One of the main factors of infertility and recurrent miscarriages are mutations in the mother and/or father. These genetic changes can affect sperm or egg production and, if passed on to the fetus, it can result in miscarriage. Genetic tests, performed on the embryos of prospective parents and during the IVF process, will help you to deliver a healthy child.
WHAT IS PGD?
Preimplantation Genetic Testing is the genetic examination of an embryo created under laboratory conditions. In this procedure, embryos obtained during in vitro fertilization are genetically examined before they are implanted in the mother’s uterus, in other words, before pregnancy begins. At the Generations Genetic Diseases Evaluation Center, all PGD applications are studied with molecular methods.
WHY SHOULD I HAVE PGT?
- For a successful and healthy pregnancy,
- If the expectant mother is 35 years of age or older,
- Repeated miscarriage,
- Repeated in vitro fertilization failures,
- If there is a known genetic disease in the family,
- If there is unexplained infertility,
We recommend that you undergo IVF and that your embryos undergo PGD. By choosing the healthiest embryo, we want to increase your chances of success and help you on your way to a happy and healthy family.
WHICH DISEASES CAN BE DETECTED WITH PGT?
Chromosomal Numerical Disorders (PGD-A): Diseases that can occur if your chromosome number is abnormal (aneuploidy), such as Down Syndrome, Edwards Syndrome, Klinefelter Syndrome.
Chromosomal Structural Disorders (PGD-SR): Diseases that can be caused by the displacement of certain regions of the chromosomes, resulting in an abnormal genetic structure.
Single Gene Diseases (PGD-M): Genetic diseases such as SMA, FMF, Thalassemia, Cystic Fibrosis, if reported in the prospective parents or their families.
WITH WHICH STUDIES IS THE PGT METHOD APPLIED?
The resulting embryos are 3. or 5. From the biopsies taken on the day; we can perform numerical analysis of a certain number of chromosomes with the FISH method, numerical analysis of all chromosomes and balanced or unbalanced translocation screening with high precision with the NGS method, numerical analysis of all chromosomes and screening of unbalanced translocations with molecular karyotyping (Microarray), genealogy, carriage and single gene diseases with Sanger sequencing and fragment analysis methods.
PGD-A CE-IVD MARK TEST
Novelty 2024!
Thermo Fisher Scientific’s PGD-A CE-IVD mark test was first implemented in Nesiller laboratory in Turkey. The PGD-A CE-IVD mark test is our most comprehensive PGD-A test. It allows selecting the most viable embryos obtained in the in vitro fertilization (IVF) procedure, increasing the accuracy and confidence for embryo transfer. What are the benefits?
- Avoid unsuccessful transfer of non-viable aneuploid embryos, increasing the pregnancy rate
- Reduces the miscarriage rate
- Reduces the risk of aneuploid syndrome
- Allows highly efficient transfer of a single embryo
- Accurate detection of haploid or triploid embryos
- Avoids the incorrect designation of “mosaic”
- Higher proportion of embryos classified as “euploid”
As Nesiller, we are pleased to be the first laboratory in our country to offer the CE-IVD approved PGT-A test, which increases pregnancy success rates in IVF for couples who want to build healthy families.
In about 10% of couples with infertility problems, the cause is due to genetic factors.
GENETICS IN MALE INFERTILITY
Approximately half of infertility cases are male infertility of genetic origin. Individuals with indications for severe oligoasthenoteratospermia, obstructive azoospermia, nonobstructive azoospermia, oligoasthenoteratospermia and recurrent implantation failure are at genetic risk.
Y CHROMOSOME MICRODELETION
The AZFa, AZFb and AZFc regions on the gene known as “azoospermia factor” or “AZF” on the long arm of the Y chromosome are associated with male infertility.
CYSTIC FIBROSIS MUTATION
Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1-2% of infertile men. People with cystic fibrosis or diagnosed with CBAVD undergo genetic testing for cystic fibrosis transmembrane regulator (CFTR) gene mutations.
GENETICS IN FEMALE INFERTILITY
In women, genetic disorders can cause infertility by affecting the reproductive cycle and/or hormonal balance. These genetic findings include chromosomal irregularities and single gene mutations. The most common genetic causes of female infertility are chromosomal abnormalities and mutations in the FMR1 gene on the X chromosome responsible for Fragile-X syndrome.
Fragile X syndrome is the most common genetic cause of autism worldwide and the most common inherited cause of mental retardation.
Women who are Fragile-X carriers do not show symptoms of Fragile-X syndrome, but may be at risk for related disorders such as Fragile-X associated Tremor/Ataxia Syndrome (FXTAS). More importantly, from a reproductive point of view, there is a risk of premature ovarian failure. This is a condition usually recognized as low AMH/high FSH during routine infertility testing.
CYTOGENETIC EXAMINATION
Cell cultures obtained from both male and female peripheral blood can be analyzed for chromosomal abnormalities in chromosome number and structure.
- Reciprocal translocation
- Robertson type translocation
Prenatal diagnosis is the examination of fetal samples at the chromosome or gene level before birth. For prenatal diagnosis, the fetal sample is obtained by invasive intervention.
Chorionic Villus Biopsy (CVS), one of these methods, is used in the 10th week of pregnancy. From the first week of pregnancy, a sample is taken from the placenta facing the uterus and genetic examination is performed.
The same examination was performed at 16 weeks of gestation. Another method called amniocentesis (AS) is also possible after the first week of pregnancy. AS is the process of taking a sample of the fluid that the fetus is in.
If for any reason you have not reached your 20th day of pregnancy If the fetus is beyond the first week of pregnancy or if there is any doubt about the results of previous studies, it is possible to perform a genetic examination of the fetal blood by taking the baby’s cord blood (cordocentesis; CS).
CVS, AS or KS are performed by Obstetricians and Gynecologists and the samples are examined at Genetic Diagnostic Centers.
Indications for Prenatal Diagnosis include;
- Advanced maternal age, especially expectant mothers after 35 years of age
- Increased risk in the results of a double test or triple test from maternal serum NIPT result
- The mother or father is a carrier of a numerical or structural chromosomal abnormality if the previous birth had a chromosomal abnormality. Sometimes both normal cells and cells with numerical chromosomal abnormalities can be found in the same person. Prenatal diagnosis is performed to prevent diseases such as Turner syndrome and Klinefelter syndrome, since mosaicism, especially in mosaic cases in terms of sex chromosomes (X and Y), may cause number differences in the baby according to the mosaicism rate.
- Chromosomal abnormalities cause 50-60% of frequent miscarriages. Trisomies are responsible for half of these. The most common trisomies are 13, 16, 18, 21. It is seen in chromosomes. For prenatal diagnosis, chromosome analysis by cytogenetic method or FISH examination can be performed.
The application of molecular genetic methods in prenatal diagnosis is important in the prevention of single gene disorders. According to the inheritance characteristics of the disease, the probability of transmission of the disease from the carrier mother or father is 25-50%. Prenatal diagnosis of these diseases, which often have severe consequences, requires that both parents are tested for carrier status.
Non-invasive prenatal testing (NIPT) is an analysis of extracellular fetal DNA to screen for chromosomal abnormalities and single gene disorders. This is the process of obtaining the fetal sample from the mother’s blood sample and not from the placenta or amniotic fluid, which requires an invasive procedure. NIPT for chromosomal abnormalities was first introduced in 2011 in the United States, Western Europe and China.
Traditional NIPT includes the detection of trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome). However, over time, many studies have extended the traditional NIPT to screen for numerical and structural abnormalities in all chromosomes simultaneously, not just these three chromosomes.
Whole Genome NIPT represents an advanced screening tool for the prenatal detection of chromosomal abnormalities, allowing the detection of clinically significant imbalances that are undetectable by conventional NIPT testing. This level of screening offers significantly higher sensitivity compared with standard screening while maintaining a high level of specificity, with the potential to improve comprehensive pregnancy management. (Francesco Fiorentino*).
The NIPT test is used in the 10th trimester of pregnancy. from the first week of pregnancy, taking into account the following indications;
- Advanced maternal age (>37 )
- Positive result in maternal serum screening
- Abnormal ultrasound findings
- History of pregnancy with aneuploidy
- Translocation carrier parent
Samples that can be used for postnatal diagnosis are peripheral blood and tissue samples.
Infants with a clinical diagnosis of a syndrome with a dysmorphologic defect are examined for microdeletions, mutations or rearrangements. Cytogenetic or molecular studies are performed depending on the desired study.
