The New World Health Organization Manual on Semen Analysis: Comments On the Review Sponsored by the American Society of Andrology and Implications for Current Assessment of Male Fertility
Eric K. Seaman MD
The World Health Organization recently released its latest version (sixth edition) of the Manual on Semen Analysis. The prior version was released in 2010. The American Society of Andrology (ASA) sponsored a review of the manual which was presented by Drs Christina Wang, Dorrie Lamm, Lars Bjorndahl and others. This Blog will serve to present some of the take home points of the review as well as point out some implications of what was and was not said with respect to the future of the field of Male Infertility.
The WHO manual is widely regarded as THE standard reference manual for andrology labs. Its latest revision is greeted with much anticipation. The ASA presentation began with a review by Dr. Christina Wang of previous editions. Her presentation detailed information including the fact that the first edition was written in 1980 utilizing the findings of several task forces on the diagnosis and treatment of male infertility. The purpose of the first manual was to understand reproductive function in men. It contained only six pages of detail with respect to the semen analysis including information on assessment of sperm density, motility, and morphology. The criteria for “normality” was based on men whose partners were currently pregnant or recently pregnant.
Dr. Wang reported that the second, third and fourth editions were printed in 1987, 1992 and 1999 respectively. The third edition set the standard for the “normal” semen analysis with information largely derived from publications by Drs. McCloud and Gold in the 1950s. The third edition was 107 pages long and introduced the concept of “Strict Criteria” as a possible standard for sperm morphology. Strict morphology became the preferred standard in the fourth and subsequent editions.
Finally, the fifth edition, released in 2010, gave more details on procedures, introduced the concept of total sperm per ejaculate as an important parameter, presented new plates for morphology, and more information on sperm preparation from semen, testis, and epididymis. The reference ranges were changed based on a population of fertile men whose partners had a time to pregnancy of less than 1 year.
The 6th edition made minor adjustments to those reference values considering “normal” to be above a sperm density and total sperm count of 16M/ml and 39 Million respectively with reference values for total and progressive motility being 42% and 30% respectively and for morphology continuing to be 4%. Additional modifications included moving anti-sperm antibody and inflammatory cell testing to being considered part of the extended exam. Motility criteria has returned to concepts of rapid, slow, non progressive and immotile.
And here is where the review became very interesting. There was a commentary that the current edition does NOT set distinct limits between fertile and infertile men. There was acknowledgment that better semen parameters were associated with shorter times to conception but also acknowledgement that men with poor semen parameters were also sometimes able to conceive. And there was a suggestion that perhaps the best use for semen analysis parameters were to assess response to treatment.
At this point, Dr, Lamm gave her presentation. She mentioned other methods to test sperm including assessment of sperm aneuploidy, DNA fragmentation and presence of cytokines. However, the utility of these tests appears to be confined to a small subset of patients. She then spent a great deal of time discussing the revamping of the use of sperm morphology assessment acknowledging that a simple percent normal morphology was of limited value and that newer assessments looking at total number of defects in morphology or an index of morphology abnormality may have more utility.
After Dr. Lamm spoke, there was additional commentary among the three presenters. Computer assisted semen analysis (CASA) was discussed as using different algorithms among different systems with a tacit acknowledgement that 2 different CASA system may give completely unrelated results and that they are best used for research-based analysis as they are reliable with respect to detecting changes in semen parameters. Morphology assessment by CASA systems was also brought into question by Dr. Lars Bjorndahl who stated that CASA systems often focus only on the sperm head and not the midpiece or principal piece (tail) due in part to a difficulty in getting the entire sperm into focus.
Therefore, what take home points can be taken from this discussion? It was refreshing to hear an acknowledgement of the limitations of semen analysis to actually diagnose male infertility or differentiate fertile from infertile male patients. Perhaps the most famous historical reference attesting to this fact (not discussed by the participants) was from Guzick et all in NEMJ, 2001 which demonstrated that traditional semen parameters failed to identify over half of men with infertility.
What is also puzzling is that given that there are available newer tests of fertility with proven utility in the diagnosis of male fertility, that these tests were omitted from the manual. Specifically, tests of sperm capacitation offer direct correlation to chances of conceptions
Cap-score is a commercially available test of male fertility available for over 3 years which offers information on chances of conception based on analysis of the percentage of sperm that have the ability to capacitate.
Capacitation describes a series of activities an individual sperm must accomplish in order to fertilize an egg. The greater the percentage able to capacitate, the higher the chances of conception
It is not clear why the manual omits any mention of sperm capacitation, Cap-score or otherwise. Perhaps we can look forward to the seventh edition embracing this new technology.
In short, the new (sixth) edition of the WHO manual serves to clarify and also, perhaps, add to our armamentarium in the struggle for conception. However, it is disappointing to know that additional material could still have been added to make the manual even more complete and helpful.
If you require medical expertise with respect to male infertility, microsurgical varicocelectomy or surgical sperm retrieval, consider an appointment with Dr. Eric K. Seaman.