What you need to know about preimplantation genetic testing (PGT-A)?

Preimplantation genetic testing for aneuploidy (PGT-A) increases the chances of a successful pregnancy, but the outcome also heavily depends on the embryo's morphology, its development speed, and the mother's age.

The influence of embryo quality (morphology) on implantation and birth rates

There is a widespread opinion that according to PGT-A results and if the embryo has a correct chromosomal set (euploidy), its morphology no longer plays any role in implantation success and pregnancy. However, studies show that despite everything, the morphological quality of the embryo is very important and should be considered when choosing the embryo to transfer into the uterus.

Thus, Zhao et al. (2018) analyzed the results of euploid embryo transfers in women under 35 and highlighted the following relationship between quality and birth rate:

• High quality (AA) and good quality (AB or BA): 50.0% and 49.7% birth rates respectively.
• Average quality (BB or AC, CA): 42.3% birth rate.
• Low quality (CB and BC): 25.0% birth rate.

The role of embryonic development dynamics

Another important predictive factor for successful implantation is the development speed of the embryo up to the blastocyst stage. This stage is characterized by the presence of 156 to 200 cells and is necessary for implantation into the uterine cavity.

Giulia et al. (2022) compared the results of euploid embryo transfers reaching the blastocyst stage on the 5th or 7th day. It was found that the probability of a child's birth is higher if the embryo reached the blastocyst stage on the 5th day, which is linked to high energy potential and mitochondrial activity. This confirms that it is better for the embryo to become a blastocyst on the 5th or, at the latest, the 6th day.

The influence of reproductive age of the woman

Reig et al. (2020) showed that the birth rate decreases with the mother's age, even in the case of transfer of a euploid embryo. Thus, the birth rate is 63% among women under 35 and drops to 53% among women over 42. This confirms the crucial importance of age for the success prognosis.

The possibility of obtaining a euploid embryo in the next cycle

If no euploid embryo is obtained during a PGT-A, this does not mean there is no chance in the future. Herlihy et al. (2022) showed that the probability of obtaining a euploid embryo during a new IVF attempt is related to the woman's age and does not depend on the results of the first cycle.

It is also important to note that during IVF with PGT programs, doctors can select the embryo to transfer more precisely, which increases the chances of successful implantation and the birth of a healthy child. Using IVF with PGT allows detection of potential chromosomal abnormalities and reduces the risk of transmitting genetic diseases to the next generation.

Complex aneuploidy, mosaicism, and chaotic embryos

In some cases, the PGT-A report contains terms such as “complex aneuploidy” (presence of three or more chromosomal anomalies) or “complex mosaicism” (presence of three or more mosaic anomalies). If six or more chromosomal anomalies are detected in an embryo, it is classified as “chaotic,” and if it has six or more mosaic anomalies, it is classified as “chaotic mosaic.” These embryos are not recommended for transfer.

What is the best time to perform a biopsy for PGT-A?

Previously, the biopsy was performed on the third day of development, when the embryo consisted of only 8 cells, which negatively impacted its viability. With the development of vitrification technology and the extension of PGT-A to all chromosomes, the blastocyst stage (5-6 days), when the embryo contains 156-200 cells and the extraction of 5-8 cells does not disturb its development, has become the optimal moment.

Additionally, biopsy on the 5th day is more informative because many embryos naturally stop developing between the 3rd and 5th days, most often due to genetic abnormalities. Moreover, mosaic cells at this stage can self-correct, reducing the risk of erroneous results.

Interpretation of mosaicism

Mosaicism is the presence of euploid and aneuploid cells within the same embryo. For evaluation, concepts of “low-level” and “high-level” mosaicism are used:

• Low level (low level mosaic)—20 to 40% of cells show anomalies.
• High level (high level mosaic)—40 to 80% of cells show aneuploidies.

Some laboratories use their own gradations. The level of mosaicism plays a decisive role in the decision to transfer or not an embryo, as it directly influences the chances of pregnancy and the birth of a healthy child.

Bibliography

1. J Assist Reprod Genet. March 16, 2020; 37(3): 595-602. The impact of age beyond ploidy: outcome data from 8175 euploid single embryo transfers — Andres Reig et al.
2. Chin Med J (Engl). June 5, 2018; 131(11): 1261-1267. Overall Blastocyst Quality, Trophectoderm Grade, and Inner Cell Mass Grade Predict Pregnancy Outcome in Euploid Blastocyst Transfer Cycles — Yan-Yu Zhao et al.
3. Hum Reprod. May 30, 2022; 37(6): 1134-1147. When is it too slow? Complete portrait of day 7 blastocysts and their standardized clinical value thanks to artificial intelligence — Danilo Cimadomo et al.
4. Fertil Steril. September 2022; 118(3): 484-491. The chances of obtaining a euploid embryo and subsequent live birth remain consistent with national age-based rates after an IVF cycle that only produced aneuploid embryos — Nola S Herlihy et al.

On our blog, we reviewed the article “Opening the future: a comprehensive guide to preimplantation genetic testing (PGT)”.