Mitochondrial Donation in a Reproductive Care Pathway for mtDNA Disease

Abstract

Pathogenic variants in mitochondrial DNA (mtDNA) are a common cause of severe, often fatal, inherited metabolic disease. A reproductive care pathway was implemented to provide women carrying pathogenic mtDNA variants with reproductive options. A total of 22 women with pathogenic mtDNA variants have commenced or completed pronuclear transfer (and thus receipt of a mitochondrial donation), and there have been 8 live births. All 8 children were healthy at birth, with no or low levels of mtDNA heteroplasmy in blood. Hyperlipidemia and cardiac arrhythmia developed in a child whose mother had hyperlipidemia during pregnancy; both of the child's conditions responded to treatment. Infant myoclonic epilepsy developed in another child, with spontaneous remission. At the time of this report, all the children have made normal developmental progress. (Funded by the U.K. National Health Service and others.).

Figure 1. Reproductive care pathway for women with pathogenic mtDNA variants.

Women are referred for reproductive advice and potential ART to limit the transmission of the pathogenic mtDNA variant. The numbers referred and progressing through each part of this pathway are shown. Women are assessed at the MRA-C or MART-C clinics for assessment prior to either PGT or PNT. *Includes three women who had PGT but had no embryos below threshold and were subsequently referred for mitochondrial donation. **Births and pregnancies since start of Mitochondrial Reproductive Care Pathway. Completed means those women who have failed to become pregnant despite a full course of treatment. 51 women who were not able to proceed with either PGT or mitochondrial donation, within their reproductive capacity, can be referred back to MRA-C. MD – mitochondrial donation.