Wishing for a Happy Father’s Day: Male Infertility Treatment

Infertility is too often thought of as a “woman’s” problem, but  the truth of the matter is that without sperm to tango with, the egg is pretty insufficient to make a baby. The good news for men is that today’s male infertility toolbox contains more diagnosis and treatment tools than what was available in their father’s day.

The traditional semen analysis provides information about the population of sperm in the ejaculate including  the number of sperm (sperm count), what percentage of sperm have motility (percent motility) , what percentage of sperm look “normal” as per specific defined expectations. What constitutes normal sperm varies depending on what criteria are used. The World Health Organization is an organization which monitors trends in fertility throughout the world and has been the defining authority on normal sperm parameters.

The World Health Organization (WHO) has developed evolving guidelines for standardized semen analysis and have recently published the fifth edition of the WHO manual for semen analysis. If you want to know more about the new reference ranges, check out Craig Neiderberger MD, expert infertility urologist’s discussion of the clinical implications of the 5th edition’s new reference values with Allan Pacey, BSc, PhD. One of the take home messages may be that it is time to move away from thinking of semen analysis in terms of abnormal or normal values, but rather in terms of population ranges or curves, a continuum of results with absolute sterility at one end, robust fertility at the other and a big area in between in which fertility is not ruled out but perhaps more difficult to achieve.

Why does the WHO edition matter? Because in earlier editions, the recommended cut offs for normal was based more on committee consensus than rigorous population data. The new WHO manual also makes a greater effort to provide detailed descriptions of how testing should be done, minimizing the lab to lab variability of these tests. One smart change was to determine volume, not by measuring in a pipette but by weighing the sample, a far more accurate method.

In edition 5, the WHO manual explains that normal ranges were identified by analyzing semen samples from a population of men whose partners conceived within 12 months of sex without contraception. Nearly two thousand samples were evaluated from men in eight countries on three continents. So although admittedly artificial parameters were used to define the lower limits of normal, a large number and variety of samples were analyzed, providing more robust data to determine reference ranges.

One problem with semen analysis as an indicator of fertility is that it takes two to tango. A male with a normal semen analysis will be unable to conceive if his partner is infertile. Conversely, an abnormal semen analysis does not guarantee sterility in every case because abnormality in one parameter such as count or motility may mean that the time to conception may be abnormally long but pregnancy can eventually be achieved. However there is no way to predict with accuracy male fertility from a semen analysis result unless the sperm count from ejaculate and testis is zero or all sperm are dead.  A normal semen analysis can’t even be used as proof of  fertility because problems with sperm egg-binding receptors or  problems with DNA integrity are not revealed by the traditional semen analysis.

A single semen analysis should never be the final verdict on fertility. Semen analysis results may vary from one sample to another due to such factors as period of abstinence (too short or too long), underlying illness, or problems with collection (loss of sample).

In a previous post, I discuss some of the limitations of semen analysis, but semen analysis is still an important clinical tool for making  treatment decisions, because the semen analysis results can help the clinician decide whether insemination or in vitro fertilization might be more likely to be effective. Even if IVF is needed, semen analysis results can be used to determine if intracytoplasmic sperm injection (ICSI) might be also necessary to achieve fertilization. For insemination, sperm must be not only present but present in adequate numbers with adequate motility (swimming ability) to be able to reach the egg and then fertilize it. In contrast, for in vitro fertilization, the egg and sperm are placed in close proximity and fewer motile sperm are necessary because the trip to the egg is short and millions of “wingmen” sperm aren’t needed to compensate for sperm normally lost en route to the egg.  ICSI sperm can be both rare and lazy (non-moving) because each sperm is carefully hand-selected and carried to the egg by the technician who manually injects the sperm into the egg. Injection does not guarantee fertilization, but it certainly bypasses  barriers sperm would have to overcome through intercourse such as possible hostile mucous, a long female reproductive tract to traverse (from vagina to Fallopian tubes), problems with sperm-egg binding ability and  weak or absent forward progression motion necessary to push into the egg.

Newer functional tests are available which may be able to shed more light on whether a sperm can actually fertilize an egg. One of the earliest sperm tests addressing function was the hamster egg sperm penetration assay (SPA) which uses  hamster eggs lacking the zona pellucida (outer shell) of the egg as a test substitute for human eggs. The percentage of sperm in the test sample able to penetrate the hamster eggs is calculated. Over time, this test lost favor because among other reasons, the test was difficult to standardize and false positives and negatives were more common than acceptable.

Another functional test, the hyaluronan binding assay (HBA) takes advantage of the fact that more mature fertilization-capable sperm seem to have a stronger affinity for the biological molecule hyaluronan then less mature, less fertilization-ready sperm. For the test, ejaculated sperm are exposed to hyaluronan-coated slides and the percent that are able to attach are determined by counting under a microscope. Results from both types of tests have been used to determine if sperm injection would be helpful due to problems with sperm penetration or binding to the egg.

When the sperm enters the egg, the work is not done. Through a series of biochemical and molecular steps, the DNA from both egg and sperm combine and form a new human being. What else could go wrong? Sadly, if the DNA in the sperm head is fragmented and deteriorated, then the sperm can’t zipper together in the fertilization dance and fertilization fails, or in some cases, fertilization may occur but embryo quality will be affected and the embryos could stop dividing causing the pregnancy to fail. Interestingly, if the fragmentation is not too severe, the egg may be able to repair local regions of DNA, but as eggs age, they are less able to perform this function, and as men age, they are more likely to produce sperm that have problems with DNA integrity.

ASRM has published a committee opinion about the value of the various DNA integrity tests in their 2008 published guideline,  “The Clinical Utility of Sperm DNA Integrity Testing” which can be downloaded from this page.  Evidence exists suggesting that damage to sperm DNA can arise from a variety of factors including  excessive heat, chemotherapy agents, radiation, varicoceles, infections, smoking and hormonal deficiencies.  Although poor sperm DNA integrity is more likely to be found in men who are having trouble getting their partner pregnant, the fact that a man has an abnormal score on a DNA integrity test, is not a reliable predictor of pregnancy success or failure. Not surprisingly, ASRM committee concluded that results of DNA integrity tests, used in isolation,  aren’t predictive of  outcomes with intercourse, IUI, IVF or ICSI.

So what’s the good news? The good news is that although the perfect semen analysis test does not exist, the available tests, taken together can help a clinician diagnose and suggest the least invasive medical intervention that is most likely to work. Furthermore,  ICSI, although not appropriate for every case still remains the most powerful tool in the male infertility tool box because ICSI makes it possible for men with only rare, immotile sperm to conceive their own biological children.

Still want to know more? More posts on semen analysis and male treatments can be found here:

What causes low or variable sperm counts?

Sperm Injection: The good, the bad and the ugly

The sisterhood of the traveling pants or do IUI’s really work?

What do semen analysis, Glen Beck and aerial photography have in common?

IVF sperm disasters: No sperm on the day of egg retrieval

 

© 2011, Fertility Lab Insider. All rights reserved.

©2011 Fertility Lab Insider. All Rights Reserved.

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