Nordic IVF outcomes improving - is the same true for the UK?

"The health of artificially conceived children has steadily improved in the last 20 years," The Guardian reports. Researchers who analysed data from Nordic countries described the decline in premature and stillbirths as "remarkable".

This was the main finding of a large cohort study comparing the health of babies born using assisted reproduction technology (ART), such as in vitro fertilisation (IVF), with those conceived naturally over the last 20 years.

They found big improvements over time in a number of areas, including reductions in the number of miscarriages and babies born prematurely or with a low birth weight. All of these can be complications of multiple births (twins, triplets, or sometimes more).

The study looked at ART in Norway, Sweden, Denmark and Finland, and it is unclear whether we could expect to see similar improvements in the UK.

While it is likely we share similar advances in technology and improved protocols with Nordic countries, there may be other important differences as a result of eligibility for treatment.

In some Nordic countries, eligibility for reproductive treatment has been extended to include couples with less severe fertility problems. This may have accounted for some of the improvements seen over the years.

The most recent UK data from 2013 (PDF, 2.54Mb) reports the ART multiple birth rate has fallen from 25% in 2008 to 16% in 2013. This would suggest a potentially similar improvement in UK outcomes for ART.

Where did the story come from?

The study was carried out by researchers from universities based in Denmark, Norway, Sweden and Finland.

It was funded by the European Society of Human Reproduction and Embryology, the University of Copenhagen, the Nordic Federation of Societies of Obstetrics and Gynecology, and the Danish Agency for Science, Technology and Innovation.
 
The study was published in the peer-reviewed medical journal Human Reproduction. The article was published on an open-access basis, meaning anyone can view it and download it for free.

Generally, The Guardian and the Mail Online reported the study accurately, though neither made it clear in their headlines this was actually research involving Nordic countries and not the UK.

What kind of research was this?

This was a population-based cohort study looking at the health outcomes of babies born through assisted reproductive technology over the last 20 years.

Assisted reproductive technology (ART) is a catch-all term for a number of techniques that can help parents to conceive and have a baby. Two of the most common are IVF and intra-cytoplasmic sperm injection (ICSI).

In IVF, a woman's eggs are removed from her ovaries by a doctor and cultured with many sperm in a laboratory. This allows fertilisation to take place "naturally", but outside the body.

If embryos develop, one, or sometimes two or three (depending on circumstances), are transferred to the woman's uterus to grow and develop into a baby.

Intra-cytoplasmic sperm injection (ICSI) differs from IVF in that a specialist selects a single sperm to be injected directly into an egg, instead of fertilisation taking place in a dish, where many sperm are placed near an egg.  

The study also included people who have had frozen embryo transfer. After IVF, a couple may have a number of unused (non-transferred) embryos. They can freeze them for use in later treatment cycles or for other purposes, such as donation.

What did the research involve?

The researchers analysed the health outcomes shortly after birth of 62,379 single babies and 29,758 twins born by ART between 1988 and 2007 in Sweden, Norway, Denmark and Finland.

They compared babies born through ART (IVF, ICSI or frozen embryo transfer) with a control group of 362,215 babies conceived naturally.

Twins conceived after ART were compared with all naturally conceived twins (n=122, 763) born in the Nordic countries during the study period.

The rates of several adverse health outcomes were stratified into the time periods 1988-92, 1993-97, 1998-2002 and 2003-07 to assess possible changes over time.

Babies born though ART were matched to naturally conceived babies according to parity (whether they were born as a single baby, twins, triplets or higher multiples) and year of birth.

Adverse outcomes they were looking at included:

• low birth weight – defined as birth weight less than 2,500g
• very low birth weight – less than 1,500g
• preterm birth – defined as birth before 37 weeks of development
• very preterm birth – birth before 32 weeks of development
• small for gestational age – less than two standard deviations
• large for gestational age – more than two standard deviations calculated using Marsal's formula
• stillbirth – defined in this study as death of the infant after more than 28 weeks of development (in the UK it is above 24 weeks)
• infant death – death of the infant in the first year of life

Statistical analysis adjusted for parity, year of birth, and country of birth.

What were the basic results?

For singletons conceived after ART, a decline in the risk of being born preterm and very preterm was observed.

The proportion of ART singletons born with a low and very low birth weight also decreased.

The stillbirth and infant death rates declined among both ART singletons and twins.

Throughout the 20-year period, fewer ART twins were stillborn or died during the first year of life compared with spontaneously conceived twins.

The researchers thought this was "presumably due to the lower proportion of monozygotic [identical] twins among the ART twins".

How did the researchers interpret the results?

Discussing the wider implications of their findings, the team says that, "It is assuring that data from four countries confirm an overall improvement over time in the perinatal [around the time of birth] outcomes of children conceived after ART.

"Furthermore, data show the beneficial effect of single embryo transfer, not only in regard to lowering the rate of multiples, but also concerning the health of singletons."

Conclusion

This study found an improvement in health outcomes around the time of birth for babies conceived using artificial reproductive technology (IVF, ICSI and frozen embryo transfer) over the last 20 years in four Nordic countries (Norway, Sweden, Denmark and Finland). 

The study sample was large and the methods robust. This means we can be relatively confident these results paint an accurate picture of what is going on in these countries.

But two questions remain: are similar results found in the UK, and what is behind the improvement?

On the first question, it is difficult to say without having direct UK data. The Nordic countries are famous for having highly developed and supportive healthcare systems, which may include differences in specific ART techniques and follow-up care.

Each country is also likely to have different eligibility criteria that must be met to receive ART. These differences could influence whether improvements in ART would be seen across other countries.

The bottom line is we can't be sure the same situation is happening in the UK based on this study. We need solid information from the UK system itself.

There are a number of possible explanations for what caused the improvements. The most important reason, the research team said, was the dramatic decline in multiple births due to elective single embryo transfer.

In IVF, there is the option of implanting a single embryo into the mother, or more than one. During the study, the rate of twin births was reduced by one-third. Twin births are much more likely when implanting more than one embryo. Some research has associated double embryo transfer with an increased risk of preterm birth and perinatal mortality in ART children.

The improvements may also reflect a change in the people who were undergoing ART. The study authors, for example, say previously only couples with severe fertility problems would be eligible to undergo ART treatment, whereas in recent years this has been extended to allow less severe cases.

ART may be less likely to be successful and may result in poorer birth outcomes in more severe cases (depending on the nature of the problem).

Refinement of clinical and laboratory skills also may have had a positive impact on the outcomes of the children.

But there has been a similar decline in multiple births through ART in the UK, dropping from one in four in 2008 to around one in six in 2012. This would suggest the quality of ART services in the UK are moving in the right direction.