Condition category
Pregnancy and Childbirth
Date applied
04/04/2018
Date assigned
18/04/2018
Last edited
18/04/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
In vitro fertilisation (IVF) techniques can help people with fertility problems to have a baby. In IVF an egg is fertilized by sperm in a test tube to create an embryo. The current methods of selecting the best embryo for replacement into the womb during IVF are imprecise. The resulting success rates for this expensive treatment are less than ideal. Success rates might be improved by a new technology that uses time-lapse imaging, where embryos are grown in a special incubator, and an inbuilt microscope and camera allows embryos to be assessed without having to remove them. In addition, images of the developing embryo are taken every five to fifteen minutes, which can give additional information (morphokinetic parameters) to aid selection. The aim of this study is to find out whether this technology increases the likelihood of live birth following fertility treatment.

Who can participate?
Couples undergoing IVF or ICSI (Intra-Cytoplasmic Sperm Injection) treatment, where the woman is between 18 and 42 years of age and the male partner is at least 18 years of age

What does the study involve?
Participants are randomly allocated to one of three treatment groups. In the first group embryos are grown in the time-lapse incubator using time-lapse imaging for embryo selection. In the second group embryos are grown in the time-lapse incubator using only standard assessment techniques. In the third group embryos are grown in standard incubators. At the end of the incubation (3-6 days after egg collection), the best embryo(s) are transferred. The woman is then followed up until a maximum of 6 weeks after the end of the pregnancy. The number of live births is taken from the patients’ medical notes or by contacting the participant.

What are the possible benefits and risks of participating?
There is no guarantee that taking part in this study will increase the chances of IVF/ICSI being successful, but participants will be helping clinicians and policy makers decide whether current IVF/ICSI guidelines need to be changed. There is no added risk using this technology for the growth and monitoring of embryos. The camera captures embryos in red light for a very short period of time – 15 milliseconds. This is the same amount of light exposure as during manual removal of embryos from the standard incubator and their examination under a standard microscope. The time lapse imaging systems are CE marked.

Where is the study run from?
Homerton University Hospital (UK)

When is the study starting and how long is it expected to run for?
September 2017 to August 2021

Who is funding the study?
1. Barts and the London Charity and Related Charities (UK)
2. Pharmasure Ltd (UK)

Who is the main contact?
1. Doris Lanz
d.lanz@qmul.ac.uk
2. Dominic Baxter
d.baxter@qmul.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Ms Doris Lanz

ORCID ID

http://orcid.org/0000-0001-9879-3069

Contact details

Barts Research Centre for Women’s Health
Women’s Health Research Unit
Centre for Primary Care and Public Health
Queen Mary University of London
Yvonne Carter Building
58 Turner Street
London
E1 2AB
United Kingdom
+44 (0)20 7882 5636
d.lanz@qmul.ac.uk

Type

Scientific

Additional contact

Mr Dominic Baxter

ORCID ID

Contact details

Barts Research Centre for Women’s Health
Women’s Health Research Unit
Centre for Primary Care and Public Health
Queen Mary University of London
Yvonne Carter Building
58 Turner Street
London
E1 2AB
United Kingdom
+44 (0)20 7882 6694
d.baxter@qmul.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

37510

Study information

Scientific title

A pragmatic, multi-centre, three-arm randomised controlled trial to assess the clinical effectiveness and safety of time lapse imaging in in-vitro fertilisation treatment

Acronym

TILT

Study hypothesis

Current methods of selecting the best embryo for replacement into the womb during in-vitro fertilisation treatment (IVF) are imprecise. The resulting success rates for this expensive treatment are less than ideal. Success rates might be improved by a new technology that uses time-lapse imaging, where embryos are grown in a special incubator, and an inbuilt microscope and camera allow embryos to be assessed without having to remove them. In addition, images of the developing embryo are taken every five to fifteen minutes, which can give additional information (so-called morphokinetic parameters) to aid selection. Current best evidence for the use of time-lapse imaging is uncertain and of moderate to low quality. The trialists propose to conduct a large-scale study giving high-quality evidence and a definitive answer to whether this technology increases the likelihood of live birth following fertility treatment.

Ethics approval

London Central Research Ethics Committee, provisional approval 08/03/2018, ref: 18/LO/0330

Study design

Randomised; Interventional; Design type: Treatment, Device

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Specialty: Reproductive health and childbirth, Primary sub-specialty: Other; UKCRC code/ Disease: Reproductive Health and Childbirth/ Other maternal disorders predominantly related to pregnancy

Intervention

A secure, web based randomisation system hosted by the Barts Women’s Health Research Centre. The randomisation will be stratified by fertility clinic, and minimised by:
1. Participant’s age (<35 years, 35 – 40 years, >40 years)
2. Type of planned first embryo transfer (fresh, frozen).

Participants are randomly allocated to one of three treatment groups:
Time-lapse imaging (intervention group 1): incubation and assessment of embryos within time-lapse imaging systems, using morphokinetic parameters in addition to conventional morphological assessment
Undisturbed culture (intervention group 2): incubation of embryos in undisturbed culture conditions within time-lapse imaging incubators, using conventional morphological embryo assessment only
Standard care (control group): incubation of embryos in standard incubators, using conventional morphological embryo assessment only

At the end of the incubation (3-6 days after egg collection), the best embryo(s) will be transferred. The woman will then be followed up until a maximum of 6 weeks after the end of the pregnancy.

The sample size calculation was based upon the primary outcome of live birth. With a 5% overall significance level (2.5% for each of the two main treatment comparisons: TLI vs. standard care, and undisturbed culture vs. standard care), 514 participants would be required per treatment arm to detect an absolute increase in the primary outcome from 26.5% to 35.25% with 80% power. Allowing for 2% loss-to-follow-up or withdrawal of consent would require 525 participants per treatment arm (1575 in total). The comparison between experimental treatment arms (TLI vs. undisturbed culture) will be performed with no impact on sample size because this statistical test will be carried out conditional to the rejection of at least one of the primary comparisons planned (TLI vs. standard care, or undisturbed culture vs. standard care). This hierarchical approach permits to maintain the overall type I error rate of 5%.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Number of live births, taken from medical notes/contacting the participant; Timepoint(s): Delivery

Secondary outcome measures

Clinical efficacy outcomes:
1. Pregnancy rate measured by pregnancy test taken from medical notes; Timepoint(s): 2 weeks after embryo transfer
2. Successful implantation of embryo(s) into womb measured by total number of gestational sacs seen on ultrasound scan/total number of embryos replaced into the womb taken from medical notes; Timepoint(s): Two weeks after embryo transfer
3. Successful clinical pregnancy measured by at least one intrauterine gestational sac taken from medical notes/contacting the participant; Timepoint(s): 6-8 weeks after embryo transfer
4. Use of elective single embryo transfer (e-SET) recorded per participant, taken from medical notes; Timepoint(s): At embryo transfer

Clinical safety outcomes:
1. Multiple pregnancy measured by two or more gestational sacs seen on ultrasound scan taken from medical notes/contacting the participant; Timepoint(s): 6-8 weeks after embryo transfer
2. Miscarriage recorded for each pregnancy loss taken from medical notes/contacting the participant; Timepoint(s): Between 6 and 24 weeks gestation
3. Stillbirth recorded as pregnancy loss taken from medical notes/contacting the participant; Timepoint(s): After 24 weeks gestation
4. Incidence of major congenital abnormality at birth recorded as a Serious Adverse Event taken from medical notes/contacting the participant; Timepoint(s): Within 6 weeks of delivery

Overall trial start date

01/09/2017

Overall trial end date

31/08/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

The inclusion criteria are broad in keeping with the latest NICE guidelines (2013) for NHS funded IVF/ICSI treatment.
Participants undergoing IVF/ICSI treatment and:
1. The woman is between 18 and 42 years of age at the time of consent
2. The male partner is at least 18 years of age at the time of consent
3. Receiving the first, second or third IVF/ICSI treatment cycle
4. Both partners give written informed consent
5. Those having at least 3 2PN embryos (showing 2 pro-nucleii which is a sign of normal fertilisation) on day of fertilization check

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 1575; UK Sample Size: 1575

Participant exclusion criteria

1. Participants who have been randomised previously to this trial
2. Participants concomitantly participating in other trials
3. IVF/ICSI treatment using donor gametes
4. Planned pre-implantation genetic diagnostics or screening (PGS/PGD)

Recruitment start date

01/05/2018

Recruitment end date

01/05/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Homerton University Hospital
Homerton Row
London
E9 6SR
United Kingdom

Sponsor information

Organisation

Queen Mary University of London

Sponsor details

QMUL Joint Research Management Office
Lower Ground Floor
5 Walden Street
London
E1 2EF
United Kingdom
+44 (0)20 7882 7275
sponsorsrep@bartshealth.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Barts and the London Charity and Related Charities; Grant Codes: MGU0374

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Pharmasure Ltd

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The CI will have primary responsibility and co-ordinate dissemination of data from this trial. A core team consisting of the co-applicants will work closely with QMUL to plan and effectively disseminate the findings of the research to all stakeholders: participants, clinical community, user groups, funding bodies, NHS commissioners and the general public. The clinical trial report and the main manuscript will be reviewed by the CIG and TSC before publication.

Dissemination to clinicians and clinical professional bodies will be through publications and presentations at major national and international conferences relevant to the speciality. The aim is to publish the findings in the highest impact peer reviewed journals and present them at the annual conferences related to the speciality. The trialists plan to publish the study protocol in an open access journal and to communicate the trial findings to the Cochrane Gynaecology and Fertility Group with a view to incorporate the results into the current Cochrane review.

Dissemination to the participants and the general public will be done through newsletters, NHS websites and through the meetings and websites of local PPI networks and Fertility Networks UK. In consultation with the investigators and appropriate journals, a press release will be issued to the media upon publication of the results.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from the CI Prof. Shakila Thangaratinam (s.thangaratinam@qmul.ac.uk). There will be restrictions on the availability of raw data for this study, due to data confidentiality and patient privacy. Researchers wishing to access the TILT trial data for the
purposes of replicating or verifying our analyses can apply to the CI at the BARC (Barts Research Centre for Women’s Health).

Intention to publish date

01/08/2022

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes