GENETIC SCREENING (PGD/PGS)
PRE-IMPLANTATION GENETIC TESTING (PGD/PGS)
TFC offers genetic testing of embryos for the screening of chromosomal abnormalities and diagnosis of specific genetic conditions. This testing is known as Pre-implantation Genetic Testing because it occurs prior to the transfer of an embryo.
There are 2 types of testing:
PGS (Pre-implantation Genetic Screening) screens for an abnormality in the number or arrangement of chromosomes, such as Down syndrome.
PGD (Pre-implantation Genetic Diagnosis) identifies a specific genetic condition such a Cystic Fibrosis or Sickle Cell Anemia.
With PGS and PGD, In Vitro Fertilization (IVF) is needed to create the embryos which undergo biopsy when the embryos are 5-6 days old. The embryos are then cryopreserved (or frozen). The removed cells are sent to a reference laboratory for analysis and the genetic testing results are available within 7-10 days after the biopsy. A frozen embryo transfer (FET) cycle is then scheduled where an embryo is transferred into the intended mother’s uterus, where it can grow and result in the birth of a healthy child.
Using PGS and PGD to screen the embryos significantly reduces the chances of having a child with a chromosomal abnormality or affected with a specific genetic condition.
PGS IS INDICATED FOR THE SCREENING OF CHROMOSOMAL ABNORMALITIES ASSOCIATED WITH:
Advanced Maternal Age
Recurrent Pregnancy Loss
Chromosomal Structural Abnormalities
Multiple Failed IVF cycles
1. ADVANCED MATERNAL AGE
A woman is born with all the eggs (oocytes) she is going to use during her reproductive lifespan. At birth she has 1-2 million eggs, by puberty about 300-400 thousand, and by menopause the eggs are mostly gone. Egg quality decreases as a woman gets older, and lower quality eggs-after fertilization-are more likely to become abnormal embryos. As a result, with advancing maternal age there are lower implantation rates, lower pregnancy rates and more miscarriages. These abnormal embryos have too many or too few chromosomes (aneuploidy). The most commonly known example is Down Syndrome (Trisomy 21), which is caused by an extra copy of chromosome 21. The risk of aneuploidy rises rapidly after age 35 for women.
The goal of PGS for advanced maternal age is:
To increase a couple’s chance for pregnancy
Reduce the risk for miscarriage
Improve the overall chance of having a healthy baby after in vitro fertilization
2. RECURRENT PREGNANCY LOSS
The American Society for Reproductive Medicine (ASRM) defines Recurrent Pregnancy Loss (RPL) as "a disease distinct from infertility, defined by 2 or more failed pregnancies.”
Causes of Recurrent Pregnancy Loss are:
Genetic: Chromosomal structural abnormalities such as abnormal karyotype
Abnormalities of the uterus
Coagulation disorders such as Thrombophilias
Autoimmune causes such as Antiphospholipid Antibody Syndrome
Endocrine and metabolic disorders, such as Diabetes
Unexplained or Idiopathic
The RPL evaluation is designed to find an explanation by ruling out the possible causes listed above. Once a cause is found, a treatment addressing the abnormality follows. Treatment may be a medical therapy when there is an autoimmune, coagulation, endocrine or metabolic cause, or a surgical procedure to correct a uterine abnormality or malformation.
Couples with structural abnormalities of their chromosomes have more miscarriages because they make embryos that have an abnormal number of chromosomes (too many or too few). Treatment options include using donor gametes (eggs or sperm) to replace the gametes from the affected parent or using PGS with IVF and then selecting an embryo with the correct number of chromosomes to transfer.
Couples with idiopathic or unexplained RPL have no explanation for their miscarriages after completing a standard RPL evaluation. This group has a tendency to have more chromosomally abnormal embryos than other couples. As a result, RPL patients benefit from PGS because a chromosomally normal embryo can be selected for transfer with a resultant increase in the implantation rate, reduction in the miscarriage rate, and an increase in the live-birth rate.
3. CHROMOSOMAL STRUCTURAL ABNORMALITIES
An abnormal structural arrangement of the chromosomes can often result in an increased incidence of miscarriages. Occasionally the abnormal structural arrangement is known from family history, or may be discovered during the evaluation for recurrent pregnancy loss after several miscarriages have occurred. While there are different types of chromosomal structural abnormalities, in general, a segment of a chromosome has moved into a different position on the same or on a different chromosome. Examples include balanced translocations, reciprocal translocations, and inversions. Children of individuals with these abnormalities can be normal (no structural abnormalities of the chromosomes), an unaffected carrier (has the parent’s abnormality but otherwise is normal) or affected (unbalanced and missing a part of a chromosome or having excess chromosome material). Regardless of which abnormal structural arrangement an individual has, PGS can be used to test the embryos for the presence of the specific abnormality present in the carrier parent. Identifying and transferring unaffected embryos greatly decreases the risk for miscarriage from a chromosomal imbalance and increases the chance of a healthy and successful pregnancy.
4. MULTIPLE FAILED IVF CYCLES
When no pregnancy occurs after multiple IVF cycles, despite transferring “good quality embryos”, a common cause is an irregular chromosomal configuration or aneuploidy. Morphologically good embryos (good looking) may appear normal but may be chromosomally abnormal. As described above, PGS screens for abnormal embryos and identifies normal embryos so that a normal or unaffected embryo may be transferred into the intended parent. Transferring a chromosomally normal embryo increases the chance of a healthy and successful pregnancy.
PGD is indicated for the diagnosis of Single Gene Disorders. Frequently, a couple is aware of a condition that runs in the family and requests Pre-implantation Genetic Diagnosis (PGD) to avoid having an affected child. In general, PGD can be performed if the specific genetic mutation that causes a condition is known. Examples of Single Gene Disorders that can be diagnosed by PGD are Tay-Sachs disease, cystic fibrosis, muscular dystrophy, sickle cell anemia, and Huntington’s disease. As with PGS, IVF is needed to create the embryos to be tested for the specific single gene disorder. Once test results are known, an unaffected embryo is transferred into the intended mother’s uterus, where it can grow and result in the birth of a healthy child.
Single gene testing can be combined with chromosome screening (PGS), to maximize the chances of having a healthy baby by also avoiding a chromosomal abnormality in the child (i.e. Down syndrome or Trisomy 21).
How accurate is PGS and PGD?
PGS and PGD are able to diagnose genetic abnormalities with approximately 98% accuracy. After PGS or PGD, additional prenatal testing is optional.