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Data from the United States Center for Disease Control and Prevention (CDC) show that a growing number of women are undergoing assisted reproductive technology (ART) cycles, including in vitro fertilization (IVF), eachyear.1 The European Society of Human Reproduction and Embryology has reported a similar trend.2 As our understanding of the pathophysiology of infertility deepens and indications for ART broaden, the proportion of couples bearing the financial and psychological cost of infertility treatments can be expected to increase. The risk of thrombosis, in particular venous thromboembolism (VTE), represents a critical additional burden of ART. Unlike the risk of VTE associated with hormonal contraception, pregnancy and the post-partum period, the danger of thrombotic complications of ART is often under-appreciated by patients and under-recognized by providers. Accordingly, women undergoing ART may be left to bear this burden alone. The pathogenesis of VTE in ART is believed to rely upon a combination of underlying patient-specific risk factors and consequences of the prescribed treatments and resultant pregnancies (►Fig. 1). Traditional VTE risk factors such as obesity, smoking, thrombophilia and inflammatory disorders frequently co-exist with and may contribute to infertility. For example, in a study of 559 pregnant patients with and 1,229 without VTE, traditional risk factors of high body mass index and limited mobility, in addition to conception via ART and multiple gestations, increased the risk of antepartum VTE.3 ART, specifically IVF, results in a high oestrogen state that favours thrombosis through several suspected mechanisms, including an increase in pro-coagulant factors, acquired activated protein C resistance, down-regulated fibrinolysis and relative deficiencies of endogenous anticoagulants, such as protein S.4 The increased risk of VTE associated with ART ranges between threeand fourfold across cohort studies compared with pregnancies resulting from natural conception.5,6Multiple gestations appear to augment the risk while early pregnancy losses are associatedwith a lowabsolute risk of VTE following ART.5,7 A sub-set of women who develop ovarian hyper-stimulation following ovulation induction bear a considerable risk of venous and arterial thrombosis.8 In theprevious issueofThrombosis andHaemostasis, Grandone et al provided additional perspective on the risk of VTE in women undergoing ART using data from the prolific RIETE Registry.9 In brief, the investigators analysed this large multicentre registry to assess thrombosis risk factors and the frequency of ART-associated VTE. Of 6,718 women with VTE, 41 suffered an event related to ART. Among 22of thesewomen who underwent a hyper-coagulable work-up, half were diagnosed with a thrombophilia, suggesting at least 27% prevalence. Consistent with other analyses, ovarian stimulationwas associatedwith an increased risk of VTE, especially during the first trimester. Unexpectedly, the risk of pulmonary embolism (PE) was fourfold higher with unsuccessful ART cycles comparedwith successful ones resulting in pregnancy. This observation contrasts an earlier study by Grandone et al that demonstrated that VTE was less frequent following failed ART cycles compared with the successful ones.10 The current analysis not only raises awareness of the overall burden of VTE in patients undergoing ART, but also highlights the potential danger of PE following failed cycles. The CDC’s 2015 Fertility Clinic Success Rates Report demonstrated that 231,936 ART cycles resulted in 74,665 pregnancies and 157,271 failed cycles.1 These data suggest a large

Oh Heavy Burden: Recognizing the Risk of Venous Thromboembolism in Women Undergoing Assisted Reproduction