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Enucleated oocyte donation: first for infertility treatment, then for mitochondrial diseases

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Abstract

There seems to be a consensus that enucleated oocyte donation (EOD) should only be used to reduce the risk of having a child with mitochondrial disorders. However, this paper argues that in the initial phase in which we are at the moment, EOD should first be used to remedy infertility caused by poor oocyte quality or poor embryonic development. That learning period will allow researchers to improve their technical skills and the knowledge of the best procedure before starting on high-risk cases. Mitochondrial carryover of pathologic mtDNA is the main cause of concern for the offspring. That risk does not exist in infertility cases. The application of EOD to treat infertility should at present be performed in a clinical research setting to obtain more evidence about efficacy and safety.

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References

  1. Human Fertilisation and Embryology Authority. Third scientific review of the safety and efficacy of methods to avoid mitochondrial disease through assisted conception: 2014 update. Report provided to the Human Fertilisation and Embryology Authority (HFEA), June 2014. https://www.hfea.gov.uk/media/2614/third_mitochondrial_replacement_scientific_review.pdf (last accessed 20/12/2021).

  2. Zhang J, Liu H, Luo S, Lu Z, Chavez-Badiola A, Liu Z, Yang M, Merhi Z, Silber SJ, Munne S, Konstantinidis M, Wells D, Tang JJ, Huang T. Live birth derived from oocyte spindle transfer to prevent mitochondrial disease. Reprod Biomed Online. 2017;34:361–8.

    Article  Google Scholar 

  3. Hyslop LA, Blakeley P, Craven L, Richardson J, Fogarty NME, Fragouli E, et al. Toward clinical application of pronuclear transfer to prevent mitochondrial DNA disease. Nature. 2016;534:383–6.

    Article  CAS  Google Scholar 

  4. Yamada M, Akashi K, Ooka R, Miyado K, Akutsu H. Mitochondrial genetic drift after nuclear transfer in oocytes. Int J Mol Sci. 2020;21:5880.

    Article  CAS  Google Scholar 

  5. Craven L, Turnbull DM. Reproductive options for women with mitochondrial disease. In: Mancuso M, Klopstock T, editors. Diagnosis and management of mitochondrial disorders. Springer Nature Switzerland; 2019. p. 371–82.

    Chapter  Google Scholar 

  6. Tang M, Guggilla RR, Gansemans Y, Van der Jeught M, Boel A, Popovic M, Stamatiadis P, Ferrer-Buitrago M, Thys V, Van Coster R, et al. Comparative analysis of different nuclear transfer techniques to prevent the transmission of mitochondrial DNA variants. Mol Hum Reprod. 2019;25:797–810.

    CAS  PubMed  Google Scholar 

  7. Sendra L, Garcia-Mares A, Herrero MJ, Alino SF. Mitochondrial DNA replacement techniques to prevent human mitochondrial diseases. Int J Mol Sci. 2021;22:551.

    Article  CAS  Google Scholar 

  8. Yamada M, Sato S, Ooka R, Akashi K, Nakamura A, Miyado K, Akatsu H, Tanaka M. Mitochondrial replacement by genome transfer in human oocytes: efficacy, concerns, and legality. Reprod Med Biol. 2021;20:53–61.

    Article  CAS  Google Scholar 

  9. Hellebrekers DMEI, Wolfe R, Hendrickx ATM, de Coo IFM, de Die CE, Geraedts JPM, Chinnery PF, Smeets HJM. PGD and heteroplasmic mitochondrial DNA point mutations: a systematic review estimating the chance of healthy offspring. Hum Reprod Update. 2012;18:341–9.

    Article  CAS  Google Scholar 

  10. Practice Committee of the American Society for Reproductive Medicine, Practice Committee of the Society for Reproductive Technology. Mature oocyte cryopreservation: a guideline. Fertil Steril. 2012;99:37–43.

    Google Scholar 

  11. Ethics Committee of the American Society for Reproductive Medicine. Planned oocyte cryopreservation for women seeking to preserve future reproductive potential: an Ethics Committee opinion. Fertil Steril. 2018;110:1022–8.

    Article  Google Scholar 

  12. Human Fertilisation and Embryology Authority. Scientific review of the safety and efficiency of methods to avoid mitochondrial disease through assisted conception: 2016 update. https://www.hfea.gov.uk/media/2611/fourth_scientific_review_mitochondria_2016.pdf (last accessed 20/12/2021).

  13. Task Force on Ethics and Law of ESHRE, Pennings G, De Wert G, Shenfield F, Cohen J, Devroey P, Tarlatzis B. The welfare of the child in medically assisted reproduction. Hum Reprod. 2007;22:2585–8.

    Article  Google Scholar 

  14. Bredenoord AL, Dondorp W, Pennings G, De Die-Smulders CEM, De Wert G. PGD to reduce reproductive risk: the case of mitochondrial DNA disorders. Hum Reprod. 2008;23:2392–401.

    Article  CAS  Google Scholar 

  15. Rodriguez-Varela C, Herraiz S, Labarta E. Mitochondrial enrichment in infertile patients: a review of different mitochondrial replacement therapies. Ther Adv Reprod Health. 2021;15:1–16.

    Google Scholar 

  16. Siristatidis C, Mantzavinos T, Vlahos N. Maternal spindle transfer for mitochondrial disease: lessons to be learnt before extending the method to other conditions? Hum Fertil. 2021. https://doi.org/10.1080/14647273.2021.1925168.

    Article  Google Scholar 

  17. Harper JC, Aittomaki K, Borry P, Cornel MC, de Wert G, Dondorp W, Geraedts J, Gianaroli L, Ketterson K, Liebaers I, Lundin K, Mertes H, Morris M, Pennings G, Sermon K, Spits C, Soini S, van Montfoort A, Veiga A, Vermeesch JR, on behalf of the European Society of Human Reproduction and Embryology and European Society of Human Genetics. Recent developments in genetics and medically assisted reproduction: from research to clinical applications. Eur J Hum Gen. 2018;26:12–33.

    Article  CAS  Google Scholar 

  18. Christodoulaki A, Boel A, Tang M, De Roo C, Stoop D, Heindryckx B. Prospects of germline nuclear transfer in women with diminished ovarian reserve. Front Endocrinol. 2021;12:635370.

    Article  Google Scholar 

  19. Tang M, Popovic M, Stamatiadis P, Van der Jeught M, Van Coster R, Deforce D, et al. Germline nuclear transfer in mice may rescue poor embryo development associated with advanced maternal age and early embryo arrest. Hum Reprod. 2020;35:1562–77.

    Article  CAS  Google Scholar 

  20. Costa-Borges N, Spath K, Miguel-Escalada I, Mestres E, Balmaseda R, Serafı́n A, et al. Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice. eLife. 2020;9:e48591.

    Article  CAS  Google Scholar 

  21. Zhang J, Zhuang G, Zeng Y, Grifo J, Acosta C, Shu Y, Liu H. Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF. Reprod BioMed Online. 2016;33:529–33.

    Article  Google Scholar 

  22. Tang M, Boel A, Castelluccio N, Barberan AC, Christodoulaki A, Bekaert B, et al. Human germline nuclear transfer to overcome mitochondrial disease and failed fertilization after ICSI. J Assist Reprod Gen. 2022. https://doi.org/10.1007/s10815-10022-02401-10817.

    Article  Google Scholar 

  23. Kostaras K, Costa-Borges N, Psathas P, Calderon G, Nikitos E. ISRCTN Registry, Spindle transfer for the treatment of infertility problems associated to poor egg quality: a pilot trial, 2019. https://doi.org/10.1186/ISRCTN11455145. (last accessed 20/12/2021).

  24. Costa-Borges N, Nikitos E, Spath K, Kostaras K, Zervomanolakis I, Kontopoulos G, et al. First registered pilot trial to validate the safety and effectiveness of maternal spindle transfer to overcome infertility associated with poor oocyte quality. Fertil Steril. 2020;114(3,suppl):e71–2.

    Article  Google Scholar 

  25. Spath K. Nuclear transfer for female-related infertility. Presentation at Progress in Nuclear Transfer technology: Scientific advancements sparkle ethical debate, November 25th, 2021, Ghent.

  26. Macklon NS, Ahuja KK, Fauser BCJM. Building an evidence base for IVF “add-ons.” Reprod Biomed Online. 2019;38:853–6.

    Article  CAS  Google Scholar 

  27. Provoost V, Tilleman K, D’Angelo A, De Sutter P, De Wert G, Nelen W, Pennings G, Shenfield F, Dondorp W. Beyond the dichotomy: a tool for distinguishing between experimental, innovative and established treatment. Hum Reprod. 2014;29:413–7.

    Article  Google Scholar 

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  1. Department of Philosophy and Moral Science, Bioethics Institute Ghent (BIG), Ghent University, Blandijnberg 2, B-9000, Gent, Belgium

    Guido Pennings

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  1. Guido Pennings
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Correspondence to Guido Pennings.

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Pennings, G. Enucleated oocyte donation: first for infertility treatment, then for mitochondrial diseases. J Assist Reprod Genet 39, 605–608 (2022). https://doi.org/10.1007/s10815-022-02428-w

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