Diagnosis and Treatment of Mitochondrial Abnormalities in Reproductive Medicine

Mitochondrial diseases are among the most prevalent inborn errors of metabolism. The overwhelming majority of mitochondrial diseases (about 85%) result from mutations in nuclear genes involved in oxidative phosphorylation, while some (15%) are caused by mutations in mitochondrial DNA (MtDNA). The familial mtDNA mutations are exclusively inherited from the mother. There are four main methods available to prevent the transmission of mtDNA mutations: preimplantation genetic diagnosis (PGD) or prenatal diagnosis (PND) followed by the selection of the best embryo or fetus, the use of complete donor oocytes, mitochondrial replacement therapy (MRT), and genome editing. However, the latter two methods are not available in reproductive medicine yet. Mitochondrial abnormalities can also disturb normal reproduction. The abnormalities of mitochondria in oocytes of older infertility patients are also believed to result in poor development. As a cure, ooplasm from fertile donor oocytes was injected into a group of patients to rejuvenate their developmentally compromised oocytes. However, this ooplasmic transfer series had to be discontinued, because two fetuses were affected by Turner’s syndrome and an increased risk of mitochondrial heteroplasmy was apprehended. Subsequently, treatments with heterologous mitochondria and autologous transfer were attempted. However, during the interim analysis of a controlled randomized trial, the transfer of autologous mitochondria to the maternal germline failed to improve embryo quality in IVF.