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Individual participant data meta-analysis of randomised controlled trials comparing freezing of embryos followed by thawed frozen embryo transfer versus fresh embryo transfer in in-vitro fertilisation (INFORM)


School of Medicine, Medical Sciences & Nutrition

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Dr D McLernon , Dr A Maheshwari , Prof S Bhattacharya No more applications being accepted Competition Funded PhD Project (UK Students Only)
Aberdeen United Kingdom Epidemiology Statistics

About the Project

Background to the project

One in seven couples experience problems conceiving. The recommended treatment for persistent infertility is in-vitro fertilisation (IVF) which bypasses natural processes within the body by mixing eggs and sperm to create embryos in a laboratory. Usually an embryo is replaced within the womb 2-5 days later (fresh embryo transfer) while others are frozen for future use. Research suggesting that freezing all embryos and replacing them later could improve treatment safety and success has led to several clinical trials comparing fresh versus frozen embryo transfer, but the results are conflicting. Frozen embryo transfer may be safer and more effective in some women, but none of the individual trials is large enough to provide definitive conclusions with any degree of precision.

Many worldwide randomised controlled trials (RCTs) have compared pregnancy rates after fresh versus frozen embryo transfer. Although they have collected data on other outcomes such as complications in the mother and baby, the number of cases in each trial is too small to provide meaningful answers. This project will aim to collect and combine data from all trials to identify groups of women who may benefit most from fresh or frozen embryo transfer depending on their characteristics.

Proposed research and techniques

In 2016, we formed a collaborative group comprising all the relevant research groups who have agreed to share their anonymised data at the level of each individual participant. There are over 11 existing trials in the world comprising over 8000 couples who have participated in clinical trials comparing fresh versus frozen embryo transfer.

This IPD-MA study will involve combining all RCTs into one large database. This will provide enough statistical power to detect any particular groups of women for whom transferring a frozen embryo has a better outcome than transferring a fresh embryo. Such analysis will adjust for the heterogeneity between trials. Different methodologies for analysis will be explored including one-stage or two-stage IPD meta-analysis approaches. All statistical models will be adjusted for treatment and patient level predictors, taking into account the clustering of patients within the trial, using fixed or random effects.

Results of this project will provide much needed guidance which will have a major impact on the delivery of IVF services and health of future generations. You will join a collaborative team in the University of Aberdeen who are known in the world of fertility research for their expertise in observational and RCT studies. There will be opportunities to develop collaborations with researchers and clinicians from the various RCT centres. You will liaise with patient representatives to conduct this synthesis of global data to guide future national and international policy on IVF treatment. Patient representatives and the public have been integral in the design and conduct for the primary trials and will continue to support this project. As this is of both national and international importance, the results will be disseminated by individualized dissemination strategies for every group of stakeholders across the globe.

Useful previous experience for the studentship

This project requires a numerically highly skilled student, preferably with a medical statistics qualification, who is interested in the meta-analysis of individual participant data and is motivated to perform high-quality research which will inform IVF policy worldwide. The University has an information page for prospective students here:

https://www.abdn.ac.uk/news/eu-referendum/prospective-students.php. 

APPLICATION PROCEDURE:

This project is advertised in relation to the research areas of APPLIED HEALTH SCIENCE. Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php.

You should apply for Degree of Doctor of Philosophy in Applied Health Science, to ensure that your application is passed to the correct person for processing.

NOTE CLEARLY THE NAME OF THE SUPERVISOR AND EXACT PROJECT TITLE ON THE APPLICATION FORM.

Candidates should contact the lead supervisor to discuss the project in advance of submitting an application, as supervisors will be expected to provide a letter of support for suitable applicants. Candidates will be informed after the application deadline if they have been shortlisted for interview.


Funding Notes

This project is part of a competition funded by the Institute of Applied Health Sciences. Full funding is available to UK candidates only. All other candidates can apply for this studentship but will have to find additional funding to cover the difference between overseas and home fees (approximately £16,625 per annum).

Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.

References

1. Maheshwari A et al. Is frozen embryo transfer better for mothers and babies? Can cumulative meta-analysis provide a definitive answer? Hum Reprod Update 2018;24(1):35-58. doi: 10.1093/humupd/dmx031.
2. Tierney JF et al. Individual Participant Data (IPD) Meta-analyses of Randomised Controlled Trials: Guidance on Their Use PLOS Med 2015; doi:10.1371/journal.pmed.1001855.
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