Pre-implantation Genetic Diagnosis (PGD)

Pre-implantation Genetic Diagnosis (PGD)

For couples considering IVF who are concerned about passing on an inherited genetic disease to their children, PGD is an excellent treatment option at Orient Hospital IVF.
Preimplantation genetic diagnosis (PGD) is a procedure whereby individual cells are biopsied from the patient's embryos before they are transferred back into the uterus.
The intention of performing the embryo biopsy is to select against embryos, which may be chromosomally or genetically abnormal -- as well as to improve implantation rates.
Common single-gene mutations that have been diagnosed with PGD and PCR include, but are not limited to:
- Cystic Fibrosis
- Beta-Thalassemia
- Sickle Celle Anemia
- Myotonic Dystrophy
- Huntington's Chorea
- Fragile X
- Duchenne's Muscular Dystrophy
- HOW PGD WORKS
- PGD requires obtaining genetic material from an egg or an embryo -- and there are two types of biopsies performed.

Polar body biopsy enables the assessment of the genetic complement of the egg and provides indirect information of the genetic status of the egg in conditions where a genetic disorder is of material origin.

Blastomere biopsy involves removing one or two cells from an early embryo, providing genetic information of maternal or paternal origin (if either parent is a carrier of a disorder) -- as well as information specific to that embryo (spontaneous mutations and sex).
Several techniques are employed to identify the genetic abnormalities.

Polymerase chain reaction (PCR) is the method used to detect single gene mutations and involves isolation and amplification of short DNA fragments.

Fluorescent In-Situ Hybridization (FISH) is a technique to determine abnormalities in the chromosomes within a particular blastomere. Fluorescently labeled probes that recognize specific sequences of a specific chromosome are allowed to hybridize to the cell. The cell may then be analyzed under a fluorescent microscope to identify the presence or absence of the particular chromosome(s) in question. This technique is employed to evaluate embryos of patients who are carriers of a numerical chromosomal abnormality -- as well as for assessment of aneuploidy that occurs more frequently as a result of reproductive aging.
However, a newer method to detect chromosome problems has replaced FISH -- and is called array CGH.

Our new Day 5 Array CGH (Comparative Genomic Hybridization) testing reveals whether an embryo has the correct number of chromosomes. Too many or too few chromosomes will result in either a non-viable embryo, a miscarriage or -- if implanted and carried to term -- an infant with a birth defect. Such chromosomal abnormalities are also thought to be major causes of IVF failure.

CGH is a screening technique that has been shown in some studies to increase IVF success rates significantly, particularly for women in their late 30's and early 40's, in couples with a history of failed fertility treatment and in patients with recurrent pregnancy loss. It can also be used in younger women to improve the selection of an embryo and may enhance the success of elective single embryo in IVF and therefore guard against the risk of multiple births.

Array CGH has two main advantages over other methods of screening. The first focuses on new, cutting-edge technology that tests DNA very quickly, so that embryos do not need to be frozen while they are checked. The second is that with a Day 5 biopsy, the diagnostic accuracy is enhanced by the fact that many cells from the trophectoderm of the blastocyst are analyzed. Moreover, because the biopsy is of the trophectoderm cells, it is thought that Day 5 biopsies may have less of a detrimental impact on embryo implantation rates.
The result is that our specialists can now ensure that only high-quality embryos are available for uterine transfer.

What is Preimplantation Genetic Screening (PGS)?
For those people with recurrent pregnancy loss or infertility, PGS applies the technology from PGD to improve their chances for a successful pregnancy. Embryos are screened for aneuploidy (missing or additional numbers of chromosomes), which is a leading cause of miscarriage and implantation failure (failure of the embryo to implant into the uterus). The goal of PGS is to identify chromosomally abnormal embryos, so they will not be transferred leaving the chromosomally normal embryos to be transferred in the attempt to achieve a successful pregnancy.

Who should have PGD and PGS?
PGD is an extremely useful tool for couples in which one or both of the partners are carriers of an inherited genetic disorder. Depending on the inheritance pattern of the disease, the risk of creating an affected child can be as high as 50%. PGD significantly reduces this risk.
PGS, on the other hand, may only be beneficial for a specific population of patients. This includes patients of advanced maternal age and women with a history of recurrent pregnancy loss. Patients must have a large number of good quality embryos in order for PGS to improve their outcome.

What are the risks of PGD?
The largest risk of PGD is not having embryos available for transfer and/or a negative pregnancy test. The results of the PGD procedure may show that all of the embryos are abnormal. In these circumstances, no embryos are transferred and the cycle is cancelled.
There is a small (0.1%) risk that the embryo may be damaged during the biopsy procedure. The risk of not getting any diagnosis on a biopsied cell also exists, although, at the Fertility Centers of New England this risk is less than 1%. Misdiagnosis is also a possible risk of PGD. Although rare, it is possible that one cell in the embryo may have different chromosome numbers than the other cells. This is referred to as mosaicism and will result in a misdiagnosis due to the fact that the information from the biopsied cell is not reflective of the entire embryo. Because PGD is the diagnosis or screening of an embryo based on the results from a single cell, there are limitations involved in using this technology, and PGD is not considered a replacement for prenatal testing.

Pre-Implantation Genetic Diagnosis Disorders
Disorders for which PGD is offered:
The number of diseases for which PGD is capable of diagnosing is growing daily as virtually any disease for which a specific single mutation is known can be tested for. This is the current list but keep in mind that it is growing all the time.
Achondroplasia (FGFR3)
ADA (Adenosine Deaminase) deficiency
Adrenal hyperplasia
Adrenoleukodystrophy (ABCD1)
Agammaglobulinemia-Bruton (TyrsKnse)
Alpha Thalassemia (HBA1)
Alpha-Antitrypsin (AAT)
Alport Syndrome (COL4A5)
Alzheimer (very early onset-PSEN1)
Beta Thalassemia (HBB)
Bloom Syndrome (Blm)
Canavan Disease (ASPA)
Charcot-Marie-Tooth, type IA
Charcot-Marie-Tooth Neuropathy - 1B
Charcot Marie Tooth Neuropathy - 2E
Choroideremia (CHM)
Chronic Granulomatous Dz (CYBB)
Citrullinemia (ASS)
Cleidocranial Dysplasia (RUNX2)
Congen. Adrenal Hyperplasia (CYP31A2)
Congen. Erythropoietic Porphyria (UROS)
Crigler Najjar (UGT1A1)
Cystic Fibrosis (CFTR)
Darier Disease (ATP2A2)
Diamond Blackfan (DBA-RSP19)
Diamond Blackfan (DBA2)
Duchenne muscular dystrophy (DMD)
Dystrophy Myotonica (DMPK)
Emery-Dreifuss Muscular Dystrophy
Epidermolysis bullosa
Epidermolytic Hyperkeratosis (KRT10) Factor
13 Deficiency (F13A1)
Familial Adenomatous Polyposis (APC)
Familial Dysautonomia (IKBKAP)
Fanconi Anemia A (FANCA)
Fanconi Anemia C (FANCC)
Fanconi Anemia F (FANC F)
Fanconia Anemia G (FANCG)
Fragile X (FMR1)
Friedreich Ataxia I (FRDA)
Gaucher Disease (GBA)
Glycogen Storage disease, type 1A
Glutaric Acidemia - 2A
Hemophilia A (F8)
Hemophilia B (F9)
HLA typing (some cases)
HLA DRBeta1 Class II MHC (HLA DRB1*)
HLA-A Class I MHC (HGNC HLA-A)
Hunter syndrome (IDS)
Huntington Disease (HD)
Hurler Syndrome (MPSI-IDUA)
Hyper IgM (CD40-ligand; TNFSF5)
Hypophosphatasia (ALPL)
Incontinentia Pigmenti (KBKG-NEMO)
Kennedy Disease (AR)
Krabbe (GALC)
LCHAD (Long chain 3-hydroxyCoA Dehydrogenase Deficiency)
Lesch-Nyhan (HPRT1)
Leukemia, Acute Lymphocytic (for HLA)
Leukemia, Acute Myelogenous (for HLA)
Leukemia, Chronic Myelogenous (for HLA)
Leukocyte Adhesion Deficiency (ITGB2)
Li-Fraumeni Syndrome (TP53)
Lymphoproliferative Disorder (X-linked)
Marfan Syndrome (FBN1)
Menkes (ATP7A)
Metachromatic Leukodystrophy (ARSA)
Mucolipidosis 2 (I-Cell)
Multiple Epiphyseal Dysplasia
Myotonic dystrophy
Myotubular myopathy
Neurofibromatosis (NF1 & NF2)
Niemann-Pick type C (NPC1)
Ornithine Transcarbamylase Deficiency (OTC)
Osteogenis Imperfecta (COL1A1)
Pachyonychia Congenita (KRT16 & KRT6A)
Periventricular Heteropia (PH)
Phenylketonuria
Polycystic Kidney Disease (AR-PKD1) Polycystic
Kidney Disease (PKD1) Retinoblastoma 1 (RB1)
Retinitis pigmentosa
Rhesus blood group D (RHD)
Rhizomelic Chondrodysplasia Puncta RCDP1
Sacral Agenesis (HLXB9)
Sanfilippo A (MPSIIIA)
Sanhoff disease
SCID-X1 (SevereCmbndImmuneDefic (IL2RG)
Sexing for X-linked Dz (AMELX/Y; ZFX/Y)
Shwachman-Diamond Syndrome (SBDS)
Sickle Cell (HBB)
Smith-Lemli-Opitz (SLOS)
Spinal muscular atrophy (SMN1)
Spinocerebellar Ataxia-3 (SCA3)
Spinocerebellar ataxia2 (SCA2)
Tay-Sachs (HEXA)
Treacher Collins (TOCF1)
Tuberous Sclerosis 1 (TSC1)
Von-Hippel Lindau
Wiskott-Aldrich Syndrome (WAS)
X-linked hydrocephalus