Condition category
Pregnancy and Childbirth
Date applied
24/12/2015
Date assigned
29/12/2015
Last edited
29/12/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
In order for a woman to become pregnant, the fertilised egg must attach (implant) itself to the lining of the womb. In vitro fertilisation (IVF) is a technique used to help people with fertility problems to have a baby. During IVF, couples donate their own sperm and eggs (or use sperm and eggs from a donor). The egg is fertilised by the sperm outside of the body to create an embryo and then returned to the woman’s womb to develop, approximately three days later (fresh embryo transfer). Although IVF has become more and more successful in recent years, there is still a relatively high failure rate. In many cases, some of the embryos are frozen so that they can be thawed out and used in IVF at a later date (frozen embryo transfer). The aim of this study is to find out the effectiveness and cost-effectiveness of using frozen embryo transfer three months after egg donation, compared to fresh embryo transfer, and whether the technique used has an effect of the health of the baby at birth.

Who can participate?
Couples undergoing their first found of IVF fertility treatment at fertility centres in the UK.

What does the study involve?
Couples are randomly allocated to one of two groups. At the start of the study, all participants donate sperm and eggs so that embryos can be created. For participants in the first group, three days after egg donation, the fertilised embryos are placed in the female participants’ womb. For participants in the second group, the fertilised embryos are frozen, for later use. These embryos are then thawed three months after the egg donation and implanted into the female participants’ womb. Women in both groups are monitored to find out how many become pregnant. For those who do, the health of the baby is assessed by the medical team at the time of birth.

What are the possible benefits and risks of participating?
There are no immediate direct benefits of taking part in the study, but participating will help to inform future fertility treatment in the UK. There are no additional risks to the standard risks involved with IVF.

Where is the study run from?
Twelve fertility units in the Scotland and England (UK).

When is the study starting and how long is it expected to run for?
March 2015 to February 2019

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
1. Ms Christina Cole (public)
christina.cole@npeu.oxa.c.uk
2. Dr Abha Maheshwari (scientific)
a.maheshwari@abdn.ac.uk

Trial website

https://www.npeu.ox.ac.uk/e-freeze

Contact information

Type

Public

Primary contact

Ms Christina Cole

ORCID ID

Contact details

NPEU Clinical Trials Unit
National Perinatal Epidemiology Unit
University of Oxford
Old Road Campus
Oxford
OX3 7LF
United Kingdom
+44 1865 617924
christina.cole@npeu.oxa.c.uk

Type

Scientific

Additional contact

Dr Abha Maheshwari

ORCID ID

Contact details

Aberdeen Maternity Hospital
Foresterhill
Aberdeen
AB25 2ZL
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Freezing of embryos in assisted conception: a randomised controlled trial evaluating the clinical and cost-effectiveness of a policy of freezing embryos followed by thawed frozen embryo transfer, compared with a policy of fresh embryo transfer in women undergoing in-vitro fertilization.

Acronym

E-Freeze

Study hypothesis

The aim of this study is to determine if a policy of freezing embryos, followed by thawed frozen embryo transfer results in a higher healthy baby rate when compared with the current policy of transferring fresh embryos.

Ethics approval

North of Scotland Research Ethics Committee, ref: 15/NS/0114

Study design

Pragmatic multi-centre parallel-group randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Other

Patient information sheet

Condition

Infertility

Intervention

Couples will be randomly allocated to either the standard care or intervention arm.

Standard care arm: Women will undergo fresh embryo transfer on day 3 or 5 (after egg collection).

Intervention arm: All good quality embryos will be frozen and couples will undergo frozen thawed embryo transfer within 3 months of the egg collection process. Couples will attend for a clinic visit and additional monitoring visits before frozen embryo transfer is performed.

Data be collected using bespoke electronic data collection forms at 6 time points between consent and 6 weeks post delivery. An emotions questionnaire will also be completed both after consent and at embryo transfer to understand how couples are feeling. And an economic questionnaire will be used to understand time and travel expenses accrued during their treatment.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

Health of the baby is determined by medical staff at the time of birth.

Secondary outcome measures

1. Live birth rate
2. Pregnancy rate (defined as positive pregnancy test - 2 weeks after embryo transfer)
3. Clinical pregnancy rate (a pregnancy diagnosed by ultrasonic visualisation of one or more gestational sacs or definitive clinical signs of pregnancy; ectopic counts as clinical pregnancy; multiple gestational sacs count as one clinical pregnancy)
4. Ongoing pregnancy (pregnancy with presence of foetal heart beat)
5. Ovarian hyperstimulation syndrome (OHSS)
6. Miscarriage rate
7. Gestational diabetes mellitus (GDM)
8. Multiple pregnancy
9. Hypertensive disorders of pregnancy (comprising pregnancy induced hypertension; pre-eclampsia and eclampsia)
10. Antepartum haemorrhage
11. Preterm delivery (defined as delivery at <37 completed weeks)
12. Very preterm delivery (defined as delivery at <32 completed weeks)
13. Low birth weight (defined as weight < 2500 g at birth)
14. Very low birth weight (defined as < 1500 g at birth)
15. Large for gestational age (defined as birth weight >90th centile for gestation, based on standardised charts)
16. Small for gestational age (defined as less than 10th centile for gestational age at delivery)
17. Congenital anomaly (all congenital anomalies identified will be included)
18. Perinatal mortality (late as well as early neonatal deaths, up to 28 days after birth)
19. Evaluation of emotional state
20. Health economic outcome measures:
20.1. Costs to the health service of treatment, pregnancy and delivery care
20.2. Modelled long-term costs of health and social care, and broader societal costs

Overall trial start date

01/03/2015

Overall trial end date

28/02/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. The female partner is between 18 and 42 years of age at the start of treatment (i.e. start of ovarian stimulation)
2. Couples who are undergoing their first cycle of IVF/ICSI treatment
3. Both partners are resident in the UK
4. Both partners are able to provide written informed consent


Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1,086

Participant exclusion criteria

Couples in whom:
1. Donor gametes are used
2. Pre-implantation genetic diagnosis is performed
3. Elective freezing of all embryos is preferred or clinically indicated (e.g. severe risk of OHSS)

Recruitment start date

01/01/2016

Recruitment end date

31/12/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Aberdeen Maternity Hospital
Aberdeen Fertility Centre Foresterhill
Aberdeen
AB25 2ZL
United Kingdom

Trial participating centre

St Mary's Hospital
Department of Reproductive Medicine, 1st Floor Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Sheffield Teaching Hospitals
Jessop Wing, Assisted Conception Unit Tree Root Walk
Sheffield
S10 2SF
United Kingdom

Trial participating centre

King's College Hospital Assisted Conception Unit
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

Princess Anne Hospital
Complete Fertility Centre Coxford Road
Southampton
SO16 5YA
United Kingdom

Trial participating centre

Hewitt Fertility Centre
Crown Street
Liverpool
L8 7SS
United Kingdom

Trial participating centre

Guy's and St Thomas' Assisted Conception Unit
11th Floor, Tower Wing Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

Hammersmith Hospital
IVF Hammersmith Du Cane Road
London
W12 0HS
United Kingdom

Trial participating centre

Nurture Fertility
The East Midlands Fertility Centre Interchange Business Park Sandiacre
Nottingham
NG10 5QE
United Kingdom

Trial participating centre

Homerton Fertility Centre
Homerton Row
London
E9 6SR
United Kingdom

Trial participating centre

Oxford Fertility Unit
Nuffield Department of Obstetrics and Gynaecology Oxford Business Park North
Oxford
OX4 2HW
United Kingdom

Trial participating centre

Birmingham Women's Fertility Centre
Mindelsohn Way
Birmingham
B15 2TG
United Kingdom

Sponsor information

Organisation

NHS Grampian

Sponsor details

NHS Grampian
Research & Development
Foresterhill House Annexe
Foresterhill
Aberdeen
AB25 2ZB
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Organisation

University of Aberdeen

Sponsor details

University of Aberdeen
Research Governance Office
Foresterhill House Annexe
Foresterhill
Aberdeen
AB25 2ZB
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes