Levine Hagai, Jørgensen Niels, Martino-Andrade Anderson, Mendiola Jaime, Weksler-Derri Dan, Mindlis Irina, Pinotti Rachel, Swan Shanna H
Braun School of Public Health and Community Medicine, Hadassah-Hebrew University, the Hebrew University Center of Excellence in Agriculture and Environmental Health, Ein Kerem Campus, PO BOX 12272, Jerusalem 9110202, Israel.
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Hum Reprod Update. 2017 Nov 1;23(6):646-659. doi: 10.1093/humupd/dmx022.
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.
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.
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.
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).
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.
目前,关于精子数量下降的报道仍存在争议,近期趋势尚不清楚。鉴于精子数量对生育、发病率和死亡率的预测价值,进行确定性的荟萃分析至关重要。
对精子浓度(SC)和总精子数(TSC)所测定的精子数量近期趋势及其受生育能力和地理区域分组的影响进行系统评价和荟萃回归分析。
检索PubMed/MEDLINE和EMBASE数据库中1981年至2013年发表的关于人类SC的英文研究。按照预定义方案筛选了7518篇摘要,并对2510篇报告SC原始数据的全文进行了审查。从185项研究中提取了42935名在1973年至2011年期间提供精液样本的男性的244个SC和TSC估计值用于荟萃回归分析,以及样本采集年份和协变量信息[生育能力分组(“未按生育能力选择”与“可育”)、地理区域分组(“西方”,包括北美、欧洲澳大利亚和新西兰与“其他”,包括南美、亚洲和非洲)、年龄、射精禁欲时间、精液采集方法、SC测量方法和精液体积、排除标准以及协变量数据完整性指标]。使用简单线性回归和加权荟萃回归模型将SC和TSC的斜率估计为样本采集年份的函数,后者针对预先确定的协变量以及生育能力和地理区域分组的影响进行了调整。通过多重敏感性分析和非线性模型检验了假设。
1973年至2011年期间,SC显著下降(未调整的简单回归模型斜率为-0.70百万/ml/年;95%CI:-0.72至-0.69;P<0.001;调整后的荟萃回归模型斜率=-0.64;-1.06至-0.22;P=0.003)。荟萃回归模型中的斜率受生育能力(交互作用P=0.064)和地理区域分组(交互作用P=0.027)的影响。1973年至2011年期间,未按生育能力选择的西方人群(-1.38;-2.02至-0.74;P<0.001)和可育西方人群(-0.68;-1.31至-0.05;P=0.033)的SC显著下降,而未按生育能力选择的其他人群和可育其他人群未观察到显著趋势。在未按生育能力选择的西方研究中,平均SC每年下降1.4%,1973年至2011年期间总体下降52.4%。TSC和SC的趋势相似,未按生育能力选择的西方人群下降幅度较大(-533万/年,-7.56至-3.11;P<0.001),对应平均TSC每年下降1.6%,总体下降59.3%。多重敏感性分析结果变化极小,且没有统计支持使用非线性模型。在仅限于1995年后数据的模型中,未按生育能力选择的西方人群中SC和TSC的斜率与整个时期相似(-2.06百万/ml,-3.38至-0.74;P=0.004和-812万,-13.73至-2.51,P=0.006)。
这项全面的荟萃回归分析报告了1973年至2011年期间精子数量(以SC和TSC衡量)显著下降,这是由北美、欧洲、澳大利亚和新西兰未按生育能力选择的男性中50%-60%的下降所驱动的。由于这些结果对公共卫生具有重大影响,迫切需要对这种持续下降的原因进行研究。