Reversible Semen Analaysis Factors

Reversible Semen Analysis Factors

This section reviews potentially reversible male-factor problems that can be uncovered with a careful review of the semen analysis results: low ejaculate volume, acidic semen pH or fructose negative, abnormal viscosity or liquefaction, and pyospermia (elevated numbers of white blood cells in the semen).


Abnormal Ejaculate Volume

 

Most labs report a normal ejaculate volume as above 1.0 cc to 2.0 cc, and the 2010 WHO guidelines use 1.5 cc as the lower limit of normal). I personally use 1.0 cc as the cutoff level for normal, although men with persistently borderline volumes (around 1.0 cc) should probably be checked for problems such as retrograde ejaculation. Usually, however, when I see a patient with a borderline ejaculate volume, it is later found to be normal upon repeat testing after a sufficient period of abstinence (see below).

Labs often report an upper limit on normal volume (for example, 6.0 cc), but I am not usually concerned about ejaculate volumes higher than this. If I see an ejaculate volume that is very high (for example, 20 cc) in someone with a neurologic disorder or someone with prior urethral surgery, then I get suspicious that the ejaculate may contain some urine that is leaking out with the ejaculate (in which case the pH should be acidic, reflecting that acidity of the urine). This is a rare finding, though, and high ejaculate volumes are typically fine, just representing a more robust production of fluid volume by the prostate and seminal vesicles.

A more worrisome finding is to have a low ejaculate volume, less than 1.0 cc. The most common reason for a low ejaculate volume is a failure to collect the entire specimen in the collection cup. It is always important to let the lab know if you have missed part of your ejaculate collection (as well as a rough estimate of what percentage of the specimen was lost) so that this can be taken into consideration during review of the test results.

 

Possible Causes of Low Ejaculate Volume

 

If none of the specimen was missed on collection, then the most common reasons for a low ejaculate volume include:

1) Short abstinence interval. Before providing a specimen for semen analysis, you should abstain from sexual activity of any kind, including masturbation, for two to five days. If you abstain for less than two days, the seminal vesicles may not have time to fully recharge, and this can contribute to a lower than normal ejaculate volume.

2) Low testosterone levels. The functions of the seminal vesicles and prostate gland are influenced by testosterone levels. Low testosterone levels can lead to a decrease in ejaculate volume in some men.

3) Retrograde ejaculation. This is a situation where the bladder neck does not tighten down as it should during ejaculation, and either all or part of the ejaculate flows backward into the bladder.  Post-ejaculatory urinalysis testing can be used to evaluated for the presence of retrograde ejaculation.  See the “Ejaculatory Dysfunction" section of this website for more details.

4) Ejaculatory dysfunction. This occurs when the muscular vas deferens does not properly transport the sperm from the epididymis to the urethra. A severe form of this, in which no fluid comes into the urethra at all, is called anejaculation. Common reasons for ejaculatory dysfunction include neurologic problems (such as spinal cord injury or diabetes mellitus) and certain medications (such as antidepressants). See “Ejaculatory Dysfunction” section later for more information using the link above.

5) Ejaculatory duct obstruction (EDO). In men with EDO, the fluid from the vas deferens and seminal vesicles is blocked from entering the urethra. This can be either a partial or complete blockage. See “Ejaculatory Dysfunction" section (link above) for further information on EDO.

6) Seminal vasculopathy. The seminal vesicles can become dysfunctional and fail to contract, leading to decreased amounts of seminal vesicle fluid entering into the ejaculate. Neurologic problems, such as diabetes mellitus, are the most common cause of seminal vasculopathy.

7) Dehydration. If a man is very dehydrated at the time of specimen collection, it can potentially play a role in decreased ejaculate volumes, although this has not been studied extensively. For men with a borderline ejaculate volume, I recommend that they come in well hydrated for any follow-up semen analysis testing, drinking enough fluids to keep the urine pale yellow (generally a good sign of adequate hydration).


Acidic Semen pH or Fructose Negative

 

The pH of the ejaculate is normally alkaline, with a pH of 7.5 or higher (the seminal vesicles produce a large volume of alkaline fluid, substantially more than the acidic fluid produced by the prostate). The seminal vesicles also produce fructose. So when the ejaculate has an alkaline pH and contains fructose, then fluid from the seminal vesicles is successfully entering the ejaculate.

The ejaculatory ducts carry the fluid from the vas deferens and seminal vesicles to the urethra, where it is joined by the prostatic fluid. Complete blockage of the ejaculatory ducts blocks all fluids coming from the testicles and seminal vesicles, so that only fluid from the prostate enters into the ejaculate. (See “Ejaculatory Dysfunction” section in this website for more information on ejaculatory duct obstruction.)

Therefore men with complete ejaculatory duct blockage typically have no sperm at all in the ejaculate (azoospermia), low ejaculate volume (less than 1.0 cc), acidic semen pH (under 7.5) and no fructose in the semen.

 

Other potential causes for abnormalities in semen pH and fructose include:

1) Lab error. Because of this possibility, when the results of the semen analysis don’t match up with what seems to be going on in the man’s body, I recommend repeat testing to rule out a simple error.

2) Incomplete collection. The last part of the semen that is ejaculated contains most of the seminal vesicle fluid. So if the last part of the specimen wasn’t collected in the container, the results could come back as abnormal.

3) Seminal vesicle inflammation. This usually causes elevated levels of semen white blood cells.

 

Of note, many fertility experts feel that semen fructose testing should never really be needed, since low volume, a complete lack of sperm, and an acidic pH should be enough to clearly indicate the presence of ejaculatory duct blockage or absence.


Abnormal Semen Liquefaction and Viscosity

 

The fluid from the seminal vesicles causes sperm to stick together, or coagulate, in order to hold the sperm near the cervical opening and protect them from the harsh vaginal environment. The enzymes in the prostatic fluid then cause the semen to gradually liquefy, thereby allowing the sperm to enter the cervical canal. The rate at which the semen liquefies is often measured as viscosity (with a normal result being under 2) or liquefaction time (with normal ranging between 5 and 25 minutes).

Sometimes a semen analysis will show a prolonged liquefaction time (more than 30 minutes) or abnormal viscosity (over 2). In most circumstances, a repeat analysis—especially one performed at a fertility-specific lab—will show normal results, so nothing further needs to be done.

 

However, a persistently abnormal finding could signify one of the following problems:

1) Dehydration. Dehydration can lead to increased semen viscosity. As noted above, I recommend repeat testing with attention to proper hydration beforehand. A good goal is to drink enough to keep the urine pale yellow.

2) Infection or inflammation. In some circumstances, infection or inflammation of the genital duct (especially of the prostate) can increase semen viscosity. High levels of white blood cells (pyospermia) are typically present if there is an active infection or inflammation. See below for more details on pyospermia.

3) Improper semen collection. Most of the prostate fluid is in the first third of the ejaculate, while the seminal vesicle fluid is generally in the last part of the specimen. If part of the collection is missed, this can have an impact on the coagulation and liquefaction of the specimen, depending on which part was lost.

 

Persistent high sperm viscosity or elevated liquefaction times are rare in the absence of dehydration or infection, but where either is a problem, it can be generally be overcome with sperm washing combined with intrauterine insemination (see "Female Fertility Treatments" section). If questions arise concerning the fertility impact of abnormal semen liquefaction, post-coital testing can be done to see if sperm are efficiently making it into the cervical canal (see “Post-Coital Testing” in "Uncommonly Used Sperm Tests" section of this website).


Elevated White Blood Cells (Pyospermia)

 

Pyospermia, or an elevated number of white blood cells (WBCs) in the semen, signifies the presence of inflammation within the male genital duct system. The laboratory diagnosis of pyospermia can be difficult, since immature sperm cells look very similar to WBCs in a semen specimen (both of which are referred to as "round cells"). For details on how to distinguish whether elevated numbers of so-called round cells in the semen actually represent the presence of pyospermia, see the "Other Semen Analysis Parameters" section of this website.

While an increased number of immature sperm cells generally is not considered to be clinically significant, inflammation in the genital duct system can have a significant negative impact on the fertility potential of some men. Inflammation can be due to either an infection (bacterial, viral, fungal) or to a non-infectious cause (for example, nonspecific inflammation of the prostate or epididymis). Only about 20 percent of genital duct inflammation seen in male infertility patients is due to an infection.

 

Fertility Impact of Pyospermia

A normal by-product of the body’s metabolic processes is reactive oxygen species (ROS), also called free radicals (for more information, see the "Oxidative Stress" section of this website).

Under normal circumstances the body is very well equipped to mop up these ROS before they can cause any damage to cells, tissues, or organs. Small amounts of ROS are produced by the sperm themselves, but white blood cells generate very large amounts of these damaging substances. In pyospermia, with its elevated levels of white blood cells, the increased amounts of ROS can overwhelm the body’s cleanup mechanisms, resulting in oxidative stress. Sperm are especially sensitive to oxidative stress-related damage because of the compact structure of their DNA (genetic material), their natural lack of antioxidants, and their inability to effectively repair damage.

 

Pyospermia has been associated with an increased risk of several male reproductive problems, including:

      1) Decreased sperm density, motility, and morphology

      2) Elevated levels of sperm DNA fragmentation

      3) Decreased pregnancy rates and poor embryo progression with IVF

      4) Inflammation-related formation of anti-sperm antibodies

 

Evaluation of Pyospermia

Clinically significant pyospermia is typically considered to be a white blood cell count over 1 million per cc or a WBC count of over 10–15 per high power field (hpf) (different labs use different methods for counting WBCs).

It is important to distinguish between asymptomatic pyospermia and symptomatic pyospermia. In asymptomatic pyospermia, a man’s semen analysis shows elevated WBC, but he has no symptoms.

Men with symptomatic pyospermia have elevated levels of semen WBCs in addition to symptoms of inflammation, which can include:

1) Discomfort in the scrotal area or in the perineum (the region behind the scrotum where the prostate gland sits)

2) Urinary symptoms, such as burning with urination, needing to urinate frequently, discomfort with urination, or cloudy foul-smelling urine

3) Urethral discharge (discolored fluid draining from the end of the penis)

 

In patients coming in for fertility-related reasons, asymptomatic pyospermia is much more common than symptomatic pyospermia. If there are symptoms associated with the elevated WBC count, then the risk of an active infection is significantly increased, and urine testing is indicated. Possible tests include a urinalysis, a urine culture, or screening for chlamydia and gonorrhea (STDs typically can be diagnosed by testing the urine, but sometimes a urethral swab is needed).

 

Diagnostic codes that can be used for these tests include:

             Diagnosis                 ICD-10 Code

             Acute cystitis                   N30.0

            Chronic cystitis                N30.2

            Prostatitis                         N41.9

            STD screening                 Z11.3

 

Treatment of Asymptomatic Pyospermia

As mentioned above, most men being evaluated for fertility who are found to have elevated levels of WBCs in their semen have asymptomatic pyospermia. In about 80 percent of these cases, the pyospermia is from non-infectious causes, meaning that somewhere in the genital duct system (most commonly the prostate) there is some inflammation not caused by an infection. Asymptomatic prostatitis, or prostate inflammation, is fairly common; usually no cause can be found.

Because most men with pyospermia do not have an infection, some fertility specialists choose not to treat them with antibiotics, and instead rely only on only anti-inflammatory medications to clear the WBCs from the genital tract. I would not want to miss the 20 percent of men whose pyospermia is the result of an infection, and so I usually treat all cases of pyospermia with a combination of antibiotics and anti-inflammatory medications. It generally takes several weeks before these medications have an effect in the genital duct system and the WBC count falls.

 

The regimen I typically use is:

1) Antibiotic for three to four weeks (sometimes as long as six weeks), either ciprofloxacin 500 mg twice a day or doxycycline 100 mg twice a day

2) Anti-inflammatory medication while taking the antibiotic; I generally recommend naproxen (Aleve) 220mg, 2 pills by mouth twice a day (with breakfast and dinner).

 

Naproxen can be bought over the counter inexpensively.  There is also a wide array of prescription anti-inflammatory medications that can be taken instead of ibuprofen, such as oxaprozin (Daypro) and celecoxib (Celebrex). These have the advantage of needing to be taken less often than naproxen. However, they are significantly more expensive and are not felt to be more effective than ibuprofen in their anti-inflammatory effect. Medications such as celecoxib are also marketed as having less gastrointestinal side effects, but they have been associated with an increased risk of cardiovascular events with prolonged use. Before taking anti-inflammatories, it is important to check with your doctor if you have a history of stomach ulcers, gastroesophageal reflux disease (GERD), or decreased kidney function or kidney disease.  Mild stomach upset can be managed with a trial of over-the-counter Pepcid or Prilosec.  However, for persistent or worsening symptoms, you should stop your anti-inflammatory and check with your doctor.

It takes time for inflammation to subside, so I recommend a repeat semen analysis four to six weeks after beginning treatment for pyospermia. I’m looking for a normal WBC level, under 1 million per cc. If WBC levels are decreasing but are still above normal at the time of the retest, then a third semen analysis ten to twelve weeks later may be indicated.

 

Treatment of Symptomatic Pyospermia

Treatment of symptomatic pyospermia is dependent on the results of the testing that was performed, such as a urinalysis or urine culture. Once the treatment is complete and the symptoms have cleared up, semen analysis is repeated six to eight weeks later. If the symptoms do not clear up, then further evaluation and treatment by a urologist is indicated.

 

For chlamydia or gonorrhea, the latest guidelines from the Centers for Disease Control recommend a single dose of one of the following:

      1) Ceftriaxone 250 mg by injection or

      2) Cefixime 400 mg by mouth or

      3) Ceftizoxime 500 mg by injection or

      4) Cefoxitin 2 g by injection along with probenecid 1 g by mouth or

      5) Cefotaxime 500 mg by injection

plus one of the following:

      1) Azithromycin 1 g by mouth in a single dose or

      2) Doxycycline 100 mg by mouth twice a day for seven days

 

If a sexually transmitted disease such as chlamydia or gonorrhea is found, the female partner should also get tested by her ob-gyn. The couple should use a condom or practice abstinence until both partners have completed their courses of treatment, to prevent spread of the infection back and forth between them.

If the urine test comes back as positive for a bacterial urinary tract infection (UTI), then the choice of antibiotic should be determined by what antibiotic the culture says the bacteria are sensitive to. Typically a ten-to-fourteen-day course of antibiotics is indicated for men, though a longer course (three to six weeks) may be necessary if the doctor suspects prostatitis as well.

Urinary tract infections are much less common in men than in women. If a man is diagnosed with a symptomatic urinary tract infection, he should see a general urologist for a basic evaluation (including a non-invasive ultrasound test to make sure that he is adequately emptying his bladder).

 

Persistent Pyospermia

If significant pyospermia persists following adequate treatment, then further testing is recommended to make sure that some hidden source of inflammation is not being missed, including potentially dangerous but rare problems like prostate cancer.

 

Potential recommended testing includes:

1) Chlamydia and gonorrhea testing by urine test or urethral swab (if not previously done). Diagnosis code (STD testing): Z11.3. These sexually transmitted diseases can be entirely silent and without symptoms in some circumstances.

2) Transrectal ultrasound (TRUS). Diagnosis code (prostatitis): N41.9. This radiologic test provides good visualization of the prostate and seminal vesicles, and can look for abnormalities in the area such as stones or abnormal masses. Not all radiology centers offer TRUS, so you may need to call around and find one that does. Urologists also typically offer TRUS in their office.

3) Prostate-specific antigen (PSA). Diagnosis code (PSA screening): Z12.5. PSA is a screening test for prostate cancer. It is typically used in conjunction with a digital rectal exam. Prostate cancer is rare in younger men, but I have seen it in men as young as thirty. A tumor in the prostate can lead to inflammatory changes and pyospermia, depending on its location within the gland. Further evaluation by a urologist is indicated for abnormalities seen on the PSA test or ultrasound imaging. If the testing all comes back as normal, then I would recommend yearly PSA and digital rectal exam with a primary care physician or general urologist.

 

Semen Cultures

Some physicians advocate a semen culture in cases of persistent pyospermia, looking for aerobic and anaerobic bacteria, as well as for other organisms such as chlamydia, gonorrhea, mycoplasma, and ureaplasma. (Treatment for mycoplasma or ureaplasma is two weeks of doxycycline combined with four weeks of ciprofloxacin.) The problem with semen cultures, however, is that they are notoriously inaccurate due to the high rates of contaminated specimens. Even with thorough washing of the hands and penis with antibacterial soap prior to semen collection, the end of the urethra closest to the penile opening is still colonized by bacteria that can contaminate the specimen (but which generally do not cause fertility problems or pyospermia). In some circumstances, such as persistent pyospermia despite treatment, a semen culture might reveal antibiotic-resistant bacteria that may respond to an alternate antimicrobial regimen. However, the high rates of specimen contamination typically make interpretation of the results difficult. I recommend ordering antimicrobial sensitivity testing in these circumstances, so that any bacteria that are grown are tested for susceptibility to different antibiotics. If multiple organisms grow from the culture, then this usually represents a contaminated specimen. If a single organism grows that is resistant to the antibiotics that were used in the past, this information can help guide further treatment.

 

Managing Persistent Pyospermia

Persistent pyospermia sometimes cannot be eliminated completely. If the tests described above don’t reveal any worrisome findings, then I put the man on antioxidants for at least three months before ordering a test for oxidative stress (See “Antioxidants and Oxidative Stress” section for more details).

If the oxidative stress test results are normal, then the impact of the pyospermia on fertility should be minimal. However, if the results are abnormal, then sperm washing can be used to decrease the impact of the WBCs. WBCs have an increased impact on sperm quality the longer that they are in contact with the sperm. Therefore, immediate sperm washing after ejaculation (combined with intrauterine insemination) can minimize the time the WBCs are in contact with the sperm, possibly limiting oxidative stress damage. This is especially true if the inflammation is felt to be in the prostate region, where the sperm spend less time, though it may be less effective for epididymal inflammation, since the sperm typically spend seven to fourteen days within the epididymis during the normal maturation process.