No area of medicine has advanced more rapidly, nor created more controversy, than the treatment of infertility.
In the 32 years since the birth of Louise Brown, the world's first test-tube baby, at Oldham General Hospital, Lancashire, enormous strides have been taken to help the millions of couples devastated by the discovery that they are unable to have a family.
Just last week, one of the pioneers of IVF, Professor Robert Edwards, received the 2010 Nobel Prize for Medicine for his ground-breaking work in treating infertility.
Yet in vitro fertilisation remains the preserve of the privileged few - because of its cost. The UK's National Health Service has never provided the three cycles of treatment that the National Institute of Clinical Excellence says it should; yesterday, a primary-care trust in Essex stopped all IVF treatment until 2011 in an attempt to curb its overspend.
Private treatment, meanwhile, costs from £3000 to £10,000 (NZ$6270 - $20,900) a cycle, and often several cycles are required. It is estimated that only one in five of those who need treatment with IVF receive it in the West, and fewer than one in 100 in the developing world.
After three decades which have seen the progressive refinement of hi-tech methods to help people reproduce, including sperm injection directly into the egg, embryo selection to avoid disease, and egg-freezing to postpone motherhood, the biggest revolution in IVF, arguably, is still to come - slashing the cost of treatment and making it available to all.
Experts believe this is already possible. The argument is that much of what is done in standard IVF is overkill - dosing women with powerful drugs to induce ovulation and using hi-tech equipment to maximise the chances of success.
Louise Brown was born from an egg produced in her mother's natural monthly cycle, extracted and fertilised in the laboratory. Nowadays, women have two to three weeks of expensive hormone injections to induce the development of multiple eggs which are then collected and fertilised. These injections can cause side effects, severe in some cases, and add substantially to the costs. The embryos are incubated for several days and then one or two are selected for replacement in the womb, while the remainder are frozen for later use in case the initial attempt fails, again adding to the costs.
An alternative, low-impact form of IVF based on generic drugs and simple equipment might have a lower success rate, but could cost as little as €200 euros (NZ$367) a cycle, excluding staff costs, and could be repeated because it is less toxic. But efforts to test it have run into difficulties. Existing IVF clinics in the West have been reluctant to co-operate - apparently because they fear it may undermine their business.
Professor Ian Cooke, education director of the International Federation of Fertility Societies and a founder member of the Low Cost IVF Foundation, says: "Most clinics in the private sector see this as competition. Usually, when we speak about it they respond with derision. I have been saying for two years that until we have data no one is going to believe us. The problem is getting it."
The Low Cost IVF Foundation, based in Massagno, Switzerland, was the brainchild of IVF pioneer Alan Trounson, now president of the California Institute of Regenerative Medicine.
Together with Professor Cooke and two other IVF specialists from Italy and Australia, who each invested US$12,500 (NZ$16,435) to establish the foundation, they set out to prove that their concept could work.
Professor Trounson says: "IVF was a gigantic step. We didn't realise it at the time; people didn't think it would work that well. We never envisaged that it would expand so dramatically around the world. Probably the major development in the field will come from something we've never thought about. I think there will be a further expansion of low-cost IVF, especially for women in developing countries who experience social discrimination with infertility. If you remove all the expensive stuff and use low-cost drugs and remove just one or two eggs, and only transfer one embryo, it can be done."
Pilot studies to test the low-cost protocol have been run in three clinics in Melbourne, Stockholm and Bologna, involving 100 cycles each. Professor Cooke estimates they yielded a birth rate per cycle of around a 12 per cent, but the numbers are small and the results have never been published.
On the basis of these figures, low-cost IVF appears far inferior to standard treatment, which has a success rate, currently, two to three times as high. That accounts for the derision of the private clinics. But comparing a complete course of treatment under the two regimes, rather than single cycles, dramatically alters the picture.
Professor Cooke points to the physical and psychological trauma caused by standard IVF, which depends on powerful drugs to stimulate the ovaries, takes months to recover from, and has a 50 per cent drop-out rate.
"That is an increasing concern," he says.
Adopting a low-cost, low-impact approach - using less toxic drugs so that recovery is quicker and patients can repeat the treatment within a month rather than having to wait three or four months before trying again - could result in a comparable take-home-baby rate.
"If you had three cycles of low-cost IVF, it is quite likely it would have the same outcome as one cycle of standard high-cost IVF," he says.
But they have to prove it. To do so they have turned to the developing world, where the need is even greater.
"If the technique can be demonstrated convincingly in the developing world, my prediction is it will come back to the developed world. That would have a huge impact on the provision of IVF over here," says Professor Cooke.
It is often thought that excess fertility is the problem in regions such as sub-Saharan Africa, given its high birth rate. However, this conceals the much bigger problem of infertility caused by untreated sexually transmitted diseases, botched abortions and pelvic infections contracted post-delivery. As many as seven out of 10 consultations for gynaecological problems in the developing world have infertility as their underlying problem.
Moreover, the social consequences of infertility are even more devastating than in the West. Infertile women may be stigmatised and excluded from social rituals such as baptism, initiation ceremonies and marriage. Womanhood is defined by motherhood in some regions, and infertile women can be seen as cursed and deprived of all social status. The stigma even extends beyond death - in some communities childless women are buried in separate graveyards.
The foundation established projects in Khartoum in Sudan, Cape Town in South Africa, and Arusha in Tanzania, but each one has run into problems. In Khartoum a key staff member left unexpectedly, and in Cape Town the local ethics committee after deliberating for three years declined to approve the project, on the grounds it would be too difficult to organise.
In Arusha, the first run of cases yielded a few pregnancies, but patients were turning up with much worse conditions than expected, including intra-uterine adhesions, fibroids and similar problems, suggesting problems with patient selection.
The difficulty of establishing projects where there had been no provision before was much greater than they had realised, Professor Cooke admits. So the foundation has adopted a new strategy - grafting low-cost facilities onto existing IVF clinics, where they can piggyback on an established set-up. They are now targeting clinics in India, Uganda, Indonesia, Ethiopia and Tunisia, and have had expressions of interest from another dozen in other countries.
In parallel to the work of the foundation, a task force has been established by the European Society of Human Reproduction and Embryology, which is aiming to set up a similar programme in Cairo, Egypt, in Paraguay, South America and in sub-Saharan Africa.
A third organisation, the International Society for Mild Approaches in Assisted Reproduction (ISMAAR), is also promoting a safer, cheaper approach to treatment, to reduce its impact on women and extend its availability.
A 2007 study found that natural-cycle IVF (without drugs), like that which led to the birth of Louise Brown, had a 43 per cent cumulative pregnancy rate over a year - equivalent to that of standard IVF but without the risks or the adverse impact on the woman.
Geeta Nargund, president of ISMAAR and head of reproductive medicine at St George's Hospital, Tooting, south-west London, says that the "adoption of high-stimulation ovulation induction regimens" had set back research into reproduction and infertility by several decades.
"One of the key reasons for the lack of public funding for IVF is its cost and complexity and the risk of side effects. Reducing cost has to be a key objective. There is no equality of access for people to IVF. That equality has to be achieved, or only the rich will be able to reproduce," she says.
The charity ISMAAR is now promoting its approach in the countries of Francophone Africa, with a series of workshops for doctors to highlight the benefits of natural-cycle and "low-drug" treatment.
"If we can make it happen in the developing world, we can make it happen in the developed world: a safer, softer and affordable treatment," says Dr Nargund.
The biggest saving is on the cost of drugs. In standard IVF, clinics in the West routinely dose women with powerful, genetically engineered forms of follicle-stimulating hormone (FSH) so they release up to a dozen eggs per cycle. The eggs are fertilised in the laboratory, and some embryos can then be frozen and retained for use if the first round of IVF doesn't work. But the drugs are very expensive, costing up to €1000 a cycle.
The low-cost alternative is clomiphene, a generic drug which causes the pituitary gland to pump out extra FSH, producing up to four eggs per cycle. It carries a price tag of just €12. There is also a saving on freezing and storing extra embryos; if another attempt is required the process can be repeated with fresh eggs and embryos because the drugs are less toxic.
Cheaper incubators or warm-water baths will be used to keep the embryos at the requisite temperature until they are ready for transfer to the womb. It may be possible to avoid the use of incubators altogether. One company has designed a device to make use of a natural incubator - the woman herself.
The INVO cell, made by a company in Beverly, Massachusetts, is a small plastic capsule into which embryos are placed in culture and the capsule, encased in a protective shell, is then placed inside the woman's vagina for three days. After removal, doctors select the best one or two embryos for transfer to the woman's womb. Not only does the device cut the cost of IVF, but it is also suitable for places where there are frequent disruptions to the electricity supply.
Further savings can be made by eliminating the use of carbon dioxide, used to maintain the acid-alkali balance of the culture medium, but less important if the embryos are cultured for only one or two days. Equipment such as microscopes and ultrasound machines, which are often more sophisticated than necessary in Western clinics, can also be supplied in simpler versions, more cheaply.
Professor Cooke says: "Currently, in most of the developing world we are probably offering conventional IVF to one per cent of the population. If we can get that up to 30 per cent that would be a huge improvement.
"If we are able to do it cheaply and tolerably efficiently, the consequences would be enormous. A lot of people would say, 'I understand there is a lower take-home-baby rate, but I can do that because it is so much cheaper and has less impact'."
He adds: "Low-cost IVF is better for the woman, the eggs are genetically superior, and there is a lower incidence of chromosomal abnormality. There is a lot to be said for it. It is getting the mechanism to make it happen that is the difficulty. We need to know if it can be implemented in different environments. The NHS ought to be interested in this. That is why it is worth continuing with."