Research question

Are discordances in non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) results attributable to the technique used for chromosomal analysis?

Design

A prospective blinded study was performed (September 2018 to December 2019). In total 302 chromosomal analyses were performed: 92 trophectoderm PGT-A biopsies and their corresponding spent embryo culture medium (SCM) evaluated by two methods (n = 184), negative controls (n = 8), and trophectoderm and inner cell mass biopsies from trophectoderm-aneuploid embryos (n = 18). Trophectoderm analyses were carried out using Veriseq (Illumina), and SCM was analysed using Veriseq and NICS (Yikon).

Results

Genetic results were obtained for 96.8% of trophectoderm samples versus 92.4% for both SCM techniques. The mosaicism rate was higher for SCM regardless of the technique used: 30.4% for SCM-NICS and 28.3% for SCM-Veriseq versus 14.1% for trophectoderm biopsies (P = 0.013, P = 0.031, respectively). No significant differences in diagnostic concordance were seen between the two SCM techniques (74.6% for SCM-NICS versus 72.3% for SCM-Veriseq; P = 0.861). For embryos biopsied on day 6, these rates reached 92.0% and 86.5%, respectively. On reanalysing trophectoderm-aneuploid embryos, the discrepancies were shown to be due to maternal DNA contamination (55.6%; 5/9), embryo mosaicism (22.2%; 2/9) and low resolution in SCM-NICS (11.1%; 1/9) and in both SCM techniques (11.1%; 1/9).

Conclusions

This is the first study evaluating the consistency of different chromosomal analysis techniques for niPGT-A. In conclusion, the diagnostic concordance between PGT-A and niPGT-A seems independent of the technique used. Optimization of culture conditions and medium retrieval provides a potential target to improve the reliability of niPGT-A.

中文翻译：

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使用两种不同的染色体分析技术对人类胚胎进行非侵入性 PGT-A 的一致结果

研究问题

非整倍体非侵入性植入前基因检测 (niPGT-A) 结果的不一致是否归因于用于染色体分析的技术？

设计

进行了一项前瞻性盲法研究（2018 年 9 月至 2019 年 12 月）。总共进行了 302 项染色体分析：92 份滋养外胚层 PGT-A 活检及其相应的废胚胎培养基 (SCM) 通过两种方法评估 ( n =  184)、阴性对照 ( n =  8) 以及来自滋养外胚层非整倍体胚胎 ( n =  18)。使用 Veriseq (Illumina) 进行滋养外胚层分析，使用 Veriseq 和 NICS (Yikon) 分析 SCM。

结果

96.8% 的滋养外胚层样品获得了遗传结果，而两种 SCM 技术均为 92.4%。无论使用何种技术，SCM 的镶嵌率都较高：SCM-NICS 为 30.4%，SCM-Veriseq 为 28.3%，而滋养外胚层活检为 14.1%（分别为P =  0.013，P =  0.031）。两种 SCM 技术的诊断一致性没有显着差异（SCM-NICS 为 74.6%，SCM-Veriseq 为 72.3%；P = 0.861）。对于第 6 天活检的胚胎，这些比率分别达到 92.0% 和 86.5%。在重新分析滋养外胚层-非整倍体胚胎时，发现差异是由于母体 DNA 污染（55.6%；5/9）、胚胎嵌合（22.2%；2/9）和 SCM-NICS 的低分辨率（11.1%；1/ 9) 和两种 SCM 技术 (11.1%; 1/9)。

结论

这是第一项评估 niPGT-A 不同染色体分析技术一致性的研究。总之，PGT-A 和 niPGT-A 之间的诊断一致性似乎与所使用的技术无关。培养条件和培养基检索的优化为提高 niPGT-A 的可靠性提供了一个潜在的目标。