Understanding the causal nature of the relationship between infertility and cardiovascular disease

Understanding the causal nature of the relationship between infertility and cardiovascular disease

The burden of infertility is high across Europe. Modest evidence indicates that infertile couples might have an increased risk of cardiovascular disease (CVD), but several questions need clarification to establish a cause-and-effect relationship. This includes understanding: whether both infertile men and women have an increased risk of CVD; how well-known risk factors for CVD (blood-pressure, body-mass index, cholesterol and smoking) relate to infertility; whether there exists common genetic determinants of infertility and CVD; and whether the connection between infertility and CVD in women can be explained by the use of assisted reproductive technologies or pregnancy complications. These questions will be answered by the INFERTILITY project. The working hypothesis of INFERTILITY is that both infertile men and women have an increased risk of CVD, and that this might at least partly reflect a greater burden of CVD risk factors. I will test this by using data from cohort studies and national health registries in Norway and the United Kingdom. I will use genetic markers as instrumental variables to establish the relationship between CVD risk factors and infertility. This is vital to understand whether infertile couples truly have an increased risk of CVD or whether infertility instead reflects a pre-existing propensity for CVD. I will conduct a genome-wide association study of infertility and identify overlapping genetic markers between any findings from this investigation and published studies of CVD. The INFERTILITY project will also clarify whether offspring cardiometabolic health trajectories differ according to parental fertility problems. This will highlight whether any relationship between infertility and CVD also crosses generations. The INFERTILITY project will elucidate whether infertile couples should be followed more closely to mitigate their risk of CVD and whether interventions targeting well-known CVD risk factors could reduce the burden of infertility.