IVF calculator offers hope for older women

February 26, 2012 by
Family, Health   No Comments Yet

published_sunday_telegraph

OLDER women hoping to conceive through IVF have been given new hope by research which shows age is not the key factor in the technique’s success.

Pioneering statistical work by Dr Mylene Yao, a former professor at Stanford University found that for some women it may only be the fifth most important factor – and that embryo quality and natural hormone levels are likely to be far more important. The finding is to be used to produce a simple test – revealed as a percentage – which will let couples decide whether to go ahead with IVF based on the likelihood it has if succeeding.  Fertility doctors are also developing an online version of the test. The new technique was unveiled at the Updates in Infertility Technology (UIT) conference in Budapest by Dr Yao, who said: ‘After applying a sophisticated analysis programme to factors governing IVF success, we found that a woman of 40 could have the same or better chances of having a live baby as a woman in her early thirties. This is a very important development as we want to get people away from thinking that probability is totally centred on age. The chance of a woman’s IVF treatment being successful is much more complex than that.’

Mylene Yao

Pioneering: Mylene Yao

Used in conjunction with an IVF consultant, the Univfy PredictIVF test – which takes just a few seconds to run – analyses 10-20 known factors that affect whether an IVF test will result in a successful live birth and is currently aimed at women who have had one IVF treatment already. Another test, PreIVF, uses the same methods to predict the probability of having a baby with the first IVF cycle.

The factors include maternal age – which is still, of course, important; it has long been known that women have fewer eggs of poorer quality as they grow older, with the menopause, at average age 51, marking the end of ovulation and menstruation completely.

But Dr Yao’s test measures other factors which can be measured through lifestyle questions, blood tests and more sophisticated clinical work. Some of these can be calculated immediately, such as Body Mass Index (BMI) – the patient’s ratio of weight to height, but others – such as embryo quality – can only be assessed after an initial attempt at IVF.

 

Other factors include sperm quality (the so-called ‘male factor’); levels of Anti-Mullerian Hormone (AMH), levels of which are known to fall off in tandem with declining fertility; Follicular Stimulating Hormone (FSH), which encourages the ‘ripening’ of eggs; and endometrial thickness – the lining of the womb measured on ultrasound.

The test takes into account how many embryos, produced in the first IVF cycle, turn into good quality eight-cell blastocysts, and how well they stand-up to freezing (or cryopreservation).

This is an increasingly common part of the IVF cycle, as experts attempt to change normal protocol so that it becomes more normal to store good quality embryos, which can be implanted during a woman’s natural cycle – which seems to improve chances of success – and to reduce the number of multiple embryo transplantation (and thus multiple births which are less safe for the mother and child).

But BMI was also vitally important (women who are overweight let alone obese by this measurement have reduced fertility) as was the number of eggs the mother produced under stimulation.

The test also measure the amount of hormones each woman was given; the Univfy test factors in whether the subject responds well to minimal stimulation and low doses of hormones. Says Dr Yao: ‘A woman who has five eggs after receiving higher doses of hormones has a different profile from a woman who has five eggs after receiving small doses of hormones.  If you looked only at the number of eggs, you would be missing this difference in their profiles, which may affect their probability of having a baby with IVF.’

All the data is routinely recorded at most IVF clinics already – although not necessarily collated or assessed in a holistic way.

Successful IVF is complex; we’re just trying to help women put the pieces of the jigsaw together” Dr Yao

Dr Yao hopes her new test will bring unbiased, personalised information to older women, uncertain whether to risk trying IVF, and also encourage younger women to start treatment sooner if their overall profile suggested they would have trouble conceiving.

In this respect, Dr Yao’s predictor test, is part of moves towards both more personalised IVF treatment and more patient-friendly therapies, compared to traditionally intervention-heavy medicine.

The Univfy test will be priced at about £300; and will soon be available at several clinics, including one in Europe and one in Canada.  Dr Yao’s company is currently customising prediction tests to several US clinics, and hopes to see the Univfy test in the UK soon.

‘Women should be aware that ovarian ageing occurs but does not necessarily match your chronological age,’ says Dr Yao. ‘Successful IVF is complex; we’re just trying to help women put the pieces of the jigsaw together.’

For those who cannot wait, a nine-question British test, developed by Professor Scott Nelson, Muirhead chair of reproductive and maternal medicine at the University of Glasgow, does exist online – although it is not clinic-specific nor validated – for anyone who wants to assess their chances of success. The calculator, available for free at ivfpredict.com, is based on data from more than 144,000 IVF cycles held by the Human Fertilisation and Embryology Authority (HFEA) – all the outcomes of treatments undergone between 2003 and 2007.

  • Also revealed at the Updates in Infertility Treatment (UIT) conference supported by Ferring:

Results of the five-year MEGASET clinical trial into the use of the latest GnRH antagonist-centred drug therapies such as the widely used Menopur suggested these may be easier and safer for the patient.

Prof Paul Devroey, Professor of Reproductive Medicine at the Free University of Brussels, Belgium, one of the authors of the study, said:  ‘The study shows antagonist therapies are safer and more comfortable for patients and although we implanted just one embryo – thus avoiding the risk of multiple births – we saw success rates of 40 per cent using fresh embryos.’

MEGASET, the largest clinical trial in fertility treatment underway currently (some embryos were frozen for future use, so the clinical trial is not considered over until these are used), reported that using this  type of IVF protocol resulted in greater safety, fewer interventions for patients, faster treatment and a slightly increased pregnancy rate

FACTORS that influence IVF success:

Embryo (or blastocyst) development: embryo quality is a clear sign whether fertilisation has been successful (fertilised eggs are known as embryos once cell division begins; they are known as blastocysts after they have divided into eight cells). Many clinics are now offering blastocyst transfer as it offers better pregnancy rates. Embryologists are increasingly skilled at examining these tiny cell clusters and deciding which ones are most likely to implant successfully and grow into healthy babies.

Total amount of gondatrophin: levels of the so-called pregnancy hormone, which occurs naturally, but is also boosted artificially during IVF.

Number of eight-cell embryos: traditionally, clinics have transferred embryos at Day 3 after fertilisation when cells have divided into four or six. But increasingly some consultants wait two extra days before implantation so that they can choose the best embryos which have divided into eight cells – the number produced which is potentially viable. Some embryos stop dividing at the four-cell stage, do not become blastocysts, and are not viable.

  • Embryo cryo-preservation: how well an embryo survives freezing, an increasingly common technique in IVF procedures, allowing embryos to be stored before being replaced in a natural cycle, or implanted as single transfers to reduce the risk of multiple births and improve safety considerations
  • Age of patient: egg quality and quantity naturally declines with age
  • Endometrial thickness: quality of womb lining affects successful transplantation
  • Total number of embryos: offers more chance of best quality embryos developing
  • Average number of cells per embryo:  again, an indicator of how well fertilisation has taken place
  • Body Mass Index: researchers have found that women with a BMI of 19-24 (normal weight to height) have a significantly better chance of pregnancy and that even one BMI point difference (eg 25) can hamper pregnancy chance
  • Age of spouse: sperm quality and quantity is affected by age too, with older fathers producing less motile, more damaged sperm.

Other variables including individual hormone levels such as Anti Mullerian hormone, follicle stimulating hormone, luteinising hormone and other blood markers

*An edited version of this article appeared in the Sunday Telegraph February 26 2012

Original scientific research published in PNAS

Victoria attended UIT as a guest of Ferring

About the Author

Victoria Lambert has been a journalist for more than 20 years, and specialises in health and medical matters. She writes for the Telegraph, the Times, the Sunday Times, the Guardian, the Mail and the Mail on Sunday. She contributes to Saga, Geographical and First Eleven magazines – where she is the agony aunt.

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