What is Pre-implantation Genetic Screening?
Chromosomal abnormalities are the most common cause of miscarriage in the first trimester and a leading cause of congenital abnormalities in live born infants. Unfortunately, rates of chromosomally abnormal embryos increase with maternal age, correlating with increased risk of miscarriage, genetic diseases, and infertility. For women between the ages 35-39 years, approximately 40-50% of embryos can be abnormal, increasing above 50% over the age of 40 years. Preimplantation genetic screening (PGS) is an option for all patients undergoing In-Vitro Fertilization (IVF) as a way of identifying chromosomally abnormal (aneuploid) embryos before embryo transfer.
PGS screens for numerical chromosomal abnormalities in all 23 chromosomes. Any embryo with a missing chromosome (monosomy) will typically cease to implant or grow past the first trimester, and although a few of those with an extra chromosome (trisomy) will go to term, they will result in a child with a genetic disease such as Down syndrome (Trisomy 21).
The high aneuploidy rate in women over 40 is the reason why many embryos will either never implant or will miscarry, making spontaneous conception very difficult. By using IVF with PGS we transfer only genetically normal embryos, leading to increased rates of implantation and decreased risk of spontaneous abortion1. Additionally, a well-designed randomized trial recently showed that transferring a single genetically normal “euploid” embryo had similar pregnancy rates compared to transferring two untested embryos, while resulting in a significantly lower risk of a twin pregnancy and associated complications2.
Who should use PGS?
PGS should be strongly considered/recommended in patients of advanced reproductive age (both maternal and paternal) and those with recurrent implantation failure or pregnancy loss. The American Society of Reproductive Medicine (ASRM) issued a practice committee brief communication stating that the value of medically recommending universal PGS for patients regardless of age or medical history has yet to be determined3. However, all patients undergoing IVF can electively choose to use PGS to select for the best embryos.
How is PGS performed?
At our laboratory, we use the most advanced type of genetic testing available, called Next-Generation Sequencing (NGS). After oocyte retrieval and fertilization, the embryo is incubated in culture media for 5-6 days, at which point it is called a “blastocyst”. The blastocyst is made up of an inner cell mass, which will ultimately develop into the fetus, and external cells called the trophectoderm, which will form the placenta. Once the embryologist confirms the morphology of the blastocyst to be normal, they remove 3-7 cells from the trophectoderm without disturbing the inner cell mass. Using this method avoids any damage to the developing inner cell mass and future fetus. The cells are then sent to an outside facility to have full 23 chromosome analysis performed, including determination and evaluation of the sex chromosomes. After cell biopsy, the embryo is cryopreserved for future transfer. It takes approximately 1-2 weeks to have the results of the genetic testing. In addition to determining the gender of each embryo (which you may choose not to have disclosed), the results show the report of each chromosome. A normal “euploid” embryo, will have 2 copies of every chromosome tested. Abnormal embryos include those with extra chromosomes (commonly known as trisomy), missing chromosomes (monosomy), or pieces of chromosomes missing (partial gains/losses).
Using NGS has significantly increased the sensitivity of detecting abnormal embryos, however, with improved detection comes and increased risk of mosaicism. Mosaicism is defined as the presence of two or more cell populations with different chromosome results. Because only the outer trophectoderm cells are biopsied, when an embryo results as mosaic, there is a very small chance that the inner cell mass may be genetically normal. However, given the risk of transferring a genetically abnormal embryo, the current standard of care is not to transfer mosaic embryos.
Overall, our goal with PGS is to select for only euploid embryos, allowing transfer of embryos with the lowest risk of miscarriage and the best chance of success to result in a healthy full term infant.
- Scott RT Jr, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, et al. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril 2013;100:697–703.
- Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, et al. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril 2013;100:100–7.e1.
- ASRM practice committee brief communication. Pre-implantation Genetic Screening for Aneuploidy: a committee opinion. 2016