Reproductive and cardio-metabolic health

Lead Research Organisation: University of Bristol

Abstract

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.

Technical Summary

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.

Publications

10 25 50

 
Description LifeCycle - IVF cohort 
Organisation Barcelona Institute for Global Health
Country Spain 
Sector Multiple 
PI Contribution We are the central organisers of the collaboration. We draft analysis plans, share these with partners, undertake individual participant study analyses and meta-analyses of data across all studies. We will write the first draft of initial papers and redraft following in put from partners
Collaborator Contribution Partners: 1. Contribute to the development of analysis plans 2. Provide individual participant data or summary results 3. Contribute to drafting manuscripts
Impact Too early for outputs
Start Year 2018
 
Description LifeCycle - IVF cohort 
Organisation Bradford Teaching Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution We are the central organisers of the collaboration. We draft analysis plans, share these with partners, undertake individual participant study analyses and meta-analyses of data across all studies. We will write the first draft of initial papers and redraft following in put from partners
Collaborator Contribution Partners: 1. Contribute to the development of analysis plans 2. Provide individual participant data or summary results 3. Contribute to drafting manuscripts
Impact Too early for outputs
Start Year 2018
 
Description LifeCycle - IVF cohort 
Organisation Erasmus University Rotterdam
Country Netherlands 
Sector Academic/University 
PI Contribution We are the central organisers of the collaboration. We draft analysis plans, share these with partners, undertake individual participant study analyses and meta-analyses of data across all studies. We will write the first draft of initial papers and redraft following in put from partners
Collaborator Contribution Partners: 1. Contribute to the development of analysis plans 2. Provide individual participant data or summary results 3. Contribute to drafting manuscripts
Impact Too early for outputs
Start Year 2018
 
Description LifeCycle - IVF cohort 
Organisation Norwegian Institute of Public Health
Country Norway 
Sector Academic/University 
PI Contribution We are the central organisers of the collaboration. We draft analysis plans, share these with partners, undertake individual participant study analyses and meta-analyses of data across all studies. We will write the first draft of initial papers and redraft following in put from partners
Collaborator Contribution Partners: 1. Contribute to the development of analysis plans 2. Provide individual participant data or summary results 3. Contribute to drafting manuscripts
Impact Too early for outputs
Start Year 2018
 
Description LifeCycle - IVF cohort 
Organisation University of Copenhagen
Country Denmark 
Sector Academic/University 
PI Contribution We are the central organisers of the collaboration. We draft analysis plans, share these with partners, undertake individual participant study analyses and meta-analyses of data across all studies. We will write the first draft of initial papers and redraft following in put from partners
Collaborator Contribution Partners: 1. Contribute to the development of analysis plans 2. Provide individual participant data or summary results 3. Contribute to drafting manuscripts
Impact Too early for outputs
Start Year 2018
 
Description LifeCycle - IVF cohort 
Organisation University of Groningen
Country Netherlands 
Sector Academic/University 
PI Contribution We are the central organisers of the collaboration. We draft analysis plans, share these with partners, undertake individual participant study analyses and meta-analyses of data across all studies. We will write the first draft of initial papers and redraft following in put from partners
Collaborator Contribution Partners: 1. Contribute to the development of analysis plans 2. Provide individual participant data or summary results 3. Contribute to drafting manuscripts
Impact Too early for outputs
Start Year 2018
 
Description LifeCycle - IVF cohort 
Organisation University of Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution We are the central organisers of the collaboration. We draft analysis plans, share these with partners, undertake individual participant study analyses and meta-analyses of data across all studies. We will write the first draft of initial papers and redraft following in put from partners
Collaborator Contribution Partners: 1. Contribute to the development of analysis plans 2. Provide individual participant data or summary results 3. Contribute to drafting manuscripts
Impact Too early for outputs
Start Year 2018
 
Description LifeCycle - IVF cohort 
Organisation University of Turin
Country Italy 
Sector Academic/University 
PI Contribution We are the central organisers of the collaboration. We draft analysis plans, share these with partners, undertake individual participant study analyses and meta-analyses of data across all studies. We will write the first draft of initial papers and redraft following in put from partners
Collaborator Contribution Partners: 1. Contribute to the development of analysis plans 2. Provide individual participant data or summary results 3. Contribute to drafting manuscripts
Impact Too early for outputs
Start Year 2018
 
Description MR-PREG 
Organisation Bradford Teaching Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Our contributions are: 1. Draft analysis plans 2. Complete analyses 3. Draft papers 4. Support other partners to lead projects
Collaborator Contribution Partners contribute to: 1. Analysis plans. So far these have been initially written by my group but partners make important contributions to revising the first draft (before we begin analyses) and to any decisions about any revisions after analyses have started 2. Data provision and/or analyses. Participants provide individual participant data for analyses in Bristol and/or undertake analyses in their groups and provide summary results 3. Critical comments on drafted papers
Impact Analyses have been completed but no publications yet.
Start Year 2018
 
Description MR-PREG 
Organisation Harvard University
Country United States 
Sector Academic/University 
PI Contribution Our contributions are: 1. Draft analysis plans 2. Complete analyses 3. Draft papers 4. Support other partners to lead projects
Collaborator Contribution Partners contribute to: 1. Analysis plans. So far these have been initially written by my group but partners make important contributions to revising the first draft (before we begin analyses) and to any decisions about any revisions after analyses have started 2. Data provision and/or analyses. Participants provide individual participant data for analyses in Bristol and/or undertake analyses in their groups and provide summary results 3. Critical comments on drafted papers
Impact Analyses have been completed but no publications yet.
Start Year 2018
 
Description MR-PREG 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Our contributions are: 1. Draft analysis plans 2. Complete analyses 3. Draft papers 4. Support other partners to lead projects
Collaborator Contribution Partners contribute to: 1. Analysis plans. So far these have been initially written by my group but partners make important contributions to revising the first draft (before we begin analyses) and to any decisions about any revisions after analyses have started 2. Data provision and/or analyses. Participants provide individual participant data for analyses in Bristol and/or undertake analyses in their groups and provide summary results 3. Critical comments on drafted papers
Impact Analyses have been completed but no publications yet.
Start Year 2018
 
Description MR-PREG 
Organisation Norwegian Institute of Public Health
Country Norway 
Sector Academic/University 
PI Contribution Our contributions are: 1. Draft analysis plans 2. Complete analyses 3. Draft papers 4. Support other partners to lead projects
Collaborator Contribution Partners contribute to: 1. Analysis plans. So far these have been initially written by my group but partners make important contributions to revising the first draft (before we begin analyses) and to any decisions about any revisions after analyses have started 2. Data provision and/or analyses. Participants provide individual participant data for analyses in Bristol and/or undertake analyses in their groups and provide summary results 3. Critical comments on drafted papers
Impact Analyses have been completed but no publications yet.
Start Year 2018
 
Description MR-PREG 
Organisation University of Copenhagen
Country Denmark 
Sector Academic/University 
PI Contribution Our contributions are: 1. Draft analysis plans 2. Complete analyses 3. Draft papers 4. Support other partners to lead projects
Collaborator Contribution Partners contribute to: 1. Analysis plans. So far these have been initially written by my group but partners make important contributions to revising the first draft (before we begin analyses) and to any decisions about any revisions after analyses have started 2. Data provision and/or analyses. Participants provide individual participant data for analyses in Bristol and/or undertake analyses in their groups and provide summary results 3. Critical comments on drafted papers
Impact Analyses have been completed but no publications yet.
Start Year 2018
 
Description MR-PREG 
Organisation University of Oulu
Country Finland 
Sector Academic/University 
PI Contribution Our contributions are: 1. Draft analysis plans 2. Complete analyses 3. Draft papers 4. Support other partners to lead projects
Collaborator Contribution Partners contribute to: 1. Analysis plans. So far these have been initially written by my group but partners make important contributions to revising the first draft (before we begin analyses) and to any decisions about any revisions after analyses have started 2. Data provision and/or analyses. Participants provide individual participant data for analyses in Bristol and/or undertake analyses in their groups and provide summary results 3. Critical comments on drafted papers
Impact Analyses have been completed but no publications yet.
Start Year 2018
 
Description UCLEB 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution One of the key partners Collaboration is concerned with the use of genetics in risk prediction and aetiology (Mendelian randomization) of cardiometabolic disease. Includes the use of metabolomics
Collaborator Contribution As above
Impact Large number of publications - See CV
Start Year 2007
 
Description UCLEB 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution One of the key partners Collaboration is concerned with the use of genetics in risk prediction and aetiology (Mendelian randomization) of cardiometabolic disease. Includes the use of metabolomics
Collaborator Contribution As above
Impact Large number of publications - See CV
Start Year 2007
 
Description UPBEAT RCT 
Organisation King's College London
Department Women's Health Academic Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution I am a co-applicant on a recently obtained MRC grant related to adding metabolomics data to this RCT I will lead analyses of this RCT and the LIMIT RCT (see other entry) in relation to long term mother and offspring outcomes in particular adiposity and metabolomics outcomes.
Collaborator Contribution See entry for LIMIT RCT collaboration
Impact Successful grant Poston L, Lawlor DA, Nelson SM, Sattar N. The UPBEAT RCT mother-child study. Stratifying and treating obese pregnant women to prevent adverse pregnancy, perinatal and longer term outcomes. MRC £825, 398: February 2014 for 48 months Published book chapter: Fraser A, Lawlor DA. Long-term consequences of maternal obesity and gestational weight gain for offspring obesity and cardiovascular risk - intrauterine or shared familial mechanisms? In: Poston L, Gillman M (eds). Obesity and Pregnancy. Cambridge Press. 2012
Start Year 2012