Comprehensive chromosome screening (CCS), also known as Preimplantation Genetic Testing for Aneuploidy (PGT-A), is a genetic test performed on embryos during in vitro fertilization (IVF). This screening helps identify embryos with an abnormal number of chromosomes before they are transferred to the uterus. Its purpose in reproductive medicine is to enhance the chances of a successful pregnancy and reduce the likelihood of certain complications. The test provides valuable information to guide decisions about which embryos are most likely to result in a healthy live birth.
What is Comprehensive Chromosome Screening?
Comprehensive Chromosome Screening (CCS) identifies numerical chromosomal abnormalities, known as aneuploidy, in embryos. This test aims to improve in vitro fertilization (IVF) outcomes by selecting embryos with a normal chromosome count for transfer.
Humans typically have 46 chromosomes, arranged in 23 pairs, with one set inherited from each parent. An embryo with this normal complement of 46 chromosomes is termed “euploid.”
In contrast, aneuploidy refers to an embryo having an abnormal number of chromosomes, either too many or too few. For example, Down syndrome (Trisomy 21) is caused by an extra copy of chromosome 21. Aneuploidy is a common occurrence in human embryos and can lead to various adverse outcomes, including failed implantation, miscarriage, or, in some cases, the birth of a child with health problems.
How the Screening is Performed
Comprehensive chromosome screening is integrated into the in vitro fertilization (IVF) process. After eggs are fertilized with sperm in the laboratory, the resulting embryos are allowed to develop for several days. The screening typically occurs when the embryo reaches the blastocyst stage, usually between five and seven days after fertilization, when it has developed into a structure containing 70 to 150 cells.
During this stage, an embryologist performs an embryo biopsy, carefully removing a small number of cells from the trophectoderm. The trophectoderm is the outer layer of cells that will eventually form the placenta, ensuring the inner cell mass, which develops into the fetus, remains undisturbed. After the biopsy, the embryo is frozen while the removed cells are sent to a specialized genetics laboratory for analysis.
The genetic analysis of these biopsied cells uses Next-Generation Sequencing (NGS) or array Comparative Genomic Hybridization (array-CGH). NGS involves sequencing thousands of small DNA pieces to determine the number of chromosomes present in the cells. These techniques meticulously examine all 23 pairs of chromosomes to identify any numerical abnormalities, providing a comprehensive assessment of the embryo’s chromosomal status.
What the Screening Reveals
The results of comprehensive chromosome screening categorize embryos primarily into three groups: euploid, aneuploid, and mosaic.
Euploid Embryos
Euploid embryos are those identified as having a normal number of chromosomes, meaning 46 chromosomes (23 pairs). Transferring euploid embryos is associated with higher implantation rates and an increased likelihood of a successful live birth, as they possess the correct genetic balance for healthy development.
Aneuploid Embryos
Conversely, aneuploid embryos are found to have an abnormal number of chromosomes, either missing or having extra copies of whole chromosomes or segments. These chromosomal imbalances often lead to implantation failure, miscarriage, or severe developmental issues if the pregnancy progresses. Consequently, aneuploid embryos are generally not recommended for transfer due to their low potential for successful pregnancy and birth.
Mosaic Embryos
A third category, mosaic embryos, contain a mixture of both normal (euploid) and abnormal (aneuploid) cells within the biopsied sample. The proportion of abnormal cells can vary, and while mosaic embryos have a reduced developmental potential compared to fully euploid embryos, some, particularly those with a lower percentage of aneuploid cells, can still result in healthy live births. The interpretation of mosaic results requires careful consideration, and decisions regarding their transfer are often made in consultation with genetic counselors and fertility specialists, balancing the potential for success against the associated risks.
Who Should Consider This Screening
Comprehensive chromosome screening is a valuable option for several patient populations undergoing IVF, aiming to improve their reproductive outcomes.
Advanced Maternal Age
One common indication is advanced maternal age, typically for women aged 35 years or older. As women age, the risk of producing eggs with an abnormal number of chromosomes significantly increases, leading to a higher incidence of aneuploidy in embryos. PGT-A can help identify chromosomally normal embryos in this group, potentially reducing the negative impact of age on IVF success rates.
Recurrent Miscarriage
Individuals with a history of recurrent miscarriage, defined as two or more failed pregnancies, may also benefit from this screening. Chromosomal abnormalities are a leading cause of miscarriage. By screening embryos for aneuploidy, PGT-A can help identify and avoid transferring embryos that are likely to result in another miscarriage.
Previous Unsuccessful IVF Cycles
Patients who have experienced previous unsuccessful IVF cycles, despite transferring embryos that appeared visually healthy, are another group for whom PGT-A is often considered. In such cases, undetected chromosomal abnormalities in the transferred embryos may have contributed to the implantation failure.
Severe Male Factor Infertility
Additionally, couples facing severe male factor infertility may be advised to consider PGT-A, as certain sperm abnormalities can also increase the risk of aneuploidy in embryos. The screening aims to increase implantation rates, decrease miscarriage rates, and reduce the overall time to achieve a successful pregnancy for these individuals.