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Trial registered on ANZCTR


Registration number
ACTRN12620000197932
Ethics application status
Approved
Date submitted
30/01/2020
Date registered
20/02/2020
Date last updated
20/02/2020
Date data sharing statement initially provided
20/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of the role of an artificial intelligence system (iDA) in embryo selection.
Scientific title
A randomised controlled trial comparing the clinical pregnancy per embryo transfer between an embryo that is selected by an artificial intellligence system (iDA) and and an embryo that is selected by an embryologist.
Secondary ID [1] 300396 0
None
Universal Trial Number (UTN)
U1111-1247-4885
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infertility 316030 0
Condition category
Condition code
Reproductive Health and Childbirth 314308 314308 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Selection of an embryo for transfer by artificial intelligence.
a) The intervention will involve use of a deep learning system, iDA, to review time lapse images (every 10 minutes for five days) taken of embryos growing in an incubator. The deep learning system will analyse these images and use a published validated process to identify which embryo has the highest likelihood of successful implantation.
b) The participants will be treated by their doctor as per normal. The embryos will be cultured as per normal. The only change for the participants will be which embryo is selected FIRST for transfer.
c) The intervention will be implemented by the embryologist following randomisation.
d) The artificial intelligence system is built into the incubators
e) The intervention will be delivered once on Day 5 of embryo culture and will direct which embryo is transferred that morning.
f) The software will be locked to ensure that the embryologist will not be able to implement the deep learning system unless the participant is randomised to use of iDA for embryo selection. All randomisation will be done through an electronic CRF which will monitor and record all randomisations.
Intervention code [1] 316689 0
Treatment: Devices
Comparator / control treatment
Selection of an embryo for transfer by an embryologist using his/her professional skills
Control group
Active

Outcomes
Primary outcome [1] 322694 0
Fetal heart rate pregnancy from the first embryo transfer.
All participants will undergo a serum assay of hCG at 10-13 days after the embryo transfer. Where the hCG level demonstrates a pregnancy, an ultrasound scan will be performed by the managing doctor at 42-46 days gestation. Both the hCG level and the ultrasound scan findngs will be recorded in the patient's own electronic medical record. The study nurse will use this data source to enter the outcome data into the electronic CRF
Timepoint [1] 322694 0
8 weeks gestation.
Secondary outcome [1] 379326 0
Live birth rate from the first embryo transfer.
This outcome will be assessed by telephone follow up of participants. In all cycles of fertility treatment, the patient is followed by by telephone and full details of the birth outcome are required to be collected and recorded in the patient's EMR.
The research team will access this record to obtain the data for entry into the study eCRF.
Timepoint [1] 379326 0
Expected date of delivery as calculated from the date of the embryo transfer
Secondary outcome [2] 379327 0
Positive hCG rate per randomized patient.
Pregnancy will be tested either through a serum hCG measurement carried out from Day 9-13 following embryo transfer or through the use of urinary sticks (25 IU/L) on day 13.
Timepoint [2] 379327 0
Day 13 following embryo transfer
Secondary outcome [3] 379328 0
Rate of non-viable intrauterine pregnancies.
The rate of non-viable intrauterine pregnancies will derived by calculating the proportion of the total number of positive hCG pregnancies (by serum testing) which do NOT result in a fetal heart pregnancy by 8 weeks gestation.
Timepoint [3] 379328 0
8 weeks gestation.
Secondary outcome [4] 379329 0
Ongoing pregnancy rate in patients with maternal age above 35
All participants will undergo a serum assay of hCG at 10-13 days after the embryo transfer. Where the hCG level demonstrates a pregnancy, an ultrasound scan will be performed by the managing doctor at 42-46 days gestation. Both the hCG level and the ultrasound scan findngs will be recorded in the patient's own electronic medical record. The study nurse will use this data source to enter the outcome data into the electronic CRF
For this endpoint, this figure will be calculated specifically for women with maternal age above 35
Timepoint [4] 379329 0
8 weeks gestation.

Eligibility
Key inclusion criteria
Inclusion Criteria
1) Women undergoing IVF or ICSI with controlled ovarian stimulation with gonadotrophins and the intention to treat by either transfer of a single fresh embryo on Day 5 or in case of a freeze all cycle, the first rewarmed embryo.
2) Age: Up to and including the 42nd completed birthday on the day of randomization.
3) Has at least two early blastocysts on Day 5
Minimum age
21 Years
Maximum age
41 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria
1) Treatment involving donated eggs
2) Intention to perform any form of preimplantation genetic testing
3) IMSI patients
4) Previous participation in this RCT
5) Where the cycle is carried out for fertility preservation.
6) If a Day 2-4 transfer is planned
7) Has a reduced likelihood of obtaining two early blastocysts on day 5 as evidenced by either:
• An AMH level of <3pmol/L or AFC <5 (if available)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Populations

The Intention-to-Treat (ITT) population will consist of all randomized women.
Per protocol (PP) population will consist of all randomized women without significant protocol violations. The ITT population and the PP population will be defined at the clean-file-meeting before the database lock.

Sample size calculation.

It is estimated from the results in clinics that clinical pregnancy is estimated to be 40% for trained embryologists. If non-inferiority margin is defined as - 5%, the lower limit of the two-sided 95% confidence interval (CI) for the difference between iDA group and Trained embryologist group shall not be less than -5% with a probability of 80% (ß=20%), with an estimation of 5% or more clinical pregnancies in iDA group, 347 women per randomization group is needed to show non- inferiority. For protection against a 5% loss to follow-up, 729 patients in total, are needed for recruitment.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment postcode(s) [1] 29139 0
2145 - Westmead
Recruitment postcode(s) [2] 29140 0
2065 - Greenwich
Recruitment outside Australia
Country [1] 22283 0
Denmark
State/province [1] 22283 0
Country [2] 22284 0
Ireland
State/province [2] 22284 0

Funding & Sponsors
Funding source category [1] 304821 0
Commercial sector/Industry
Name [1] 304821 0
Vitrolife
Address [1] 304821 0
Gustaf Werners gata 2, 421 32 Västra Frölunda, Sweden
Country [1] 304821 0
Sweden
Primary sponsor type
Commercial sector/Industry
Name
Vitrolife
Address
Gustaf Werners gata 2, 421 32 Västra Frölunda, Sweden
Country
Sweden
Secondary sponsor category [1] 305154 0
None
Name [1] 305154 0
Address [1] 305154 0
Country [1] 305154 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305233 0
IVFAustralia HREC
Ethics committee address [1] 305233 0
176 Pacific Highway, Greenwich 2065, NSW
Ethics committee country [1] 305233 0
Australia
Date submitted for ethics approval [1] 305233 0
30/05/2019
Approval date [1] 305233 0
21/06/2019
Ethics approval number [1] 305233 0
Project No. 155

Summary
Brief summary
The project is a randomised controlled trial to evaluate the clinical effects of a deep learning system, (IVY). IVY studies the images of each embryo during culture. Previous work shows that it is a good predictor of which embryo has highest chance of implanting. This project aims to investigate what effects, if any, this has on the success rate from IVF.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99702 0
Dr Peter Illingworth
Address 99702 0
IVFAustralia,
176 Pacific Highway,
Greenwich
NSW 2065
Country 99702 0
Australia
Phone 99702 0
+61 294251700
Fax 99702 0
+61288441580
Email 99702 0
peter.illingworth@ivf.com.au
Contact person for public queries
Name 99703 0
Dr Peter Illingworth
Address 99703 0
IVFAustralia
176 Pacific Highway,
Greenwich
NSW 2065
Country 99703 0
Australia
Phone 99703 0
+61 294251700
Fax 99703 0
+61288441580
Email 99703 0
peter.illingworth@ivf.com.au
Contact person for scientific queries
Name 99704 0
Dr Peter Illingworth
Address 99704 0
IVFAustralia
176 Pacific Highway,
Greenwich
NSW 2065
Country 99704 0
Australia
Phone 99704 0
+61 294251700
Fax 99704 0
+61288441580
Email 99704 0
peter.illingworth@ivf.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data after deidentification
When will data be available (start and end dates)?
Immediately following publication. No end date
Available to whom?
Case by case at the discretion of the sponsor
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Access by contacting principal investigator by email peter.illingworth@ivf.com.au
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 6678 0
Study protocol
Citation [1] 6678 0
Link [1] 6678 0
Email [1] 6678 0
peter.illingworth@ivf.com.au
Other [1] 6678 0
Type [2] 6679 0
Informed consent form
Citation [2] 6679 0
Link [2] 6679 0
Email [2] 6679 0
peter.illingworth@ivf.com.au
Other [2] 6679 0
Type [3] 6682 0
Ethical approval
Citation [3] 6682 0
Link [3] 6682 0
Email [3] 6682 0
peter.illingworth@ivf.com.au
Other [3] 6682 0
Summary results
No Results