PGD

Preimplantation Genetic Diagnosis (PGD) and Embryo Biopsy

What is PGD?

Preimplantation Genetic Diagnosis (PGD) is a state-of-the-art reproductive technology used in conjunction with in vitro fertilization (IVF) to select embryos free of chromosomal abnormalities and specific genetic disorders for transfer to the uterus. These genetic conditions can interfere with embryo implantation, result in pregnancy loss, or result in the birth of a child with physical problems, developmental delay, or mental retardation. By selecting embryos that have tested negative for these genetic abnormalities, we hope to improve the chances of a pregnancy occurring, as well as increase the probability that the embryos that do create a pregnancy will be healthy and unaffected by the specific genetic conditions(s) tested for. PGD can only be performed within the context of an IVF cycle where eggs and sperm, fertilized in a laboratory, develop into embryos.

Who should consider PGD?

PGD may be beneficial to many couples. If you say ‘yes’ to any of the following questions, PGD may be something to consider and discuss with your RBA physician:

• Are you a woman over 35?
• Have you and your partner had multiple miscarriages or failed IVF cycles?
• Do you or your partner carry a chromosome rearrangement, such as an inversion or translocation?
• Are you or your partner carriers of a specific genetic disorder (i.e. cystic fibrosis, sickle cell disease, Fragile X syndrome, or any other genetic disorder)?
• Do you have a long history of unexplained infertility?

How is PGD performed?

With PGD, the egg is fertilized in a laboratory via standard IVF procedures. Then, in what is known as an embryo biopsy, a single cell is taken from a Day 3 embryo, or several cells are taken from a Day 5 or 6 blastocyst. The cells are removed and the chromosomes examined for genetic abnormalities using one of several techniques.

In a technique known as Fluorescent In-Situ Hybridization (FISH), fluorescently labeled probes that recognize specific sequences of a specific chromosome are allowed to hybridize (attach) to the cell. The cell may then be analyzed under a fluorescent microscope to identify the presence or absence of the particular chromosomes in question. FISH includes testing for 9 of the 23 chromosome pairs, specifically: 13, 15, 16, 17, 18, 21, 22, X, and Y. These 9 chromosome pairs are responsible for at least 70% of chromosomally-abnormal pregnancy losses, and are the most common chromosome abnormalities affecting live births. In some cases, a more limited FISH panel may be done, involving less than 9 chromosome pairs.

Another PGD technique known as Comparative Genomic Hybridization (CGH) is a microarray technology that compares the DNA in the embryo sample to a known normal control using tens of thousands of genetic markers throughout the human genome. CGH allows testing of all 23 pairs of chromosomes in an embryo.

The particular PGD technique used and day of embryo biopsy is dependent upon each patient’s specific circumstances and will be discussed with your RBA physician.

Is PGD Safe? What are the risks to the resulting child?

Yes. Data from many years of PGD and thousands of live births have shown no reported increase in congenital abnormalities over the general population risk (3-5%). We believe that the reason for this is that the embryo biopsy in PGD is performed very early in the embryo’s development, when the cells are still all identical and each cell is capable of becoming any part of a baby. Therefore, removal of a  few of the cells does not alter the ability of that embryo to develop into a complete, normal pregnancy. Despite these encouraging results, it is important to emphasize that PGD is still a relatively new procedure, and long-term follow-up of these children is needed to assure the procedure’s overall safety.

How accurate is PGD?

Clinical misdiagnosis, in which an abnormal embryo thought to be normal is transferred, or a normal embryo thought to be abnormal is discarded, is a risk. Depending on the particular situation, misdiagnoses are believed to occur in about 5-10% of embryos. There is also a small risk that a cell will be non-analyzable or only partially-analyzable. Embryos that have no PGD result may be transferred if they demonstrate normal development, but the benefits of PGD will not apply. In addition, PGD cannot detect abnormalities of chromosomes or genes which are not specifically included in the test, nor can it detect abnormalities if they occur in only some of the cells of the embryo (mosaicism). It is highly recommended that traditional prenatal diagnosis in the form of chorionic villous sampling (CVS) or amniocentesis is performed if a pregnancy is established after PGD.

Risks of PGD

PGD is a highly technical procedure, requiring a high level of expertise by laboratory personnel performing each step of the procedure. At RBA, embryologists performing the biopsy and fixation procedures have extensive experience in micromanipulation and cytogenetic techniques, and the embryo damage rate is minimal (<1%). In the rare cases that an embryo is damaged, it can be identified right away by viewing it under a microscope, and would not be selected for transfer. There is some evidence that embryo biopsy may slightly reduce the chance for pregnancy implantation.  The amount of reduction is unclear and RBA has had close to a thousand successful pregnancies result from embryos in which PGD was used.

What happens if there are healthy embryos that are not used?

All decisions about which embryos to transfer and how to use excess remaining embryos are made together with the couple and their RBA physician.

Other questions?

Feel free to contact our genetic counselor, Jamie Dokson, for any additional questions regarding PGD.

In addition, other IVF centers capable of performing embryo biopsy have the option of sending cells to the RBA laboratory for FISH analysis.