The problem of infertility affects more and more couples in developed countries. Some of the causes of male and female infertility may be genetically determined. These include genetic disorders of sperm production, recurrent miscarriages due to abnormal fetal karyotype, premature ovarian failure (menopause before 40) or congenital adrenal hyperplasia.

Some time ago, the World He alth Organization included infertility on the list of civilization diseases. It is estimated that up to 20 percent. couples have difficulties conceiving a child (approx. 2 million couples in Poland). We talk about infertility when during 12 months of regular intercourse (in Poland it is up to two years) without the use of contraception, fertilization does not take place.

The most important thing is to know the cause of infertility

Even seemingly unnoticeable changes in genes (mutations) may result in the lack of offspring. It is a situation that has a strong psychological impact, causing negative (psychosocial) consequences for the infertile couple, which is why it is so important to perform appropriate genetic tests and find out the cause. By understanding the problem, specialists can make decisions about appropriate conventional treatment or the use of assisted reproductive methods. In some cases, it is only possible to adopt a child. The most important thing, however, is that thanks to a diagnosis, a couple can avoid many stressful situations (even several years of unsuccessful efforts).

However, not all causes of infertility are currently established. It is estimated that approx. 30 percent. cases remain unanswered, approx. 35 percent. is associated with female infertility, similarly - about 35 percent. is male infertility.

When should a couple look for the genetic determinants of the lack of offspring?

As previously mentioned,the cause of infertilitymay lie on the side of both the woman and the man. Signals that may indicate a genetic determinant of infertility in a woman may be:

  • recurrent miscarriages (i.e. loss of consecutive pregnancies),
  • primary amenorrhea due to lack of ovarian function,
  • premature termination of ovarian function.

On the other hand, the suspicion of the genetic basis of infertilitymale should be suspected in the case of:

  • lack of sperm in semen (so-called azoospermia),
  • sperm count less than 5 million / ml (so-called oligospermia) and their abnormal mobility (so-called asthenozoospermia),
  • repeated miscarriages at your partner.

Genetic causes of infertility should also be sought in the presence of: disorders in the development of the genital organs, other congenital changes in the body structure, abnormal development of tertiary sexual characteristics and congenital hypogonadotrophic hypogonadism (caused by the abnormal functioning of the pituitary gland in the brain).

What genetic tests for infertility can be performed?

According to the recommendations of the Polish Society of Reproductive Medicine, in the case of searching for the causes of infertility (as well as before starting the procedure of assisted reproduction), the following genetic tests should be performed:

  • Firstly, examining the karyotype in both partners.
  • Testing the CFTR gene, also in both partners.
  • Study of the AZF region of the Y chromosome in men.

If the cause of infertility is not found, it is recommended to consult a geneticist and extend the research for men: AR gene testing; for women: FMR1 gene testing, F5 and F2 gene testing; for both sexes: study of the CYP21A2 gene.

Karyotype test

The best known and relatively easy to study are chromosomal aberrations (i.e. changes in the structure or number of chromosomes). The test consists in determining the number and structure of chromosomes in each of the future parents. In selected groups of patients, after excluding other common causes of infertility, chromosomal aberrations are observed in 7-15% of men and in 15-35% of women in primary infertility (when a woman cannot become pregnant at all) and in about 5-10% of couples with secondary infertility (when a woman already has a child but cannot become pregnant).

Karyotype is a morphological description of a set of chromosomes found in all cells that make up our body (so-called somatic cells). In humans, there are two groups of chromosomes: autosomes - there are 44 (22 pairs) and sex chromosomes - 1 pair: XX for a woman and XY for a man. The correct human karyotype is therefore diploid - each autosomal chromosome occurs in duplicate, one from each parent, and sex is determined by a pair of sex chromosomes, XX in women and XY in men.

The reasons for the inability to produce offspring vary depending on the type of changes in the karyotype. It often happens that carriers of chromosomal aberrations:

  • men have reduced semen parameters,
  • women menstrual disorders in primary infertility and impediment or lack of egg production related to hormonal disorders in secondary infertility.

It also happens that when fertilization occurs, the fertilized cell has incomplete genetic material and pregnancy usually ends in a miscarriage, usually before the 20th week. Depending on the type of chromosomal aberration found, there is a risk of giving birth to a child with a syndrome of defects and impaired development (physical and psychomotor), miscarriage or the inability to conceive.

Male infertility

Correct sperm test results are commonly assumed as the index of male fertility. In cases of severe disorders of spermatogenesis, genetic diseases are quite common causes, including mutations in the CFTR gene, microdeletions of the AZF region on the Y chromosome, and mutations of the AR gene on the X chromosome. from obstruction of exit roads.

The cause of this condition in 10% of cases is a congenital defect (bilateral lack of vas deferens) caused by mutations in the CFTR gene. Lack of sperm in semen may also be due to disorders of spermatogenesis (sperm production). In over 25% of cases, this condition is caused by microdeletions in the AZF region of the Y chromosome. On the other hand, mutations damaging the AR gene may cause the syndrome of insensitivity to male sex hormones - androgens, and disrupt the development of sexual characteristics. It is estimated that mutations in the AR gene may be responsible for 2-3% of cases of absence or a significant reduction in the number of sperm in semen.

Recurrent miscarriages

Miscarriage is the termination of a clinically proven pregnancy by week 20. About 20-25% of women experience at least one miscarriage in their lifetime. The term recurrent miscarriage is defined as three or more consecutive spontaneous abortions, which occurs in approximately 3-5% of all women. The risk of miscarriage increases with age, and risk factors include high body weight, smoking, and exposure to certain chemical agents, but are largely genetic abnormalities.

More than 50% of spontaneous miscarriages are due to abnormal karyotype of the fetus, despite normal karyotypes in both parents (in these cases trisomy of chromosomes 13, 18 and 21 is the most common).

The second important factor is the carrier of mutations in the F5 and F2 genes encoding the factors of the blood coagulation system. In addition to deep vein thrombosis, they can cause women to form clots in the placenta with the resulting deathplacenta and fetus. In these cases, miscarriages are usually observed after 10 weeks. The detection of this type of genetic predisposition enables the initiation of anticoagulation therapy and prevents miscarriage.

Premature loss of ovarian function

This term is used to describe the onset of menopause before the age of 40. The estimated frequency of the disease is 1: 100 women and 1: 1000 women under 30 years of age. Genetic factors are among the causes of the disease, including chromosomal aberrations and gene mutations. In family cases (about 20-30%), the disease is most often caused by mutations in the FMR1 gene located on the X chromosome.

Early detection of genetic predisposition to extinction of ovarian function enables mutation carriers to make a decision about planning having children, and in some cases to use assisted reproductive methods (prenatal diagnosis is then recommended). In women with a premature menopause, hormone replacement therapy (reducing the risk of osteoporosis and heart disease) is indicated.

Congenital adrenal hyperplasia

Mutations in the CYP21A2 gene can cause congenital adrenal hyperplasia, resulting in errors in the production of sex hormones and fertility problems. Performing the above-mentioned tests, in addition to the possible explanation of the cause of infertility, also helps in a more precise determination of the risk for a given couple of giving birth to a child with selected genetic abnormalities. Before performinggenetic test , it is recommended to consult a geneticist so that he or she chooses the appropriate genetic tests based on family history.

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Pregnancy