Male Fertility & Infertility

 
 

A semen analysis is a specialized test which can provide valuable information on the fertility potential of males. It is also a requirement following vasectomy and vasectomy reversal to ensure technical success. It is important to understand how to collect a proper specimen. It is also important to understand the interpretation of a semen analysis result - and especially the limitations of semen analysis in the evaluation of infertile males.

Instructions for Semen Analysis Specimens

Please be aware that Lifelabs and BC Biomed only accept semen specimens at specific times. The specialty labs at the reproductive medicine clinics require appointments to provide on-site samples.

If you are having a post-vasectomy semen analysis, no special preparation is required. Please refer to the Vasectomy section for timing and number of collections to ensure the procedure has been successful

  • If you are having a semen analysis because you are having difficulty achieving a pregnancy, there are a few general guidelines which will make the results more reliable

  1. Abstain for about 4 days prior to your specimen and keep the same abstinence interval for each specimen you provide*

  2. If you need more than one specimen, space them a few weeks apart

  3. Try and collect the specimen during a time when your wife is unlikely to be ovulating (e.g. during menstruation)

  4. Take your specimen to the laboratory as soon as possible, ideally within 1 hour of collection

  5. Keep the specimen warm by placing the collection container in a shirt pocket

* For every additional day up to about 7 days, the sperm concentration can increase about 25%. This makes comparison of results very difficult if different abstinence intervals are used. This effect is most pronounced for the first few days.

Locations and collection times for semen specimens

Lifelabs

Pacific Centre for Reproductive Medicine

Novavita Lab

Semen Analysis Interpretation

Semen analysis (SA) should be interpreted in the context of the complete male and female evaluation - it should never be evaluated in isolation. 

Semen Analysis is not a diagnostic test which can differentiate fertile from infertile men*.

*With the sole exception of men with azospermia (no sperm)

This oft quoted but frequently ignored fundamental fact about semen analysis has lead to flawed interpretation of SA. It is inaccurate to simply state that the semen analysis, or any one particular semen analysis parameter for that matter, is either 'normal' or 'abnormal'. With the exception of men without sperm, there is always a possibility of conception so long as the partner is not sterile.  By understanding this fundamental concept, the question "Is my semen analysis normal?" can then be appropriately restated as: 

'How do my semen analysis results affect the chances that we will achieve a pregnancy over a given length of time?"

Putting your semen analysis in perspective involves consideration of:

  1. The rest of your clinical evaluation

  2. You and your partner's past fertility history

  3. Your partner's current fertility status

  4. The length of time you have been attempting to achieve a pregnancy

While it is possible to make comment on the general chances of achieving a pregnancy for a man with specific semen analysis parameters with a standardized 'reference spouse' (i.e. an otherwise healthy woman between the ages of 20-30 with no prior pregnancy history and with no prior attempts at achieiving a pregnancy), this sort of assessment is not applicable to the majority of couples who are seen with fertility problems. An individualized assessment which takes into account male and female factors is always required.

Measurements: Standard Semen Analysis Parameters

Before reviewing what the implications of the different parameters are on the chances of conceiving, it is helpful to understand what is actually measured and what is involved with these measurement. The commonly measured parameters in routine semen analysis are:

  1. Concentration: the number of sperm in a specific volume of semen fluid. Usually expressed as million per milliliter (M/ml); this is the same as giga per litre (billion/litre).

  2. Volume: the volume of ejaculate

  3. Motility: a measure of sperm movement

  4. Morphology: the appearance of the sperm. Abosolute size of different components such as the head, midpiece, and tail are measured against a standard (more on this later)

  5. Other: some reports will include a pH, liquifaction, viability and the presence of other cells such as red blood cells or white blood cells. 

NOTE: some laboratory requisitions inappropriately label the concentration as 'Total Sperm Count'. You can tell if this is the case by looking at the units - if the units are a 'number/volume', then it is a concentration. If the unit is just a 'number' then it is a total count. You can easily determine the total sperm count by multiplying the semen volume by the sperm concentration.

Variation in Semen Analysis Results 

Any variation in the semen analysis report from measurement to measurement may result from 3 possible causes:

  1. An actual change in the fertility status of a man

  2. Natural biological variation

  3. Laboratory error

Normal Biological Variation

It is perfectly normal for there to be variation in these parameters from sample to sample within the same individual even if there has been absolutely no change in that persons intrinsic fertility potential. This is known as 'normal biological variation'. Just as no one wakes up the exact same every day, semen analyses parameters will vary from day to day also.

Laboratory Error

Measurement of these parameters is a human endeavour and therefore subject to error. This is known as 'laboratory error'. Most men ejaculate tens if not hundreds of millions of sperm. It is not currently possible (nor would it make any difference) to measure every single sperm in a sample. In fact, only a very small proportion of the sperm in a sample are assessed - much less than 1% of 1% of the sample. Out of 100 million sperm, only a few hundred are actually counted. Concentration, for example, is estimated by counting the number of sperm within a very small volume using a microcell counter. Based on the number of sperm within the known volume, the total number of sperm or a sperm concentration can be estimated. Because only a very small sample is measured, there is great potential for inaccuracy. For example, it has been demonstrated that if a pooled semen sample (i.e. collected from many men and mixed together) is sent to enough labs, that some of the labs will report that no sperm are present even though there are many millions of sperm present - just by chance the sample of fluid taken from the main sample will not have any sperm! Using a computer to do the measuring (CASA - computer aided semen analysis) provides only a modest benefit over using a human.

The average degree of variation between the parameters on an 2 separate sample (covariance) in a male who is healthy and has not had a change in his fertility status is about 60%, but between individual measurements may be well over 100%!

This is to say that there is a significant amount of normal biological variation and laboratory error built into the end results of any semen analysis report. Implications for measurement:

  1. A semen analysis with sperm concentration that is acceptable is likely to be reliable and does not need to be repeated.

  2. Never rely on a single semen analysis with a low sperm count to make clinical decisions. Repeat it.

As a result, great caution should be exercised when using semen analysis results to determine if there has been a significant change in a man's intrinsic fertility status or by inappropriately assigning a greater degree of precision and accuracy to a semen analysis report than is diagnostically achievable. (references: Keel et al Fertility and Sterility 2006; Carlsen et al Fertility and Sterility 2004)

Figure: This graph shows how the concentration in a single man naturally varies over time with several measurements. These are the normal 'ups and downs' found in sperm production and with lab variance. Despite the sometimes dramatic changes in conc…

Figure: This graph shows how the concentration in a single man naturally varies over time with several measurements. These are the normal 'ups and downs' found in sperm production and with lab variance. Despite the sometimes dramatic changes in concentration, this man's intrinsic fertility potential was unchanged. The take home message is not to get too excited by the changes seen between a couple of semen analysis reports. They are more likely the result of normal variation than an indicator of increased or decreased fertility potential. Consistent changes which trend either upwards or downwards are required before it can be stated if things are getting 'better or worse'.

Using the Semen Analysis Report to Determine the Probability of a Pregnancy

It is impossible to use the semen analysis parameters to predict the chances of pregnancy without knowledge about the other factors that might impact a couples ability to conceive. Remeber, it always takes two. The one exception is in a man who has no sperm - even if nothing is known about his partner, it can be stated with certainty that they will not be able to conceive naturally unless he sperm appear in the ejaculate. For everyone else, the assessment is individualized. Having said that, some general comments  can be made regarging semen analysis results in terms of the probability of conception - increased or decreased - regardless of what is happening with a man's partner.

Despite all of the parameters that are reported on a semen analysis report, the only parameters that have been proven to correlate with the chances of naturally achieving a pregnancy are:

  1. Concentration of sperm (total sperm count provides a similar estimate) - THIS IS BY FAR THE MOST IMPORTANT PARAMETER

  2. Concentration

  3. Concentration

  4. Concentration

In short, with the exception of sperm concentration every other parameter measured on the semen analysis can be disregarded (with very few exceptions).

There is no such thing as a 'normal' semen analysis or 'normal' concentration. What is most important is to assess how any specific sperm concentration affects the chances of conception. Intuitively, more sperm is better and this is true to some extent. The relationship between sperm concentration and the chances of pregnacy can be roughly summarized as follows:

  • Sperm concentration > 40-50 million/mL: statistically optimal. The man with sperm concentration 50 million/mL has the same probability of achieving a pregnancy as one with 400 million/mL (this is the same for all concentrations in between) 

  • Sperm concentration 15-20 million/mL: statistically reduced probability of conception but modest clinical effect - about a 10-20% absolute reduction in the pregnancy rate compared to the optimal group.

  • Sperm concentation < 15 million/mL: statistically reduce probability of conception and a substantial clinical effect of at least 20% reduction in the pregnancy rate compared to the optimal group. 

Scenario 1: Using semen analysis to determine the probability of pregnancy in 'First Pregnancy Planners'

Parameters

  1. No known prior pregnancy history

  2. No prior evaluation for infertility, but no known concerns either

  3. Just starting to attempt a pregnancy (Time 0 starts with the first attempt at unprotected intercourse)

  4. Female age <30 years old

INFERTILITY_SEMEN_ANALYSIS_CONCENTRATION_PRIMARY_PLANNERS.png

Scenario 2: Using Semen Analysis to Predict Pregnancy in Infertile Couples

There is significantly less data on using semen analysis to predict pregnancy in infertile couples - which is a problem since this is the group we are most interested in. However, the chances for conception overall are quite favorable in couples labelled as 'infertile' during years 2 and 3, even if nothing is known about a man's semen analysis. Some semen analysis reports use reference ranges from a study published in the New England Journal of Medicine by Guzick et al in 2001 titled 'Sperm morphology, motility and concentration in fertile and infertile men'. This study used a 'case-control' design rather than a 'prospective cohort' design which did not account for the prevalence of the semen analysis parameters in the general infertile and fertile populations. The bottom line is that the study over-estimated by far the ability of various semen analysis parameters to distinguish men who will have difficulty conceiving from those who will not. 

Taking some 'extreme' examples of semen analysis parameters will help put the probability of conception of infertile couples in perspective. (references: Collins et al Fertility and Sterility 1995; Snick et al. Human Reproduction 1997) 

Example 1: Couples unable to conceive for 1 year. No major female factor identified. No prior fertility history. If the sperm concentration is <20 million/ml, 1 in 3 couples will conceive within 2 years of being declared infertile. 

Example 2: Couples unable to conceive for 1 year. No major female factor identified. No prior fertility history. If the total motile count is <5 million/ml, 1 in 4 couples will conceive with 2 years of being declared 'infertile'.

Unless the sperm concentration is very low, there is still a reasonable chance that a couple will be able to conceive in the 2 years after they are declared infertile—The probability is usually greater than 1 in 3.

The data on couples in who the male has low counts and are observed for prolonged periods is limited. In the modern era, most are managed with IVF. Here is some historical data which remains relevant in predicting the chances of natural conception with low sperm counts. It comes from Schoysman and Gerris, Acta Eur Fertil 1983).

Motile Sperm Count Pregnancy (%) after 5 years Pregnancy (%) after 12 years
0.1-1 3.9 8.7
1-5 11.9 26.6
5-10 22.1 34.3
10-15 45 58.5
15-20 68.6 82.0

Pyospermia (Leukocytospermia)

Pyospermia (leukocytospermia) is the presence of white blood cells in the ejaculate. Pyospermia may be an indicator of inflammation in the male reproductive tract.

About 80% of patients with pyospermia do not have evidence of an infection based on bacteriologic testing. In those in who do have an infection the most common organisms are CMV (cytomegalovirus), HPV (genital warts), HHV or HSV (herpes) with only rare cases containing Chlamydia (about 10% of those with an infection or 2% overall). The bigger issue is that it is unclear if or how much of an issue pyospermia is in males - the relative prevalence in the general vs. the infertility population is unknown. It is entirely possible that the majority of men with pyospermia do not have impairment in fertility potential

Management options
- Antioxidants.
- Use of antibiotics, either empiric or targeted to cultures. Commonly used empiric antibiotics are doxycycline, Septra or Ciprofloxacin
- Increase frequency of ejaculation.

The data on the utility of empiric antibiotics is insufficient to draw any conclusions on effectiveness. Most of the studies lack control groups, were at high risk of bias and the substantial random background fluctuation in semen analysis parameters as well as the confounding factors of female fertility in assessing outcomes make it challenging to provide much meaningful advice. In regard to potential outcomes after use of antibiotics, improvement in the semen analysis parameters has been reported in about two thirds of patients but this may simply be regression to the mean, resolution in the pyospermia is seen in about one half of patients and then bacteriologic cure in about a third of patients. The most important outcome is an improvement in the pregnancy rate and this has only been seen in a small minority of the studies that have looked at this. References: DOI 10.5535/wjmh.2016.34.3.165 and 10.1016/j.fertnstert.2006.08.109

Hopefully this has helped you understand the role of semen analysis in couples attempting to achieve a pregnancy naturally. You can make an appointment with Dr. Poon if you have further questions regarding your particular scenario.

A Final Word on 'Reference Ranges', 'Normal and Abnormal Semen Analysis' 

The 'reference ranges' published on semen analysis reports should be disregarded. The relationship between sperm concentration, morphology and the probability of conception is such that using a 'cutpoint' or 'lower limit' is too crude. Also, the distribution of all of the measured semen analysis parameters in the male population do not follow a bell-shaped distribution ('normal' in statistical parlance). As a result, calculated 'averages' have no clinical utility nor statistical meaning. Finally, the reference ranges are continually changing. Over the past several decades, the lower limit of what is considered 'acceptable' has continued to decrease. Most recently, the World Health Organization published revised reference ranges for semen analysis parameters in late 2010. 'Acceptable morphology' has decreased from ≥14% to ≥5% using the Kruger Strict criteria. Therefore men who were told they were 'abnormal' before would now be considered 'normal'. The approach taken by the WHO ignores the actual relationship between semen analysis results and conception. 

The best way to approach interpretation of semen analysis parameters is not to state that they are 'normal' or 'abnormal' but instead to look at the parameters of importance (which will depend on the context in which the results are being applied) and determining what if any effect they will have on the probability of achieving a pregnancy - and also determining to what degree they will have that effect.

On the Web

General Urology Web Sites

CFAS Patient Resources: patient information website for the Canadian Fertility and Andrology Society

Reproductive Facts: patient information website for the American Society for Reproductive Medicine