More and more people are waiting longer to have children. While there are many reasons why people may want to put off that decision, about a third of couples will have difficulty getting pregnant if the woman is over 35. This is because women’s fertility begins to decline around that age.
But researchers in an ongoing clinical trial say rapamycin, a drug commonly used to prevent organ transplant failure, could extend a woman’s childbearing years by up to five years. This is based on early reporting of results from the small pilot study they conducted, which has not yet been peer-reviewed.
Although it is still too early to say whether rapamycin It could be the future of fertility treatments (we’ll have to wait two years for the clinical trial to be completed), but there are reasons to be optimistic about the results they have reported.
Numerous studies in mice have shown that rapamycin is beneficial for many aspects of aging, including fertility.
Future fertility can originate before birth. While in the mother’s womb, 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 even before birth. This means that every woman is born with all the follicles she will ever have. This is known as “ovarian reserve.” This early-established ovarian reserve can affect a woman’s ability to become pregnant during 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 broken down by the ovary. As a woman ages, her ovarian reserve decreases until she only has a limited number of good quality follicles left. At this point, some of the ovarian hormones circulating in her body decrease, starting menopause.
The average age of menopause is 51, although it can vary greatly from woman to woman depending on her ovarian reserve. Some women experience early menopause (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 impact a woman’s parenting plans.
But if it were possible to delay ovarian aging, a woman’s fertility could be prolonged, something that rapamycin could achieve.
Repurposing rapamycin
Rapamycin is a bacterial compound that allows cells to survive longer in the laboratory. It is commonly used in organ transplant patients to weaken their immune system and prevent the body from rejecting the new organ. It is also used to treat certain vascular conditions by slowing cell growth (such as tumors).
There is increasing evidence that rapamycin may also have benefits in treating aging.
Research in mice shows that it can counteract age-related muscle loss. A daily dose of rapamycin has also been shown to improve the life expectancy of older mice by 10 percent.
In terms of fertility, studies have shown that a daily dose of rapamycin delays ovarian aging and menopause in mice. Older female mice given a diet containing rapamycin experienced an increase in their reserve of primordial follicles (the ovarian reserve).
Furthermore, 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 do the same in humans? This is what one research team has set out to investigate. The team recruited 50 women aged between 35 and 45, who were in perimenopause, for their pilot study.
For three months, the women received 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 initial results were very encouraging: they suggest the drug could reduce ovarian ageing by 20 per cent in women without side effects. The researchers hope this could mean five extra years of fertility.
Rapamycin may trigger this positive effect by restricting the number of primordial follicles that are 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 less follicle 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 have achieved, this means they will now be able to move on to the next phase of their experiment: recruiting 1,000 women.
The initial results are expected to be confirmed again and prove that rapamycin is a useful treatment for ovarian aging in a peer-reviewed study. Further studies will then be needed to investigate whether this fertility is prolonged.
But if the clinical trial shows that rapamycin is beneficial, this could help women with low ovarian reserve and those hoping to prolong their fertility.
Furthermore, this study highlights the potential for repurposing existing drugs to treat other conditions that affect women’s health and wellbeing. This is something that members of my team and I are also doing at the University of Central Lancashire. We are currently investigating in cells whether repurposing commonly used diabetes drugs can improve the uterus and facilitate embryo implantation. We are also investigating these targets to treat ovarian cancer.
First uploaded on: 27-07-2024 at 20:30 IST
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