Preimplantation Genetic Testing (PGT) Preimplantation genetic testing (PGT) is a screening test that can be performed on embryos created via in vitro fertilization (IVF) to genetically analyze the embryos prior to transfer. One of the most common reasons that an embryo transfer does not result in a pregnancy is due to abnormal chromosomal constitution of the embryo. PGT-A (testing embryo for aneuploidy) can ensure that the embryo selected for transfer has the correct number of chromosomes, thereby reducing the chances for a failed IVF cycle and reducing the chance of miscarriage.
In addition, a missing or an extra chromosome in the embryo can lead to congenital abnormality such as turner and Down syndromes. PGT-SR (testing embryos for structural rearrangements such as translocation or inversion) can prevent spontaneous abortion and partial trisomy or monosomy. PGT-M (testing embryos for single gene disease) can prevent single gene disorders (like sickle cell anemia), or the which can cause hereditary diseases and birth defects.
Who are good candidates for PGT?
Screening for monogenic diseases (PGT-M) Some patients seek IVF with PGT to reduce the chance of a specific genetic condition occurring in their children. This type of PGT is called preimplantation genetic testing for monogenic disorders (PGT-M). In some cases, the patient themselves may have a genetic condition such as neurofibromatosis type 1 or Marfan syndrome that could be passed on to their children. In other cases, both members of a couple may be carriers for a recessive genetic condition such as cystic fibrosis or sickle cell anemia, or the individual using their eggs may be a carrier for an X-linked condition such as Fragile X syndrome.
HLA matching is also available for families with certain blood disorders who may wish for an embryo that could be an HLA match for a sibling or other family member.
Our physicians and genetic counselor work closely with such patients and other ART centers to offer services for designing personalized testing for their embryos. The goal of PGT-M is to predict which embryos are free of the genetic condition for which they are at risk, allowing the physician to select those embryos for transfer. PGT-M can greatly reduce the risk of having an affected child prior to pregnancy.
Screening for chromosome abnormalities (PGT-A and PGT-SR): PGT can also evaluate an embryo’s chromosomes, the structures in every cell that contain our genes. It is not uncommon for embryos have random chromosome abnormalities such as missing or extra chromosomes, also known as aneuploidy. Embryos with aneuploidy are more likely to result in a miscarriage or failed IVF cycle. Less commonly, aneuploidy may result in the birth of a child with a chromosome condition such as Down syndrome (trisomy 21).
In a typical IVF cycle, embryos are chosen for transfer based on their appearance under the microscope, which is referred to as their quality grade. The embryo’s appearance can give us some indication of its potential to result in a successful pregnancy, but it is not perfect. Preimplantation genetic testing for aneuploidy (PGT-A) provides additional information about the reproductive potential of the embryos and may help select the best embryo for transfer. PGT-A is most often considered for patient who have had recurrent pregnancy losses (miscarriages), multiple unexplained failed IVF cycles, a prior pregnancy or child with certain chromosome abnormalities, or based on the age of the individual providing their eggs. While PGT-A can be performed for any IVF cycle, there are both benefits and limitations that should be carefully discussed with your physician to determine if PGT-A is right for you.
One final type of PGT called PGT-SR is for structural rearrangements. This type of PGT is performed when a patient or their partner has a rearrangement of their own chromosomes such as a translocation or inversion. A person with a structural rearrangement of their own chromosomes is at increased risk to produce embryos with missing or extra pieces of chromosomes. Embryos with missing or extra pieces of chromosomes are more likely to result in a miscarriage or a child with serious health issues. PGT-SR can help to reduce those risks. Candidates for PGT-A include:
How are PGT-A, PGT-SR and PGT-M performed on embryos during IVF? The first step to the three types of PGT, which is embryo biopsy, is the same. The second step is analysis of the biopsy by a laboratory to conduct genetic testing on DNA. For PGT-A and PGT-SR comprehensive chromosomal screening usually by aCGH or NGS techniques will be performed.
Sometimes FISH technique performs for just two chromosomes involved in the translocation. In both forms of testing, usually the biopsy is at the blastocyst (day 5 or day 6 of embryo culture) stage of development, but sometimes blastomere biopsy in cleavage stage (dya three) performs. The blastocyst consists of two cell types, trophectoderm (TE) that allows the placenta to develop and the inner cell mass (ICM) that later develops into the baby. The biopsy removes 3-10 cells from the trophectoderm (pre-placenta) for laboratory testing for genetic disorders. The cells that are destined to make the baby are not disturbed. Results are usually available within 7-10 days following the biopsy.
The blastocyst is frozen right after it is biopsied to wait for the results of the testing and then is thawed and transferred to the woman in a subsequent cycle.
PGT risks: There are no documented health risks for children born after PGT testing beyond the normal health risks to mother and child through IVF. Handling of the embryo, its biopsy, freezing, and thawing results in a small risk of damage leading to an embryo that does not implant. Generally, around 5% of embryos evaluated by PGT are lost due to such damage. Another risk of PGT is inaccuracy in test findings due to mosaicism in the embryonic cells, which means sometimes the biopsied cells (specially in cleavage stage) are different from other cells of the embryo. For this reason, it is recommended that the patient undergo typical prenatal testing when she is pregnant, such as amniocentesis.
Family Balancing (Gender Selection): In some society desire for determining the sex of child before conception is very prominent. In the other side some of the genetic diseases such as hemophilia, are X linked and can be prevented in next generation by sex selection of the offspring.
Pre-determination of offspring gender in natural conception have been tried for many years, but with very limited success. Controlling the time of sex intercourse and ovulation time may be is the most successful in vivo method, but this method just increases the likelihood of conception with a desired child sex.
Reproduction via in vitro fertilization can increase the chance of controlling the sex of offspring to nearly one hundred percent. Although this method was mainly for prevention of sex related genetic diseases, but nowadays it performs for family balancing. The aim of family balancing is to control the sex of offspring according to gender of previous child/children of the couples. It means that, if you have one or more boys, you can request to transfer a girl through an ART procedure. And Vic versa if you have daughter/s, you can request transfer of male embryo. Usually we do not accept sex selection for the first child, except for genetic diseases, which even we have better solution for this problem (PGT-M).
For sex selection we can use FISH technique, which just determine the sex of embryos, and aCGH, which in addition to sex determination, it is a method for ensuring the correct constitution of other chromosomes (PGT-A).