Does IVF cut birth defect risk in babies with older mothers?

"Women aged 40 or over are less likely to have babies with birth defects if they conceive by IVF," the Daily Mail reports, while The Daily Telegraph says: "Older mothers have healthier babies if they conceive using IVF".

Both headlines misinterpret the results of a study that looked at births in South Australia between 14 and 30 years ago.

Researchers wanted to see which maternal factors were linked to the risk of birth defects, and how this risk compared between women who conceived naturally and those who had two types of fertility treatment: either in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).

Overall, they found there were three lifestyle factors linked to birth defects: maternal age, whether the mother was a smoker, and how many children she'd had before.

Among the smaller proportion of women who had IVF or ICSI, increasing age was not linked with birth defects with either of these individual fertility methods. However, when the researchers combined the two groups they found reduced risk of birth defects for women over 40. 

However, this finding does not prove that fertility treatment is definitely "safer" in older women and more likely to result in a healthy baby. These analyses involve smaller numbers of women and babies. There is also likely to be a complex interplay between a wide range of factors and the risk of birth defects.

You can reduce the risk of pregnancy complications by taking the recommended vitamin D and folic acid supplements and avoiding smoking, drinking alcohol and taking illegal drugs.

Where did the story come from?

The study was carried out by researchers from the University of Adelaide and the University of Melbourne.

It was funded by the National Health and Medical Research Council and the Australian Research Council.

The study was published in the peer-reviewed British Journal of Obstetrics and Gynaecology.

Both the Mail and the Telegraph's reporting may give a confusing message to older women planning a pregnancy that fertility treatment is the safer way to conceive a healthy baby after the age of 40.

The media do not present the full nature of the links and also grouped their reporting to talk of IVF being linked to reduced risk. In fact IVF was not linked with increased age at all - neither an increased or decreased risk - it was only when pooling with ICSI that a significant result was found.

What kind of research was this?

This retrospective cohort study aimed to look at the maternal factors associated with birth defects in women who either conceived naturally or had two different types of fertility treatment: in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).

IVF and ICSI are both assisted reproduction techniques. In IVF, an egg is incubated in the laboratory with many sperm, while in ICSI a single sperm is directly injected into the egg.

ICSI may be used when there are problems with the sperm that may limit the chances of conception happening "naturally" in IVF – for example, problems with how well the sperm can "swim" towards the egg.

A cohort study can look at the links between particular maternal factors, the conception method and the chances of a birth defect.

But it's likely there is a complex interaction of confounding factors associated with all these issues, meaning one has not necessarily caused the other.

What did the research involve?

The study reviewed all assisted reproduction technologies carried out in South Australia over a 16-year period from 1986 to 2002.

This was linked to data on birth outcomes from the South Australian Birth Defects Register (SABDR). The register includes a record of all live births, stillbirths, terminations, birth weight and congenital defects. Birth defects were also followed up for five years.

Maternal medical conditions, pre-existing and pregnancy-related, were reviewed in the women's medical records.

The researchers looked at the statistical link between maternal factors and birth defects, and compared this between babies either conceived naturally or by IVF and ICSI.

What were the basic results?

There were 2,211 IVF births, 1,399 ICSI births, and 301,060 naturally conceived births during the study period.

There were double the proportion of women aged 40 or over in the IVF (112, 5.1%) and ICSI (63, 4.5%) groups compared with the natural conception group (4,992, 1.7%).

The prevalence of any birth defects was 7.1% (157) in the IVF group, 9.9% (138) in the ICSI group, and 5.8% (17,408) in the natural conception group.

The researchers found several factors were associated with an increased risk of birth defects in each of the groups; including three lifestyle factors.

Age

Compared with women aged 30 to 34:

• natural conception group: age above 35 increased risk, age below 30 decreased risk
• IVF group: age below 30 increased risk, but no link for age above 35
• ICSI group: no link with any age
• However, pooling the IVF and ICSI groups found an increased risk for women below 30 and a decreased risk for women above 40"

Number of previous children or births

Compared with one previous birth:

• natural conception group: increased risk with first birth, decreased risk for two or more prior births
• IVF group: no link
• ICSI: increased risk with first birth, no link for two or more births

Smoking

• natural conception group: increased risk
• IVF and ICSI: no link

How did the researchers interpret the results?

The researchers concluded: "The usual age–birth defect relationship is reversed in births after IVF and ICSI, and the associations for other maternal factors and defects vary between IVF and ICSI." 

Conclusion

The media has rather a simplistic take on this retrospective cohort study. The study has not proven that women are more likely to have a healthier baby if they have IVF if they are over the age of 40.

The misguided headlines may prompt some women aged 40 or over to think they should seek fertility treatment to give them the best chance of having a healthy baby.

But, regardless of your age, there is no reason to consider fertility treatment if you are able to conceive naturally.

Despite the large cohort included in this study, some of the analyses only looked at small numbers – for example, the number of birth defects was small, and there was only a small number of women aged over 40 relative to the whole population.

This means it's possible that some of the links found may be down to chance, particularly as the study did not set out to explore the link with any specific factor. .

Also, having IVF over the age of 40 didn't decrease the risk of birth defects, as the media has implied – there was no significant link with increased age in the IVF group. It was only when pooling with the ICSI group that a statistical link was found.

The study also looked at data from between 14 and 30 years ago in Australia. This may not be relevant to either women in the UK or current lifestyles and medical care.

There is likely to be a complex interaction between different factors associated with the age a women has a baby, the conception method and reasons for this choice, and the risk of birth defects.

Despite careful adjustment for confounding, in a population-level observational study it is always going to be difficult to fully account for all factors.

Paternal factors are one notable exception that haven't been considered. As such, there is a high chance that confounding factors have influenced any of the links found.

Overall, the findings of this study should not be of concern to women aged over 40, many of whom go on to have healthy pregnancies without the need for fertility treatment.