Prevention of mitochondrial disease inheritance by assisted reproductive technologies: Prospects and challenges

BackgroundMitochondrial diseases are caused by the mutations in both nuclear and mitochondrial DNA (mtDNA) and the treatment options for patients who have mitochondrial disease are rather limited. Mitochondrial DNA is transmitted maternally and does not follow a Mendelian pattern of inheritance. Since reliable and predictable detection of mitochondrial disorders in embryos and oocytes is unattainable at present, an alternative approach to this problem has emerged as partial or complete replacement of mutated mtDNA with the wild-type mtDNA through embryo manipulations. Currently available methods to achieve this goal are germinal vesicle transfer (GVT), metaphase chromosome transfer (CT), pronuclear transfer (PNT) and ooplasmic transfer (OT).Scope of reviewWe summarize the state of the art regarding these technologies and discuss the implications of recent advances in the field for clinical practice.Major conclusionsCT, PNT and GVT techniques hold promise to prevent transmission of mutant mtDNA through ARTs. However, it is clear that mtDNA heteroplasmy in oocytes, embryos and offspring produced by these methods remains as a legitimate concern.General significanceNew approaches to eliminate transmission of mutant mtDNA certainly need to be explored in order to bring the promise of clinical application for the treatment of mitochondrial disorders. This article is part of a Special Issue entitled Biochemistry of Mitochondria, Life and Intervention 2010.

► Recent studies for prevention of mitochondrial disease inheritance are digested. ► Exchanging of gamete cytoplasmic material is the way to prevent the inheritance. ► Currently available cell fusion methods cause mtDNA heteroplasmy. ► Further studies need to be performed carefully before the clinical application.