BACKGROUND Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality. OBJECTIVE AND RATIONALE To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group. SEARCH METHODS PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981-2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973-2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group ('Unselected by fertility' versus 'Fertile'), geographic group ('Western', including North America, Europe Australia and New Zealand versus 'Other', including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models. OUTCOMES SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models -0.70 million/ml/year; 95% CI: -0.72 to -0.69; P < 0.001; slope in adjusted meta-regression models = -0.64; -1.06 to -0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (-1.38; -2.02 to -0.74; P < 0.001) and among Fertile Western (-0.68; -1.31 to -0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (-5.33 million/year, -7.56 to -3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (-2.06 million/ml, -3.38 to -0.74; P = 0.004 and -8.12 million, -13.73 to -2.51, P = 0.006, respectively). WIDER IMPLICATIONS This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed.

Temporal trends in sperm count: a systematic review and meta-regression analysis.

In 1992 Carlsen et al. reported a significant global decline in sperm density between 1938 and 1990 [Evidence for Decreasing Quality of Semen during Last 50 Years. Br Med J 305:609-613 (1992)]. We subsequently published a reanalysis of the studies included by Carlsen et al. [Swan et al. Have Sperm Densities Declined? A Reanalysis of Global Trend Data. Environ Health Perspect 105:1228-1232 (1997)]. In that analysis we found significant declines in sperm density in the United States and Europe/Australia after controlling for abstinence time, age, percent of men with proven fertility, and specimen collection method. The declines in sperm density in the United States (approximately 1.5%/year) and Europe/Australia (approximately 3%/year) were somewhat greater than the average decline reported by Carlsen et al. (approximately 1%/year). However, we found no decline in sperm density in non-Western countries, for which data were very limited. In the current study, we used similar methods to analyze an expanded set of studies. We added 47 English language studies published in 1934-1996 to those we had analyzed previously. The average decline in sperm count was virtually unchanged from that reported previously by Carlsen et al. (slope = -0.94 vs. -0.93). The slopes in the three geographic groupings were also similar to those we reported earlier. In North America, the slope was somewhat less than the slope we had found for the United States (slope = -0.80; 95% confidence interval (CI), -1.37--0.24). Similarly, the decline in Europe (slope = -2.35; CI, -3.66--1.05) was somewhat less than reported previously. As before, studies from other countries showed no trend (slope = -0.21; CI, -2.30-1.88). These results are consistent with those of Carlsen et al. and our previous results, suggesting that the reported trends are not dependent on the particular studies included by Carlsen et al. and that the observed trends previously reported for 1938-1990 are also seen in data from 1934-1996.

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The question of declining sperm density revisited: an analysis of 101 studies published 1934-1996.

The link between varicoceles and male infertility has been a matter of debate for more than half a century. Varicocele is considered the most common correctable cause of male infertility, but some men with varicoceles are able to father children, even without intervention. In addition, improvements in semen quality after varicocelectomy do not always result in spontaneous pregnancy. Studies regarding possible pathophysiological mechanisms behind varicocele-induced infertility have tried to address these controversies. Oxidative stress seems to be a central mechanism; however, no single theory is able to explain the differential effect of varicoceles on infertility. As a consequence, careful patient selection for treatment based on couple fertility status, varicocele grade, and semen quality is critical for achieving a chance of a subsequent pregnancy. A substantial amount of data on the effects of varicocelectomy has been gathered, but inadequate study design and considerable heterogeneity of available studies mean that these data are rarely conclusive. Current evidence suggests a beneficial effect of varicocelectomy on semen quality and pregnancy outcomes in couples with documented infertility only if the male partner has a clinically palpable varicocele and affected semen parameters.

Varicocele and male infertility

https://www.europeanurology.com/article/S0302-2838(16)30396-7/pdf/varicocele-is-associated-with-impaired-semen-quality-and-reproductive-hormone-levels-a-study-of-7035-healthy-young-men-from-six-european-countries

Varicocele Is Associated with Impaired Semen Quality and Reproductive Hormone Levels: A Study of 7035 Healthy Young Men from Six European Countries.

Are varicoceles associated with increased deoxyribonucleic acid fragmentation

A group of 598 allegedly fertile men requesting vasectomy were investigated; varicocele was found in 97 (16.2%) of these men. The mean ages and age distributions of men with and without varicocele were not significantly different. Reproductive histories (number of pregnancies, living children and spontaneous abortions, as well as incidence of present pregnancy) were similar in both groups. The average seminal characteristics (semen volume, sperm count, total sperm count, percentage of motile spermatozoa, quality of motility, morphology) were not different for men with and without varicocele, except for a slight, but significantly higher incidence of oval-headed sperm in men without varicocele. However, the incidence of varicocele was significantly higher in men with sperm counts below 40 million/ml. Three important observations may be made from this study: 1) the incidence of varicocele in this prevasectomy population was similar to that reported for the general population, but lower than the incidence reported for male partners of infertile couples; 2) in this population of allegedly fertile men, the presence of a varicocele did not significantly affect reproductive performance; 3) even though the incidence of varicocele was higher in men with sperm counts below 40 million/ml, the average seminal characteristics were not different in men with and without varicocele.

D. A. M. Mastrorocco

Papers

Reproductive History and Semen Analysis in Prevasectomy Fertile Men with and without Varicocele