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Transferring single embryos: Education ain't enough

23 May 2011

By Dr Alan Thornhill

Scientific Director, The London Bridge Fertility, Gynaecology and Genetics Centre

Appeared in BioNews 608
When asked why having twins isn't a good idea, I struggle. I start trotting out the party line, the obstetric risks and risks to the babies themselves, and then begin to shuffle my feet. It's complicated, I say, hoping they will move onto another topic.

The truth is, it's not that complicated at all. You just need to ask the following question: Would fewer premature or low-birthweight babies and the associated medical problems be a good thing for couples and the country? The answer is always yes and it is that straightforward.

With current technology and expertise, we can significantly reduce multiple births from IVF by simply transferring fewer embryos. This policy has worked well elsewhere, notably Scandinavia, and is now working in the UK thanks to a target set by the Human Fertilisation and Embryology Authority (HFEA) (1) to achieve a maximum of 10 percent twin births from IVF after 2012. Fertility clinics are largely compliant and we are progressing nicely.

Simple. Job done. But is it? Before we start patting ourselves on the back, there are still some unanswered questions. The tricky part of achieving any target is how to get there. So how do most of us get there? The UK's reported increases in elective Single Embryo Transfer (eSET) and subsequent decrease in multiple pregnancy have been achieved mainly by clinics using blastocyst transfer in fresh IVF cycles.

While blastocyst transfer can increase implantation rates and decrease the time to achieve live birth (particularly in younger women), it involves extended culturing of embryos. This may lead to increases in imprinting disorders (2), monozygotic twinning rates (3), pre-term birth (4) and a skew in sex ratio in favour of males (5). Some of these findings have been corroborated anecdotally by HFEA-held national data.

It's ironic that a policy to reduce the incidence of one type of twins (dizygotic - DZ) may inadvertently increase the incidence of another type (monozygotic - MZ). Furthermore, MZ twins (which result from an embryo splitting during early preimplantation development) have far worse and more frequent complications than their dizygotic counterparts - those which arise from two separate fertilised eggs. In some centres, one in 20 successful IVF cycles with blastocyst transfer may result in a monozygotic twin pregnancy. 'So blastocyst may not be all it's cracked up to be' - quips my friend. Well let's just say the jury is still out.

Health providers all agree: twins bad, monozygotic twins very bad. The problem comes when my friend follows up with a question I dread: 'If having twins is so bad - why has the limit been set at 10 percent and not five percent or even lower?' Indeed, a number of Scandinavian countries have already achieved the five percent mark without resorting to blastocyst culture and transfer.

No doubt a huge amount of discussion and evidence went into deciding on this limit (6). Perhaps the reduction in multiple births is part of a larger cost-reduction exercise since it is well established that twin pregnancy and birth costs far exceed those for singletons?

Whether or not this is the case, it is imperative that all non-IVF related procedures (such as stimulated intrauterine insemination) that result in many multiple pregnancies and births be subject to the scrutiny IVF has received. Moreover, the underlying causes of reproductive tourism, such as a shortage of donor gametes in the UK, also need to be urgently addressed. Multiple births from these sources could soon outstrip those from UK- based IVF cycles.

Considering the sector appears to be 'largely compliant', it was an interesting and perhaps bold decision by the HFEA to make the target percentage a license condition, instead of simply asking for the implementation of a multiple births minimisation strategy. The aim is, no doubt, to provide regulatory teeth but I can see challenges ahead.

There are always problems with targets and quotas. They undermine the reality of biological variation among patients, the doctor-patient relationship and the subsequent decision-making process. By introducing the new 10 percent live birth target as a license condition, there is a danger centres may feel pressurised into making poorer decisions for patients and become more paternalistic.

Indeed, fertility clinics may promote eSET to patients for whom it isn't the best option, as may have already happened in some centres where this policy has affected success rates. It may also encourage centres to inadvertently choose a cynical strategy to meet the target by selecting only younger patients for eSET while the greater risks of multiple pregnancy in older patients remain unaddressed. But the sector is largely compliant. We are on target. Mission accomplished.

The thought of targets and quotas where patient care is concerned sends a chill through most people. As my friend reminds me: 'So you have a multiple birth target and it is a good thing like the NHS attempting to reduce waiting lists'. An embarrassed silence follows. In a sector described by its own regulator as 'largely compliant', I am disappointed that the 'carrot and stick' mentality is still promoted. Punish the transgressors and reward the good. I am not sure how compliant centres are to be rewarded. That they need any more reward than safer IVF suggests that implementing eSET policy may have been more painful than expected.

While the policy to reduce multiple births is always sold on risk reduction, it is helpful to consider what many patients consider the biggest risk when they undergo IVF - failure. In the post eSET-era, it is easy to forget failure is the number one adverse outcome resulting from IVF treatment. All centres must get better at dealing with this reality both technically and in terms of emotional support for patients.

We must remember that, in an environment where most people pay for their own treatment, first-time success is a strong driving force. That, coupled with a desire for twins (to get 'two for the price of one' - as many patients put it), is why it can be difficult to convince patients to transfer a single embryo.

As Person Responsible at a licensed UK clinic, my life would be far easier knowing all patients receive the maximum information on multiple pregnancy risks and are perhaps encouraged to have eSET to meet the current target. But the provision of fertility treatment is not about making my life easier and should never be about achieving a quota (like fishing) or meeting arbitrary targets (like parking tickets). It is about helping people achieve something personal and important to them without being paternalistic.

Recently, I was asked by a senior clinical colleague to sit in on a consultation with a patient who had healthy nine-month-old twins following a successful fresh IVF cycle and was considering further treatment using her frozen blastocysts. Clearly, it was part of our job to warn her about the risks of transferring two embryos. I even played the 'what if you have quadruplets?' card. Short of begging, I don't think we could have done any more to change her mind. We didn't beg. We didn't force her. She didn't change her mind. She may well have twins.

The evidence that twin pregnancies are more risky than singleton pregnancies is not new but it has taken time for anyone in the UK to do something about it. Until both patients and providers consider a singleton birth as the optimal outcome and multiple pregnancy as an adverse outcome there will always be the potential for conflict between patients, providers, PCTs and the regulator.

For many couples, education is not sufficient – a cultural shift is required.

SOURCES & REFERENCES
Human Fertilisation and Embryology Authority (HFEA) | 13 May 2001
 
2) DeBaun MR, et al  Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19
Am J Hum Genet. 72(1):156-60 | 2003
 
3) Vitthala S, et al The risk of monozygotic twins after assisted reproductive technology: a systematic review and meta-analysis
Hum Reprod Update. 15(1):45-55 | 2009
 
4) Källén B, et al Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome?
Fertil Steril. 94(5):1680-3 | 2010
 
5) Dean et al The effect on human sex ratio at birth by assisted reproductive technology (ART) procedures--an assessment of babies born following single embryo transfers, Australia and New Zealand, 2002-2006
BJOG 117(13):1628-3 | 2010
 
6) One Child At A Time - Reducing Multiple Births After IVF
Report of the expert group on Multiple Births After IVF, Professor Peter Braude. | 2011
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

30 May 2017 - by Dr Jane Currie 
A moving love story, but a missed opportunity to explore ethical issues in IVF...
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Single embryo transfer reduces the risk of death within a month of birth for babies conceived via IVF, according to an Australian study...
16 January 2012 - by Dr Lux Fatimathas 
The transfer of one or two embryos during IVF should be dependent on the age of the mother, according to a UK study...
19 December 2011 - by Dr Rebecca Hill 
In what is now synonymous with Progress Educational Trust (PET)'s ethos, the final session of the annual conference, 'The Best Possible Start in Life: The Robust and Responsive Embryo', was a free-form debate. Following on from the previous sessions where a wealth of eminent researchers gave informative and often provocative talks, Guardian columnist Zoe Williams had the task of chairing what proved to be an entertaining debate...
03 October 2011 - by Dr Rebecca Hill 
The National Institute for Health and Clinical Excellence (NICE) has issued new guidelines saying that women pregnant with twins or triplets should be monitored more closely, receiving specialist care from a team of healthcare professionals...

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