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Evaluating the application value of NGS-based PGT-A by screening cryopreserved MDA products of embryos from PGT-M cycles with known transfer outcomes

  • Assisted Reproduction Technologies
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Abstract

Purpose

To determine the application value of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidies (PGT-A).

Methods

We conducted a retrospective case–control study on a cohort of frozen-thawed embryo transfer (FET) cycles following preimplantation genetic testing for monogenic disorders (PGT-M) between 2014 and 2017. Cycles that produced live births or early miscarriages were divided into live birth group (n = 76) or miscarriage group (n = 19), respectively. The NGS-based aneuploidy screening was performed on the multiple displacement amplification (MDA) products of the embryonic trophectoderm biopsy samples that were cryopreserved following PGT-M.

Results

In the live birth group, 75% (57/76) embryos were euploid and 14.5% (11/76) were aneuploid. The remaining 10.5% (8/76) embryos were NGS-classified mosaic with the high- (≥ 50%) and low-level (< 50%) mosaicism rates at 7.9% (6/76) and 2.6% (2/76), respectively. In the miscarriage group, only 23.5% (4/17) embryos were aneuploid, while 58.8% (10/17) were euploid and 17.6% (3/17) were NGS-classified mosaic with the high- and low-level mosaicism rates at 11.8% (2/17) and 5.9% (1/17), respectively. For live birth and miscarriage groups, the transferable rate was 82.9% (63/76) and 70.6% (12/17), respectively, whereas the untransferable rate was 17.1% (13/76) and 29.4% (5/17), respectively.

Conclusion

The application of NGS-based PGT-A remains questionable, as it may cause at least one in six embryos with reproductive potential to be discarded and prevent miscarriage in less than one in three embryos in single-gene disease carriers.

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Acknowledgements

The study was supported by the National Natural Science Foundation of China (32000589), Guangdong Basic and Applied Basic Research Foundation (2114050000636), National Key R&D Program of China (2016YFC1000205), and Guangdong Provincial Key Laboratory of Reproductive Medicine (2012A061400003). We sincerely thank all of the staff of the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University for their contributions to this study.

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Authors and Affiliations

  1. Reproductive Medicine Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China

    Xiaoting Shen, Dongjia Chen, Chenhui Ding, Yan Xu, Bing Cai, Yali Wang, Jing Wang, Rong Li, Jing Guo, Jiafu Pan, Han Zhang, Yanhong Zeng & Canquan Zhou

  2. Guangdong Provincial Key Laboratory of Reproductive Medicine, 58 Zhongshan Er Lu, Guangzhou, Guangdong, China

    Xiaoting Shen, Dongjia Chen, Chenhui Ding, Yan Xu, Bing Cai, Yali Wang, Jing Wang, Rong Li, Jing Guo, Jiafu Pan, Han Zhang, Yanhong Zeng & Canquan Zhou

  3. The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, China

    Yu Fu

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  1. Xiaoting Shen
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Contributions

X.T.S. and D.J.C. contributed to the interpretation of data and drafted the article. C.H.D., Y.X., Y.F., and B.C. were responsible for the analysis of data and revising the manuscript critically for important intellectual content. Y.L.W., J.W., R.L., J.G., J.F.P., H.Z., and Y.H.Z. participated in the acquisition of data. C.Q.Z. contributed to the conception and design and critical review of the article. All authors have approved the final version of the manuscript to be published.

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Correspondence to Canquan Zhou.

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Xiaoting Shen and Dongjia Chen contributed equally to this work and share first authorship.

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Shen, X., Chen, D., Ding, C. et al. Evaluating the application value of NGS-based PGT-A by screening cryopreserved MDA products of embryos from PGT-M cycles with known transfer outcomes. J Assist Reprod Genet 39, 1323–1331 (2022). https://doi.org/10.1007/s10815-022-02447-7

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