Original Title: E-FREEZE: a randomised controlled trial evaluating the clinical and cost-effectiveness of a policy of freezing all embryos followed by thawed frozen embryo transfer, compared with a policy of fresh embryo transfer in women undergoing in-vitro fertilization

Authors' objectives: One in seven couples experience difficulty in conceiving. Many of them will require in-vitro fertilization (IVF) which is recommended by NICE as the effective treatment for infertility. IVF involves hormone injections to stimulate a woman s ovaries to produce a number of eggs which are removed by a minor operation. The eggs are then mixed with sperm to create embryos in the laboratory. Conventionally, these embryos are replaced within the womb a few days after they are created (fresh embryo transfer). Remaining embryos are usually frozen such that they can be thawed and transferred at a later date (thawed frozen embryo transfer). Until recently it has been universally believed that a fresh embryo has the best chance of resulting in a pregnancy. Thawed frozen embryo transfers have therefore generally only been used where the transfer of a fresh embryo has been unsuccessful, or when a woman has decided to return for a second pregnancy. Although this way of providing IVF is still the one which is most widely used, associated pregnancy rates are low (25% live birth rate) despite a number of technological advances. In addition, pregnancies resulting from IVF treatment incur an increased risk of complications to mother and baby. These risks appear to be higher after fresh as opposed to frozen embryo transfer. Over the last decade, embryo freezing techniques have improved substantially and recent research suggests that transfer of thawed frozen embryos could lead to higher pregnancy rates as well as fewer complications (both for the mother and the baby) as compared to fresh embryo transfer. An alternative policy which could potentially improve IVF outcomes and reduce complications, therefore, is to avoid fresh embryo transfer, freeze all embryos followed by thawing and replacing them at a later date. However, the existing evidence base is not robust enough to justify such a major change in the way IVF is provided. Hence we propose a large multicentre randomised controlled trial across 10 IVF centres in the UK to evaluate the clinical effectiveness and economic value of a policy of freezing all embryos followed by thawed frozen embryo transfer, compared with the current practice of fresh embryo transfer in women undergoing IVF. We plan to conduct this project over a four year period starting in 2015. This project will be coordinated by a Clinical Trials Unit and will involve multiple IVF centres from across the country. We will recruit 1,086 women (543 will have fresh embryo transfer and 543 will have all created embryos frozen to be thawed and transferred later) over a 2 year period. All resulting pregnancies will be followed up until delivery (Details of sample size calculation are provided in detailed protocol). The proposed outcome measures address both safety (safety of women undergoing IVF i.e. OHSS, complication in pregnancy- miscarriages, preterm delivery and low birth-weight baby) as well as effectiveness of the IVF treatment (pregnancy rates). Since changing the way IVF is currently delivered will have cost implications, we will also assess the short and longer term costs of both embryo transfer policies from both a health service as well as a broader societal perspective.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/1311582/#/

Year Published: 2022

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/AEFU1104

Requestor: NIHR Health Technology Assessment programme

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk