Can Preimplantation Genetic Testing really improve the chance of getting pregnant

By Dr.Pornwaratt Niyomrattanakit, Ph.D. Genetics Laboratory Manager

What is Preimplantation Genetic Testing?

 in fertility treatment process that fertilization happens outside the body (In Vitro Fertilization or IVF),when an egg and a sperm cell fuse together, a complete fertilization occurs and the embryo cultured under suitable conditions grow well, before transferring the embryo back into the mother’s uterus, there is an important.

process called Preimplantation Genetic Testing. Embryo genetic testing aims to improve the chance of getting pregnant with a healthy baby. There are two types of preimplantation genetic testing: Preimplantation Genetic Diagnosis (PGD) and Preimplantation Genetic Screening (PGS).

PGD is a test to diagnose abnormalities of genes in order to identify one or more particular diseases (PGD for single gene disorders) and avoid inherited diseases in the event that a father or a mother knows that he or she or a family member is a carrier. These diseases include thalassemia (40% of Thais are carriers), a respiratory disease called cystic fibrosis, Duchenne Muscular Dystrophy, etc. Sometimes PGD is not related to identifying gene defects but aims to find a suitable genetic form for the benefits from the genetic disease treatment plan of the family members. By doing stem cell transplantation such as PGD for HLA typing in the case when the father and the mother are thalassemia carriers and have the first child with thalassemia, PGD for HLA typing enables selection to have a child born free of the disease. It has the benefit of transplanting the younger sibling’s bone marrow for the older one as it helps select children with matching white blood tissue types.

PGS is a test to determine whether the embryo’s cells have normal number of chromosomes or not (Aneuploidy Screening or Chromosomal
Aberation). PGS does not check deeply at the level of genes so it is a screening test to look for embryos with a normal number of chromosomes and it can determine the gender of an embryo. The benefit of this test is that it can be used to avoid occurrence of genetic diseases with X-linked recessive inheritance such as glucose–6-phosphate dehydrogenese deficiency, Hunter’s Syndrome, Ocular Albinism, Hemophilia A, B and Anhidrotic Ectodermal Dysplasia. However, PGD and PGS cannot detect other abnormalities that may arise during prenatal development.

In both types of Preimplantation Genetic Testing, we need to remove embryo’s cell(s) out for genetic testing process. At present removing embryo’s cell(s) (embryo biopsy) can be done in two stages: 1) When the embryo reaches day 3 (the embryo is in the cleavage stage and it normally has 8 cells known as blastomeres). 2) When the embryo reaches day 5 (the embryo is in the blastocyst stage and we remove some cells from the trophectoderm layer of the blastocyst embryo for the test) and trophectoderm.

A number of studies say that removing one cell while an embryo is in the cleavage stage (an embryo aged 3 days) via a proper method such as using laser to make a hole through the embryo cell wall to pull a cell out will not affect the embryo development and babies born through PGD cell testing during this stage will be as healthy as normal babies. We do not find that collection of a small number of cells from the trophectoderm component for the test will harm the developing fetus. These cells will grow to be placenta so it will not have an impact on the embryo who grows from the cell component called inner cell mass (ICM). Embryos tested with no defects found will then be selected to transfer into the mother’s uterus.

History of PGD - PGS

In vitro fertilization was first successfully used in 1978. Not many years after that, scientists began to wonder how we can be sure whether an embryo will develop to be a healthy baby. Therefore, it was the beginning of effort to develop genetic testing method of an embryo by removing one or more cells out to evaluate its genetic materials. It was not until 1990 that the first birth of pregnancy after implantation of an embryo that had been through genetic testing came out. After that fertility treatment technologies have improved dramatically. Over the past twenty years we have learned a lot about PGD/PGS but much still remains to be learned for further discovery and broader application.

Who might benefit from PGD/PGS?

In general, there are 5 groups of patients undergoing fertility treatment that are recommended to do PGS or PGD:

• Patients having treatment when the female age is over 35 (Advanced
   Maternal Age: AMA).
• Patients that have had IVF failure.
• Patients knowing that themselves or any of their family members has any genetic disease.
• Patients that have chromosomal translocations.
• Patients that have had recurrent miscarriages.

Risk of Aneuploidy and maternal age

The main factor that indicates the need for PGS of an embryo (to check the number of chromosome) is advanced maternal age of over 35. The reasons embryos of older mothers should get PGS are that women of advancing age have less efficient cell proliferation and increased rates of eggs with an abnormal number of chromosomes. If fertilization occurs, the embryo will also have an abnormal number of chromosomes.

Women’s eggs with an abnormal number of chromosomes are often found. As women get older, the chance of producing eggs with an abnormal number of chromosomes increases. In general, about 30-60 % of human embryos have an abnormal number of chromosomes

If we choose not to do a chromosomal test of an embryo, What is the risk of having a baby with abnormal chromosomes?

According to the above reported information, we can see that the rates of having abnormal embryos become higher as mothers get older which is the result of abnormalities from egg proliferation process. In humans, we have natural mechanism to prevent implantation of embryos with abnormal numbers of chromosomes. Normally, an embryo with severe abnormalities such as having a whole chromosome extra or missing or both extra and missing will not be able to develop and reach the implantation stage. And even if this embryo can grow until it implants itself into the uterus wall, it is likely to stop growing later and will finally end up in a miscarriage. Some types of chromosomal abnormalities are not harmful to the fetus survival in the womb. The baby will grow until it is born but will have abnormalities that can be seen clearly. Examples are: Down syndrome, caused by an extra copy of Chromosome 21; Patau syndrome, a condition with an extra copy of chromosome 13; or Edward syndrome, due to an extra copy of chromosome 18.

Currently, in the process of helping couples with fertility problems to have a baby via A.R.T. Assisted Reproductive Technology. Preimplantation Genetic Testing is an important step that should not be overlooked especially when patients undergoing treatment fall into the above mentioned 5 high risk groups.

Can PGD really help improve the chance of becoming pregnant?

Many research studies show that Preimplantation Genetic Testing results in lower miscarriage rates, higher pregnancy rates and better live birth rates. However, there are many techniques used in evaluating the number of chromosomes and they have different levels of resolution and different pregnancy rates. For example, by testing chromosomes via Fluorescence In Situ Hybridization (5 C), we can evaluate 5 chromosomes including chromosomes 13, 18, 21, X, and Y. Therefore, this method is used to check chromosomes with more chances of being abnormal and it can tell the gender of an embryo. It cannot tell us about the remaining 19 pairs of chromosomes while PGS that uses more advanced technology (24-Chromosome Aneuploidy Screening) can check all 24 chromosomes. It has been reported that 24-Chromosome PGS has higher pregnancy rates. Today there are 5 methods of chromosome testing that can check all 24 chromosomes as follows. 

       • Karyolite BoBs (BACs on Beads)
       • Array Comparative Genomic Hybridization (aCGH)
       • Single Nucleotide Polymorphism microarrays
       • Quantitaive real time polymerase chain
         reaction(qPCR)
       • Next Generation Sequencing for 24 chromosome    
         aneuploidy screening.

Studies to identify abnormalities of an embryo using aCGH and SNP array methods found that chromosomes most frequently found abnormal are chromosomes 16, 21, 22, 1, 2, and 4 respectively. This means that 24-chromosome testing will help screen out abnormal embryos better.

Sources: jetanin.com
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