Preimplantation Genetic Testing
for Aneuploidy (PGT-A)
PGT-A determines if an embryo contains the normal number of chromosomes prior to pregnancy, transfer of which can optimize the success of an In Vitro Fertilization (IVF) cycle and reduce the chance of miscarriage.
Understanding Chromosomes: Aneuploidy & Euploid
Chromosomes are the blueprints of our body and are important for healthy development. They are the structures in our cells that carry our genetic information (genes).
Most individuals have 46 chromosomes in each of our cells, which come in 23 pairs (including pairs 1 through 22 and a 23rd for X [female] or Y [male]); one copy of each chromosome is inherited from the egg, and the other from the sperm. Embryos with the correct number of chromosomes (46) are Euploid, which have a better chance of leading to a successful pregnancy.
Aneuploidy refers to an abnormal number — too many or too few — of chromosomes. If an egg or sperm is missing or has an extra chromosome, the embryo with a missing or extra chromosome is Aneuploidy. The most well known example of aneuploidy is Down Syndrome, which is caused by an extra copy of chromosome 21. Edwards Syndrome and Turner Syndrome are also known aneuploidy.
Aneuploidy does not typically run in families, but occurs spontaneously in developing eggs and embryos. Up to 60% of early miscarriages are due to aneuploidy, the risk for aneuploidy increases with a woman’s age.
Benefits of PGT-A
PGT-A (formerly known as PGS), refers to genetic tests conducted on embryos before they are implanted in an IVF cycle
These tests are the only way to determine if an embryo contains the normal number of chromosomes prior to pregnancy.
PGT-A enables selection of an embryo with the normal number of chromosomes, reducing the chance of failed implantation, an early miscarriage, or a child with a chromosome abnormality (that can cause birth defects and intellectual disabilities).
Without PGT-A, embryos are selected for transfer based only on their physical appearance, which is not always correlated with chromosomal content. Therefore, a well-developed embryo may be selected for transfer, but may not result in a pregnancy because it is aneuploidy.
Every couple is at risk of producing embryos with chromosomal abnormalities. This risk increases with maternal age. Most embryos with chromosomal abnormalities fail to implant or result in miscarriage.
PGT-A offers a way to select the best embryo(s) for transfer to maximizes the chances of having a successful IVF cycle.
Indications for PGT-A
Reproductive Genetic Innovations offers testing for all 24 chromosomes, using Next-Generation Sequencing and state-of-the-art technologies with the capacity to test all the chromosomes.
PGT-A is performed on embryo biopsy samples. Following oocyte (egg) retrieval and fertilization, one or more cells are removed from a blastocyst (day 5 to 6 embryo) and are transported to RGI for PGT-A analysis. PGT-A does not require the submission of any parental DNA samples or work-up prior to testing.
Next-Generation Sequencing (NGS)
In Next-Generation Sequencing, the DNA sequence of embryo biopsies is directly analyzed.
This is used primarily to identify if there are extra or missing copies of whole chromosomes. This testing may sometimes detect smaller pieces of duplicated or deleted chromosomal material. The high sensitivity of NGS results in DNA of certain chromosomes being missing (Mosaicism). Some of these mosaic chromosomes can be transferred if there are no non-mosaic embryos. RGI genetic counselors can guide patients through management options if such circumstances arise. Accuracy for this testing is 98%, when performed on a blastocyst (day 5/6) embryo biopsy.
Resources:
Madjunkov, M., Sharma, P., Baratz, A., Glass, K., Abramov, R., Logan, N., Madjunkova, S., & Librach, C. (2024). Prenatal cell-free DNA screening for chromosomal aneuploidies after euploid embryo transfer shows high concordance with preimplantation genetic testing for aneuploidy results and low positive predictive values. Fertility and Sterility, 122(1), 47-55.
Wang L, Wang X, Li M, Liu Y, Ou X, Chen L, Shao X, Quan S, Duan J, He W, Shen H, Sun L, Yu Y, Cram DS, Leigh D, Yao Y. PGT-A: The biology and hidden failures of randomized control trials. Prenat Diagn. 2022 Aug;42(9):1211-1221. doi: 10.1002/pd.6199. Epub 2022 Jul 25. PMID: 35765263.
Wang L, Wang X, Liu Y, Ou X, Li M, Chen L, Shao X, Quan S, Duan J, He W, Shen H, Sun L, Yu Y, Cram DS, Leigh D, Yao Y. IVF embryo choices and pregnancy outcomes. Prenat Diagn. 2021 Dec;41(13):1709-1717. doi: 10.1002/pd.6042. Epub 2021 Oct 14. PMID: 34480803.
Tiegs AW, Tao X, Zhan Y et al. A multicenter, prospective, blinded, nonselection study evaluating the predictive value of an aneuploid diagnosis using a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy assay and impact of biopsy. Fertil Steril 2021;115(3):627-637
Forman, E.J., Upham, K.M., Hong, K.H., Zhao, T., Treff, N.R., Scott, R.T. (2013). Comprehensive chromosome screening alters traditional morphology-based embryo selection: A randomized clinical trial. Fertility and Sterility, 100(3), 870-875.
Scott RT Jr, Ferry K, Su J, Tao X, Scott K, Treff NR. Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study. Fertil Steril. 2012 Apr;97(4):870-5. doi: 10.1016/j.fertnstert.2012.01.104. Epub 2012 Feb 2. PMID: 22305103.
