Complications of IVF

“Fears of complications with IVF babies dismissed in new study” is the headline in The Guardian . Research based on 1.2 million births in Norway looked at the babies of women who had conceived once by IVF and once spontaneously. It found little difference between the siblings, and concludes that the risks associated with IVF are likely to be related to existing fertility problems in the parents and not a result of techniques used during assisted fertilisation, the newspaper explains.

The Daily Telegraph also reported some of the results of this study, saying “babies conceived through IVF are much more likely to die at birth”. These results are consistent with many other studies looking at the outcome of assisted fertilisation pregnancies. The newspaper did not directly discuss the implications found in the comparison of IVF and non-IVF siblings.

This large study used complex statistical methods to try to tease out the risks related to the various factors. It is reliable and should be reassuring to women undergoing IVF. However, it is important to note that the risks of complications in an individual birth are in fact quite low (around 1% perinatal deaths in this study).

Where did the story come from?

Dr Liv Bente Romundstad from the Department of Obstetrics and Gynaecology at St Olavs University Hospital in Trondheim, and other colleagues from around Norway, UK and France, carried out the research. The study was funded by the Trondheim Hospital and the Norwegian Research Council. It was published in the peer-reviewed medical journal The Lancet .

What kind of scientific study was this?

This was a cohort study in which the researchers used data from the Medical Birth Registry of Norway. This has records of more than 2.2 million births, which occurred in Norway between 1967 and 2006. The researchers had information about pregnancy across the population as it had been recorded on standard forms by midwives or doctors within one week of delivery for all deliveries after 16 weeks gestation. This information included details about the mother’s health, antenatal and birth history, and it was linked to the “Statistics Norway” database. The researchers were able to identify outcomes for all the babies, because in Norway each baby is given a unique identification number.

From the data on 1,305,228 births from January 1984 to the end of June 2006, the researchers excluded records where there was missing data on the number of children, or if the mother was less than 20 years old or had had more than six children. Only single babies (not twins or other multiple births) who were born at 22 weeks or later, and weighed 500g or more, were assessed. After this process, they found 1,200,922 births following normal conception and 8,229 after assisted fertilisation.

First, the researchers assessed differences in birthweight, gestational age, and the chances that babies were born small for their gestational age, were born prematurely or died in the period around birth (perinatal death). They analysed the relationships between all these variables, using a model that looked at all mothers as a whole (the whole study population analysis). They also divided the mothers into groups for their year of birth, maternal age, and number of children, and assessed them separately.

After this whole study population analysis, the researchers then looked at whether the risks associated with IVF were due to the IVF technique itself or whether they were due to other factors linked to the fertility of the parents. In order to do this, they compared the health of babies born to mothers who had experienced both an assisted fertilisation (IVF) conception and a normalone. There was information for 2,546 Norwegian women available for analysis. These “sibling-relationship comparisons” looked at whether there were differences between the brothers or sisters born to women after both assisted fertilisation and normal conception. The researchers also took into account the order of conception (if IVF occurred before spontaneous conception or the other way around). They adjusted the results for maternal age, number of previous babies, sex of the baby, time between pregnancies and year of delivery.

What were the results of the study?

In the whole study population analysis, assisted-fertilisation conceptions were associated with lower average birthweight (a difference of about 25g), shorter duration of gestation (about two days), and an increased risk of babies being too small for their gestational age, or dying in the period around birth.

In the sibling-relationship comparisons, where spontaneously conceived babies were compared with their assisted-fertilisation conceived sibling, there was an average difference of only 9g in birthweight and 0.6 days in gestational age, and these differences were not statistically significant.

There was also no statistically significant difference in the rates of small-for-gestational age births and perinatal mortality when the assisted fertilisation babies were compared with the spontaneous conception babies in the sibling-relationship comparisons.

What interpretations did the researchers draw from these results?

The whole study population results, which showed that the risk of adverse events is higher with IVF, are consistent with many other studies looking at the outcome of assisted fertilisation pregnancies compared with spontaneous pregnancies.

However, looking at the babies born to women who had conceived both spontaneously and after assisted fertilisation, there was no difference in birthweight, gestational age, risk of small-for-gestational-age babies, and preterm delivery between siblings.

The researchers conclude that adverse outcomes of assisted fertilisation seen in the general population could therefore be attributable to the factors leading to infertility, rather than to factors related to the IVF technique itself.

What does the NHS Knowledge Service make of this study?

This study has successfully compared the outcomes in the babies of individual women who had become pregnant following both assisted (IVF) conception and a normal (spontaneous) conception.

• This is a novel approach made possible by the large population-based database. As a large study, it has provided reliable results. Even so, the researchers say that the study was not large enough (powered enough) to study births that occurred before 32 weeks of gestation, or to study the perinatal mortality among women who had conceived both spontaneously and after assisted fertilisation.
• It is possible that some of the conceptions were misclassified, i.e. recorded incorrectly, particularly for those women where conception occurred outside of Norway.

Overall, the study confirms that birthweight, gestational age, and risks of small-for-gestational-age infants and preterm delivery did not differ among brothers and sisters born to women who had conceived both spontaneously and after assisted fertilisation. This should provide reassurance to mothers that any adverse effects following assisted fertilisation are more likely to be due to underlying infertility than to the technology of IVF itself.

Sir Muir Gray adds...

The main complication is multiple births but IVF is standard treatment now.