Mitochondrial Donation in a Reproductive Care Pathway for mtDNA Disease

Area of Science:

• Genetics
• Reproductive Medicine
• Mitochondrial Biology

Background:

• Pathogenic mitochondrial DNA (mtDNA) variants cause severe inherited metabolic diseases.
• Limited reproductive options exist for women carrying these pathogenic mtDNA variants.
• Pronuclear transfer offers a potential solution for preventing transmission of mtDNA diseases.

Purpose of the Study:

• To evaluate the reproductive care pathway involving pronuclear transfer for women with pathogenic mtDNA variants.
• To assess the health and mtDNA heteroplasmy levels in infants born following mitochondrial donation.

Main Methods:

• Implementation of a reproductive care pathway for women with pathogenic mtDNA variants.
• Pronuclear transfer procedure for mitochondrial donation.
• Monitoring of live births, infant health, and mtDNA heteroplasmy levels.

Main Results:

• 22 women commenced or completed pronuclear transfer, resulting in 8 live births.
• All 8 infants were healthy at birth with no or low mtDNA heteroplasmy in blood.
• Two infants experienced treatable conditions (hyperlipidemia, cardiac arrhythmia, infant myoclonic epilepsy) with normal developmental progress.

Conclusions:

• Pronuclear transfer provides a viable reproductive option for women at risk of transmitting mtDNA diseases.
• Mitochondrial donation via pronuclear transfer results in healthy infants with low levels of pathogenic mtDNA.
• This approach represents a significant advancement in preventing severe inherited metabolic disorders.