The semen analysis has been used to diagnose male factor infertility since the 1930’s. In the 1980’s the World Health Organization (WHO) published a manual describing the proper methods for performing the semen analysis. They also published normal and abnormal values. It was these values that became the method for identifying male factor infertility. There is considerable concern amongst reproductive endocrinologists and andrologists about the accuracy for using the semen analysis to identify male factor infertility. So why does this concern exist?
To understand the shortcomings of the semen analysis, it is necessary to determine how the current semen analysis (SA) came into existence. The WHO manual sets the standards for the performance of the SA. The first manual was published in 1980. The purpose for the manual was to standardize worldwide how the SA was performed. The manual is very complete in describing how the various parts of the SA need to be performed. Therefore, any laboratory that performs the SA according to the instructions in the WHO manual will produce the same results as any other WHO guided lab anywhere in the world. Thus, the results from a SA from a patient in Ohio can be interpreted by a physician in Oregon if that patient should happen to move during the infertility workup and treatment. The WHO manual serves a valuable service because of this standardization as to how the SA is to be performed.
Different numbers / different meanings?
The controversy arose because the WHO also published values they identified as normal or abnormal. The ideal method for assigning these normal values would have been to correlate the results from the SA to pregnancy rates. Unfortunately, that was not done. Instead the WHO combined the results from many studies which reported the results from a number of SA. The WHO then arranged the frequency of the values from the combined semen analyses and defined abnormal vales as those that were the lower 5% of the values for the combined semen analyses. For example, if 95% of the values for the results from many men were greater than 40 million per ml, then any man who had a value of less than 40 million was considered to have an abnormal normal value and thus could be classified as having male factor infertility.
Criticism immediately was put forth about the establishment of the abnormal vales. The validity of this criticism can be seen when considering that there have been a total of five editions of the WHO manual and each edition had changing abnormal vales. For example, the 1980 edition considered a normal count (million/ ml of semen) to be > than 20 million. But the most recent edition (2010) defined a normal count as > 15 million. The effect of this is that many couples who were considered to have male factor are now considered normal. This weakness of the SA results in significant waste of therapy. Somewhere between 15 – 39% of the males considered infertile by the 1999 criteria would be reclassified as normal under the 2010 criteria.
Another criticism of the 2010 WHO edition is that all data used was derived from men where the couple had a pregnancy within the last year. All samples were from couples who were not only fertile but were highly fertile because the achieved a pregnancy within one year of trying and thus were not infertile. Further criticism comes from the fact the data was derived from a small number of males (1953) obtained from five studies from seven countries on three continents. There were no studies from Asia, Africa, the Middle East, or Latin America. Finally 55% of the data came from Paris, Turku, Edinburgh, and Copenhagen. The establishment of normal values for morphology was even more contentious.
Given the situation where the WHO manual defines how the SA is done and what values are considered normal, the question remains: How are physicians and patients to define male factor infertility? The diagnosis is based upon the total picture for the couple combined with the results of the SA. Obviously, if a man consistently has no sperm in the SA, there is a very severe male factor that will require assisted reproductive technology to diagnoses and treat. The history, genetic evaluation of the man, and potentially testicular biopsy can identify the man who can be treated with IVF and intracytoplasmic sperm injection (ICSI) with a high chance of achieving a pregnancy if there are no other factors identified in the female. For a man with a normal SA and a history of having fathered a pregnancy, no matter what the outcome of that pregnancy, there is no evidence for male factor infertility and other causes for the couple’s infertility need to be sought. But what about the grey zone? One study has suggested using the total motile sperm count (no inclusion of morphology) and dividing men into three groups: > 20 million, 5-20 million, and < 5 million. In situations, where the man consistently has < 5 million TMS, the diagnosis is severe male factor and IVF with ICSI is indicated. For men with > 20 million, no history of a pregnancy and a diagnosis for the couple of unexplained infertility, the man will need a complete history, physical, and health screening performed to identify subtle causes of male factor infertility. For those men with 5-20 million TMS, a number of therapies might be appropriate such as dietary supplements, empiric use of fertility enhancing medications or, ultimately, IVF with ICSI.
The bottom line.
So where does this leave a man? Diagnostic testing will identify a cause for an abnormal semen analysis 50% of the time. This can help direct appropriate therapy. Only a few men will have no sperm and thus will not have a child that is genetically his given the current state of the technology. For most men diagnosed with male factor infertility, there exists technology that gives them a very good chance that they can genetically father a child. However, the chance of pregnancy needs to be evaluated in the context of potential female infertility factors.
There are many paths on this journey. Achieving a successful pregnancy involves both the male and the female. Some reproductive endocrinologists have been trained in andrology (the study of male reproduction). Thus, the most comprehensive approach is to consult with a physician trained in both male and female reproduction and proceed with both the woman and the man concomitantly so that a complete picture can be achieved.