The Future of Assisted Reproductive Technology – Part 2

Gene Correction and IVF

Scientific advancements are rapidly changing the field of reproductive technology making procedures safer, more efficient, affordable and more accessible to many afflicted with infertility. In the last two decades, aneuploidy screening and genetic testing of embryos prior to their implantation became a routinely used practice to increase the chances of a healthy pregnancy. However, recent developments are taking it one step further, from the selection of a healthy embryo to correction of the genetic condition. Two examples of genetic correction technologies are CRISPR (discussed in our last blog), and Mitochondrial Replacement Therapy (MRT).
MRT is aiming to correct fatal DNA mutations in the intracellular energy-producing powerhouse, the mitochondria.
Unlike the chromosomal DNA, which is found in the nucleus and carries our entire genetic makeup, the mitochondria contain its own unique DNA (mtDNA), which consists of only 37 genes, responsible for normal mitochondrial function. Unlike nuclear DNA, mtDNA is inherited exclusively from the mother, therefore if the mother carries a mutation in her mtDNA all of her offspring will be affected. There are several genetic diseases linked to specific mutations in the mtDNA, which may result in debilitating or even fatal outcomes (i.e., Mitochondrial myopathy, Leber’s hereditary optic neuropathy, Leigh Syndrome, etc.). Until recently, women affected by a mitochondrial disease that wanted to conceive could either use donor egg IVF or take a chance with the severity of illness in the offspring and treat the symptoms.
Mitochondrial Replacement Therapy (MRT) was developed to allow an affected mother to inherit her nuclear DNA but no her mitochondrial DNA to her offspring. In this procedure, the nucleus of the donor egg is replaced with the nucleus of the mother. This replacement results in a ‘hybrid egg’ which consists of healthy mitochondria from the donor and the chromosomal DNA from the mother. (see illustration).

Mitochondrial Replacement Therapy (MRT)

This innovative technology provides hope to women who are suffering from mitochondrial diseases and wish to become parents.

A year ago history was made with the publication of the first MRT baby being born.
In this case, MRT was used to replace the mitochondria in the egg of Leigh syndrome’s patient. Leigh syndrome is a severe neurological condition characterized by progressive loss of mental and movement abilities that typically results in death. The patient who suffered multiple undiagnosed pregnancy losses and deaths of offspring agreed to take part in this experimental MRT procedure. The ‘corrected’ egg was successfully fertilized and developed into a healthy embryo, which resulted in a healthy pregnancy and the delivery of a full term healthy baby boy. Follow-up of the child’s development is needed to determine the long-term impact of this procedure on the offspring.
MRT is a promising new technology that carries great promise to completely prevent the inheritance of mitochondrial disease. The technology was approved by the British parliament for routine clinical use and is pending approval in other countries. More clinical research is still required before the Canadian Reproductive Society adopts this technology.



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