Egg quality can decrease with age, and one way to overcome this is through a technique called mitochondrial donation. This technique can also be used to prevent the transmission of mitochondrial diseases. Mitochondrial donation can be performed in several ways, with the two primary methods being spindle and pronuclear transfer.
What Is Mitochondrial Donation?
Many couples undergoing IVF face the challenge of poor egg quality, which can reduce their chances of success and pregnancy. Its relevance increases with advancing female age and, in some cases, is related to mitochondrial function.
Mitochondria are tiny cellular organs, or organelles, that produce energy for the cell and have their DNA (mitochondrial DNA). Egg cells demand a high energy amount, and so they contain a high number of mitochondria. With increasing age, these mitochondria can become dysfunctional and produce less energy. It can lead to problems with the egg and embryos to stop developing.
One way to potentially overcome this is by using mitochondrial donation. It involves replacing defective mitochondria with healthy ones from a donor while retaining the patient's DNA. The healthy mitochondria produce more energy for the egg, allowing the embryo to develop further and potentially implant for a pregnancy.
How Is Spindle Transfer Performed in Mitochondrial Donation?
Spindle transfer is a technique used to create embryos with healthy mitochondria from a donor egg while preserving the genetic material from the intended mother.
What Is the “Spindle” in Spindle Transfer?
The spindle apparatus is a component of cells of a network of fibers that grab chromosomes to separate them. Chromosomes must be separated during cell division or the formation of eggs or sperm. In an egg, the spindle and chromosomes are contained within a nucleus that can be manipulated in the laboratory.
Now, let’s review the steps of spindle transfer using the diagram below:
I. In the first step, the nucleus (containing the spindle and chromosomes) is removed from the mother's and the donor's egg. Note the mother's egg contains unhealthy mitochondria, while the donor's contains healthy mitochondria.
II. The mother's egg nucleus is retained, while the donor's nucleus is discarded. The donor egg is now enucleated, meaning it lacks a nucleus and DNA but still contains healthy mitochondria.
III. The mother's nucleus is transferred to the donor's enucleated egg cell. The egg can now be fertilized with the partner's sperm, allowing the embryo to develop with healthy mitochondria.
How Is Pronuclear Transfer Performed in Mitochondrial Donation?
Like spindle transfer, pronuclear transfer is a technique used to create embryos with healthy mitochondria from a donor egg with the genetic material from the intended mother.
What Is the “Pronucleus” in Pronuclear Transfer?
In pronuclear transfer, a “pronucleus” is transferred. The pronucleus (plural: pronuclei) is a nucleus that contains the DNA from the egg or the sperm cell. Pronuclei form after an egg is fertilized with sperm within about 24 hours:
The two pronuclei can be seen shortly after insemination, and they move toward each other to eventually unite to form the DNA of the embryo. Since these pronuclei contain the egg and sperm DNA, they can be transferred to an enucleated donor with healthy mitochondria.
Let’s look at the steps for pronuclear transfer using the diagram below:
I. In the first step, the patient's and the donor's eggs are fertilized with sperm.
II. Once fertilized, pronuclei form in each egg.
III. The pronuclei (containing both the sperm and egg DNA) are removed from the patient's and the donor's egg. The donor egg is now enucleated, meaning it lacks pronuclei and DNA but still contains healthy mitochondria.
IV. The patient's pronuclei are transferred to the enucleated donor egg. Since pronuclei have been transplanted, no further fertilization is needed, and an embryo will begin to develop.
Pronuclear transfer may be preferred over spindle transfer, as the pronuclei are less sensitive to manipulation than the spindle. Using pronuclear transfer also requires the egg to be fertilized first, and eggs that succeed in fertilizing are likely of higher quality; the technique can act as a screen for better−quality eggs.
Mitochondrial Carryover
Spindle and pronuclear transfer procedures involve transferring structures from the patient's egg into an enucleated donor egg. Some of the patient's mitochondria may be transferred to the donor egg during this process. It is called mitochondrial carryover and can lead to an embryo with mitochondria from both the patient and the donor.
It may not be much of a concern for patients with egg quality issues, but it would be a problem for patients with mitochondrial disorders. Klopstock et al. (2016) state that there are typically hundreds of thousands of mitochondria in an egg cell, and carryover may introduce a few thousand of the patient's mitochondria. Hyslop et al. (2016) showed that optimizing the pronuclear transfer technique can minimize carryover; however, it cannot guarantee that it is prevented.
Why Choose IFG for Mitochondrial Replacement Therapy?
At IFG, we are dedicated to providing top−tier medical services & personalized care. Our mission is to make patients feel valued, understood, and supported throughout their fertility journey. We take the time to listen to your concerns, answer your questions, and develop a tailored treatment plan that addresses your specific health needs.
Among our many innovative treatments, we are proud to offer Mitochondrial Replacement Therapy (MRT), a groundbreaking treatment developed to address and effectively manage mitochondrial diseases. Choose IFG, and let us help you on your journey to a brighter, healthier future!
Conclusions
Mitochondrial donation can be performed by spindle transfer or pronuclear transfer and is an effective technique to overcome issues with poor egg quality, particularly for older patients. It can also be effective for patients with mitochondrial disorders who don’t want to pass the disorder on to their children.
- In spindle transfer, the spindle (anchored to the DNA) is transferred from a patient’s egg to an enucleated donor egg (without its nucleus and DNA).
- The egg is first fertilized, then structures called pronuclei (which contain the DNA) are transferred to an enucleated donor egg during pronuclear transfer.
Nevertheless, there is a risk of the patient’s mitochondria being transferred to the donor egg (mitochondrial carryover). It may be a concern for patients with mitochondrial disorders, and it is crucial to discuss these issues with your doctor when considering the procedure.
