Zouves Fertility Center, Foster City California, USA; School of Biosciences, University of Kent, Canterbury, UK.
School of Biosciences, University of Kent, Canterbury, UK.
Reprod Biomed Online. 2019 Sep;39(3):403-412. doi: 10.1016/j.rbmo.2019.03.214. Epub 2019 Apr 4.
Conflicting data exist on the utility of quantification of mitochondrial DNA (mtDNA) levels as a predictor of blastocyst implantation in the IVF clinic. The current study determined whether blastocysts with highly elevated mtDNA levels could result in healthy pregnancies and births, and whether mitochondrial functional output might be a readout of cell stress in the embryo.
mtDNA levels were determined in 109 blastocysts used in clinical transfers into 100 women, noting their clinical outcomes. In a separate set of embryos, mitochondrial function was quantified in a model of embryo stress, aneuploidy. Measurement of mtDNA levels made use of surplus material from the process of preimplantation genetic testing for aneuploidies, and followed recently proposed unifying guidelines for mtDNA quantification.
Unusually high mtDNA levels did not preclude blastocyst implantation and healthy births. An analysis of 109 blastocysts showed no significant difference between mtDNA levels in implanted (n = 55) versus non-implanted (n = 54) blastocysts. No obvious differences in the degree of mitochondrial functional output were detected in a model of embryo stress.
Measurement of mtDNA copy number might not provide any advantage in embryo prioritization and could lead to a deselection of blastocysts that would result in healthy pregnancies and births. Furthermore, the quantification of mitochondrial functional output in a model of cellular stress might suggest that mitochondria are not clear targets for biomarker identification as it relates to blastocyst viability. Any suggested link between mtDNA levels, mitochondria or their output with blastocyst transfer outcome requires further validation.
关于线粒体 DNA(mtDNA)水平定量作为体外受精(IVF)临床中囊胚植入预测指标的效用,存在相互矛盾的数据。本研究旨在确定高度升高的 mtDNA 水平的囊胚是否能够导致健康的妊娠和分娩,以及线粒体功能输出是否可能是胚胎细胞应激的一个指标。
在 100 名女性的 109 个临床转移囊胚中测定 mtDNA 水平,记录其临床结局。在胚胎应激(非整倍体)的模型中,另一个胚胎组中定量测定线粒体功能。mtDNA 水平的测量利用了胚胎植入前遗传学检测非整倍体过程中的剩余材料,并遵循了最近提出的 mtDNA 定量统一准则。
异常高的 mtDNA 水平并不妨碍囊胚植入和健康分娩。对 109 个囊胚的分析显示,植入(n=55)与未植入(n=54)囊胚之间的 mtDNA 水平无显著差异。在胚胎应激模型中,线粒体功能输出的程度没有明显差异。
mtDNA 拷贝数的测量可能在胚胎优先排序中没有任何优势,并且可能导致选择不适合健康妊娠和分娩的囊胚。此外,在细胞应激模型中对线粒体功能输出的定量可能表明,线粒体不是与囊胚活力相关的生物标志物识别的明确靶点。mtDNA 水平、线粒体或其输出与囊胚转移结果之间的任何建议联系都需要进一步验证。