Looking forward to human sperm morphology.

In this issue ofHumanReproduction, Augeret al. (2016) examine sperm abnormalities in fertile and infertile men, and those with testicular cancer, extendingwhatwas published in themost recent version of theWHOLaboratory Manual for the Examination and Processing of Human Semen (WorldHealthOrganization, 2010) onnormal sperm forms.That publicationattempted for thefirst timetoraise thequalityof semenanalysis tothat accepted in other branches ofmedicine for clinicalmeasurements, by providing reference values and threshold limits for semen parameter values (Cooper et al., 2010). The reference population chosen was fertile men for several reasons, not the least of which was that a man’s fertility can be precisely defined in terms of time to pregnancy of his partner after unprotected intercourse. For this population a lower limit of values of parameters considered to be essential for fertility were generated, below which values are consistent with the provider’s being from another, most likely infertile, population. As higher values of these parameters are unlikely to be associated with infertility, the fifth centile was chosen as the one-sided lower limit of the 95% confidence interval. Sperm morphology has been one of the parameters traditionally accepted tobeassociatedwithmale fertility,but thedifficulty in recognizing a ‘potentially fertilizing’ (‘normal’, ‘typical’ or ‘perfect’) spermatozoon has taxed the mind of many over the years (Brazil, 2010), as has been getting agreement in the assessment of such sperm cells by technicians within a laboratory and between institutes (Pacey, 2010). For the WHO manual, the decision to accept ‘normal’ forms as those to be assessed was based on the studies showing (i) that the presence of a homogeneous subpopulation of spermatozoa of similar appearancewas associated with fertility in vivo and in vitro, and thesewere considered those ‘typical’ of fertility, or ‘normal’ forms (Menkveld, 2010); (ii) that it is possible to get agreement in assessment of ‘normal’ forms by technicians if rigorous quality control and assurance processes are implemented (Pacey, 2010); and (iii) that the lower limit should allow the possible prediction of fertility. However, in a special issue of the Asian Journal of Andrology presenting comments and dissenting views on the most recent WHO manual (Handelsman and Cooper, 2010), two criticisms of the usefulness of assessing ‘normal’ sperm formsweremade.Onewas that the extremely low percentage of such forms as the normal lower limit (4%) in fertile men’s semen made it impossible to separate fertile from infertile men (Auger, 2010; Eliasson, 2010; Skakkebaek, 2010). The low percentage of such ‘normal’ forms resulted from the adoption of a very critical classification of forms, by rejecting borderline cases as abnormal (Menkveld, 2010).A return to themore relaxedapproach (borderline formsaccepted as normal), as used in earlierWHOmanuals, was urged by some (Auger, 2010; Eliasson, 2010; Skakkebaek, 2010), as it should provide greater values and anexpectedhigher possibility of distinguishing fertile from infertile men. A second criticismwas the decision to ignore completely abnormal sperm forms, by those (Amann, 2010; Auger, 2010; Eliasson, 2010) who argued that these forms could provide information on the nature of the infertility (e.g. testicular function).However, agreementbetween technicians in the assessment of each of themany abnormal sperm forms (e.g. ‘cigar-shaped’, ‘pyriform’, ‘amorphous’), similar to that shown for ‘normal forms’, hadnot then, andstill hasnot,beendemonstrated.Tosomeextent the present article (Auger et al., 2016) fills this gap. Auger and colleagues have studied themorphology of seminal spermatozoa from 926 fertile men, defined as perWHO (2010) [excluding the morphological criterion], 1747 infertile men and 273 testicular cancer patients. By using standard seminal smear-staining procedures, the recognitionof ‘normal’ forms [differing fromWHO(2010) in thatborderline cases were included in the classification] and 15 defined abnormal forms (Auger et al., 2010), highly experienced and quality control-proven technicians at one centre estimated the percentages of each form in semen from the three categories of men. As in WHO (2010) they provided the fifth centile of normal forms from fertile men as the lower limit cut-off, which at the higher value of 23% reflects the less strict categorization or normal forms used. They also demonstrated that there were more abnormal sperm heads than abnormal tails in fertile men—the abnormality being of texture and outline rather than size—and that generally only two abnormalities per sperm cell were found per fertile men. As expected, the infertile men and cancer patients had lower percentages of normal forms than the fertile men, and higher percentages of abnormal forms, but the cancer patients had higher percentages ofmicroandmacro-cephalic forms, andof spermatozoawith acrosomal abnormalities and excess residual cytoplasm, than the infertilemen. There were also more defects per abnormal sperm cell in these groups than in the fertile controls.