Genetic Causes of Infertility

Understanding Infertility

Infertility is when there is a failure to conceive after a year or more of regular unprotected sexual intercourse. It happens in couples who want to become parents but are not able to become pregnant because of male, female, or unexplained factors. It is believed that the most common cause of infertility is related to genetic factors. In vitro fertilization (IVF) and other medical treatments are available to treat infertility.

Genetic Conditions Causing Infertility in Females:

Certain genetic factors impact female fertility. Changes in DNA (deoxyribonucleic acid) that affect one or more genes cause genetic disorders.

Infertility in females can be due to a few genetic disorders, such as:

1. Turner Syndrome: In this syndrome, females are born with a changed X chromosome or only one chromosome (usually there are two chromosomes). There is no proper development of the ovaries in this condition. This syndrome can lead to primary ovarian insufficiency, where the ovaries stop working after 40. Therefore, the eggs do not develop properly, and further, it leads to no ovulation.

2. Kallmann Syndrome: Several different changes cause this syndrome. There is a delay or absence of puberty as this syndrome leads to the brain making low levels of gonadotropin-releasing hormone (GnRH).

3. Fragile X Premutation: FMR1 is a gene present on the X chromosome. In the fragile X premutation, there is a specific change in the FMR1 gene. Due to the FMR1 genetic change, fertility is limited, as the ovaries are less productive. This syndrome can lead to primary ovarian insufficiency.

Genetic Conditions Causing Infertility in Males:

Male fertility can be reduced due to numerous genetic disorders.

Genetic disorders include:

1. Y-Chromosome Microdeletions: This condition causes male infertility. The Y chromosome is generally present in males and contains many other genes. When an area of a gene is missing, it is known as a deletion. Microdeletions on the Y chromosome affect the production of sperm.

2. Klinefelter Syndrome: In this syndrome, males have an extra X chromosome. They have two X chromosomes and one Y chromosome. Male infertility is mostly caused by this syndrome, which also affects the production of sperm. Sometimes, there is no sperm at all in males with Klinefelter syndrome.

3. Changes in the CFTR Gene: Male fertility challenges might be present due to changes in the CFTR gene, and this can lead to genetic disorders such as cystic fibrosis. Male fertility is impacted in various ways, such as low sperm count and blocking the transport of sperm through the male reproductive system.

4. Kallmann Syndrome: The production of testosterone is reduced due to low production of GnRH, which is essential for sperm development.

What Are the Genetic Factors Driving Male and Female Infertility?

Genetic factors are one of the most influential reasons why couples experience infertility. Factors include:

• A piece of a chromosome is missing due to deletion.

• The chromosome is upside down due to inversion.

• A mutation is a change in a gene’s DNA sequence.

• Chromosomes are too many or too few, known as aneuploidy.

• Pieces of chromosomes are attached to the incorrect chromosome, known as a translocation.

What Are the Genetic Causes of Female Infertility?

For women, there are decreased chances of conceiving if there are cases of endometriosis or early menopause apparent in their family. There can be female infertility due to some chromosomal abnormalities or gene mutations. This will cause difficulty for a woman to ovulate.

Some of the examples are

1. Kallmann syndrome.

2. Mutations in cystic fibrosis.

3. Primary ciliary dyskinesia is a disease of the airway or part of the lung.

What Are the Genetic Causes of Male Infertility?

Chromosomal abnormalities or gene mutations mainly cause male infertility. This will affect the production of sperm or sometimes block it. Mutations causing male infertility are rare.

Some of the examples are

1. Mutations in cystic fibrosis.

2. Y chromosome deletion.

3. Klinefelter syndrome.

Infertility could be due to multiple causes. Infertility treatment will be more effective only when the cause is identified correctly. However, even genetic factors can be overcome with advances and proper treatment protocols.

What Are the Tests Required to Diagnose Infertility?

Fertility issues can be diagnosed through the following steps:

• Medical and sexual history evaluation.

• Physical examination.

• Sperm count, shape, and movement are checked through semen analysis.

• Levels of different hormones and signs of ovulation are to be checked through blood tests.

• Structural issues in the reproductive system can be checked through imaging tests.

• Infertility genetic testing is done if the doctor finds a genetic factor that is playing a role in the fertility challenges.

• Preconception carrier screening is done through blood samples. This will screen for multiple genetic diseases that could affect fertility.

• A karyotype can also be checked through blood tests to check if all 23 sets of chromosomes are present.

What Is Perimplantation Genetic Testing (PGT)?

PGT helps in screening the embryos for single-gene and chromosomal abnormalities before transferring them to the uterus during the IVF cycle.

The main advantages of PGT are

1. There is a lower chance of passing a genetic disease to a child.

2. The chances of a successful pregnancy and birth are increased with IVF treatment with a genetically normal embryo.

How Are Fertility Issues Caused by Genetic Disorders Treated?

Various treatment options are decided based on the type of condition that is causing fertility concerns. Surgery is usually chosen when there are structural changes in the reproductive system that impact fertility. When an individual is not able to conceive naturally, other approaches are opted for, including intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI). One of the diagnostic tools is preimplantation genetic testing (PGT), which helps to screen embryos for chromosomal abnormalities.

Conclusion

Male, female, or both abnormalities in genetics can lead to infertility. Sperm abnormalities are caused by genetic disorders in males, and ovulation issues are caused by genetic disorders in females, both leading to infertility in individuals. A diagnostic tool, such as preimplantation genetic testing, helps to evaluate embryos to check for any kind of genetic disorders before transferring them to the uterus.

Note from iCliniq:

Genetic counselors are mostly qualified healthcare providers who help couples determine what genetic tests are required and mandatory. They can also help couples make informed decisions by determining the most effective treatment for their genetic issues.