Oocyte aging refers to the natural process by which a woman’s eggs (oocytes) age over time. This is no surprise because as we get older, so do all the cells that are born with us. Oocyte aging is the main cause of infertility for women in older age brackets.
As oocytes age, they face cellular changes that make it more difficult to conceive. These cellular changes can include:
1. DNA Damage: Over time, oocytes accumulate DNA damage, which can lead to an increased risk of chromosomal abnormalities in embryos.
2. Mitochondrial Dysfunction: Mitochondria are the energy-producing organelles in cells. Oocyte aging can result in mitochondrial dysfunction, which can affect the energy supply needed for fertilization and early embryo development.
3. Decline in Quantity and Quality: As women age, the number of viable oocytes decreases, and the remaining ones may have structural abnormalities or impaired function, reducing the chances of successful fertilization and healthy embryo development.
4. Telomere Shortening: Telomeres are protective caps at the ends of chromosomes. Oocyte aging is associated with telomere shortening, which can impact the ability of oocytes to divide properly during fertilization.
5. Cumulative Effects: These cellular changes can accumulate over time, making it more challenging for older women to conceive naturally and increasing the likelihood of pregnancy complications.
In summary, oocyte aging at the cellular level involves a range of biological changes that affect the quality, quantity, and functionality of a woman’s eggs, contributing to age-related declines in fertility and an increased risk of pregnancy-related issues.
What if we can slow down this process, and maybe reverse it a little? It is no surprise that many women in advanced age brackets suffer from infertility and turn to donor eggs as an alternative option.
At North Cyprus IVF Center, we have been focusing on pregnancy in more advanced age brackets by offering treatments such as Cytoplasmic transfer, tandem IVF cycle and IVF with donor eggs. However, we are now introducing a break-through protocol that can combat age associated decline in female fertility and improve both oocyte count and quality in women in more advanced age brackets. For many years, supplementation with DHEA, myoinositol or antioxidant support have been the mainstay for treating women with diminished ovarian function. In recent years, we have seen some benefits with the use of human growth hormone, but this has also been quite limited in its reach.
Recent advances in anti-aging research provide us with deepening knowledge about how our cells function and more specifically, why they dysfunction. At the core of cellular aging lies epigenetic changes and cellular damage over time. Cellular aging can be slowed down or even reversed to some degree with interventions that can undo the damage acquired over time. Anti-aging research currently revolves around the role of sirtuins, NAD+ and senolytics when it comes to promoting cellular health and longevity.
Sirtuins are a group of proteins (specifically, SIRT1 to SIRT7) that play a crucial role in cellular health and longevity, and they are often associated with anti-aging processes. Here’s how they function in the context of antiaging:
1. DNA Repair: Sirtuins are involved in repairing damaged DNA, which is a key factor in aging. They help to maintain the integrity of the genetic code and prevent mutations that can lead to cellular dysfunction and aging.
2. Cellular Defense: Sirtuins promote cellular defense mechanisms, such as autophagy, which is the process of removing damaged or dysfunctional cellular components. This helps maintain cellular health and functionality.
3. Gene Regulation: Sirtuins influence gene expression by modifying histones, which are proteins that package DNA. By deacetylating histones, sirtuins can switch genes on or off, regulating various processes like metabolism, inflammation, and stress response.
4. Longevity Pathways: Sirtuins are linked to pathways like the NAD+ (nicotinamide adenine dinucleotide) system, which is crucial for energy metabolism and cellular function. Activating sirtuins with compounds like resveratrol or calorie restriction can potentially extend lifespan.
5. Cellular Stress Response: Sirtuins are involved in the body’s response to various stresses, such as oxidative stress and DNA damage. By enhancing the cellular stress response, they can help protect cells from age-related damage.
In summary, sirtuins are important regulators of various cellular processes that can impact aging. Activating sirtuins through lifestyle choices or potential therapies is a promising avenue for anti-aging research, as they can help maintain cellular health and potentially extend lifespan. Animal research shows that activating sirtuins can extend the lifespan by almost 30%. However, it’s important to note that while sirtuins show substantial benefits in animal studies, their role in human aging is still an area of ongoing research.
Both animal and human clinical studies show evidence for improved oocyte count and quality in IVF treatments1,2,3 after sirtuin pathways are activated.
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme that plays a vital role in various cellular processes. NAD+ is a critical molecule in cellular processes related to energy production, DNA repair, and cell signaling. Its levels and proper regulation are essential for maintaining cellular health, and researchers are exploring ways to modulate NAD+ levels as a potential strategy for promoting longevity and combating age-related diseases.
Recent animal and human clinical studies show significant positive correlation with increased NAD+ levels (through supplementation) and improved fertility as a result of improved oocyte parameters such as count, quality and fertilization capacity4,5.
Scientific research and clinical work show a clear benefit in IVF outcomes, providing support for the claims of cellular regeneration and improved longevity that have been attributed to the activation of sirtuin-NAD+ pathways.
Building upon scientific evidence, we have designed a specific protocol for oocyte anti-aging at North Cyprus IVF Center. This protocol involves activation of sirtuins via certain lifestyle changes such as intermittent fasting as well as sirtuin activating supplements for the duration of relevant parts of oogenesis. Similarly, our protocol involves increasing cellular NAD+ levels via oral supplementation as well as IV drips prior to the IVF procedure.
This protocol is mostly suited for women in more advanced age brackets (37+) who have diminished ovarian activity or a history of failed IVF cycles due to oocyte quality. Each patient’s protocol can slightly vary depending on their ovarian assessment. Therefore, the specific supplementation protocol is provided once our physicians assess your reproductive function. As a general idea, your protocol would involve:
Resveratrol, NMN, Quercetin oral supplementation for several weeks prior to oocyte retrieval.
Glutathione and NAD+ IV infusion immediately prior to oocyte retrieval.
Feel free to contact us for more information on how we can help improve your ovarian activity!
References:
1. Okamoto, N. et al. (2022) ‘Short-term resveratrol treatment restored the quality of oocytes in aging mice’, Aging, 14(14), pp. 5628–5640. doi:10.18632/aging.204157.
2. Vo, K.C., Sato, Y. and Kawamura, K. (2023) ‘Improvement of oocyte quality through the sirt signaling pathway’, Reproductive Medicine and Biology, 22(1). doi:10.1002/rmb2.12510.
3. Iljas, J.D., Wei, Z. and Homer, H.A. (2020) ‘SIRT1 sustains female fertility by slowing age‐related decline in oocyte quality required for post‐fertilization embryo development’, Aging Cell, 19(9). doi:10.1111/acel.13204.
4. Pollard, C.-L. et al. (2022) ‘NAD+, sirtuins and parps: Enhancing oocyte developmental competence’, Journal of Reproduction and Development, 68(6), pp. 345–354. doi:10.1262/jrd.2022-052.
5. Bertoldo, M.J. et al. (2020) ‘NAD+ repletion rescues female fertility during reproductive aging’, Cell Reports, 30(6). doi:10.1016/j.celrep.2020.01.058.