Value of embryonic mitochondrial DNA in predicting the effectiveness of assisted reproductive technologies


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Abstract

Research evidence suggests that a sufficient level of mitochondrial DNA (mtDNA) in cumulus cells and oocytes is associated with the high potential of female germ cells for fertilization and is an essential factor contributing to the pre-implantation embryonic development. Several studies have shown that a reduced mtDNA copy number is associated with a higher pregnancy rate. Objective: To investigate if mtDNA content in trophectoderm (TE) cells during preimplantation genetic testing for aneuploidy (PGT-A) could be a new marker for an embryo's implantation potential. Materials and methods: The mtDNA content of trophectoderm cells was analyzed in 244 euploid embryos after OGT-A using the NGS technique. Results: Analysis of euploid embryo transfer results showed that the mtDNA content in TE blastocyst cells was not associated with ART outcomes. Also, there was no association between the mtDNA level and embryo sex. A relationship was noted between the degree of early blastocyst expansion and mtDNA level. Blastocysts with TEs corresponding to excellent grade A had higher mtDNA content. The mtDNA copy number was significantly lower in embryos biopsied on day six after fertilization compared to biopsied embryos on day 5 of culture. The mtDNA content in all TE cells in euploid embryos was statistically insignificantly correlated with maternal age. Conclusion: The study findings suggest that mtDNA content in TE cells is not predictive for the embryo implantation potential and ART effectiveness. It should be emphasized that blastocysts with an increased mtDNA levels in TE cells was associated with the birth of healthy children in the ART program. These results confirm that the quantitative mtDNA content is one of the critical factors associated with blastocyst development and depends on the day of embryo culture.

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About the authors

Oksana S. Nepsha

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: o_nepsha@oparina4.ru
PhD. (Biol. Sci.), Researcher at the BV. Leonov Department of Assisted Technologies for the Treatment of Infertility

Elena V. Kulakova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: e_kulakova@oparina4.ru
PhD, Senior Researcher, Professor BV. Leonov Department of IVF

Alexey N. Ekimov

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: a_ekimov@oparina4.ru
doctor-laboratory geneticist, Head of the Group of preimplantation genetic screening of the Laboratory of Molecular Genetic Methods

Yulia S. Drapkina

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: yu_drapkina@oparina4.ru
PhD, researcher, Professor BV. Leonov Department of IVF

Natalia P. Makarova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: np_makarova@oparina4.ru
Dr. Biol. Sci., Senior Researcher at the BV. Leonov Department of Assisted Technologies for the Treatment of Infertility

Elizaveta E. Kraevaya

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: e_kraevaya@oparina4.ru
Ph.D., Junior Researcher at the BV. Leonov Department of Assisted Technologies for the Treatment of Infertility

Elena A. Kalinina

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: e_kalinina@oparina4.ru
Dr. Med. Sci., Professor, Head of the BV. Leonov Department of Assisted Technologies for the Treatment of Infertility

References

  1. World Health Organization. Sexual and reproductive health. 2020. Available at: https://www.who.int/reproductivehealth/topics/infertility/perspective/en/
  2. SART: Society for Reproductive Technology. National Summary Report. Final National Summary Report for 2016. Available at: https://wwwsartcorsonlinecom/rptCSR_PublicMultYearaspx?reportingYear=2016
  3. Gardner D.K., Schoolcraft W.B. In vitro culture of human blastocysts. In: Jansen R., Mortimer D., eds. Towards reproductive certainty: fertility and genetics beyond. Parthenon Press, Carnforth; 1999: 378-88.
  4. Bromer J.G., Ata B., Seli M., Lockwood C.J., Seli E. Preterm deliveries that result from multiple pregnancies associated with assisted reproductive technologies in the USA: a cost analysis. Curr. Opin. Obstet. Gynecol. 2011; 23(3): 168-73. https://dx.doi.org/10.1097/GCO.0b013e32834551cd.
  5. Timofeeva A.V., Chagovets V.V., Drapkina Yu.S., Makarova N.P., Kalinina E.A., Sukhikh G.T. Cell-free, embryo-specific sncRNA as a molecular biological bridge between patient fertility and IVF efficiency. Int. J. Mol. Sci. 2019; 20(12): 2912. https://dx.doi.org/10.3390/ijms20122912.
  6. Кулакова Е.В., Калинина Е.А., Трофимов Д.Ю., Макарова Н.П., Хечумян Л. Р., Дударова А.Х. Вспомогательные репродуктивные техно -логии у супружеских пар с высоким риском генетических нарушений. Преимплантационный генетический скрининг. Акушерство и гинекология. 2017; 8: 21-7. https://dx.doi.org/10.18565/aig.2017.8.21-7.
  7. Долгушина Н.В., Коротченко О.Е., Бейк Е.П., Абдурахманова Н.Ф., Ильина Е.О., Кулакова Е.В. Клинико-экономический анализ эффективности преимплантационного генетического скрининга у пациенток позднего репродуктивного возраста. Акушерство и гинекология. 2017; 11: 56-61. https: //dx.doi.org/10.18565/aig.2017.11.56-61.
  8. Tarn J.J., Garcia-Perez M.A., Hamatani T., Cano A. Infertility etiologies are genetically and clinically linked with other diseases in single metadiseases. Reprod. Biol. Endocrinol. 2015; 13: 31. https://dx.doi.org/10.1186/s12958-015-0029-9.
  9. Fragouli E., Spath K., Alfarawati S., Kaper F., Craig A., Michel C.-E. et al. Altered levels of mitochondrial DNA are associated with female age, aneuploidy, and provide an independent measure of embryonic implantation potential. PLoS Genet. 2015; 11(6): e1005241. https://dx.doi.org/10.1371/journal.pgen.1005241.
  10. Diez-Juan A., Rubio C., Marin C., Martinez S., Al-Asmar N., Riboldi M. et al. Mitochondrial DNA content as a viability score in human euploid embryos: less is better. Fertil. Steril. 2015; 104(3): 534-41.e1. https://dx.doi.org/0.1016/j.fertnstert.2015.05.022.
  11. Harvey A.J. Mitochondria in early development: linking the microenvironment, metabolism and the epigenome. Reproduction. 2019; 157(5): R159-R179. https://dx.doi.org/10.1530/REP-18-0431.
  12. Vaught R.C., Dowling D.K. Maternal inheritance of mitochondria: implications for male fertility? Reproduction. 2018; 155(4): R159-R168. https://dx.doi.org/10.1530/REP-17-0600.
  13. Archer S.L. Mitochondrial dynamics - mitochondrial fission and fusion in human diseases. N. Engl. J. Med. 2013; 369(23): 2236-51. https://dx.doi.org/10.1056/NEJMra1215233.
  14. Ciesielski G.L., Oliveira M.T., Kaguni L.S. Animal mitochondrial DNA replication. Enzymes. 2016; 39: 255-92. https://dx.doi.org/10.1016/bs.enz.2016.03.006.
  15. Popov L.-D. Mitochondrial biogenesis: an update. J. Cell. Mol. Med. 2020; 24(9): 4892-9. https://dx.doi.org/10.1111/jcmm.15194.
  16. Королькова А.И., Мишиева Н.Г., Мартазанова Б.А., Бурменская О.В., Веюкова М.А., Екимов А.Н., Трофимов Д.Ю., Абубакиров А.Н. Значимость копийности митохондриальной ДНК в клетках кумулуса пациенток позднего репродуктивного возраста. Акушерство и гинекология. 2019; 10: 108-14. https://dx.doi.org/10.18565/aig.2019.10.108-114.
  17. Cecchino G.N., Garcia-Velasco J.A. Mitochondrial DNA copy number as a predictor of embryo viability. Fertil. Steril. 2018: 111(2): 205-11. https://dx.doi.org/10.1016/j.fertnstert.2018.11.021.
  18. Hashimoto S., Morimoto N., Yam anaka M., Matsumoto H., Yamochi T., Goto H. et al. Quantitative and qualitative changes of mitochondria in human preimplantation embryos. J. Assist. Reprod. Genet. 2017; 34(5): 573-80. https://dx.doi.org/10.1007/s10815-017-0886-6.
  19. Ravichandran K., McCaffrey C., Grifo J., Morales A., Perloe M., Munne S. et al. Mitochondrial DNA quantification as a tool for embryo viability assessment: retrospective analysis of data from single euploid blastocyst transfers. Hum. Reprod. 2017; 32(6): 1282-92. https://dx.doi.org/10.1093/humrep/dex070.
  20. Fragouli E., McCaffrey C., Ravichandran K., Spath K., Grifo J.A., Munne S. et al. Clinical implications of mitochondrial DNA quantification on pregnancy outcomes: a blinded prospective non-selection study. Hum. Reprod. 2017; 32(11): 2340-7. https://dx.doi.org/10.1093/humrep/dex292.
  21. Lledo B., Ortiz J.A., Morales R., Garcia-Hernandez E., Ten J., Bernabeu A. et al. Comprehensive mitochondrial DNA analysis and IVF outcome. Hum. Reprod. Open. 2018; 2018(4): hoy023. https://dx.doi.org/10.1093/hropen/hoy023.
  22. Klimczak A.M., Pacheco L.E., Lewis K.E., Massahi N., Richards J.P., Kearns W.G. et al. Embryonal mitochondrial DNA: relationship to embryo quality and transfer outcomes. J. Assist. Reprod. Genet. 2018; 35(5): 871-7. https://dx.doi.org/10.1007/s10815-018-1147-z.
  23. Treff N.R., Zhan Y., Tao X., Olcha M., Han M., Rajchel J. et al. Levels of trophectoderm mitochondrial DNA do not predict the reproductive potential of sibling embryos. Hum. Reprod. 2017; 32(4): 954-62. https://dx.doi.org/10.1093/humrep/dex034.
  24. Victor A., Griffin D., Dardner K.G., Brake A., Zouves C., Barnes F. et al. Births from embryos with highly elevated levels of mitochondrial DNA. Reprod. Biomed. Online. 2019; 39(3): 403-12. https://dx.doi.org/10.1016/j.rbmo.2019.03.214.
  25. Victor A., Brake A.J., Tyndall J.C., Griffin D.K., Zouves C.G., Barnes F.L. et al. Accurate quantitation of mitochondrial DNA reveals uniform levels in human blastocysts irrespective of ploidy, age, or implantation potential. Fertil. Steril. 2017; 107(1): 34-42.e3. https://dx.doi.org/10.1016/j.fertnstert.2016.09.028.
  26. Lee Y.-X., Chen C.-H., Lin S.-Y., Lin Y.-H., Tzeng C.-R. Adjusted mitochondrial DNA quantification in human embryos may not be applicable as a biomarker of implantation potential. J. Assist. Reprod. Genet. 2019; 36(9): 1855-65. https://dx.doi.org/10.1007/s10815-019-01542-6.
  27. Shang W., Zhang Y., Shu M., Wang W., Ren L., Chen F. et al. Comprehensive chromosomal and mitochondrial copy number profiling in human IVF embryos. Reprod. Biomed. Online. 2018; 36(1); 67-74. https://dx.doi.org/10.1016/j.rbmo.2017.10.110.
  28. Wu F.S.Y., Weng S.P., Shen M.S., Ma P.C., Wu P.K., Lee N.C. Suboptimal trophectoderm mitochondrial DNA level is associated with delayed blastocyst development. J. Assist. Reprod. Genet. 2021; 38(3): 587-94. https://dx.doi.org/10.1007/s10815-020-02045-5.
  29. Королькова А.И., Мишиева Н.Г., Мартазанова Б.А., Бурменская О.В., Екимов А.Н., Трофимов Д.Ю., Веюкова М.А., Кириллова А.О., Абубакиров А.Н. Повышение эффективности программ ЭКО на основании определения копийности митохондриальной ДНК в трофэктодерме эмбрионов. Акушерство и гинекология. 2019; 3: 98-104. https://dx.doi.org/10.18565/aig.2019.3.98-104.

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