Reproductive and cardio-metabolic health

We are trying to find out how to improve the success of in-vitro fertilisation (IVF) and make sure that women who have conceived by IVF or ‘naturally’ have a healthy pregnancy and birth.
IVF is common. In an average school class of 30 children 1 will have been born by IVF. New ways of using IVF might improve success rates but they need to be carefully evaluated.
Whether women conceive by IVF or naturally up to 40% will have one or more of pregnancy loss, high blood pressure or high blood sugar in pregnancy, a premature birth or an infant who is born unhealthily small or large. We do not know how to prevent these problems or predict which women will experience them.
We will use data from very large studies and new methods that help us to determine causes from ‘confounders’ (factors that fool us into thinking that something is a cause when it is not). This will allow us to work out how to improve IVF and prevent pregnancy problems. It will also improve our understanding of what risk factors in pregnancy affect children’s risk of being obese or having diabetes or heart problems later in their lives.

Our aim is to provide the evidence base that will improve treatment success with IVF and enable stratified and effective antenatal care in IVF and spontaneous conceptions (SC).
This is important because up to 40% or pregnancies are affected by one or more of miscarriage, stillbirth, hypertensive disorders of pregnancy, gestational diabetes, preterm birth or delivery or a small or large for gestational aged infant, but we do not know the best way of preventing these. IVF is now the commonest treatment for infertility with >250K IVF cycles completed per year in the UK and on average 1 in 30 primary school children were born as a result of in vitro fertilisation (IVF). Success rates vary by couple and treatment characteristics but are between 20-30%. There are suggestions that IVF per se, and pregnancy complications in IVF and SC have important adverse effects on future offspring cardio-metabolic health, but whether these associations are causal and if so their magnitude is unclear.
Our objectives are to accurately predict and identify causal paths for: (i) response to IVF; (ii) healthy pregnancy and perinatal outcomes in IVF and SC; and (iii) offspring cardio-metabolic health.
Methods
Our focus will primarily be on maternal smoking, physical activity, sleep patterns, adiposity, pregnancy metabolic profiles and fetal (cord-blood) DNA methylation as potential predictors or risk factors.
We will use data from detailed clinical and general pregnancy/birth cohorts. We will work with relevant consortia, including the EuroCHILD pan-European birth cohort that we are involved in establishing from 26 existing cohorts, early growth genetics (EGG) consortia, in which we co-lead maternal-offspring genetic analyses, the Genetics of Diabetes In Pregnancy (GENdip) consortia that we have recently developed, and the pregnancy/birth cohorts working group aligned to the Consortia Of METabolomics Studies (COMETS), which we lead, as well as the Pregnancy And Child Epigenetics (PACE) consortia, which we work closely with alongside Relton’s MRC Integrative Epidemiology Unit programme. We will triangulate results across the following analytical methods applied to these data sources: multivariable regression (MV), Mendelian randomization (MR), non-genetic instrumental variable (IV) analyses, within sibship and negative control studies.
Translation
Building on our successful impact on clinical guidelines in the first five-years of this programme, we will continue to work with relevant clinicians, patient groups and NICE guideline developers. For new methodological developments we will provide and share datasets and code and widely disseminate these.