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.
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.
Authors: Björn Heindryckx; Jitesh Neupane; Mado Vandewoestyne; Christodoulos Christodoulou; Yens Jackers; Jan Gerris; Etienne Van den Abbeel; Rudy Van Coster; Dieter Deforce; Petra De Sutter Journal: Mitochondrion Date: 2014-08-23 Impact factor: 4.160
Authors: M Tang; R R Guggilla; Y Gansemans; M Van der Jeught; A Boel; M Popovic; P Stamatiadis; M Ferrer-Buitrago; V Thys; R Van Coster; D Deforce; P De Sutter; F Van Nieuwerburgh; B Heindryckx Journal: Mol Hum Reprod Date: 2019-12-01 Impact factor: 4.025
Authors: P Reynier; P May-Panloup; M F Chrétien; C J Morgan; M Jean; F Savagner; P Barrière; Y Malthièry Journal: Mol Hum Reprod Date: 2001-05 Impact factor: 4.025
Authors: Hong Ma; Ryan C O'Neil; Nuria Marti Gutierrez; Manoj Hariharan; Zhuzhu Z Zhang; Yupeng He; Cengiz Cinnioglu; Refik Kayali; Eunju Kang; Yeonmi Lee; Tomonari Hayama; Amy Koski; Joseph Nery; Rosa Castanon; Rebecca Tippner-Hedges; Riffat Ahmed; Crystal Van Dyken; Ying Li; Susan Olson; David Battaglia; David M Lee; Diana H Wu; Paula Amato; Don P Wolf; Joseph R Ecker; Shoukhrat Mitalipov Journal: Cell Stem Cell Date: 2016-11-10 Impact factor: 24.633
Authors: Paul de Laat; Saskia Koene; Lambert P W J van den Heuvel; Richard J T Rodenburg; Mirian C H Janssen; Jan A M Smeitink Journal: J Inherit Metab Dis Date: 2012-03-09 Impact factor: 4.982