Increased venous thrombosis incidence in pregnancies after in vitro fertilization

Study question: Is venous thrombosis risk increased in pregnancies after in vitro fertilization?

Summary answer: The venous thrombosis incidence was significantly increased in pregnancies after in vitro fertilization; especially in the first trimester and in the first 6 weeks post-partum.

What is known already: In vitro fertilization without pregnancy is not associated with increased venous thrombosis incidence.

Study design, size, duration: This national register-based cohort study covered the period from 1995 to 2005.

Participants/materials, setting, methods: All Danish pregnancies conceived by in vitro fertilization (n = 18 787) were included. Venous thrombosis incidence rates in pregnancies after in vitro fertilization were compared with venous thrombosis incidence rates in reference pregnancies, by calculating incidence rate ratios.

Main results and the role of chance: In total, 48 cases were identified. In pregnancies after in vitro fertilization, the overall venous thrombosis incidence rate was 28.6 per 10 000 pregnancy-years (95% confidence interval (CI) 20.6-39.6) in comparison to 10.7 per 10 000 woman-years in reference pregnancies. Post-partum, the venous thrombosis incidence rate was 27.9 per 10 000 woman-years (95% CI 15.8-49.1) after in vitro fertilization in comparison to 17.5 per 10 000 woman-years in reference pregnancies. The overall venous thrombosis incidence rate ratio during in vitro fertilization (IVF) pregnancies compared with reference pregnancies was 3.0 (95% CI 2.1-4.3). The venous thrombosis incidence rate ratios during pregnancy were 2.8 (95% CI 1.9-4.1) in singleton IVF pregnancies and 4.4 (95% CI 2.4-8.3) in multiple IVF pregnancies, compared with reference pregnancies. The venous thrombosis incidence rate ratio post-partum was 1.2 (95% CI 0.6-2.8) for singleton IVF pregnancies and 3.9 (95% CI 1.7-8.8) for multiple IVF pregnancies compared with reference pregnancies. The post-partum venous thrombosis risk was higher in multiple IVF pregnancies compared with singleton IVF pregnancies. Maternal age, smoking and parity did not significantly affect the venous thrombosis risk. Ovarian hyperstimulation syndrome and polycystic ovarian syndrome did increase the risk of venous thrombosis during pregnancy. Caesarean section also increased the post-partum venous thromboembolism risk, but the increase was not significant.

Limitations, reasons for caution: Other known confounders in our reference population could have contributed to the results. Access to such data may have helped to explain the observations, but would not have changed the conclusion that IVF pregnancies have an increased risk of venous thrombosis compared with other pregnancies.

Wider implications of the findings: Our study adds new insights by demonstrating an excess venous thrombosis incidence post-partum after in vitro fertilization. The high venous thrombosis incidence in first trimester after in vitro fertilization supports previous studies. Our findings are generalizable to other Western Countries.

Study funding/competing interests: Expenses for the acquirement of data were covered by a grant from The Secretary of Doctors further education, Central Denmark Region. None of the authors have any competing interests to declare.

Trial registrations number: Not applicable.