Clinical trial NCT06780605: Correlation of the Genetic Constitution of the Spent Blastocyst Media
Official title: Observational Study to Investigate the Correlation of the Genetic Constitution of the Spent Blastocyst Media (SBM) with the Inner Cell Mass (ICM) and Multifocal Trophectoderm (TE) Biopsies
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Infertility (IVF Patients)
Keywords: PGT-A
Trophectoderm
Inner cell mass
Blastocyst
Infertility
In vitro fertilization
niPGT-A
Embryo development
Embryonic cell-free DNA
Embryo selection
Lead sponsor: Igenomix
Sponsor class: INDUSTRY
First posted: 2025-01-17
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Donated embryos to research from patients undergoing IVF/ICSI or PGT-A cycles will be eligible for the study after informed consent signature.

Brief summary: The main objective of this study is to improve niPGT-A (non-invasive Preimplantation Genetic Testing for Aneuploidies) to avoid the need of a biopsy to perform the genetic analysis of the embryo and to help in understanding the genetic constitution of different parts of the blastocyst (early stage of an embryo development).

For this purpose, we aim to analyses the genetic material released by the embryo to the culture medium (also called Spent Blastocyst Media, SBM) from about 200 blastocysts donated to research by participants of assisted reproduction treatments.

The results will be correlated with the ones obtained from performing the same analysis on biopsies taken from the outer (trophectoderm, TE) and the inner (inner cell mass, ICM) layer of cells in different locations to investigate the mechanisms and origin of the blastocyst genetic content released to the culture medium during preimplantation embryo development.

Detailed description: The study and selection of embryos before transfer is a key step for the success of infertility treatments in assisted reproduction. The current techniques applied are called preimplantation genetic testing of aneuploidies (PGT-A) and are highly sensitive and specific, although they require the retrieval of four to six cells (a biopsy) from an embryo at an early stage of development (blastocyst stage).

Nowadays, the alternatives for embryo selection given to young and healthy women or to couples that do not want to undergo PGT-A are based on studying the morphology and development of the embryos. Unfortunately, these are not reliable methods to know if the embryos have the right number of chromosomes.

A new method called non-invasive PGT-A (niPGT-A) analyses the genetic material released by the embryo to the culture medium (Spent Blastocyst Media, SBM) where the embryo grows in the IVF lab. This genetic material allows for identification of the chromosome number of the embryo. In a previous pilot study, the results of the analysis of the culture media were concordant with the results of the embryo biopsy in 85% of cases.

The current study will analyze the genetic constitution of the SBM and correlate the results of the same analysis on the inner cell mass (ICM) and trophectoderm (TE) cells taken in different locations (multifocal biopsy) to improve our understanding of the mechanisms and origin of the embryo genetic content released to the culture medium during its preimplantational development.

Once this prospective and observational study is approved by the competent Research Ethics Committee, the recruitment and selection of patients will follow. Every potential participant will be asked to sign the study informed consent only after finishing their assisted reproductive treatment.

To comply with the design of this pilot study, a total number of 200 blastocysts donated to research after IVF/ICSI or PGT-A cycles has been estimated to generate enough results. After warming, blastocysts will be subjected to multifocal biopsies of TE, ICM isolation and collection of the SBM. This part of the study will be performed in the collaborating centers. Samples will be shipped to Igenomix Spain for the genetic research and further data analysis.

The expected duration of the study is 18 months. Embryos will be included in the different participating centers for an estimated period of 9 months. Participants involvement in the study is just linked to the moment of the consent form signature for the embryo donation. This study will not imply any modification of a scheduled IVF/ICSI or PGT-A cycles nor extra visits to the recruiting centers.

Eligibility criteria: Inclusion Criteria:

* Study informed consent form, approved by the Ethics Committee, signed.
* Any patient with aneuploid or euploid blastocysts from PGT-A cycles donated for research.
* Patients undergoing regular IVF/ICSI cycles aiming to donate surplus embryos for research.
* Embryos from own or donated oocytes can be included.
* Embryos fertilized with donated sperm can be included.
* Only blastocysts with proper re-expansion and good quality after thawing will be included.

Exclusion Criteria:

* Blastocysts that had not survived to vitrification, that had not re-expanded properly or having poor ICM or TE quality.

Note: No exclusion criteria specific to the patients' background will be considered.

Primary outcomes:
measure: Chromosomal status of the embryos
timeFrame: Up to 6/7 days of embryo development
Secondary outcomes:
Other outcomes:
Locations:
city: Nicosia
country: Cyprus
facility: British Cyprus IVF Hospital
city: Nicosia
country: Cyprus
facility: Ventus IVF Center
Study officials:
affiliation: Igenomix
name: Pere Mir Pardo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Igenomix
name: Luis Navarro Sanchez, PhD
role: PRINCIPAL_INVESTIGATOR
References: