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 throughout this site.
Embryos can be analyzed for one or more of the following reasons:
- Aneuploidy – A condition in which there is an extra or missing chromosome. An example of aneuploidy is Down Syndrome. There is an increased incidence of aneuploidy as women age.
- Gender Selection -The determination of whether an embryo is male or female. This is a very accurate way for patients to have a boy or a girl through family balancing.
- Translocations – A change in chromosome structure in which chromosomes are attached to each other or pieces of different chromosomes have been interchanged.
- Single Gene Disorders – Disorders or diseases caused by the inheritance of a single mutated gene. Diseases such as Cystic Fibrosis, Tay Sachs, Alpha and Beta Thalassemia and Sickle Cell Anemia are examples of a mutated gene.
- Recurrent Pregnancy Loss – Genetic testing of embryos can look for genetic causes to repeated pregnancy losses.
- IVF Treatment Failure – one of the most common reasons why IVF doesn’t work is related to genetic abmormalities within the embryos.
Advanced Age & Aneuploidy As a woman’s eggs age, the risk of chromosome and genetic abnormalities increases drastically. This causes a lower chance of pregnancy and a higher chance of a miscarriage. It has been known for many years that as a woman ages, her eggs are more prone to genetic errors. These genetic errors will cause the embryos to become genetically abnormal. Most genetically abnormal embryos do not make a pregnancy. Abnormal embryos that do make a pregnancy may result in a miscarriage or a baby with a chromosome disorder such as trisomy 21, or Down Syndrome. Blood testing in pregnancy (MSAFP or triple and quad marker screening) has been used along with ultrasounds and amniocentesis (drawing out fluid from around the baby) to test for chromosome problems during early pregnancy. Preimplantation testing allows for screening of genetic problems before the embryo is placed in the uterus. This avoids a pregnancy with a genetic problem which will drastically increase pregnancy rates and reduce miscarriage rates. Abnormal embryos are not used when PGD or PGS (FISH or CGH) is used.
Gender Selection Help having a boy or girl is now within reach of many couples. When a couple has a boy or girl already and would like to add to their family without having multiple children in order to have the desired sex, genetic screening can help. The X and Y chromosomes determine if you will have a boy or girl. By testing the chromosomes of the embryo, we can know if you will have a boy or girl before you become pregnant. This allows couples to balance their family by using gender selection. While the use of technology for this purpose is not acceptable to everyone, the technology is available to those who find family balancing desirable.
Translocations (unbalanced translocations & Robertsonian translocations) Translocations are genetic abnormalities where the genetic material from one chromosome has relocated to another chromosome. The person with the abnormality possess all of the genetic material they need but the genes are not in the normal places. A problem arises when the genetic material is passed on to the embryo. Missing or extra genetic information can be passed along. This leads to genetic abnormalities or birth defects. Preimplantation genetic diagnosis can determine which embryos do not show evidence of the translocation. This helps avoid miscarriages and increases the chances of a healthy baby.
Single Gene Disorders There is a wide range of genetic diseases that can be evaluated using the genetic testing techniques. Current technology doesn’t offer a cost effective way to screen for all of the disorders at once. It is more effective to screen for a genetic disorder that is known within the family. Testing for single gene disorders is more complicated than the other tests and often has higher costs. A blood sample may be needed in advance so that the genetics center can create a probe to identify the genetic abnormality within the embryos tested. More information will be provided to you during your consultation if you desire single gene testing. The following is a list of disorders that can be tested. This is only a sample list and many more diseases are add all the time thanks to ongoing research.
- Alagille syndrome
- Alpers disease
- Alpha-1 antitrypsin deficiency
- Alpha-thalassemia
- Alport syndrome
- Anti-Kell antibodies
- Becker muscular dystrophy
- Beta-thalassemia
- Breast cancer (BRCA 1 & 2)
- Carbamoyl phosphate synthetase deficiency
- Central core disease
- Cerebral arteriopathy (CADASIL)
- Charcot-Marie-Tooth syndrome 1A & 1B
- Chronic granulomatous disease (CGD)
- Congenital adrenal hyperplasia
- Congenital disorder of glycosylation
- Congenital nephrotic syndrome
- Connexin 26
- Crigler-Najjar syndrome type I
- Crouzon syndrome
- Cystic fibrosis
- Czech dysplasia
- Dejerine-Sottas syndrome
- Duchenne muscular dystrophy
- Early-onset Alzheimer disease
- Early-onset torsion dystonia
- E-cadherin
- Ectodermal dysplasia
- Emery-Dreifuss muscular dystrophy
- Epidermolysis bullosa (dominant dystrophic)
- Epidermolysis bullosa – Herlitz junctional (Gene 1 or 2)
- Epidermolytic palmoplantar keratosis
- Facioscapulohumeral muscular dystrophy
- Familial adenomatous polyposis
- Familial amyotrophic lateral sclerosis (Lou Gehrig’s disease)
- Fechtner syndrome
- Fragile X syndrome
- Fumarase deficiency
- Galactosemia
- Gaucher disease type 2
- Goldberg-Shprintzen syndrome
- Gorlin syndrome
- Hemophilia A or B
- Hirschsprung’s disease
- HLA matching
- HLA match for Wiskott-Aldrich syndrome
- HLA match with beta-thalassemia
- HLA match with Diamond-Blackfan anemia
- HLA match with Hyper-IgM
- HLA match with sickle cell anemia
- Holt-Oram syndrome
- Hunter syndrome (Mucopolysaccharidosis II A)
- Huntington disease
- Hyper-IgM syndrome
- Hypochondroplasia
- Hypophosphatasia
- Hypophosphatemic rickets
- Incontinentia pigmenti
- Infantile neuroaxonal dystrophy
- Juvenile neuronal ceroid lipofuscinosis
- Juvenile retinoschisis
- Late-infantile neuronal ceroid lipofuscinosis (Batten disease)
- Lowe oculocerebrorenal syndrome
- Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
- Medullary thyroid carcinoma (RET)
- Metachromatic leukodystrophy
- Mucopolysaccharidosis III B
- Multiple endocrine neoplasia type 2A
- Multiple hereditary exostoses
- Myotonic muscular dystrophy
- Myotubular myopathy
- Nail-patella syndrome
- Nemaline myopathy
- Nephrogenic diabetes insipidus
- Neurofibromatosis type 1
- Neurofibromatosis type 2
- Norrie disease
- Oculocutaneous albinism
- Ornithine transcarbamylase deficiency
- Osteogenesis imperfecta type 1
- Palmoplantar hyperkeratosis
- Pendred syndrome
- Pericentric inversion of X chromosome
- Polycystic kidney disease (ADPKD – Gene 1)
- Polycystic kidney disease (ADPKD – Gene 2)
- Polycystic kidney disease (ARPKD)
- Proximal myotonic myopathy
- Psoriasis (susceptibility gene)
- Pulmonary alveolar proteinosis
- Retinoblastoma
- Rhesus D disease
- Saethre-Chotzen syndrome
- Sandhoff disease
- Sickle-cell anemia
- Spinal muscular atrophy type 1, 2, or 3
- Stickler syndrome
- Thyroid cancer
- Transthyretin amyloidosis
- Treacher-Collins syndrome
- Tuberous sclerosis (Gene 1)
- Tuberous sclerosis (Gene 2)
- Ullrich congenital muscular dystrophy
- Vitelliform macular dystrophy
- Von Hippel-Lindau disease
- Wilms tumor
- Wiskott-Aldrich syndrome
- Wolman disease
- X-linked adrenoleukodystrophy
- X-linked choroideremia
- Zellweger syndrome
Recurrent Pregnancy Loss (RPL) is defined as the occurrence of three or more consecutive losses of clinically recognized pregnancies prior to the 20th week of gestation (ectopic and molar pregnancies are not included). Evaluation of healthy women is not recommended after a single first trimester or early second trimester spontaneous miscarriage as these are relatively common, sporadic events. The risk of another pregnancy loss after two consecutive miscarriages is 24 to 29 percent, therefore, evaluation and treatment of RPL can reasonably be started after two consecutive miscarriages. Many doctors may advise their patients to wait until three losses to start a diagnostic evaluation. In many cases, there is not an identified cause for recurrent pregnancy losses. A very high percentage of pregnancy losses occur because of genetic or chromosome abnormalities occurring in the embryos. Some women have predisposing factors that cause them to have genetically abnormal embryos at a higher rate than other women even though she has a normal chromosome analysis herself.
Preimplantation genetic screening for aneuploidy (chromosome number) can avoid most miscarriages to to abnormalities due to missing or extra chromosomes. PGD / PGS will not affect pregnancy losses caused by other problems such as fibroids, blood clotting disorders, and antibodies such as antiphospholipid antibodies and anticardiolipin antibodies. (APA, LAC, ACA). Women with multiple pregnancy losses may wish to consider genetic screening of their embryos. This option can be discussed along with other topics concerning recurrent pregnancy losses during a consultation with on of our doctors.
One of the most common causes for a failed IVF cycle is the absence of genetically normal embryos. While many other factors may also affect the success of an in vitro fertilization treatment (IVF), genetically abnormal embryos is a leading cause of IVF not working. Laboratory culture conditions used to grow embryos to the more advanced stage and uterine abnormalities are the other leading causes of IVF failure. When IVF doesn’t work, many problems are blamed for the lack of success. Many labs and clinics have adjusted many variables in order to increase the chances of having a positive pregnancy test and healthy baby. It is very surprising to find how many embryos are genetically abnormal. Women may have factors affecting their ovaries that cause them to make genetically abnormal embryos at a much higher rate that expected. This leads to an unsuccessful IVF treatment. At California IVF: Davis Fertility Center, Inc., our success with donor eggs, frozen embryos, and pre implantation genetic screening (PGS & PGD) stands as a testament to the high quality laboratory and embryology services. We will be happy to discuss your options for improving your outcome with genetic testing. It must be understood that the testing will not make the embryos normal and in some cases, we will not recommend genetic testing if it will not likely improve your chances of having a baby.
Genetic testing of embryos is not likely to help a woman who goes through IVF treatments and has a low number of eggs that results in only a few embryos available for transfer. If all of the available embryos were put into the uterus, a normal embryo would have been put into the uterus if there was one present. Genetic testing is useful for avoiding the situation where the good embryos are placed into cryo storage. The freezing and thawing may affect the success of future attempts using the frozen embryos. A program with a high success rate using frozen embryos can rival the chances of genetically tested embryos, but multiple transfers may be necessary. Patients must also consider the cost of the genetic testing. The advantages and disadvantages of genetic testing can be discussed at your consultation with one of our doctors.
The most commonly used techniques for PGD include FISH and CGH . Information on the technical aspects of preimplantation genetic diagnosis can be found here. This link will review the various types of PGD and PGS including CGH and FISH technology.
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. We remain committed to bringing our patients the latest developments to improve the chances of having a safe pregnancy and a healthy baby.
If you have any questions about our services or the use of preimplantation genetic diagnosis (PGG) with your fertility treatments, or to screen for an inherited genetic disorder, please contat our office. We are always happy to answer your questions.
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)
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.
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.