Infertility is on the rise. Everywhere in developed countries, couples find it more and more difficult to conceive.
There are many reasons for this increase in infertility, such as:
- Rising obesity rates
- Unhealthy nutrition, like consuming insufficient amounts of B vitamins, omega-3 fatty acids, iodine, iron, and other micronutrients important for fertility
- Rising cases of endometriosis
- Hypothyroidism (a slowly functioning thyroid gland)
- Women becoming pregnant at later ages
It’s estimated that 12 percent of women in the US have problems getting pregnant.
After age 35, this has increased to one in three women.
After the age of 35, the risk of birth defects increases dramatically.
To deal with this aging-related decline in fertility, some women who want to focus on their career, or for other reasons, opt to freeze their egg cells for later, so that the egg cells accumulate less damage as the years go by (R).
There are, unfortunately, almost no efficient and safe pharmacological treatments to increase fertility. However, improving diet and lifestyle can go a long way.
Eating unhealthy foods, being overweight or (pre)diabetic increases the risk of infertility. Consuming a healthy diet improves fertility.
A (small) deficiency in important micronutrients can also increase the risk of infertility. These are nutrients like B vitamins, iodine, omega-3 fatty acids, vitamin D, iron, zinc and so on.
The book “The Fertility Diet”, written by Harvard scientists including Professor Walter Willett, goes deeper into this (R).
NMN, aging and infertility
There is a a very interesting substance that could also increase fertility: nicotinamide mononucleotide (NMN).
NMN is one of the most researched substances regarding aging and aging-related diseases.
NMN is a building block for NAD+, a molecule that enables many proteins to maintain and repair the DNA and the epigenome – the epigenome determines which genes are switched on or off (dysregulation of the epigenome plays a very important role in aging).
For example, NAD+ helps proteins like sirtuins and PARPs to repair DNA damage.
During aging, NAD+ levels decrease. This leads to cells being less able to repair and maintain their DNA and epigenome.
Especially egg cells are very vulnerable to DNA damage.
Egg cells decline precipitously with aging
Every woman is born with a finite pool of egg cells. At birth, a woman has about 1 to 2 million egg cells. At puberty, only around 300 000 egg cells remain. At age 37 women only have around 25 000 egg cells left.
The egg cells are not renewed during a woman’s lifetime, so every egg cell is as old as the woman herself. During her lifetime, egg cells become more and more genetically unstable. DNA damage accumulates, especially in the form of chromosomes that didn’t separate properly during egg cell division (because the spindle assembly checkpoint surveillance system didn’t work properly for example). This leads to chromosomal defects, which may contribute to infertility, stillbirth, or chromosomal diseases in the newborn, like Down syndrome.
NMN improves egg cell viability and fertility
NMN can help to mitigate, and even partially reverse, this and other damage in egg cells.
Professor David Sinclair, one of the most well-known longevity researchers, wrote about case reports of women taking NMN and improving not just their energy levels and metabolism, but also increasing fertility.
For example, Sinclair wrote about an elderly menopausal woman, who started to get her periods again when taking NMN (R).
Other studies already described the potential benefits of sirtuin-boosting molecules on fertility (R).
A recent study in mice showed that NMN can substantially improve fertility in old female mice.
12- to 14-month-old mice received NMN in their drinking water (fertility starts to decline in mice around 8 months). NMN improved DNA stability and reduced meiotic (cell-dividing) defects.
More specifically, NMN treatment rescued spindle assembly, which is very interesting. Normally, the spindles pull apart different chromosomes when the oocytes (egg cells) divide. Often, this process goes awry in old egg cells, leading to too many or too few chromosomes ending up in the new egg cells.
Mice that received NMN restored the quality of their egg cells, improved ovulation rate, the quality of the blastocysts (the small clumps of cells from which the embryo is formed), increased life births and litter size.
Interestingly, the low dose of NMN (0.5 g per liter of drinking water) improved fertility more than the high dose (2 g/L). Both doses improved fertility nonetheless.
Jumpstart Fertility is a company capitalizing on these insights. Jumpstart Fertility aims to use NMN and NMN-derived molecules to restore fertility in animals and humans. They had impressive results in animals, and want to expand to humans.
Jumpstart Fertility is a subsidiary of Life Biosciences, one of the biggest companies that focus on the latest technologies and insights of targeting aging.
Main source(s): NAD+ Repletion Rescues Female Fertility during Reproductive Aging, Cell, 2020 (https://www.cell.com/cell-reports/pdf/S2211-1247(20)30083-8.pdf)