Multi-center Study to Validate niPGT-A

NCT03520933 | Completed

• 1 other identifier: IGX1-NIP-CS-18-02-SUB1
• Study Type: observational
• Target: 2,586
• Locations: 8 countries
• Sites: 10

Brief Summary

Abnormal chromosome number, or aneuploidy, is common in human embryos. It is responsible for more than half of all miscarriages, and it is the leading cause of congenital birth defects. Besides, it has been described that aneuploidy may also affect embryo implantation. Therefore, selecting embryos that have the best chance of implanting and growing into a healthy baby is one of the most important steps in the field of assisted reproduction. Recent advances in genetic technologies, such as Next-Generation Sequencing (NGS), have allowed aneuploidy to be detected with greater sensitivity. The application of this technique to trophectoderm biopsies, taken from embryos before transfer to the uterus, has provided insight into the clinical impact of chromosomal status. This process of screening embryos to make sure they have the right number of chromosomes and to look for any structural abnormalities in the chromosomes is called Preimplantation Genetic Testing for Aneuploidy (PGT-A). It requires specific equipment and trained personnel that will add costs and risks, so non-invasive techniques are sought as an alternative. These non-invasive procedures have been explored by some groups analyzing the spent culture medium where the embryo is cultured up to the time of transfer or freezing. In daily routine, this media is discarded after finishing the embryo culture, but it has been reported that contains traces of embryonic cell-free DNA (cfDNA) that can represent the genetic load of the embryo. However, at the moment there is a high variability in results across studies, with a percentage of concordant results between the media and the trophectoderm biopsy ranging from 3.5 to 85.7%. Thus, the main objective of this project is to validate a new non-invasive method for PGT-A (niPGT-A), based on improved collection and analysis of the culture media to achieve higher rates of sensitivity and specificity and to decrease the effect of some intrinsic difficulties such as low embryonic cfDNA input, mosaicism and maternal contamination.

Conditions

Aneuploidy; Chromosome Abnormality; Infertility

Keywords

Embryo; Blastocyst; Non-invasive; PGT-A; Chromosome; Aneuploidy; Spent culture medium; Trophectoderm biopsy

Outcome Measures

Primary Outcomes (1)

• Chromosomal status of the embryos

  Concordance on number and structure of the chromosomes between biopsy and spent blastocyst media samples analysis results.

  6 to 7 days of embryo development

Secondary Outcomes (4)

• Pregnancy rate

  20 weeks

• Clinical miscarriage rate

  20 weeks

• Analysis of the Products of Conception (POC)

  Up to 20 weeks

• Live birth rate

  40 weeks

Study Arms (1)

Embryos undergoing PGT-A / niPGT-A

Embryos from IVF patients between 20 and 44 years of age, undergoing PGT-A for any medical indication, with own oocytes or ovum donation cycles and with single embryo transfer (SET)

Diagnostic Test: PGT-A; Diagnostic Test: niPGT-A

Interventions

PGT-A DIAGNOSTIC_TEST

PGT-A will be carried out following the usual clinical practice: Trophectoderm biopsy samples from blastocysts are analyzed by NGS to screen for numerical chromosomal abnormalities.

Embryos undergoing PGT-A / niPGT-A

niPGT-A DIAGNOSTIC_TEST

Non-invasive preimplantation genetic test for embryo aneuploidy analyzing the spent culture media where the embryo is incubated up to the time of vitrification. This media contains traces of embryonic cell-free DNA (cfDNA) that can represent the genetic load of the embryo.

Embryos undergoing PGT-A / niPGT-A

Eligibility Criteria

• Age: 20 Years - 44 Years
• Gender Eligibility Details: IVF patients
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Embryos from IVF patients between 20 and 44 years of age, undergoing PGT-A for any medical indication, with own oocytes or ovum donation cycles and with single embryo transfer (SET).

You may qualify if:

• PGT-A cases with trophectoderm biopsy and SET for any medical indication and signed written informed consent form approved by the EC/IRB after having been duly informed of the nature of the research and voluntarily accepted to participate in the study.
• ICSI (Intra Cytoplasmic Sperm Injection), IVF (In Vitro Fertilization) or ICSI/IVF performed in fresh oocytes from couples are allowed.
• Note: Donor sperm is allowed.
• Only fresh oocytes allowed.
• Fresh and Deferred Embryo Transfer are allowed. Note: In case of Deferred Embryo Transfer, embryos must be vitrified always after the blastocyst biopsy.
• Age: 20-44 years of age (both included).

You may not qualify if:

• A known abnormal karyotype in a member of the couple.
• Preimplantation Genetic Testing for Monogenic diseases (PGT-M) or Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) cases excluded.

Sponsors & Collaborators

• Igenomix: lead

Study Sites (10)

San Diego Fertility Center

San Diego, California, 92130, United States

Location

Boston IVF Fertility Clinic

Boston, Massachusetts, 02109, United States

Location

Dominion Fertility

Arlington, Washington, 22203, United States

Location

Pregna Medicina Reproductiva

Buenos Aires, C1425DGQ, Argentina

Location

Nilo Frantz - Centro de Reprodução Humana

Boa Vista, Porto Alegre, 91330-002, Brazil

Location

Genera Rome

Rome, Roma, 00197, Italy

Location

NASCERE

Mexico City, Mexico City, 05120, Mexico

Location

Inmater - Clínica de Fertilidad

Lima, 15036, Peru

Location

ProcreaTec

Madrid, 28036, Spain

Location

Bahçeci Group

Istanbul, 07720, Turkey (Türkiye)

Location

Related Publications (1)

• Sakkas D, Navarro-Sanchez L, Ardestani G, Barroso G, Bisioli C, Boynukalin K, Cimadomo D, Frantz N, Kopcow L, Andrade GM, Ozturk B, Rienzi L, Weiser A, Valbuena D, Simon C, Rubio C. The impact of implementing a non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) embryo culture protocol on embryo viability and clinical outcomes. Hum Reprod. 2024 Sep 1;39(9):1952-1959. doi: 10.1093/humrep/deae156.

  PMID: 39059790 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

* Culture media: Embryonic cell-free DNA (cfDNA) * Trophectoderm biopsy * Inner cell mass biopsy

MeSH Terms

Conditions

Aneuploidy; Chromosome Aberrations; Infertility

Condition Hierarchy (Ancestors)

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

Study Officials

• Carmen Rubio, BSc PhD

  Igenomix

  PRINCIPAL INVESTIGATOR

• Carlos Simón, MD PhD

  Igenomix

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2018
• First Posted: May 11, 2018
• Study Start: April 27, 2018
• Primary Completion: December 19, 2022
• Study Completion: February 10, 2023
• Last Updated: May 24, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1); TU (1); ES (1); AR (1); IT (1); PE (1); BR (1); US (3)