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Adjusted mitochondrial DNA quantification in human embryos may not be applicable as a biomarker of implantation potential

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

Abstract

Objective

To evaluate the feasibility of adjusted mitochondrial DNA quantification in human embryos as a biomarker for implantation potential.

Design

Double-blind, observational, prospective analysis of an Asian population in a single university-affiliated in vitro fertilization center. A total of 1617 embryos derived from 380 infertile couples were collected. The DNA from blastomere biopsy (n = 99) or trophectoderm biopsy (n = 1518) were analyzed with next-generation sequencing.

Results

The adjusted mtDNA quantification followed a non-normal distribution in both types of the embryos. When stratified by ploidy status, the adjusted mtDNA quantification was significantly higher in aneuploid trophectoderm than in euploid cells, but not in blastomeres. The adjusted mtDNA quantification of embryos showed significant but very weak positive correlation in total trophectoderm cells with maternal age (Spearman’s correlation, r = 0.095, p = 0.0028) but neither in blastomeres nor stratified by ploidy status. The median adjusted mtDNA quantification was also significantly higher in aneuploid blastocysts than in euploid ones while corrected with embryo morphology. Viable embryos did not contain significantly different quantities of adjusted mtDNA compared with nonviable embryos (implanted n = 103, non-implanted n = 164; median 0.00097 vs. 0.00088, p = 0.21) in 267 transferred blastocysts.

Conclusion

Quantification of adjusted mitochondria DNA in human embryos was significantly lower in euploid blastocysts than in aneuploid blastocysts. However, no statistically significant differences regarding implantation outcome were evident. To our best knowledge, this study provides the largest scale and the first correlation data between mitochondria copy number and human embryo implantation potential in Asians.

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Acknowledgments

The authors thank all the embryologists of the reproductive center of Taipei Medical University Hospital for embryo biopsy and sample preparation. We also thank the bioinformatics support provided by the Genomics Center for Clinical and Biotechnological Applications of the National Yang-Ming University VGH Genome Research Center. Genomics Center for Clinical and Biotechnological Applications is supported by the National Core Facility for Biopharmaceuticals, Ministry of Science and Technology. We also thank the Taipei Medical University Hospital for financial support. Finally, we thank the Genetics Generation Advancement Corporation for supporting this study in various forms, including sample preparation and interpretation, technical support, and extremely helpful discussions.

Funding

This study was partially supported by research grants NSC96-2314-B-038-019 and MOST-104-2314-B-038-063-MY2 from the Ministry of Science and Technology, Taiwan, Academia Sinica (BM10501010036, BM10601010024), National Healthy Research Institute (MG-1050SP-07, MG-106-SP-07), and Taipei Medical University Hospital (108TMUH-NE-01). The funders played no role in the conduct of the study or the writing of the manuscript.

Author information

Authors and Affiliations

  1. Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan

    Yi-Xuan Lee

  2. Division of Infertility, Department of Obstetrics and Gynecology, Taipei Medical University Hospital, No.250, Wusing St., Sinyi District, Taipei City, 110, Taiwan

    Yi-Xuan Lee, Chi-Huang Chen, Shyr-Yeu Lin & Chii-Ruey Tzeng

  3. Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Chi-Huang Chen, Shyr-Yeu Lin & Chii-Ruey Tzeng

  4. Department of Obstetrics and Gynecology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Yi-Hui Lin

  5. Genetics Generation Advancement Corporation (GGA Corp.), Taipei, Taiwan

    Yi-Hui Lin

  6. Center for Reproductive Medicine, Taipei Medical University Hospital, No.250, Wusing St., Sinyi District, Taipei City, 110, Taiwan

    Chii-Ruey Tzeng

Authors
  1. Yi-Xuan Lee
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  2. Chi-Huang Chen
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Corresponding author

Correspondence to Chii-Ruey Tzeng.

Ethics declarations

This study was reviewed and approved by the Taipei Medical University joint institutional review board (TMU-JIRB, approval number: N201707027). Patient informed consent for analysis of surplus DNA product was obtained with the approval of the ethical committee.

Conflict of interest

Dr. Yi-Hui Lin serves as a medical consultant for Genetics Generation Advancement Corporation. The other authors declare that they have no conflict of interest.

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Lee, YX., Chen, CH., Lin, SY. et al. Adjusted mitochondrial DNA quantification in human embryos may not be applicable as a biomarker of implantation potential. J Assist Reprod Genet 36, 1855–1865 (2019). https://doi.org/10.1007/s10815-019-01542-6

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  • DOI: https://doi.org/10.1007/s10815-019-01542-6

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