Purpose

To provide a comprehensive analysis of mtDNA quantity in D5 and D6 blastocysts, as well as a further insight to the origin of delayed blastocyst development.

Methods

A retrospective cohort analysis of 829 D5 and 472 D6 blastocysts from 460 patients who underwent in vitro fertilization (IVF) with next-generation sequencing (NGS)–based preimplantation genetic testing for aneuploidy (PGT-A). The quantity of trophectoderm mtDNA was extrapolated from the NGS data, followed by the analysis of mean mtDNA levels between D5 and D6 blastocysts of the same ploidy (aneuploid/euploid) and transfer outcomes (positive/negative clinical pregnancy).

Results

D5 blastocysts had significantly higher euploidy rate and clinical pregnancy rate when compared with D6 blastocysts. The proportion of blastocysts derived from patients ≧ 40 years old were similar between the D5 and D6 cohorts. When blastocysts with identical ploidy were analyzed, the D5 cohorts all had significantly higher mean mtDNA levels than their D6 counterparts. Similarly, when embryo transfers with identical outcome were analyzed, the D5 cohorts also had significantly higher mean mtDNA levels than the D6 cohorts. Trophectoderm mtDNA level was independent of maternal age and blastocyst morphology grades.

Conclusions

Our data provided further evidence D5 blastocysts contained significantly greater mtDNA quantity than D6 blastocysts, and mtDNA quantity could be a key factor that affects the development rate of blastocysts. Furthermore, one must avoid using an arbitrary threshold when incorporating mtDNA quantity into the embryo selection criteria, as the observed value may have vastly different clinical implication when blastulation rate is also considered.

中文翻译：

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次优的滋养外胚层线粒体 DNA 水平与胚泡发育延迟有关

目的

提供对 D5 和 D6 囊胚中 mtDNA 数量的全面分析，以及进一步了解延迟囊胚发育的起源。

方法

对 460 名接受基于下一代测序 (NGS) 的非整倍体植入前基因检测 (PGT-A) 的体外受精 (IVF) 患者的 829 个 D5 和 472 个 D6 囊胚进行回顾性队列分析。从 NGS 数据推断滋养外胚层 mtDNA 的数量，然后分析相同倍性（非整倍体/整倍体）和转移结果（阳性/阴性临床妊娠）的 D5 和 D6 囊胚之间的平均 mtDNA 水平。

结果

与D6囊胚相比，D5囊胚的整倍体率和临床妊娠率显着升高。来自≥ 40 岁患者的囊胚比例在 D5 和 D6 组之间相似。当分析具有相同倍性的囊胚时，D5 组的平均 mtDNA 水平均显着高于 D6 组。同样，当分析具有相同结果的胚胎移植时，D5 组的平均 mtDNA 水平也显着高于 D6 组。滋养外胚层 mtDNA 水平与母体年龄和囊胚形态等级无关。

结论

我们的数据提供了进一步的证据，证明 D5 囊胚比 D6 囊胚含有显着更多的 mtDNA 数量，并且 mtDNA 数量可能是影响囊胚发育速度的关键因素。此外，在将 mtDNA 数量纳入胚胎选择标准时，必须避免使用任意阈值，因为当还考虑囊胚形成率时，观察值可能具有截然不同的临床意义。