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A novel embryo biopsy morphological analysis and genetic integrality criterion system significantly improves the outcome of preimplantation genetic testing

  • Assisted Reproduction Technologies
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Abstract

Purpose

While efforts have been made to establish blastocyst grading systems in the past decades, little research has examined the quality of biopsy specimens. This study is the first to correlate the morphology of biopsied trophectoderm (TE) cells to their quality and subsequent genetic testing results of preimplantation genetic testing (PGT), through an innovative Morphological Analysis and Genetic Integrality Criterion (MAGIC) system.

Methods

Biopsied TE cells were first evaluated according to the MAGIC procedure, followed by whole-genome amplification (WGA) and library construction, and then sequenced using the Illumina X Ten Platform. Copy number variation (CNV) and allele drop-out (ADO) rates as well as test failure rates were compared and analyzed.

Results

Our data explores the relationship between TE cell morphology and its quality and final genetic testing outcome, which is established based on the MAGIC system. MAGIC guarantees that only high- or good-quality TE cells are used for genetic testing to generate excellent data uniformity and lower ADO rates. Low-quality cells containing biopsied TE cell mass are responsible for the “background noise” of CNV analysis.

Conclusion

The MAGIC application has effectively decreased the false-positive mosaicism, hence to ensure the stability and veracity of detection results, to avoid misdiagnoses, and to improve accuracy, as well as to avoid re-biopsy procedures. The study also contributes to understand how the IVF laboratory and the molecular biology laboratory depend on each other to achieve good-quality PGT results, which are clinically relevant for the patients.

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Data availability

All data, code, and materials used in the analysis are available upon request.

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Acknowledgements

We would like to acknowledge the staff of the Department of Obstetrics and Gynecology in Peking University Third Hospital for assistance during the patient’s IVF-ET treatment.

Funding

This project is funded by the National Natural Science Foundation of China (82125013, 82288102) and the National Key Research and Development Program (2019YFA0801400).

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Authors and Affiliations

  1. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, No. 49, North Garden Road, Haidian district, Beijing, 100191, China

    Ying Kuo, Xiaohui Zhu, Qianying Guo, Yuqian Wang, Shuo Guan, Ping Liu, Rong Li, Zhiqiang Yan, Liying Yan & Jie Qiao

  2. National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China

    Ying Kuo, Xiaohui Zhu, Qianying Guo, Yuqian Wang, Shuo Guan, Ping Liu, Rong Li, Zhiqiang Yan, Liying Yan & Jie Qiao

  3. Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University, Beijing, 100191, China

    Ying Kuo, Xiaohui Zhu, Qianying Guo, Yuqian Wang, Shuo Guan, Ping Liu, Rong Li, Zhiqiang Yan, Liying Yan & Jie Qiao

  4. Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, China

    Ying Kuo, Xiaohui Zhu, Qianying Guo, Yuqian Wang, Shuo Guan, Ping Liu, Rong Li, Zhiqiang Yan, Liying Yan & Jie Qiao

  5. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China

    Yuqian Wang & Jie Qiao

  6. Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China

    Yuqian Wang & Jie Qiao

  7. Beijing Advanced Innovation Center for Genomics, Beijing, 100871, China

    Jie Qiao

Authors
  1. Ying Kuo
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  2. Xiaohui Zhu
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  3. Qianying Guo
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  6. Ping Liu
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  7. Rong Li
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  8. Zhiqiang Yan
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  9. Liying Yan
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Contributions

Ying Kuo and Xiaohui Zhu carried out the experimental work, data collection, acquisition of data, analysis of data, and preparation of the manuscript. Qianying Guo, Yuqian Wang, and Shuo Guan participated in the design and coordination of IVF-PGT experimental work. Ping Liu, Rong Li, Zhiqian Yan, Liying Yan, and Jie Qiao guided the study design, organized the discussion, and drafted the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Zhiqiang Yan, Liying Yan or Jie Qiao.

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The authors declare no competing interests.

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Ying Kuo and Xiaohui Zhu are joint first authors.

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Kuo, Y., Zhu, X., Guo, Q. et al. A novel embryo biopsy morphological analysis and genetic integrality criterion system significantly improves the outcome of preimplantation genetic testing. J Assist Reprod Genet 40, 2659–2668 (2023). https://doi.org/10.1007/s10815-023-02924-7

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  • DOI: https://doi.org/10.1007/s10815-023-02924-7

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