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Bioinformatic identification of euploid and aneuploid embryo secretome signatures in IVF culture media based on MALDI-ToF mass spectrometry

  • Embryo Biology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

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.

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Acknowledgements

We thank Virginia Center for Reproductive Medicine and their patients for the provision of the samples.

Funding

This research was fully funded by private funding from MAP Sciences Ltd.

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Authors and Affiliations

  1. MAP Sciences, Priory Business Park, Bedford I-lab Stannard Way, Bedford, MK44 3RZ, UK

    Ricardo J. Pais, Raminta Zmuidinaite, Stephen Butler, Sholeh Keshavarz & Ray Iles

  2. Centro de investigação Interdisciplinar Egas Moniz (CiiEM), Instituto Universitário Egas Moniz, Caparica, 2829-511, Portugal

    Ricardo J. Pais

  3. Virginia Center for Reproductive Medicine, 11150 Sunset Hills Rd #100, Reston, VA, 20190, USA

    Fady Sharara

  4. George Washington University, 2121 I St NW, Washington, DC, 20052, USA

    Fady Sharara

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  1. Ricardo J. Pais
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Contributions

R.J. Pais, F. Sharara, R. Zmuidinaite, S. Butler, S. Keshavarz and R. Iles participated in the design of the study. F. Sharara collected patient data; R. Zmuidinaite and S. Keshavarz generated the mass sectral data. R.J. Pais wrote the python scripts. R. Zmuidinaite and R. Pais analysed the data and wrote the paper. R.J. Pais, F. Sharara, R. Zmuidinaite, S. Butler and R. Iles contributed to critically review and edit the draft.

Corresponding author

Correspondence to Ray Iles.

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Conflict of interest

R. Pais and F. Sharara declare no conflict of interest. R. Zmuidinaite and S. Keshavarz are employees of MAP Sciences Ltd. and declare no conflict of interests. RK Iles and SA Butler declare a potential conflict of interest through part ownership of shares in MAP Sciences Ltd.

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Pais, R.J., Sharara, F., Zmuidinaite, R. et al. Bioinformatic identification of euploid and aneuploid embryo secretome signatures in IVF culture media based on MALDI-ToF mass spectrometry. J Assist Reprod Genet 37, 2189–2198 (2020). https://doi.org/10.1007/s10815-020-01890-8

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  • DOI: https://doi.org/10.1007/s10815-020-01890-8

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