ClinicalTrials.gg
TerminatedNCT04000152niPGT-A_RCTUpdated Oct 1, 2025

RCT Study to Validate niPGT-A Clinical Benefit.

An interventional study of niPGT-A and Morphology criteria in Aneuploidy, Chromosome Abnormality and Infertility, sponsored by Igenomix. Terminated at 8 sites in 5 countries. Open to female participants aged 20 Years to 40 Years. Per ClinicalTrials.gov, last updated 2025-10-01.

Sponsored by Igenomix (part of Vitrolife) · Not applicable, Interventional, and Diagnostic

Why this study was terminated
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
Phase
Not applicable
Study type
Interventional
Enrollment
296
Allocation
Randomized
Ages
20 Years to 40 Years
Sex
Female
01

Study 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.

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.

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.

02

Conditions studied

  • Aneuploidy
  • Chromosome Abnormality
  • Infertility

Keywords

  • Blastocyst
  • Non-invasive
  • PGT-A
  • Aneuploidy
  • Spent culture medium
  • Trophectoderm biopsy
  • Sustained implantation
  • Miscarriage
  • Livebirth
03

In context

Aneuploidy

73 studies on the registry are indexed under Aneuploidy; 10 are open to participants now.

This study's enrollment of 296 is above the median of 200 across 34 interventional studies indexed under Aneuploidy.

Browse Aneuploidy studies →

Lead sponsor

Igenomix is the lead sponsor of 31 studies on the registry; 3 are open to participants now.

First submitted before Igenomix became part of Vitrolife.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 40 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patients whose written 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.

Exclusion criteria

Exclusion Criteria:

  • 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.
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
296 participants (actual)

Study arms

  • Active comparator
    Control group (group 1)

    Deferred single day 6/7 blastocyst transfer with blastocyst selection according to morphology.

    Other: Morphology criteria

  • Experimental
    Intervention group (group 2)

    Deferred single day 6/7 blastocyst transfer with blastocyst selection according to the analysis of the spent culture media (niPGT-A).

    Diagnostic Test: niPGT-A

Interventions

  • Diagnostic testniPGT-A

    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.

  • OtherMorphology 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.

06

What researchers measure

Primary outcomes

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

    Number and structure of the embryo chromosomes

    Time frame: 7 days

  2. Ongoing pregnancy rate

    Number of ongoing pregnancies per single embryo transfer

    Time frame: Over 12 weeks

Secondary outcomes

  1. NGS results of the SBM

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

    Time frame: 7 days at least

  2. Non-Invasive Prenatal Testing (NIPT)

    Incidence of chromosomal abnormalities in NIPT within ongoing pregnancy cases

    Time frame: Up to 12 weeks

  3. Clinical miscarriage rate

    Number of clinical miscarriages per total number of ongoing pregnancies

    Time frame: 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

    Time frame: Up to 20 weeks

  5. Cumulative ongoing pregnancy rate

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

    Time frame: 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

    Time frame: Up to 6 months after the ovum pick-up

  7. Live birth rate

    Number of babies born per embryo transfer

    Time frame: Over 40 weeks

  8. Cumulative live birth rate

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

    Time frame: 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.

    Time frame: Over 40 weeks

07

Study locations

8 sites
  • Crecer: Centro de Reproducción y Genética Humana
    Mar del Plata, Buenos Aires, Argentina
  • Saresa - Reproducción Humana Asistida
    Salta, Salta Province 4400, Argentina
  • Nilo Frantz - Centro de Reprodução Humana
    Boa Vista, Porto Alegre 91330-002, Brazil
  • Vida - Centro de Fertilidade
    Rio de Janeiro, Rio de Janeiro 22793-080, Brazil
  • Hôpital Foch
    Suresnes, Suresnes 92150, France
  • Società Italiana Studi di Medicina della Riproduzione (S.I.S.M.e.R.)
    Bologna, Bologna 40138, Italy
  • Centro Procreazione Assistita DEMETRA
    Florence, Firenze 50141, Italy
  • Hospital Ruber Internacional
    Madrid, Madrid 28035, Spain
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Jun 2020 to primary completion in Apr 2025, 57 months.

How these figures are worked out, and which studies are left out of them.

Registered
Jun 25, 2019
First posted
Jun 27, 2019
StartActual
Jun 29, 2020
Primary completionActual
Apr 18, 2025
CompletionActual
Apr 18, 2025
Last update
Oct 1, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Oct 1, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04000152
Lead sponsor
Igenomix
Responsible party
Sponsor
First posted
Jun 27, 2019
Start date
Jun 29, 2020
Primary completion
Apr 18, 2025
Completion
Apr 18, 2025
Last update
Oct 1, 2025

Study contacts

Carmen Rubio, PhD
principal investigator · Igenomix S.L.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Sep 2025. You cannot join it, but the record below documents what was studied.

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