National Medical Policy
|
|
- Annabelle Watson
- 7 years ago
- Views:
Transcription
1 National Medical Policy Subject: Policy Number: Preimplantation Genetic Diagnosis in Assisted Reproduction NMP245 Effective Date*: October 2005 Updated: September 2015 This National Medical Policy is subject to the terms in the IMPORTANT NOTICE at the end of this document For Medicaid Plans: Please refer to the appropriate Medicaid Manuals for coverage guidelines prior to applying Health Net Medical Policies The Centers for Medicare & Medicaid Services (CMS) For Medicare Advantage members please refer to the following for coverage guidelines first: Use Source Reference/Website Link National Coverage Determination (NCD) National Coverage Manual Citation Local Coverage Determination (LCD)* Article (Local)* Other X None Use Health Net Policy Instructions Medicare NCDs and National Coverage Manuals apply to ALL Medicare members in ALL regions. Medicare LCDs and Articles apply to members in specific regions. To access your specific region, select the link provided under Reference/Website and follow the search instructions. Enter the topic and your specific state to find the coverage determinations for your region. *Note: Health Net must follow local coverage determinations (LCDs) of Medicare Administration Contractors (MACs) located outside their service area when those MACs have exclusive coverage of an item or service. (CMS Manual Chapter 4 Section 90.2) If more than one source is checked, you need to access all sources as, on occasion, an LCD or article contains additional coverage information than contained in the NCD or National Coverage Manual. Preimplantation Genetic Diagnosis Sep 15 1
2 If there is no NCD, National Coverage Manual or region specific LCD/Article, follow the Health Net Hierarchy of Medical Resources for guidance. Current Policy Statement Many benefit plans specifically exclude in vitro fertilization (IVF) and related procedures. Health Net does not cover IVF services associated with preimplantation genetic diagnosis (PGD) unless the plan specifically covers IVF. Health Net, Inc. considers preimplantation genetic diagnosis (PGD) as an adjunct to in vitro fertilization (IVF) medically necessary to deselect embryos affected by flawed genetic make-up, when the results of the genetic test will impact clinical decision making and/or clinical outcome, and any of the following are met: 1. Women > 35 years of age to test for suspected aneuploidy - one or a few chromosomes above or below the normal chromosome number, e.g., three number 21 chromosomes or trisomy 21 (characteristic of Down syndrome) is a form of aneuploidy. 2. Couples at high risk for aneuploid pregnancy (e.g., prior aneuploid pregnancy) 3. Couples at high risk for single gene disorders* who meet any of the following: One partner has the diagnosis, is a known carrier or has a family history of a single gene, autosomal dominant chromosomal disorder Both partners are known carriers of a single gene autosomal recessive chromosomal disorder One partner is a known carrier of a single X-linked disorder 4. Couples who already have one child with a genetic problem and are at high risk of having another 5. There have been three or more prior failed attempts at IVF 6. Women with > 2 miscarriages (recurrent pregnancy losses) related to parental structural chromosome abnormality 7. Repeated implantation failure defined as the absence of a gestational sac on ultrasound at 5 weeks post-embryo transfer (e.g., > 3 embryo transfers with high quality embryos or the transfer of 10 embryos in multiple transfers) 8. To determine the sex of an embryo only when there is a documented history of an X-linked disorder, such that deselection of an affected embryo can be made on the basis of sex alone. 9. To evaluate human leukocyte antigen (HLA) status in families with a child with a malignant cancer or genetic disorder who is likely to be cured or whose life expectancy is expected to be substantially prolonged by a cord blood stem cell transplant after all other clinical options have been exhausted, and in whom there is no other source of a compatible bone marrow donor other than an HLA matched sibling. Preimplantation Genetic Diagnosis Sep 15 2
3 *Note: Single gene disorders include autosomal recessive diseases (e.g., cystic fibrosis, beta-thalassemia, Tay-Sachs), autosomal dominant diseases (e.g., Marfan's syndrome, myotonic dystrophy) and X-linked diseases (e.g., Duchenne and Becker's muscular dystrophy, hemophilia, fragile-x syndrome). Note: When the specific criteria noted above are met, we consider the polar body biopsy / cleavage stage embryo biopsy procedure to obtain the cell and the genetic test associated with PGD medically necessary. List of Genetically Determined Disorders Achondroplasia Alpha-1-antitrypsin deficiency Cystic fibrosis Fanconi anemia Hemophilia A and B Muscular dystrophy (Duchenne and Becker) osis type I Phenylketonuria Retinitis pigmentosa Spinal muscular atrophy Fragile X syndrome Rett syndrome Barth's syndrome Down's syndrome Adenosine deaminase deficiency Beta thalassemia Epidermolysis bullosa Gaucher disease Huntington disease Ornithine transcarbamylase (OTC) deficiency Myotonic dystrophy Retinoblastoma Sickle cell disease Tay Sachs disease Lesch-Nyhan syndrome Charcot-Marie-Tooth disease Turner syndrome Health Net, Inc. considers PGD not medically necessary for any of the following because there is a paucity of peer-reviewed studies: 1. The genetic code associated with the condition is not known to allow diagnosis with current genetic testing techniques 2. Genetic diagnosis is uncertain, e.g., due to genetic/molecular heterogeneity or uncertain mode of inheritance 3. PGD for the purposes of carrier testing to determine carrier status of the embryo (determination of carrier status is performed on individuals contemplating reproduction) 4. PGD for adult-onset/late-onset disorders (e.g., Alzheimer's disease; cancer predisposition) Health Net, Inc. considers PGD investigational for any of the following because although studies continue to be done, additional peer-reviewed studies are necessary to determine the safety, efficacy and long-term outcomes for these scenarios: Preimplantation Genetic Diagnosis Sep 15 3
4 1. PGD for the purpose of HLA typing of an embryo to identify a future suitable stem cell, tissue or organ transplantation donor; PGD has not been established as the standard of care for assessing the suitability of embryos for stem cell transplantation. 2. Testing of embryos for non-medical gender selection or non-medical traits. 3. The affected or sick child has an acute medical condition prohibiting safe stem cell transplantation or has extremely low life expectancy, such that there isn t enough time for the PGD test to be developed, applied and the birth of the HLAmatched sibling. Codes Related To This Policy NOTE: The codes listed in this policy are for reference purposes only. Listing of a code in this policy does not imply that the service described by this code is a covered or noncovered health service. Coverage is determined by the benefit documents and medical necessity criteria. This list of codes may not be all inclusive. On October 1, 2015, the ICD-9 code sets used to report medical diagnoses and inpatient procedures will be replaced by ICD-10 code sets. Health Net National Medical Policies will now include the preliminary ICD-10 codes in preparation for this transition. Please note that these may not be the final versions of the codes and that will not be accepted for billing or payment purposes until the October 1, 2015 implementation date. ICD-9 Codes Other metabolic and immunity disorders Cystic fibrosis Thalassemias Sickle-cell disease Constitutional aplastic anemia Cerebral lipidoses Congenital hereditary muscular dystrophy Hereditary progressive muscular dystrophy Other fetal abnormality causing disproportion; unspecified as to episode of care or not applicable, delivered, with or without mention of antepartum condition, or antepartum condition or complication Known or suspected fetal abnormality affecting management of mother; unspecified as to episode of care or not applicable, delivered, with or without mention of antepartum condition, or antepartum condition or complication , 1, 3 Elderly multigravida Spina bifida and other congenital anomalies of nervous system Chromosomal anomalies Marfan syndrome Other nonspecific abnormal findings on radiological and other examination of body structure V17.2 Family history of other neurological diseases V18.1 Family history of other endocrine and metabolic diseases V18.2 Family history of anemia Preimplantation Genetic Diagnosis Sep 15 4
5 V18.3 Family history of other blood disorders V18.4 Family history of mental retardation V19.5 Family history of congenital anomalies V19.8 Family history of other condition V23.81 Supervision of elderly primigravida V23.82 Supervision of elderly multigravida V23.89 Supervision of other high-risk pregnancy V28.0 Screening for chromosomal anomalies by amniocentesis V28.1 Screening for raised alpha-fetoprotein levels in amniotic fluid V28.2 Other screening based on amniocentesis V28.8 Other specified antenatal screening V82.4 Maternal postnatal screening for chromosomal anomalies V83.81 Cystic fibrosis gene carrier V83.89 Other genetic carrier status ICD-10 Codes D56.0- D56.9 Thalassemia D57.0- D Sickle-cell disorders D D61.09 Constitutional aplastic anemia E75.02 Tay-Sachs disease E75.19 Other gangliosidosis E75.4 Neuronal ceroid lipofuscinosis E75.02 Tay-Sachs disease E75.19 Other gangliosidosis E75.4 Neuronal ceroid lipofuscinosis E E72.9 Other disorders of amino-acid metabolism E84.0- E84.9 Cystic Fibrosis G71.0 Muscular dystrophy G71.2 Congenital myopathies O O Supervision of elderly primigravida and multigravida O O Supervision of other high risk pregnancies O33.7 Maternal care for disproportion due to other fetal deformities O35.0XX0- O35.0XX9 Maternal care for known or suspected fetal abnormality and Damage Q05.0- Q05.9 Spina Bifida Q06.0- Q06.9 Other congenital malformations of spinal cord Q Q87.89 Marfan s syndrome Q90.0- Q99 Chromosomal abnormalities, not elsewhere classified R93.8 Abnormal findings on diagnostic imaging of other specified body structures Z13.89 Encounter for screening for other disorder Preimplantation Genetic Diagnosis Sep 15 5
6 Z14.1 Cystic fibrosis carrier Z14.8 Genetic carrier of other disease Z36 Encounter for antenatal screening of mother Z81.0 Family history of intellectual disabilities Z82.0 Family history of epilepsy and other diseases of the nervous system Z83.2 Family history of diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism Z Z83.49 Family history of other endocrine, nutritional, and metabolic diseases Z82.79 Family history of other congenital malformations, deformations and chromosomal abnormalities Z84.89 Family history of other specified conditions CPT Codes DMD (dystrophin) (eg, Duchenne/Becker muscular dystrophy) deletion analysis, and duplication analysis, if performed Tier 1 Molecular Pathology Procedures MGMT (0-6-methylguanine-DNA methyltransferase) (eg. Glioblastoma multiforme), methylation analysis HLA Class II typing, low resolution (eg. Antigen equivalents);one locus (eg, HLA-DRB1, -DRB3/4/5, -DQB1, -DQA1, -DPB1, or DPA1), each HLA Class II typing, high resolution (i.e., alleles or allele groups); one locus (eg, HLA-DRB1, -DRB3/4/5, -DQB1, -DQA1, -DPB1, or DPA1), each Tier 2 Molecular Pathology Procedures Molecular pathogen procedure, Level 1 (eg, identification of single germline variant (eg. SNP) by techniques such as restriction enzyme digestion or melt curve analysis) Molecular pathogen procedure, Level 2 (eg, 2-10 SNPs, 1 methylated variant, or 1 somatic variant [typically using nonsequencing target variant analysis], or detection of a dynamic mutation disorder /triplet repeat) Molecular pathogen procedure, Level 3 (eg, >10 SNPs, 2-10 methylated variants, or 2-10 somatic variants [typically nonsequencing target variant analysis], immunoglobulin and T-cell receptor gene rearrangements, duplication/deletion variants of 1 exon, loss of heterozygosity (LOH), uniparental disomy (UPD) (Revised in 2015) Molecular pathogen procedure, Level 4 (eg, analysis of single exon by DNA sequence analysis, analysis of >10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning or duplication/deletion variants of 2-5 exons) (Revised in 2015) Molecular pathogen procedure, Level 5 (eg, analysis of 2-5 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of 6-10 exons, or characterization of a Preimplantation Genetic Diagnosis Sep 15 6
7 dynamic mutation disorder/triplet repeat by Southern blot analysis) (Revised in 2015) Molecular pathogen procedure, Level 6 (eg, analysis of 6-10 exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of exons), regionally targeted cytogenomic array analysis (Revised in 2015) Molecular pathogen procedure, Level 7 (eg, analysis of exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of exons, cytogenomic array analysis for neoplasia) Molecular pathogen procedure, Level 8 (eg, analysis of exons by DNA sequence analysis, mutation scanning or duplication/deletion variants of >50 exons, sequence analysis of multiple genes on one platform Molecular pathogen procedure, Level 9 (eg, analysis of >50 exons in a single gene by DNA sequence analysis Molecular diagnostics; molecular isolation or extraction, each nucleic acid type (i.e., DNA or RNA) (CPT Codes deleted in To report see 81161, ) Molecular diagnostics; amplification of patient nucleic acid (e.g. PCR, LCR), single primer pair, each primer pair (CPT Codes deleted in To report see 81161, ) Molecular diagnostics; amplification, target, multiplex, each additional nucleic acid sequence beyond 2 (List separately in addition to code for primary procedure) (CPT Codes deleted in To report see 81161, ) In situ hybridization, (FISH), per specimen; initial single probe stain procedure (Revised in 2015) Biopsy, oocyte polar body or embryo blastomere, microtechnique (for preimplantation genetic diagnosis); less than or equal to 5 embryos Biopsy, oocyte polar body or embryo blastomere, microtechnique (for preimplantation genetic diagnosis); greater than 5 embryos 2015 CPT Code MLH1 (mutl homolog 1, colon cancer, nonpolyposis type 2) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; promoter methylation analysis HCPCS Codes S3625 S3835 S3837 S3840 S3841 S3842 S3843 Maternal serum triple marker screen including alpha-fetoprotein (AFP), estriol, and human chorionic gonadotropin (hcg) (Code deleted in 2014) Complete gene sequence analysis for cystic fibrosis genetic testing (Code deleted in 2013) Complete gene sequence analysis for hemochromatosis genetic testing (Code deleted in 2013) DNA analysis for germline mutations of the ret proto-oncogene for susceptibility to multiple endocrine neoplasia type 2 Genetic testing for retinoblastoma Genetic testing for von Hippel-Lindau disease DNA analysis of the F5 gene for susceptibility to Factor V Leiden thrombophilia (Code deleted in 2013) Preimplantation Genetic Diagnosis Sep 15 7
8 S3845 Genetic testing for alpha-thalassemia S3846 Genetic testing for hemoglobin E beta-thalassemia S3847 Genetic testing for Tay-Sachs disease (Code deleted in 2013) S3848 Genetic testing for Gaucher disease (Code deleted in 2013) S3849 Genetic testing for Niemann-Pick disease S3851 Genetic testing for Canavan disease (Code deleted in 2013) S3853 Genetic testing for myotonic muscular dystrophy S4011-S4022 In vitro fertilization Scientific Rationale Update September 2015 Girardet et al. (2015) completed a study that provides an overview of 10 years of experience of preimplantation genetic diagnosis (PGD) for cystic fibrosis (CF) in the author s center. Owing to the high allelic heterogeneity of CF transmembrane conductance regulator (CFTR) mutations a powerful universal test has been set up based on haplotyping eight short tandem repeats (STR) markers together with the major mutation p.phe508del. Of 142 couples requesting PGD for CF, 76 have been so far enrolled in the genetic work-up, and 53 had 114 PGD cycles performed. Twentynine cycles were canceled upon in vitro fertilization (IVF) treatment because of hyper- or hypostimulation. Of the remaining 85 cycles, a total of 493 embryos were biopsied and a genetic diagnosis was obtained in 463 (93.9%), of which 262 (without or with a single CF-causing mutation) were transferable. Twenty-eight clinical pregnancies were established, yielding a pregnancy rate per transfer of 30.8% in the group of seven couples with one member affected with CF, and 38.3% in the group of couples whose both members are carriers of a CF-causing mutation [including six couples with congenital bilateral absence of the vas deferens (CBAVD)]. So far, 25 children were born free of CF and no misdiagnosis was recorded. This test is applicable to 98% of couples at risk of transmitting CF. Scientific Rationale Update September 2012 Stem cell transplantation has significantly improved the prognosis for many life threatening diseases, (e.g., children affected with Fanconi's anemia). Identification of a disease-free embryo that is also HLA compatible to the affected child and can provide cord blood stem cells for transplantation will significantly improve the probability of survival of the affected sibling. PGD has been used successfully to identify HLA-compatible unaffected embryos to permit treatment of an affected sibling by cord blood transfusion or bone marrow transplantation. However, very few of the embryos tested (about 16 percent) will be both unaffected and an HLA match for the affected sibling. In addition, finding an HLA-matched donor is not always possible, especially for minorities. While autologous hematopoietic stem cells provide perfectly compatible tissue, this type of transplantation is not appropriate in many cases, due to the presence of the disease to be treated in the collected autologous stem cells. Each full sibling potential donor has only a 25 percent chance of being fully HLA-matched with a sibling who requires a transplant. Therefore, many patients do not have an HLAidentical relative. When a suitable related donor is not available, a search is conducted to identify a potential unrelated HLA-matched donor. Finding an appropriate donor through a national registry is a lengthy process that is not always successful, especially for individuals who are not of Northern European descent. As a result, many patients who might benefit from HCT are not afforded this opportunity, or die during the extended process of securing a donor. Preimplantation Genetic Diagnosis Sep 15 8
9 Harper et al. (2012) For the last 20 years, preimplantation genetic diagnosis (PGD) has been mostly performed on cleavage stage embryos after the biopsy of 1-2 cells and PCR and FISH have been used for the diagnosis. The main indications have been single gene disorders and inherited chromosome abnormalities. Preimplantation genetic screening (PGS) for aneuploidy is a technique that has used PGD technology to examine chromosomes in embryos from couples undergoing IVF with the aim of helping select the chromosomally 'best' embryo for transfer. It has been applied to patients of advanced maternal age, repeated implantation failure, repeated miscarriages and severe male factor infertility. Recent randomized controlled trials (RCTs) have shown that PGS performed on cleavage stage embryos for a variety of indications does not improve delivery rates. At the cleavage stage, the cells biopsied from the embryo are often not representative of the rest of the embryo due to chromosomal mosaicism. There has therefore been a move towards blastocyst and polar body biopsy, depending on the indication and regulations in specific countries (in some countries, biopsy of embryos is not allowed). Blastocyst biopsy has an added advantage as vitrification of blastocysts, even post biopsy, has been shown to be a very successful method of cryopreserving embryos. However, mosaicism is also observed in blastocysts. There have been dramatic changes in the method of diagnosing small numbers of cells for PGD. Both array-comparative genomic hybridisation and single nucleotide polymorphism arrays have been introduced clinically for PGD and PGS. For PGD, the use of SNP arrays brings with it ethical concerns as a large amount of genetic information will be available from each embryo. For PGS, RCTs need to be conducted using both array-cgh and SNP arrays to determine if either will result in an increase in delivery rates. Scientific Rationale Update October 2011 Colls et al. (2009) Preimplantation genetic diagnosis (PGD) for gender selection for non-medical reasons has been considered an unethical procedure by several authors and agencies in the Western society on the basis that it could disrupt the sex ratio, that it discriminates against women and that it leads to disposal of normal embryos of the non-desired gender. In this study, the analysis of a large series of PGD procedures for gender selection from a wide geographical area in the USA shows that, in general, there is no deviation in preference towards any specific gender except for a preference of males in some ethnic populations of Chinese, Indian and Middle Eastern origin that represent a small percentage of the US population. In cases where only normal embryos of the non-desired gender are available, 45.5% of the couples elect to cancel the transfer, while 54.5% of them are open to have embryos transferred of the non-desired gender, this fact being strongly linked to cultural and ethnic background of the parents. In addition this study adds some evidence to the proposition that, in couples with previous children of a given gender, there is no biological predisposition towards producing embryos of that same gender. El-Toukhy et al. (2010) completed a review to inform the clinician about the application, success rates and limitations of preimplantation genetic diagnosis (PGD) for hematologic disease to enable clinicians to offer couples with reproductive risk a realistic view of possible treatments. The history and ethics involved in performing PGD together with human leukocyte antigen (HLA) testing (PGD-H) to create matched siblings suitable for hematopoietic stem cell transplant (HSCT) are discussed. The greatest diagnostic hurdle in PGD is the paucity of molecular material in the single embryonic cell. PGD to exclude embryos carrying serious hematologic disease is a viable alternative to prenatal diagnosis for couples whom wish to avoid having affected children and for whom therapeutic termination of affected pregnancies is unacceptable. PGD is not available for all hematologic mutations, is Preimplantation Genetic Diagnosis Sep 15 9
10 expensive, time consuming and does not guarantee a pregnancy. PGD-H is more diagnostically and ethically challenging, especially when there is the time constraint of urgent provision of HLA-matched stem cells for a sick sibling. To date there is only a handful of reported cases of successful HSCT from siblings created by embryo selection. Pre-implantation genetic diagnosis (PGD) has been proposed as a method for selecting HLA-matched embryos in order to create a tissue matched child that can serve as a stem cell donor. After delivery of the HLA-matched baby, umbilical cord blood (UCB) cells can be collected and cryopreserved for transplantation to the sick sibling or the affected child. Using pre-implantation HLA typing to have a tissuematched child that can serve as a haematopoietic stem cell donor to save a loved one s life. This is generally known as the creation of saviour siblings. Haematopoietic stem cells are found in the umbilical cord blood, bone marrow and peripheral blood. Despite recent promising results of using stem cells from the umbilical cord blood of so called saviour siblings for curing patients with blood diseases and certain types of cancer, this method has been met with much opposition. Concerns related to the risks of preimplantation genetic diagnosis (PGD) for the child to be born, the intention to have a donor child, the limits that should be placed on what cells or organs can be used from the child and whether the recipient can be someone other than a sibling). Preimplantation tissue typing has been proposed as a method for creating a tissue matched child that can serve as a haematopoietic stem cell donor to save its sick sibling in need of a stem cell transplant. Despite recent promising results, many people have expressed their disapproval of this method. Scientific Rationale Update February 2011 Tay Sachs Disease Altaruscu et al. (2007) Preimplantation genetic diagnosis (PGD) for single gene defects is described for a family in which each parent is a carrier of both Tay-Sachs (TS) and Gaucher disease (GD). A multiplex fluorescent polymerase chain reaction protocol was developed that simultaneously amplified all four familial mutations and 10 informative microsatellite markers. In one PGD cycle, seven blastomeres were analysed, reaching a conclusive diagnosis in six out of seven embryos for TS and in five out of seven embryos for GD. Of the six diagnosed embryos, one was wild type for both TS and GD, and three were wild type for GD and carriers of TS. Two remaining embryos were compound heterozygotes for TS. Two transferable embryos developed into blastocysts (wt/wt and wt GD/carrier TS) and both were transferred on day 5. This single cycle of PGD resulted in a healthy live child. Allele drop-out (ADO) was observed in three of 34 reactions, yielding an 8% ADO rate. The occurrence of ADO in single cell analysis and undetected recombination events are primary causes of misdiagnosis in PGD and emphasize the need to use multiple polymorphic markers. So far as is known, this is the first report of concomitant PGD for two frequent Ashkenazi Jewish recessive disorders. Fragile X Syndrome Malcov et al. (2007) Fragile X syndrome is caused by a dynamic mutation in the FMR1 gene. Normal individuals have <55 CGG repeats in the 5 untranslated region, premutation carriers have repeats and a full mutation has >200 repeats. Female carriers are at risk of having affected offspring. A multiplex nested polymerase chain reaction protocol is described for preimplantation genetic diagnosis (PGD) of fragile X syndrome with simultaneous amplification of the CGG-repeat region, the Sry gene and several flanking polymorphic markers. The amplification Preimplantation Genetic Diagnosis Sep 15 10
11 efficiency was > or =96% for all loci. The allele dropout rate in heterozygotic females was 9% for the FMR1 CGG-repeat region and 5-10% for the polymorphic markers. Amplification failure for Sry occurred in 5% of single leukocytes isolated from males. PGD was performed in six patients who underwent 15 cycles. Results were confirmed in all cases by amniocentesis or chorionic villous sampling. Five clinical pregnancies were obtained (31% per cycle), four of which resulted in a normal delivery and one miscarried. This technique is associated with high efficiency and accuracy and may be used in carriers of full mutations and unstable high-order premutations. Giardet et al. (2008) Two multiplex PGD protocols were developed allowing the detection of the common homozygous deletion of the telomeric spinal muscular atrophy gene (SMN1), together with two microsatellites located on each side of SMN1. The molecular genetics laboratory of the university hospital in Montpellier. PATIENT(S): A couple who had already given birth to a child affected with SMA.) In vitro fertilization using intracytoplasmic sperm injection (ICSI) and blastomere biopsy. MAIN OUTCOME MEASURE(S): Improvement of PGD for SMA. Two different multiplex protocols were set up on 81 (multiplex A) and 64 single cells (multiplex B) from normal controls, affected patients, and individuals with homozygous SMN2 deletion. In one PGD cycle that used one of these protocols, two embryos were transferred, which resulted in the birth of a healthy baby. Analysis of microsatellite markers in addition to the SMN1 deletion allows the detection of contamination, the study of ploidy of the biopsied blastomeres, and the performance of an indirect genetic diagnosis, thereby increasing the reliability of the results. This PGD assay may be applied to all families with the common deletion of SMN1 and also to couples in whom one of the partners carries a small intragenic mutation in SMN1, identified in about 6% of affected individuals who do not lack both copies of SMN1. Shaw et al. (2008) Thirty-three members of 7 families participated in carrier test and disease detection of SMA. Prenatal genetic diagnosis was performed if both parents were carriers or any family members had SMA. DNA extracted from blood, chorionic villi and amniotic fluid was amplified and used for DHPLC. Twenty SMA carriers, seven SMA affected cases, and six normal individuals were identified. SMA status was demonstrated by genotyping and total copy number determinations of SMN1 and SMN2. Families 1-3 were classified as group one (SMA affecting previously born child). Group two, comprising families 4 and 5, had lost a child due to an unknown muscular disease. Group three (SMA-affected parent) comprised families 6 and 7; carrier testing was done. DHPLC prenatal genetic diagnosis was made in seven pregnancies, one in each family (affected, n=2; carrier, n=3; normal, n=2). Pregnancy was terminated for the two affected fetuses. The others were delivered uneventfully and SMA free. DHPLC prenatal diagnosis of SMA and determination of SMA status in adults is possible, and SMN1 and SMN2 copy numbers can be determined. Alpha-1-antitrypsin deficiency Alpha-1 antitrypsin (AAT) deficiency emphysema is an inherited disorder affecting approximately 100,000 Americans. Affected patients have little or no blood and tissue levels of AAT (also called alpha-1 protease inhibitor, alpha1-pi, or A1-PI), which protects the lung from destruction by enzymes in the lung that normally digest bacteria and other invaders. Unchecked, this enzyme progressively damages healthy lung tissue leading to decreased lung function and emphysema. The prognosis for patients with high-risk phenotypes for AAT deficiency emphysema is poor although symptomatic treatments and more definitive lung surgery are options. Preimplantation Genetic Diagnosis Sep 15 11
12 Cystic Fibrosis Norton et al. (2008) Recent advances in genetic technology have substantial implications for prenatal screening and diagnostic testing. The past year has also seen important changes in recommendations surrounding the genetic counseling that occurs in the provision of such testing. Multiple screening tests for single gene disorders, chromosomal abnormalities, and structural birth defects are now routinely offered to all pregnant women. Ethnicity-based screening for single gene disorders includes Tay Sachs disease, cystic fibrosis, and hemoglobinopathies. Recent discussions have involved, not only additional disorders that warrant screening, but a re-evaluation of the paradigm of selecting disorders for population-based screening. Testing for chromosomal abnormalities has seen the introduction of first-trimester screening, as well as strategies to improve detection through sequential testing. Changes in recommendations for screening compared with diagnostic testing, and a move away from maternal age-based dichotomizing of testing, have had major implications for provision of genetic counseling by providers of prenatal care. Advances in genetic testing have resulted in tremendous benefits to patients, and challenges to providers. New approaches to education and counseling are needed to assure that all patients receive a complete and balanced review of their prenatal genetic-testing options. Fanconi Anemia Modern Ashkenazi Jewish (AJ) populations (Ashkenazic Jews or Ashkenazim) descended from the Jewish communities of Germany, Poland, Austria, and Eastern Europe. Approximately 90% of the 5.7 million individuals of Jewish descent in the USA today are of AJ origin. Certain childhood-onset autosomal recessive genetic disorders are more common among the AJ community including Tay-Sachs disease, Canavan disease, familial dysautonomia, Bloom syndrome, Fanconi anemia group C, Gaucher disease, mucolipidosis type IV, Niemann-Pick disease type 1A, cystic fibrosis, and primary dystonia type 1 (torsion dystonia). Over the last few decades, the molecular basis of these diseases has been elucidated providing the tools and the opportunity to perform preconceptual carrier screening for these disorders in this ethnic group. The relatively homogeneous genetic make-up of the AJ population has resulted in there being a relatively limited number of disease-causing sequence variants accounting for the majority of cases of each disease which has allowed for the development of screening panels with a high level of sensitivity and specificity for the AJ population. As a result of the autosomal recessive mode of inheritance for these disorders, if both members of a couple are carriers, they have a 25% chance of having a child with the disorder. Fifteen autosomal recessive disorders were reviewed in order to determine whether or not they should be included in an AJ screening panel. The 15 disorders are: alpha-1-antitrypsin deficiency (AAD), Bloom syndrome (BLM), Canavan disease (CD), CF, deafness neurosensory autosomal recessive 1 (DFNB1), FD, familial hyperinsulinism (FHI), Fanconi anemia type C (FAC), Gaucher disease type 1 (GD), glycogen storage disease type 1A (GSD), maple syrup urine disease type 1b (MSUD), mucolipidosis type IV (MLIV), Niemann-Pick disease types A and B (NPDA&B), nonclassical congenital adrenal hyperplasia (NCAH), and Tay-Sachs disease (TSD). There is controversy, however, surrounding which diseases should be included in such screening panels. While serious, generally fatal disorders such as Tay-Sachs disease and Canavan disease are clear candidates for screening; the argument is not as clear for disorders with variable clinical presentation and reduced penetrance such as Gaucher disease or primary dystonia. Fares et al. (2008) completed a study, with a database containing the results of 410 genotyping assays was screened. Ten thousand seventy eight nonselected healthy Preimplantation Genetic Diagnosis Sep 15 12
13 members of the AJ population were tested for carrier status for the following diseases; Gaucher disease (GD), cystic fibrosis (CF), Familial dysautonomia (FD), Alpha 1 antitrypsin (A1AT), Mucolipidosis type 4 (ML4), Fanconi anemia type C (FAC), Canavan disease (CD), Neimann-Pick type 4 (NP) and Bloom syndrome (BLM). The results demonstrated that 635 members were carriers of one mutation and 30 members were found to be carriers of two mutations in the different genes related to the development of the above mentioned diseases. GD was found to have the highest carrier frequency (1:17) followed by CF (1:23), FD (1:29), A1AT (1:65), ML4 (1:67) and FAC (1:77). The carrier frequency of CD, NP and BLM was 1:82, 1:103 and 1:157, respectively. The frequency of the disease-causing mutations screened routinely among the AJ population indicated that there are rare mutations with very low frequencies. The screening policy of the disease-causing mutations should be reevaluated and mutations with a high frequency should be screened, while rare mutations with a lower frequency may be tested in partners of carriers. Hemophilia A for Hemophilia A/Factor 8 Deficiency Laurie et al. (2010) Preimplantation genetic diagnosis (PGD) is an option for couples at risk of having a child with hemophilia A (HA). Although many clinics offer PGD for HA by gender selection, an approach that detects the presence of the underlying F8 mutation has several advantages. The objection was to develop and validate analysis protocols combining indirect and direct methods for identifying F8 mutations in single cells, and to apply these protocols clinically for PGD. A panel of microsatellite markers in linkage disequilibrium with F8 were validated for single-cell multiplex polymerase chain reaction. For point mutations, a primer extension genotyping assay was included in the multiplex. Amplification efficiency was evaluated using buccal cells and blastomeres. Four clinical PGD analyses were performed, for two families. Results: Across all validation experiments and the clinical PGD cases, approximately 80% of cells were successfully genotyped. Following one of the PGD cycles, healthy twins were born to a woman who carries the F8 intron 22 inversion. The PGD analysis for the other family was complicated by possible germline mosaicism associated with a de novo F8 mutation, and no pregnancy was achieved. Conclusions: PGD for the F8 intron 22 inversion using microsatellite linkage analysis was validated by the birth of healthy twins to one of the couples. The other family's situation highlighted the complexities associated with de novo mutations, and possible germline mosaicism. As many cases of HA result from de novo mutations, these factors must be considered when assessing the reproductive options for such families. Per the American Congress of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion. Number 430 March Preimplantation Genetic Screening for Aneuploidy states the following: Preimplantation genetic screening differs from preimplantation genetic diagnosis for single gene disorders and was introduced for the detection of chromosomal aneuploidy. Current data does not support a recommendation for preimplantation genetic screening for aneuploidy using fluorescence in situ hybridization solely because of maternal age. Also, preimplantation genetic screening for aneuploidy does not improve in vitro fertilization success rates and may be detrimental. At this time there are no data to support preimplantation genetic screening for recurrent unexplained miscarriage and recurrent implantation failures; its use for these indications should be restricted to research studies with appropriate informed consent. Preimplantation genetic screening differs from preimplantation genetic diagnosis (PGD) for single gene disorders. In order to perform genetic testing for Preimplantation Genetic Diagnosis Sep 15 13
14 single gene disorders, PGD was introduced in 1990 as a component of in vitro fertilization programs. Such testing allows the identification and transfer of embryos unaffected by the disorder in question and may avoid the need for pregnancy termination. Assessment of polar bodies as well as single blastomeres from cleavage stage embryos has been reported, although the latter is the approach most widely practiced. Preimplantation genetic diagnosis has become a standard method of testing for single gene disorders, and there have been no reports to suggest adverse postnatal effects of the technology. Preimplantation genetic diagnosis has been used for diagnosis of translocations and single-gene disorders, such as cystic fibrosis, X- linked recessive conditions, and inherited mutations, which increase one s risk of developing cancer. In contrast, in the latter half of the 1990s, preimplantation genetic screening was introduced for the detection of chromosomal aneuploidy (2 4). Aneuploidy leads to increased pregnancy loss with increasing maternal age and also was thought to be a major cause of recurrent pregnancy loss in patients using assisted reproductive technologies. However, when compared with the molecular diagnostics available for PGD of single gene disorders, the current technologies available for preimplantation genetic screening for aneuploidy are more limited. Preimplantation genetic screening using fluorescence in situ hybridization is constrained by the technical limitations of assessing the numerical status of each chromosome. Typically assessed are the chromosome abnormalities associated with common aneuploidies found in spontaneous abortion material, and because of this, and other limitations noted in this Committee Opinion, a significant false-negative rate exists. Therefore, this form of testing should be considered a screening test, and not a diagnostic test, as is the case for PGD for single gene disorders. Because preimplantation chromosome assessment tests a single cell, there are certain limitations: Testing a single cell prohibits confirmation of results. There is a limit to the number of tests that can be done with a single cell. Embryo mosaicism of normal and aneuploid cell lines may not be clinically significant. Guidelines for counseling on limitations of this screening have been developed by the American Society for Reproductive Medicine. Recommendations of ACOG: Current data does not support a recommendation for preimplantation genetic screening for aneuploidy using fluorescence in situ hybridization solely because of maternal age. Preimplantation genetic screening for aneuploidy does not improve in vitro fertilization success rates and may be detrimental. At this time there are no data to support preimplantation genetic screening for recurrent unexplained miscarriage and recurrent implantation failures; its use for these indications should be restricted to research studies with appropriate informed consent. Scientific Rationale Initial With recent advances in genetics, there are a good number of inherited disorders, which can now be diagnosed at a molecular level. For couples who are carriers or affected by any of a variety of genetic diseases and are at high risk for transmitting Preimplantation Genetic Diagnosis Sep 15 14
15 it to their offspring, it is currently possible to detect the disorder during pregnancy. This is done by one of two approaches: chorionic villus sampling in the first trimester or amniocentesis in the second trimester. However the couples have the dilemma of whether or not to terminate the pregnancy if the genetic abnormality is present. In some cases this may also not be a viable option for religious or moral reasons. An alternative would then be to diagnose the condition in embryos before the pregnancy is established. Only the unaffected embryos would then be transferred to the uterus. This new technique that combines advances in molecular genetics and assisted reproductive technologies is referred to as preimplantation genetic diagnosis (PGD). It does not involve the manipulation of genes in embryos; rather, it selects among embryos. PGD involves several steps: the creation of an embryo via IVF; the removal of one or two cells from the embryo; the genetic testing of these cells for specific genetic conditions; and the subsequent transfer of unaffected embryos to a woman s uterus. Currently, IVF is the only available technique for obtaining an embryo in the very early stages of development. One to two single cells, blastomeres, are removed from early cleavage stage embryos (6 8-cell stage) at approximately 3 days' postfertilization. The blastomere contains genetic material that can be analyzed to identify three categories of disorders, including aneuploidy and structural chromosomal abnormalities, single-gene disorders, and X-linked disorders. Although couples with a high risk of transmitting a genetic defect to their offspring may have normal fertility, they would need to go through the IVF procedure to provide embryos for screening. Fertility specialists can use the results of this analysis to select only mutation-free embryos for implantation into the mother's uterus, hence preventing the physical and psychological trauma associated with possible termination. Clinical and practical considerations include that the embryo must be healthy enough to survive the procedure. It is estimated that only 2.5% of eggs collected will form a viable unaffected pregnancy. Maternal age is an important factor, particularly for aneuploidy screening in women older than 35 years of age, as this increases the likelihood of finding a chromosomal abnormality and decreases the success rate of IVF. With PGD, couples are much more likely to have healthy babies. Although PGD has been practiced for years, only a few specialized centers worldwide offer this procedure. PGD should be offered for 3 major groups of disease, including (1) sex-linked disorders, (2) single gene defects, and (3) chromosomal disorders. X-linked diseases are passed to the child through a mother who is a carrier. They are passed by an abnormal X chromosome and manifest in sons, who do not inherit the normal X chromosome from the father. Affected fathers have sons who are not affected, and their daughters have a 50% risk of being carriers if the mother is healthy. Sex-linked recessive disorders include hemophilia, fragile X syndrome, most of the neuromuscular dystrophies (currently > 900 neuromuscular dystrophies are known), and hundreds of other diseases. Sex-linked dominant disorders include Rett syndrome, incontinentia pigmenti, pseudohyperparathyroidism, and vitamin D resistant rickets. This genetic test is currently available to couples whose offspring are at a high risk (25-50%) for a specific genetic condition due to one or both parents being carriers or affected by the disease. Also the genetic code associated with the condition must be known in order to allow diagnosis. Currently, it is not feasible to routinely screen women at lower risks, such as women over age 35 for Downs Syndrome, since the means of establishing a pregnancy is with the help of IVF. Preimplantation Genetic Diagnosis Sep 15 15
16 PGD is used to identify single gene defects such as cystic fibrosis, Tay-Sachs disease, sickle cell anemia, and Huntington disease. In such diseases, the molecular abnormality is detectable with molecular techniques using PCR amplification of DNA from a single cell. Although progress has been made, some single gene defects have a wide variety of rare mutations (e.g., cystic fibrosis has approximately 1000 known mutations). Only 25 of these mutations are currently routinely tested. Because most of these rare mutations are not routinely tested, a parent without any clinical manifestations of cystic fibrosis could be a carrier. This allows the possibility for a parent carrying a rare mutation gene to be tested as negative but still have the ability to pass on the mutant cystic fibrosis gene. The last group includes chromosomal disorders in which a variety of chromosomal rearrangements, including translocations, inversions, and deletions, can be detected using FISH. Some parents may have never achieved a viable pregnancy without using PGD because previous conceptions resulted in chromosomally unbalanced embryos and were spontaneously miscarried. The risk of aneuploidy in children increases as women age. The chromosomes in the egg are less likely to divide properly, leading to an extra or missing chromosome in the embryo. The rate of aneuploidy in embryos is greater than 20% in mothers aged years and is nearly 40% in mothers aged 40 years or older. The rate of aneuploidy in children is % in mothers aged years and is % in mothers older than 40 years. The difference in percentages between affected embryos and live births is due to the fact that an embryo with aneuploidy is less likely to be carried to term and will most likely be miscarried, some even before pregnancy is suspected or confirmed. Therefore, using PGD to determine the chromosomal makeup of embryos increases the chance of a healthy pregnancy and reduces the number of pregnancy losses and affected offspring with so-called serious inherited disorders such as Tay Sachs; Trisomies 13, 18, and 21; cystic fibrosis; muscular dystrophy; Huntington disease; Lesch-Nyhan; and neurofibromatosis. PDG is also presently has much wider indications than prenatal diagnosis, including common diseases with genetic predisposition and preimplantation human leukocyte antigen typing, with the purpose of establishing potential donor progeny for stem cell treatment of siblings. Many hundreds of apparently healthy, unaffected children have been born after preimplantation genetic diagnosis, presenting evidence of its accuracy, reliability and safety. Preimplantation genetic diagnosis appears to be of special value for avoiding age-related aneuploidies in patients of advanced reproductive age, improving reproductive outcome, particularly obvious from their reproductive history, and is presently an extremely attractive option for carriers of balanced translocations to have unaffected children of their own. Many people fear that PGD will be used to select a child of a preferred sex. PGD could also be used in attempts to select a future child's cosmetic, behavioral, and other non-disease traits. However, the genetic laws of independent assortment make it difficult for PGD to be used for any traits that depend on two or more genes. Thus, PGD provides an alternative to germline modification as a way to prevent the births of children with serious genetic diseases, most of which are single-gene disorders, but does not open the door to escalating and species-altering applications. Research continues in the area of PGD. There is now a rapidly growing list of disorders for which PGD has been applied successfully, including cystic fibrosis, Tay- Sachs disease, hemophilia A and B, retinitis pigmentosa, numerous inborn errors of metabolism, fragile X syndrome, Duchenne muscular dystrophy, and chromosomal abnormalities, to name a few. The risks of PGD are similar to risks for IVF, namely Preimplantation Genetic Diagnosis Sep 15 16
17 multiple-fetal pregnancies and the twofold increased risk for major birth defects and low birth weight. Preliminary studies show no increased risk for spontaneous abortions. The data from long-term follow-up of children conceived after PGD, however, have yet to be collected. Review History October 2005 November 2006 November 2007 February 2011 October 2011 September 2012 September 2013 September 2014 September 2015 Medical Advisory Council initial approval Medical Advisory Council - no changes Update no revisions Update. Added Medicare Table. No revisions. Update - no revisions Update no revisions Update no revisions. Code updates Update no revisions. Code updates. Update no revisions. Code updates. This policy is based on the following evidence-based guidelines: 1. American College of Obstetricians and Gynecologists, American College of Medical Genetics: Preconception and Prenatal Carrier Screening for Cystic Fibrosis: Clinical and Laboratory Guidelines. Washington, DC; American College of Obstetrics and Gynecology; October, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology: A practice committee report: Preimplantation genetic diagnosis. Birmingham, Ala. June National Ethics Committee on Assisted Human Reproduction. Guidelines for Preimplantation Genetic Diagnosis in New Zealand. Consultation Document. September Thornhill AR, dedie-smulders CE, Geraedts JP, et al. European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium. Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) Available at: 5. Developments in infertility therapy. Diagnosis of genetic disease in embryos. Australian Family Physician Vol. 34, No. 3, March International Working Group on Preimplantation Genetics, International Congress of Human Genetics: Preimplantation Genetic Diagnosis: Experience of Three Thousand Cycles. Report of the 11th Annual Meeting of International Working Group on Preimplantation Genetics, in association with 10th International Congress of Human Genetics. Vienna, Austria; May, American Society For Reproductive Medicine. Preimplantation Genetic Diagnosis Fact Sheet. 12/ Preimplantation genetic testing: a Practice Committee opinion. Practice Committee of the Society for Assisted Reproductive Technology; Practice Committee of the American Society for Reproductive Medicine. Fertil Steril 2007;88: Hayes. Medical Technology Directory. Genetic Testing for Tay-Sachs Disease. Updated March 6, Archived November 12, Hayes. Genetic Test Overview. Fragile X Syndrome (FMR1) for Mental Retardation. August 7, 2008, Updated August 1, Archived July 13, Hayes. Genetic Test Overview. Y Chromosome Microdeletion Analysis for Male Infertility. November 14, 2008, Updated December 6, Archived December 14, 2013 Preimplantation Genetic Diagnosis Sep 15 17
18 12. American Congress of Obstetricians and Gynecologists (ACOG). ACOG Committee Opinion. Number 430. March Preimplantation Genetic Screening for Aneuploidy. Reaffirmed Hayes. Genetic Test Overview. Spinal Muscular Atrophy (SMA) for Progressive Muscle Weakness. January 23, 2009, Updated January 31, Updated January 17, Archived February 23, Hayes. Genetic Test Evaluation Overview. Ashkenazi Jewish Genetic Screening Panel for Risk Assessment. February 18, 2009, Updated February 15, Updated February 13, Archived March 18, Hayes. Genetic Test Overview. COL1A1 and COL1A2 Testing for Osteogenesis Imperfecta Types I to IV. February 20, 2009, Updated February 14, Archived March 20, Hayes. Genetic Test Overview. GTE Report: Charcot-Marie-Tooth Type 1A (PMP22). Published: August 5, Updated Aug 23, 2010, Updated July 31, Archived June 30, Hayes. Genetic Test Overview. Spinocerebellar Ataxia Type 1 (SCA1) for Movement Disorders. March 3, 2010, Updated February 10, Archived March 9, Hayes. Genetic Test Overview. GTE Report: Myotonic Dystrophy Types 1 and 2 Published: March 9, Latest Update Search: Mar 31, 2010, Updated March 2, Archived April 9, Hayes. Genetic Test Overview. Spinocerebellar Ataxia Type 2 (SCA2) for Movement Disorders. March 3, 2010, Updated February 10, Archived March 23, Hayes. Genetic Test Overview. Spinocerebellar Ataxia Type 3 (SCA3; Machado- Joseph Disease) for Movement Disorders. March 3, 2010, Updated February 13, Archived February 27, Hayes. Genetic Test Overview. Spinocerebellar Ataxia Type 6 (SCA6) for Movement Disorders. March 31, 2010, Updated March 13, Archived April 11, Hayes. Genetic Test Overview. Spinocerebellar Ataxia Type 7 (SCA7) Movement Disorder. April 29, 2010, Updated April 18, Archived May 29, Hayes. Genetic Test Overview. GTE Report: Huntington Chorea/Disease (HD) for Diagnostic, Predictive, and Prenatal or Preimplantation Genetic Diagnosis Purposes. Published: April 29, Updated May 6, 2010, Updated April 25, Archived May 29, Hayes. Genetic Test Overview. Comparative Genomic Hybridization (CGH) Microarray for Chromosomal Imbalance. April 12, 2010, Updated February 7, Updated May 22, Updated May 19, Hayes. Genetic Test Overview. Marfan Syndrome. May 7, 2010, Updated April 27, Archived May 2, Hayes. Genetic Test Overview. Spinocerebellar Ataxia Type 12 (SCA12) for Movement Disorders. June 15, 2010, Updated June 2, Archived Hayes. Genetic Test Overview. Spinocerebellar Ataxia Type 17 (SCA17) for Movement Disorders. June 17, 2010, Updated May 22, Archived July 25, Hayes. Genetic Test Overview. GTE Report: Neurofibromatosis Type 1 (NF1). Published: November 17, 2010, Updated April 5, Updated April 2, Hayes. Genetic Test Overview. GTE Synopsis: Hemophilia A (Factor VIII Deficiency). Published: January 24, 2011, Updated June 19, Updated July 11, Updated June 8, Preimplantation Genetic Diagnosis Sep 15 18
19 30. American College of Obstetricians and Gynecologists (ACOG). Committee Opinion. Family History as a Risk Assessment Tool. Number 478. March Reaffirmed Hayes. GTE. Cystic Fibrosis Transmembrane Regulator (CFTR) for Cystic Fibrosis. May 30, Updated May 20, Updated May 13, Hayes. Medical Technology Directory. Genetic Carrier Testing for Cystic Fibrosis. June 7, Updated August 1, Archived July 7, Hayes. GTE Overview. Tay-Sachs Disease (TSD) Testing in Individuals of Non- Jewish Origin. December 8, Updated December 11, Updated December 4, Hayes. GTE Synopsis. X-Linked Intellectual Disability (XLID) Multigene Panels. November 6, Updated December 4, Hayes. GTE. FMR1 Testing for Fragile X-Associated Tremor/Ataxia Syndrome. May 20, Archived July 16, References Update September Baker MW, Atkins AE, Cordavado SK, et al. Improving newborn screening for cystic fibrosis using next-generation sequencing technology: a technical feasibility study. Genet Med Feb 12. doi: /gim [Epub ahead of print] 2. Girardet A, Ishmukhametova A, Willems M, et al. Preimplantation genetic diagnosis for cystic fibrosis: the Montpellier center's 10-year experience. Clin Genet Feb;87(2): doi: /cge Epub 2014 May Lim RM, Silver AJ, Silver MJ, et al. Targeted mutation screening panels expose systematic population bias in detection of cystic fibrosis risk. Genet Med Apr 16. doi: /gim [Epub ahead of print] 4. Loukas YL, Thodi G, Molou E, et al. Clinical diagnostic Next-Generation sequencing: The case of CFTR carrier screening. Scand J Clin Lab Invest Apr 15:1-8. [Epub ahead of print] 5. Redin C, Gérard B, Lauer J, et al. Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. J. Med. Genet. 2014;51(11): Salinas DB, Sosnay PR, Azen C, et al. Benign outcome among positive cystic fibrosis newborn screen children with non-cf-causing variants. J Cyst Fibros Mar 28. pii: S (15) doi: /j.jcf [Epub ahead of print]. References Update September Girardet A, Ishmukhametova A, Willems M, et al. Preimplantation Genetic Diagnosis for Cystic Fibrosis: the Montpellier centre's 10-year experience. Clin Genet Apr 25. doi: /cge [Epub ahead of print]. 2. Olson H, Shen Y, Avallone J, et al. Copy number variation plays an important role in clinical epilepsy. Ann Neurol May 9. doi: /ana [Epub ahead of print]. 3. van Minkelen R, van Bever Y, Kromosoeto JN, et al. A clinical and genetic overview of 18 years neurofibromatosis type 1 molecular diagnostics in the Netherlands. Clin Genet Apr;85(4): doi: /cge Epub 2013 Jun 25. References Update September Abotalib Z. Preimplantation genetic diagnosis in Saudi Arabia. Bioinformation Apr 30;9(8): Preimplantation Genetic Diagnosis Sep 15 19
20 2. Collins SC. Preimplantation genetic diagnosis: technical advances and expanding applications. Curr Opin Obstet Gynecol Jun;25(3): Qiao J, Wang ZB, Feng HL, et al. The root of reduced fertility in aged women and possible therapentic options: Current status and future perspects. Mol Aspects Med Jun Rubio C, Bellver J, Rodrigo L, et al. Preimplantation genetic screening using fluorescence in situ hybridization in patients with repetitive implantation failure and advanced maternal age: two randomized trials. Fertil Steril Apr;99(5): References Update September Chang LJ, Chen SU, Tsai YY, et al. An update of preimplantation genetic diagnosis in gene diseases, chromosomal translocation, and aneuploidy screening. Clin Exp Reprod Med. 2011;38(3): Gabbe: Obstetrics: Normal and Problem Pregnancies, 6th ed. Preimplantation Genetic Diagnosis Saunders, An Imprint of Elsevier. 3. Harper JC, Sengupta SB. Hum Genet Feb;131(2): Epub 2011 Jul 12. Preimplantation genetic diagnosis: state of the art Lentz: Comprehensive Gynecology, 6th ed. Fertilization and early cleavage Mosby, An Imprint of Elsevier. 5. Lubin BH, Greene MF. Collection and storage of umbilical cord blood for hematopoietic cell transplantation. March 22, UpToDate. 6. Mastenbroek S, Twisk M, van der Veen F, Repping S. Preimplantation genetic screening: A systematic review and meta-analysis of RCTs. Hum Reprod Update. 2011;17(4): Musters AM, Repping S, Korevaar JC, et al. Pregnancy outcome after preimplantation genetic screening or natural conception in couples with unexplained recurrent miscarriage: A systematic review of the best available evidence. Fertil Steril. 2011;95(6): , 2157.e1-e3. 8. Paulson R. In vitro fertilization. August 2, UpToDate. 9. Tulandi T, Al-Fozan HM. Management of couples with recurrent pregnancy loss. UpToDate. June 11, UpToDate. 10. Tur-Kaspa I. Clinical management of in vitro fertilization with preimplantation genetic diagnosis. Semin Reprod Med Aug;30(4): Epub 2012 Jun 21. References Update October Colls P, Silver L, Olivera G, et al. Preimplantation genetic diagnosis for gender selection in the USA. Reprod Biomed Online. 2009;19 Suppl 2: Cooper AR, Jungheim ES. Preimplantation Genetic Testing: Indications and Controversies. Clinics in Laboratory Medicine. Volume 30, Issue 3, September Debrock S, Melotte C, Spiessens C, et al. Preimplantation genetic screening for aneuploidy of embryos after in vitro fertilization in women aged at least 35 years: a prospective randomized trial. Fertil Steril 2010; 93: El-Toukhy T, Bickerstaff H, Meller S. Preimplantation genetic diagnosis for haematologic conditions. Current Opinion in Pediatrics Feb;22(1): Fischer J, Colls P, Escudero T, Munné S, et al. Preimplantation genetic diagnosis (PGD) improves pregnancy outcome for translocation carriers with a history of recurrent losses. Fertil Steril. 2010;94(1): Harper JC, Harton G. The use of arrays in preimplantation genetic diagnosis and screening. Fertil Steril 2010; 94:1173. Preimplantation Genetic Diagnosis Sep 15 20
The following chapter is called "Preimplantation Genetic Diagnosis (PGD)".
Slide 1 Welcome to chapter 9. The following chapter is called "Preimplantation Genetic Diagnosis (PGD)". The author is Dr. Maria Lalioti. Slide 2 The learning objectives of this chapter are: To learn the
More informationPreimplantation Genetic Diagnosis. Evaluation for single gene disorders
Preimplantation Genetic Diagnosis Evaluation for single gene disorders What is Preimplantation Genetic Diagnosis? Preimplantation genetic diagnosis or PGD is a technology that allows genetic testing of
More informationOptional Tests Offered Before and During Pregnancy
Plano Women s Healthcare Optional Tests Offered Before and During Pregnancy Alpha-Fetoprotein Test (AFP) and Quad Screen These are screening tests that can assess your baby s risk of having such birth
More informationObstetrical Ultrasound and Prenatal Diagnostic Center
Obstetrical Ultrasound and Prenatal Diagnostic Center Prenatal Diagnosis: Options and Opportunities Learn about various screening options including Early Risk Assessment (ERA), now available to women of
More informationMEDICAL POLICY SUBJECT: PRENATAL GENETIC TESTING. POLICY NUMBER: 4.01.03 CATEGORY: Laboratory Test
MEDICAL POLICY SUBJECT: PRENATAL GENETIC TESTING PAGE: 1 OF: 8 If a product excludes coverage for a service, it is not covered, and medical policy criteria do not apply. If a commercial product, including
More informationPreimplantation Genetic Diagnosis (PGD) for Fanconi Anemia and HLA matching
Preimplantation Genetic Diagnosis (PGD) for Fanconi Anemia and HLA matching Andria G. Besser, BEd, MS, CGC Licensed Genetic Counselor Reproductive Genetics Institute Chicago, IL Outline PGD overview In
More informationREI Pearls: Pitfalls of Genetic Testing in Miscarriage
The Skinny: Genetic testing of miscarriage tissue is controversial and some people question if testing is helpful or not. This summary will: 1) outline the arguments for and against genetic testing; 2)
More informationConsent to Perform Preimplantation Genetic Screening (PGS) using. Comparative Genomic Hybridization (acgh) or Next Generation Sequencing (NGS)
Consent to Perform Preimplantation Genetic Screening (PGS) using Array Comparative Genomic Hybridization (acgh ) or Next Generation Sequencing (NGS) Purpose The purpose of Preimplantation Genetic Screening
More informationCarrier Screening For Genetic Diseases Preconception Consent (Female and/or Male Partner)
Carrier Screening For Genetic Diseases Preconception Consent (Female and/or Male Partner) The goal of our practice at ARMS is to make sure that you receive optimal care to improve your chances of having
More informationLEUKODYSTROPHY GENETICS AND REPRODUCTIVE OPTIONS FOR AFFECTED FAMILIES. Leila Jamal, ScM Kennedy Krieger Institute, Baltimore MD
LEUKODYSTROPHY GENETICS AND REPRODUCTIVE OPTIONS FOR AFFECTED FAMILIES Leila Jamal, ScM Kennedy Krieger Institute, Baltimore MD 2 Outline Genetics 101: Basic Concepts and Myth Busting Inheritance Patterns
More informationPreimplantation genetic diagnosis new method of screening of 24 chromosomes with the Array CGH method...2
August 2012 content 8 Preimplantation genetic diagnosis new method of screening of 24 chromosomes with the Array CGH method...2 Maintaining fertility new opportunities in GENNET...3 Hysteroscopy without
More informationPreimplantation Genetic Diagnosis (PGD) in Western Australia
Preimplantation Genetic Diagnosis (PGD) in Western Australia Human somatic cells have 46 chromosomes each, made up of the 23 chromosomes provided by the egg and the sperm cell from each parent. Each chromosome
More informationUNIT 13 (OPTION) Genetic Abnormalities
Unit 13 Genetic Abnormailities 1 UNIT 13 (OPTION) Genetic Abnormalities Originally developed by: Hildur Helgedottir RN, MN Revised (2000) by: Marlene Reimer RN, PhD, CCN (C) Associate Professor Faculty
More informationCHROMOSOMES Dr. Fern Tsien, Dept. of Genetics, LSUHSC, NO, LA
CHROMOSOMES Dr. Fern Tsien, Dept. of Genetics, LSUHSC, NO, LA Cytogenetics is the study of chromosomes and their structure, inheritance, and abnormalities. Chromosome abnormalities occur in approximately:
More informationMedical Policy Preimplantation Genetic Testing
Medical Policy Preimplantation Genetic Testing Table of Contents Policy: Commercial Coding Information Information Pertaining to All Policies Policy: Medicare Description References Authorization Information
More informationCarol Ludowese, MS, CGC Certified Genetic Counselor HDSA Center of Excellence at Hennepin County Medical Center Minneapolis, Minnesota
Carol Ludowese, MS, CGC Certified Genetic Counselor HDSA Center of Excellence at Hennepin County Medical Center Minneapolis, Minnesota The information provided by speakers in workshops, forums, sharing/networking
More informationMendelian inheritance and the
Mendelian inheritance and the most common genetic diseases Cornelia Schubert, MD, University of Goettingen, Dept. Human Genetics EUPRIM-Net course Genetics, Immunology and Breeding Mangement German Primate
More informationCorporate Medical Policy Genetic Testing for Fanconi Anemia
Corporate Medical Policy Genetic Testing for Fanconi Anemia File Name: Origination: Last CAP Review: Next CAP Review: Last Review: genetic_testing_for_fanconi_anemia 03/2015 3/2016 3/2017 3/2016 Description
More informationGene mutation and molecular medicine Chapter 15
Gene mutation and molecular medicine Chapter 15 Lecture Objectives What Are Mutations? How Are DNA Molecules and Mutations Analyzed? How Do Defective Proteins Lead to Diseases? What DNA Changes Lead to
More informationChromosomes, Mapping, and the Meiosis Inheritance Connection
Chromosomes, Mapping, and the Meiosis Inheritance Connection Carl Correns 1900 Chapter 13 First suggests central role for chromosomes Rediscovery of Mendel s work Walter Sutton 1902 Chromosomal theory
More informationPrenatal screening and diagnostic tests
Prenatal screening and diagnostic tests Contents Introduction 3 First trimester routine tests in the mother 3 Testing for health conditions in the baby 4 Why would you have a prenatal test? 6 What are
More informationBalanced. translocations. rarechromo.org. Support and Information
Support and Information Rare Chromosome Disorder Support Group, G1, The Stables, Station Rd West, Oxted, Surrey. RH8 9EE Tel: +44(0)1883 723356 info@rarechromo.org I www.rarechromo.org Balanced Unique
More informationMinimum standards for ICSI use, screening, patient information and follow-up in WA fertility clinics. January 2006
Minimum standards for ICSI use, screening, patient information and follow-up in WA fertility clinics January 2006 1. BACKGROUND ICSI has been shown to be effective for male factor infertility and it also
More informationPreimplantation Genetic Diagnosis Ethical Aspects. Sonya Al-Mohammed, MBBS, Arab Board, MSc*
Bahrain Medical Bulletin, Vol. 36, No. 4, December 2014 Education-Family Physician Corner Preimplantation Genetic Diagnosis Ethical Aspects Sonya Al-Mohammed, MBBS, Arab Board, MSc* In vitro fertilization
More informationIn - Vitro Fertilization Handbook
In - Vitro Fertilization Handbook William F. Ziegler, D.O. Medical Director Scott Kratka, ELD, TS Embryology Laboratory Director Lauren F. Lucas, P.A.-C, M.S. Physician Assistant Frances Cerniak, R.N.
More informationMCB41: Second Midterm Spring 2009
MCB41: Second Midterm Spring 2009 Before you start, print your name and student identification number (S.I.D) at the top of each page. There are 7 pages including this page. You will have 50 minutes for
More informationMEDICAL GENETICS GENERAL OBJECTIVE SPECIFIC OBJECTIVES
SUBJECT MEDICAL GENETICS CREDITS Total: 4.5 Theory 2.5 Practical 2 GENERAL OBJECTIVE To provide students with terminology and knowledge from the field of human genetics that will enable them to understand
More informationChapter 16 Reproductive Technology, Gene Therapy, and Stem Cells (modified)
Chapter 16 Reproductive Technology, Gene Therapy, and Stem Cells (modified) Assisted Reproductive Technologies (ART) Artificial insemination (AI) In vitro fertilization (IVF) Gamete intrafallopian transfer
More informationGenetic Mutations. Indicator 4.8: Compare the consequences of mutations in body cells with those in gametes.
Genetic Mutations Indicator 4.8: Compare the consequences of mutations in body cells with those in gametes. Agenda Warm UP: What is a mutation? Body cell? Gamete? Notes on Mutations Karyotype Web Activity
More informationMolecular Genetic Analysis of Single Cells
268 Molecular Genetic Analysis of Single Cells Francesco Fiorentino, Ph.D. 1 1 GENOMA - Molecular Genetics Laboratory, Rome, Italy Semin Reprod Med 2012;30:268 283 Address for correspondence and reprint
More informationWhitney Fasbender. The University Of Kansas School of Nursing
The Savior Child: Having a Child to Save a Sibling Is this Right? Whitney Fasbender The University Of Kansas School of Nursing About the author: A native of Cheney, Kansas, Whitney was inducted into Delta
More informationDIAGNOSING CHILDHOOD MUSCULAR DYSTROPHIES
DIAGNOSING CHILDHOOD MUSCULAR DYSTROPHIES Extracts from a review article by KN North and KJ Jones: Recent advances in diagnosis of the childhood muscular dystrophies Journal of Paediatrics and Child Health
More informationMy Sister s s Keeper. Science Background Talk
My Sister s s Keeper Science Background Talk Outline Acute promyelocytic leukemia (APL) APL Treatment Savior Siblings In vitro fertilization (IVF) Pre-implantation Genetic Diagnosis (PGD) Risks of donating
More informationThe correct answer is c A. Answer a is incorrect. The white-eye gene must be recessive since heterozygous females have red eyes.
1. Why is the white-eye phenotype always observed in males carrying the white-eye allele? a. Because the trait is dominant b. Because the trait is recessive c. Because the allele is located on the X chromosome
More informationHUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY AND ADVISORY COMMITTEE ON GENETIC TESTING CONSULTATION DOCUMENT ON PREIMPLANTATION GENETIC DIAGNOSIS
HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY AND ADVISORY COMMITTEE ON GENETIC TESTING CONSULTATION DOCUMENT ON PREIMPLANTATION GENETIC DIAGNOSIS Introduction 1. This document considers the current and
More informationStem Cell Quick Guide: Stem Cell Basics
Stem Cell Quick Guide: Stem Cell Basics What is a Stem Cell? Stem cells are the starting point from which the rest of the body grows. The adult human body is made up of hundreds of millions of different
More informationCorporate Medical Policy Carrier Testing for Genetic Disease
Corporate Medical Policy Carrier Testing for Genetic Disease File Name: Origination: Last CAP Review: Next CAP Review: Last Review: carrier_testing_for_genetic_disease 12/2013 8/2015 8/2016 8/2015 Description
More informationHUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY REPORT:
HUMAN FERTILISATION AND EMBRYOLOGY AUTHORITY REPORT: Introduction 1. Preimplantation tissue typing is a new technique which allows the selection of embryos in order to bring about the birth of a child
More informationEach person normally has 23 pairs of chromosomes, or 46 in all. We inherit one chromosome per pair from our mother and one from our father.
AP Psychology 2.2 Behavioral Genetics Article Chromosomal Abnormalities About 1 in 150 babies is born with a chromosomal abnormality (1, 2). These are caused by errors in the number or structure of chromosomes.
More informationAssisted Reproductive Technologies at IGO
9339 Genesee Avenue, Suite 220 San Diego, CA 92121 858 455 7520 Assisted Reproductive Technologies at IGO Although IGO no longer operates an IVF laboratory or program as such, we work closely with area
More information4. All cord blood banks should be subject to the same standards, regulations and accreditation requirements.
WMDA Policy Statement on the Utility of Autologous or Family Cord Blood Unit Storage The WMDA Board adopted this policy on 25 th of May 2006. Policy updated _April 2011 The Cord Blood Working Group and
More informationMarrying a relative. Is there an increased chance that a child will have genetic problems if its parents are related to each other?
Marrying a relative Is there an increased chance that a child will have genetic problems if its parents are related to each other? The simple answer to this question is Yes, there is an increased chance.
More informationAct of 5 December 2003 No. 100 relating to the application of biotechnology in human medicine, etc
Act of 5 December 2003 No. 100 relating to the application of biotechnology in human medicine, etc Cf. earlier Acts of 5 August 1994 No. 56 and 12 June 1987 No. 68 Chapter 1. Purpose and scope 1-1. Purpose
More informationThe genetic screening of preimplantation embryos by comparative genomic hybridisation
Vol. 11, Suppl. 3 51 The genetic screening of preimplantation embryos by comparative genomic hybridisation Maria V Traversa 1, James Marshall, Steven McArthur, Don Leigh Genea, Sydney, Australia Received:
More informationGene Therapy and Genetic Counseling. Chapter 20
Gene Therapy and Genetic Counseling Chapter 20 What is Gene Therapy? Treating a disease by replacing, manipulating or supplementing a gene The act of changing an individual s DNA sequence to fix a non-functional
More informationBackground document on preimplantation and prenatal genetic testing. Clinical Situation. Legal situation 1
DH-BIO/INF (2015) 6 Background document on preimplantation and prenatal genetic testing Clinical Situation Legal situation 1 1 Part II of this document presents the legal situation in Council of Europe
More informationCarrier detection tests and prenatal diagnosis
Carrier detection tests and prenatal diagnosis There are several types of muscular dystrophy and about 50 neuromuscular conditions, all of which fall under the umbrella of the Muscular Dystrophy Campaign.
More informationSAVE A LIFE... BY GIVING LIFE!
SAVE A LIFE... BY GIVING LIFE! FOLLOW US ON: HÉMA-QUÉBEC PUBLIC CORD BLOOD BANK www.hema-quebec.qc.ca Scan this code with your smart phone to access the page Register to the Public Cord Blood Bank on the
More informationEthical issues in assisted reproductive technologies. Effy Vayena
Ethical issues in assisted reproductive technologies Effy Vayena Assisted Reproductive Technologies (ART) All treatments or procedures that include the in vitro handling of human oocytes and human sperm
More information5. All cord blood banks should be subject to the same standards, regulations and accreditation requirements.
WMDA Policy Statement for the Utility of Autologous or Family Cord Blood Unit Storage (This policy statement has been approved and adopted by the WMDA board on the 25 th of May 2006) The Cord Blood Registries
More informationPatient Information. for Childhood
Patient Information Genetic Testing for Childhood Hearing Loss Introduction This document describes the most common genetic cause of childhood hearing loss and explains the role of genetic testing. Childhood
More informationGenetic Testing in Research & Healthcare
We Innovate Healthcare Genetic Testing in Research & Healthcare We Innovate Healthcare Genetic Testing in Research and Healthcare Human genetic testing is a growing science. It is used to study genes
More informationBecker Muscular Dystrophy
Muscular Dystrophy A Case Study of Positional Cloning Described by Benjamin Duchenne (1868) X-linked recessive disease causing severe muscular degeneration. 100 % penetrance X d Y affected male Frequency
More informationGene Mapping Techniques
Gene Mapping Techniques OBJECTIVES By the end of this session the student should be able to: Define genetic linkage and recombinant frequency State how genetic distance may be estimated State how restriction
More informationWhat Is Genetic Counseling? Helping individuals and families understand how genetics affects their health and lives
What Is Genetic Counseling? Helping individuals and families understand how genetics affects their health and lives What does the career involve? Explore family histories to identify risks Reducing risks
More informationPreimplantation Genetic Diagnosis (PGD) and Childhood Diagnostic Evaluation
IG O Preimplantation Genetic Diagnosis (PGD) and Childhood Diagnostic Evaluation KD Carsten Bergmann carsten.bergmann@bioscientia.de carsten.bergmann@uniklinik-freiburg.de Controversies Conference on ADPKD
More informationPreimplantation Genetic Diagnosis: Prenatal Testing for Embryos Finally Achieving Its Potential
J. Clin. Med. 2014, 3, 280-309; doi:10.3390/jcm3010280 OPEN ACCESS Journal of Clinical Medicine ISSN 2077-0383 www.mdpi.com/journal/jcm Review Preimplantation Genetic Diagnosis: Prenatal Testing for Embryos
More informationA Guide to Prenatal Genetic Testing
Patient Education Page 29 A Guide to Prenatal Genetic Testing This section describes prenatal tests that give information about your baby s health. It is your choice whether or not to have these tests
More informationGENETIC TESTING FOR INHERITED MUTATIONS OR SUSCEPTIBILITY TO CANCER OR OTHER CONDITIONS MED207.110
GENETIC TESTING FOR INHERITED MUTATIONS OR SUSCEPTIBILITY TO CANCER OR OTHER CONDITIONS MED207.110 COVERAGE: Pre- and post-genetic test counseling may be eligible for coverage in addition to the genetic
More informationPreimplantation genetic screening (PGS)
Preimplantation genetic screening (PGS) Dagan Wells Reprogenetics UK In vitro fertilization (IVF) A highly successful medical intervention Infertility treatment revolutionized Estimated that >5 million
More informationAssisted reproductive technologies (ART) in Canada: 2011 results from the Canadian ART Register
1 Assisted reproductive technologies (ART) in Canada: 2011 results from the Canadian ART Register Joanne Gunby, M.Sc. CARTR Co-ordinator Email: gunbyj@mcmaster.ca Supported by the IVF Directors Group of
More informationThe Rh Factor: How It Can Affect Your Pregnancy
The American College of Obstetricians and Gynecologists f AQ FREQUENTLY ASKED QUESTIONS FAQ027 PREGNANCY The Rh Factor: How It Can Affect Your Pregnancy What is the Rh factor? How does a person get the
More informationThe California Prenatal Screening Program
The California Prenatal Screening Program Quad Marker Screening One blood specimen drawn at 15 weeks - 20 weeks of pregnancy (second trimester) Serum Integrated Screening Prenatal Patient Booklet - English
More informationGenetics in Family Medicine: The Australian Handbook for General Practitioners Testing and pregnancy
Genetics in Family Medicine: The Australian Handbook for General Practitioners Testing and pregnancy Testing and pregnancy GP s role 3 Counselling before and during pregnancy 3 Collecting the family history
More informationThe Ethics of Stem Cell Research and Prenatal Genetic Alteration
The Ethics of Stem Cell Research and Prenatal Genetic Alteration Blake Rodgers, Brandon Peterson Introduction Technological advancements associated with the medical industry create opportunities to conduct
More informationGenetics Review for USMLE (Part 2)
Single Gene Disorders Genetics Review for USMLE (Part 2) Some Definitions Alleles variants of a given DNA sequence at a particular location (locus) in the genome. Often used more narrowly to describe alternative
More informationPREIMPLANTATION GENETIC DIAGNOSIS
PREIMPLANTATION GENETIC DIAGNOSIS Peter Braude, Susan Pickering, Frances Flinter and Caroline Mackie Ogilvie Preimplantation genetic diagnosis (PGD) is an evolving technique that provides a practical alternative
More informationNon-Invasive Prenatal Testing (NIPT) Factsheet
Introduction NIPT, which analyzes cell-free fetal DNA circulating in maternal blood, is a new option in the prenatal screening and testing paradigm for trisomy 21 and a few other fetal chromosomal aneuploidies.
More informationNot All Stem Cells are the Same
Cord Blood Banking and Transplantation Jennifer Willert, M.D. Hematology/Oncology Blood and Marrow Transplant Rady Children s Hospital San Diego Clinical Professor UCSD Not All Stem Cells are the Same
More informationMedical Devices; Exemptions From Premarket Notifications; Class II Devices; Autosomal
This document is scheduled to be published in the Federal Register on 10/27/2015 and available online at http://federalregister.gov/a/2015-27198, and on FDsys.gov 4164-01-P DEPARTMENT OF HEALTH AND HUMAN
More informationChapter 4 Pedigree Analysis in Human Genetics. Chapter 4 Human Heredity by Michael Cummings 2006 Brooks/Cole-Thomson Learning
Chapter 4 Pedigree Analysis in Human Genetics Mendelian Inheritance in Humans Pigmentation Gene and Albinism Fig. 3.14 Two Genes Fig. 3.15 The Inheritance of Human Traits Difficulties Long generation time
More informationRECURRENT PREGNANCY LOSS DR.RAJALAKSHMI SRINIVASAN SPECIALIST GYNECOLOGIST ZULEKHA HOSPITAL DUBAI
RECURRENT PREGNANCY LOSS DR.RAJALAKSHMI SRINIVASAN SPECIALIST GYNECOLOGIST ZULEKHA HOSPITAL DUBAI RECURRENT PREGNANCY LOSS -RM Clinically recognized consecutive or non consecutive pregnancy losses before
More informationPROVIDER POLICIES & PROCEDURES
PROVIDER POLICIES & PROCEDURES BRCA GENETIC TESTING The purpose of this document is to provide guidance to providers enrolled in the Connecticut Medical Assistance Program (CMAP) on the requirements for
More informationChromosomes, Karyotyping, and Abnormalities (Learning Objectives) Learn the components and parts of a metaphase chromosome.
Chromosomes, Karyotyping, and Abnormalities (Learning Objectives) Learn the components and parts of a metaphase chromosome. Define the terms karyotype, autosomal and sex chromosomes. Explain how many of
More informationFREQUENTLY ASKED QUESTIONS ABOUT IVF
FREQUENTLY ASKED QUESTIONS ABOUT IVF Is there something we can do to improve our chances of succes? Even though IVF treatment is a medical process on which you have no influence, there are a number of
More informationEmbryonic Choices. Scientist Toolkit for Public Engagement: Clinical Embryology, Genetics and Haematology
Embryonic Choices An A-level workshop on Assisted Conception and Saviour Siblings Scientist Toolkit for Public Engagement: Clinical Embryology, Genetics and Haematology Pathology: the science behind the
More informationA Kantian Ethical Analysis of Preimplantation Genetic Diagnosis by Emily Delk
A Kantian Ethical Analysis of Preimplantation Genetic Diagnosis by Emily Delk Introduction In an era where new genetic and reproductive technologies are increasing, ethical concerns continue to grow as
More informationReproductive Technology. Chapter 21
Reproductive Technology Chapter 21 Assisted Reproduction When a couple is sub-fertile or infertile they may need Assisted Reproduction to become pregnant: Replace source of gametes Sperm, oocyte or zygote
More informationA test your patients can trust.
A test your patients can trust. A simple, safe, and accurate non-invasive prenatal test for early risk assessment of Down syndrome and other conditions. informaseq Prenatal Test Simple, safe, and accurate
More informationGuidance For Research Involving Human Embryonic Stem Cells, Germ Cells, And Cells Obtained From Cord Blood
Guidance For Research Involving Human Embryonic Stem Cells, Germ Cells, And Cells Obtained From Cord Blood Supreme Council of Health Department of Research Guidance Regarding Research Involving Human Embryonic
More informationFirst Trimester Screening for Down Syndrome
First Trimester Screening for Down Syndrome What is first trimester risk assessment for Down syndrome? First trimester screening for Down syndrome, also known as nuchal translucency screening, is a test
More informationGenetic testing. The difference diagnostics can make. The British In Vitro Diagnostics Association
6 Genetic testing The difference diagnostics can make The British In Vitro Diagnostics Association Genetic INTRODUCTION testing The Department of Health published Our Inheritance, Our Future - Realising
More informationOverview of Genetic Testing and Screening
Integrating Genetics into Your Practice Webinar Series Overview of Genetic Testing and Screening Genetic testing is an important tool in the screening and diagnosis of many conditions. New technology is
More informationGenetics and Pregnancy Loss
Genetics and Pregnancy Loss Dorothy Warburton Genetics and Development (in Pediatrics) Columbia University, New York Estimates of Pregnancy Loss from Conception 1000 fertilized eggs (27% are lost) 728
More informationCHAPTER 15 THE CHROMOSOMAL BASIS OF INHERITANCE. Section B: Sex Chromosomes
CHAPTER 15 THE CHROMOSOMAL BASIS OF INHERITANCE Section B: Sex Chromosomes 1. The chromosomal basis of sex varies with the organism 2. Sex-linked genes have unique patterns of inheritance 1. The chromosomal
More informationThis fact sheet describes how genes affect our health when they follow a well understood pattern of genetic inheritance known as autosomal recessive.
11111 This fact sheet describes how genes affect our health when they follow a well understood pattern of genetic inheritance known as autosomal recessive. In summary Genes contain the instructions for
More informationInfluences on Birth Defects
Influences on Birth Defects FACTS About 150,000 babies are born each year with birth defects. The parents of one out of every 28 babies receive the frightening news that their baby has a birth defect There
More informationHelping you find the one match.. Guide for Unrelated Stem Cell Transplant Patients OneMatch Stem Cell and Marrow Network BLOOD.
Helping you find the one match.. Guide for Unrelated Stem Cell Transplant Patients OneMatch Stem Cell and Marrow Network BLOOD.CA WWW This guide is intended for patients in need of an unrelated volunteer
More informationCHAPTER 1 BACKGROUND AND CORD BLOOD BANK (CBB) ORGANIZATION
CHAPTER 1 BACKGROUND AND CORD BLOOD BANK (CBB) ORGANIZATION Chapter 1 BACKGROUND AND CORD BLOOD BANK (CBB) ORGANIZATION 1.1 OVERVIEW OF THE CORD BLOOD TRANSPLANTATION STUDY Bone marrow transplantation
More informationGENETIC TESTING AND MARFAN SYNDROME
GENETIC TESTING AND MARFAN SYNDROME Genetic testing for mutations in fibrillin-1 (FBN1) and other genes has become an important and reliable option to aid in the diagnosis of Marfan syndrome and related
More informationCytogenetic and Molecular Diagnosis in Gestational Disorders
Cytogenetic and Molecular Diagnosis in Gestational Disorders Katherine Geiersbach, M.D. Assistant Professor, Department of Pathology University of Utah School of Medicine Medical Director, Cytogenetics
More information14.3 Studying the Human Genome
14.3 Studying the Human Genome Lesson Objectives Summarize the methods of DNA analysis. State the goals of the Human Genome Project and explain what we have learned so far. Lesson Summary Manipulating
More informationGenetics, Ethics &Meaning. Module 4
Genetics, Ethics &Meaning INItiative (GEMINI) Life Sciences and Society @University of Michigan Module 4 Myths versus Facts The University of Michigan s Stem Cell Research Environment A Case Study MYTH:
More informationCLINICAL GUIDELINES. Lab Management Program. Effective January 15, 2016
CLINICAL GUIDELINES Lab Management Program Effective January 15, 2016 CareCore National, LLC d/b/a evicore healthcare (evicore) Clinical guidelines for medical necessity review of lab management services.
More informationDNA Fingerprinting. Unless they are identical twins, individuals have unique DNA
DNA Fingerprinting Unless they are identical twins, individuals have unique DNA DNA fingerprinting The name used for the unambiguous identifying technique that takes advantage of differences in DNA sequence
More informationLecture 6: Single nucleotide polymorphisms (SNPs) and Restriction Fragment Length Polymorphisms (RFLPs)
Lecture 6: Single nucleotide polymorphisms (SNPs) and Restriction Fragment Length Polymorphisms (RFLPs) Single nucleotide polymorphisms or SNPs (pronounced "snips") are DNA sequence variations that occur
More informationInformation leaflet. Centrum voor Medische Genetica. Version 1/20150504 Design by Ben Caljon, UZ Brussel. Universitair Ziekenhuis Brussel
Information on genome-wide genetic testing Array Comparative Genomic Hybridization (array CGH) Single Nucleotide Polymorphism array (SNP array) Massive Parallel Sequencing (MPS) Version 120150504 Design
More informationREPRODUCTIVE MEDICINE AND INFERTILITY ASSOCIATES Woodbury Medical Arts Building 2101 Woodwinds Drive Woodbury, MN 55125 (651) 222-6050
REPRODUCTIVE MEDICINE AND INFERTILITY ASSOCIATES Woodbury Medical Arts Building 2101 Woodwinds Drive Woodbury, MN 55125 (651) 222-6050 RECIPIENT COUPLE INFORMED CONSENT AND AUTHORIZATION FOR IN VITRO FERTILIZATION
More informationPlaying God? The Ethics of Genetic Manipulation
Playing God? The Ethics of Genetic Manipulation Lawrence M. Hinman, Ph.D. Co-Director Center for Ethics in Science & Technology Professor of Philosophy University of San Diego 4/7/2009 Lawrence M. Hinman
More informationRoche Position on Human Stem Cells
Roche Position on Human Stem Cells Background Stem cells and treating diseases. Stem cells and their applications offer an enormous potential for the treatment and even the cure of diseases, along with
More information