Overview of PGD Technology

For the past few years, the use of array comparative genome hybridization (aCGH) offered a substantial improvement in preimplantation genetic screening (PGS), increasing the number of tested chromosomes from a handful to 24 chromosomes. Unfortunately, his seemingly improved technology came at a cost since aCGH is estimated to have at least 2% error rate.

What makes array CGH prone to errors?

Array CGH is an indirect measurement as it relies on hybridization signals. During the hybridization process, clinical samples are labeled with a fluorescent dye and then hybridized against an array of known chromosome regions. Signals coming from each array are then scanned and analyzed using normal male and female references.

One key limitation of array CGH and other hybridization techniques is the susceptibility to signal saturation. In the case of PGS, hybridization signals arising from multiple chromosomes are beyond the aCGH sensitivity level, thus preventing the detection of polyploidy which is the presence of more than the two normal sets of chromosomes.

A second technical limitation of aCGH is detection of sex chromosome abnormalities such as Triple X (XXX), Klinefelter (XXY), or XYY syndromes. While failure to detect Triple X is due to the saturation issue, the limited detection of XXY and XYY syndromes is a result of aCGH’s limited sensitivity in Y chromosome detection.

The Y chromosome is relatively small compared to the X chromosome and it is riddled with repetitive sequences which present challenges for probe design and detection using aCGH. Considering this, it is not surprising that gender selection by aCGH is sometimes inconclusive due to the same effect.

Impact on IVF outcome

Misdiagnosis reduces implantation and pregnancy success rates, and it is linked to the transmission of genetic disorders to newborns, not to mention a psychological and financial impact on patients. For this reason, clinicians, researchers, and IVF professionals are constantly searching for new diagnostic tools with higher accuracy and lower cost for patients.

Alternative and Future Trend

Next Generation Sequencing has revolutionized the field of genetic testing, and preimplantation genetic diagnosis is not an exception. Today, with recent technology improvements, NGS is a practical and affordable option for IVF centers that demand faster, more reliable, and more accurate testing for their clients. In contrast to aCGH, Next Generation Sequencing provides direct sequencing of actual embryo DNA at single nucleotide level, providing coverage, sensitivity, and precision superior to any existing technology.