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In vitro fertilization increased PE, VTE risk in pregnant women
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Women who become pregnant following in vitro fertilization have an increased risk of pulmonary embolism and venous thromboembolism during their first trimesters, according to results of a cross-sectional study.
Infertility affects more than 10% of couples worldwide. Approximately 5 million people have been born after in vitro fertilization since 1978, and it is widely considered a safe and effective technique.
Embolism is a leading cause of maternal mortality and, although the increased risk during normal pregnancy is well established, no information exists on risk in pregnant women who undergo in vitro fertilization, according to background information in the study.
Peter Henriksson, MD, a professor in the department of clinical sciences in Danderyd Hospital at Karolinska Institute in Sweden, and colleagues compared the risk for pulmonary embolism (PE) or venous thromboembolism (VTE) in pregnant women after in vitro fertilization with age- and time-matched women undergoing normal pregnancy.
Researchers identified 23,498 women in the Swedish population who gave birth after in vitro fertilization and 116,960 individually matched women with natural pregnancies between 1990 and 2008.
Both groups had a median patient age of 33.
Study results showed VTE occurred in 4.2 per 1,000 women after in vitro fertilization compared with 2.5 per 1,000 women with natural pregnancies. The risk after in vitro fertilization increased during the pregnancy (HR=1.77; 95% CI, 1.41-2.23) and differed between trimesters (P=.002).
The risk of VTE in the in vitro fertilization cohort increased particularly in the first trimester, according to the study results (HR=4.22; 95% CI, 2.46-7.26).
Risks did not differ between the two groups before pregnancy or in the year after delivery (HR=1.29; 95% CI, 0.82-2.02).
PE occurred in 19 women who underwent in vitro fertilization compared with 70 of the individually matched women undergoing normal pregnancy.
A higher proportion of women who underwent in vitro fertilization experienced PE in the first trimester (HR=6.97; 95% CI, 2.21-21.96).
Although researchers observed a low absolute risk for PE — roughly two to three additional cases per 10,000 pregnancies — the condition remains difficult to diagnose.
“Efforts should focus on the identification of women at risk of thromboembolism, with prophylactic anticoagulation considered in women planning to undergo in vitro fertilization,” Henriksson and colleagues concluded.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Margaret Ragni, MD, MPH
This cross-sectional study of the Swedish national patient registry of women with children born from 1990 to 2008 reports that those undergoing in vitro fertilization (IVF) had a sevenfold higher rate of venous thromboembolism (VTE) during pregnancy than age-matched controls. The greatest risk was in the first trimester, but some risk continued throughout pregnancy.
These findings suggest there may be a group of women undergoing IVF at risk for VTE who might benefit from thromboprophylaxis. Whether the risk is related to the hormones used in the IVF procedure, whether hormone-related risk early in pregnancy influences future VTE risk as hormones increase during pregnancy, or whether there are other risk factors (eg, whether they have risk factors for VTE such as obesity, immobilization or thrombophilia) is not known.
VTE already is increased in pregnancy, and it is the leading cause of maternal death. These data suggest we need to have a high level of suspicion for VTE in women undergoing IVF, as well as a low threshold for diagnostic tests. Because it is not possible to perform a randomized clinical trial during pregnancy, it is difficult to determine whether thromboprophylaxis — that is, empiric low-molecular–weight heparin (the drug of choice in pregnancy) — would be beneficial.
However, if a group at risk could be identified, then thromboprophylaxis during pregnancy might be a consideration. Certainly hematologists are faced with managing such women without level 1 guidelines (ie, from a randomized controlled clinical trial) as they are not available, nor are they expected to be. In this situation, cross-sectional and prospective cohort studies may be helpful, as in the CHEST guidelines, to help address such questions. The next steps would include defining those at risk and modeling cost-benefit analyses of thromboprophylaxis among patients undergoing in vitro fertilization.
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