"A new study has found that women who undergo IVF have a higher risk of experiencing blood clots and pulmonary embolism while they are pregnant," ITV News has reported.
These findings come from a Swedish study that looked at over 20,000 women who gave birth after conceiving through IVF, and compared them to over 100,000 similarly aged women who gave birth at around the same time having conceived naturally. It found that blood clots in the veins and in the lungs were more common during pregnancy in women who had conceived through IVF, particularly in the first trimester.
The chances of getting a blood clot were relatively low. This increase in risk seen in women with IVF pregnancies was equivalent to about an extra 17 cases of blood clots (thrombosis) in the veins and an extra two cases of blood clots in the lungs (pulmonary embolism) per 10,000 women who received IVF.
This study’s strengths are its large size and the comparability of the two groups in terms of their ages and when they gave birth. Its limitations include only reporting on women who had live births, and the inability to pinpoint exactly why women in the IVF group may have higher risks.
This study is sure to prompt further research into the link.
In the interim, it is hoped that awareness of the increase in risk in women who are pregnant after IVF could help doctors diagnose the condition more rapidly.
Where did the story come from?
The study was carried out by researchers from the Karolinska Institute in Sweden and was funded through agreements between the Institute, Stockholm County Council and the Swedish Research Council. The study was published in the peer-reviewed British Medical Journal.
The Daily Mail helpfully included a description of the low absolute increase in risk of lung clots, which helps to put the findings in context: in the study, the rate of pulmonary embolism was around 8 per 10,000 women who received IVF, compared with 6 per 10,000 who conceived naturally – an increase of 2 per 10,000 women.
In percentage terms, women with a natural pregnancy had a 0.06% chance of having a pulmonary embolism and women with an IVF-assisted pregnancy had a 0.08% chance.
What kind of research was this?
This was a cross sectional study comparing the rates of blood clots in pregnant women who conceived through IVF with those in women who conceived naturally.
The researchers note that the risk of blood clots is known to increase during natural pregnancies.
Studies on the risk of blood clots in IVF pregnancies have had varied findings, suggesting either no difference compared to natural pregnancies, or an increase in risk in the first trimester (first 12 weeks).
The researchers say that no studies have looked specifically at clots in the lungs (pulmonary embolism), and that they are a major cause of maternal death in the developed world.
This type of study can tell us how common an event is in one group, and whether it differs in another group, however, it does not explain to us why there is a difference.
For example, differences in rates between the groups of women in this study might be due to their IVF treatment, but could also be due to other differences between the groups of women.
The researchers tried to reduce this possibility by matching the women in the two groups for the factors that could affect blood clot risk.
What did the research involve?
The researchers used national records to identify 23,498 women who had given birth between 1990 and 2008 after conceiving through IVF. Their average age was 33 years.
About 17% of these women had multiple births, which is a more common occurrence in IVF pregnancies when more than one embryo is transferred. For each of these women they then selected up to five women who were of a similar age when they gave birth at around the same time but who had conceived naturally.
This gave them a control group of 116,960 women with natural pregnancies.
The researchers obtained information about the women’s characteristics from various national registries. They used patient registries to identify whether any of these women had experienced a blood clot in a vein (venous thromboembolism or VTE) or a blood clot in the lungs (pulmonary embolism or PE – usually a consequence of a VTE) between 1987 and 2008. They split the time period into the time before, during, and up to one year after their pregnancy.
The researchers then compared these rates between the two groups of women. They also compared how common blood clots were in each trimester of the women’s pregnancies. They took into account factors known to be associated with risk of blood clots including the women’s ages, body mass indices (BMIs), smoking, multiple birth and other factors.
What were the basic results?
There was no difference in blood clot risk in the two groups of women before their pregnancies, or in the year after delivery.
The researchers found that more women who conceived by IVF had blood clots in their veins (VTE) during pregnancy than women who conceived naturally. Out of every 10,000 women with IVF pregnancies, 42 had a VTE compared to 25 out of every 10,000 with natural pregnancies.
When separated by trimester, the increase was greatest in the first trimester.
In the first trimester, 15 out of every 10,000 women with IVF pregnancies had a VTE, compared to three out of every 10,000 women with natural pregnancies. In the second (around weeks 13 to 27) and third trimesters (28 weeks onwards), the difference between the groups was not statistically significant.
Blood clots in the lungs (pulmonary embolism or PE) were less common than VTEs, but the risk was also raised in the IVF group.
Out of every 10,000 women with IVF pregnancies, eight had a PE compared to six out of every 10,000 with natural pregnancies.
This increase in risk again focused on the first trimester, with PE occurring in three out of every 10,000 women with IVF pregnancies, compared to less than one (0.4) out of every 10,000 women with natural pregnancies. In the second and third trimesters, the difference between the groups was not statistically significant.
Taking into account factors which could affect clot risk, such as BMI and smoking did not affect the difference between the groups.
How did the researchers interpret the results?
The researchers concluded that IVF “is associated with an increased risk of pulmonary embolism and venous thromboembolism during the first trimester”.
They note that although the risk of pulmonary embolism is low in absolute terms, the condition is a leading cause of maternal death and therefore it is crucial that professionals are aware of the potential risk and are alert to symptoms.
This large study provides information on how common blood clots are in women who have conceived through IVF compared to similar women who conceive naturally. The study’s strengths are its size, and making the two groups comparable in terms of maternal age and when they gave birth.
However, there are a number of points to note:
- The women who had IVF in these studies gave birth between five and 23 years ago. The practices in IVF may have changed over this period, and this could mean that rates for women receiving IVF nowadays could differ.
- The registries assessed only include women who had a live birth; therefore, it does not include women with miscarriages or still births, or where the mother died in pregnancy or labour. This could under-estimate cases of blood clots.
- Although the researchers tried to take into account factors that could influence clot risk, there may be other factors that are playing a role. For example, there are some conditions that affect fertility, but also increase the risk of clots, and these could be having an effect.
- The researchers had to rely on data recorded in registries, and some data may be missing or incorrect. For example, information on outpatient diagnoses of blood clots was only available from 1997, whereas inpatient diagnoses were available for the entire period being studied. However, the authors report that data in these national registries is considered to be of good quality.
- Women with an IVF pregnancy may be monitored more closely than women with a natural pregnancy, and this could mean that more clots are picked up in this group. The authors say that they cannot rule this out, but think it is unlikely as the increase in risk was not seen after the pregnancy and it was not constant across the pregnancy – with a greater increase in the first trimester.
- The research cannot pinpoint the reason for the increase in risk in the IVF group. One possibility is that it relates to the increase in oestrogen levels that occur in women receiving treatment to stimulate egg production prior to IVF, but it is not possible to prove this conclusively from this study.
As the researchers point out, the absolute increase in the number of cases of clots in the lungs of women who give birth through IVF is low, with about an additional two women affected per 10,000 pregnancies.
Overall, the results of this study could help doctors to be on their guard if they see symptoms in women who have conceived through IVF, to help them diagnose and treat the condition appropriately.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
ITV News, 16 January 2013
Daily Mail, 16 January 2013
Links to the science
BMJ. Published online January 15 2013