Infertility is defined as the failure to conceive despite one year of regular unprotected intercourse. A couple should consider evaluation sooner if either partner has a known risk factor for infertility (e.g., advanced female age, male with a history of undescended testicles), or if the couple has concerns about their fertility potential. In most cases, it is recommended that both partners be evaluated simultaneously to prevent any delays in successful treatment.
Approximately 15% of couples will experience infertility, and of these, 20% will have a male factor that is solely responsible; male factors will contribute in an additional 30% of cases. Generally, male infertility is identified by abnormalities on a semen analysis; however, other issues can contribute to infertility despite normal semen.
The causes of male infertility are widely varied, and are best evaluated by a urologist who specializes in male reproductive health. Some causes of male infertility can be identified and reversed (or improved) with specific surgery or medication while other causes can be identified but not reversed. Occasionally the underlying cause of infertility or an abnormal semen analysis cannot be identified, in which case it is termed idiopathic. These cases may be amenable to non-specific or empiric treatment to improve the chances of conception.
The purpose of the male infertility evaluation is to: 1) identify and correct the reversible causes of male infertility with the goal of allowing a couple to conceive through intercourse, or with the least amount of technology; 2) identify irreversible conditions that may be amenable to treatment with assisted reproductive technology (ART) using the male partner’s sperm; 3) identify irreversible conditions in which the man’s sperm are not obtainable, in which case the couple may consider donated sperm or adoption; 4) identify medical diseases that may be associated with infertility and require treatment; and 5) identify specific genetic causes of infertility that may be transmitted to and impact offspring.
What to expect during an evaluation
History and physical exam
A man’s evaluation begins with a thorough reproductive, medical and surgical history. Important components of this history include: 1) duration of infertility, coital timing and frequency, and sexual health; 2) prior paternity or fertility treatments; 3) childhood illnesses and development; 4) medical illnesses, prior infections, and medications; 5) prior surgeries or traumas; and 6) exposure to potential gonadal toxins, such as heat, radiation, chemical solvents or pesticides.
A thorough physical exam includes assessment of body habitus, hair distribution, breast development and the external genitalia. Specific attention is given to the size and consistency of the testicles as well as the structures within the spermatic cords: the vasa deferentia and possible varicoceles.
A semen analysis is the most important laboratory evaluation for a man with infertility, and in many circumstances is performed prior to the initial consultation. To allow for an accurate interpretation of the results, the test must be performed in a standardized fashion: 2 to 5 days of ejaculatory abstinence; no exposure to lubricants that may be toxic to sperm; and maintenance of the specimen at body temperature (or near to) with delivery to the laboratory within one hour. A semen analysis provides information on the volume of the ejaculate, sperm concentration and motility, and appearance of sperm under the microscope (morphology). Reference values for semen are set forth by the World Health Organization (WHO) (Table 1). Men may have significant variation in their semen parameters; therefore it is important to have at least two semen analyses before any conclusions are drawn. Further, there can be laboratory variation in how semen analyses are performed so your doctor may ask you to perform additional tests to confirm results.
Table 1. WHO Semen Analysis Reference Values
1.5 – 5.0 mL
Total motile sperm count
>20 million motile sperm
>30% normal WHO 1992
>14% normal Kruger Strict
Specialized tests can be performed on semen and may be recommended by your physician under certain circumstances. These tests include assessment of leukocytes, anti-sperm antibodies, reactive oxygen species, and sperm DNA integrity. If the ejaculate volume is low, a post-ejaculate urinalysis should be performed to evaluate for retrograde ejaculation.
The testes produce male hormones (testosterone and its metabolites) and mature sperm in response to specific hormonal signals from the brain (the hypothalamus and the anterior pituitary gland). Hormonal abnormalities can contribute to poor sperm production (spermatogenesis) and may be correctable in certain circumstances. The endocrine tests include measurement of serum testosterone (T), follicle stimulating hormone (FSH), lutenizing hormone (LH), prolactin (PRL), and occasionally estradiol (E2). Not all men require endocrine evaluation, but testing should be done when ejaculate volume is low, sperm concentration is <10 million/mL, or if there are specific symptoms or circumstances associated with endocrinopathy.
Ultrasound (US) is a non-invasive imaging test that utilizes high frequency sound waves to visualize internal structures of the body. US of the scrotum and its contents may be performed when physical exam findings are unclear. Transrectal US (TRUS) should be performed when the ejaculate volume is low without other explanation. The purpose of TRUS is to visualize the prostate, seminal vesicles and ejaculatory ducts to evaluate for ejaculatory duct obstruction (EDO).
Genetic abnormalities may cause infertility by affecting spermatogenesis or sperm transport. Certain genetic abnormalities that cause male infertility can be transmitted to and affect the health of offspring. Therefore, the results of genetic testing may not only direct the approach to therapy, but can also provide information on the presence of abnormalities that may impact offspring. The most common known genetic factors that contribute to male infertility are: 1) Y-chromosomal microdeletions that result in azoospermia or oligospermia, 2) Klinefelter’s Syndrome, an abnormality of chromosomal number that results in poor testicular function, and 3) cystic fibrosis gene mutations that result in congenital absence of the vas deferens (CBAVD).
Specific Disorders and Treatment Approach
Once diagnosis is complete, there are three approaches to treating the infertile male. Medical therapy may be used to reverse or improve certain types of inflammation or hormone deficiency. Surgery may be recommended to treat problems with the male anatomy, such as ductal obstruction (from vasectomy or EDO) or varicocele. If neither medical nor surgical therapy is appropriate, assisted reproductive technologies should be considered. Even in cases where no sperm are found in the ejaculate, sperm may be retrieved from the testicle using minimally invasive techniques. Once sperm is retrieved, pregnancy is possible with the use of intracytoplasmic sperm injection (ICSI).
Hypogonadotrophic hypogonadism (HH) results when the testicles receive inadequate hormone signals from to the brain to function normally. The causes of HH are widely varied but include medical or surgical diseases. In this situation, the replacement of the pituitary hormones (FSH and LH) can restore the function of the testes.
Inflammation of the prostate or other parts of the reproductive tract can lead to poor sperm production or function. If there is evidence of an infection, treatment with an antibiotic is appropriate. In some cases, inflammation may be present without infection in which case empiric therapy with anti-inflammatory or antioxidant medications may be beneficial.
Anejaculation (inability to ejaculate)
Anejaculation has a variety of causes that include pelvic nerve damage from diabetes mellitus, multiple sclerosis or abdominal-pelvic surgery and spinal cord injury. It is important to distinguish ejaculatory failure from erectile dysfunction (the inability to achieve an erection), premature ejaculation (ejaculating before one desires) and retrograde ejaculation (ejaculating into the bladder and not into the penis). Rectal probe electroejaculation is a commonly performed technique that may enable anejaculatory patients to produce an ejaculate capable of achieving a pregnancy. With this technique, the pelvic nerves undergo controlled stimulation such that a reflex ejaculation is induced and semen can be collected.
A varicocele is defined as dilated, dysfunctional veins within the spermatic cord and scrotum. Varicoceles may be associated with low sperm count and motility. An improvement in semen quality can be expected in roughly two-thirds of patients who have varicocele repair and research has suggested that natural pregnancy rates increase after treatment. The varicocele remains the most correctable factor when poor semen quality is discovered, but since it is very common, the operation should only be considered if other infertility risk factors are absent. Varicoceles can be corrected by venous embolization, laparoscopy or through a small inguinal or subinguinal incision.
Vas Deferens or Epididymal Blockage
Infection or traumatic injury to the genital tract can result in scarring and blockage of the male reproductive tract, however, the most common cause of a surgically correctable blockage is prior vasectomy. Roughly 6% of men who have a vasectomy undergo a vasectomy reversal (vasovasostomy or epididymovasostomy). The success of a vasectomy reversal depends on many factors, the most important of which are the skill of the surgeon and the findings at the time of surgery. In the best of circumstances, 85-99% of patients can expect a return of sperm after vasovasostomy. When surgical correction of an obstructed vas or duct is not desired, sperm extraction techniques can be performed in conjunction with ART.
Ejaculatory Duct Obstruction
Ejaculatory duct obstruction is diagnosed in approximately 10% of men without sperm in the ejaculate. Blockage of the ducts within the prostate may be caused by cysts, stones, or scar tissue. The condition may be effectively treated with an outpatient procedure that involves resection of the ducts as they traverse the prostate.
Sperm Extraction Procedures
Intracytoplasmic sperm injection (ICSI) has revolutionized the treatment of male infertility. With this technology, only a small number of healthy sperm are required to foster pregnancy. This has led to the recent development of new surgical techniques to provide viable sperm for egg fertilization from men with low or no sperm count. Potential sources of sperm include the vas deferens, epididymis and testicle. The underlying reason for azoospermia will ultimately dictate the source of sperm that is used and the chances for successful retrieval. It is important to realize, however, that in vitro fertilization (IVF) technology with intracytoplasmic sperm injection is required to achieve a pregnancy with these extraction procedures, and thus success rates are intimately tied to a complex and complementary program of assisted reproduction for both partners.