Decline in multiple birth rate from IVF

“Birth rates for IVF twins and triplets have begun to fall in line with government targets aimed at reducing health risks caused by multiple pregnancies,”_ The Guardian_ reported.

The news is based on the publication of figures by the Human Fertilisation and Embryology Authority (HFEA), demonstrating that attempts to reduce the number of multiple births – considered to be the single biggest risk of fertility treatment – is on target. The HFEA is encouraging IVF clinics to transfer only a single embryo to the uterus at a time. The target for January 2009 to March 2010 was that no more than 24% of live births from assisted reproduction techniques should be multiple births.

The rate of multiple pregnancies is also falling and the rate of single embryo transfer increasing. Importantly, the overall rate of successful pregnancy has been consistent. Each year the boundary level is reduced, and the most recent target set last month aims for a multiple birth rate of 15% by March next year.

Why were these targets made?

Before the decision was made to reduce the number of multiple pregnancies, IVF usually involved transplanting more than one embryo into the uterus at a time to maximise the chances of a successful pregnancy. However, multiple pregnancies and births are associated with greater risks for both baby and mother.

In 2007, the HFEA introduced a policy to promote the transfer of only a single embryo to the uterus, and started to collect data on the rate of single embryo transfer to the uterus (eSET) across the estimated 50,000 fertility procedures performed every year in the UK. The HFEA policy is part of a wider national initiative to reduce the number of multiple births resulting from fertility treatment, which has involved various professional bodies, patient groups and NHS funding bodies.

Prior to 2009, there was no maximum target rate of multiple pregnancies that could result from fertility treatment. The first target level was set in 2009/2010, which required that fertility clinics have a rate of no more than 24% multiple births from assisted reproduction techniques. For 2010/2011, the target was lowered again to 20%, and now, in April 2011 the target has been set to 15%, which UK clinics are expected to meet by this time next year. The ultimate aim is a multiple birth rate of no more than 10% each year.

What are the risks of multiple pregnancies?

Jane Denton, Director of the Multiple Births Foundation, was quoted by the HFEA saying, ‘There is no doubt that a multiple pregnancy creates risks for both mother and babies.’

It is a well-established fact that multiple pregnancy and multiple birth carry a higher risk than single pregnancy. These include an increased risk:

of miscarriage and other pregnancy complications
of prematurity and low birth weight
of neonatal mortality: HFEA quote 19 deaths within the first month of life for every 1,000 live births for multiple babies, compared to three deaths for every 1,000 live births for single babies
of cerebral palsy: HFEA quote 6.2 cases for every 1,000 live births for twins compared to 1.7 cases for every 1,000 live births for single babies
of the newborns requiring special neonatal care
to the mother of pregnancy-induced high blood pressure (hypertension) and pre-eclampsia, pregnancy diabetes, assisted or interventional delivery (for example, a caesarean), and mortality

By how much has the rate of multiple births dropped?

The 2011 report, ‘Improving outcomes for fertility patients: multiple births’ sets out data on the rate of single embryo transfer and multiple births since 2008, when figures were first collected. The main findings are:

In 2008, only 4.8% of embryo transfers were elective single embryo transfers (eSET) and the rate of multiple pregnancy was 26.7%.
Between 2008 and mid-2009, multiple births fell from 23.6% of live births to 22%.
In the first half of 2010, the rate of eSET had increased to 14.7%, and multiple pregnancies was 22%.
Concern had been expressed that a reduction in multiple births, brought about by an increase in eSET, might negatively impact on pregnancy and live birth. However, these rates have remained largely unchanged since the introduction of the targets. The overall pregnancy rate for all ages was 26.5% in 2008, 31.4% in 2009, and 31.3% in 2010. The live birth rate for each cycle started was 23.7% in 2008 and 23.6% in the first three months of 2009.
The largest fall in multiple pregnancy rates has been among women aged 18-35 years old: in 2008, the rate of eSET was 6.8% and the rate of multiple pregnancies was 31.2%; in 2010, the rate of eSET had increased to 22.1% and multiple pregnancies had fallen to 23.9%.

The HFEA’s 2011 assessment of the data from the past three years also shows that:

The vast majority of women who receive eSET (87.3%) are aged 37 or under and around two-thirds of all women who receive IVF fall into this age bracket.
67.3% of women receiving eSET were on their first cycle of IVF, 17.1% on their second and 15.6% on three or more (most clinics focus their eSET strategies on the woman’s first IVF attempt).
Women who received eSET in a fresh cycle in 2009 had, on average, seven embryos available, and 59.6% of women who received eSET froze one or two of their unused embryos, which is in line with professional guidance.
The majority of women (81.5%) who had an early multiple pregnancy (two or more fetal heartbeats detected on the ultrasound) went on to have a multiple live births. Almost a fifth (18.5%) lost one or more fetuses and gave birth to only one live baby. Of women with an early multiple pregnancy who suffered a miscarriage, around a third of them lost all of the fetuses, resulting in no live births.

What changes have been made to reduce the rate of multiple pregnancies?

As the HFEA says, multiple births are a risk of IVF but an avoidable one. The HFEA restricts the number of embryos that can be transferred in a treatment cycle of IVF to a maximum of two in women aged under 40; and three for women aged 40 and over who are using their own eggs. This is reported to have effectively reduced triplet births, though the proportion of twin births remains high.

The key priority of the new targets was to transfer just one embryo in women who are most likely to get pregnant and are therefore most at risk of a multiple birth. This mostly applies to ‘younger women’.

The HFEA say that since the introduction of the targets there has been marked changes in clinical practice with an increase in elective single embryo transfers, particularly in women under 35. It has resulted in this age group having the greatest drop in multiple pregnancies.

It is recognised that eSET would not be suitable for everyone, and as the HFEA highlight, every person needs to be treated as an individual. Careful selection of women who are most likely to have a good outcome from eSET, while taking into account fresh and subsequent frozen embryo transfers, can help to maintain overall live birth rates while minimising multiple births. Professional bodies recommend that younger women with three or more good quality embryos qualify for eSET.

Practically, the report finds that the stage of development the embryo has reached when it is transferred can influence the risk of having a multiple pregnancy. The risk of multiple pregnancy is almost completely eliminated if only one embryo is transferred, and will only occur if the embryo splits in two (resulting in identical twins, a rate of about 1.64%, standard for all conceptions).

In cycles where more than one embryo is transferred, the transferral of two blastocyst stage embryos (which have been grown in the laboratory for five to six days after fertilisation) is more likely to result in a multiple pregnancy than the transferral of two cleavage stage embryos (which have been grown for only two to three days).

Blastocyst transfer is said to be relatively new in the UK and until recently, most embryos were transferred in the cleavage stage. There has been an increase in the rate of blastocyst transfers from 8.4% in January 2008, to 27.6% in June 2010. However, in line with current targets, there has been an increase in proportion of these that are single blastocyst transfers (eSET) rather than double transfers (DET).

Almost three-quarters of women who currently undergo blastocyst transfers are 37 years of age or under. The report noted that most cycles use the woman’s fresh eggs and transfer a fresh embryo. Frozen cycles are more likely to involve DET.

What happens now?

As the HFEA says, it is promising news that the rate of multiple pregnancies and multiple births has fallen while the rate of transfer of single embryos has increased. Importantly, this has been achieved while maintaining the rate of overall pregnancy and live birth rates. However, the HFEA says that figures could still be improved as the rate of double embryo transfer is still higher than it should be.

The most recent target was set by the HFEA last month. By April 2012, it is hoped that there will be a rate of no more than 15% multiple pregnancies as a result of fertility treatment. The HFEA has an ultimate aim of a multiple birth rate of not more than 10% each year. Monitoring of the outcomes of fertility treatment will continue.

Where can I get more information?

The One at a time website is a professionally led site aimed at reducing the number of multiple births from assisted reproduction. It provides the public with information on the risk of multiple births, their options, and information about bringing up twins and triplets, including the accounts of other parents.

The site aims to promote best practice among health professionals with access to guidelines (Elective Single Embryo Transfer: Guidelines for Practice British Fertility Society and Association of Clinical Embryologists, 2008). There is also HFEA information on targets and information from other professional bodies. It also aims to provide clinics with the tools to change their clinical practice.