Genetic Causes Of Male Infertility

Genetic Causes Of Male Infertility

According to latest statistics reported by the American Society for Reproductive Medicine (1), male causes are solely responsible for 40% cases of infertility in the United States. Besides trivial issues such as intake of certain medications or uncontrolled medical conditions; some cases are also due to more serious genetic causes. It is imperative to mention that management of infertility due to genetic causes is more complicated and requires more innovative treatments.

What Is The Pathophysiology Of Male Infertility Due To Genetic Causes?

Genetic causes of male infertility involve three primary mechanisms:

  • Quantitative reduction in the sperm production
  • Production of morphologically abnormal sperms
  • Obstruction to the natural flow of sperms through the male reproductive tracts

There are two primary types of genetic mutations that may culminate in the male infertility:

  • Chromosomal abnormalities
  • Single gene mutations

Some causes of male infertility are idiopathic (i.e. no disease process can be identified as the cause of infertility). Many of these unknown problems can be diagnosed with the aid of modern molecular techniques, while providing new insights on the treatment strategies.

What Are Chromosomal Abnormalities?

These include the following disorders:

  • Klinefelter‚Äôs Syndrome: This is a congenital condition that affects approximately 200,000 males each year in the US. People who are born with this disorder have an extra X chromosome in their genetic composition. The normal male genotype is 46XY, whereas males with – Klinefelter‚Äôs Syndrome has 47XXY. This extra X chromosome can either come from an egg or sperm during the embryonic development. It is a fairly common disorder however, many men remain undiagnosed until late into adult life. Men with this condition are infertile owing to absent/markedly reduced sperm production (azoospermia), and low serum levels of testosteMale Infertility and Cancer Risks imagerone. Patients with Klinefelter‚Äôs syndrome need lifelong testosterone therapy after puberty.
  • Y chromosome Deletions: In this condition, a part of genetic material required for spermatogenesis is absent from the Y chromosome in the affected males. This usually occurs spontaneously during the development of embryo. Most of these men have low sperm counts rendering them infertile. The brothers of¬†the patient may not be affected.
  • Down‚Äôs syndrome: This is a genetic condition in which there are three copies of Chromosome 21 (Trisomy 21). As it is an autosomal condition, both male and females can harbor this mutation. Apart from infertility, these people also suffer from a lot of other physical and mental abnormalities.

What Are Single Gene Mutations?

Single gene mutations are less common when compared to chromosomal abnormalities, merely because most cases are incompatible with life. One example of single gene mutation that may present with male infertility is congenital absence of Vas Deferens.

Congenital absence of Vas Deferens (CAVD): This rare disorder results from a mutation in the Cystic Fibrosis (CFTR) gene. The sperm production is normal; however parts of the male reproductive tract including vas deferens, epididymis and seminal vesicles are underdeveloped or absent, resulting in the inability of sperms to flow into the ejaculate. In Cystic Fibrosis, affected person may also have lung and bowel problems as well.

How To Diagnosis Male Infertility Due To Genetic Causes?

1) Klinefelter’s syndrome can be diagnosed prenatally by micro-invasive techniques like amniocentesis or chorionic villus sampling. The affected individual will have infantile-sized testes after puberty. A blood test for karyotyping may reveal abnormalities in the chromosomal number. The serum levels of key male hormones are also abnormal including Testosterone, FSH and LH.

2) Y chromosome deletions can also be diagnosed by karyotyping.

3) Down’s syndrome is usually diagnosed in the antenatal period by ultrasonograpy. Various micro- invasive techniques can also be used to obtain fetal tissue for genetic diagnosis. After birth, the diagnosis can be confirmed via physical examination (distinct facial/bodily features).

4) CAVD can be diagnosed by mutational analysis of CFTR gene. Both partners should be tested.

How To Manage Male Infertility Caused By Genetic Abnormalities?

Intracytoplasmic Sperm Injection (ICSI) is one of the assisted reproductive methods in which the sperms are retrieved from the male testicular tissue for implantation with the egg. This technique can address fertility issues in males suffering from Klinefelter’s Syndrome, Y chromosome deletion and CAVD as about half of these patients have enough sperms for fertilization.

Donor Insemination is also an option if the male is totally infertile, and wishes to have children. This involves implantation of the donated sperms to achieve a viable pregnancy successfully.

Genetic counseling should be offered to all the couples opting for ICSI or other assisted techniques, as patients with Y chromosome deletions can pass on the defect to their male progeny, and if both partners have CAVD, the offspring will also develop Cystic fibrosis. Preimplantation genetic diagnosis can prevent such issues.



2. Plaseska-Karanfilska, D., Noveski, P., Plaseski, T., Maleva, I., Madjunkova, S., & Moneva, Z. (2012). Genetic causes of male infertility. Balkan Journal of Medical Genetics, 15(Supplement), 31-34.

3. Giacco, D. L., Chianese, C., Ars, E., Ruiz-Casta√Ī√©, E., Forti, G., & Krausz, C. (2014). Recurrent X chromosome-linked deletions: discovery of new genetic factors in male infertility. Journal of Medical Genetics, 51(5), 340-344.

4. Jungwirth, A., Giwercman, A., Tournaye, H., Diemer, T., Kopa, Z., Dohle, G., … & EAU Working Group on Male Infertility. (2012). European Association of Urology guidelines on Male Infertility: the 2012 update. European urology, 62(2), 324-332.

%d bloggers like this: