Causes and Risk Factors
Common causes for male infertility are impaired sperm production, impaired sperm delivery, and testosterone deficiency (hypogonadism).
Infertility can result from a condition that is present at birth (congenital) or can develop later (acquired). Causes for infertility include the following:
• Defect or obstruction in the reproductive system (e.g., cryptorchidism, anorchism)
• Disease (e.g., cystic fibrosis, sickle cell anemia, sexually transmitted disease [STD])
• Hormone dysfunction (caused by disorder in the hypothalamic-pituitary-gonadal axis)
• Infection (e.g., prostatitis, epididymitis, orchitis)
• Injury (e.g., testicular trauma)
• Medications (e.g., to treat high blood pressure, arthritis)
• Metabolic disorders such as hemochromatosis (affects how the body uses and stores iron)
• Retrograde ejaculation (i.e., condition in which semen flows backwards into the bladder during ejaculation)
• Systemic disease (e.g., high fever, infection, kidney disease)
• Testicular cancer
Retrograde ejaculation occurs when impairment of the muscles or nerves of the bladder neck prohibit it from closing during ejaculation. It may result from bladder surgery, a congenital defect in the urethra or bladder, or disease that affects the nervous system. Diminished or "dry" ejaculation and cloudy urine after ejaculation may be signs of this condition.
Hypogonadism may be present at birth (congenital) or may develop later (acquired). Causes of the condition are classified according to their location along the hypothalamic-pituitary-gonadal axis:
• Primary, disruption in the testicles
• Secondary, disruption in the pituitary gland
• Tertiary, disruption in the hypothalamus
The most common congenital cause is Klinefelter syndrome. This condition, which is caused by an extra X chromosome, results in infertility, sparse facial and body hair, abnormal breast enlargement (gynecomastia), and smaller than normal testes.
Congenital hormonal disorders such as leutenizing hormone-releasing hormone (LHRH) deficiency and gonadotropin-releasing hormone (GnRH) deficiency (e.g., Kallmann syndrome) also may cause testosterone deficiency.
Other congenital causes include absence of the testes (anorchism; may also be acquired) and failure of testicles to descend into scrotum (cryptorchidism).
Acquired causes for testosterone deficiency include the following:
• Damage to the pituitary gland, hypothalamus, or testes
• Glandular malformation
• Head trauma affecting the hypothalamus
• Infection (e.g., meningitis, syphilis, mumps)
• Isolated LH deficiency (e.g., fertile eunuch syndrome)
• Testicular trauma
• Tumors of the pituitary gland, hypothalamus, or testicles
To learn more about testosterone deficiency including symptoms, diagnosis, and treatment, see details on testosterone deficiency.
The search for the cause of infertility usually begins with the male, because male examination and testing is less complicated. A thorough examination and a review of the man's medical and surgical history are necessary, because chronic disease, pelvic injury, childhood illness, abdominal or reproductive organ surgery, recreational drug use, and medications can affect fertility. Physical examination may detect testicular irregularities (e.g., varicocele, absence of vas deferens, tumor), evidence of hormonal disorders (e.g., underdeveloped reproductive organs, enlarged breast tissue), or evidence of testosterone deficiency.
Assessing reproductive-fertility history is important; specialists typically inquire about the following:
• Early puberty (may result from hormonal disorder)
• Late puberty (may result from Kallmann's syndrome)
• Previous pregnancy
• Sexual intercourse timing (understanding ovulation)
• STDs (can cause scarring, obstruction)
• Use of lubricants (may kill sperm)
A semen analysis, usually performed by a fertility specialist, is used to examine the entire ejaculate, because seminal fluid can affect sperm function and movement. Generally, three semen samples are taken at different times to account for variables such as temperature and error. Most specialists prefer three samples that differ no more than 20% from one another before proceeding with diagnosis.
Six sperm factors are analyzed in semen analysis:
• Concentration (sperm/milliliter; cc)
• Morphology (sperm shape; normal structure associated with sperm health)
• Motility (or mobility; % sperm movement)
• Standard semen fluid test (thickness, color)
• Total motile count (total number of moving sperm)
• Volume (total volume of ejaculate)
Azoospermia is the absence of sperm in the semen. Men with normal reproductive tracts and hormone systems can have azoospermia due to a lack of sperm-producing tissue in the testes or an obstruction. Obstructions can be viewed with x-ray. The World Health Organization has established criteria for normal sperm concentration, morphology, and motility. Total motile sperm count, which should be about 40 million, is calculated by multiplying volume by concentration by motility.
The semen fluid test looks at factors that may impede sperm performance. Abnormally thick semen may cause sperm to swim more slowly through cervical mucus, obstructing fertilization. Abnormal sperm shape (i.e., disfigured or multiple heads or tails) usually indicates poor sperm health. Infertility is likely if 60% or more of sperm in semen is abnormally shaped.
Other tests are concerned specifically with sperm's ability to swim through cervical mucus and bind to and penetrate an egg. The postcoital Sims-Huhmer, or sperm-mucus interaction test, examines whether the sperm are able to swim through the female reproductive tract. This ability is referred to as forward progression. In the middle of the menstrual cycle, the cervical mucus becomes watery. Intercourse is recommended during this time, followed, the next day, with an inspection of the mucus to determine if
• enough semen was delivered to the cervix;
• sperm are healthy and do not show large numbers of clumped, motionless, or dead cells; and
• sperm are swimming energetically through the cervical mucus.
The sperm penetration assay (SPA), or sperm-oocyte interaction test, examines the ability of sperm to penetrate the egg by combining it with a hamster egg. The immunobead test looks at semen for the presence of antibodies that damage sperm.
Post-ejaculation urinalysis may identify diseases that affect fertility, such as kidney disease, diabetes, and repeated urinary tract infection (UTI). Blood tests identify disorders that impair testosterone and sperm production.
At least one-half of male fertility problems can be treated so that conception is possible. There are three categories of treatment for male infertility:
• Assisted reproduction
• Drug therapy
Assisted reproduction therapy includes methods to improve erectile dysfunction, induce ejaculation, obtain sperm, and inseminate an egg:
o Sperm retrieval and washing
o In vitro fertilization (IVF)
o Intracytoplasmic sperm injection (ICSI)
o Gamete intrafallopian transfer (GIFT)
Electroejaculation: This procedure can be used to produce ejaculation when neurological dysfunction prevents it. An electrical rectal probe generates a current that stimulates nerves and induces ejaculation; semen dribbles out through the urethra and is collected. Retrograde ejaculation is associated with the procedure and sodium bicarbonate is usually taken the day before to make the urine alkaline (nonacidic) and nondetrimental to sperm. Candidates for electroejaculation include men who have undergone testis removal (orchiectomy), retroperitoneal lymph node dissection (RPLND), and those with spinal cord injuries.
Sperm retrieval: This technique is used to obtain sperm from the testes or epididymis when obstruction, congenital absence of the vas deferens, failed vasectomy reversal, or inadequate sperm production causes azoospermia. Using a technique called micro epididymal sperm aspiration (MESA), a surgeon makes an incision in the scrotum and gathers sperm from the epididymis, the elongated, coiled duct that provides for the maturation, storage, and passage of sperm from the testes. Percutaneous epididymal sperm aspiration (PESA, or fine needle aspiration) is similar to MESA but does not involve microsurgery. A physician uses a needle to penetrate the scrotum and epididymis and draws sperm into a syringe. Testicular sperm extraction (TESE), the removal of a small amount of testicular tissue, is used to retrieve sperm from men with impaired sperm production, or when MESA fails. (see also Testis Biopsy)
These procedures are done under local anesthesia, usually take about 30 minutes, and may cause pain and swelling.
Sperm washing: This procedure isolates and prepares the healthiest sperm for insemination. Sperm and washing medium are combined and spun rigorously (centrifuged) and the process is repeated if necessary. The process separates sperm from white blood cells and fatty acids (prostaglandins) in the semen that may hinder sperm motility. It also concentrates sperm, which increases the chance for conception.
Sperm retrieved by MESA, PESA, or TESE may be used in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). IVF involves combining eggs with sperm in a laboratory, providing proper fertilization conditions, and transferring the resulting embryos to the uterus. To retrieve an egg, a specialist uses ultrasound to guide a fine needle through the vaginal wall and into the ovary or makes an incision in the abdomen to get to the ovary (laparoscopy). Once the eggs are retrieved, they are combined with prepared sperm in a sterile dish for 2 to 4 days. After fertilization, the embryos are transferred to the uterus. IVF is used most commonly for infertility caused by female reproductive abnormalities.
Intracytoplasmic sperm injection (ICSI) may be used with immotile sperm during in vitro fertilization. Using a tiny glass needle, one sperm is injected directly into a retrieved mature egg. The egg is incubated and transferred to the uterus.
Fertilization occurs in 50% to 80% of cases and approximately 30% result in a live birth. The egg may fail to divide or the embryo may arrest at an early stage of development. Younger patients achieve more favorable results and poor egg quality and advanced maternal age result in lower success rates.
ICSI does not increase the incidence of multiple pregnancies. Long-term information about the health and fertility of children conceived through this procedure is not available because it was first performed in 1992.
While excess sperm from MESA or PESA can usually be frozen for future use, most TESE-derived sperm are not of sufficient quality or quantity for frozen storage (cryopreservation). Multiple MESA or PESA procedures are not recommended, since repetition can lead to scarring.
Gamete intrafallopian transfer (GIFT) This procedure is recommended for couples with unexplained fertility problems and normal reproductive anatomy. Mature eggs and prepared sperm are combined in a syringe and injected into the fallopian tube using laparascopy. Embryos that result from this procedure naturally descend into the uterus for implantation.
Average conception rate for these procedures is about 30%.
Drug therapy for male infertility includes medications to improve sperm production, treat hormonal dysfunction, cure infections that compromise sperm, and fight sperm antibodies. The administration of testosterone is similar to that used to treat testosterone deficiency. Tamoxifen (Nolvadex®), an antiestrogen agent, may be used to stimulate gonadotropin (a male hormone) release, which leads to testosterone production. Antibiotics, like levofloxacin (Levaquin®) and doxycycline (Periostat®), are used to treat fertility-impairing infections of the urinary tract, testes, and prostate, and STDs.
Surgery for male infertility is performed to treat reproductive tract obstruction and varicocele. Vasoepididymostomy is a microsurgical procedure that corrects obstruction in the coiled tube that connects the testes with the vas deferens (epididymis). Obstructions commonly result from STDs and also include cysts and tubal closure (atresia), which is usually genetic. Vericocelectomy, the removal of a varicocele from the testes, often results in increased sperm count.