By Lauren Ting - Singapore
Introduction
In-vitro fertilisation (IVF) is a technique available to allow people with infertility to have a baby. During this process, an egg is removed from the woman’s ovaries before ovulation; then, it is fertilised with sperm in a laboratory. Following this, the embryo is then injected into the woman’s womb to grow and develop into a foetus ("Mitochondrial Diseases").
What is mitochondrial disease?
The mitochondria is an organelle, colloquially known as the cell's powerhouse, because it produces the required energy to power its biochemical reactions. Mitochondrial disease is a group of disorders that affect the mitochondria, requiring the mitochondria to produce more energy, particularly in high-energy demand organs such as the heart, muscles, and brain. When the number or function of mitochondria in the cell is disrupted, less energy is produced, and organ dysfunction results. Mitochondrial disease can cause a vast array of health concerns, including fatigue, metabolic strokes, seizures, cognitive disabilities, impairment of hearing, loss of motor control, and more. These symptoms can present at any age, from infancy until late adulthood.
Mitochondrial diseases are incurable and can be fatal within days or even hours of birth. Some families have this disease inherently by genetics. Utilising the technique of swapping the mitochondria is seen as the only option for them to have a healthy child of their own. As babies inherit all their mitochondria from their mother, harmful mutations in the “batteries” can affect all of the children a woman has. Hence, for affected women, natural conception is often a gamble.
What is 3 way IVF and how does it work?
3 way IVF is a reproductive technology used to allow mothers with mitochondrial disease to have a genetically related child without the disease being passed on to the child. This reduces the mutations that occur in the DNA of cellular organelles known as mitochondria, which resides in the cell cytoplasm (“Three-Parent IVF: The Benefits and the Risks”).
This procedure includes pronuclear transfer and maternal spindle transfer:
Pronuclear transfer
Eggs and the sperm are collected from the mother and father respectively as in normal IVF, fertilisation is carried out in vitro.
Mother’s faulty mitochondria are removed from the pronuclei of successful embryos.
The donor egg is also fertilised and the pronuclear are removed and destroyed.
The parents' pronuclei are then inserted into the donor's fertilised egg (Rulli).
Maternal spindle transfer
Eggs are taken from the mother but are not initially fertilised.
Spindle group is removed when the nucleus is arrested in metaphase II.
Spindle group is then planted in the donor egg which also had its spindle group removed.
Egg is then fertilised by sperm and left to develop before inserting into the mother.
The Resulting embryo contains a nucleus with the mother and father’s DNA as well as healthy mitochondria from the donor DNA (“Three-Parent IVF: The Benefits and the Risks”).
Challenges and limitations of this reproductive technology
Although this procedure may seem like a substantial way to prevent mitochondrial disease for future infants, there are some challenges and limitations that come with it.
MRT raises ethical concerns about the future of genetic editing, particularly the possibility of creating ‘designer babies’. While intended for medical purposes, the technology might normalise genetic modifications for aesthetic or non-essential traits, exacerbating social inequalities. In countries like the UK, where MRT is tightly regulated, debates about expanding its applications could emerge, risking societal divides over access to genetic enhancements (Poulton).
Moreover, children born through MRT, with DNA from three individuals, may face challenges regarding their identity and mental health. Questions about their origins, particularly if mitochondrial donors seek legal or social recognition, could create confusion. For instance, Alana Saarinen, born through an early mitochondrial transfer, expressed curiosity about her donor, highlighting potential emotional complexities for MRT offspring (Rulli).
The long-term health effects of MRT remain unknown, with potential risks like developmental disabilities and organ malfunctions. Early studies, such as a 2018 Nature report, suggest mitochondrial-nuclear incompatibility could lead to complications. While initial cases like the 2016 MRT birth in Mexico appear successful, the lack of long-term follow-up studies underscores significant medical uncertainties (“Three-Parent Baby Raises Issues of Long-Term Health Risks”).
Conclusion
In summary, the introduction of three-way IVF represents a remarkable move forward in the field of reproductive medicine. This is particularly for families struggling with the devastating impact of mitochondrial disease. By employing innovative techniques such as pronuclear transfer and maternal spindle transfer, this technology offers a beacon of hope for individuals who are faced with the prospect of passing on these debilitating conditions to their children. With its ability to reduce the risk of mitochondrial disorders and provide a pathway to healthy genetic inheritance, three-way IVF holds immense promise for reshaping the landscape of assisted reproductive technologies.
Bibliography:
Children’s Hospital of Philadelphia. “Mitochondrial Disease.” Children’s Hospital of Philadelphia, www.chop.edu/conditions-diseases/mitochondrial-disease.
Cleveland Clinic. “Mitochondrial Diseases.” Cleveland Clinic, my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases.
Oxford University. “Three-Parent Baby Raises Issues of Long-Term Health Risks.” University of Oxford, 24 Sept. 2016, www.ox.ac.uk/research/three-parent-baby-raises-issues-long-term-health-risks.
Rulli, Tina. “What Is the Value of Three‐Parent IVF?” Hastings Center Report, vol. 46, no. 3, 2016, pp. 38–47. Wiley Online Library, doi:10.1002/hast.594.
“Three-Parent IVF: The Benefits and the Risks.” Medical News Today, 19 Feb. 2015, www.medicalnewstoday.com/articles/289706.
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