Preembryo Genetic Diagnosis (PGD)
Preimplantation genetic diagnosis (PGD) is a technology used to screen genetically abnormal embryos. PGD involves the removal of cells from a developing embryo obtained from an IVF cycle. The two major groups of patients that may benefit from PGD are patients with inherited genetic diseases for example: cystic fibrosis, sickle cell disease or Tay Sachs disease as well as patients that are carriers of chromosomally abnormal rearrangements that have had recurrent miscarriages. The technique involves removal of cells from the embryo. These cells undergo genetic testing using probes designed to detect the specific abnormality. Screening and transferring of only normal embryos will reduce the risk of a genetically abnormal child as well as miscarriage. While PGD can reduce risk it cannot completely eliminate it. Confirmation studies using chorionic villi sampling (CVS), amniocentesis or other testing is still recommended. Embryo biopsy until recent has been performed on day three embryos having 4-8 cells, usually 1 or 2 cells are removed for testing. Day three embryo biopsies have been shown to compromise implantation rates and have been replaced by day five embryo biopsy. At the day five stage the embryo typically has anywhere from 100-150 cells. Day five biopsy targets cells away from the inner cell mass destined to develop into the fetus, and does not seem to affect implantation. Florida Institute for Reproductive Medicine is now one of a select group of programs performing laser day five embryo biopsy/PGD.
Preembryo Genetic Screening (PGS)
Preembryo genetic screening (PGS) involves going through an IVF cycle removing cells from an embryo for genetic screening. The key word is screening, we are not looking for a specific genetic disease or chromosomal arrangement as with PGD. The most common indication for PGS is advanced maternal age, i.e. as a woman ages an increasing percentage of her eggs will be genetically abnormal resulting in abnormal embryos. Women in their late 30s, early 40s can expect anywhere from 60-90% of their embryos to be chromosomally abnormal. Even women in their 20s may have up to a 40% abnormality rate. PGS offers the hope of improving IVF pregnancy rates and decreasing miscarriage rates. Prior studies using PGS to try to improve pregnancy rates have been disappointing – this is believed to be because of two unique problems associated with day three embryo biopsy. With day three embryo biopsy only 1or 2 cells are available for diagnosis. This represents an eighth to a quarter of the total number of cells available to develop the fetus – resulting in decreased implantation rates. In addition it is known that a day three embryo may contain more than one cell line. One cell line may be normal another abnormal. It has been shown that on occasion abnormal cell lines can self correct leading to an incorrect diagnosis. Biopsy on a day five embryo allows for the removal of multiple cells that can be targeted away from the cells destined to produce the fetus. We have not seen decreased implantation rates with day five biopsied embryos and have seen markedly improved pregnancy rates suggesting more accurate genetic diagnosis. Day five biopsy/PGS now offers the very realistic option of single embryo transfer avoiding the risks associated with a pregnancy (up to 40% rate of twins with the transfer of two day five embryos). Pregnancy rates of 60-70% have been reported with the transfer of a single chromosomally normal embryo. There may be unknown associated risks with day five embryo biopsy, i.e increased risk of identical twining and a phenomena known as imprinting (developmental abnormality). Preliminary studies have not shown an increased incidence of either entity, but more extensive studies with longer follow up will be required to evaluate these risks. Florida Institute for Reproductive Medicine is now one of a select group of programs performing laser day five embryo biopsy/PGS.