More and more people are waiting longer to have children. While there are many reasons why people may want to delay this decision, around a third of couples will have difficulty conceiving if the female partner is over 35. This is because women’s fertility begins to decline at this age.
But researchers in an ongoing clinical trial say rapamycin, a drug commonly used to prevent organ transplant failure, could extend a woman’s fertile years by up to five years.
These results are based on early reporting of the results of the small pilot study they conducted, which has not yet been peer-reviewed.
While it’s still too early to tell whether rapamycin could be the future of fertility treatments – it’s now two years before the clinical trial is completed – there are reasons to be optimistic about the results they’ve reported.
Numerous studies in mice have shown that rapamycin is beneficial for many aspects of aging, including fertility.
Future fertility can occur before birth. In the mother’s uterus, female gametes (eggs) surrounded by specialized cells in the ovaries form “primordial follicles.” Each follicle contains a single egg that enters a dormant state until it is recruited for use at puberty.
Many follicles die before birth. This means that every woman is born with all the follicles she will ever have. This is called the “ovarian reserve.” This early ovarian reserve can affect a person’s ability to become pregnant throughout her reproductive years.
During each menstrual cycle, several dozen follicles will be recruited (selected) – but only one dominant follicle will release its egg to be fertilized. The other recruited follicles will be degraded by the ovary.
As a woman ages, her ovarian reserve diminishes until she has only a limited number of good quality follicles left. At this point, some of the ovarian hormones circulating in her body decrease, triggering menopause.
The average age of menopause is 51, although this age can vary considerably from woman to woman depending on her ovarian reserve. Some women experience early menopause (occurring before age 45).
About 1% of women may even experience premature menopause, which occurs before age 40. Since menopause directly affects fertility, early menopause could seriously affect a woman’s plans to have children.
But if it were possible to delay the aging of the ovaries, it could prolong a woman’s fertility. That’s what rapamycin could do.
Reuse of rapamycin
Rapamycin is a bacterial compound that allows cells to survive longer in the laboratory.
It is commonly used in patients who have had an organ transplant to weaken their immune system so that the body does not reject the new organ. It is also used to treat certain vascular diseases by slowing cell growth (such as tumors).
There is growing evidence that rapamycin may also have beneficial effects on aging.
Research in mice shows that rapamycin can counteract age-related muscle loss. A daily dose of rapamycin has also been shown to improve the lifespan of older mice by 10%.
Regarding fertility, studies have shown that a daily dose of rapamycin delays ovarian aging and menopause in mice.
Older female mice fed a diet containing rapamycin had an increase in their supply of primordial follicles (the ovarian reserve).
Additionally, these mice also had successful litters later in life, suggesting that rapamycin may have the potential to delay premature menopause in women.
But can the drug have the same effect in humans? That’s what a research team set out to find out. They recruited 50 perimenopausal women aged 35 to 45 for their pilot study.
For three months, the women received either a weekly dose of rapamycin or a placebo. Ovarian reserve was monitored by transvaginal ultrasound and several blood tests to detect various ovarian hormones.
Researchers say early results are very encouraging: they suggest the drug could reduce ovarian ageing by 20% in women without side effects. Researchers hope this could translate into five extra years of fertility.
Rapamycin may trigger this positive effect by limiting the number of primordial follicles recruited and activated per menstrual cycle.
In women receiving rapamycin, only 15 follicles were recruited per menstrual cycle, compared with 50 in women of the same age. With lower follicular recruitment, ovarian reserve appears to be prolonged.
Previous research in mice has shown that rapamycin recruits fewer follicles, which may preserve ovarian reserve.
Maintain fertility
The initial study cohort size was quite small. But given the promising results the researchers say they’ve seen, it means they can now move on to the next phase of their experiment: recruiting 1,000 women.
Hopefully the initial results will be confirmed again and show that rapamycin is a useful treatment for ovarian aging in a peer-reviewed study. Further studies will then be needed to determine whether this fertility is prolonged.
But if the clinical trial shows that rapamycin is beneficial, it could help women with low ovarian reserve and those hoping to prolong their fertility.
Additionally, this study highlights the potential for repurposing existing drugs to treat other conditions affecting women’s health and wellbeing. This is also something that my team and I are doing at the University of Central Lancashire.
We are currently studying in cells whether repurposing commonly used diabetes drugs can improve the uterus and facilitate embryo implantation. We are also studying these targets to treat ovarian cancer.
Stéphane Berneau, Lecturer, School of Pharmacy and Biomedical Sciences, University of Central Lancashire
This article is republished from The Conversation under a Creative Commons license. Read the original article.