How to evaluate the azoospermic male? ASRM committee recommendations

The Practice Committee of the American Society for Reproductive Medicine (ASRM) in collaboration with the Society for Male Reproduction and Urology recently issued guidelines about the diagnosis and evaluation of the azoospermic male partner. The committee opinion was published recently in journal Fertility and Sterility.

Of all the infertility cases about 30% is because of ‘male-factor’ of whom about 10-15% of men will receive the diagnosis of azoospermia. Recent studies have documented a decline in sperm count globally with a concurrent increase in male factor infertility.

Azoospermia is classified into 3 categories-pre-testicular, testicular, and post-testicular according to the etiology but in clinical practice, azoospermia is commonly classified as obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) which can be of central or testicular origin. 

 

Azoospermic men with normal size testes with normal serum follicle-stimulating hormone (FSH) levels are more likely to have obstructive azoospermia, while men with a significant elevation in FSH have a testicular failure, and thus testicular NOA.

On the other hand, low gonadotropins levels with low to low-normal T points towards a diagnosis of central NOA.

According to the American Society for Reproductive Medicine (ASRM) Practice Committee, the evaluation begins with a standard reproductive history and physical examination, followed by measurement of serum FSH and testosterone(T), luteinizing hormone (LH), free T, estradiol, and prolactin. Most experts state that an FSH >7.6 mIU/mL would be considered abnormal.

Semen volume and FSH levels play an essential part in determining the etiology of azoospermia. If men have low semen volume and normal FSH the lab test should be repeated after 2-3 days of abstinence, with attention to proper collection technique. A post-ejaculate urinalysis is advised to rule out retrograde ejaculation. If there is no retrograde ejaculation and semen pH is < 7.2, a transrectal ultrasound (TRUS) is the next step to identify a possible ejaculatory duct obstruction (EDO).

In men with normal semen volume, determining serum FSH and testicular volume is critical to decide in favor of testicular biopsy for the prognostic purpose. Elevation of serum FSH along with low testicular volume strongly suggests NOA. In case sperm retrieval is planned for ICSI, the testicular biopsy is deferred till the sperm retrieval when a biopsy sample is concurrently sent to the lab.

A normal testicular biopsy indicates an obstruction at some level in the reproductive tract. If the cause of OA is not iatrogenic, then the cause is a bilateral epididymal obstruction. It should be confirmed by surgical exploration. Vasography is only indicated if reconstructive surgery is planned simultaneously.

In men with the congenital bilateral absence of the vasa deferentia (CBAVD or vasal agenesis), unilateral renal agenesis should be ruled out. Most men with vasal agenesis will also have seminal vesicle hypoplasia or agenesis which manifests as low semen volume and pH.

CBAVD is also strongly associated with mutations of the CFTR gene. Hence, before planning a sperm retrieval for ICSI in men with CBAVD or congenital unilateral absence of the vas deferens (CUAVD), genetic testing should be offered to female partner to rule out her carrier status (∼4%) for CFTR gene.

Men with suspected NOA due to an elevated FSH and a normal ejaculate volume have bilateral testicular atrophy.  They should be offered genetic testing to exclude chromosomal abnormalities and Y-chromosome microdeletions (YCMD). A diagnostic testicular biopsy is not usually indicated in such cases. 

Low gonadotropins levels may be because of feedback inhibition secondary to exogenous T or illicit anabolic-androgenic steroid use, a high T level with suppressed gonadotropins will be confirmatory in such instances.

In men with markedly elevated serum FSH levels, the diagnostic testicular biopsy is only indicated when there is uncertainty about the etiology of the azoospermia- obstructive or nonobstructive. In all other cases, a testicular biopsy is done when sperm retrieval is planned for ICSI.

A diagnostic biopsy is also not necessary in patients with expected obstruction and normal FSH levels.

Full-text Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Male Reproduction and Urology

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