Semen Analysis: Uses and Limitations

June 19, 2010Carole No Comments »

A brief history of the discovery of sperm maps the dead ends and blind alleys traveled by early scientists who were puzzled by human reproduction. It may seem incredible to us today but human sperm weren’t discovered until Anton Leeuwenhoek (1632-1723), and his student Johan Ham, used a home-made microscope to look at the swimming “sperm animals” in their semen. Leeuwenhoek proposed that sperm somehow entered the egg to fertilize it. This crazy idea was rejected by many of his scientific colleagues.

It wasn’t until a century later, that Lazzaro Spallanzani, an Italian priest-scientist studied reproduction in frogs and proved that frog semen did fertilize the frog egg. However, based on flawed experiments, he concluded that the fluid portion of the semen and not the semen “worms” was actually responsible for creating the new life. Reproductive science took another step backward when the “spermists” and “ovists” argued that either the sperm or the egg contained preformed little people inside them, which were somehow activated by the sex act.  It wasn’t until 1875 when Oscar Hertwig performed experiments using sea urchins that proved that genetic material from the sea urchin sperm entered the egg and somehow mixed with genetic material of the egg to create a new embryo.

The first semen analysis consisted of looking for sperm in cervical swab samples collected after sex. In the “Foreword to Semen Analysis in 21st Century Medicine special issue in Asian Journal of Andrology”, there’s a historic description of the sample collection procedure as a practice deemed “… dabbling…. incompatible with decency and self-respect…”. This 1800’s era semen analysis was limited to determining whether sperm was absent or present in the cervical swab. It wasn’t until 1929 that a paper was published describing a method to count sperm. In the 1940’s, clinical books on semen analysis were published and semen analysis finally entered clinical respectability.

The 1st edition of World Health Organizations (WHO) Semen Manual was published in 1980, and with the recent publication of the fifth edition, the WHO manual  is still the primary clinical reference for semen analysis. The standard semen analysis today determines the  number and concentration of sperm in the ejaculate, what percentage of sperm are swimming (percent motile) in the ejaculate, the quality of the swimming (progressively motile versus immotile, circular motion, quivering etc), the percent viable (non-dead) sperm in the ejaculate and the percent normally shaped sperm (morphology). In addition to these descriptive parameters, newer functional tests can also be part of the test to see if sperm can bind to the egg or if sperm DNA is intact.

In spite of everything we can test and report about sperm quality and quantity,  there is still controversy and debate over the clinical usefulness of semen analysis for determining male fertility.

How can this be?? Well, the problem is that it is hard to determine clinical reference ranges for male fertility in the population. Only the complete absence of sperm in the ejaculate (azoospermia) is conclusive for male infertility–at least with intercourse. For some of these men, if they still produce sperm, surgical collection of sperm from the testicle or epididymis and the use of ICSI can restore the ability to conceive a child.

The number of sperm may be less important than the progressive motility of sperm. A man may have 5o million sperm per milliliter, but if all are non-motile or weakly motile, this man is infertile by intercourse. ICSI can help if the sperm are alive, just not motile.  We sometimes use a dye-exclusion test to tell if non-motile sperm are alive or dead. Live sperm have intact membranes which keep the dye out of the cell so they don’t become stained. Dead sperm take up the color of the dye. So, a man can have a high sperm count but all the non-moving sperm may be dead. ICSI is not usually helpful for these cases because the DNA integrity is likely poor  with non-viable sperm, making the DNA interaction at fertilization unlikely to succeed. ICSI can’t resurrect dead sperm.

The appearance of sperm may not  be significant in determining fertility although much has been made of using Kruger’s strict criteria compared to WHO morphology to determine what a normal sperm looks like. If the tech is picking a normal sperm visually for ICSI, the percent normal in the ejaculate isn’t important as long as the tech can find the same number of normal sperm as there are eggs to inject.

The presence of a very low number of normal sperm is sometimes used by the clinician to decide which treatment to do: ICSI instead of IVF or  IVF instead of  IUI. I could probably find a scientific study to back up either position:  morphology assessment is critical/useless for improving clinical outcomes. You will find strong positions on both sides.

Unless the sperm has a morphological (shape) abnormality like a huge or double head or abnormally small head that suggests a chromosomal abnormality, morphology is probably not a predictor of genetic abnormality. I remember a mouse study in which researchers deliberately picked the ugliest mouse sperm to use for mouse ICSI and generated apparently normal looking and acting mouse offspring. Now, whether these mice would have gone to Harvard, we’ll never know, but maybe we get too hung up on determining percent normal sperm in an ejaculate.

Along the same lines, humans have the most abnormal sperm in the animal kingdom. All the domesticated and research animals that have been well studied have very little variance in the look of their sperm. By comparison, primate, and particularly human sperm is a mess. Yet we have over 6 billion humans running around so sex (and ART) apparently does a good job of weeding these uglies out or some variation in shape is allowable and the job still gets done.

Another reason that semen analysis is a poor indicator of male fertility is that it takes two to tango. A man with a borderline semen analysis result may be able to impregnate his female partner because she is super fertile and in a sense can meet him more than halfway. If his partner has fertility issues of her own, than his own lower count may be a greater problem.

Still, we forge on to try to make semen analysis a meaningful predictor of fertility. The World Health Organization has published an article on the average range of semen analysis parameters for 4500 men in 14 countries who conceived children with their partners in less than 12 months of trying (men defined as fertile).

“Average value,(range of values)”  for men in this fertile study group are shown for each sperm parameter listed below.

semen volume, 1.5 ml (1.4–1.7)

total sperm number, 39 million per ejaculate (33–46)

sperm concentration, 15 million per ml (12–16)

vitality, 58% live (55–63)

progressive motility, 32% (31–34)

total (progressive and non- progressive) motility, 40% (38–42)

morphologically normal forms, 4.0% (3.0–4.0).

Since these men were not partnered with a “standardized fertile woman”, the effect of various levels of  female fertility with different partners can’t be determined, but is probably averaged out over this large group.

Even men with superior numbers in a semen analysis can be infertile due to molecular defects (like the absence of functional binding receptors) that are not detected with a semen analysis. Over the years, various functional tests like zona-binding assays and DNA integrity assays  have been used to try to determine how well sperm will function, but none of these functional tests have replaced the standard semen analysis.

Take home messages:

  • Do have a relatively inexpensive semen analysis done-preferably by a fertility lab, not hospital lab-   to rule out azoospermia (zero sperm in the ejaculate), absence of motility or a high percentage of dead sperm before you go ahead with more expensive interventions.
  • Don’t get too hung up on morphology, especially if ICSI is being used,  the jury is still out on how important it really is.
  • Progressive motility is a good thing to have, especially if numbers are on the low side.
  • All men have poor semen compared to the rest of the animal kingdom so we tend to grade on a curve in the lab and use ICSI a lot.

© 2010, Carole. All rights reserved.

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