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Live birth derived from oocyte spindle transfer to prevent mitochondrial disease

Reproductive BioMedicine Online, Volume 34, Issue 4, April 2017, Pages 361 - 368


Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause fatal or debilitating mitochondrial disorders. The severity of clinical symptoms is often associated with the level of mtDNA mutation load or degree of heteroplasmy. Current clinical options to prevent transmission of mtDNA mutations to offspring are limited. Experimental spindle transfer in metaphase II oocytes, also called mitochondrial replacement therapy, is a novel technology for preventing mtDNA transmission from oocytes to pre-implantation embryos. Here, we report a female carrier of Leigh syndrome (mtDNA mutation 8993T > G), with a long history of multiple undiagnosed pregnancy losses and deaths of offspring as a result of this disease, who underwent IVF after reconstitution of her oocytes by spindle transfer into the cytoplasm of enucleated donor oocytes. A male euploid blastocyst wasobtained from the reconstituted oocytes, which had only a 5.7% mtDNA mutation load. Transfer of the embryo resulted in a pregnancy with delivery of a boy with neonatal mtDNA mutation load of 2.36–9.23% in his tested tissues. The boy is currently healthy at 7 months of age, although long-term follow-up of the child's longitudinal development remains crucial.

Keywords: Mitochondria, Nuclear transfer, Meiotic spindle, Oocyte, Leigh syndrome, Cytoplasm.


a New Hope Fertility Center, Punto Sao Paulo, Lobby Corporativo, Américas 1545 Providencia, Guadalajara, Mexico

b New Hope Fertility Center, 4 Columbus Circle, New York, NY 10019, USA

c Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA

d Department of Obstetrics and Gynecology, Division of Reproductive Biology, NYU School of Medicine, 180 Varick Street, New York, NY 10014, USA

e Infertility Center of St Louis, St Luke's Hospital, St Louis, MO 63017, USA

f Reprogenetics, 3 Regent Street, Livingston, NJ 07078, USA

* Corresponding authors.