Preimplantation Genetic Testing (PGT)



What is PGT?


When embryos are created during natural conception or in an IVF laboratory, sometimes things could go wrong.


Some embryos may have abnormal chromosome numbers (aneuploidy) or structures (rearrangements).


These abnormalities can include additional, fewer chromosome copies, chromosomal translocations, and inversions, all of which lead to the wrong amount or locations of genetic material. Aneuploidy is a particularly common error in the female germ cell, which is made even more susceptible to ageing1. Depending on the severity of such abnormalities, some embryos fail to develop at all, whereas others give rise to offspring with severe disabilities.


Some embryos can also carry faulty genes (monogenic mutations) that cause diseases.


If one or both parents carry a gene mutation, their child is at an increased risk of developing the genetic disease. Some of these diseases are lethal, whilst others may require lifelong treatment. Some well-known examples are cystic fibrosis, sickle cell anemia, and Huntington disease.


Before embryos are transferred to the uterus, PGT can be performed to select genetically healthy embryos – those that are not affected by chromosomal abnormalities or faulty genes.


The benefit of genetic testing at a preimplantation stage as compared to traditional post-conception diagnostic tests (ie. Amniocentesis, chorionic villus sampling) is that only genetically healthy embryos are transferred to the uterus, preventing the difficult decision of terminating a pregnancy if post-conception diagnostic results turn out unfavourable2. This is particularly valuable for people who are at high risk of having a child affected with adverse genetic conditions or have had previous pregnancy complications.


What can it test?


PGT for aneuploidy (PGT-A) tests whether an embryo has the normal 46 chromosomes or has extra or fewer chromosomes (aneuploidy). The result is used for selecting embryos with the correct chromosome numbers.

PGT for monogenic conditions (PGT-M) can be designed to test a genetic disorder caused by a specific gene, knowing the location of the faulty gene. This may be helpful for parents who carry a genetic mutation known to cause severe genetic diseases such as Cystic fibrosis.


PGT for structural rearrangements (PGT-SR) can be used to detect structural abnormalities of chromosomes. This test is advised for parents who themselves carry a chromosomal rearrangement, which may affect their embryos.


What is involved?


The first step is to generate embryos in standard in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle. PGT can only be performed with assisted reproductive technologies because some cells must be removed from the embryo (biopsy). The embryos are then carefully grown in the laboratory. During the next few days, embryos keep dividing and grow into a ball of cells. Usually, on day 5 or 6, a few cells are taken from each embryo to be used in genetic testing (biopsy). While genetic testing is underway, the embryos are usually frozen to halt growth. Embryos that are tested genetically healthy will be thawed and used to transfer or kept frozen for future transfer. Embryos that did not pass the tests are discarded.


Who should consider PGT?


- If you or your partner have a hereditary genetic disease and are worried about passing the genetic condition to your child.


- If you or your partner has a known family history of chromosome abnormality.


-If you had a chromosomal abnormality (ie. Trisomy) in a previous pregnancy.


- If you are at a more advanced maternal age (>35 years old)If you have had unexplained recurrent miscarriages.


-If past embryo transfers or fertility treatments have been repeatedly unsuccessful

Important considerations


It should be noted that PGT, like all alternative fertility methods, can only help increase the chance of having a healthy child or preventing miscarriages. It does not guarantee a successful pregnancy, live birth or a child with no genetic conditions.


PGT result is intended for selecting embryos but cannot fix any detected errors.

PGT is not a perfect tool. Although errors are unlikely, they could occur due to technological limitations when dealing with small samples. Therefore, it is possible for a genetic abnormality to go undetected and couples at risk of genetic conditions are advised to consider confirming PGT results during pregnancy using post-conception diagnostic tests3.


Although most embryos survive the biopsy required for PGT, some may be lost in this procedure4. Whether this invasive procedure has long-term effects on the surviving embryos are currently unknown.


An embryo may be mosaic, meaning that the embryo contains cells with both normal and abnormal genetic material5. In such cases, the PGT result may only hold true to some cells in the embryo6. Therefore, there is the possibility that an embryo with the potential to develop into a healthy baby may be discarded due to a false positive result based on a few cells carrying abnormal chromosomes. Similarly, an abnormal embryo may be selected for transfer due to a false negative result generated from a few cells that carry normal genetic materials.


PGT comes at an additional cost in addition to an IVF cycle. Please contact a fertility specialist at Zeta Fertility for more information.


References


1. Greaney, J., Wei, Zhe., Homer, H. (2018). Regulation of chromosome segregation in oocytes and the cellular basis for female meiotic errors. Human Reproduction Update, 24(2), 135-161.


2. Lamb, B., Johnson, E., Francis, L., Fagan, M., Riches, N., Wilson, A., Johnstone, E. (2018). Pre-implantation genetic testing: decisional factors to accept or decline among in vitro fertilization patients. Journal of Assisted Reproduction and Genetics, 35(9), 1605-1612.


3. Brezina, P. R., & Kutteh, W. H. (2015). Clinical applications of preimplantation genetic testing. BMJ, 350, g7611.


4. Cimadomo, D., Capalbo, A., Ubaldi, F. M., Scarica, C., Palagiano, A., Canipari, R., & Rienzi, L. (2016). The impact of biopsy on human embryo developmental potential during preimplantation genetic diagnosis. BioMed Research International, 2016.


5. Gleicher N, Vidali A, Braverman J, Kushnir VA, Barad DH, Hudson C, et al. Accuracy of preimplantation genetic screening (PGS) is compromised by degree of mosaicism of human embryos. Reprod Biol Endocrinol. 2016;14(1):54


6. Spinella F, Fiorentino F, Biricik A, Bono S, Ruberti A, Cotroneo E, et al. Extent of chromosomal mosaicism influences the clinical outcome of in vitro fertilization treatments. Fertil Steril. 2018;109(1):77-83

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