Mitochondrial DNA content is not related with pregnancy but with euploidy

Introduction Altered levels of mitochondrial DNA were found to be associated with female age, aneuploidy and implantation potential ( Fragouli et al., 2015 ). The quantity of mtDNA was found to be significantly higher in embryos from older women and in aneuploid embryos. Blastocysts that successfully implanted tended to contain lower mtDNA quantities than those failing to implant (below the threshold of 0.003). The aim of our study was to correlate the mitochondrial DNA content with female age, euploidy and the subcategories of aneuploidy (monosomies, trisomies and mosaics). Material and Methods This observational study was based on 2494 embryos belonging to 483 patients (mean female age: 35.7) applying for preimplantation genetic screening (PGS) due to advanced maternal age (>37), a history of abnormal fetal karyotype or structural abnormalities. Good or top-quality blastocysts (at least 4BB) were biopsied and analyzed by next generation sequencing (NGS) (PGM platform, ThermoFisher). 1084 embryos were euploid and 1157 aneuploid, of which 404 were pure monosomic(s), 315 pure trisomic(s), 438 diagnosed with mixed monosomies and trisomies and 253 mosaics. Results Female age was not found to be correlated with the mitochondrial DNA content (p=0.27). However, the mitochondrial DNA content tends to increase with age (correlation coefficient, R=0.02). Although implanted embryos had an increased level of mitochondrial DNA content, it did not reach statistical significance either and no threshold could be established (p=0.33). Nevertheless, when euploid blastocysts were compared with aneuploids, the mitochondrial DNA content was found to be significantly decreased in euploids (p Conclusions Mitochondrial DNA content was not found as being a biomarker of successful implantation. However, it is related with euploidy in this series of 2494 embryos as euploid blastocysts had a decreased level of mitochondrial DNA. The quiet embryo hypothesis postulates that a low oxidative phosphorylation rate from the zygote to the morula stage limits reactive oxygen species production thus maximizing viability, a postulation that may be extended to euploid blastocysts.