Reasons for Male Infertility: Genetics and Chromosomal Issues

The genetic conditions Klinefelter syndrome, Kallmann syndrome and cystic fibrosis all lead to abnormal development of the reproductive organs, which can make it difficult for men to father a child. But a diagnosis of one of these conditions isn't the end of all hope when it comes to starting a family. Learn about the symptoms and causes of these disorders, as well as potential treatments for men who struggle with related infertility.

Klinefelter syndrome

Males who are born with an extra X chromosome—XXY instead of the typical XY—have a genetic condition known as Klinefelter syndrome. Either the sperm or the egg that came together during fertilization had an extra X chromosome. Males with Klinefelter may have:

• An extra X chromosome in all cells. This is the most common type.
• An extra X chromosome in some cells. This is known as mosaic Klinefelter, and there are not as many symptoms.
• More than one extra X chromosome. This is rare and symptoms are more severe.

Klinefelter syndrome often isn't recognized until adulthood, when a man tries to conceive a child. In addition to infertility, symptoms of Klinefelter syndrome include smaller than normal testicles and lower production of the male sex hormone testosterone, which plays a major role in male sexual development before birth and during puberty. This shortage of testosterone can lead to delayed puberty, breast enlargement, decreased muscle mass and bone density and a reduced amount of body and facial hair.

Kallmann syndrome

Kallmann syndrome is a rare genetic disorder caused by the underdevelopment of nerves in the brain that signal the hypothalamus, a part of the brain vital in controlling the release of hormones. The syndrome is present from birth and is caused by a deficiency of gonadotropin-releasing hormone (GnRH), which is produced from cells in the hypothalamus. Also known as idiopathic hypogonadotropic hypogonadism with anosmia, Kallmann syndrome is characterized by an impaired sense of smell and delayed or absent puberty.

Some males with Kallmann syndrome exhibit symptoms, such as an abnormally small penis (micropenis) and undescended testes (cryptorchidism), before puberty. However, symptoms typically become more apparent during puberty, when genital enlargement, facial and pubic hair growth and lowering of the voice do not develop. Some men with Kallmann syndrome report having a low sex drive and erectile dysfunction (ED), or the inability to get and maintain an erection during intercourse. Other symptoms include a failure of one of the kidneys to develop, abnormal bones in the fingers and toes, a cleft lip, hearing loss and abnormal eye movements.

Without treatment, most men with Kallmann syndrome will not be able to father a child.

Cystic fibrosis

Cystic fibrosis (CF) is a genetic disease that causes severe damage to the respiratory and digestive systems and occurs as a result of a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A sudden mutation, or change, in the CFTR gene causes the body's mucus to become abnormally thick and sticky. This buildup of mucus affects various organs such as the lungs, liver, pancreas and intestines.

Approximately 98 percent of men with CF are infertile because they are born without a sperm canal, a condition called congenital bilateral absence of the vas deferens (CBAVD). Sperm cannot make it into the semen and therefore cannot reach and fertilize an egg during sexual intercourse. The lack of sperm in the semen can cause men to have thinner ejaculate and lower semen volume. Although the vas deferens is missing, the sperm is not, and sperm production is actually typical in the vast majority of men with CF and CBAVD.

Treatment for male infertility

Many men with infertility caused by Klinefelter, Kallmann or CF can have children through various treatment methods. For some men with minimal sperm production due to Klinefelter, a procedure known as intracytoplasmic sperm injection (ICSI) may help. This procedure involves injecting a single live sperm directly into an egg.

Men with Kallmann syndrome may benefit from a hormone replacement therapy known as gonadotropin therapy. Injections of human chorionic gonadotropin (hCG) can aid the development of sexual characteristics during puberty and later may induce fertility.

Many infertile men with CF benefit from assisted reproductive technology (ART). This involves obtaining sperm through surgical extraction, normal ejaculation or a sperm donor. The sperm is then inserted into the female genital tract or used to perform in vitro fertilization (fertilizing the egg with sperm outside the body) or ICSI.

If you have Klinefelter or Kallmann syndrome or cystic fibrosis, know that there are fertility treatment options available. Talk with your doctor about the symptoms you are experiencing, and they can develop a treatment plan to address your infertility and, hopefully, help you become a father.