Technique used for world's first 'three-parent baby' unveiled

Technique used for world's first 'three-parent baby' unveiled
Scientists have unveiled the details of a pioneering IVF technique that led to the birth of the world's first 'three-parent baby' last year, providing new hope to families with inheritable mitochondrial disorders to have healthy children in the future.

The procedure using mitochondrial replacement therapy (MRT) resulted in the birth of a healthy baby boy to a carrier of Leigh Syndrome, a progressive, fatal neurological disorder caused by a mutation in the mother's mitochondrial DNA.

MRT enabled the parents to have a healthy child after the loss of two children to Leigh syndrome. The parents of the baby, a Jordanian couple, had been trying to start a family for almost 20 years. After suffering four miscarriages and the death of their first two babies, couple sought out the help of John Zhang and his team at the New Hope Fertility Centre in New York City.

The severity of the disease is associated with the percentage of affected mitochondria or the mutation load. The mother is asymptomatic as her mutation load is only 24.5 per cent, less than half the expected 60 per cent threshold load for the disease.

Her son, born on April 6 last year after IVF with MRT, had a mutation load ranging from 2.36 to 9.23 per cent, depending on the tissues tested, well below the expected threshold for the condition. It is currently unknown whether the mutation load will remain the same throughout his life.

The researchers used an electrofusion technique to transfer the nuclear genome from the mother's egg (leaving behind most of the mother's mitochondria) to the cytoplasm of a donor egg containing only healthy mitochondria.

This egg was then fertilised by the father's sperm and transferred to the mother's womb and a baby boy was born at 37 weeks after an uneventful pregnancy. Two methods of cell fusion have been used in the past by various groups researching MRT.

Most groups have utilised a virus to accomplish cell fusion, however, the extent of viral DNA carryover is unknown. The other method involves a metered electrical pulse to initiate cell fusion. Comparably, electrofusion is a more demanding technically, but has no risk of viral DNA carryover.

The ovarian stimulation and egg collection procedures, mitochondrial replacement and fertilisation were carried out at a private fertility clinic in New York. The frozen embryo was then transferred to an affiliated fertility clinic in Mexico, where it was implanted in the patient's womb.

"Thirty years ago it was discovered that certain rare diseases are associated with abnormal, mutated mitochondria in human cells," said Jacques Cohen, Director of the ART Institute of Washington.

"It is only now that the combination of this knowledge-base and clinical strategy has allowed the birth of a baby free of mitochondrial disease, after decades of ethical and political debate," said Cohen. The research was published in the journal Reproductive BioMedicine Online (RBMO).

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