Deep Dive

Azoospermia

Azoospermia is a catch-all term used to describe situations where the lab finds no sperm during semen analysis tests. Roughly 1% of US males have azoospermia and it’s responsible for 10 – 20% of male infertility cases. This is one of the few male factor diagnoses where there is not much ambiguity about what’s going on, and what needs to be done.

For semen not to be produced, typically one of three things has gone awry: the testicles were not stimulated (pre-testicular azoospermia — 2% of cases), the testicles could not produce sperm (testicular azoospermia – 60% of cases), or sperm was produced, but not ejaculated (post-testicular azoospermia – 35 - 40% of cases).

Pre-testicular Azoospermia


Typically, pre-testicular azoospermia is driven by a hormone imbalance: the hypothalamus doesn't signal to the pituitary to secrete certain hormones, or that message is being delivered and the pituitary ignores it. Often the hormones that aren’t being produced are key to producing sperm: FSH, LH, and testosterone. (Related to this, men with azoospermia are two to three times more likely to eventually develop thyroid cancer.)

Most of the time, lifestyle factors like diet, obesity, drug use (including testosterone and steroids), are responsible, and so the effects can be reversed. Typically, the patient will be given supplements of FSH and LH, and tapered off of testosterone (if using), so the body will begin to produce the hormone naturally again. In about 90% of cases, men with pre-testicular azoospermia begin ejaculating sperm after roughly 6 months of treatment.

Testicular Azoospermia


In this situation, the testicles are properly stimulated (so the issue is not pre-testicular), but simply cannot produce sperm. This is also known as non-obstructive azoospermia, and is the form of azoospermia that is probably hardest to treat.

Diagnosing testicular azoospermia can be either relatively painless, or more complex. If the man records an elevated FSH or LH, it can be relatively easy to make the testicular azoospermia diagnosis. If those levels read normally, it may be unclear if the underlying issue is testicular in nature, or a blockage. If the urologist cannot find an obstruction (for instance, absence of a vas deferens, the duct that connects the testes to the urethra), then a biopsy might be in order.

Testicular azoospermia comes in a variety of types, some treatable, and others not. The issue may result from varicocele, in which case surgical treatment is an option with reasonable success.

In some cases, the testicles can produce sperm that are fully mature, and in that case, through an invasive procedure called microTESE, in conjunction with IVF and ICSI, sperm can be retrieved in about 60% of cases. Surprisingly, we haven’t seen data on what pregnancy or birth rates are after MicroTese plus IVF with ICSI.

In other circumstances, many of which are congenital, the odds of successful intervention are low and the couple may be faced with considering a sperm donor, or adoption.

Post-testicular Azoospermia


Typically post-testicular azoospermia is caused by some sort of blockage, namely a vasectomy, a missing vas deferens, or an infection in the ejaculatory duct. Occasionally, a trans-rectal ultrasound (TRUS) is needed to make a diagnosis. If it appears the man is missing the vas deferens, there is a major risk he is a carrier for cystic fibrosis, and at this point the couple should undergo carrier screening, including consulting with a genetic counselor, and discuss the risks of conceiving naturally.

Microsurgery of the reproductive tract returns sperm to the ejaculate of men who had a vasectomy in 70 – 95% of the patients, and between 30 – 75% can then father children without IVF. If the vasectomy has been in place for 15 years or longer, there is a 30% likelihood of conceiving without IVF. These are not easy procedures and the surgeon requires a wealth of experience.

In circumstances where the ejaculatory duct is blocked, surgery typically results in 50 – 75% of men producing sperm in their ejaculate, and 25% achieving pregnancy without IVF.

TESE and MicroTESE


In many circumstances for both obstructive and non-obstructive azoospermia, the urologist needs to retrieve sperm directly from the testicle. There are a variety of methods to do this, and the one that’s utilized depends on the skill of the urologist, and the risk to the patient.

For patients with testicular azoospermia, there is a fair amount of literature suggesting that MicroTESE should be the standard of care, with sperm detection rates of 61% vs. 40% for TESE, and likely less morbidity on account of less tissue extracted. What makes MicroTESE a more efficient procedure is that it allows the surgeon to project which tubules in the scrotum are more likely to contain sperm. MicroTESE is often significantly more expensive, around 50% more than TESE, and its availability relies on the number of qualified local urologists who can perform it.

For patients with non-obstructive azoospermia who require sperm retrieval, the American Urological Association seems to have no preference on where the retrieval should be from (testicle or epididymis), or the technique used.

Once sperm has been successfully extracted, it’s then used during IVF with ICSI to fertilize the woman’s eggs. Typically, in a cycle where IVF and ICSI are used with retrieved sperm, fertilization rates are 35 – 75%, pregnancy rates are 25 – 57%, and birth rates are 20 – 30%.