Mitochondrial donation is a technique used to replace faulty mitochondria in an egg cell with healthy mitochondria from a donor. It is increasingly used to prevent mitochondrial disease transmission but is also being investigated to improve egg quality. It could be beneficial for older patients with lower−quality eggs. In this article, we will look at some of the evidence for mitochondrial donation in improving egg quality.
What Is Mitochondrial Donation?
Mitochondria are tiny cellular organs, or organelles, that produce energy for the cell. With increasing age, these mitochondria can become dysfunctional and produce less energy, leading to embryos that stop developing.
One way to overcome this is by using a technique called 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. You can read more about mitochondrial donation & its different methods, like pronuclear transfer and spindle transfer, in our blog post:
How Is Mitochondrial Donation Performed?
What Research Has Been Done Using Mitochondrial Donation?
Despite its potential, mitochondrial donation is not extensively researched due to restrictive laws in many countries, where it is a form of genetic modification. In nations like the UK and Australia, where it is legal, its use is restricted to individuals with mitochondrial disorders and not to those with poor egg quality.
Early Experiments with Mitochondrial Donation
Experiments with mitochondrial donation were performed in 2009 in non−human primates to prevent the transmission of mitochondrial disorders. In this study, four healthy macaques were born using a type of mitochondrial donation called spindle transfer. These macaques showed normal health and development over three years of follow−up.
In 2010, researchers performed a different type of mitochondrial donation called pronuclear transfer using human fertilized eggs, resulting in embryos that developed to the blastocyst stage. Two distinct research teams used the spindle transfer method of mitochondrial donation on human eggs in 2013, which developed to the blastocyst stage (Paull et al. 2013; Tachibana et al. 2013).
The First Mitochondrial Donation Baby
Despite the limited evidence for the safety and effectiveness of mitochondrial donation, the world’s first mitochondrial donation baby was born in 2016, involving a woman who had the inheritable mitochondrial disorder Leigh syndrome that led to the death of her first two children. John Zhang, with the New Hope Fertility Center, created embryos in the US and then sent them to Mexico to be transferred to avoid US regulations. This work was published in 2017 with more details.
Zhang's team used the spindle transfer technique on five donor eggs, resulting in four blastocysts, and were tested by preimplantation genetic testing for aneuploidy (PGT−A). A euploid embryo was transferred, and a healthy baby boy was born, with genetic testing showing that there was about 6% of the mother's mitochondrial DNA detectable in the baby. This carryover was the spindle transfer technique result, and the researchers expected that the low levels would not result in any health problems in the child. No further follow−up was performed.
Zhang and his team performed another round of mitochondrial donation in a 2016 study. In this case, they used the technique to overcome embryo arrest, in which all the patient’s embryos consistently stopped developing at the 2−cell stage. After pronuclear transfer, five embryos progressed to the 4−cell stage. The patient transferred all five embryos and conceived triplets. Following a fetal reduction procedure for twins, both babies were unfortunately lost due to complications at 24 and 29 weeks. Genetic analysis showed that the fetuses were euploid and contained mitochondria from the donor.
Recent Advances in Mitochondrial Donation
In 2023, researchers performed a pilot study involving spindle transfer in 25 women with infertility due to poor egg quality. Before mitochondrial donation, these women had an average of 6.4 ovarian stimulation cycles without any pregnancies, with nine patients never even having an embryo that could be transferred.
After mitochondrial donation, these patients produced 53 good−quality embryos, with 24 − euploid. Overall, there was a 36.8% clinical pregnancy rate after transfer and a live birth rate of 31.6%. Six babies were born, which were all healthy, with one baby showing significant maternal mitochondrial carryover.
What Does the Future of Mitochondrial Donation Look Like?
- In 2015, the UK became the first country in the world to license clinics to perform mitochondrial donation for this purpose. The Newcastle Fertility Centre was the first to receive this license, and a trial is ongoing to investigate the safety and effectiveness of the technique. The first live births were reported in 2023, with no further details provided due to privacy concerns.
- In 2022, Australia passed legislation permitting mitochondrial donation for those with mitochondrial disorders. In 2023, Australia launched the mitoHOPE pilot program to perform a five−year clinical trial on mitochondrial donation.
Depending on the results of these trials, other countries may follow in regulating mitochondrial donation. For instance, Singapore issued a report in 2021 stating that it would wait for additional evidence on mitochondrial donation before allowing its use. Refer to our blog post to read further about this topic: How Is Mitochondrial Donation Regulated in Different Countries?
IFG: Your Trusted Partner in ART
With years of experience in the field, IFG has assisted numerous international families worldwide. Our global perspective and cultural sensitivity enable us to provide a welcoming and supportive environment for all our patients, regardless of their backgrounds. We understand the unique challenges and strive to make their fertility journey as smooth and stress−free as possible. Moreover, we are particularly proud to offer Mitochondrial Donation, a pioneering treatment designed to address and effectively manage mitochondrial diseases.
Our team of specialists holds memberships and certifications from prestigious organizations such as the American Society for Reproductive Medicine (ASRM), the European Society of Human Reproduction and Embryology (ESHRE), and the Israeli Medical Association (IMA), ensuring that we stay at the forefront of advancements in fertility treatment. Choose IFG and experience the difference our specialized services and experienced team can make in your fertility journey!
Conclusions
Mitochondrial donation may be an effective technique to overcome issues of poor egg quality and can help prevent the transmission of mitochondrial disorders. Although the technique has not been extensively studied due to legal and ethical concerns, the existing evidence is promising.
Different studies have shown that mitochondrial donation can help manage embryo arrest and lead to the development of good−quality embryos, some of which are euploid after PGT−A. Based on limited evidence, babies born from mitochondrial donation appear to be healthy, although in some cases, there is significant maternal mitochondrial carryover. While this is mainly a concern for patients with mitochondrial disorders, it is vital to discuss the risks of this technique with your doctor.
