combination with morphological grading, may be a novel, non-invasive, early biomarker to improve identification of viable embryos with high developmental potential.

KEYWORDS:

blastocyst; cell-free DNA; human embryos; implantation; mtDNA

PMID:
25232043
DOI:
10.1093/molehr/gau086
[Indexed for MEDLINE]

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