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| Preimplantation Genetic Testing (PGD/PGS) |  |
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IVF Breakthroughs
| Zouves Fertility Center offers the very latest advances in IVF treatment, and therefore, the greatest chance for success. This video gives you an overview of our breakthrough procedures and a glimpse into our state-of-the-art IVF Laboratory. |
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Preimplantation Genetics Testing (PGS/PGD)
Testing done in Reference Lab
PGD for Single Gene Disorders | PGS for aneuploidy | Advantages | Benefits | Risks | Procedure | Time Requirements | Recommendations and Follow-up | Confidentiality | Fees | Implantation Rates
Preimplantation Genetic Testing (PGS/PGD) is a relatively new procedure in which eggs or embryos are tested for certain genetic conditions prior to being replaced in the womb.
Children born in the United States have a 3% to 4% chance of a major birth defect. Some of these abnormalities occur because of a problem with a single gene which is inherited from one or both of the parents, while other abnormalities are related to an abnormal number of chromosomes (aneuploidy). Both of these problems can be diagnosed before embryos are transferred to the uterus and this diagnostic procedure is called preimplantation genetic testing.
The majority of procedures are performed for aneuploidy or abnormalities in the number of chromosomes and this problem increases with increasing maternal age. This is called Preimplantation Genetic Screening (PGS). Studies have also shown that up to 85% of aneuploids are caused by the egg while the sperm may cause the remainder.
With respect to single gene defects, these defects can be dominant and are transmitted by one parent alone with a risk of an affected child being 50% (e.g. Myotonic Dystrophy) or these defects can be recessive and both parents must have the gene with a risk of an affected child being 25% (e.g. Cystic Fibrosis, Sickle Cell Anemia or Tay-Sachs Disease). There are now more than 60 single gene diseases that can be identified through Preimplantion testing and this is called PGD. Most of these genetic syndromes are relatively uncommon.
In keeping with our goal of providing the latest technological advances to help our patients achieve a viable, healthy pregnancy, Zouves Fertility Center offers PGD and PGS. Preimplantation Genetic testing is an intricate procedure which involves removing a single cell from a three-day-old embryo and testing it for chromosomal disorders. This permits the selection of embryos, which are less likely to have chromosomal abnormalities and also embryos that may be free of a known single gene disorder, thereby increasing the likelihood of a healthy baby and decreasing the chances of having to terminate a pregnancy found to be abnormal through chorionic villus sampling or amniocentesis. Even in optimal situations, like egg providers under age 30, the percentage of embryos that have normal chromosomes may only be approximately 50%. This may explain the frustration that patients and IVF specialists feel when apparently normal looking embryos are transferred with negative results or recurrent losses, sometimes even after multiple IVF attempts. Chromosomal abnormalities in embryos are therefore responsible for a significant proportion of failed implantations after hormonal, uterine and immunological factors have been excluded.
Couples can benefit from PGS when the woman is 35 or older, by testing for age-related chromosomal disorders, also called aneuploidy, or when there is a single gene defect within a family. Younger women with repeated unexplained miscarriages can also benefit from this test. The purpose is to select and replace only those embryos that appear to be normal so that women may increase the chance of conceiving while reducing the probability of losing the pregnancy or carrying an abnormal baby to term. PGS for aneuploidy can determine the presence of absence of a certain number of chromosomal disorders, but cannot detect genetic disease nor predict congenital malformation
PGS for aneuploidy
Females are born with all the eggs they will have in their lifetime. As a woman advances in age, her eggs are exposed to aging processes that include chromosomal abnormalities. Thus, the chance of conceiving a chromosomally abnormal baby increases with age. In complete contrast, sperm in the male are newly made every 65-75 days. Chromosomes are string-like structures found in the center of the cell, the nucleus. Chromosomes contain genes that are made of DNA, the molecule that contains inherited information. Normal human cells contain 23 pairs of chromosomes, a total of 46. We receive 23 chromosomes from each parent. If an error occurs leading to the egg or sperm having an extra or missing chromosome, the embryo created by that egg or sperm would have an extra or missing chromosome. This situation is called aneuploidy. If the aneuploidy involves chromosomes such as 13, 18, 21, X or Y, the pregnancy may still carry on until birth, even though the fetus has a chromosomal disorder. This produces an effect called Down's syndrome. The effects of other common aneuploidies include Turner's syndrome and Klinefelter's syndrome. These disorders are non-fatal, in that the fetus can carry to term and result in a live birth, although the baby is abnormal. Overall, the risk of aneuploidy is known to increase with maternal age, from 1/385 at 30, 1/179 at 35, 1/63 at 40 and at the age of 45 the chance of delivering an affected child is 1/19.
Advantages
PGS for aneuploidy provides three advantages for conception and child bearing. The first is to improve the chances of pregnancy. Even though only about 9 out of 23 chromosomes can be tested, these 9 are the ones that most commonly cause problems. By replacing only embryos believed to be chromosomally normal, there is an increase in implantation for those patients at risk, as shown in two recent studies. The second advantage is a reduction in pregnancy loss.
For women of 35 and over, as much as 35% of pregnancies are miscarried sooner or later; in up to 50% of these cases, the chromosomal abnormality of aneuploidy is the cause. These figures are approximately the same whether the pregnancy is after an IVF procedure or in the general population. Again, recent studies have shown a possible reduction in pregnancy loss by half after PGS for aneuploidy. Thirdly, and most importantly, is the increased chance of giving birth to a chromosomally normal baby.
Benefits
More than 20% of embryos from women aged 35 to 39 are generally affected; over 40, almost 40% of embryos are affected. These high numbers are not reflected in live births because most of the affected embryos will fail to attach to the womb; and those that do, will miscarry earlier or later during the pregnancy. Any embryo with a missing chromosome (monosomy) will cease to grow before implantation (except monosomy X and 21), and only a few of those carrying an extra chromosome (trisomy) will go to term. These are believed to be the main reasons why pregnancy and birth rates in women of 40 and over are so low. We have seen the most beneficial effect of PGS of aneuploidy in women 38 and older. However, PGS for aneuploidy is not only recommended for women 38 and older but also for younger patients with a history of previous trisomic conceptions, miscarriages, or repeated IVF failure. The purpose of PGS is therefore to select for replacement only those embryos believed to be chromosomally normal; aiming to achieve higher implantation per embryo replaced, a reduction in pregnancy loss, and a higher proportion of healthy offspring.
Risk
Physicians and scientists are uncertain of the risks involved in microsurgery of the embryos, but believe them to be acceptably low. Numerous animal studies and same human studies show that the microsurgery of the embryo needed to remove the cells, does not affect the normal development of the baby. This procedure, however, has been performed in a limited number of studies on human embryos, so the precise negative effects if any, are unknown. In animal studies there have been no apparent problems and preliminary evidence with human true.
It should be understood that only a subset of the chromosomes that are present in each biopsied cell could be diagnosed. Sometimes chromosome anomalies are present in a cell yet not in other cells of the same embryo and vice-versa, in a condition called mosaicism. Therefore, analysis of a single cell has limitations, and wrong diagnoses do happen, either false-positive or false-negative, in as much as ten percent (10%) of embryos. Geneticists are unable to detect other chromosome abnormalities such as translocations or other structural abnormalities that involve less than whole extra or missing chromosomes. Other congenital malformations or genetic diseases cannot be tested using FISH. As with all IVF pregnancies, prenatal testing should be performed by chorionic villus sampling or amniocentesis to confirm the development of a normal fetus.
Even though there have been more than 2000 live births after PGS of aneuploidy worldwide to date (May 2004), this procedure is still relatively new; and therefore, the major risk is that the procedure will not be successful in spite of all best efforts. Although a rare occurrence (0.1%), it is possible that egg(s) or embryo(s) may be accidentally damaged during biopsy. Furthermore, a relatively large number of the eggs or embryos may be abnormal providing a very limited number of embryos for replacement. In about eleven percent (11%) of the cases, none of the embryos may be normal, and embryo replacement should then not be performed; while a disappointing outcome, it is likely that the cycle would have failed without PGS or an abnormal conception would have occurred. Finally, the tests may fail in any individual case because of unforeseen technical malfunctions. These malfunctions may include but not be limited to: death of the embryo being biopsied, loss of the blastomere after biopsy yielding no result, and/or loss of biopsy cells during transit to the analysis laboratory. It is, therefore, not possible to guarantee pregnancy after PGS or even to promise that there will be benefits for any individual case.
Procedure
The preferred method of PG Testing is to remove one cell from an embryo (blastomere) on Day 3 of development; at this stage the embryo usually has 6 to 10 developing identical cells, each with a full complement of chromosomal material. The embryo(s) remain in incubation while the cell is analyzed.
PGD/PGS is accomplished by making a small opening in the embryo(s) outer shell (zona pellucida) and the blastomere is extracted with a micropipette. The Day 3 embryo is exposed to an elevated level of sucrose in order to reduce the size of their cells. This is to simplify the removal of cell(s), because connections between them can be very firm. The process also requires the temporary removal of calcium and magnesium from the culture medium. Normally, only a single cell is removed from each embryo as it is expected to be identical to all the other cells, but it may be necessary to remove a second cell according to circumstances. In either of the above cases, the analysis of the biopsied cell(s) uses a technique called fluorescence in-situ hybridization or FISH, which takes two days. The cells are glued to a glass slide and heated and cooled and their DNA is 'labeled' with colored fluorescent dyes called probes, one for each chromosome analyzed. At present, the test can check about 9 chromosomes out of 23. Once the FISH procedure is complete, the geneticist counts the colors using a powerful microscope, thereby distinguishing normal and abnormal cells. This information is then related to the normalcy of the associated embryo being held in culture. After this process the biopsied and analyzed cells are no longer viable in any way, and the slides on which they sit are placed in a deep freeze for future reference.
Time Requirements
The process takes up to 36 hours, and results will be brought immediately to the IVF program to allow patient consultation and discussion of the outcome. Embryo replacement of "normal" embryos will take place in the morning of Day 5 of development. The slides containing the tested cells and remains will be frozen for future reference and the patient-couple fully informed of the results upon request.
Recommendations and Follow-up
When any pregnancy is achieved after an IVF procedure, we strongly recommend a comprehensive genetic analysis of the fetus between 10-16 weeks. This can be chorionic villii sampling or an amniocentesis that provide samples of cells taken from the fluids of the placenta. The fetus should also be checked with ultrasound to monitor growth and development.
Scientists of Saint Barnabas Medical Center sincerely request that these results be forwarded to our PGD Program Coordinator, Jill Fischer, M.S. (email or telephone 973-322-2858).
Similarly, after birth and periodically thereafter we will send you a questionnaire that will inform the team of the progress of the child.
Confidentiality
Any information obtained during this study and identified with the patient(s) will remain confidential and will be disclosed only with patient's permission. The Food and Drug Administration (FDA), the Society for Assisted Reproductive Technology (SART) in conjunction with the Center for Disease Control (CDC), as well as licensed state and federal laboratory inspectors may verify the records.
Fees
Fees for PG Testing are in addition to the cost of the IVF cycle, over and above those related to your normal IVF and/or egg donation procedure, and the latter are described on a separate cost evaluation sheet. If the PG Testing procedure is paid for but not performed, your payment will be refunded.
Implantation Rates
If one looks at the implantation rate of embryos that test normal on PGS, it appears as though each normal embryo in patients over 40, carries 15% change of making a baby. PGS in patients where the egg provider is under 35 yields a 38% chance of a baby with one embryo that test normal. From this, we can see that we still need to be aggressive when transferring embryo after age 40.
In addition, the proportion of embryos that test genetically normal at PGS appears to be around 45% under age 35 and this percentage drops to somewhere between zero and 20% after age 40. There are individual instances where patients, at all ages, may have either no normal embryos or more that the expected percentage for their age.
| Single Gene Disorders |
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A-thalassaemia Achondroplasia Adrenoleukodystrophy (ALD) Alagille syndrome Alpha-1-antitrypsin Aiport disease (X-linked) (ATS) Alpha-thalassemia Amyloid precursor protein (APP) mutation ARPKD B-thalassaemia Becker muscular dystrophy Breast cancer (BRCA1/BRCA2) Canavan Congenial Adrenal Hyperplasia Charcot-Marie-Tooth disease (1A) Chromosomal translocations Cystic fibrosis Dehydrogenase deficiency (MCAD) Down syndrome Duchenne muscular dystrophy Dystonia 128230 Epidemolysis bullosa Familial dysautonomia Fanconi anemia FAP Fragile X syndrome Gaucher disease Hemophilia HLA genotyping Hoit-Oram syndrome HSNF 5 mutation Huntington Disease Hypophosphatasia |
Incontinentia Pigmenti Kell disease Klinefelter syndrome LCHAD Lesch-Nyhan syndrome Limb-Girdle muscular dystrophy (2B) Marfan Syndrome Medium chain acyl-CoA Multiple epiphysial dysplasisia Myotubular myopathy NF1 and NF2 Norrie disease Ornithine transcarbamylase deficiency Osteogenesis imperfecta P53 mutations (Li_Fraumeni syndrome) Phenylketonuria Polycystic kidney disease (PKD1) PKD2 and 3 PKU Retinitis pigmentosa Retinoblastoma RhD SCA6 Sickle cell anemia Sonic hedgehog mutations Spinal muscular atrophy Tay-Sachs disease Tuberous sclerosis Turner syndrome Ulnar-Mammary syndrome Von Hippel-Lindau disease X-linked trydrocephaly X-linked hyper lgM syndrome |
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Most genetic diseases can be diagnosed by PGD. If you have a genetic disease, contact Zouves Fertility Center and we will find out whether the embryos can be tested for your condition. |
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