AzTrials
AzTrials

AneuploidyniPGT-A_RCTNCT04000152

RCT Study to Validate niPGT-A Clinical Benefit.

A study testing niPGT-A and Morphology criteria in people with Aneuploidy and Chromosome Abnormality, run by Igenomix at 8 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 20 to 40 years, women only
Conditions the study is for
Aneuploidy, Chromosome Abnormality, Infertility
What is being tested?
niPGT-A and Morphology criteria
Could I receive a placebo?
No, everyone receives an active treatment
How many people
296 participants
Where
8 sitesin 5 countries
Study dates
29 Jun 2020to 18 Apr 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 40 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • Assisted hatching and artificial collapse before collecting SBM samples. Note: Both procedures are allowed only after collecting the culture media sample.
  • 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.

Trial locations and contacts

8 sites in 5 countries.

8 sites in 5 countries

Argentina2 sites
  • Crecer: Centro de Reproducción y Genética Humana

    Mar del Plata, Buenos Aires

  • Saresa - Reproducción Humana Asistida

    Salta, Salta Province, 4400

Other trials in Argentina

Brazil2 sites
  • Nilo Frantz - Centro de Reprodução Humana

    Boa Vista, Porto Alegre, 91330-002

  • Vida - Centro de Fertilidade

    Rio de Janeiro, Rio de Janeiro, 22793-080

Other trials in Brazil

Italy2 sites
  • Società Italiana Studi di Medicina della Riproduzione (S.I.S.M.e.R.)

    Bologna, Bologna, 40138

  • Centro Procreazione Assistita DEMETRA

    Florence, Firenze, 50141

Other trials in Italy

France1 site
  • Hôpital Foch

    Suresnes, Suresnes, 92150

Other trials in France

Spain1 site
  • Hospital Ruber Internacional

    Madrid, Madrid, 28035

Other trials in Spain

About this study

Official 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.

Chromosomal aneuploidies are linked with spontaneous miscarriages and abnormal offspring in human pregnancies. In addition, some types of aneuploidies 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.

Read more

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.

Read the detailed description

Current Preimplantation Genetic Testing for Aneuploidy (PGT-A) techniques analyze the full chromosome content of a single or few cells with high sensitivity and specificity using Next-Generation Sequencing (NGS). Although shown to be efficient, the technique suffers from some limitations. It requires an embryo biopsy, specific technical skills and it still remains expensive. Therefore, non-invasive techniques for assessing embryo ploidy status are sought as an alternative. Such non-invasive approaches would have various advantages over current strategies, including the elimination of a costly micromanipulation biopsy procedure and the avoidance of risks associated with cell removal. Furthermore, it would be more advantageous, especially for those patients who undergo in vitro fertilization (IVF) treatment but do not have PGT-A indication or they are not willing to have their embryos tested with invasive techniques.

One of the recent advances in the field is the identification of embryonic cell-free DNA (cfDNA) during embryo culture in the lab. It is released to the culture drop (SBM) and represents the chromosome content of the embryo. In a recent pilot study, we analyzed the concordance rates between trophectoderm (TE) biopsy and SBM. In SBM collected on day 6/7 of development, the results were concordant with TE biopsies in 84% of samples, with a false-positive rate of 8.6% and a false-negative rate of 2.5%. These findings are encouraging and were the base for the design of the current RCT study.

The main objective of this study is to evaluate the potential clinical benefits of a new non-invasive method for PGT-A, based on the analysis of the embryonic cfDNA released into SBM.

Considering a dropout rate of around 30% (mainly due to treatment or monitoring failures and no day 6/7 blastocysts to transfer), a total of 1108 participants will be randomized before the ovum pick-up. They will be allocated on a balanced way (1:1 ratio) in one of the two arms: 1) Deferred transfer of a single frozen day 6/7 blastocyst which selection was based on the chromosomal status according to the analysis of the SBM; 2) Deferred transfer of a single frozen day 6/7 blastocyst which selection was based on standard embryo morphology (Gardner criteria). Reproductive outcomes (defined following The International Glossary on Infertility and Fertility Care, 2017) will be compared between the two groups.

As this is an open study, both physician and patient will receive the results of the analysis of the culture media. The control group will also have access to these results but at the end of their participation in the study and if she or her physician request it. Additional tests of chromosomal abnormalities (NIPT and POC) could be performed (with no extra cost) under request to ensure patient´s safety and efficacy of the SBM analysis.

Data exported from the medical records and source documents will be duly codified to protect the clinical and personal information of patients in accordance with the current legislation. This information will be exported to an electronic Case Report Form (eCRF). An interim analysis of this data is planned once 30% of the recruitment has been reached. Besides, the study will be overseen by an independent Data Monitoring Committee after 30% of patients´ recruitment.

Being tested
niPGT-A, Morphology criteria
Keywords
Blastocyst, Non-invasive, PGT-A, Aneuploidy, Spent culture medium, Trophectoderm biopsy, Sustained implantation, Miscarriage, Livebirth
Medical subject headings
Aneuploidy, Chromosome Aberrations, Infertility, Abortion, Spontaneous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • niPGT-ADiagnostic test

    Two scenarios should be considered according to the results in the SBM analysis:

    1. The couple decides to transfer the blastocyst selected according to the SBM result (blastocyst prioritization system).
    2. 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.

    In the exceptional case of getting a non-informative result for all the SBM analysed, the niPGT-A could be performed again on new SBM samples collected after an additional culture of the embryos for, at least, 8 hours.

  • Morphology criteriaOther

    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.

Study groups in NCT04000152
Study groupRoleWhat they receive
Control group (group 1)Active comparatorDeferred single day 6/7 blastocyst transfer with blastocyst selection according to morphology.
Receives: Other: Morphology criteria
Intervention group (group 2)ExperimentalDeferred single day 6/7 blastocyst transfer with blastocyst selection according to the analysis of the spent culture media (niPGT-A).
Receives: Diagnostic Test: niPGT-A

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Non-invasive analysis of the chromosomal status of the embryo

    Number and structure of the embryo chromosomes

    Measured: 7 days

  2. Ongoing pregnancy rate

    Number of ongoing pregnancies per single embryo transfer

    Measured: Over 12 weeks

Secondary outcomes (9)
  1. NGS results of the SBM

    Informativity rates and prioritization category of the SBM analysis results with embryo development, culture conditions and collection time

    Measured: 7 days at least

  2. Non-Invasive Prenatal Testing (NIPT)

    Incidence of chromosomal abnormalities in NIPT within ongoing pregnancy cases

    Measured: Up to 12 weeks

  3. Clinical miscarriage rate

    Number of clinical miscarriages per total number of ongoing pregnancies

    Measured: Up to 6 months after the ovum pick-up

  4. Analysis of the Products of Conception (POC)

    Incidence of chromosomal abnormalities in POC within miscarriage cases

    Measured: Up to 20 weeks

  5. Cumulative ongoing pregnancy rate

    Cumulative ongoing pregnancy rate per patient in the 6 months after the pick-up

    Measured: Over 6 months after the ovum pick-up

  6. Time to get an ongoing pregnancy

    Time to get an ongoing pregnancy within the 6 months after the pick-up

    Measured: Up to 6 months after the ovum pick-up

  7. Live birth rate

    Number of babies born per embryo transfer

    Measured: Over 40 weeks

  8. Cumulative live birth rate

    Cumulative live birth rate per patient in the 6 months after the pick-up

    Measured: Over 6 months after the ovum pick-up

  9. Obstetrical outcomes comparison

    To compare birth weight, gestational age, APGAR, type of delivery, pregnancy complications, etc.

    Measured: Over 40 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2019
  2. Study start29 Jun 2020
  3. Primary completion18 Apr 2025
  4. Study completion18 Apr 2025

Why it stopped: The recruitment was halted on Mar 1st 2024, after the Data Monitoring Committee, due to low recruitment speed and sustained high dropout rate. Other elements impacted negatively, including the SARS-COV-2 pandemic or the inability to include new sites

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
296 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04000152
Sponsor's protocol ID
IGX1-NIP-CS-18-05
Acronym
niPGT-A_RCT
Status last verified
Sep 2025
First submitted
25 Jun 2019
Last updated
1 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing niPGT-A and Morphology criteria in people with Aneuploidy and Chromosome Abnormality, run by Igenomix at 8 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Argentina, Brazil, Italy, France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was stopped early (reason given: The recruitment was halted on Mar 1st 2024, after the Data Monitoring Committee, due to low recruitment speed and sustained high dropout rate. Other elements impacted negatively, including the SARS-COV-2 pandemic or the inability to include new sites). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Non-invasive analysis of the chromosomal status of the embryo (time frame: 7 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2025.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in