Male Factor Infertility

What is infertility?
Infertility is defined by the American Society for Reproductive Medicine (ASRM) as a disease of the reproductive system that impairs the body’s ability perform the basic function of reproduction. Although conceiving a child may seem to be simple and natural, the physiological process is quite complicated and depends on the proper function of many factors, including the following, as listed by the ASRM:

• production of healthy sperm by the man

• production of healthy eggs by the woman

• unblocked fallopian tubes that allow the sperm to reach the egg

• the sperm’s ability to fertilize the egg

• the ability of the fertilized egg to become implanted in the uterus

• adequate embryo quality

Who is affected by infertility?  
The average chance to conceive for a normally fertile couple having regular, unprotected intercourse is approximately 25 percent during each menstrual cycle. In most couples, conception occurs within about 12 months. However, infertility affects about 10 percent of couples of childbearing age. Infertility is not just a woman’s concern. A problem with the male is the sole cause, or a contributing cause, of infertility in about 40 percent of infertile couples. About one-fourth of infertile couples have more than one cause or factor related to their inability to conceive. About 10 to 15 percent of couples have no identifiable cause for their infertility after medical investigation.

What are the risk factors for men regarding infertility?
The following is a list of risk factors related to male infertility (also called male factor or male factor infertility):

• history of prostatitis or genital infection
  
  
• testicular trauma or torsion
  
  
• history of precocious puberty (puberty occurring at a young age) or delayed puberty (puberty occurring at an older age)

• exposure to toxic substances or hazards on the job, such as lead, cadmium, mercury, ethylene oxide, vinyl chloride, radioactivity, and x-rays

• cigarette or marijuana smoke

• heavy alcohol consumption

• exposure of the genitals to high temperatures

• hernia repair

• undescended testicles

• prescription drugs for ulcers or psoriasis

• DES taken by mother during pregnancy

• mumps after puberty

What causes male factor infertility?
The main causes of male infertility can be divided into the following categories:

• sperm disorders
  Problems with the production and maturation of sperm are the most common causes of male infertility. Sperm may be immature, abnormally shaped, or unable to move properly. Or, normal sperm may be produced in abnormally low numbers (oligospermia) or seemingly not at all (azoospermia). This problem may be caused by many different conditions including the following:

• infectious diseases or inflammatory conditions such as the mumps virus
  
  
• endocrine or hormonal disorders such as Kallman's syndrome or pituitary problem 
  
  
• immunological disorders in which some men produce antibodies to their own sperm
  
  
• environmental and lifestyle factors
  
  
• genetic diseases (most are associated with sperm abnormalities, either directly or indirectly):

• cystic fibrosis - an inherited condition that typically involves the lungs and pancreas, but can present also as a cause of infertility with or without mild sinus problems; 6 to 10 percent of men with obstructive azoospermia have congenital bilateral absence of the vas deferens (CBAVD), which means they were born without the vas deferens; of these, 70 percent may have cystic fibrosis or carry a mutation in the cystic fibrosis gene.
  
  

• Noonan syndrome - an inherited condition which can occur in either males or females. In males, this syndrome can cause abnormal gonadal (testicular) function.
  
  

• myotonic dystrophy - an inherited condition with progressive multi-system involvement, resulting in infertility (underdeveloped testes and abnormal sperm production), in some cases.
  
  

• hemachromatosis - an inherited condition affecting iron storage. Eighty percent of men with hemochromatosis have testicular dysfunction.
  
  

• sickle cell disease - an inherited condition affecting the normal production of hemoglobin.
  
  

• sex reversal syndrome - a male who has the sex chromosomes of a genetic female (XX, instead of XY), resulting in azoospermia and other characteristics.
  
  

• androgen receptor gene mutations - an inherited condition in which a man is genetically male (46,XY), but has infertility due to a defect in receptors for testosterone.
  
  

• chromosomal abnormalities - men with an extra X sex chromosome, known as Klinefelter syndrome, often do not produce sperm or produce very low quantities of sperm.
  
  

• chromosome rearrangements - in some persons, there are the usual number of chromosomes (46) in the nucleus (center) of cells, but rearrangements in the chromosome material, where a piece of a chromosome has exchanged places with another, has taken place; men with either azoospermia or oligospermia have a higher frequency of chromosome rearrangements than is found in the general population.
  
  

• deletions in the Y chromosome - in some persons, there are the usual number of chromosomes (46) in the body cells, but small sections of the Y chromosome are missing or deleted; anywhere from 3 to 30 percent of men with either azoospermia or oligospermia have deletions in the Y chromosome.

• anatomical abnormalities
  Obstructions of the genital tract can cause infertility by partially or totally blocking the flow of seminal fluid. Some of these abnormalities may be of congenital (present at birth) origin or the result of a genetic defect. Others could have occurred due to infection or inflammation of the urogenital tract, surgery that left scar tissue in the genital tract, or the presence of varicose veins in the scrotum (scrotal varicoceles). 
  
  
• immotile cilia syndromes 
  In this condition, the sperm count is normal but the spermatozoa are non-motile such as in Kartagener's syndrome, an inherited disorder.
  
  
• mitochondrial deletions
  Mitochondria are structures in the cell responsible for energy production. There are actually a set of genes in the mitochondria, separate from the normal chromosome set contained in the nucleus. Recently, it has been discovered that these genes, when altered or deleted, can affect a person’s health and/or fertility.
  
  
• liver disease, renal disease, or treatment for seizure disorders
  
  
• other factors 
  Other factors may arise from the defective delivery of sperm into the female genital tract, which could be caused by impotence or premature ejaculation.

How is male factor infertility diagnosed?
In addition to a complete medical history and physical examination, diagnostic testing for male factor infertility may include the following:

• multiple semen analysis - at least two semen examples are collected on separate days to examine the semen and sperm for various factors, such as semen volume, consistency, and pH, and the sperm count, motility, and morphology (shape).

• other tests (to determine the cause of sperm abnormalities or diseases of the male reproductive system)

Treatment for male factor infertility:
Specific treatment for male factor infertility will be determined by your physician based on:

• your age, overall health, and medical history

• extent of the disease

• your tolerance for specific medications, procedures, or therapies

• expectations for the course of the disease

• your opinion or preference 

There is a range of treatment options currently available for male factor infertility. Treatment may include:

• assisted reproductive technologies (ART)
  This type of treatment may include the following:

• artificial insemination
  Artificial insemination involves the placement of relatively large numbers of healthy sperm either at the entrance of the cervix or into the partner's uterus, bypassing the cervix, to have direct access to the fallopian tubes.
  
  
• IVF, GIFT, and other techniques 
  In vitro fertilization (IVF) or gamete intra-fallopian transfer (GIFT) have been used for the treatment of male infertility. As is the case with artificial insemination, IVF and similar techniques offer the opportunity to prepare sperm in vitro, so that oocytes are exposed to an optimal concentration of high quality, motile sperm.
  
  
• microsurgical fertilization (microinjection techniques such as intracytoplasmic sperm injection, or ICSI) 
  This treatment is used to facilitate sperm penetration by injection of a single sperm into the oocyte. Fertilization then takes place under the microscope.

• drug therapy
  A small percentage of infertile men have a hormonal disorder that can be treated with hormone therapy. Hormonal imbalances caused by a dysfunction in the mechanism of interaction between the hypothalamus, the pituitary gland, and the testes directly affect the development of sperm (spermatogenesis). Drug therapy may include gonadotrophin therapy, antibiotics, or another medication deemed appropriate.

• surgery
  Surgical therapy in male infertility is designed to overcome anatomical barriers that impede sperm production and maturation or ejaculation. Surgical procedures to remove varicose veins in the scrotum (varicocele) can sometimes serve to improve the quality of sperm.

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