Preımplantatıon Genetıc Testıng And Gender Selectıon
In the past, couples at risk of transmitting a serious genetic anomaly had no other option than amniocentesis to diagnose the health of their unborn child. Amniocentesis isn't risk-free, and it's done late in a pregnancy (in the second trimester), which makes it harder to decide whether to keep the pregnancy going or end it.
To avoid having to face this situation, many couples resort to a recent technique called preimplantation genetic testing, or PGT.
What is Preimplantation Genetic Testing?
Preimplantation genetic testing (PGT) is a series of genetic assays to evaluate abnormalities in embryos that are created during in-vitro fertilization (IVF). It is performed before the transfer of the embryos to the uterus by taking one or more cells from each embryo. The purpose of genetic testing before IVF is to reduce the risk of pregnancy complications or the possibility of a genetic disease in the embryo prior to pregnancy, especially if the parents present inheritance patterns for a particular disorder.
PGT for Gender Selection
Gender selection, also called sex selection, is another medical practise of PGT that allows the parents to choose the sex of their baby in their IVF journey. It is an additional step of PGT, which is performed after in vitro fertilization has taken place and before the healthy embryo has been implanted. There are 2 fundamental motives behind sex selection operation:
to avoid gender linked chromosomal abnormalities, and
Benefits of PGT
PGT is highly accurate for all tests it serves: single gene disorders, chromosomal anomalies, and sex selection. It provides high pregnancy and live birth success rate because;
it’s highly safe procedure to perform,
it eliminates the possibility of abnormalities, thus decreases the ratio of misscarriage,
it aims a pregnancy with healthiest embryo and desired sex,
it increases the success rate of implantation for the patients who have experienced multiple IVF cycle failures.
Types of Preimplantation Genetic Testing
A chromosomal or genetic defect that may exist in an embryo may cause problems, including single gene disorders (like cystic fibrosis), chromosomal gains or losses (such as Down or Turner syndromes), or problems that may end up with failed IVF cycle or miscarriage. IVF screening for genetic disorders is necessary to avoid such problems. There are two types of PGT to detect these several types of abnormalities.
Preimplantation genetic testing for aneuploidy (PGT-A), formerly called preimplantation genetic screening (PGS), aims to detect chromosomal gains or losses, like in Down syndrome.
PGT-A is the type of genetic testing where the gender of the embryo can be selected, since the gender is also expressed through the chromosomes. People who are seeking a solution to gender selection, can apply for PGT-A.
Preimplantation genetic testing for monogenic disorders (PGT-M), on the other hand, aims to detect single gene disorders, such as cystic fibrosis or sickle cell anemia. PGT-M was formerly called preimplantation genetic diagnosis (PGD).
While PGT-A is the main cause of miscarriage and is more commonly performed during fertility genetic testing, PGT-M is also important to eliminate the possibility of an inherited disease, especially if there is a diagnosed case in the family tree.
Preimplantation genetic testing for structural chromosomal rearrangement (PGT-SR) is another type of testing to detect chromosomal defects. It is typically performed if there are known chromosomal rearrangements, such as translocation or inversion. A person with a chromosomal rearrangement is at high risk of producing embryos with chromosomal gain or losses, which may result in a miscarriage or a child with serious health issues.
Who Should Have Pre Genetic Testing?
PGT is typically advised when parents have or are a carrier of a known genetic disorder. It is also recommended if there is a history of recurrent miscarriages, IVF failures, male factor infertility, and/or unexplained infertility. PGT can also be performed if a woman is above her maternal age, which is 35, since the quality of eggs decreases exponentially with age, which may cause genetic modifications on the egg.
How Is Embryo Genetic Testing and Gender Selection Performed?
Women ovulate one or two eggs every month. However, one or two eggs is not generally aimed to achieve a successful pregnancy under lab conditions. So, the goal is to retrieve as many eggs as possible. To be able to do so, your ovaries need to be stimulated to ovulate more than 2 eggs. This is achieved by special medications and injections.
It is a safe but unnatural process for a woman, so you will be monitored throughout the process to ensure that desired outcome will be achieved, and your ovaries are not hyperstimulated. For this purpose, regular vaginal ultrasound or blood testing might be asked in your follow-up appointments.
Your follicles will be ready to be retrieved generally after 10 to 14 days.
Follicles get ready to be retrieved when they are mature enough. The size they counted as mature is approximately 15-20 mm in diameter. This procedure is performed 2 to 3 days after your last injection with transvaginal ultrasound aspiration method and you will be sedated for the procedure.
During the procedure, an ultrasound probe will be placed into your vagina in order to locate the follicles. Then, a needle will be inserted through your vagina and into a follicle, and an egg will be extracted from the follicle using a suction device connected to the needle. The more eggs retrieved, the higher the chance of pregnancy.
Fertilization step can be performed either;
-Conventional insemination, which is basically overnight incubation of mature eggs with high-quality fresh semen, or
-Intracytoplasmic sperm injection (ICSI), which is the direct introduction of single healthy sperm to mature eggs.
Genetic screening for embryos requires the DNA material of the embryo to be performed. Both PGS and PGD processes begin with a biopsy of one or more cells from embryos developed in the IVF cycle. The biopsy includes several different techniques, as described below.
Polar Body Biopsy
Polar bodies are the byproduct of meiotic divisions of the embryonic development stage. They don’t have the ability to get fertilized under normal conditions. Therefore, this strategy doesn’t have any effect on embryonic development. However, it can only analyze maternal abnormalities, excluding parental or mitotic division-related problems. Nonetheless, it eliminates the necessity for embryo cryopreservation, therefore, is a valid technique for countries with legal restrictions on cryopreservation.
Blastomere Biopsy of Cleavage-Stage Embryos
PGD is commonly performed with the blastomere biopsy technique. It is commonly performed when the embryo has reached six to eight cells, which generally occurs 3 days after insemination. Either one or two blastomeres are removed. While removing two cells is considered more accurate, it may affect the vitality of the embryo since 2 cells mean approximately 30% of the embryo. However, the removal of only one cell is also controversial because a diagnosis based on only one cell might be misleading. Blastomere biopsy is also available for fresh embryo transfer as polar body biopsy,therefore, eliminates embryo cryopreservation.
Trophectoderm Biopsy of Blastocyst
A blastocyst is composed of two different cell types: the inner cell mass, the precursor of fetal tissues, and the trophectoderm (TE), which comprises the wall of the blastocyst and turns into the placenta as the embryo develops. Since a blastocyst is composed of 100 to 150 cells, multiple cells can be removed for IVF genetic testing, which will cause a loss of approximately 10% of the cells, leading to higher survival rates for the embryo. Additionally, the genome of the cells in the blastocyst stage are considered active, which allows more accurate results.
PGS is commonly performed with the trophectoderm biopsy technique. It is quite common to freeze (cryopreserve) excess embryos at their blastocyst stage since blastocysts are generally on day 5 or 6.
PGT evaluation, Gender Selection and Embryo Transfer
After the cells are taken, several molecular techniques may be applied to analyze the cells. Common techniques are: Array-Comparative Genomic Hybridization (aCGH), Next Generation Sequencing (NGS), Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), and fluorescent in situ hybridization (FISH). All of these methods aim to find the single gene and chromosomal abnormalities, or the sex of the embryo.
Test results are evaluated carefully and only embryos with desired sex and no diagnosed genetic or chromosomal defects are transferred to the uterus during the next stage of the IVF cycle. Selected embryos are then implanted in the fertility clinic.
After the implantation is completed and successful pregnancy achieved, prenatal genetic testing, chorionic villus sampling and/or amniocentesis, can also be applied to confirm that the desired outcome has been achieved.
Commonly, more than one fetus are implanted, if available, to secure a successful pregnancy. However, it may also cause multiple pregnancies if more than one embryo is able to attach to the placenta, which can decrease the chances of a healthy pregnancy or may cause early delivery. The higher the number of fetuses, the higher the risk a mother carries. Therefore, a fetal reduction procedure may help maintain a healthy pregnancy and minimize the risks and complications such as miscarriage, early delivery, dissabilities that may occur during the pregnancy.