More and more people are delaying having children. There are many reasons why they want to put off the decision, but about one-third of couples have difficulty conceiving once the female partner is over 35. This is because women’s fertility begins to decline around that age.
But researchers in an ongoing clinical trial claim that rapamycin, a drug commonly used to prevent organ transplant failure, could potentially extend a woman’s fertility period by up to five years.
This is based on early reporting of results from a small pilot study they conducted, which has not yet been peer-reviewed.
Although it’s still too early to say whether rapamycin is the future of fertility treatment (we have to wait two years for clinical trials to be completed), there are some reasons to be optimistic about the reported findings.
Numerous studies in mice have shown that rapamycin is beneficial for many aspects of aging, including fertility.
Future fertility can begin before birth. While in the mother’s uterus, a woman’s gametes (eggs) form “primordial follicles” surrounded by specialized cells in the ovaries. Each follicle contains a single egg and remains dormant until it is available during puberty.
Even before birth, many follicles die, meaning that every woman is born with a lifetime supply of follicles, known as the “ovarian reserve.” This early establishment of ovarian reserve can affect your ability to conceive throughout your reproductive years.
During each monthly menstrual cycle, dozens of follicles are recruited (selected) and only one, the dominant follicle, releases an egg for fertilization. The other recruited follicles are broken down by the ovaries.
As women age, their ovarian reserve decreases and only a limited number of good follicles remain. At this point, some of the ovarian hormones circulating in the body decrease, and menopause begins.
The average age of menopause is 51, but this varies widely depending on a woman’s ovarian reserve. Some women experience early menopause (occurring before age 45).
About 1% of women may also experience premature menopause, which occurs before age 40. Because menopause directly affects fertility, early menopause can have serious implications on a woman’s plans to have children.
However, if we could slow down ovarian aging, we might be able to extend female fertility, and this may be something that rapamycin could achieve.
Repurposing rapamycin
Rapamycin is a bacterial compound that allows cells to survive longer in a laboratory environment.
It is often used in organ transplant patients to weaken the immune system so that they don’t reject the new organ, and it is also used to treat certain vascular diseases by slowing cell growth (such as in tumors).
Increasing evidence suggests that rapamycin may also have an effect against aging.
Studies in mice have shown it can help prevent age-related muscle loss, and daily administration of rapamycin has been shown to extend the lifespan of elderly mice by 10%.
With regard to fertility, studies have demonstrated that daily administration of rapamycin to mice delays ovarian aging and menopause.
Older female mice fed a diet containing rapamycin had an increased pool of primordial follicles, or ovarian reserve.
Moreover, these mice continued to have offspring, suggesting that rapamycin may delay early menopause in women.
But does the drug have the same effect in humans? That’s what the research team set out to investigate. They recruited 50 peri-menopausal women, aged 35 to 45, into a pilot study.
The women received either rapamycin or a placebo every week for three months, and their ovarian reserve was monitored with transvaginal ultrasound and several blood tests to detect various ovarian hormones.
Researchers claim that the initial results are very promising, suggesting that the drug has the potential to reduce ovarian aging in women by 20 percent without any side effects, which they hope could mean an extra five years of fertility.
Rapamycin may cause this positive effect by limiting the number of primordial follicles that are recruited and activated per menstrual cycle.
Women who received rapamycin formed only 15 follicles per menstrual cycle, compared with 50 in women of the same age. Fewer follicles appear to prolong ovarian reserve.
Previous studies in mice have shown that rapamycin may reduce the number of follicles and preserve ovarian reserve.
Maintaining fertility
The initial cohort size of the study was fairly small, but given what the researchers claim are promising results, they will likely move forward with the next phase of the experiment, which will involve recruiting 1,000 women.
Hopefully, the initial results will be confirmed again and peer-reviewed studies will show that rapamycin is an effective treatment for ovarian aging. Additional studies will then be needed to investigate whether this fertility extension occurs.
However, if rapamycin is shown to be beneficial in clinical trials, it could be useful for women with low ovarian reserve and those wishing to extend their fertility period.
Furthermore, this research highlights the potential for existing medicines to be repurposed to treat other conditions for women’s health and wellbeing, which is something that myself and my team members are doing at the University of Central Lancashire.
We are currently studying in cells whether repurposing commonly used diabetes medications can improve the uterus to make it easier for an embryo to implant, and we are also investigating these targets to treat ovarian cancer.
Stéphane Berneau, Lecturer in Pharmacy, University of Central Lancashire
This article is republished from The Conversation under a Creative Commons license. Read the original article.