Time Lapse Imaging Trial (TILT)
Research type
Research Study
Full 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
IRAS ID
236942
Contact name
Khalid S. Khan
Contact email
Sponsor organisation
Queen Mary University of London
ISRCTN Number
ISRCTN17792989
Duration of Study in the UK
3 years, 5 months, 30 days
Research summary
Summary of Research
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.
We 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.The study will be conducted at UK hospitals licensed by the Human Fertilisation and Embryology Authority. We are planning to recruit 1575 couples to this study over 2 years. We will approach couples who are planning to undergo either IVF or ICSI (Intra-Cytoplasmic Sperm Injection) treatment, and include them in the study if both partners give written informed consent. We exclude participants if there are less than three successfully fertilised eggs available for incubation. Participants would be randomly allocated to one of three treatment groups: a) embryos grown in the time-lapse incubator, using time-lapse imaging for embryo selection, or b) embryos grown in the time-lapse incubator, using only standard assessment techniques (where the expected benefit is "undisturbed culture"), or c) embryos grown in standard incubators. 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.
Summary of Results
Study Background:
Many couples experience problems becoming pregnant. They often undergo procedures such as in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) where an embryo is implanted into the womb to help them become pregnant.
The success rate of IVF/ICSI depends on the ability to select the best embryo for transfer. There is a lack of evidence regarding the best method to choose which embryo to use. National guidelines and fertility experts have recommended further research into methods to improve embryo selection.
Time lapse imaging (TLI) is a newer technology available in IVF/ICSI laboratories where a series of images are captured at regular intervals during embryo growth. It is thought to improve the accuracy for embryo selection from a group of available embryos. In addition, it provides an undisturbed environment for the embryos when they are developing. Its potential benefits are an increased likelihood of successful treatment, i.e. live birth.
TILT was a large, multi-centre research study carried out to provide a definitive answer to whether the TLI technology is more effective and safer than currently used care.Objectives:
The objective of the trial was to determine if the use of TLI or undisturbed culture in IVF/ICSI treatment resulted in a higher live birth rate when compared to current standard methods of embryo incubation and assessment and to assess whether TLI was more effective and safer than currently used care.
Methods:
TILT was a pragmatic, multi-centre, three-arm parallel group, blinded randomised controlled trial using re-randomisation, conducted across seven centers in the UK and Hong Kong. It was carried out over a period of four years. Women were randomly assigned to one of three treatment arms. 1575 participants were randomly assigned to receive either TLI (525 participants), undisturbed culture (525 participants) or standard care (525 participants). Recruitment started in June 2018 and active recruitment was completed in September 2022. The study follow-up period was completed in October 2023.
Results:
Between 21st June 2018 and 30th September 2022, the trial recruited 2191 participants. 1575 were randomised and allocated to either receive time lapse imaging (525 participants), undisturbed culture (525 participants) or standard care (525 participants).
Live birth data were available for 1558 of 1575 (98.92%) participants. The live birth rate was 175 of 520 (33.7%) in the TLI group, 189 of 516 (36.6%) in the undisturbed culture group and 172 of 522 (33.0%) in the control group.
The clinical pregnancy rate was 219 of 519 (42.2%) in the time lapse intervention group, 225 of 518 (43.4%) in the undisturbed culture group and 212 of 519 (40.9%) in the control group with no significant differences between groups.
Pre-specified subgroup analysis showed no difference in any primary or secondary outcomes for different age groups (less than 35 years, greater than 35 years) or based on the method of embryo replacement (fresh, frozen).
This trial demonstrated that in women having IVF/ICSI treatment, the use of time lapse imaging systems either for undisturbed embryo culture and embryo selection, or undisturbed culture alone, did not result in a significant increase in live birth. There was no significant increase in pregnancy rate or clinical pregnancy rate or a significant decrease in pregnancy loss or multiple births for either intervention.Conclusion:
The trial recruited to target, and the aims of the trial were met.
This trial showed that for women having IVF treatment the use of TLI systems does not significantly increase the incidence of live births.Compliance statement:
The trial was conducted in accordance with the protocol, principles of Good Clinical Practice and the UK Policy Framework for Health and Social Care Research.Publication and dissemination:
The publication of the trial results will be submitted to a peer reviewed journal early 2024. We are planning dissemination through various channels to staff groups and the public, such as blogs and social media posts.REC name
London - Central Research Ethics Committee
REC reference
18/LO/0330
Date of REC Opinion
8 Mar 2018
REC opinion
Favourable Opinion