Authors: Dr Antoine Abu Musa (Chief Medical Officer, NOW-fertility) and Alessandra Ripanelli (Senior Fertility Nurse, NOW-fertility)
The term “ovarian reserve” refers to the number and quality of the eggs, also known as oocytes, and plays a crucial role in a woman’s ability to conceive. During fetal life the ovaries are endowed with the entire stock of follicles, which has to serve a woman’s reproductive needs for the rest of her life. As women age, the ovarian reserve naturally declines, making it more challenging to conceive.
The reduction in quality and quantity of oocytes is called low or poor ovarian reserve (POR), and is usually age related. It can however occur in younger women due to various factors, including genetics, lifestyle, and environmental.
Although for many years the declining ovarian reserve has been known as an irreversible process, recent studies on mice and pigs have shown a potential non-invasive solution to reverse the oocytes’s ageing status. Particularly, some studies have focused the attention on a molecule called Nicotinamide Mononucleotide (NMN), the most researched substance regarding ageing and ageing-related diseases.
What is Nicotinamide Mononucleotide (NMN)?
NMN is derived from Vitamin B3 (niacin) and is present naturally in food such as avocado, broccoli, cabbage, and tomatoes. NMN is a molecule that plays a central role in the production of nicotinamide adenine dinucleotide (NAD+), a coenzyme found in all living cells. NAD+ is involved in several essential cellular processes, including energy metabolism, DNA repair, and gene expression. As we age, NAD+ levels in our cells naturally decline, contributing to cellular dysfunction and age-related health issues. By the age of 50 years our NAD+ levels are about half of what they were in our 20’s. This decline is accelerated by factors such as stress, poor sleep, lack of healthy nutrition, and the use of drugs and alcohol.
Research done using cell culture, animal models and some human clinical investigations has shown that supplementing with NMN can elevate NAD+ levels, potentially mitigating some age-related health problems. The concept is that by increasing NAD+, cells may function more efficiently and repair DNA damage more effectively, which in turn could impact various age-related health pathways, extend cells’ lifespan, improve energy level, enhance metabolism and fertility.
How does this relate to fertility and egg quality?
Eggs are cells extremely vulnerable to DNA damage. In fact, abnormal DNA structures in the eggs can result in infertility, miscarriage, or birth abnormalities.
Although there are no human studies with respect to the effect of NMN on fertility yet, the limited research in mice has revealed positive outcomes. In 2020, two studies investigated the impact of NMN supplementation on various aspects of fertility and reproductive outcomes in aging female mice. Both studies demonstrated a higher ovulation rate, improved oocytes’ competency and fertilisation, better quality of the blastocysts, and an increased number of live births.
A most recent study published in 2023 suggested that NMN supplementation is beneficial for delaying the ageing process in porcine eggs. NMN significantly reduced reactive oxygen species (ROS) in senescence porcine eggs treated with NMN supplementation and increased the mitochondrial membrane potential of aged eggs compared with that of untreated eggs. Furthermore, NMN supplementation significantly increased the blastocyst formation rate, enhancing the development ability of senescence eggs during in vitro aging.
Are these supplements safe?
NMN is generally considered safe for consumption when used at recommended dosages.
However, long-term safety data in humans is limited.
Conclusion
The potential relationship between NMN, NAD+, and ovarian reserve offers an exciting area of research with the potential to impact women’s reproductive health and fertility. While preliminary studies in animals have shown promising results, it is essential to approach the topic with caution and await further research to confirm the benefits and safety of NMN to improve ovarian reserve and possibly ovarian response to hormone treatment in women undergoing assisted conception treatment.
References
NAD+ Repletion Rescues Female Fertility during Reproductive Aging. Bertoldo et al., Cell Rep. 2020 February 11; 30(6): 1670–1681
Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes.Miao Y, et al. Cell Rep. 2020.
β-Nicotinamide mononucleotide rescues the quality of aged oocytes and improves subsequent embryo development in pigs. Li et al., PLoS One 2023 Oct 5;18(10):e0291640.
Doi: 10.1371/journal.pone.0291640.
