A study has found that "the risk of women dying during pregnancy increases more than threefold after IVF," The Daily Telegraph reported. It said researchers believe the increased risk may come from the body rejecting donated eggs or from underlying health problems that "may come to the fore during artificial conception".
This study from the Netherlands looked at all deaths potentially related to IVF, since the procedure was first used in the country in 1984. It found six out of 100,000 deaths were related to IVF treatment itself. However, no IVF treatment-related deaths have occurred there since 1997 when practices changed, so these deaths rates do not apply to IVF today. For IVF pregnancies, there were a relatively low 42.5 estimated deaths out of 100,000 women.
The estimated rate of IVF pregnancy-related deaths may have been higher when compared with women conceiving naturally, but this is not unexpected given that women receiving IVF tend to be older and therefore at greater risk of adverse pregnancy outcomes. The main value in this study is in highlighting how difficult it is to collect data on negative outcomes of IVF pregnancies. The researchers' suggestion to collect more information on IVF pregnancies seems sensible.
The study was carried out by researchers from Radboud University Nijmegen Medical Centre and other academic and medical institutions in Holland. It is not clear how the study was funded. The work was published in the (peer-reviewed) medical journal_ Human Reproduction._
The_ Telegraph_ had written a short article about this research that failed to highlight the rarity of death during pregnancy and the failure of this research to adjust for age (which is likely to confound the relationship between IVF treatment and pregnancy complications).
This was a cross-sectional study assessing all deaths ‘that may have been related to IVF in the Netherlands’. The first IVF treatment in the Netherlands was performed in 1984 and the researchers collected data on all maternal deaths between then and 2008 (the time of the study) from a variety of different sources.
The researchers explain there is no single reliable source for data relating to IVF complications in the Netherlands. As a solution, they used several sources with an aim of collecting all data on deaths that were possibly related to IVF treatment between 1984 and 2008. This included information collected by the national IVF Working Committee and involved contacting all gynaecologists in all the hospitals in the Netherlands for any mortality data relating to IVF treatment or in the pregnancy after IVF treatment. They also used data from a large cohort study called OMEGA and from the Netherlands Society of Obstetrics and Gynaecology. There was some overlap between these data sources.
Maternal deaths were defined as the death of a woman during delivery, or their death within 42 days of a termination from any cause related to (direct death) or aggravated by (indirect death) the pregnancy, but not from accidental or incidental causes.
From these data, the researchers calculated the maternal mortality rate, which was the number of direct and indirect maternal deaths for every 100,000 live births up to 42 days after termination of pregnancy. These were separated into three categories: directly related to IVF treatment, directly related to IVF pregnancy and, not known to be related to either.
In their discussion, the researchers make comparisons between the mortality rates from their study and equivalent rates in women who conceive naturally, and also the general population for women whose deaths were not related to treatment or pregnancy. These comparisons were non-statistical.
Between 1984 and 2008, there were six deaths related directly to IVF treatment and 17 related to IVF pregnancies. From these figures, and by assuming that over the study period, approximately 100,000 women would have received IVF and that about 40% of them would have got pregnant, the researchers estimate the following:
In total, the mortality rate (death from causes not related to IVF treatment or pregnancy) in the study population was 31 for every 100,000 women. This was less than half that of overall mortality for women aged 20–50 years in the general population (71.3 for every 100,000 women a year).
The researchers conclude that the better overall mortality in women receiving IVF is probably due to the ‘healthy woman effect’. This means that women receiving IVF are likely to be healthier and have a higher socio-economic status than the general population.
The increase in deaths related to IVF pregnancies is likely to be due to the high number of multiple pregnancies and the use of donor egg IVF in older women.
They say that, “the fact that only a few deaths directly related to IVF are reported in the literature whereas we observed six in the Netherlands indicates worldwide under-reporting of IVF-related mortality”. They highlight the importance of reporting all deaths related to IVF to the appropriate organisations.
This cross-sectional study determined the rate of deaths due to IVF treatment or pregnancies in the Netherlands between 1984 and 2008. The Daily Telegraph’s headline and report are potentially misleading. The news article focuses primarily on the increased risk of women’s bodies rejecting donated eggs or underlying health problems coming to the fore. However, it is a fact that women who have IVF tend to be older and are therefore at greater risk of having adverse outcomes.
Also, the report that risk of death is three times higher than natural conceptions fails to mention that the actual number of women who died of potential IVF related problems in this study remained relatively low, at only 43 for every 100,000 women who had IVF.
There are a number of important points to consider when interpreting this study and the reporting of it in the media:
The researchers clearly state that their study illustrates how difficult it is to collect data about deaths that may be related to IVF and therefore it is difficult to draw valid conclusions from it. The study's main value is that it highlights this difficulty, and the researchers’ call for better recording of this information seems sensible and would enable better monitoring of the safety of IVF.