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Quantitative relationship between mitochondrial DNA (MTDNA) amounts and implantation can help improve pregnancy outcomes

      Objective

      Euploid embryos with mtDNA quantities above a calculated threshold have been shown to have very low implantation potential. The aim of this study was to use high-resolution next generation sequencing (hr-NGS), already being utilized for preimplantation genetic screening (PGS), to further define the implantation potential of embryos with mtDNA quantities that fall below this calculated threshold.

      Design

      Retrospective analysis

      Materials and Methods

      mtDNA levels were quantified in 124 euploid blastocysts generated from 84 couples (average maternal age = 35.74+ 0.30 years) undergoing PGS; hr-NGS (Ion Torrent, Life Technologies) was used for both tests. All IVF procedures were conducted at a single center. Euploid embryos were transferred without regard to mtDNA results; implantation rates were collected as part of routine clinical follow-up and were then correlated to absolute mtDNA quantities.

      Results

      Only 2% (3/124) of embryos had mtDNA quantities above the established mtDNA threshold previously shown to be correlated with low implantation potential. The 121 embryos that fell below this threshold were classified into four quartiles based on mtDNA quantities. 66% of these embryos were distributed within the lower two (“higher implantation”) quartiles and 34% within the upper two (“lower implantation”) quartiles. The implantation rates in the lower two quartiles (73.9%, 71.2%) were significantly higher than the implantation rates in the upper two quartiles (51.7%, 53.8%; P=0.03, Chi Square). No difference in maternal age was observed between the four quartiles.

      Conclusions

      mtDNA quantities were successfully measured via hr-NGS in all embryos in conjunction with routine PGS. In addition, mtDNA quantities were able to be further categorized beyond the previously defined threshold, into groups with higher and lower implantation potential (p=0.03). The identification of such unique thresholds may additionally facilitate improved selection among euploid embryos for transfer.