What is Pre-implantation Genetic Diagnosis?

Pre-implantation genetic diagnosis (PGD) is a reproductive technology used along with an IVF cycle. Cells are removed from embryos belonging to patients at risk of passing on a genetic disease to their future children and tested. Healthy embryos can subsequently be chosen for transfer.

PGD may be considered in all IVF cycles; however, those who might benefit most from this test are couples at increased risk for chromosome abnormalities or specific genetic disorders. This includes women who have had repeated miscarriages, or who have had a previous pregnancy with a chromosomal abnormality. Additionally, women over 38 years of age and men with some types of sperm defects may produce embryos with higher rates of chromosome abnormalities.

Conventionally, the only way to diagnose genetic diseases in the foetus is by means of genetic analysis of aspirated amniotic fluid from amniocentesis conducted at the latter stage of pregnancy. A positive and confirmatory genetic diagnosis from amniocentesis will result in two choices: allowing the infant to fully develop and try to live with the inherited abnormality, or terminating the pregnancy through optional abortion. Both scenarios can potentially prove to be very difficult and traumatic for the couples especially when it is done during the later stages of pregnancy.

PGD in Cyprus is as an alternative pre-natal diagnostic tool. The procedure empowers the couples to make early choices prior to implantation eliminating the worry regarding transmission of the genetic defect to the offspring.

PGD in Cyprus can be used to screen for more than 400 genetic diseases using the following parameters of diagnosis:

1.     Aneuploidy Screening

2.     Single Gene Disorder

3.     Chromosomal Translocation


Aneuploidy Screening

Aneuploidy is defined as an abnormal number of chromosome sets within a cell’s nucleus. Our PGD in Cyprus program conducts routine aneuploidy screening in all transferred embryos to significantly reduce the chance of birth defects from occurring. Aneuploidy is also a common cause of miscarriage. The most common abnormalities seen in aneuploidy associated with miscarriages in pregnancy include:

Abnormal sex chromosomes,

Triploidy (having 3 copies of all the chromosomes),

Trisomy (having 3 copies of a set of chromosomes),

and Monosomy (having only one set of chromosomes).

When is PGD performed?

After embryos are created in the laboratory using IVF, they are incubated for three days. On the third day, PGD biopsy is performed by removing one or two cells from the embryo as samples for testing. The genetic material from the nucleus of the cells is tested for the presence of any abnormalities. The complete PGD test results are available on the fifth day where the Embryone doctor will then be discussing with you thoroughly the results of the PGD test and their implications. You will be guided accordingly on the selection process of the embryo by the Embryone medical staff before transfer to the uterus for implantation.

How are the cells taken from the embryo?

PGD in Cyprus is done at the 8-cell stage of development (day 3). The embryologist selects a normal looking embryo and samples one to two cells for testing. The selected embryo is placed under a very powerful microscope where a laser is beamed towards its outer shell (the zona pellucida) to create a small opening from which one or two cells will be aspirated for testing.

It is imperative that one or both sampled cells contain a nucleus because that is where the genetic material needed for testing is located. In the advent that the cell sampled doesn’t contain any nucleus, or the nucleus spontaneously breaks open during preparation, the embryo shall therefore be declared “without any nucleus” or “anuclear”. The absence of the nucleus is not conclusive of a genetically unhealthy or healthy embryo, it will mean that the sex and genetic health status of embryo was not assessed as expected.

How is PGD carried out?

PGD in Cyprus testing is rapid and is completed within 48 hours from sampling. The testing of one or two cells in PGD uses Fluorescence in-situ Hybridization (FISH) to facilitate its speedy analysis in time for the embryo transfer scheduled on the fifth day. The FISH technique uses a small DNA probe utilized with fluorescent microscopy to recognize unique chromosomal patterns which light up (fluoresce) upon contact with the probe during observation.

Which chromosomes are being tested?

The PGD in Cyprus process makes use of a five probe FISH method that screens for five chromosomes commonly involved in aneuploidy; X, Y, 13, 18, and 21. Aberrations in either chromosomes will usually result in the most common genetic abnormalities observed in humans. Normal cells will present with two FISH signals or fluorescence on each numbered chromosome. In sex chromosomes, a double X signal for female, and an X and a Y signal for a male.

Which genetic disorders can PGD in Cyprus detect?

PGD in Cyprus can determine the sex of the tested embryo. In the same way, it can also detect many genetic disorders of an embryo. The following genetic disorders are among the many possible diagnoses that can be detected using PGD:

Adrenoleukodystrophy (ALD)
Alport’s syndrome
Amyotrophic Lateral Sclerosis (ALS)
Becker Muscular Dystrophy
Bruton’s Agammaglobulinemia
Centronuclear Myopathy
Cerebellar Ataxia
Coffin Lowry syndrome
Colour blindness
Complete and Partial androgen insensitivity syndrome (CAIS and PAIS)
Hirshsprung’s disease
Congenital Cystic Fibrosis
Congenital Hydrocephalus
Down syndrome
Duchenne-Muscular Dystrophy
Fabry’s disease
Factor 9 Deficiency
Factor 8 Deficiency
Fragile X Syndrome
Friedrich’s Ataxia
Gardener Syndrome
Glucose-6-phosphate dehydrogenase deficiency (G6PD)
Glycogen Storage Disease
Happle Syndrome
Haemophilia A and B
Hunter’s syndrome
Huntington’s Chorea
Hypohidrotic Ectodermal Dysplasia
Idiopathic Hypoparathyroidism
Diabetes Insipidus (DI)
Kennedy disease
XXY (Klinefelter’s Syndrome)
Lesch-Nyhan syndrome (LNS)
Lowe Syndrome
Marfan syndrome
Menkes disease
Nasodigitoacoustic syndrome
Nonsyndromic deafness and X-linked nonsyndromic deafness
Norrie disease
Occipital horn syndrome
Prostate Cancer
Retinitis Pigmentosa
Rett syndrome
Sickle Cell Anaemia
Siderius X-linked mental retardation syndrome
Simpson-Golabi-Behmel syndrome
Tay-Sachs Disease
Turner syndrome
von Willebrand Disease
Wiskott-Aldrich syndrome
Severe Combined Immunodeficiency (SCID)
Sideroblastic anaemia

Which embryos are chosen for transfer?

Any normal looking test embryo may be a candidate for transfer. Some embryo samples appearing to be normal upon genetic examination, may physically (morphologically) present abnormally however. In the same way, embryos that may morphologically appear normal can still be defective genetically. Because of these innate variations in embryo quality, the PGD in Cyprus criteria necessitates embryos to be both normal physically and genetically to qualify for uterine transfer. We are increasing the chance of a successful pregnancy if we follow this protocol in embryo selection.

The comprehensive results of PGD in Cyprus will be explained to you by the doctor, who will also make recommendations regarding number of embryos to be transferred.

What happens to the embryos that are not chosen?

Embryos that are not selected for uterine transfer are cryogenically stored for future use.

What is the actual process for PGD?

In order to perform PGD in Cyprus procedures on embryos, all patients will be required to have in vitro fertilisation (IVF) regardless of fertility status. The prospective mother will be hormonally stimulated to produce multiple eggs for collection and the father will provide a sperm sample. IVF will subsequently be carried out to produce embryos. After 3 days in the incubator, the embryos should have developed to the 8-cell stage. Routine cell biopsy testing on these cells shall be performed to determine whether they are clear of or affected by the genetic condition being tested for.

Can gender selection and multiple types of genetic testing be performed on the same cell sample?

The PGD in Cyprus process necessitates the destruction of the sampled cells because of the DNA sample extraction process that involves the dissolution of the cell membrane. For this very reason, other DNA procedures could no longer be performed with absolute accuracy and certainty.

What are the preparatory procedures for single gene PGD?

There is a huge variety of genetic diseases that can effectively be analysed using the PGD in Cyprus procedures. Embryone customizes their own DNA probes that are used during embryo testing. Each probe set are individually customized per couple at Embryone.

The Embryone doctor must initially gather blood samples from both parents for mutation verification testing, and the active priming of the polymorphic markers used in each assay. For confirmatory purposes, Embryone may require blood samples and cheek swabs from other blood relatives and siblings. The Embryone genetic professional will validate the diagnostic single gene PCR protocol after performing extensive pre-clinical trials on sample lymphocytes or cheek cell samples. This will aid in the evaluation of the single gene amplification efficiency, and the ADO rates of each primer that shall be utilized in the PGD in Cyprus procedure.

In most common single gene disorders, genetic professionals can perform the probe creation with validation within a period of two weeks. For genetic diseases with variable mutations, the preparation phase may take at least 4 to 6 weeks. Patient coordinators will update you on the timelines of the procedure as we go through the process to keep you well-informed with developments.

What happens during genetic analysis for single gene disorders?

As soon as the customized DNA probes are created, IVF is performed. The embryo(s) will then be biopsied and polymerase chain reaction (PCR)is used to carry out DNA amplification in vitro. PCR is used to replicate DNA to a significant quantity with multiple copies of the gene for analysis. PCR is very sensitive and specific at the same time, making it the most ideal tool for the PGD in Cyprus procedure. Gene amplification can make it possible for our geneticists to perform multiple gene screening procedures for diagnoses.

What is chromosomal translocation?

Chromosomal translocation means that a fragmented part of a chromosome adheres with another chromosome. Translocation between chromosomes that does not result in the loss of genetic material (chromosome fragment) is known as a balanced translocation. Balanced translocations may be phenotypically normal because it is only a defect in chromosomal rearrangement; thus, results in a normal foetus.

The definitive implication on the outcome of a chromosomal translocation is that the offspring may have extra or missing genetic material which results in congenital anomalies among infants. In the example below, the father has a balanced chromosomal translocation on two pairs of chromosomes (number 3 and 7) while the mother possesses a normal set of chromosomes. There will be potentially different outcomes that the offspring can inherit:

A. None of the chromosomes from the father that were involved in the balanced translocation resulting in a healthy baby.
B. Both paternal chromosomes that were involved in the balanced translocation resulting in a normal baby but who may pose as a carrier of the same balanced translocation similar to the paternal origin.
C. One paternal chromosome from the balanced translocation, and normal maternal chromosomes. This will result in an unbalanced translocation where the unmatched pair results in missing or excess genetic materials. This genotype may express physical or mental disabilities in the offspring. Large missing portions of genetic material in the part of the unbalanced translocation would most likely conclude in a miscarriage.

PGD for chromosomal translocations

Patients who undergo PGD in Cyprus for chromosomal translocations will require IVF. A genetic analysis will then be conducted on the sampled cells from the embryo before uterine transfer. Biopsy is performed on day 3 of embryo development at the 8-cell stage. The biopsied cells are exposed to the FISH method that matches the different chromosomal fragments using fluorescein analysis. The embryos will first be tested for unbalanced genetic translocations. A second test on determining defect in chromosomes X, Y, 13, 18, and 21 will also be done using the FISH procedure. Cells tested using FISH analysis can no longer be used for other genetic testing purposes as the sampled cells may become destroyed in the process.

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