Mitochondria are tiny structures inside our cells that generate energy. They are crucial for powering every cell in our body, including egg cells and embryos.
This article explores how mitochondria work, their importance in producing energy, and their impact on fertility and embryonic development. We will also discuss how improving mitochondrial health can enhance reproductive outcomes.
What Are Mitochondria?
Mitochondria are tiny cellular organs, or organelles, that produce energy for all of our cells, including the egg cell and the cells of the embryo. Mitochondria have their genetic material, known as mitochondrial DNA (mtDNA), that contains essential genes for producing energy.
Using sugars from our diet and oxygen from the air we breathe, mitochondria produce a molecule called adenosine triphosphate (ATP). ATP is a kind of energy currency in the egg and can fuel all energy−requiring biochemical activities, like cell division or DNA synthesis. Mitochondria make this ATP through a series of biochemical reactions collectively known as cellular respiration. During cellular respiration, energy in the sugars from food is converted into ATP in the mitochondria, which the cell can use.
There are different stages of cellular respiration, with one called the “electron transport chain” shown below. This stage involves many key protein components embedded in the inner membrane of the mitochondria, which helps extract energy from sugars in food.
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CNX OpenStax, CC BY 4.0, via Wikimedia Commons
One of these protein components is labeled as “Q” in the diagram, which represents Coenzyme Q10 (CoQ10) – a popular supplement for infertility patients! Taking CoQ10 can improve mitochondria health because, in some cases, the egg or embryo may have insufficient or damaged CoQ10, which can prevent the mitochondria from producing the energy that the egg or embryo needs.
The Link Between Mitochondrial Health & Egg Quality
As you might imagine, the mitochondria are important for egg quality! An egg cell has about 100,000 mitochondria (Pikó and Matsumoto 1976), which are needed to help with energy−demanding processes like fertilization and cell division. These mitochondria are passed onto the embryo (the embryo’s mitochondria come from the egg – not the sperm). During the egg retrieval stage of IVF, several eggs are collected. The quality of these eggs is important for a successful IVF cycle, but what does it mean to have a “good quality” egg?
Case Studies of Mitochondrial Replacement
Generally, good−quality eggs fertilize and develop into healthy blastocysts that can implant and lead to a successful pregnancy. Not all eggs are good quality; some can have trouble fertilizing or developing into a blastocyst. Some studies have shown that embryos that stop developing or arrest have problems with their mitochondria:
- In one study (Tang et al. 2020), researchers used a mouse model for embryo arrest, where mouse embryos would stop developing at the 2−cell stage. When they replaced the mitochondria in the eggs with healthy mitochondria, the mouse embryos produced blastocysts.
- In a study with pigs, embryo arrest was reversed by injecting healthy mitochondria into eggs (Cagnone et al. 2016).
- In a 30−year−old woman with embryos arresting at the 2−cell stage, replacing the mitochondria in her eggs with healthy mitochondria allowed the embryos to develop further (Zhang et al. 2016).
Female age is also related to egg quality, and mitochondria are involved in this process!
The Impact of Aging on Mitochondria
As women get older, there's an increased risk of miscarriage (Magnus et al. 2019) and a lower chance of live birth after embryo transfer (Center for Disease Control and Prevention, 2020 National ART Summary). Discover how live birth rates decrease with age in the figure below.
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(Center for Disease Control and Prevention, 2020 National ART Summary)
With increasing age, errors or mutations can accumulate in mitochondrial DNA, and this can cause problems with mitochondrial components (Cimadomo et al., 2018). For example, a mutation in mitochondrial DNA can cause errors in CoQ10, which could prevent it from functioning normally. It could lead to reductions in the energy output of mitochondria.
Consequences of Lower Energy Levels
Additionally, some studies have shown that the number of mitochondria in eggs can decrease with age (Chan et al. 2005). Having fewer mitochondria could mean less energy produced for the egg. So, with increased age, there’s generally a reduction in the amount of energy an egg cell has. It can cause problems with how the egg develops. Egg cells need to go through a specialized type of cell division called meiosis. During meiosis, the egg separates its chromosomes (containing the DNA), so there’s half of them. This way, half of the chromosomes from an egg cell can combine with the other half in a sperm cell to make the correct number during fertilization.
Lower energy levels in the egg cell might cause errors in how the egg separates chromosomes, resulting in an egg with the wrong number of chromosomes (also known as aneuploidy). Aneuploidy is considered the leading cause of miscarriage and is tightly linked to advancing female age (Cimadomo et al. 2018).
What Can Be Done to Improve Mitochondrial Health?
Some evidence has shown that dietary supplements like CoQ10 can improve IVF success rates, although the evidence is mixed (Showell et al., 2020). An emerging technology called mitochondrial donation can also help in enhancing mitochondrial health. 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.
In 2023, researchers performed mitochondrial donation in women with infertility due to poor egg quality. These women had experienced multiple unsuccessful IVF cycles without achieving any pregnancies, and in some cases, they did not even produce an embryo suitable for transfer. After mitochondrial donation, many patients produced good−quality embryos, and 31.6% of them went on to have a live birth. Many countries have banned mitochondrial donation because of ethical concerns and a lack of data on the technique’s safety and effectiveness. However, the UK and Australia have authorized its use for patients at risk of passing on mitochondrial disorders.
Check our post to explore how mitochondrial donation is regulated: How Is Mitochondrial Donation Regulated in Different Countries?
Mitochondrial Replacement Therapy at IFG
While many people find mitochondrial replacement therapy (MRT) intimidating and unattainable, we can solve your problems and know how to help you! IFG is renowned for its highly experienced doctors and a dedicated team committed to making your experience as stress−free and comfortable as possible. We understand our clients' emotional and physical challenges and are dedicated to providing compassionate support throughout their fertility journey.
At IFG, we prioritize a transparent communication process from start to finish, so please do not hesitate to reach out with any questions. Our multilingual coordinators are available to assist with your inquiries, provide detailed information, and schedule consultations with our specialists to address all your needs. Furthermore, you may refer to our post for additional info on mitochondrial donation and its applications in various studies: Investigating Mitochondrial Donation.
Conclusions
Mitochondria produce energy for the cell by converting the energy in sugars from food into ATP. Mitochondria have their DNA that provides the instructions for making the components mitochondria need to make ATP. If there are problems with the mitochondria, the egg or embryo might not have enough energy to perform cell division or other critical functions.
Research has shown that replacing dysfunctional mitochondria in eggs with healthy ones can reverse embryonic arrest, suggesting a direct link between mitochondria health and embryo development. Decreased mitochondrial energy can lead to errors in how an egg separates its chromosomes, resulting in aneuploidy, a primary cause of miscarriage that’s closely linked with advanced female age. 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 process has not been extensively studied due to legal and ethical considerations, the existing evidence is promising.
