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Pre-implantation Genetic Testing In IVF

Dr Alex Re genetic testing IVF

What is pre-implantation genetic testing (PGT)?

A significant portion of embryos created by either natural conception or Assisted Reproductive Technology may carry genetic abnormalities such as incorrect number of chromosomes. These mistakes are usually fatal as they lead to implantation failures or miscarriages. Although it may sound horrible, these failed pregnancies are actually nature’s screening mechanism to ensure that genetically healthy babies are born.

But very rarely, an embryo carrying mistakes that are not serious enough to cause a miscarriage may lead to a live birth with serious genetic problems. This is why post-conception genetic tests are performed to screen for genetic disorders like Down Syndrome. In addition, as a woman reaches 35 years old, the chances of genetic mistakes occurring dramatically increase, making pregnancy screening very important.

Much like how a pregnant woman can use a first trimester screening to test for genetic abnormalities, pre-implantation genetic testing does the same job but in an IVF treatment, at a much earlier time.  

Main differences between PGT and post-conception testing

PGT is performed at a very early stage of embryo development (day 5 after fertilization) because the embryos are grown in a medium culture that embryologists can access. In a natural pregnancy, the first genetic screening is done at around 10-12 weeks. This means that for an embryo tested abnormal with PGT, it will not be transferred into a woman’s uterus and thus will not result in a pregnancy. But if a woman finds out she is already carrying an embryo with genetic mistakes, the family may have to make the tough decision of terminating the pregnancy.  

 What can PGT test for?

  • Aneuploidy: Incorrect (extra or fewer) numbers of chromosomes
  • Monogenic conditions: Known genetic mutations that cause monogenic diseases such as Cystic Fibrosis
  • Structural rearrangements: Structural abnormalities of chromosomes that may lead to implantation failures and miscarriages

How is PGT performed?

Biopsy

This is currently the most used technique for PGT. It involves taking 5-6 cells from a blastocyst embryo (day 5), which in most cases have the same genetic information as other cells. The biopsy takes cells that are going to form the placenta instead of the embryo itself, therefore usually does not affect development. However, there are concerns that invading into the embryo may damage it in ways that we don’t yet know.

Cell-free DNA Screening

One of the alternative but new approaches to poking a needle into the embryo is by sampling DNA from the culture medium that houses the embryo. While this is promising and does not do any damage to the growing embryo, the medium also contains the mother’s DNA. This makes figuring out the embryo’s genetic makeup tricky. Since this alternative approach is still being investigated, researchers may find solutions in the future.

Blastocoel Fluid Testing

This is another new way of testing that still involves going inside the embryo, but only taking fluid instead of cells. This approach is less invasive than biopsy, while also taking DNA directly from within the embryo. However, this is also an active area of research and more studies are needed to improve its accuracy.

If you would like to find out if PGT if of benefit to you and your partner please discuss it at your next appointment.

References

ReproductiveFacts. Age and Fertility. https://www.reproductivefacts.org/news-and-publications/patient-fact-sheets-and-booklets/documents/fact-sheets-and-info-booklets/age-and-fertility/

Scott, Richard T, Upham, Kathleen M, Forman, Eric J, Hong, Kathleen H, Scott, Katherine L, Taylor, Deanne, … Treff, Nathan R. (2013). Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertility and Sterility, 100(3), 697–703. https://doi.org/10.1016/j.fertnstert.2013.04.035

Vera-Rodriguez, Diez-Juan, Jimenez-Almazan, Martinez, Navarro, Peinado, … Simon. (2018). Origin and composition of cell-free DNA in spent medium from human embryo culture during preimplantation development. Human Reproduction, 33(4), 745–756. https://doi.org/10.1093/humrep/dey028

Palini, S., Galluzzi, De Stefani, Bianchi, Wells, Magnani, & Bulletti. (2013). Genomic DNA in human blastocoele fluid. Reproductive BioMedicine Online, 26(6), 603–610. https://doi.org/10.1016/j.rbmo.2013.02.012