Assuming that there was not a problem in collecting the specimen, the absence of sperm on a semen analysis—a condition known as azoospermia—requires thorough evaluation. Azoospermia can be divided into two major categories: obstructive and nonobstructive.

Obstructive azoospermia occurs when the duct carrying the sperm from the testicle to the urethra becomes blocked. This blockage may be the result of previous surgery on the scrotum or testicle, or even follow repair of an inguinal hernia. During hernia surgery, the vas deferens may be inadvertently damaged or even cut.

Scar tissue that blocks the vas deferens can form either postoperatively or as the result of an infection (most commonly gonorrhea, though other infectious diseases may also cause blockage of the sperm duct).

Some men are born without a vas deferens on either side. Congenital bilateral absence of the vas deferens (CBAVD) is associated with the gene for cystic fibrosis and is a rather unusual presentation of cystic fibrosis as it occurs in the absence of any chronic lung disease. For this reason, any man with azoospermia associated with congenital absence of the vas deferens should undergo genetic testing to determine whether he carries the gene that causes cystic fibrosis.

Nonobstructive azoospermia results from dysfunctional sperm production as opposed to an anatomic issue and can represent a more problematic situation. The failure of sperm production in an otherwise normal testis may be the result of either a testicular issue or a pituitary or hypothalamus issue. If a hormonal evaluation reveals normal levels of prolactin and thyroid hormone, then testicular sperm production may have failed. If this finding is associated with an elevated FSH level, then the chance of finding any sperm production in the testis is quite unlikely. A testicular biopsy is often performed to assess whether any sperm are present within the testis. Even very low levels of sperm production may allow for attempts at IVF using ICSI. Genetic testing to rule out a chromosomal problem is often suggested in cases of very low or absent sperm production. We suggest that men undergoing a testicular biopsy arrange for cryopreservation (freezing) of viable sperm in order to avoid having to undergo a second biopsy procedure.

The use of IVF with ICSI can allow couples to successfully achieve pregnancy even in cases of obstructive or nonobstructive azoospermia. Sperm that is removed from the epididymis or the testicle may look excellent but is incapable of fertilizing an egg since it has not undergone the final changes that result in fully capacitated sperm. The introduction of ICSI in 1993 revolutionized the treatment of male factor infertility. To obtain sperm for use in IVF/ICSI, a needle aspiration of the testis or epididymis can be performed under local anesthesia in cases of obstructive azoospermia. If the male partner has nonobstructive azoospermia, a urologist usually performs a testicular biopsy in the hospital while the patient is under general anesthesia as sperm production may be severely impaired, necessitating the removal of more testicular tissue in order to have an adequate sample. In either case, the testicular tissue or the sperm aspirate can be frozen in liquid nitrogen and maintained relatively indefinitely. If a testicular biopsy reveals no mature sperm, then the only option is to use donor sperm or to pursue adoption.

Occasionally, the sperm retrieved through a testicular biopsy or needle aspiration is of exceedingly poor quality. In such cases, a repeat testicular biopsy on the day of egg collection for IVF or even use of a cryopreserved specimen from an anonymous sperm donor may be considered as a backup plan.

Rarely, men with diabetes or those taking certain antihypertensive medications may suffer from retrograde ejaculation. In this condition, there is no emission of fluid with male orgasm because all of the fluids travel backward into the bladder instead of out through the urethra. Retrograde ejaculation can easily be diagnosed by checking the post-ejaculation voided urine for sperm.

Sperm present in the man’s urine can be washed and used for either insemination or IVF. Pretreatment with bicarbonate the night before sperm collection may improve sperm quality by increasing the pH of the urine.

One final (and interesting) cause of azoospermia is anabolic steroid abuse. Some men with azoospermia may have used testosterone or other steroids as part of their strength and conditioning training. High doses of these steroids can suppress sperm production. Sperm production can be reinitiated in such patients by stopping the steroids and starting gonadotropin therapy (analogous to ovulation induction therapy in women). Although clomiphene citrate has been used to improve sperm quality in men, most studies reveal it to have little to no benefit.

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