Preimplantation Genetic Diagnosis Services (PGD)
Preimplantation Genetic Diagnosis (PGD) is a revolutionary technique in the realm of In Vitro Fertilization (IVF) that offers prospective parents valuable insights into the genetic health of embryos before implantation. Understanding what PGD entails, how it works, and its implications is crucial for those exploring assisted reproductive technologies.
Preimplantation Genetic Diagnosis (PGD) stands at the forefront of reproductive technology, seamlessly integrated into the In Vitro Fertilization (IVF) process. This groundbreaking procedure is meticulously designed to delve into the intricate genetic composition of embryos before their implantation, empowering prospective parents with crucial insights. By shedding light on potential genetic disorders, PGD equips individuals and couples with the knowledge needed to make informed decisions that profoundly impact the trajectory of their family’s future. This advanced genetic screening tool not only enhances the precision of assisted reproductive techniques but also represents a pivotal stride towards ensuring healthier pregnancies and minimizing the risk of hereditary conditions.
Preimplantation Genetic Diagnosis (PGD) emerges as a specialized genetic testing marvel within the realm of In Vitro Fertilization (IVF). This sophisticated procedure unfolds during the early stages of IVF and revolves around a meticulous examination of embryos to detect any underlying genetic abnormalities before the critical phase of implantation. By scrutinizing the genetic makeup of embryos, PGD provides a comprehensive understanding of their health, empowering prospective parents with the knowledge necessary for making informed decisions regarding their family planning journey. This technique serves as a powerful tool in the hands of fertility specialists, offering a proactive approach to ensuring the birth of healthy offspring.
The intricate workings of Preimplantation Genetic Diagnosis (PGD) involve a precise methodology that unfolds within the initial stages of In Vitro Fertilization (IVF). PGD operates by delicately extracting a single cell from the developing embryo, a process meticulously conducted to minimize any potential impact on the embryo’s overall health. This isolated cell undergoes a thorough genetic analysis, unveiling valuable information about the embryo’s genetic status. The primary objective of this procedure is twofold: to increase the likelihood of a successful pregnancy and to minimize the risk of genetic disorders by selectively choosing embryos with optimal genetic health. Through this sophisticated technique, PGD emerges as a beacon of hope for individuals and couples seeking to build their families with a heightened focus on genetic well-being.
PGD tests for various genetic conditions and chromosomal abnormalities, ensuring that only embryos free from specific genetic disorders are selected for implantation during IVF. This helps in preventing the transmission of hereditary diseases to future generations.
IVF with PGD has shown to significantly increase the success rates of pregnancy by selecting embryos with optimal genetic health. The precision of PGD contributes to higher implantation rates and lowers the chances of miscarriage.
PGD is an additional service that can be incorporated into the standard IVF procedure. While it provides crucial genetic information, it is not a mandatory component of IVF.
PGD is specifically designed to be integrated into the IVF process, as it requires the retrieval of embryos for genetic analysis. It is not a standalone procedure and is not performed independently of IVF.
While Preimplantation Genetic Diagnosis (PGD) within In Vitro Fertilization (IVF) is generally considered a safe and well-established procedure, it is essential to acknowledge the minimal risks associated with the broader IVF process. One potential risk involves the chance of infection, primarily associated with the embryo retrieval site. However, it is crucial to note that clinics adhere to stringent sterilization protocols to minimize this risk significantly. Additionally, some individuals may experience mild discomfort or swelling at the retrieval site, which is typically temporary and resolves without long-term consequences. Overall, the risks associated with PGD IVF are minimal, and the meticulous medical procedures employed during IVF contribute to maintaining a high standard of safety. In the vast majority of cases, the benefits of PGD, including informed embryo selection and reduced genetic risks, far outweigh these potential drawbacks.
The timeline for In Vitro Fertilization (IVF) with Preimplantation Genetic Diagnosis (PGD) is a dynamic process influenced by several factors. Typically spanning several weeks, the journey begins with ovarian stimulation, a phase aimed at maximizing egg production. Subsequent to this, the eggs are retrieved, marking a crucial step in the IVF process. The retrieved eggs undergo fertilization, leading to the development of embryos. At this juncture, the integration of PGD adds an additional layer of meticulous genetic testing to ensure optimal embryo selection. The overall duration of IVF with PGD is also contingent on individual circumstances, such as the response to ovarian stimulation and the specific requirements of each case. While the process demands time and patience, the comprehensive approach of IVF with PGD significantly enhances the chances of a successful pregnancy, offering hope and a tailored solution to individuals and couples embarking on their fertility journey.
The cost of IVF with PGD varies depending on geographical location, clinic reputation, and specific patient needs. It is essential to consult with fertility specialists to obtain accurate cost estimates and explore potential financial assistance options.
PGD allows for the selection of embryos based on gender, providing prospective parents with the option to choose the sex of their child. This aspect of PGD has both ethical and personal considerations.
PGD is a highly accurate technique, with success rates exceeding 90% in detecting genetic abnormalities. The precision of PGD enhances the likelihood of a healthy pregnancy and reduces the risk of passing on hereditary diseases.
PGD is designed to have minimal impact on embryos. The removal of a single cell for genetic analysis is carefully conducted to ensure the embryo’s overall health and development remain unaffected. Studies have shown that PGD does not cause significant harm to embryos.
The following are among the many possible diagnoses that could be detected by PGD:
Amyotrophic Lateral Sclerosis (ALS)
Becker Muscular Dystrophy
Coffin Lowry syndrome
Complete and Partial androgen insensitivity syndrome (CAIS and PAIS)
Congenital Cystic Fibrosis
Factor 9 Deficiency
Factor 8 Deficiency
Fragile X Syndrome
Glucose-6-phosphate dehydrogenase deficiency (G6PD)
Glycogen Storage Disease
Haemophilia A and B
Hypohidrotic Ectodermal Dysplasia
Diabetes Insipidus (DI)
XXY (Klinefelter’s Syndrome)
Lesch-Nyhan syndrome (LNS)
Nonsyndromic deafness and X-linked nonsyndromic deafness
Occipital horn syndrome
Sickle Cell Anaemia
Siderius X-linked mental retardation syndrome
von Willebrand Disease
Severe Combined Immunodeficiency (SCID)
In order to perform PGD at Cyprus IVF Centre, all clients must undergo in vitro fertilisation regardless of fertility status. The prospective mother or egg donor will be hormonally induced to produce excess follicles for IVF egg retrieval, which will then be joined with sperm from the father or sperm donor as per a regular IVF process to create embryos. After three days in the incubator, the embryos should eventually develop into its eight-cell stage (morula). Routine cell biopsy testing on these cells shall be performed to determine whether they are normal and healthy. A normal finding in the sampled cells will essentially infer that the source embryo is healthy and would ultimately give rise to healthy babies.
In short, no. The DNA sample extraction process affects the cell membrane to the point that any other DNA testing can’t be performed accurately.
PGD is done before the embryo’s genetic material becomes “active”. As the cells are identical at this stage, they each have the potential to become any part of the baby and therefore completely safe.
Embryos are created in the laboratory as per the usual IVF procedure, joining eggs and sperm. Then the fertilised embryos are incubated for three days. On the third day, a PGD biopsy is performed by removing one or two cells from the embryo as samples and the genetic materials from the nucleus of the cells are tested for the presence of any abnormalities. On the fifth day, the fertility specialist will thoroughly discuss the completed test results with you and guide you on the selection process of the embryo before uterine transfer.
PGD is done at the eight-cell stage of development. The embryologist at our fertility clinic selects a normal looking embryo and samples one or two cells for testing. The selected embryo is placed in a powerful microscope where a laser is beamed towards its outer membrane (zona pellucida) to create a tiny opening on the membrane. From the tiny opening, the cells will be aspirated for testing. The hole in the membrane closes automatically after the procedure, preventing additional cells from falling out.
The genetic material that needs to be tested is found in the nucleus, so if the sampled cells do not contain a nucleus or the nucleus breaks open, the testing will be inconclusive. This doesn’t mean that the embryo is genetically unhealthy, but it cannot be confirmed.
Sometimes, the sampled cells may contain two nuclei. This irregularity may mean a genetic abnormality in the embryo or could be normal in cases where the sampling was collected at the time of active cell division by less experienced embryologists.
PGD at Cyprus IVF Centre is quicker than other genetic testing methodologies as it should be done within 48 hours from sampling. To test the cells in PGD, our fertility clinic uses Fluorescence in-situ Hybridization (FISH) to facilitate its speedy analysis in time for a day-5 embryo transfer.
In the FISH technique, a small DNA probe is used with a powerful microscope to recognise unique chromosomal patterns which light up or fluoresce upon contact with the probe during observation. The DNA probe shines light in various colours allowing multiple chromosomes to be tested simultaneously.
For our PGD process at Cyprus IVF Centre, the fertility doctor and team use a 5-probe FISH method that screens the five most important chromosomes – X, Y, 13, 18, and 21. Irregularities in these chromosomes will usually result in the most common genetic abnormalities observed in humans. Normal cells will present with 2 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. This particular FISH method can fluoresce 5 chromosomes at a time and then can be washed and the next 5 chromosomes can be illuminated by the DNA probes. The repeated washing and testing will enable the 5-probe FISH method to test the rest of the DNA sequence. On the downside, the probe washing process can affect the integrity of the chromosomes tested and the accuracy of the test results as a whole. For this reason, only the five most important chromosomes are tested.
During PGD, any normal looking embryo has the potential to be transferred. However, some embryo samples that appear to be normal upon genetic examination may physically present abnormally and fragment spontaneously. In the same way, embryos that may appear physically normal can still be defective genetically. Because of these variations in embryo testing, the PGD criteria at Cyprus Fertility Centre requires embryos to be normal both physically and genetically for them to qualify for uterine transfer.
Our fertility doctor will fully explain the results to you and advise you on how many embryos to be transferred in order to promote successful embryo implantation – three to four being the optimal number of blastocysts for IVF success.
Ultimately, the choice will be yours after receiving our guidance.
Embryos not selected for uterine transfer are cryogenically stored for future use, up to 2 years.
Aneuploidy is having an abnormal number of chromosome sets within a cell nucleus causing birth defects and often miscarriage. At Cyprus IVF Centre, we routinely conduct aneuploidy screening in all embryos to be transferred as part of our IVF treatment, to significantly reduce the chance of birth defects during pregnancy. The most common abnormalities 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).
PGD methodology can be used to help prevent couples with serious inheritable diseases passing to their offspring.
Conventionally, the only way to diagnose genetic diseases from the foetus is by means of genetic analysis of aspirated amniotic fluid from amniocentesis. This diagnostic procedure is done at the latter stage of pregnancy. A positive and confirmatory genetic diagnosis from amniocentesis will require one of two choices: a) allowing the infant to fully develop and try to live with the inherited abnormality or b) terminating the pregnancy through optional abortion. Both scenarios are difficult and traumatic for parents especially during the later stages of pregnancy.
PGD can now be used as an alternative pre-natal diagnostic tool for expectant parents. The procedure empowers couples to make early choices before embryo implantation. Where an embryo is detected to carry a disorder trait, the other sets of embryos will still be examined carefully to find a normal or unaffected embryo to be transferred.
At the beginning of the PGD process, our fertility specialist will gather blood samples from both parents for mutation verification testing and our IVF centre may require blood samples and cheek swabs from other blood relatives. The genetic professor of Team Miracle will validate the diagnostic single cell PCR protocol after performing extensive pre-clinical trials on sample lymphocytes (white blood cells in the immune system) or cheek cell samples.
Our IVF clinic’s Team Miracle customises their own DNA probes that are used during testing, specifically for each couple. Because of this expertise, the Cyprus IVF Centre is internationally acclaimed for our ability to detect the rarest of genetic disorders known to man.
As soon as the customized DNA probes are created, the doctor simultaneously performs the IVF process. The embryo will then be biopsied using the polymerase chain reaction (PCR) to reproduce the process of DNA replication in vitro. The PCR is very sensitive and specific, making it the most ideal tool for PGD. Gene amplification can make it possible for our geneticists to perform multiple gene screening procedures for diagnoses.
In most common single gene disorders, genetic professors can perform probe creation with validation within a period of two weeks. For genetic diseases with variable mutations, the preparation phase may last for at least 4 to 6 weeks. Patient coordinators will update you on the timelines of the procedure as we go through the whole process to keep you abreast with the developments.
All cells in the body are controlled by long thin strands of Deoxyribonucleic acid (DNA) which are found in the nucleus of the cell. The DNA exerts its control by delivering at least 30,000 genetic instructions needed for the growth and development of each cell of the body. Normal DNA contains 46 strands called chromosomes arranged in 23 pairs. By convention the chromosomes are numbered 1 to 22 according to their size, with chromosome 1 being the longest and the 22nd being the shortest. The 23rd pair is referred to as the sex chromosomes that determines our gender. Each chromosome contains a short and a long arm which is separated by a narrow area in the centre. It will only take a small amount of blood or cheek cells for one to study a person’s chromosomes under microscopy.
During spermatogenesis (sperm formation) and oogenesis (egg formation), one of the pairs of DNA strands goes to each sperm or egg. Consequently, eggs and sperm will only contain 23 chromosomes each. All egg cells contain an X sex chromosome while sperm may carry either an X or a Y sex chromosome. During their union in fertilisation, the resulting embryo should contain 46 chromosomes with half of the chromosomes from the egg and the other half from the sperm. For normal foetal development, the correct number of chromosomes must be present.
Chromosomal translocation means that a fragmented part of a chromosome pairs with another chromosome. If this pairing does not result in a loss of genetic material, then it is a balanced translocation and because its only defect is in rearrangement, it results in a foetus. If there is a loss of genetic material, the result is usually a miscarriage. The effect of a balanced translocation is that the offspring may have congenital abnormalities. This occurs in 1 out of 625 births and cannot be repaired.
In the given example, 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. These are the different possibilities that could occur:
The offspring can inherit:
Couples who decide to have PGD at Cyprus Fertility Centre will undergo a standard IVF procedure. A genetic analysis will then be done on the sampled cells from the embryo before uterine transfer. A biopsy is performed on the third day of development where the embryo has reached the eight-cell stage. The biopsied cells are exposed to the FISH procedures that match the different fragments of the DNA for fluorescein analysis. In cases of IVF and PGD translocation, 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 modality. Tested cells for FISH methods can no longer be used for other purposes for sampled cells may be destroyed in the process.