Study of Abnormally Fertilized Embryos (SAFE)

Igenomix

Status: Not yet enrolling

Conditions: Infertility (IVF Patients)

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

Study type: Observational

Funder types: Industry

Identifiers

NCT06940973

EJC-SAFE-24-02

Details and patient eligibility

About

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.

Full description

Chromosomes are cellular structures containing the majority of the genetic information of a living organism. Gametes (oocytes and spermatozoa) contain only a single set of 23 chromosomes within structures known as pronuclei (PN). Upon fertilization, the 23 chromosomes from the oocyte and the 23 chromosomes from the sperm combine to form a 2PN zygote, which contains a total of 46 chromosomes.

In assisted reproduction (ART) laboratories, the embryologists can determine through morphological evaluation whether the fertilization process was normal (2PN) or abnormal (0PN, 1PN, or >2PN). For an ART treatment, only a successfully fertilized oocyte (2PN) that develops to the blastocyst stage may be suitable for embryo transfer. However, previous studies have demonstrated that some embryos from oocytes with abnormal fertilization may possess a normal chromosomal content and could be used in ARTs when embryos from normal fertilization are not available.

There are genetic analysis techniques to determine not only if an embryo is euploid (contains a normal number of chromosomes) but also to assess if it is haploid, diploid or triploid (1PN, 2.1PN, and 3PN respectively). These techniques may be applied to "rescue" embryos with abnormal fertilization that are currently being discarded. This approach could be beneficial for IVF patients with a limited number of viable embryos available (diminished ovarian reserve cases, advanced maternal age, poor response to ovarian stimulation, etc.).

The current prospective and observational study has been approved by the competent Research Ethics Committee and every potential participant will be asked to sign the study informed consent.

The 300 embryos that will be part of the study will be recruited in the laboratory of the collaborating center on the day of fertilization after performing the conventional IVF procedures. Following these same routine procedures, biological samples from both parents will also be stored to perform the genetic analysis to determine the origin of the chromosomal anomalies. A biopsy will be taken from the selected embryos when they reach the blastocyst stage for the genetic analysis that will allow detecting whether there is indeed any chromosomal anomaly. All embryos not confirmed as chromosomally normal will be thawed, washed, and cultured for a second biopsy to confirm their previous diagnosis and the origin of the chromosomal abnormalities. For this new analysis, in addition to the biopsies, individual samples of the culture media of the thawed blastocysts will be collected and stored. Samples will be shipped to Igenomix for the genetic research and further data analysis.

The expected duration of the study is 18 months. Embryos will be included in the participating center for an estimated period of 13 months. Participants involvement in the study is just linked to the moment of the consent form signature. Exceptionally, embryos from abnormal fertilization that were informed as chromosomally normal after the first biopsy can be considered to transfer providing there are no other embryos available. If the patient decides to proceed with the transfer, her clinical follow-up will be part of the study until achieving ongoing pregnancy (12 gestational weeks). After that, her participation in the study will end but her physician will continue monitoring the pregnancy until delivery, if applicable, in accordance with the standard clinical practice.

Enrollment: 300 estimated patients

Sex: All

Ages: 18 to 49 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• No exclusion criteria have been considered for this study.

Trial design

300 participants in 1 patient group

Blastocysts from abnormally fertilized oocytes during assisted reproduction

Description:

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.

Treatment:

Genetic: TE rebiopsies and spent blastocyst media collection

Diagnostic Test: PGT-A

Genetic: Parental samples