What is Preimplantation Genetic Testing (PGT) ?

PGT-A (Preimplantation Genetic Testing for Aneuploidy) is genetic screening of embryos for chromosomal abnormalities. It involves biopsy of embryos reaching the blastocyst stage during In Vitro Fertilization (IVF) to determine which embryos have normal chromosome number and structure.

PGT-M (Preimplantation Genetic Testing for Monogenic disease) is preimplantation genetic testing of embryos to detect hereditary single gene (monogenic) defects, such as cystic fibrosis (CF). The technique decreases the risk of transmitting hereditary disease to the children. PGT-M requires biopsy of the embryos to select normal or unaffected embryos for transfer during IVF treatment.

Typically, during IVF, 1 or 2 embryos are transferred into the uterus 5-7 days after fertilization at the blastocyst stage. Not all embryos progress to the blastocyst stage and not all blastocysts are genetically normal. Selecting the right embryo for transfer is tricky because looks can be deceiving. The embryo may look good and still be genetically abnormal.

Remarkably, about 40% of chromosomally abnormal embryos can reach the blastocyst stage. Not surprisingly, when a single non-biopsied blastocyst is transferred, the ongoing pregnancy rate in patients under the age of 35 is only about 40%. Transfer of two non-biopsied embryos results in 55% ongoing pregnancy rate.

Chromosome abnormalities (aneuploidy) in human embryos is the major cause of in vitro fertilization (IVF) failure and miscarriage. The incidence of chromosomal abnormalities in embryos increases exponentially in women over the age of 35 years.

Data from embryo biopsy demonstrates that the incidence of genetically abnormal embryos increases from 30% to 50% in patients under 35 years of age to 80% in women 42 years of age or older. This explains why live birth rates per IVF egg-retrieval cycle decrease from 55% in young patients (under 35) to about 15% in women aged 41–42 years.

How Is Preimplantation Genetic Testing (PGT-A or PGT-M) Done?

Embryo biopsy utilizes sophisticated microscopic laser technology to remove 5-15 cells from the trophectoderm layer of the embryo which later in pregnancy becomes the placenta. The cells destined to become the fetus are not disturbed. The cells are then sent to the genetic laboratory for Next-Generation Sequencing (NGS) analysis of the chromosomes to determine if the embryo is genetically normal (PGT-A). The cells can also be tested for hereditary monogenic or single gene defect (PGT-M).

What are the potential benefits of embryo biopsy?

  • It can help detect chromosomal or genetic abnormality.
  • Reduces multiple pregnancy rate by helping select a single healthy embryo for transfer.
  • It decreases risk to couples or individuals with serious inherited genetic disorder from transmitting it to their children.

Should we routinely biopsy all embryos?

Embryo biopsy is indicated in selected cases such as:

  • Known parental chromosome abnormality.
  • In cases of parental single gene defect, such as cystic fibrosis, sickle cell disease or spinal muscular atrophy. to minimize the risk of transmission of serious hereditary disease to the children.
  • Recurrent pregnancy loss due to abnormal fetal chromosomes.
  • Gender selection or family balancing.

There are several challenging concerns regarding universal embryo genetic screening.

  • False positive results, which may result in the discarding of otherwise healthy genetically normal embryos.
  • Embryo damage during the biopsy, which decreases the implantation potential of transferred (normal) embryos.
  • False negative results are uncommon but have been reported.
  • Increased cost and complexity of IVF treatment.

A recent (2020) multicenter Randomized Control Trial (RCT) embryo biopsy or PGT-A demonstrated no overall improvement in live birth rate in women aged 25–40 years.

To learn more about PGD at Boca Fertility give us a call at 1.844.773.3855