Clinical trial NCT06940973: Study of Abnormally Fertilized Embryos
Official title: Prospective Observational Study of the Morphokinetics and Ploidy of Blastocysts With Abnormal Fertilization (1PN, 2.1PN and 3PN) to Identify the Origin of Fertilization Alterations
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
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
Lead sponsor: Igenomix
Sponsor class: INDUSTRY
First posted: 2025-04-23
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Diploidy rate in haploid embryos from IVF/ICSI
timeFrame: 3 months
measure: Diploidy rate in triploid embryos from IVF/ICSI
timeFrame: 3 months
Secondary outcomes:
measure: Origin of the chromosomal abnormalities in embryos with a non-diploid chromosomal content
timeFrame: 6 months
measure: Pregnancy rate of euploid embryos from abnormal fertilization
timeFrame: 2 weeks after the embryo transfer
measure: Implantation rate of euploid embryos from abnormal fertilization
timeFrame: Up to 4 weeks after the embryo transfer
measure: Biochemical pregnancy rate of euploid embryos from abnormal fertilization
timeFrame: 4 weeks after the embryo transfer with euploid embryos from abnormal fertilization
measure: Ectopic pregnancy rate of euploid embryos from abnormal fertilization
timeFrame: 4-5 weeks after the embryo transfer
measure: Clinical miscarriage rate of euploid embryos from abnormal fertilization
timeFrame: Up to 12 gestational weeks
measure: Ongoing pregnancy rate of euploid embryos from abnormal fertilization
timeFrame: Over 12 gestational weeks
measure: Voluntary termination rate of euploid embryos from abnormal fertilization
timeFrame: Up to 12 gestational weeks
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Equipo Médico Crespo Valencia
state: Comunidad Valenciana
Study officials:
affiliation: Igenomix
name: Pere Mir Pardo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Igenomix
name: Carmen Rubio Lluesa, PhD
role: PRINCIPAL_INVESTIGATOR
References: