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Preimplantation genetic diagnosis is an advanced reproductive technology in which a single cell, or blastomere, is removed from the embryo and evaluated by genetic testing for various reasons. The most common reason is for the prevention of genetic diseases, which may be present in the embryo either from spontaneous mutations or from disorders inherited from the parents. The procedure involves making a small hole in the outer shell, or zona, using an acid solution or a laser with the assistance of a specialized microscope. A small micromanipulation pipette is then used to gently pull out a single cell, which can be used for genetic testing.

The name “Preimplantation Genetic Diagnosis” is a form of genetic screening. A more correct name for this testing is Preimplantation Genetic Screening, or PGS. The names are often used interchangeably. Some professionals prefer to use the the distinction of “diagnosis” when the screening process is looking for a specific disease that the parents are known to have. The term “screening” is preferred when the embryos are being evaluated for possible problems such as the number of chromosomes or testing for a boy or girl embryo before having a baby. This site uses the terms interchangeably depending on the content being discussed.

Pre implantation Genetic Diagnosis (PGD) is the genetic testing of a single cell from an embryo prior to transfer of the embryo to the uterus. The analysis of an embryo can be performed when the cell of an embryo is removed by a process called Embryo Biopsy. This procedure is performed by the embryologist. The cell is then fixed on a slide for analysis later in the case of FISH (fluorescent in situ hybridization) or placed in a small container in the case of CGH (comparative genomic hybridization). The cell is then sent for genetic testing. Depending on the type of test, it can take 1 to 10 days to get the test results. Most tests are completed within 1-2 days and the embryos can still be placed into the uterus at a normal time for IVF treatments. If longer time is needed, the embryos can be frozen until the test result is obtained.

Learn more about the reasons for performing preimplantation genetic screening (PGS), including gender selection, as well as the possible diseases that may be evaluated by preimplantation genetic diagnosis (PGD)

Coordinating PGD or PGS

When PGD or PGS is desired, the clinic will need advanced notice. The embryologist must have time blocked off to perform the genetic biopsy as this can take several hours. An additional person must be in the lab to perform the cell fixation procedures. Lastly, the genetics testing center must be ready to receive the cells for testing. There are additional steps that need to be taken in the process, including a meeting to discuss the PGD process and possible outcomes. While this is an option that is becoming more attractive to couples, it has limitations that you should discuss before deciding to proceed. Your doctor can discuss preimplantation genetic screening during your initial consultation. In vitro fertilization or intracytoplasmic sperm injection is still required in order to produce embryos that can be used for the cell biopsy. Like everything else, California IVF: Davis Fertility Center, Inc. will work hard to make this process as easy and efficient as possible.

The Process

The process for preimplantation genetic screening (or preimplantation genetic diagnosis) is the same for the various screening techniques (FISH, CGH, etc) up to the time of the actual embryo biopsy procedure. FISH analysis is used for gender selection, aneuploidy screening (chromosome number), single gene disorders, and translocations. CGH, or comparative genomic hybridization, uses the polar bodies from the eggs to allow for genetic testing of chromosome numbers. The two techniques are discussed below. Additional techniques are available but are used less frequently.

Microarray Preimplantation Genetic Diagnosis (MA PGD)
Microarray PGD is one of the latest technologies for testing embryos for genetic abnormalities. This technique requires a blood test from the parents to create a fingerprint of their DNA profiles. This fingerprint is used to compare the DNA from the embryos to make certain there is a chromosome from each parent for the 23 pairs of chromosomes. One of the biggest advantages of this technique is the ability to test all of the target chromosoems in less than 2 days. 24 chromosome testing involves testing for the 23 pairs of chromsomes, but the X and Y chromosome (23rd pair) are counted individually (24 chromosomes). The other advantage of this testing is that in addition to determining the correct number of chromosomes, the test is able to calculate the estimated accuracy of the result to avoid errors. In the event an embryo receives both copies of a specific chromosome from one parent (uniparental disomy), this test is able to detect that as well, avoiding additional genetic issues such as Angleman syndrome. These and other technical advantages make this one of the best possible tests for screening embryos for genetic diseases. California IVF: Davis Fertility Center, Inc. is a leader in the Sacramento area when it comes to PGD. Experience matters when it comes to embryo biopsy. Contact us today about the latest advancements in genetic testing that can help you have a healthy baby.

Technology in this field continues to update. In early 2010, California IVF: Davis Fertility Center, Inc., announced a cooperative effort with Gene Security Network to offer Sacramento area and Northern California region patients the option of combining 24 chromosome analysis with screening for single gene disorders. This now gives us the ability to avoid a known inherited disease that exists in a patients family at the same time we test for the presence of the 23 pairs of chromosomes.

Fluorescent in situ hybridization (FISH)
For procedures evaluating the genetic make up of an embryo using FISH, the embryos are grown to the day 3 stage. The embryos are numbered sequentially and a single cell is removed from each embryo. The cells are then attached to a glass slide (fixation). This glass slide is numbered according to which embryo was biopsied. The procedure is repeated until all of the embryos have been biopsied. The slides are carefully packaged and sent to the genetics testing facility by a courier.

Once the slides arrive at a the genetics testing center for evaluation, they will undergo the FISH procedure. This procedure involves using fragments of DNA that are specific to each chromosome being tested. The probes are placed on the slide with the cell from the embryo and will attach to the chromosome target. A probe for chromosome 18 for example should attach to the slide in two places, on target on each of the two chromosomes. If there is only one chromosome present, there will be only one probe bound to the slide. If there are 3 chromosomes present, there will be 3 probes bound to the slide. The probe contains a chemical marker that will glow. This fluorescent signal can be detected and the number of markers can be counted. In the above example for chromosome 18, there should be two signals on the slide for chromosome 18. Additional probes are applied for the other chromosome markers being evaluated.

Comparative Genomic Hybridization (CGH)
CGH is a form of preimplantation genetic screening that tests the chromosomes expelled by the eggs during the normal cell division process and following fertilization. These cells are referred to as the polar bodies and contain the half of the female DNA that is not being given to the baby. If the chromosomes in the polar bodies are abnormal, the chromosomes remaining in the embryo are usually abnormal as well. CGH can use cells from a day 5 embryo for genetic testing as well. This is referred to as a blastocyst biopsy.

Because CGH typically takes more than 5 days to get a result, the embryos are usually frozen and transferred at a later time. This is called an asynchronous transfer since the embryos are transferred out of sync from a normal IVF cycle. Delayed embryo transfer is another commonly used term to describe the transfer when CGH is used. Patients will undergo the normal IVF process so the cell biopsy can be performed. After the embryos have been frozen and the results are reviewed, the patient can then undergo a frozen embryo transfer. It is very important that a program have an excellent rate of freezing and thawing embryos or the process of cryopreservation may damage normal embryos and reduce the chance of implantation or pregnancy. California IVF: Davis Fertility Center, Inc. is very proud of the success of our frozen embryo program.

Once the cells are shipped to the genetics center where the DNA from the cell biopsy will be merged, or hybridized, with DNA that is known to be normal. Color markers are used to label the DNA and the color markers are evaluated for missing (loss of DNA) or extra (gain of DNA). This allows the cytogeneticist to determine if there are the appropriate numbers of chromosomes present in the case of aneuploidy testing. A similar technique is used when CGH is being used to test for other abnormalities.

The Results

Once the results of the PGS testing is available, the results are discussed with the patients and only the normal embryos are used to attempt a pregnancy. When the testing is performed for aneuploidy, or the number of chromosomes present in the embryo, the embryos with the normal numbers of chromosomes can be selected for transfer. Normally one or two embryos will be placed into the uterus. The extra embryos are frozen for use at a later time. In the setting of sex selection, or gender selection, the embryos with the desired sex can be used to make a boy or a girl.

PGD/PGS allows the doctor and embryologist to use the genetically normal embryos during the initial embryo transfer. This increases the chances of the IVF procedure working on the first try. When all of the chromosomes are tested and considered normal, the rates of pregnancy are likely to be extremely high. We feel that the anticipated rate of success for a pregnancy on the first try will exceed 85% when at least half of the chromosomes are tested and two embryos are transferred. Our current experience shows the rate to be higher than expected. This will likely improve as more chromosomes are tested and the techniques become more refined and cost effective.

California IVF: Davis Fertility Center, Inc. is a private practice infertility clinic located near Sacramento and serving the Northern California region and beyond. We offer PGD & PGS for genetic testing of all types of disorders as well as gender selection for family balancing. We have experience using the genetic techniques above for a variety of disorders and are very proud of our high level of success. We are working hard to reduce the cost of genetic tests and evaluating the options for integrating other techniques for genetic testing of embryos to include spectral karyotype analysis and array CGH. This is just one of the ways that California IVF is trying to evolve to help people have a baby and grow their family.