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

Abstract

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.

Keywords: andrology; environmental effects; epidemiology; human reproduction; male infertility; meta-analysis; semen analysis; semen quality; sperm count; systematic review.

Figure 1

PRISMA Flow chart showing the selection of studies eligible for meta-regression analysis.

Figure 2

(a) Mean sperm concentration by year of sample collection in 244 estimates collected in 1973–2011 and simple linear regression. (b) Mean total sperm count by year of sample collection in 244 estimates collected in 1973–2011 and simple linear regression.

Figure 3

(a) Meta-regression model for mean sperm concentration by fertility and geographic groups, adjusted for potential confounders. (b) Meta-regression model for mean total sperm count by fertility and geographic groups, adjusted for potential confounders. Meta-regression model weighted by sperm concentration (SC) SE, adjusted for fertility group, time × fertility group interaction, geographic group, time × geographic group interaction, age, abstinence time, semen collection method reported, counting method reported, having more than one sample per men, indicators for study selection of population and exclusion criteria (some vasectomy candidates, some semen donor candidates, exclusion of men with chronic diseases, exclusion by other reasons not related to fertility, selection by occupation not related to fertility), whether year of collection was estimated, whether arithmetic mean of SC was estimated, whether SE of SC was estimated and indicator variable to denote studies with more than one estimate. Total sperm count (TSC) meta-regression models weighted by TSC SE, adjusted for similar covariates and method used to assess semen volume.