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Eleven healthy live births: a result of simultaneous preimplantation genetic testing of α- and β-double thalassemia and aneuploidy screening

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Abstract

Purpose

To evaluate the efficacy of preimplantation genetic testing (PGT) for α- and β-double thalassemia combined with aneuploidy screening using next-generation sequencing (NGS).

Methods

An NGS-based PGT protocol was performed between 2017 and 2018 for twelve couples, each of which carried both α- and β-thalassemia mutations. Trophectoderm biopsy samples underwent whole-genome amplification using multiple displacement amplification (MDA), followed by NGS for thalassemia detection and aneuploidy screening. A selection of several informative single nucleotide polymorphisms (SNPs) established haplotypes. Aneuploidy screening was performed only on unaffected noncarriers and carriers. Unaffected and euploid embryos were transferred into the uterus through frozen-thawed embryo transfer (FET).

Results

A total of 280 oocytes were retrieved following 18 ovum pick-up (OPU) cycles, with 182 normally fertilized and 112 cultured to become blastocysts. One hundred and seven (95.5%, 107/112) blastocysts received conclusive PGT results, showing 56 (52.3%, 56/107) were unaffected. Thirty-seven (66.1%, 37/56) of the unaffected were also identified as euploid. One family had no transferable embryos. Unaffected and euploid embryos were then transferred into the uterus of the other 11 couples resulting in 11 healthy live births. The clinical pregnancy rate was 61.1% (11/18) per OPU and 68.8% (11/16) per FET, with no miscarriage reported. Seven families accepted the prenatal diagnosis and received consistent results with the NGS-based PGT.

Conclusion

This study indicated that NGS could realize the simultaneous PGT of double thalassemia and aneuploidy screening in a reliable and accurate manner. Moreover, it eliminated the need for multiple biopsies, alleviating the potential damages to the pre-implanted blastocysts.

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Acknowledgments

The authors are grateful for the support from the Guangdong Provincial Key Laboratory of Reproductive Medicine (2012A061400003) and Guangzhou Science and Technology Project: Development and Application of The Reagents for Preimplantation Diagnosis and Screening by Next-Generation Sequencing (201704020217).

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Authors and Affiliations

  1. Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China

    Dongjia Chen, Xiaoting Shen, Yan Xu, Chenhui Ding, Yanwen Xu & Canquan Zhou

  2. Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, 510080, Guangdong, China

    Dongjia Chen, Xiaoting Shen, Yan Xu, Chenhui Ding, Yanwen Xu & Canquan Zhou

  3. Peking Medriv Academy of Genetics and Reproduction, Peking, 102629, China

    Changsheng Wu & Guirong Zhang

Authors
  1. Dongjia Chen
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  2. Xiaoting Shen
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  3. Changsheng Wu
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  4. Yan Xu
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  5. Chenhui Ding
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  7. Yanwen Xu
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Contributions

D.C. and X.S. designed and performed the experiments, collected and analyzed data, and wrote the manuscript. C.W., Y.X., and C.D. conducted the experiment and contributed to the interpretation of the results. C.Z., Y-W.X., and G.Z. conceived, designed, supervised the experiments, and revised the manuscript. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Guirong Zhang, Yanwen Xu or Canquan Zhou.

Ethics declarations

Ethical approval was obtained from the Research Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University. A detailed written consent was obtained from each family for being included in this study.

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The authors declare that they have no conflicts of interest.

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Dongjia Chen and Xiaoting Shen are the joint first author

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Chen, D., Shen, X., Wu, C. et al. Eleven healthy live births: a result of simultaneous preimplantation genetic testing of α- and β-double thalassemia and aneuploidy screening. J Assist Reprod Genet 37, 549–557 (2020). https://doi.org/10.1007/s10815-020-01732-7

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  • DOI: https://doi.org/10.1007/s10815-020-01732-7

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