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Pre Implantation Genetic Diagnosis Pgd

Overview of Pre-Implantation Genetic Screening

Pre-Implantation Genetic Testing is a new generation alternative to prenatal genetic testing methods such as chorionic villus sampling (CVS) and amniocentesis for couples who are known to have a high risk of transmitting a genetic disorder to their offspring. While prenatal genetic testing methods can be employed only at a certain time during pregnancy, PGD/PGS offers genetic testing on embryos prior to pregnancy, therefore, eliminates the likelihood of being pregnant with an offspring with genetic problems. The origins of PGD/PGS dates back to 1968 when Edwards and Gardner performed the very first micro-surgical embryo biopsy on rabbit embryos by staining rabbit blastocyst sex chromatin with euchrysine 2GNX. However, it was not until the early 1990s where the first PGD/PGS case was performed to screen sex of the embryo for a sex-linked autosomal recessive disorder.

PGD can be applied to over 170 conditions that can be classified as x-linked disorders, single gene defects and chromosomal abnormalities and can be used for genetic testing in the case of common disorders with genetic predispositions and non-genetic cases such as HLA typing. One of the major advantages of having PGD as an option is that; it eliminates the risk of being pregnant with a genetically abnormal child and minimizes the necessity of a prenatal diagnosis which may force the couple to opt for selective abortion, which is an emotionally burdening experience. However, on the negative side, use of PGD/PGS required that the couple undergoes IVF treatment, which is an invasive and expensive procedure. However, overall benefits may outweigh the financial burden.

Pre-implantation genetic testing technology improves the likelihood of a successful pregnancy and birth for three distinctly different groups of patients. The first group consists of couples with infertility related to recurrent miscarriage or unsuccessful IVF cycles. This group of patients usually belong in the “unexplained infertility” group and they may be recommended to seek “Pre-Implantation Genetic Screening” (PGS) in order to screen their embryos for chromosomal aneuploidies.  The second group of couples include those who are in more advanced age brackets and carry the risk of having genetically abnormal children due to aging of the oocytes or sperm. These patients are also recommended to use PGS as a means of increasing their chances of successful pregnancy and as a means of minimizing the rish of having a disordered child. The third group of patients are the ones who are at risk for passing on a known inherited genetic disease to their offspring. Either one of the parents may possess the disease or both parents can carry the allele for the disease. In such cases, detection of the precise gene mutation and testing the embryos using “Pre-Implantation Genetic Diagnosis” (PGD) will be the right path to follow.

There are two distinct names for this technology. PGD (Pre-implantation Genetic Diagnosis) refers to embryo selection as a response to a known genetic disorder running in the family, therefore, it is applied purely for genetic disease prevention purposes. PGS (Pre-implantation Genetic Screening), on the other hand, refers to applying the exact same method of embryo selection even though there is no known genetic disorder in the male or the female partner. PGS is the terms used when this technology is used for selecting embryos in order to increase chances of success with pregnancy in couples with unexplained infertility problems, or selecting the gender of the offspring.

Pre-Implantation Genetic Screening (PGS) for Major Genetic Disorders:

This is the treatment option chosen by patients due to being in older age brackets or for selecting the sex of their baby. As age increases, so does the likelihood of having a child with chromosomal abnormalities. Therefore, PGS is an effective tool which can help us identify the genetically defected embryos and only transfer the genetically healthy ones into the uterus to generate a pregnancy. PGS genetic screening is performed as a part of an In Vitro Fertilization cycle where multiple eggs are produced, retrieved from the ovaries and fertilized with the husband’s sperm in the Embryology Laboratory. IVF is necessary to give us access to the embryo in vitro. At their earliest stage of development, one or two cells are removed from each embryo through a procedure called embryo biopsy. These cells are analyzed in the PGD Laboratory to determine which embryos are free of genetic abnormalities. This sophisticated and technologically advanced testing identifies which embryos are free of abnormalities and more able to achieve the patient’s goal of a healthy baby. PGS can screen for genetic disorders in chromosomes X, Y, 13, 18 and 21, which make up for about 85% of all major genetic conditions such as Down’s syndrome. Also, more advanced testing systems now allow us to screen your embryos for all 24 chromosomes. (Each person has 22 set of non-sex chromosomes from each parent and 2 sex-chromosomes). This system allows us to screen all of the embryos for all chromosomal aneuploidies. The cost of this option is slightly higher. Depending on the patient’s condition, age and the specific reason why PGS is required, we will be able to recommend which type of testing would be more appropriate in your case.

PGS genetic testing is also an option when families would like to select the gender of their baby for family balancing purposes. The embryo biopsy will not only allow us to select embryos that are free of genetic abnormalities, but will also allow us to determine the sex of the embryos. Once PGS is performed, the chance of having a baby of desired sex is very close to 100% once pregnancy is achieved. This process is also known as gender selection (sex selection) IVF.

Pre-Implantation Genetic Diagnosis (PGD) for Known Gene Mutations:

PGD testing is also an option when patients require screening for a specific genetic disorder. When the gene that carries the genetic disorder is identified, single gene analysis can be performed in order to screen for the specific disorder. This method can be used for X-linked diseases such as haemophilia and Duchenne’s Muscular Dystrophy and many other single gene disorders such as sickle cell anemia, cystic fibrosis, and many other single gene disorders that have a known cause. If there is no proper diagnosis of the gene mutation and the specific gene that is causing the specific genetic problem has not been precisely detected, then we will need an additional testing period until we can detect the gene responsible for the genetic mutation and then we can proceed with the rest accordingly. X-linked diseases are often caused due to a gene mutation on the X-chromosome. The reason is, X and Y chromosomes are not the same size and they do not contain a similar number of genes. If a gene on the X chromosome is defected and does not have an equivalent on the Y chromosome, then the child is likely to acquire the mutation. More information on the differences between X and Y chromosomes can be found in the “Scholarly Perspective” section below.

Once the gene mutation has been identified, a special PGD probe can be built which will help us screen all of your embryos and make sure that we select the ones that do not carry this mutation. If there is a known mutation running in the family, then obtaining paternal and maternal blood samples will allow us to run necessary testing which will allow us to design a specific probe to detect the specific gene mutation. With the special PGD probe, we will be able to genetically analyze all of your embryos to detect the mutation. Those embryos that have been detected with the mutation will be discarded and those that are healthy will be transferred into the uterus to generate pregnancy.

PGS or PGD will necessitate the use if standard IVF/ICSI procedures that are used for infertile couples. The reason is, even though you may not have an infertility issue, IVF/ICSI treatment is the only way we can culture your embryos outside of the womb, therefore, IVF/ICSI is a necessary step before we can carry out the genetic testing on your embryos.

Methods used in Pre-Implantation Genetics

Next generation sequencing method in Cyprus for PGD

A number of methods have been developed for pre-implantatin genetics. It all started with FISH in 1990s where pre-implantation genetic screening became available commercially instead of more invasive pre-natal diagnosis. With developing technology in assisted reproduction, more advanced methods have become available. Now, next generation sequencing is the latest and most advanced method of genetically healthy embryo selection. North Cyprus IVF Center is the ONLY clinic in Cyprus to offer next generation sequencing as a PGS/PGD technology in house. With this new technology, we do not only offer you a more sophisticated means of genetically healthy embryo selection, but we also offer an unparallelled service which can also eliminate the likelihood of many cancers in your unborn child! Below we provide more detailed account of each pre-implantation genetic testing method.


    • FISH: Is an abbreviation for Fluorescent in situ hybridization. This method is the simplest embryo screening technique used to check for the chromosomal content of embryos created in an IVF cycle. FISH method can be utilized at different stages of embryo development including polar body biopsies, blastomeres and trophectoderm biopsies. However,  the most common FISH biopsy is done on the blastomeres of a cleavage stage embryo (Day 3 embryos of 8 cells). With FISH technique, the blastomeres are fixated on a glass slide and are hybridised using DNA probes. There are different probes for a different set of chromosomes. The most commony used FISH probe is the 5-chromosome probe which screens chromosomes X, Y, 13, 18 and 21. These are the main chromosomes which contribute to majority of chromosomal abnormalities observed at birth. FISH is used for major chromosomal disorders and sex selection. However, it fails to screen embryos at the more sophisticated genetic level. FISH also fails to report any chromosomal translocations or deletion. Therefore, it is now used only as a screening technology when there is no known genetic disease. We still employ FISH as an embryo screening technology for older patients and patients seeking gender selection for family balancing purposes as it provides an accurate, yet cheaper technology.
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Array CGH: This method is called Array Comparative Genome Hybridization (CGH), which is an advanced version of FISH. This method is able to analyze the whole chromosome content of a biopsied cell rather than a pre-determined set of embryos. The array CGH has many available probes for each of the 24 chromosomes found in humans. These multiple probes enable the array CGH method to screen multiple locations on each and every chromosome at the same time. Furthermore, in addition to standard chromosomal analysis, the array CGH technique can also test for chromosomal translocations and other abnormalities.

  • Next-Generation Sequencing: North Cyprus IVF Center is the only owner of Next Generation DNA Sequencing technologies in entire Cyprus. This technology is not available in most clinics around the world, and we are proud of being in the top 10% IVF clinics offering this sophisticated technology to our patients. Next-generation sequencing (NGS) is currently the latest and most advanced technology in embryo screening. NGS goes one step further than array CGH and is able to identify mosaicism in the developing embryo. Mosaic embryos contain cells with different genetic compositions (some cells being euploid and some being aneuploid), making them more susceptible to genetic disorders. For example, one cell in the embryo may have an extra copy of a chromosome, whereas the rest of the cells are normal. Although the transfer of mosaic embryos may result in the birth of a normal child, it can also result in implantation failure, miscarriage, or a child born with genetic abnormalities. The ability to screen for mosaicism can reduce the incidence of genetic dis- orders and improve the success rate of IVF. The most important clinical application of NGS is whole genome sequencing (WGS), which provides a comprehensive survey of a person’s (or an embryo’s) genome. WGS can also be used to evaluate a cancer genome to identify specific mutations and variations within tumors. Sequencing the whole genome yields an extensive amount of genetic information about an individual, some of which can be acted upon. Thus, WGS could be used to identify a genetic predisposition for certain diseases in the future, and patients who are aware of such a predisposition can be monitored more closely.
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With its advanced technology, NGS also allows clinicians to screen for many diseases with a known genetic origin, including breast cancer, ovarian cancer, and prostate cancer. For example, in women with a family history of breast cancer, the fetus could be screened for the BRCA1 and BRCA2 gene mutations, both of which are associated with an increased risk of developing breast cancer. Embryos that are free of these mutations could then be selected for transfer. Women can also have their own DNA tested to determine if they have a genetic predisposition for certain diseases. Thus, NGS can be an invaluable resource for patients with a significant family history of inheritable diseases- not only limited to cancers. NGS screening can be performed for any known gene mutation which results in a known disorder.

Both array CGH and Next Generation Sequencing technologies successfully screen embryos for chromosomal abnormalities, chromosomal translocations and deletions. However, what makes NGS different from array CGH is the fact that NGS is capable of detecting mosaicism in embryos. Mosacism is observed when embryos’ cells have different genotypes. Next generation DNA sequencing can successfully determine if an embryo has mosaicism and detects which chromosome is affected by this condition. It has been shown via research and clinical studies that pre-implantation genetics can:

  • – Increase embryo implantation rates via the selection of viable embryos only
  • – Reduce spontaneous abortion rates by minimizing the risk of a genetical abnormality
  • – Increase ongoing pregnancy rates
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Next generation sequencing provides a comprehensive overview of different DNA variations, genetic recombination and other mutations that cannot be obtained via any other method of screening. The most important application of NGS in a clinical setting is resequencing of genomic DNA. This is known as whole genome sequencing (WGS) which provides a comprehensive genetic survey of a person’s (or an embryo’s) genome as well as cancer genome where detailed information about mutations and variations can be obtained. Sequencing the whole genome provides extensive amount of genetic information about an individual, some of which can be actionable. If a mutation is detected, this can mean possibility of a future disease, which can mean taking appropriate action or increasing the frequency of check-ups and monitoring for an early detection.

NGS with its advanced technology also allows us to screen embryos for many diseases of known genetic origin, such as breast cancer, ovarian cancer, prostate cancer to name a few. Women with breast cancer in their family can especially utilize this technology to screen for BRCA1 and BRCA2 gene mutations and select the mutation-free embryos for transfer, making sure pregnancy can be generated with an embryo that is free of such gene mutations. This is an invaluable resource for patients who have a history of breast/ovarian cancer in their family.

Next generation sequencing does not only allow us to offer pre-implantation genetic screening for breast cancer and many other genetically related diseases, but also lets us offer the same screening to adults through their blood sample and let them know if they have such mutations. Patients with these mutations can know that they have the likelihood of having such diseases and take necessary precautions.

Contact us for more information!