Purpose

Embryo genotyping in IVF clinics aims to identify aneuploid embryos, and current methodologies rely on costly, invasive and time-consuming approaches such as PGT-A screening. MALDI-ToF-based mass spectral analysis of embryo culture has been demonstrated to be a non-invasive, affordable and accurate technique that is able to capture secretome profiles from embryo culture media extremely quick. Thus, aneuploid embryo genotypes can be distinguished from euploids from these profiles towards the development of novel embryo selection tools.

Methods

A retrospective cohort study, including 292 spent media samples from embryo cultures collected from a single IVF clinic in USA. There were 149 euploid and 165 aneuploid embryos previously analysed by PGT-A next-generation sequencing techniques. Secretome mass spectra of embryos were generated using MALDI-ToF mass spectrometry in the UK. Data was systematically analysed using a fully automated and ultra-fast bioinformatic pipeline developed for the identification of mass spectral signatures.

Results

Distinct spectral patterns were found for euploid and aneuploid genotypes in embryo culture media. We identified 12 characteristic peak signatures for euploid and 17 for aneuploid embryos. Data analysis also revealed a high degree of complementarity among regions showing that 22 regions are required to differentiate between genotypes with a sensitivity of 84% and a false positive rate of 18%.

Conclusion

Ultra-fast and fully automated screening of an embryo genotype is possible based on multiple combinations of specific mass spectral peak signatures. This constitutes a breakthrough towards the implementation of non-invasive and ultra-fast tools for embryo selection immediately prior to transfer.

中文翻译：

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基于 MALDI-ToF 质谱法的 IVF 培养基中整倍体和非整倍体胚胎分泌组特征的生物信息学鉴定。

目的

IVF 诊所中的胚胎基因分型旨在识别非整倍体胚胎，目前的方法依赖于昂贵、侵入性和耗时的方法，例如 PGT-A 筛查。基于 MALDI-ToF 的胚胎培养质谱分析已被证明是一种非侵入性、经济实惠且准确的技术，能够极快地从胚胎培养基中捕获分泌组谱。因此，非整倍体胚胎基因型可以从这些概况中与整倍体区分开来，以开发新的胚胎选择工具。

方法

一项回顾性队列研究，包括从美国一家试管婴儿诊所收集的胚胎培养物中的 292 个用过的培养基样本。之前通过 PGT-A 下一代测序技术分析了 149 个整倍体和 165 个非整倍体胚胎。在英国使用 MALDI-ToF 质谱法生成胚胎的分泌组质谱。使用为识别质谱特征而开发的全自动和超快速生物信息学管道系统地分析数据。

结果

在胚胎培养基中发现整倍体和非整倍体基因型的不同光谱模式。我们确定了整倍体的 12 个特征峰特征和非整倍体胚胎的 17 个特征峰。数据分析还揭示了区域之间的高度互补性，表明需要 22 个区域来区分基因型，灵敏度为 84%，假阳性率为 18%。

结论

基于特定质谱峰特征的多种组合，可以对胚胎基因型进行超快速和全自动筛选。这构成了在移植前立即实施非侵入性和超快速胚胎选择工具的突破。