Freezing our future
Frozen ova may be the ‘bright new dawn in reproductive medicine’, writes Amanda Hooton. But we mustn’t count our chickens too soon.
Early last year, a baby was born in Melbourne as a result of assisted reproductive technology. Many people described the birth as miraculous, a word used a fair bit in this field. Even so, this one was something special.
It was the result of a frozen egg, fertilised by a frozen sperm, forming an embryo that was also frozen before being transferred to the mother. As Lyndon Hale, chairman of Melbourne IVF puts it: “that bloody kid was frozen so many times…” The ellipsis is where the miracle occurred.
On a US website, women are hoping for the same miracle. “It is a fantastic feeling to know I’ve done what I can to preserve my fertility,” writes Megan, a 36-year-old classical acupuncturist who elected to freeze her eggs until she is “emotionally and financially prepared” for motherhood.
She froze her eggs with Extend Fertility, a company founded in 2003 (by a female MBA graduate in her mid-30s, who promptly froze her own eggs). The idea behind Extend Fertility, and similar companies, is that a woman can halt her biological clock by freezing her eggs. When she decides to become a mother, she can then utilise them via normal IVF.
Marketed as “insurance” egg freezing, it sounds simple and straightforward, but is in fact complex and expensive. It costs several thousand dollars a cycle, and women must undergo lengthy periods of hormone injections to stimulate egg production. Nor is success assured.
People speak airily of egg banks, equating them with sperm banks and possessed of the same characteristics: millions of eggs, easy collection, successful storage.
In fact, there’s no such thing as an egg bank, and egg freezing, as senior research fellow at Royal Women’s Hospital Melbourne IVF Debra Gook puts it, is “extremely tricky”.
Sperm and embryo freezing have been possible since 1953 and 1983 respectively, and these days, in IVF terms, both are relatively successful. But oocyte cryopreservation, as it’s officially known, remains the least successful.
A woman is born with all the eggs she will ever have. They mature and are released throughout her reproductive life. As she gets older – from around the age of 35 – they become less viable. Thus protecting – and if necessary preserving – them is vital if she plans to be a mother.
But freezing is a hit and miss affair. The human oocyte is the largest cell in the human body, and, with its single x chromosome, one of the most fragile. “If you freeze an embyro at the four-cell stage, you can lose one cell and the others will continue,” explains Gook. “And with sperm, you’ve got so many – even if you lose half you’re still OK. But the egg, in its mature state, is quite vulnerable. And it contains a very large volume of water.
“So when you freeze it, the ice forms crystals, which are like needles that pierce the cell membrane. As soon as that happens, the cell dies.”
Because of this, IVF technology has developed within a framework in which, essentially, other things are frozen so eggs don’t have to be. Under normal circumstances, an IVF cycle will involve sometimes frozen sperm, often frozen embryos, but never frozen eggs.
Until now. In January, the Medical Journal of Australia (MJA) received a letter from seven medics at two Australian clinics, in Queensland and South Australia. It reported four live births, one ongoing pregancy, and an ectopic pregnancy following egg freezing in 13 women. For a technology that’s achieved only 200-odd births worldwide, it was an amazing result.
In New Zealand the situation is different. Women are allowed to freeze their eggs but currently those eggs cannot be thawed and used in reproduction.
Professor Sylvia Rumball, chair of New Zealand’s Advisory Committee on Assisted Reproductive Technology (Acart), is part of a team assessing what New Zealand should allow in terms of new technologies. Some procedures, such as in vitro fertilisation, are already accepted and allowed without consultation with ethics committees. But other procedures, such as thawing eggs, remain in technological limbo.
In 2005, an order effectively banning the use of frozen eggs was introduced while the committee assessed the scientific and ethical evidence behind whether permission should be granted for eggs to be thawed and used in reproduction.
The committee will give its recommendations to Health Minister Pete Hodgson by late December. A key consideration is the fact technology is changing all the time, and it is crucial to ascertain whether eggs can be frozen and thawed without damage, she says.
“Countries have to weigh up if they want to be first off the block or wait to see what evidence has been amassed by other people.”
So are we witnessing a bright new dawn in reproductive medicine? The authors of the Australian medical journal’s letter think so. Their results, they say, “suggest that oocyte cryopreservation may at last be coming of age”. If so, part of the success is certainly due to a new freezing technique known as vitrification.
Traditionally, eggs have been frozen by slowly replacing the water inside the egg with a kind of anti-freeze solution. These eggs must be rehydrated when defrosted, and as well as the risk of ice crystals this process can toughen the outer membrane of the egg, making it more difficult to fertilise.
But a new technique that uses very high concentrations of anti-freeze in an extremely quick exchange is beginning to have success. Gook estimates this snap-freezing process has only been responsible for 20 babies worldwide so far; but as it’s already successfully in use for embryo freezing, many are pinning their hopes to it.
Despite the recent advances, the chances of producing a healthy baby from a single frozen egg remain low: around 2%. Most women will undertake several transfers; but the numbers are stacked against them.
Given this reality, and the costs – both financial and emotional – many specialists believe it’s irresponsible to offer egg freezing to anyone, except as a last resort. “At this point, we would only consider assisting people who are desperate,” adds Michael Chapman, medical director of IVF Australia.
“For instance, a 25-year-old woman suffering from Hodgkins, whose treatment will render her infertile. And we’d regard the technology as experimental – we would not charge for it. We don’t believe the technology is good enough to offer it responsibly. The success rates just aren’t high enough.”
Dr Richard Fisher, medical director of Fertility Associates, which runs private clinics in New Zealand, said just one woman had become pregnant from a frozen egg process in New Zealand, but she later miscarried. The woman sought permission before the 2005 order came into effect.
His firm has frozen eggs from 14 women, some of whom had them extracted early due to cancer. Others were opposed to having embryos frozen so chose to have eggs frozen instead. A third group, of about two or three women, were in their late 30s or early 40s and wanted to preserve their eggs before their biological clock ticked too loudly.
Fisher, also a member of Acart, is keen to see New Zealand recommend the use of frozen eggs as long as it proceeds with caution. He believes there is evidence coming from countries like Japan and Italy, which have done the most research in this area, to prove there is no significant increase in risk. But concerns about risks, just as there were predicted with IVF in the 1980s, are unlikely to be alleviated for several years.
Clinics that have had successful babies born, such as Repromed in Adelaide and Melbourne IVF, are cautious about being too upbeat – doctors talk reluctantly of “a handful” of babies and “no more than 10″. What is clear is that they’ve all been very recent: the first in South Australia in 2005; two in Melbourne last year; those mentioned in the MJA, also in 2006. This fits with the international situation: the first frozen-egg baby in Canada was born in 2005; the first twins in the world in Italy only a year ago.
Nor are the women who have become mothers willing to talk. It’s known that the triple-frozen Melbourne baby was the result of a failure of sperm availability on the day of extraction but we don’t know the ratio of boys to girls; whether they’re healthy; or anything about their progress.
Lyndon Hale at Melbourne IVF is more upbeat than most, but even he’s cautious. “Based on recent successes, we do believe it to be viable,” he admits. “We would take a single woman worried about her eggs aging, yes. But we would need to see her several times; we’d need her to go through counselling. What we don’t want is for women to see it as a false hope: an insurance policy.”
Even if egg-freezing does become a lot more sucessful, it will not be problem-free, because female fertility never has been.
The Catholic church, for instance, still forbids the freezing of embryos. (This prohibition, echoed in Italian law, has ironically contributed to the development of egg freezing technology, since if embryos cannot be frozen in IVF, eggs have to be.) Pro-life and anti-technology groups, meanwhile, still insist on “natural” procreation or none at all.
But just as the contraceptive pill was reviled, so egg-freezing is often portrayed as a threat to the fabric of society. Offer women the chance to delay motherhood, cry the critics, and you will create a world filled with 50- and 60-year-old mothers; orphaned young people; shattered families.
And there is always the dilemma of affordability.
“Even if a woman said `I don’t care, I will pay for endless cycles out of my own pocket’,” says Mark Bowman, deputy medical director of Sydney IVF, “I would still have significant reservations, knowing the success rates”.
For now, at least, this seems the dominant view. So until things change, we can only hope that for the women who need them – whatever their reasons – the miracles continue.
