Study of Abnormally Fertilized Embryos

NCT06940973 | Not Yet Recruiting

• 1 other identifier: EJC-SAFE-24-02
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to determine the diploidy rate of haploid and triploid embryos from in vitro fertilization (IVF) cycles. The main questions it aims to answer are:

• Can a molecular genetic fertilization check of abnormally fertilized embryos be used to expand opportunities for couples undergoing assisted reproduction treatment?
• Is the chromosomal loss or gain present in abnormally fertilized embryos predominantly maternal in origin? For this purpose, we will evaluate the morphokinetics and ploidy of about 300 embryos with different types of abnormal pronuclear patterns (1PN, 2.1PN, and 3PN) that reach the blastocyst stage. Whenever possible, embryos with a non-diploid chromosomal complement will also be assessed to determine the origin (maternal or paternal) of the chromosomal set that has been lost or gained. Study subjects will follow their previously scheduIed IVF/ICSI treatment and no additional visits/interventions will be required for participating.

Conditions

Infertility (IVF Patients)

Keywords

PGT-A; niPGT-A; Blastocyst; Infertility; In vitro fertilization; Ploidy; Embryo development; Time-lapse culture; Triploid; Haploid; Abnormal fertilization; Pronuclei

Outcome Measures

Primary Outcomes (2)

• Diploidy rate in haploid embryos from IVF/ICSI

  Number of 2PN blastocysts from abnormally fertilized oocytes (1PN)

  3 months

• Diploidy rate in triploid embryos from IVF/ICSI

  Number of 2PN blastocysts from abnormally fertilized oocytes (2.1PN and 3PN)

  3 months

Secondary Outcomes (8)

• Origin of the chromosomal abnormalities in embryos with a non-diploid chromosomal content

  6 months

• Pregnancy rate of euploid embryos from abnormal fertilization

  2 weeks after the embryo transfer

• Implantation rate of euploid embryos from abnormal fertilization

  Up to 4 weeks after the embryo transfer

• Biochemical pregnancy rate of euploid embryos from abnormal fertilization

  4 weeks after the embryo transfer with euploid embryos from abnormal fertilization

• Ectopic pregnancy rate of euploid embryos from abnormal fertilization

  4-5 weeks after the embryo transfer

Study Arms (1)

Blastocysts from abnormally fertilized oocytes during assisted reproduction

During the conventional ICSI/IVF procedures in the laboratory, the embryologist observing fertilization will identify embryos with an abnormal pronuclear pattern and preselect them for the study. These embryos will be cultured in a time-lapse incubator following the laboratory's standard practice. All recorded morphokinetic parameters, along with the corresponding images, will be documented. Each embryo will be monitored, its developmental quality assessed and recorded to determine whether it reaches the blastocyst stage. If so, the researchers will contact the patient to ask consent for these embryos to be included in the study. Embryos with an abnormal pronuclear pattern that fail to reach the blastocyst stage due to developmental blockage will be discarded. No drugs or medical devices will be used.

Genetic: Parental samples; Diagnostic Test: PGT-A; Genetic: TE rebiopsies and spent blastocyst media collection

Interventions

Parental samples GENETIC

On fertilization, following the conventional ICSI/IVF procedure, samples from cumulus cells (obtained during the routine oocyte denudation process) and surplus sperm cells present in seminal plasma will be retrieved. These samples will be stored frozen at -20°C until they are sent to Igenomix. There, they will be used to perform the genetic analysis required to achieve the study's objectives, provided the patient consents to participate. If the patient ultimately chooses not to participate, these samples will be destroyed. Parents may be asked to provide a saliva sample for the same purpose in cases where obtaining the samples during fertilization was not possible or if the collected samples were unsuitable for processing in the laboratory. The saliva sample may be collected at the clinic during one of the scheduled visits for reproductive treatment or, alternatively, by the parents at home using a kit provided by the clinic.

Blastocysts from abnormally fertilized oocytes during assisted reproduction

PGT-A DIAGNOSTIC_TEST

On day 3 of development, assisted hatching will be performed to facilitate biopsy at the blastocyst stage. Each embryo will be biopsied in the laboratory using conventional trophectoderm (TE) biopsy techniques on day +5, +6, or +7 of development, depending on when they reach the appropriate blastocyst stage. After biopsy, blastocyst will be vitrified following the clinical routine protocol and store until the genetic results are available. The biopsy samples will be placed in a PCR tube labeled with its corresponding study-specific code and stored in a cold rack at 4°C before being transferred to a freezer at -20°C. Finally, the samples will be sent to the Igenomix for preimplantation genetic testing for aneuploidy.

Blastocysts from abnormally fertilized oocytes during assisted reproduction

TE rebiopsies and spent blastocyst media collection GENETIC

After obtaining the PGT-A results, any embryo not genetically confirmed as euploid and without ploidy abnormalities will be thawed, washed, and cultured for rebiopsy. A complementary analysis using next-generation sequencing (NGS) techniques will be performed to confirm the diagnosis and determine the origin of the abnormalities. For this additional analysis, in addition to the new biopsies, the individual culture medium of each embryo will be aspirated after an incubation period of 8 to 24 hours. The collected medium will be placed in PCR tubes and stored in a freezer at -20°C before being sent to the laboratory. Regardless the result of these complementary analysis, no rebiopsied blastocyst will be considered for clinical purposes.

Blastocysts from abnormally fertilized oocytes during assisted reproduction

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Embryos from subjects undergoing assisted reproductive treatment with oocytes exhibiting an abnormal number of pronuclei (1PN, 2.1PN, and/or 3PN). Recruitment of subjects for the study will be conducted through routine consultation with the principal investigator and collaborators, as long as they meet the selection criteria.

You may qualify if:

• ART patients who sign the Informed Consent of the study.
• Age: oocytes from women ≤ 49 years and semen from men ≤ 60 years. Donation of gametes is allowed.
• ≥1 blastocysts from oocytes with an abnormal pronuclear pattern (1PN, 2.1PN, and/or 3PN) and with the presence of 2 polar bodies (PB), cultured in a time-lapse incubator.

Sponsors & Collaborators

• Igenomix: lead

Study Sites (1)

Equipo Médico Crespo Valencia

Valencia, Valencia, 46015, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

Cummulus cells and seminal plasma or saliva from both parents. Blastocyst trophectoderm biopies. Spent blastocyst media with embryonic cell-free DNA.

MeSH Terms

Conditions

Infertility; Triploidy

Condition Hierarchy (Ancestors)

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

Study Officials

• Pere Mir Pardo, PhD

  Igenomix

  PRINCIPAL INVESTIGATOR

• Carmen Rubio Lluesa, PhD

  Igenomix

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carlos A Gomez De La Cruz, BSc MSc

CONTACT

+34963905310; carlos.gomez@igenomix.com

Study Design

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

Study Record Dates

• First Submitted: April 16, 2025
• First Posted: April 23, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 23, 2025

Record last verified: 2025-04

Locations

ES (1)