Somewhere in a freezer at a Melbourne fertility clinic, sits something that belongs to six-year-old Stella Davis.
It was removed from her when she was a toddler, while she was undergoing intensive chemotherapy for a germ cell cancer that was refusing to go away.
The tissue sample, taken from one of Stella’s ovaries, is of no use to her now. And it might not be for decades to come, if ever.
But it represents hope.
There is a risk that Stella may not be able to have children of her own in the future, because of the multiple rounds of chemotherapy she had to endure after the discovery of a large tumour on her tail bone.
In response, doctors at the Royal Children’s Hospital in Melbourne offered her parents the option of preserving some of her ovarian tissue.
Stella’s mother Lara MacEwen said making the decision to preserve her daughter’s ovarian tissue was an easy one.
“I’m very realistic,” she said.
“We know that there isn’t a 100 per cent chance that it is going to work, but you have to be hopeful, and science and technology is progressing so fast.
“Who knows where we will be in 15 years or so?”
One might assume that any parent of a child in Stella’s situation would do all they could to help their child.
But the issue is more fraught than it appears, success with tissue from young children is unproven and could rely on technology that does not yet exist.
The topic has been recently investigated by University of Melbourne bioethicist Rosalind McDougall and her colleagues, who found that for many children the removal of reproductive tissue was ethically permissible, but not ethically required – which meant the decision was up to parents.
“Even though the surgery to collect the tissue is quite straightforward, the techniques of using the tissue are still being developed,” Dr McDougall said.
“[In cases where doctors believe] it is going to be medically safe for a child, it is appropriate to offer the procedure but because of the speculative nature of the future benefit we think it is justifiable for parents to go forward with the procedure – or decide not to.”
Although 80 per cent of paediatric cancer patients now survive their illness, 16 per cent of girls will be left infertile and treatment can also deplete boy’s sperm.
The Royal Children’s Hospital has, since 2013, been routinely offering the fertility preservation procedure for appropriate patients, with tissue samples taken from 100 girls and 40 boys.
These cases were guided by an ethical framework, which asks clinicians to consider questions such as whether the child has already received treatment that may have damaged the tissue, whether the procedure could delay cancer treatment and if parents realised that the procedure would not guarantee future fertility.
The process sees ovarian or testicular tissue taken from young cancer patients and frozen in a process of “cryopreserving”, in the hope that by the time the children are grown, medical technology will have advanced to allow the tissue to be used to create a baby.
In girls, it is thought the harvested tissue may be replanted when the patient is ready to have children.
Royal Children’s Hospital paediatric oncologist Professor Michael Sullivan said it was also conceivable that eggs could one day be recovered from the frozen ovarian tissue.
Professor Sullivan said that globally there had been at least 100 births using cryopreserved ovarian tissue, but only one report of a live birth from tissue that was removed before the girl hit puberty.
“That’s because tissue has only been stored for a relatively short time,” he said.
The technology is less advanced when it comes to boys. It is estimated that births relying on testicular tissue for sperm “may be decades away”.
Women who are overweight or obese and planning to get pregnant should be encouraged to reduce their weight, experts say, as new research shows an increasing proportion of poor health outcomes for mothers and their children are linked to excessive weight during pregnancy.
Researchers at the University of Sydney examined more than 40,000 pregnant women over a 25-year period and found the prevalence of overweight and obese first-time mothers had increased and the number of women within a normal body mass index (BMI) range had fallen.
At the same time, the proportion of poor health outcomes attributable to excessive weight during pregnancy had steadily increased.
“This includes maternal complications such as pre-eclampsia, gestational diabetes and caesarean birth, as well as complications for the baby, including being large for gestational age,” said senior author Kirsten Black.
Associate Professor Black said previous efforts to reduce the risks of maternal obesity in pregnant women had failed, and that obesity prevention strategies needed to target women prior to getting pregnant.
“The sentiment from nutritionists and obstetricians is that the greatest impact on adverse outcomes will occur if women lose weight before they get pregnant,” she said.
Dropping one weight class would improve health outcomes
Researchers analysed the BMIs, demographic characteristics and health outcomes around the time of birth of 42,582 first-time mothers at Sydney’s Royal Prince Alfred Hospital between 1990 and 2014.
“We were interested in looking at how the trends had changed over time in obesity, and to what extent that was impacting on a range of adverse health outcomes,” Associate Professor Black said.
They found the number of women who were overweight increased from 12.7 to 16.4 per cent; the prevalence of obesity rose from 4.8 to 7.3 per cent, while the proportion of women in a normal BMI range fell from 73.5 to 68.2 per cent.
“As a consequence of that, we saw a rise in a whole range of adverse outcomes such as caesarean sections, prematurity, gestational diabetes, stillbirths, foetal abnormality, pre-eclampsia and foetal macrosomia [larger than average baby],” Associate Professor Black said.
A substantial number of those outcomes could have been avoided with obesity prevention strategies that reduce pre-pregnancy weight, she said.
“Were overweight and obese women to have moved down one BMI category during 2010 to 2014, 19 per cent of pre-eclampsia, 15.9 per cent of foetal macrosomia, 14.2 per cent of gestational diabetes, and 8.5 per cent of caesarean deliveries … could have been averted,” the authors wrote.
Pre-conception health is key
Once women are already pregnant it may be too late to reduce the risks of maternal obesity, Associate Professor Black said.
“There have been a number of studies that have tried to alter the impact of obesity on adverse outcomes in women who are already pregnant, so instituting things like exercise and dietary changes,” she said.
“But the results have been disappointing in all those trials… so it’s important women optimise their health before pregnancy.”
In addition to population-wide strategies to reduce obesity, the gynaecologist said health professionals needed to get better at having “healthy conversations” with people about their weight.
“There are a range of conditions for which women should be advised on around pregnancy … so we need to also ensure that there is greater access to pre-conception care.”
Painkiller taken by mother in first three months of pregnancy could potentially reduce child’s number of eggs, say researchers.
Ibuprofen taken by women in their first three months of pregnancy might reduce a daughter’s number of eggs, potentially affecting the child’s future fertility, according to research carried out on human cells in the lab.
Previous work in rodents has suggested that painkillers including ibuprofen might affect the ovaries and hence fertility, while recent research in men has linked prolonged high doses of ibuprofen to disruption of male sex hormones. Up to 30% of women are thought to take ibuprofen during pregnancy.
“We know that fertility rates have declined over recent years, and essentially we are looking for a potential reason why that might be the case,” said Rod Mitchell, co-author of the research from the University of Edinburgh. “Because it is a relatively recent decline, it is felt that environmental factors [including painkillers] in addition to societal factors might have a role to play.”
Writing in the journal Human Reproduction, Mitchell and colleagues from France and Denmark report how they examined the impact of ibuprofen on developing ovaries using ovarian tissue taken from 185 terminated human foetuses aged between seven and 12 weeks.
In the first step of the study, the team analysed blood taken from the umbilical cords of 13 of the foetuses whose mothers had taken ibuprofen in the hours before termination, to reveal that ibuprofen did indeed cross the placental barrier.
For each of the 185 foetuses, tissue was then cultured under multiple conditions, with one sample exposed to no ibuprofen and others bathed in various concentrations of the drug in a dish, reflecting concentrations that would circulate in humans.
After seven days, compared to samples not exposed to ibuprofen, those bathed in the painkiller at a concentration on a par with the cord blood levels had an average of 50% fewer ovarian cells, and between 50 and 75% fewer “germ cells” – cells that develop into eggs. This was down to an increase in cell death and fewer cells multiplying.
Further experiments showed that the damage began as early as two days after exposure to the ibuprofen for foetuses aged 8–12 weeks. After a five day recovery period for a subset of the samples, only a partial recovery from the effects of the ibuprofen was observed, but only germ cells appeared to bounce back.
But Mitchell cautions that the situation in the body might differ from that in a dish, that it is not clear what level of germ cell loss would be tolerated before fertility is affected, or whether the ovaries could more fully recover over a longer period.
“If we see effects on germ cells, which we do in the dish, that could indicate that there are potential for effects in ‘real life’ and potential for effects on fertility – but we haven’t shown or proved that by what we have done [in this study],” he said.
William Colledge, professor of reproductive physiology at the University of Cambridge, who was not involved in the research, said the study was interesting since it looked at a period in which women might not realise they were pregnant. But he had reservations.
“It is a big step to go from something that happens in the petri dish to saying, well, that definitely may happen in a pregnant woman – although it shows that we could be cautious,” he said, adding that the number of germ cells in the ovaries naturally declines from a peak of about three million mid-pregnancy. “At best [women] are only releasing one [egg] each month. So you can cope with the loss of quite a lot of these eggs,” he said.
Menopause. It’s a condition that affects millions of women, and it involves some pretty significant changes — as well as symptoms.
Here are a few answers to some of the most common questions about menopause.
What is menopause, and when does this usually happen?
Menopause is defined as not having your period for 12 months — a change that signifies the end of all monthly menstrual cycles you will experience. It happens when sex hormones like estrogen and progesterone begin to decrease.
According to the Mayo Clinic, a non-profit organization that focuses on clinical practice, education and research, menopause may occur in your 40s and 50s, but the average age in the United States is 51.
What are the symptoms of menopause?
The following symptoms can occur during the years leading up to menopause, according to the Mayo Clinic:
Weight gain and slowed metabolism
Thinning hair and dry skin
Loss of breast fullness
What is perimenopause?
Perimenopause, or the “transition to menopause,” refers to the years leading up to menopause when the reproductive function starts to slow down. Irregular periods are common, and many of the other symptoms may resemble those seen in menopause. According to the North American Menopause Society, a nonprofit organization based in Ohio, this transition may last an average of four to eight years. Importantly, pregnancy is still possible during perimenopause.
What is premature or early menopause?
Early menopause occurs before the age of 40. There could be a number of reasons, including genetic or autoimmune causes.
I keep hearing about hot flashes … What are those?
Hot flashes are experienced by the majority of women going through menopause. Changes in hormone levels –- specifically estrogen — can cause the blood vessels in the skin to dilate, leading to sweating, rapid heart rate and flushing/redness of the face. Hot flashes can be associated with mood changes and other symptoms.
When a hot flash is occurring, there can be a feeling of intense heat in the face, neck, or other parts of the body. Although skin temperature may briefly change during this time, there is no change in core temperature.
What can I do to make menopause easier? Are there any treatments?
Menopause treatments focus mainly on helping to manage symptoms. Your doctor will be able to explain the risks and benefits of different therapies.
Hormone therapy: Estrogen, usually in combination with progesterone
Selective estrogen receptor modulators (SERMs)
Vaginal estrogen: used to relieve vaginal dryness Antidepressants: to help with mood symptoms
Vitamin D: to maintain bone density (strength)
What is the treatment for a hot flash?
Daily exercise, limiting triggers, and sleeping in a comfortable environment can all help to prevent or reduce the duration of a hot flash. If none of these options work, women can speak to their physician about starting a variety of treatment options, ranging from over the counter products to antidepressants and hormone replacement therapy (HRT).
Will there be any long term health consequences?
The change in hormone levels that occur during menopause may lead to increases in risk for heart disease, stroke, or osteoporosis. There may be additional health issues that come up as well so routine follow-up and screening with a physician are recommended.
A study has cast doubt on a popular fertility test that claims to predict the probability of falling pregnant.
Ovarian reserve testing involves a blood test to measure levels of the anti-Müllerian hormone, which is secreted by cells in developing egg sacs. Women who have less ovarian reserve are considered to be closer to menopause.
These so-called “egg-timer tests” have become more popular in recent years, as some women delay having children to pursue careers or until they’re in a stable relationship.
But a recent study in the peer-reviewed Journal of the American Medical Association found AMH testing is not an indicator of natural fertility. Researchers found a lower ovarian reserve was not associated with the ability to conceive among some women.
The study looked at women aged 30-44, with no history of infertility and who had been trying to conceive for three months or less.
Melbourne IVF medical director Dr Lyndon Hale, whose clinic offers AMH testing, says the method helps to determine whether IVF might be difficult for a particular woman. But it does not predict the likelihood of natural conception.
“I’ve seen a lady with very low AMH and after a month off the pill she was pregnant. It [AMH level] doesn’t tell me anything about the quality of the oocytes (eggs) remaining,” Dr Hale told The New Daily.
“However, I knew if she did IVF she would only ever get a small number of eggs.”
As women age, their remaining eggs start to decline in number and quality.
Dr Hale says AMH testing should be used alongside other clinical considerations, including menstrual cycles and age.
Professor Robert Norman, a reproductive and infertility expert from the University of Adelaide, says the best predictor of fertility is age.
“Age is everything – your optimal fertility is between 20 and 34,” he says.
According to Jean Hailes for Women’s Health, fertility starts to decline after age 28, significantly after 35 and dramatically after 40.
Professor Norman said the JAMA finding did not surprise him. But he believes AMH testing is here to stay.
The test started as part of IVF procedures, but is increasingly being marketed as a standalone fertility prediction tool, he says.
“It’s a test that’s going to be popular among women and their partners,” he says.
“It may make a difference between someone deciding, ‘I’m going to have a child when I’m 30, versus when I’m 37’. It’s a piece of information that could help people get pregnant naturally and avoid IVF, rather than driving them to it.”
How much does it cost?
In Australia, AMH testing generally ranges from $50-$100 per blood test.
The cost of follow-up procedures – such as freezing eggs or IVF – can run into six figures.
If you are having trouble conceiving, a fertility specialist might:
Check for genetic or medical conditions (such as diabetes)
Check medication or substance use
Conduct an immunisation review
Order a blood test to check for hormone changes
Test your partner’s sperm count
Increasing natural fertility
Manage stress and take the time to relax
Reduce alcohol and caffeine intake
Source: Jean Hailes for Women’s Health
For a complete and individual fertility assessment, speak to your GP or specialist.
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