RCT Study to Validate niPGT-A Clinical Benefit.

NCT04000152 | Terminated DMC

• 1 other identifier: IGX1-NIP-CS-18-05
• Study Type: interventional
• Target: 296
• Locations: 5 countries
• Sites: 8

Brief 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.

Conditions

Aneuploidy; Chromosome Abnormality; Infertility

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Non-invasive analysis of the chromosomal status of the embryo

  Number and structure of the embryo chromosomes

  7 days

• Ongoing pregnancy rate

  Number of ongoing pregnancies per single embryo transfer

  Over 12 weeks

Secondary Outcomes (9)

• NGS results of the SBM

  7 days at least

• Non-Invasive Prenatal Testing (NIPT)

  Up to 12 weeks

• Clinical miscarriage rate

  Up to 6 months after the ovum pick-up

• Analysis of the Products of Conception (POC)

  Up to 20 weeks

• Cumulative ongoing pregnancy rate

  Over 6 months after the ovum pick-up

Study Arms (2)

Control group (group 1)

ACTIVE COMPARATOR

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

Other: Morphology criteria

Intervention group (group 2)

EXPERIMENTAL

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

niPGT-A DIAGNOSTIC_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.

Intervention group (group 2)

Morphology criteria OTHER

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.

Control group (group 1)

Eligibility Criteria

• Age: 20 Years - 40 Years
• Gender Eligibility Details: IVF patients between 20 and 40 years of age undergoing fertility treatment with their own oocytes, with no intention or medical indication for PGT-A.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Igenomix: lead

Study Sites (8)

Crecer: Centro de Reproducción y Genética Humana

Mar del Plata, Buenos Aires, Argentina

Location

Saresa - Reproducción Humana Asistida

Salta, Salta Province, 4400, Argentina

Location

Nilo Frantz - Centro de Reprodução Humana

Boa Vista, Porto Alegre, 91330-002, Brazil

Location

Vida - Centro de Fertilidade

Rio de Janeiro, Rio de Janeiro, 22793-080, Brazil

Location

Hôpital Foch

Suresnes, Suresnes, 92150, France

Location

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

Bologna, Bologna, 40138, Italy

Location

Centro Procreazione Assistita DEMETRA

Florence, Firenze, 50141, Italy

Location

Hospital Ruber Internacional

Madrid, Madrid, 28035, Spain

Location

MeSH Terms

Conditions

Aneuploidy; Chromosome Aberrations; Infertility; Abortion, Spontaneous

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Diseases; Urogenital Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications

Study Officials

• Carmen Rubio, PhD

  Igenomix S.L.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2019
• First Posted: June 27, 2019
• Study Start: June 29, 2020
• Primary Completion: April 18, 2025
• Study Completion: April 18, 2025
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

BR (2); IT (2); FR (1); AR (2); ES (1)