Genetic screenings are the most up-to-date and advanced techniques used to test for genetic disorders via direct examination of DNA. Pre-implantation genetic diagnosis (PGD) is primarily used to detect irregularities in the number or structure of embryo chromosomes. PGD is used in In Vitro Fertilisation (IVF).
When an embryo has abnormal chromosomes, it can prevent implantation to the uterine lining, or result in a miscarriage or the birth of a child with physical and/or mental disabilities.
PGD can assist in preventing these outcomes by identifying the affected embryos during their development in the laboratory, before they are transferred back to the patient’s uterus during an IVF cycle.
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If an error occurs and the egg or sperm has an extra or a missing chromosome, the embryo created by that egg or sperm will have an extra or a missing chromosome, resulting in a condition known as aneuploidy.
Ordinary human cells (embryonic cells) contain 46 chromosomes in 23 pairs. We obtain 23 chromosomes from each parent. The initial 22 pairs of chromosomes are the same for men and women. The 23rd pair determines the gender of a child. A female has two “X” chromosomes, whereas a male has an “X” and a “Y”.
This means a woman can only pass an X to her child in her egg. The man passes either the X or the Y in the sperm, therefore determining the gender of the child. If something goes wrong and the egg or sperm contains an additional or a missing chromosome, the embryo created by that egg or sperm will have either an extra or a missing chromosome, leading to a condition known as aneuploidy. Having an extra chromosome is referred to as trisomy (tri = three of a given chromosome) and having a chromosome missing is known as monosomy (mono = one of the chromosomes).
In the case that aneuploidy involves any of the larger chromosomes, the embryo may not attach to the lining of the uterus, or may cease development soon after attachment, leading to miscarriage. If the aneuploidy applies to chromosomes such as 13, 18, 21, X or Y, the pregnancy may continue until birth, in spite of the chromosomal disorder. The most common of these is an extra number 21, known as Down syndrome or trisomy 21 (three 21 chromosomes). Other common aneuploidies are Klinefelter syndrome (XXY), trisomy 13 and trisomy 18.
The results of a chromosome condition are dependent on which chromosome is additional or missing, and can include both physical variances and mental impairment.
The possibility of aneuploidy in a pregnancy increases with a woman’s age. Females carry all their eggs as a fetus, and are therefore born with all the eggs they will have in their lifetime. A woman’s eggs will age at the same rate as she does. In males, however, the sperm is not as old as the man, as it is made every 65-75 days.
It is believed that the risk of aneuploidy increases based on advanced maternal age, as over time, the chromosomes in the egg are less likely to divide correctly, causing the egg to have an extra or a missing chromosome.
PGD for aneuploidy distinguishes the chromosomally abnormal embryos so only chromosomally normal embryos are selected and transferred to the uterus in order to achieve more pregnancies, reduce the number of miscarriages and reduce the number of affected babies.
There are two options available for PGD of embryos: polar body biopsy and embryo or blastomere biopsy. The PGD team of doctors, geneticists and embryologists will determine which procedure is best based on the individual circumstances of each case.
Two small cells, known as the polar bodies, are produced by the maturing egg. These cells degenerate after the egg is fertilised.
The chromosomal content of these cells enables us to deduce the chromosomal content of the egg. To test the polar body, an incision is made in the shell (zona pellucida) of the egg. The polar body is cautiously removed and examined while the egg remains in culture in an incubator.
Examination of polar bodies offers information only from the mother. Chromosome abnormalities that may occur after fertilisation will not be detected through polar body biopsies.
To assess an embryo, some blastomeres or embryonic cells are removed through a microscopic incision made in the outer shell of the embryo during its fifth day of development (blastocyst stage). The embryo is kept frozen in storage while the cells are examined by PGD.
Two methods are offered to analyse the biopsied cells: Advanced Embryo Selection (AES) using array Comparative Genomic Hybridisation (CGH), and Fluorescence In Situ Hybridisation (FISH).
Comparative Genomic Hybridisation (CGH) testing consists of all chromosomes, including X and Y, being examined and compared with a sample of normal DNA. A computerised scanner reads the outcomes of the slides, which are then confirmed by a scientist.
CGH delivers more accurate information than standard genetic testing has offered in the past. The CGH test can distinguish chromosomal genetic disorders such as Down and Edwards syndromes.
To find out more about genetic screening using array CGH, please read our Advanced Embryo Selection using array CGH Fact Sheet.
The Fluorescence In Situ Hybridisation technique (FISH) uses probes identified by different fluorescent dyes. These fluorescent probes are applied to the biopsied cells where they adhere to the chromosomes. The number of chromosomes of each type (of colour) can then be counted. The geneticist can then differentiate between the normal cells and those with aneuploidy. FISH is able to test only a limited number of chromosomes.
At City Fertility Centre, we recommend the use of CGH testing over FISH as all 23 pairs of chromosomes, including those relating to gender, can be tested, delivering more thorough and complete results.
Advanced embryo selection is used by individuals and couples of varying ages for a range of reasons. It is recommended for patients who experience:
This cutting-edge technology allows us to assist individuals and couples to increase implantation rates and reduce the chance of miscarriage or chromosomal genetic disorders in their child.
Studies show that the chance of a woman delivering a baby with aneuploidy is on average 1% if she is aged 35-39 and 3.5% if she is between 40 and 45. PGD reduces the chance of having an affected baby, however, no genetic testing of the embryo is 100% accurate.
We recommend that prenatal testing, through chorionic villous sampling (CVS) or amniocentesis, be completed in the resultant pregnancy to confirm our diagnosis from PGD and to rule out disorders for which we do not test.
Approximately 35% of pregnancies in women 35 years of age and older are miscarried. Aneuploidy is the cause of at least 50% of these losses. By transferring only chromosomally normal embryos, the number of pregnancies going to term should increase.
Recent studies show a significant reduction in pregnancy losses after PGD, from 23% to 9%. The increase in the implantation rate and the substantial decrease in pregnancy losses resulted in a noticeable rise in ongoing pregnancies and babies delivered.
Pregnancy rates after IVF decline with maternal age. Aneuploid embryos have far lesser survival rates than normal embryos, and half of them (those missing a chromosome) rarely implant.
It appears that the decline in pregnancy rates with maternal age is generally the result of an increase in the number of aneuploid embryos in older women. Pregnancy rates can be increased by performing PGD for aneuploidy and transferring only chromosomally normal embryos.
PGD also reduces the number of IVF cycles necessary to achieve a successful outcome and reduces the risk of multiple-pregnancy by transferring just one single normal embryo.
The risk of damaging an embryo during biopsy is less than 1%, but in the case that an embryo is damaged during the biopsy, it may not be fit for transfer into the uterus.
Some biopsied cells may fail to produce a test result, due to:
The total potential risk is less than 2% per cycle. Embryos without a result from AES may still be transferred but the benefits of AES will not apply and prenatal testing through CVS or amniocentesis is advised.
The risk of a clinical misdiagnosis leading to a fetus or baby with chromosomal abnormalities after AES is less than 2%. Due to the low risk of misdiagnosis, we strongly recommend prenatal testing by CVS or amniocentesis.
A different option to PGD is to undergo an IVF cycle without genetic testing of the embryos. During the resulting pregnancy, standard prenatal testing for abnormalities (CVS, amniocentesis and ultrasound examination) may be carried out, identifying certain abnormalities in the fetus.
It is important to understand all aspects of PGD before making the decision to undergo the procedure. The risks, benefits and alternatives of this testing should be discussed thoroughly with your genetic counsellor, treating specialist and/or the scientist performing the procedures.
To find out more about PGD, please read our Pre-Implantation Genetic Diagnosis (PGD) Fact Sheet and Advanced Embryo Selection Using Array CGH Fact Sheet.