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Majority of transferred mosaic embryos developed healthy live births revealed by a preclinical study using embryonic morphology assessment and noninvasive PGT-A on cell-free DNA in blastocoel fluid

Journal of Assisted Reproduction and Genetics volume 39, pages 2483–2504 (2022)Cite this article

Abstract

Purpose

This preclinical study aimed to evaluate whether using transferred mosaic embryos (primarily selected by embryonic morphology assessment (EMA) and compared by the noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) on cell-free DNA in blastocoel fluid (BF)) increases the rates of clinical pregnancies (CPs) and healthy live births (HLBs) and to investigate whether niPGT-A could provide valuable genetic information for the EMA-selected transferred mosaic embryos.

Methods

This study collected 215 blastocyst culture samples and 182 BF samples. Cell-free DNA from the BF was amplified and examined by next-generation sequencing–based niPGT-A. All 182 patients underwent EMA. However, only 147 underwent in vitro fertilization and embryo transfer, and only 113 clinical outcomes were followed up. Comprehensive chromosome screening for the chorionic villus sampling of spontaneous miscarriages and noninvasive prenatal testing for ongoing pregnancies were also performed.

Results

The implantation rate was 77.55% in 147 transferred high-quality embryos selected by EMA. Among 113 CPs, 16 led to spontaneous miscarriage (14.16%), and 97 resulted in HLBs (85.84%). According to the niPGT-A results for 113 patients with clinical outcomes, 80.4% had CP (euploid, 20.54%; single aneuploid, 1.79%; mosaic chromosome aneuploid and/or segmental aneuploid, 58.04%). Of all the mosaic aneuploids, 90.76% were false positive, transforming to euploid.

Conclusions

Transferred EMA-selected embryos showed higher implantation rates. The niPGT-A of BF provided valuable genetic status (“-ploid”) information, which helped reduce aneuploid-induced implantation failure and miscarriage, thereby increasing the CP and HLB rates. Additionally, majority of the transferred embryos with complex/chaotic mosaic aneuploid would likely develop HLBs.

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Acknowledgements

The authors would like to thank Mr. Anthony Liu from the State Key Laboratory of Reproductive Medicine, The Center for Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, for the critical readings and valuable comments.

Funding

This work was supported by the National Nature and Science Foundation of China (81730041 to JY Liu, 82071719 to W Wu), National Key R&D Program of China (2016YFC1000207 to DW Wang), National Key Research and Development Program of China (2017YFC1001301 to W Wu), Jiangsu Provincial Project (BL20122009 and YXZXB2016001 to JY Liu), and Fudan Scholar Grant to B-L Wu.

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Authors and Affiliations

  1. State Key Laboratory of Reproductive Medicine, The Center for Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Lingbo Cai, Qiao Zeng, Chao Gao, Wei Wu, Jiandong Shen, Yugui Cui & Jiayin Liu

  2. Institute of Biomedical Science, Fudan University, Children’s Hospital and Shanghai Medical College, Fudan University, Shanghai, 2100032, China

    Bai-Lin Wu

  3. Departments of Pathology and Laboratory Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, MA, 02115, USA

    Bai-Lin Wu

  4. State Key Laboratory of Reproductive Medicine, Genetic Laboratory, The Center for Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Dao Wu Wang

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  1. Lingbo Cai
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Cai, L., Zeng, Q., Gao, C. et al. Majority of transferred mosaic embryos developed healthy live births revealed by a preclinical study using embryonic morphology assessment and noninvasive PGT-A on cell-free DNA in blastocoel fluid. J Assist Reprod Genet 39, 2483–2504 (2022). https://doi.org/10.1007/s10815-022-02651-5

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Keywords

  • Noninvasive preimplantation genetic testing for aneuploidy (niPGT-a)
  • Blastocoel fluid (BF)
  • Chorionic villus sampling (CVS)
  • Embryo morphology assessment
  • Mosaic embryo
  • In vitro fertilization (IVF)