The days of a one-size-fits-all approach in IVF are slipping away into history, as experts look to find better fertility treatments suited to individual patients.
The issue of multiple pregnancies
Ask most couples what they want from IVF and most of them would settle for twins. Treatment is done in one go, a ready-made family after years of heartache. But ask experts in IVF about twins, and you'll get a much different answer.
Today, all of our professional societies in reproductive medicine, as well as regulatory authorities like the Human Fertilisation and Embryology Agency (HFEA) in Britain, name twins as the most serious 'side effect' of IVF. Multiple pregnancies, they say, carry the highest risks of prematurity, low birth weight, and even defects like cerebral palsy.
A Danish review of many studies on this subject found that on average IVF twins are born three weeks before IVF singletons and have a mean birth weight 1,000 grams lower. Moreover, IVF twins have a perinatal mortality rate twice as high as IVF singletons, and substantially more are admitted to neonatal intensive care units.
So it’s also fair to say that, despite the great technological advance in IVF, there are still risks associated with treatment. In Britain, around one in five IVF and ICSI pregnancies are multiple. And, while many couples might welcome the idea – even the reality – of twins in one go, two bundles of fun can often spell double trouble before too long.
Single embryo transfer (SET)
In 2009, the HFEA set a target that IVF clinics in Britain should reduce their multiple pregnancy rate to 10% in just three years - from a current rate of around 20%. With the support of the British Fertility Society, the HFEA declared that the best way to achieve this was with a policy of single embryo transfer, or SET. If only one embryo was transferred, they reasoned, a twin pregnancy would be impossible.
In countries like Sweden and Finland, the adoption of SET policies have seen multiple pregnancy rates fall to around 10%, with no decline in overall pregnancy rates provided that spare embryos are frozen and transferred if needed in later cycles.
The emergence of mild IVF
It was out of such policies - and the recognition that IVF couples simply don't need as many eggs as was formerly believed - that the idea of mild IVF emerged. Drug doses could be lower, treatment times shorter, and the risks reduced. For although rare, there is still a real risk associated with IVF’s drug treatment. Ovarian hyperstimulation syndrome, or OHSS, happens when the ovaries over-respond to fertility drugs; mild reactions may mean nothing more than bloating and cancelled treatment, but severe cases usually require hospitalisation and careful monitoring.
It’s for these reasons – multiple pregnancy and the fear of OHSS – that interest in a mild form of IVF has grown in recent years. And the idea, now tested in studies from some of the world’s leading IVF groups, is that a package of mild IVF can reduce the multiple pregnancy rate and cut the risk of OHSS.
The IVF Lite programme
The cornerstone of the London Women’s Clinic’s IVF Lite programme is SET, but even that is not as simple as it sounds. Important studies also show that success rates in SET might not be quite as high as when two embryos are transferred, and that is not attractive to either clinics or their patients.
'Success’, however, depends on how you measure it. There’s no doubt what success means to patients – and that's a healthy baby born at minimum risk and at competitive cost. The IVF Lite package comprises a short course of low-dose fertility drugs, single embryo transfer and an outcome measured as a healthy baby delivered after a treatment course of up to three cycles. So for ‘success’, don’t think pregnancy per treatment cycle, think live birth from a course of up to three treatment cycles. Three embryos may still be transferred, but just one each time.
So the other key to all emerging mild IVF programmes is embryo freezing. Clinics still hope to get as many good quality embryos as possible, but only one will be transferred in the first cycle. The rest will be frozen for later transfers if the first is not successful. The very latest freezing technology, known as vitrification, is used which reduces embryos to a glass-like state in just a few seconds; survival rates and IVF results are excellent.
Mild IVF treatment is generally less stressful
But there's also another reason for the growing interest in mild IVF, and that's a wish to lower the stress threshold of IVF and make the whole treatment package more patient-friendly. Infertility and its treatment can be as stressful to some patients as a bereavement or divorce.
Indeed, a study in 1997 showed clearly how levels of anxiety and depression among IVF patients rise as the day of their pregnancy test approaches, and fall dramatically as soon as it's over. Similarly, a 2009 review showed a positive correlation between pre-treatment anxiety and IVF outcome, describing IVF treatment as psychologically demanding. A further 2009 study of reasons for drop-out from IVF programmes found 'treatment burden' cited by 60 per cent of female respondents, with 'relationship strain' and 'poor prognosis' a little behind. A similar study from the USA also found 'stressful organizational care' (assembly-line treatment, ever-changing staff) and 'poor patient-centred care' (lack of empathy, poor listening skills) as the main reasons for drop-out. An important Dutch study from 2007, which compared mild IVF with conventional IVF, found that fewer patients dropped out of the mild programme than from the conventional because of lower stress levels.
Gynecologist Peter Bowen-Simpkins, clinical director of the London Women’s Clinic in Swansea, points out that not every couple is suitable for mild IVF. 'That’s why we must adopt a policy of careful patient selection,' he says, 'to ensure that those joining our mild IVF programme will get the best out of it.' Because the drug doses are lower than in conventional IVF there is a risk of a poor response in some patients, with too few eggs available. 'So our initial investigations will try to assess each patient's ovarian reserve as a guide to response,' he adds.
Individualised IVF treatment
What it all comes down to, of course, is that a one-size-fits-all approach is no longer thought appropriate in IVF, but that treatments are best individualised according to each patient's medical history, age and fertility assessment. What's right for a young healthy patient having her first cycle of IVF may not be best for a woman over 35 with a record of unsuccessful IVF behind her. Mild IVF might suit the former, but not the latter. Similarly, couples whose infertility is a result of the male partner's sperm problems (and who are having ICSI) may also benefit from a mild approach.
In the Dutch clinical trial noted above, 404 IVF patients were randomised to either a mild protocol or a more conventional one. Over a 12-month study period, live birth rates were comparable in each group - 43.4 per cent for the mild strategy and 44.7 per cent for the conventional. The investigators indicated that the results justified a change of emphasis in measuring outcome - from pregnancy rates per transfer to a more relevant full-term live birth.