Merzenich et al, BMC Public Health 2010, 10:24 http://www.biomedcentral.com/1471-2458/10/24 actual data [11,16,25]. However, it has been argued by the authors of the original meta-analysis that at least some of the earlier papers in fact did include men with semen quality in the range below 60 million/ml [26]. Sperm concentration, sperm motility and sperm mor- phology are related to each other: factors that cause dete- rioration of one of them usually also have negative impact on the other two [27]. Sperm motility, followed by sperm concentration is the best predictor of fertility [28]. The WHO has given normal limits for semen characteristics. These values are higher than those associated with infer- tility. They are not based on population samples of fertile men or unselected men, but rather reflect the lower range of men still being fertile [17]. With regard to semen analy- ses in epidemiological studies the definition of a genuine reference range for human sperm output based on empir- ical sampling is needed (considering geographical region, ethnicity and age). Furthermore, for clinical or epidemio- logical studies, it would be preferable to investigate more than one outcome parameter. Perspectives Jorgensen et al. [29] investigated 1082 male partners from pregnant women in four European cities (Copenhagen, Denmark; Paris, France; Edinburgh, Scotland; and Turku, Finland). Semen analysis was standardized, inter-labora- tory differences in assessment of sperm concentration were evaluated, and morphology assessment centralized. Lowest sperm concentrations and total counts were detected for Danish men, followed by French and Scot- tish men. Finnish men had the highest sperm counts. Fur- thermore, semen quality of a 'standardized' man (30 years old, fertile, ejaculation abstinence of 96 h) was estimated. These data may also serve as a reference point for future studies on time trends in semen quality in Europe. In another study [30] 968 young men from the general pop- ulation in Denmark, Norway, Estonia and Finland were examined according to the same study protocol. Possible confounders including age of man, year of birth, year of participation in the study, season of year and duration of abstinence were evaluated, and included in the statistical analysis when appropriate. Inter-laboratory differences in assessment of sperm concentrations were controlled by an external quality control programme and morphology assessment was performed by one person. The men examined were recruited from groups attending a com- pulsory medical examination (military service), and not selected for known fertility or semen quality. Moreover, the majority of participants had no prior knowledge of their fertility potential. This cross-sectional study shows that a geographical gradient exists in the Nordic-Baltic area with regard to semen parameters, somewhat similar to the gradient in incidence of testicular cancer. However, it has to be kept in mind that the participation rate in this study was below 20%. Page 4 of 5 Carlsen et al. [1] speculate that environmental rather than genetic factors might be responsible for the secular trend in semen quality, which seems to be supported by the observation of increased testicular cancer incidence in many countries [31,32]. However, a possible causal relationship between sperm quality and environmental factors cannot be investigated by description of time- trends and correlation studies. Individual data of both semen quality and data on exposure to environmental factors have to be analysed in analytic case-control or cohort studies. Maternal factors during pregnancy deserve further investigation because they have changed over time and because they might influence male repro- ductive disorders like cryptorchidism, hypospadias, low sperm counts and testicular cancer [33]. This would cor- respond to a lifecourse approach regarding the investiga- tion of the semen quality and its determinants. Furthermore, fertility status and semen quality might be predictors of male health and life expectancy [34], which gives an important public health perspective for further studies. Summary The debate on declining semen quality is still ongoing [35,36]. The many studies which examined possible changes in semen quality have produced conflicting con- clusions mainly due to the heterogeneity between studies and differences in quality standards. Furthermore, the results of studies are frequently biased e.g. by selection criteria of volunteers or other confounding factors. The observed time trend in semen quality might be an arte- fact, since the methodological differences between stud- ies might be time dependent as well. Intensive research will be necessary in both clinical and epidemiological domains. More studies are needed with strict method- ological standards that investigate semen quality obtained from large samples of healthy men representa- tive for the normal male population. Competing interests The authors declare that they have no competing interests. Authors' contributions All authors made substantial contribution to the conception and design of the paper. HZ revised the paper critically and gave important intellectual input. MB is the principal investigator of the SANCO project and senior author of this manuscript. She contributed to design, analysis and details of the manuscript. All authors read and approved the final manuscript. Acknowledgements The paper summarized information of a final report of the study "Systematical analysis of studies on decreasing sperm quality" which was funded by the European Commission (SANCO), Project 17.020100/04/390129. Author Details Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, Mainz Received: 1 October 2009 Accepted: 19 January 2010 Published: 19 January 2010 TB©hM2iCs0ia1Psr0utaibMnclieOcriHpzseanvliatAchicla2eb0tls1ea0lf;a,rl1oitc0miec2nl:eh4sedtipsBt:r/iobwMuwtewd.CbueiondmtreadltLhctedn.teraml.csomft/h14e7C1r-e2a4t5iv8e/1C0o/m24monsAtributionLicense(htp:/creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.