Vitamin May be Key to Pregnancy for Older Women
A simple vitamin supplement could boost the odds for women over the age of 35 trying to conceive safely, say researchers.
By Sharon Kirkey, Postmedia NewsSeptember 21, 2011
Canadian scientists are working on a way to make older human eggs young again — and maybe even slow menopause — experiments that could make it easier for women in their 40s and perhaps beyond to have babies.
The answer may lie in a single vitamin.
Toronto fertility doctors say their experiments in mice show that co-enzyme Q10 makes older mice produce more and healthier eggs. The doctors are now preparing to test the supplement on women 35 and older undergoing fertility treatments.
The work comes as women are pushing back motherhood ever later in life. Across Canada, pregnancies in women over 35 are increasing, and fertility clinics are seeing more women over 40. “Our mean age for patients first coming to see us is now 37,” said Dr. Robert Casper, medical director of the Toronto Centre for Advanced Reproductive Technology. Five years ago, it was 33.
Not only do older women find it more difficult to get pregnant, they run an elevated risk of miscarrying or of conceiving embryos with chromosomal abnormalities that cause conditions such as Down syndrome.
A woman is born with all the eggs she will ever have, and by the time she reaches her late 30s, the quality of those eggs begins an irreversible slide. They have less chance of leading to a normal live birth.
Eggs have 46 chromosomes to begin with, but they undergo a change when a woman ovulates. Each egg discards 23 of its own chromosomes and, if it’s fertilized, takes in 23 from the sperm cell to replace them. But this takes a lot of energy.
The energy in eggs, and essentially in all human cells, is produced by mitochondria, little power packs inside all our cells. But these weaken with age so that they don’t produce as much energy, resulting in a steady decline in tissue and organ function.
“Somebody who is 20 will have eggs with 20-year-old mitochondria in them, and somebody who’s 40 will have 40-year-old mitochondria that will produce less energy,” said Casper, professor in the division of reproductive sciences at the University of Toronto and a senior scientist at the Samuel Lunenfeld Research Institute at Toronto’s Mount Sinai Hospital.
If there isn’t enough energy to separate the chromosomes properly, some get left behind. “They don’t get pulled out,” Casper explains. Extra chromosomes can lead to aneuploidy, an abnormal number of chromosomes, the stringlike structures that carry our genetic material.
“That’s why Down syndrome increases with age — it’s all an energy issue,” Casper said. “It’s not that there is anything wrong with the eggs, it’s just that the batteries have run down.”
Casper’s team has been studying mitochondria for years, trying to understand whether it’s possible to boost energy production in human eggs. Together with Dr. Andrea Jurisicova, an associate professor in the department of obstetrics and gynecology at the University of Toronto, the researchers originally tried injecting young mitochondria into old mouse eggs, using a preparation made from cord-blood stem cells, which are fetal cells, so that the old eggs would have young, healthy mitochondria.
The technique worked — it improved the quality of the eggs and the embryos. The problem was, the embryos had two different mitochondrial DNA — essentially, two different mothers. When Canada’s Assisted Human Reproduction Act outlawed mitochondrial gene replacement in 2004, Casper’s team abandoned that avenue of research. Now they’re working on a different tack, using co-enzyme Q10. Mitochondria need co-enzyme Q10 to make energy. The vitamin is also a powerful anti-oxidant that may prevent mitochondrial DNA damage, Casper said.
Co-enzyme Q10′s production by the body also decreases as we get older, starting around age 25.
“One of the theories about why we get old and die in the first place is that our cells just run out of energy — the mitochondria stop working properly and there’s just not enough energy for cellular function so organs start to fail,” Casper said. “A simple explanation could be that there’s not enough fuel from the co-Q10 around.”
In a pilot study using 52-week old mice — mid-life for a mouse, and the equivalent of 40 to 50 for a human — Casper’s team gave half the group co-enzyme Q10, and the other half a placebo. Next they compared eggs retrieved from both groups of mice with eggs from 10-week old mice.
“What we found was that just treating the mice with co-Q10 we got more eggs when we gave them fertility drugs,” Casper said. The nuclear spindles that pull the chromosomes apart were more like those in young eggs. The litter size was bigger, and the eggs from the vitamin-treated mice had improved mitochondrial function. Even more surprising, when the researchers examined the mouse ovaries, there were significantly more egg follicles in the old mice treated with the co-Q10 — suggesting, Casper said, “that we actually were able to delay the onset of the equivalent of menopause in the mice.”
The glitch is that the mice were pre-treated for 18 weeks — the equivalent of 10 years or so relative to a human lifespan.
“We might be able to delay menopause, but it might take a decade of pre-treatment,” Casper said.
“The question is: how long do you have to give it, and can there be so much damage already in the mitochondria that it doesn’t make any difference?” Either way, it could take years of women taking the supplement to stave off menopause. “You’d probably have to have it in your cornflakes.”
The more immediate application might be in improving an older woman’s fertility by improving her egg quality.
When word got out about his early research on the Internet, women undergoing fertility treatments began taking co-enzyme Q10. Casper is now trying to recruit women over 35 for a study testing whether taking 600 mg daily of the supplement can lead to a higher number of chromosomally normal eggs.
The rub is that, as soon as the researchers explain the mouse results, none of the women want to be randomized to the placebo group, “especially if they’re 40.” “They just want to move ahead and get going,” said Casper, who will be discussing his work Thursday — in a talk entitled “Can we rejuvenate old eggs?” — at the annual meeting of the Canadian Fertility and Andrology Society, the body representing Canada’s fertility doctors. As reported by Postmedia Monday, the meeting was originally closed to the media. The board has now decided to open the meeting to reporters.
The Toronto researchers need 50 women for their study; they’re up to 25 so far, after a year-and-a-half of trying.
If the mice experiments hold up in the clinical trials, the implications would be significant, Casper said. “Women could get pregnant easier when they’re older.”
It could also buoy calls for more single-embryo transfers. For years fertility clinics have been putting three, four or more embryos back into women over 40 in the hope that at least one would implant and a baby would result.
“It’s not so much that these women get multiple pregnancies,” Casper said. “Most of them still don’t get pregnant because they don’t have any normal eggs left.
“The only strategy we have right now to try to improve the pregnancy rates in older women is to induce multiple ovulation and get more eggs to work with, so there’s more chance there will be a normal one there.”
“If we could improve the percentage of normal eggs, you wouldn’t have to put back so many embryos.”
The other hope is that, “if we can increase the energy for chromosome separation, then we could eliminate Down syndrome and other chromosomal abnormalities,” said Casper.
Almost one in five births in Canada is to a mother over the age of the 35 — an age when the risks involved with childbirth and pregnancy start to increase. Mothers older than 40 are three times more likely to develop serious pregnancy-related complications such as gestational diabetes and hypertension compared to their younger counterparts, according to a report released last week by the Canadian Institute for Health Information.
skirkey@postmedia.com
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