What are the genetic causes of infertility and what treatments are available? I wanted to give frequently asked questions and answers on this subject here once again…
THE IMPORTANCE OF GENETIC EXAMINATION IN MALE INFERTILITY: In recent years, advances in the field of genetics have enabled us to obtain very important information about the causes of male infertility. Deletions in the genes on the Y chromosome, one of the sex chromosomes, cause a decrease in sperm production in the testicle or no sperm production at all, even though the body structure and functions are normal. Likewise, in genetic diseases such as number anomalies in sex chromosomes, such as the most common 47 XXY Klinefelter syndrome, testicular development may be inadequate and sperm production may be reduced. In addition, if the ducts that carry sperm from the testicles are not present at birth, although there is normal sperm production in the testicle, sperm cannot be seen in the semen because there is no way out. This is genetically caused by a disease called Congenital Bilateral Vas Deferens Agenesis (CBAVD).
WHAT IS PREIMPLANTATION GENETIC DIAGNOSIS PROCESS AND IN WHICH COUPLES IS IT APPLIED AND WHAT ARE THE ADVANTAGES?
Today, genetic diseases can be identified during pregnancy or after birth. However, possible genetic diseases in the baby can only be determined in the fourth month of pregnancy by methods such as ultrasonography and amniocentesis, and if a serious abnormality is detected, the pregnancy is terminated around the 5th month. This situation traumatizes the expectant mother and father psychologically and physically. In recent years, developments in genetic science allow genetic examination to be carried out on embryos developed in the laboratory using in vitro fertilization methods, before pregnancy occurs, and the placement of selected healthy embryos into the uterus of the expectant mother. This method is called pre-pregnancy genetic diagnosis (Preimplantation Genetic Diagnosis - PGD). Pre-pregnancy genetic diagnosis is carried out by taking a cell from the embryos that develop as a result of fertilization of the egg and sperm cells obtained from the expectant mother and father in a laboratory environment. Special methods called Fluorescence In Situ Hybridization (FISH) or Polymerase Chain Reaction (PCR) are used for genetic diagnosis. Diagnosis of numerical chromosome disorders such as monosomy or trisomy (Down syndrome and other trisomies) and single gene diseases (such as hemophilia, Mediterranean anemia, cystic fibrosis, muscular dystrophies) in the unborn baby is possible with PGT. Thus, the birth of healthy babies is ensured by transferring disease-free, healthy embryos to the expectant mother.
Pre-pregnancy diagnosis: In couples who are carriers of a genetic or hereditary disease, in couples who have previously had a child or children with a genetic disease, in the identification of diseases that show genetic predisposition for the purpose of HLA genotyping (tissue typing), in women in the older age group (37 years and above) accepted for assisted reproductive techniques, in couples with recurrent early pregnancy miscarriages, in couples who could not achieve pregnancy with assisted reproductive techniques despite numerous applications or in couples who lost their pregnancies due to miscarriages, chromosomal disorders or genetic disorders accompanied by severe male infertility. It is applied in diseases.
WHAT IS THE IMPORTANCE OF PGT IN DISEASES LIKE THALASSEMIA, HEMOPHILIA ETC AND IS IT POSSIBLE TO PERFORM TISSUE TYPING IN EMBRYOS?
Individuals transmit the hereditary disease they carry to their children at varying rates. Therefore, identifying genetic diseases in couples and embryos is important for couples to have healthy children. Today, it has become possible to identify many hereditary diseases at the embryo level with the DNA analysis method. In order to identify the genetic disorder that causes a hereditary disease, the structure of the gene that causes the disease must be determined. As a result of the research, the structure of many genes that cause diseases such as B-thalassemia, Hemophilia, Cystic Fibrosis, Sickle Cell Anemia, Muscular Dystrophies and Fragile X have been determined and methods for their genetic diagnosis have been developed.
With this method, genetic analyzes are first performed to show the genetic disorder in the blood samples of the parents and, if any, the sick children. Afterwards, the genetic structure that causes the disease is multiplied using special methods in the cells taken from the embryos obtained by in vitro fertilization of couples who are carriers of hereditary diseases, and the gene region of the screened disease can be identified by DNA analysis method. As a result, while embryos carrying hereditary diseases are eliminated, healthy embryos can be transferred to give birth to children without genetic diseases. As a result of the research, the structure of many genes that cause diseases such as B-thalassemia, Cystic Fibrosis, Sickle Cell Anemia, Hemophilia, Muscular Dystrophies and Fragile X have been determined and methods for their genetic diagnosis have been developed. Moreover; In diseases such as B-thalassemia, Fanconi anemia and leukemia, in addition to detecting healthy embryos by DNA sequence analysis method, HLA genotyping (tissue typing) process can also be applied at the same time and the tissue type of the embryos can be determined. In families with children diagnosed with thalassemia or leukemia by HLA genotyping method, after determining the tissue types of the mother, father and child, embryos whose tissue type is compatible with the patient child can be selected among the embryos that do not carry the disease. Healthy pregnancies achieved in this way provide treatment for sick children by using the cord blood and bone marrow of healthy born children.
With this method, the family is also protected from medical and psychological trauma due to pregnancy termination following the prenatal diagnosis process. Moreover; Pre-pregnancy diagnosis is a very important technique as it enables families to have healthy children and provides treatment opportunities for sick people due to the health problems that sick people face throughout their lives, difficulties in treating diseases and high treatment costs. As a result of today's studies, it will be possible to identify many more diseases in embryos by determining the genetic structure of diseases.
CAN IT BE KNOWN WHETHER THE FERTILETED EGGS (EMBRYOES) ARE ABNORMAL BEFORE THEY ARE PLACED INTO THE WOMEN? Yes. By applying preimplantation genetic diagnosis, embryos with chromosomal disorders can be selected and only healthy ones can be transferred.
ARE THERE PRECAUTIONS THAT CAN BE TAKEN ABOUT GENETIC PROBLEMS BEFORE PREGNANCY OCCURS? Yes. Preimplantation Genetic Diagnosis method is applied for this purpose. With this method, embryos obtained through in vitro fertilization in families at risk for hereditary diseases are examined and healthy embryos that are found to be free of disease are transferred. The success rate decreases as the woman gets older (35-45), and when pregnancy is achieved, it may end in miscarriage. Since chromosomal disorders in eggs increase with age, embryos obtained from couples undergoing in vitro fertilization treatment are biopsied when they reach the third day. Following the evaluation of one or two cells obtained within a few hours using molecular diagnostic methods, healthy embryos are separated and transferred. It provides information about the chromosomal disorders that increase most with age and are compatible with life (Trisomy 13, 16, 18, 21, 22, 15, 17 and X,Y). With this method, the pregnancy rate can be increased and the risk of miscarriage is reduced in older women who obtain sufficient embryos.
WHO IS GENETIC EXAMINATION RECOMMENDED IN EMBRYO? There is no need for genetic examination of embryos in every couple included in the in vitro fertilization program, however, this examination is recommended for couples with certain characteristics and risks. These features can be listed as follows:
1. In couples who are carriers of a genetic or hereditary disease,
2. In couples who have previously had a child or children with a genetic disease,
3. Assisted reproductive techniques (in older age group women (37 years and above) accepted for in vitro fertilization,
4. In couples with recurrent early pregnancy losses and miscarriages,
5. In couples who have not been able to achieve pregnancy despite the application of assisted reproductive techniques many times or who have lost their pregnancies due to miscarriages,
6. In cases of chromosomal disorders or genetic diseases associated with severe male infertility,
7. For the purpose of HLA genotyping (tissue typing)
8. Identification of diseases that show genetic predisposition
WHAT ARE THE ADVANTAGES OF PREIMPLANTATION GENETIC DIAGNOSIS?
1. It increases the chance of pregnancy and reduces the chance of miscarriage.
2. Families are enabled to have healthy children.
3. The family is protected from medical and psychological trauma due to pregnancy termination.
4. In diseases such as thalassemia, the baby to be born with tissue typing provides treatment opportunities for the sick children of the family.
5. Pre-pregnancy diagnosis; It is a much more useful and cheaper diagnostic method compared to the health problems that sick people face throughout their lives, the difficulties in treating diseases, and the high treatment costs.
CAN GENETIC DISEASES BE OBSERVED IN THE EMBRYO OF COUPLES WITH NORMAL CHROMOSOME ANALYSIS? Yes. In genetic tests performed on blood cells taken from couples, the chromosome structure may be found to be normal. However, the embryo receives half of its genetic structure from the mother's egg cell and the other half from the father's sperm cell. For this reason, although the genetic structure of the body cells is normal, some couples may have chromosomal disorders that can only be seen in the reproductive (egg or sperm) cells, and this disorder can be transferred to the embryos. Such genetic disorders in embryos can be detected with pre-pregnancy genetic diagnosis.
CONNECTED MARRIAGE IN THE EMERGENCE OF GENETIC DISEASES WHAT IS THE EFFECT?
Consanguineous marriages are marriages made between people who are related by blood. According to the degrees of kinship, the closest one is cousin marriages, which we call first degree consanguineous marriages, and they are marriages between the children of aunts, uncles and uncles. The rate of consanguineous marriage in our country is 21-40% and varies depending on the region. In general, anomalies resulting from various reasons are detected in 2-3 of every 100 children born in society. This risk can increase to 4-5% in couples who are married to consanguineous relatives.
WHO ARE THE PEOPLE AT GENETIC RISK? Couples who are carriers of a genetic or hereditary disease, couples who have previously had a child or children with a genetic disease, couples with structural anomalies in their body, a history of children with mental retardation, sexual development anomalies, developmental delay and short stature, couples with a genetic disease in close relatives (such as a 1st cousin), couples with recurrent miscarriages and stillbirths, women over 37 years of age, and couples who cannot achieve pregnancy despite the application of assisted reproductive techniques many times. In these couples, a detailed family history should first be taken by a geneticist and a family tree should be created. It is necessary to obtain detailed information about the disease considered in the family and previous pregnancies, if any. Sick children and family members should be examined and necessary tests should be requested. After all these procedures, if the disease is diagnosed or a genetic cause is detected, the couples are given detailed information about the detected problems. The family is informed about the problems that the genetic disease may cause, its consequences, risks in new pregnancies, and what to do before and after pregnancy. After these procedures, the risks of couples' new pregnancies can vary from no risk of recurrence to 100%. While preimplantation genetic diagnosis may be recommended for some couples, genetic diagnosis during the prenatal period is recommended for some patients.
WHAT IS THE ROLE OF GENETIC FACTORS IN THE OCCURRENCE OF INFERTILITY? Today, reduced fertility is detected in approximately 15% of couples. In most of these cases, the cause is male infertility. The pathogenic cause of male infertility, especially in people without sperm, is obstructive azoospermia, characterized by decreased sperm production due to Y chromosome microdeletions or congenital absence of the vas deferens due to cystic fibrosis transmembrane regulator (CFTR) gene mutations. In addition, numerical anomalies in sex chromosomes and structural chromosome disorders also cause problems in spermatogenesis and therefore in fertilization. In addition, KAL (X-linked inherited Kalman syndrome), DAX1 (X-linked inherited Congenital Adrenal Hypoplasia), GNRHR (GnRH secretion disorder) and PC1 (prohormone convertase 1) gene mutations that cause hypogonadotropic hypogonadism and Androgen Receptor gene mutations can be observed together with spermatogenesis failure. In addition, carriers of some genetic disorders may be observed in couples with a history of recurrent pregnancy losses or stillbirth, which are called secondary infertility.
CAN GENETIC PROBLEMS BE IDENTIFIED AFTER PREGNANCY? Yes. There are some screening tests that should be applied during pregnancy. (11–14 screening test - double test - triple test...) These screening tests give us information about the genetic risk during pregnancy. 11–14 when such a risk is identified. It is possible to perform chromosome analysis of the baby by taking a biopsy from the fetus's partner at 2 weeks or by taking a sample of the fluid in the baby at 16-18 weeks. In addition, ultrasonography also helps us in this regard.
For more information about pre-transfer genetic diagnosis (pgt), please click.
To get detailed information about in vitro fertilization treatment, in vitro fertilization prices and our in vitro fertilization center, please Click here.