When couples experience difficulty conceiving, about 20% of the time a male factor is solely responsible for the cause; and males are a contributing factor in roughly 30 – 40% of cases. That’s more than men would like to admit, which is why it’s so important to diagnosis the actual problem quickly instead of letting the possibilities toy with your head.

This blog will review the recent recommendation from the American Society for Reproductive Medicine on the “Diagnostic Evaluation of the Infertile Male.”

Once a diagnosis of male factor infertility is established, the evaluation pursues three general areas:

  • Anatomic
  • Hormonal
  • Genetic

The Sperm Analysis

The WHO 5th edition in 2010 updated the lower limits of acceptable sperm parameters. A sperm analysis (SA) should be obtained between 2-5 days from the male’s last ejaculation. The most important values are: sperm concentration >= 15 million/mL; sperm motility >= 40%; and sperm morphology >= 4%. A normal SA does not ensure adequate fertilization potential and fertility, but an abnormal SA (depending upon the degree) does not preclude natural fertility. Following a medical history, one abnormal sperm analysis warrants an evaluation by a urologist trained in male reproduction, preferably fellowship trained. Irrespective of fertility, a severely abnormal sperm analysis may represent testicular cancer.

Of note, when there is a very low sperm count and low volume, post ejaculation analysis of urine may identify sperm. This condition is called retrograde ejaculation and can be seen in men with diabetes or following pelvic surgery. Fortunately this is easily treated by obtaining sperm from the bladder after adjusting for pH then followed by intrauterine insemination of the washed sperm.

Initial Evaluation

A comprehensive reproductive history should consist of reviewing intercourse frequency, prior pelvic/sexually transmitted infections, exposure to sperm impairing agents e.g. chemotherapy and heat, childhood/adult diseases, and medications. True infections demonstrated by white blood cells (not round cells) in the sperm analysis can impair fertility. The history is followed by a thorough physical examination including assessment for appropriate sexual development, the presence of a Varicocele and normal anatomy. Specifically, the absence of the male reproductive Vas Deferens Ducts (Congenital Bilateral Absence of the Vas Deferens or CBAVD) not only results in no sperm in the ejaculate (azoospermia) but also is highly correlative with being a carrier for Cystic Fibrosis.

Appropriate testing for the infertility male may include scrotal ultrasound to confirm anatomy, hormone testing (may include FSH, LH, testosterone and prolactin), and genetic screening, specifically a karyotype and microdeletions on the Y chromosome. Testing for antisperm antibodies (ASA) is not recommended since it is a rare cause of infertility. While routine ASA testing is not necessary, the presence in men with azoospermia suggests an obstructive cause for the lack of sperm in the ejaculate.

Sperm Function Testing

Nonmotile sperm can undergo special testing to determine which sperm are viable to use with IVF-ICSI. Further, abnormal DNA fragmentation impairs sperm function and may increase miscarriage. Unfortunately, there is no proven treatment for abnormal DNA fragmentation results so this testing is not currently recommended. Several other tests are available such as sperm penetration assays but they have not been proven to effect treatment.


CBAVD has an 80% association with carrier status for Cystic Fibrosis and it is recommended to test the female partner for Cystic Fibrosis despite a negative test in the male due to the potential of missed mutations. Further, chromosomal abnormalities are present with severely low to absent sperm in 5-15% of men so a karyotype is recommended. In this same group of men, there is a 7% risk of microdeletions in the Y chromosome that is often inherited and transmissible to sons. Depending on which microdeletion, one may predict the chance for sperm retrieval on testicular biopsy. Lastly, sperm may possess chromosome abnormalities contributing to infertility and miscarriage but testing has limited application.

Men with severe low sperm (<5million/mL) or no sperm should have a genetic evaluation and option for genetic counseling prior to IVF.

A thorough evaluation for a male factor should occur after normal attempts for natural fertility or sooner if a predisposed condition exists.

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