Could a drug made for lung patients help older women have babies? – The Irish News
Egg-freezing 'packages', paid leave for fertility appointments and discounts for IVF: these are among the perks being offered by banks, law firms, supermarkets and other employers as a way to retain and recruit female employees.
But while this support will put fertility treatment within the reach of many more women, it won't necessarily increase their odds of motherhood.
As with natural conception, with IVF (in vitro fertilisation, where an egg is fertilised by sperm in a lab) a reduction in the number and quality of eggs means success rates fall with age.
A woman under 35 has a one-in-three chance of having a baby per round of IVF using her own eggs; by her mid-40s, the odds of success are 4 per cent.
Infertility not being able to conceive despite having regular unprotected sex for a year affects one in seven UK couples.
The emotional rollercoaster of infertility treatment was eloquently highlighted recently by actress Jennifer Aniston, who described spending years "throwing everything" at trying to become a mother.
The 54-year-old said in November last year: "It was a challenging road. I was going through IVF, drinking Chinese teas, you name it." She added that, for her, "the ship has sailed".
But scientists continue to tease out the secrets of women's reproductive health from rejuvenating ageing ovaries to preventing miscarriages to make motherhood more achievable for millions.
Here, we look at some of the most promising options.
One reason a woman's fertility falls with age is that her ovaries release eggs less regularly, starting in her 30s when she still has thousands of eggs left. Tackling this is "one of the biggest challenges in reproductive medicine", says Professor Rebecca Robker, a biomedical scientist at the University of Adelaide.
She recently led a study showing that pirfenidone, a drug used to treat lung fibrosis (where a stiffening of the lung tissue makes it difficult to breathe) can more than double the number of eggs produced by ageing ovaries.
In experiments on 12-month-old mice (equivalent to 35 years in humans), Professor Robker found ovaries become stiffer with age (they had more fibrosis). But when mice were given pirfenidone, it softened the ovaries, making them produce more eggs than untreated mice, the journal Science Advances reported last year.
Researchers believe fibrosis 'traps' eggs in the ovaries, preventing their growth and release and pirfenidone gives them room to expand and break free.
Professor Robker said: "We might anticipate that an anti-fibrosis treatment would provide a woman of advanced reproductive age a greater chance of producing any eggs, as well as a chance of producing more than one."
She hopes to start clinical trials of these drugs in future.
Could an injection of a woman's own blood make later-in-life motherhood easier to achieve?
Doctors at Lubeck University, Germany, are investigating whether platelet-rich plasma (PRP) blood processed to be extra-rich in platelets, which are cells involved in clotting and blood vessel repair can 'wake up' resting eggs in women in their late 30s and early 40s.
"Age-related infertility is one of the most pressing problems in reproductive medicine," says Georg Griesinger, a professor of reproductive medicine, leading the trial. "As IVF doctors, we frequently encounter older patients who only produce one or two oocytes [eggs] or none. The only option for these women is to use oocytes from a donor, but many want to have a child that is genetically theirs."
PRP is already used in other areas of medicine, including orthopaedics it's thought that proteins released by the platelets speed up healing of damaged tendons. Now, doctors are studying whether these proteins can also activate immature eggs, coaxing them into maturing so more eggs can be collected before IVF.
Early studies of the technique in Greece have been promising, with women who have gone through the menopause becoming pregnant after treatment.
In a new trial, 140 women will have a teaspoonful of PRP or a placebo injected into their ovaries. The number of eggs they then produce will be counted, with the first results due next year.
If the treatment is effective, it is simple enough for widespread use and could cost less than 900 a patient, says Professor Griesinger.
"Platelet-rich plasma isn't without promise," adds Grace Dugdale, a reproductive biologist and founder of preconception website Balance Fertility. "However, the results so far are mixed and there are also potential safety concerns, including whether it might increase the risk of cancer."
A new drug aims to overcome one of the main IVF hurdles: implantation failure.
In IVF, the egg is fertilised in the lab, creating an embryo, then transferred to the woman's womb.
The embryo needs to implant in the womb lining (endometrium) to continue growing. But in more than half of IVF cycles the embryo doesn't implant properly, so the woman either doesn't become pregnant or quickly miscarries. Currently, there are no drugs to improve implantation.
A new treatment from Spanish biotech company Oxolife aims to boost implantation rates by improving the structure of the endometrium and its blood supply, providing the embryo with oxygen and nutrients. In animal trials the drug, OXO-001, increased implantation rates by up to 15 per cent, according to unpublished results.
A small-scale trial on women showed the tablets were safe; they are now being trialled on 350 women undergoing IVF. The women will take either OXO-001 or placebo tablets daily before and after embryo transfer, with pregnancy rates compared.
The first results are due next month: 75 babies have already been born to women taking part in the trial, although it's not yet known how many of these took the active drug.
The company website states OXO-001 "acts directly on the endometrium to enhance and improve the embryo implantation process", although the exact mechanism is undisclosed.
"The endometrium is like a nest that receives the embryo and if that nest isn't well prepared, implantation will not take place," says Dr Agnes Arbat, a doctor and clinical pharmacologist and Oxolife's CEO. "Clinicians tell us they'd be more than happy with a 3 per cent increase in implantation rates. Based on the data we have, we're hoping for 5-7 per cent."
Grace Dugdale says: "Implantation failure is an issue in IVF there are definitely times when a good embryo inexplicably fails to implant. There are lots of causes and, while we don't know exactly how this drug works, new treatments are definitely needed."
Doctors are increasingly interested in the role of the vaginal microbiome the delicate balance of 'good' and 'bad' bacteria in the vagina in fertility. The theory is that if 'bad' bacteria overgrow, they can travel to the womb, hampering implantation chances.
A 2016 study in Denmark of IVF patients found women whose vaginal microbiomes were 'out of balance' (where harmful bacteria start to outnumber the beneficial ones) had just a 9 per cent chance of getting pregnant, compared to 44 per cent of those with normal microbiomes. (An imbalanced vaginal microbiome is very common, occurring in 20 per cent of the general population and 30 per cent of IVF patients, often without symptoms.)
Now researchers at Aarhus University Hospital in Denmark are testing whether a probiotic powder packed with 'good' bacteria can boost a woman's chances of becoming a mother. Almost 350 women with an abnormal vaginal microbiome have received the treatment with preliminary results due in weeks.
Professor Glenn Gibson, a microbiologist at Reading University, says: "This research on the vaginal microbiome is being well carried out and its results could have large implications for IVF and resulting pregnancy rates."
The ability to grow large quantities of a woman's eggs in the lab could lead to a kinder form of IVF, say Edinburgh University scientists. An early IVF step is egg stimulation (a woman injects herself daily with fertility hormones for ten to 12 days to increase the number of eggs she produces).
Side-effects include breast tenderness, bloating, nausea and mood swings, and a risk of ovarian hyperstimulation syndrome (OHSS), which causes the ovaries to swell painfully.
Up to a third of women undergoing IVF have mild OHSS; one in 100 develop moderate or severe OHSS, which is potentially fatal. The hormone injections are also expensive potentially adding 1,000 to the bill for an IVF cycle. Courses may need to be repeated. The new approach could bypass this.
"Women are born with a large store of immature eggs," says researcher Evelyn Telfer, a professor of reproductive biology at Edinburgh.
"They ovulate only 0.1 per cent of them; the other 99.9 per cent degenerate and die. We're working on a way of preserving these immature eggs and growing them outside the body."
In 2018, Edinburgh researchers became the first in the world to grow human eggs to maturity in the lab thanks to a discovery that a certain level of tension in ovarian tissue helps keep eggs in their immature state; relaxing the tissue kick-starts development. They have now started studies in sheep to check if the offspring from lab-grown eggs are healthy.
Successful animal studies could mean the first women could be treated in five to 10 years. In future, instead of undergoing the stress and expense of multiple rounds of hormone injections to produce eggs for IVF, women could have a sliver of one of their ovaries removed through keyhole surgery.
The immature eggs would then be triggered into growing in the lab, with one small piece of tissue potentially yielding thousands of eggs more than enough for their IVF needs.
Sarah Norcross, director of the fertility charity Progress Educational Trust, says: "Although this is some way off, the principle of being able to generate greater numbers of eggs is really exciting.
"Anything that reduces the grim regimen of hormone injections that women have to go through as part of IVF would be welcomed by a lot of them."
Solo dmg media
More:
Could a drug made for lung patients help older women have babies? - The Irish News