Mitochondrial Donation and Preimplantation Genetic Testing for mtDNA Disease

Area of Science:

• Reproductive Medicine
• Genetics
• Mitochondrial Biology

Background:

• Mitochondrial DNA (mtDNA) diseases pose risks to children born to mothers with pathogenic mtDNA variants.
• Mitochondrial donation by pronuclear transfer offers a method to reduce mtDNA disease transmission.
• This technique involves transferring the nuclear genome to an enucleated donor egg.

Purpose of the Study:

• To evaluate the efficacy and safety of mitochondrial donation (pronuclear transfer) and preimplantation genetic testing (PGT) for women at risk of transmitting mtDNA disease.
• To assess the impact of these methods on reducing pathogenic mtDNA variant transmission.

Main Methods:

• Offered pronuclear transfer to patients with homoplasmic or elevated heteroplasmic pathogenic mtDNA variants.
• Offered PGT to patients with heteroplasmic pathogenic mtDNA variants.
• Monitored clinical pregnancies, live births, and heteroplasmy levels in infants.

Main Results:

• Clinical pregnancies were achieved in 36% (pronuclear transfer) and 41% (PGT) of patients.
• Pronuclear transfer resulted in 8 live births and 1 ongoing pregnancy; PGT resulted in 18 live births.
• Infants born via pronuclear transfer showed significantly reduced levels of maternal pathogenic mtDNA variants, ranging from undetectable to 16% heteroplasmy.

Conclusions:

• Mitochondrial donation via pronuclear transfer is compatible with human embryo viability.
• An integrated program of pronuclear transfer and PGT effectively reduces the transmission of both homoplasmic and heteroplasmic pathogenic mtDNA variants.
• These methods provide a viable option for women to have genetically related children with a lower risk of mtDNA disease.