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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04000152




Registration number
NCT04000152
Ethics application status
Date submitted
25/06/2019
Date registered
27/06/2019
Date last updated
12/05/2020

Titles & IDs
Public title
RCT Study to Validate niPGT-A Clinical Benefit.
Scientific title
Randomized Controlled Clinical Study to Assess the Benefit of Non-invasive PGT-A, by the Analysis of Spent Blastocyst Media, as a Tool for Embryo Prioritization in Infertile Patients Undergoing Assisted Reproduction.
Secondary ID [1] 0 0
IGX1-NIP-CS-18-05
Universal Trial Number (UTN)
Trial acronym
niPGT-A_RCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aneuploidy 0 0
Chromosome Abnormality 0 0
Infertility 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Diagnosis / Prognosis - niPGT-A
Other interventions - Morphology criteria

Active Comparator: Control group (group 1) - Deferred single blastocyst transfer with blastocyst selection according to morphology.

Experimental: Intervention group (group 2) - Deferred single blastocyst transfer with blastocyst selection according to the analysis of the spent culture media (niPGT-A).


Diagnosis / Prognosis: niPGT-A
Two scenarios should be considered according to the results in the SBM analysis:
The couple decides to transfer the blastocyst selected according to the SBM result (blastocyst prioritization system).
The couple decides to biopsy the blastocysts (if SBM results show low euploidy score). This PGT-A analysis will be offered for free but the outcome of these transfers will be excluded for the analysis per completed protocol. However, all transfers will be included in the intention-to-treat analysis.

Other interventions: Morphology criteria
Embryos for transfer will be selected by the only applicable technique, the assessment of morphology according to Gardner´s criteria, which is the most standardized method.

Intervention code [1] 0 0
Diagnosis / Prognosis
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Non-invasive analysis of the chromosomal status of the embryo - Number and structure of the embryo chromosomes
Timepoint [1] 0 0
7 days
Primary outcome [2] 0 0
Ongoing pregnancy rate - Number of ongoing pregnancies per single embryo transfer
Timepoint [2] 0 0
Over 12 weeks
Secondary outcome [1] 0 0
NGS results of the SBM - Informativity rates and prioritization category of the SBM analysis results with embryo development, culture conditions and collection time
Timepoint [1] 0 0
7 days at least
Secondary outcome [2] 0 0
Non-Invasive Prenatal Testing (NIPT) - Incidence of chromosomal abnormalities in NIPT within ongoing pregnancy cases
Timepoint [2] 0 0
Up to 12 weeks
Secondary outcome [3] 0 0
Clinical miscarriage rate - Number of clinical miscarriages per total number of ongoing pregnancies
Timepoint [3] 0 0
Up to 6 months after the ovum pick-up
Secondary outcome [4] 0 0
Analysis of the Products of Conception (POC) - Incidence of chromosomal abnormalities in POC within miscarriage cases
Timepoint [4] 0 0
Up to 20 weeks
Secondary outcome [5] 0 0
Cumulative ongoing pregnancy rate - Cumulative ongoing pregnancy rate per patient in the 6 months after the pick-up
Timepoint [5] 0 0
Over 6 months after the ovum pick-up
Secondary outcome [6] 0 0
Time to get an ongoing pregnancy - Time to get an ongoing pregnancy within the 6 months after the pick-up
Timepoint [6] 0 0
Up to 6 months after the ovum pick-up
Secondary outcome [7] 0 0
Live birth rate - Number of babies born per embryo transfer
Timepoint [7] 0 0
Over 40 weeks
Secondary outcome [8] 0 0
Cumulative live birth rate - Cumulative live birth rate per patient in the 6 months after the pick-up
Timepoint [8] 0 0
Over 6 months after the ovum pick-up
Secondary outcome [9] 0 0
Obstetrical outcomes comparison - To compare birth weight, gestational age, APGAR, type of delivery, pregnancy complications, etc.
Timepoint [9] 0 0
Over 40 weeks

Eligibility
Key inclusion criteria
- Patients whose written informed consent approved by the Ethics Committee (EC) has been
obtained, after having been duly informed of the nature of the study and voluntarily
accepted to participate after being fully aware of the potential risks, benefits and
any discomfort involved.

- IVF patients intending to undergo deferred day 6/7 blastocyst SET for any medical
indication.

- All the oocytes/embryos from the cycle should follow the laboratory protocol described
in the study (embryo culture and vitrification on day 6/7).

- ICSI, IVF or ICSI/IVF performed in fresh own oocytes from couples not undergoing
PGT-A. Note: Donor sperm is allowed.

- Female age: 20-40 years, both included.
Minimum age
20 Years
Maximum age
40 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- A known abnormal karyotype if the couple provides it at consultation. If not,
karyotype is not compulsory.

- Couples planning to undergo PGT-M or PGT-SR cases will be excluded.

- Surrogate pregnancy (in those countries where it is allowed).

- ERA test and embryo transfer according to ERA result.

- Time-lapse culture systems are not allowed after day 4 of culture.

- Presence of pathologies or malformations that affect the uterine cavity such as
polyps, intramural myomas = 4cm or submucosal, septum or hydrosalpinx during the
patient's participation in the study. Patients suffering these pathologies before or
after their inclusion in the study can participate if the pathology is corrected
before performing any study procedure.

- Any illness or medical condition that is unstable or which, according to medical
criteria, may put at risk the patient's safety and her compliance in the study.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
SA
Recruitment hospital [1] 0 0
Fertility SA - Adelaide Fertility & IVF Clinic - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
Argentina
State/province [5] 0 0
Buenos Aires
Country [6] 0 0
Argentina
State/province [6] 0 0
Salta
Country [7] 0 0
Brazil
State/province [7] 0 0
Porto Alegre
Country [8] 0 0
Brazil
State/province [8] 0 0
Rio De Janeiro
Country [9] 0 0
Italy
State/province [9] 0 0
Firenze
Country [10] 0 0
Italy
State/province [10] 0 0
Torino
Country [11] 0 0
Spain
State/province [11] 0 0
Madrid
Country [12] 0 0
Turkey
State/province [12] 0 0
Istanbul

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Igenomix
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Chromosomal aneuploidies are linked with spontaneous miscarriages and abnormal offspring in
human pregnancies. In addition, some types of aneuploidy are reported to prevent
implantation. Thus, there is a need to identify the embryos with highest implantation
potential on in vitro fertilization (IVF) programs.

Since embryo morphology and kinetics have a weak association with embryo ploidy,
trophectoderm biopsy plus Next-Generation Sequencing (NGS) is becoming a very popular
approach to determine the embryo chromosomal status. This technique is called Preimplantation
Genetic Testing for Aneuploidy (PGT-A). Although shown to be efficient, it is invasive for
the embryo, requires specific technical skills and it remains expensive. Therefore, the
development of a non-invasive, rapid and cheaper method for assessing embryo ploidy status
would represent a progress in the field of IVF.

The non-invasive approach has been explored by some groups that analyzed the Spent Blastocyst
Medium (SBM) where the embryo was incubated up to the time of transfer or freezing. In daily
routine, this media is discarded after finishing the culture of the embryo. Importantly,
though, this media reportedly contains traces of embryonic cell-free DNA (cfDNA) that can
represent the genetic load of the embryo.

On the basis of that, the hypothesis of this study is that embryo prioritization according to
the analysis of the embryonic cfDNA in the SBM could improve ongoing pregnancy rate in 10
percentual points compared to standard blastocyst transfer based on morphology.
Trial website
https://clinicaltrials.gov/show/NCT04000152
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Carmen Rubio, PhD
Address 0 0
Igenomix S.L.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Carlos Gómez, BSc MSc
Address 0 0
Country 0 0
Phone 0 0
+34 963905310
Fax 0 0
Email 0 0
carlos.gomez@igenomix.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04000152