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Human germline nuclear transfer to overcome mitochondrial disease and failed fertilization after ICSI

Maoxing Tang, Annekatrien Boel (UGent) , Noemi Castelluccio (UGent) , Arantxa Cardona Barberán (UGent) , Antonia Christodoulaki (UGent) , Bieke Bekaert (UGent) , Mina Popovic, Frauke Vanden Meerschaut (UGent) , Petra De Sutter (UGent) , Björn Menten (UGent) , et al.
(2022) JOURNAL OF ASSISTED REPRODUCTION AND GENETICS. 39. p.609-618
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Abstract
Purpose Providing additional insights on the efficacy of human nuclear transfer (NT). Here, and earlier, NT has been applied to minimize transmission risk of mitochondrial DNA (mtDNA) diseases. NT has also been proposed for treating infertility, but it is still unclear which infertility indications would benefit. In this work, we therefore additionally assess the applicability of NT to overcome failed fertilization. Methods Patient 1 carries a homoplasmic mtDNA mutation (m.11778G > A). Seventeen metaphase II (MII) oocytes underwent pre-implantation genetic testing (PGT), while five MII oocytes were used for spindle transfer (ST), and one in vitro matured (IVM) metaphase I oocyte underwent early pronuclear transfer (ePNT). Patients 2-3 experienced multiple failed intracytoplasmic sperm injection (ICSI) and ICSI-assisted oocyte activation (AOA) cycles. For these patients, the obtained MII oocytes underwent an additional ICSI-AOA cycle, while the IVM oocytes were subjected to ST. Results For patient 1, PGT-M confirmed mutation loads close to 100%. All ST-reconstructed oocytes fertilized and cleaved, of which one progressed to the blastocyst stage. The reconstructed ePNT-zygote reached the morula stage. These samples showed an average mtDNA carry-over rate of 2.9% +/- 0.8%, confirming the feasibility of NT to reduce mtDNA transmission. For patient 2-3 displaying fertilization failure, ST resulted in, respectively, 4/5 and 6/6 fertilized oocytes, providing evidence, for the first time, that NT can enable successful fertilization in this patient population. Conclusion Our study showcases the repertoire of disorders for which NT can be beneficial, to overcome either mitochondrial disease transmission or failed fertilization after ICSI-AOA.
Keywords
Genetics (clinical), Developmental Biology, Obstetrics and Gynecology, Genetics, Reproductive Medicine, General Medicine, Pronuclear transfer, Spindle transfer, Mitochondrial DNA disease, Female infertility, Fertilization failure, ASSISTED OOCYTE ACTIVATION, PREIMPLANTATION GENETIC DIAGNOSIS, HEREDITARY OPTIC NEUROPATHY, PRONUCLEAR TRANSFER, TRANSFER RESTORES, HUMAN EMBRYOS, REPLACEMENT, TRANSMISSION, MUTATIONS, PREVENT

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MLA
Tang, Maoxing, et al. “Human Germline Nuclear Transfer to Overcome Mitochondrial Disease and Failed Fertilization after ICSI.” JOURNAL OF ASSISTED REPRODUCTION AND GENETICS, vol. 39, 2022, pp. 609–18, doi:10.1007/s10815-022-02401-7.
APA
Tang, M., Boel, A., Castelluccio, N., Cardona Barberán, A., Christodoulaki, A., Bekaert, B., … Heindryckx, B. (2022). Human germline nuclear transfer to overcome mitochondrial disease and failed fertilization after ICSI. JOURNAL OF ASSISTED REPRODUCTION AND GENETICS, 39, 609–618. https://doi.org/10.1007/s10815-022-02401-7
Chicago author-date
Tang, Maoxing, Annekatrien Boel, Noemi Castelluccio, Arantxa Cardona Barberán, Antonia Christodoulaki, Bieke Bekaert, Mina Popovic, et al. 2022. “Human Germline Nuclear Transfer to Overcome Mitochondrial Disease and Failed Fertilization after ICSI.” JOURNAL OF ASSISTED REPRODUCTION AND GENETICS 39: 609–18. https://doi.org/10.1007/s10815-022-02401-7.
Chicago author-date (all authors)
Tang, Maoxing, Annekatrien Boel, Noemi Castelluccio, Arantxa Cardona Barberán, Antonia Christodoulaki, Bieke Bekaert, Mina Popovic, Frauke Vanden Meerschaut, Petra De Sutter, Björn Menten, Sofie Symoens, Arnaud Vanlander, Dominic Stoop, Paul Coucke, and Björn Heindryckx. 2022. “Human Germline Nuclear Transfer to Overcome Mitochondrial Disease and Failed Fertilization after ICSI.” JOURNAL OF ASSISTED REPRODUCTION AND GENETICS 39: 609–618. doi:10.1007/s10815-022-02401-7.
Vancouver
1.
Tang M, Boel A, Castelluccio N, Cardona Barberán A, Christodoulaki A, Bekaert B, et al. Human germline nuclear transfer to overcome mitochondrial disease and failed fertilization after ICSI. JOURNAL OF ASSISTED REPRODUCTION AND GENETICS. 2022;39:609–18.
IEEE
[1]
M. Tang et al., “Human germline nuclear transfer to overcome mitochondrial disease and failed fertilization after ICSI,” JOURNAL OF ASSISTED REPRODUCTION AND GENETICS, vol. 39, pp. 609–618, 2022.
@article{8738943,
  abstract     = {{Purpose Providing additional insights on the efficacy of human nuclear transfer (NT). Here, and earlier, NT has been applied to minimize transmission risk of mitochondrial DNA (mtDNA) diseases. NT has also been proposed for treating infertility, but it is still unclear which infertility indications would benefit. In this work, we therefore additionally assess the applicability of NT to overcome failed fertilization. Methods Patient 1 carries a homoplasmic mtDNA mutation (m.11778G > A). Seventeen metaphase II (MII) oocytes underwent pre-implantation genetic testing (PGT), while five MII oocytes were used for spindle transfer (ST), and one in vitro matured (IVM) metaphase I oocyte underwent early pronuclear transfer (ePNT). Patients 2-3 experienced multiple failed intracytoplasmic sperm injection (ICSI) and ICSI-assisted oocyte activation (AOA) cycles. For these patients, the obtained MII oocytes underwent an additional ICSI-AOA cycle, while the IVM oocytes were subjected to ST. Results For patient 1, PGT-M confirmed mutation loads close to 100%. All ST-reconstructed oocytes fertilized and cleaved, of which one progressed to the blastocyst stage. The reconstructed ePNT-zygote reached the morula stage. These samples showed an average mtDNA carry-over rate of 2.9% +/- 0.8%, confirming the feasibility of NT to reduce mtDNA transmission. For patient 2-3 displaying fertilization failure, ST resulted in, respectively, 4/5 and 6/6 fertilized oocytes, providing evidence, for the first time, that NT can enable successful fertilization in this patient population. Conclusion Our study showcases the repertoire of disorders for which NT can be beneficial, to overcome either mitochondrial disease transmission or failed fertilization after ICSI-AOA.}},
  author       = {{Tang, Maoxing and Boel, Annekatrien and Castelluccio, Noemi and Cardona Barberán, Arantxa and Christodoulaki, Antonia and Bekaert, Bieke and Popovic, Mina and Vanden Meerschaut, Frauke and De Sutter, Petra and Menten, Björn and Symoens, Sofie and Vanlander, Arnaud and Stoop, Dominic and Coucke, Paul and Heindryckx, Björn}},
  issn         = {{1058-0468}},
  journal      = {{JOURNAL OF ASSISTED REPRODUCTION AND GENETICS}},
  keywords     = {{Genetics (clinical),Developmental Biology,Obstetrics and Gynecology,Genetics,Reproductive Medicine,General Medicine,Pronuclear transfer,Spindle transfer,Mitochondrial DNA disease,Female infertility,Fertilization failure,ASSISTED OOCYTE ACTIVATION,PREIMPLANTATION GENETIC DIAGNOSIS,HEREDITARY OPTIC NEUROPATHY,PRONUCLEAR TRANSFER,TRANSFER RESTORES,HUMAN EMBRYOS,REPLACEMENT,TRANSMISSION,MUTATIONS,PREVENT}},
  language     = {{eng}},
  pages        = {{609--618}},
  title        = {{Human germline nuclear transfer to overcome mitochondrial disease and failed fertilization after ICSI}},
  url          = {{http://doi.org/10.1007/s10815-022-02401-7}},
  volume       = {{39}},
  year         = {{2022}},
}
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