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.

Genital tract infections and infertility.

Sperm DNA fragmentation in infertile men with genitourinary infection by Chlamydia trachomatis and Mycoplasma.

Oxidative stress (OS), defined as an overabundance of reactive oxygen species (ROS) or a deficiency of antioxidants, has been linked to sperm damage and male infertility. There are many sources of OS and inflammation including varicocele, tobacco usage, alcohol, obesity/metabolic syndrome, leukocytospermia, sexually transmitted disease (i.e., Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum), bacterial prostatitis, microorganism mutations leading to more OS, and viral infections (i.e., human immunodeficiency virus, hepatitis). This review is focusing on infection and inflammation-mediated OS, the inflammatory markers underlying pathology, clinical significance in male infertility, and a brief description of the recommended treatment modalities.

Role of oxidative stress, infection and inflammation in male infertility.

Background
Genital ureaplasmas (Ureaplasma urealyticum and Ureaplasma parvum) and mycoplasmas (Mycoplasma genitalium and Mycoplasma hominis) are potentially pathogenic species playing an etiologic role in both genital infections and male infertility. Reports are, however, controversial regarding the effects of these microorganisms infections in the sperm seminological variables. This study aimed at determining the frequency of genital ureplasmas and mycoplasmas in semen specimens collected from infertile men, and at comparing the seminological variables of semen from infected and non-infected men with these microorganisms.

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Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis and Mycoplasma genitalium infections and semen quality of infertile men

Aim: To investigate the clinical value of the screening of Ureaplasma urealyticum and Mycoplasma hominis in routine semen analysis. Ma

Ureaplasma urealyticum and Mycoplasma hominis in men attending for routine semen analysis. Prevalence, incidence by age and clinical settings, influence on sperm characteristics, relationship with the leukocyte count and clinical value.

The purpose of this study was to ascertain whether analysis of the physical properties of ejaculate also has any diagnostic potential for evaluating the function of these accessory sex glands. Diverse normal and abnormal states of coagulation, liquefaction, volume, viscosity and pH were studied with regard to the levels of biochemical markers of the seminal vesicles (fructose and inorganic phosphorus) and prostate (calcium, zinc and acid phosphatase). Fructose and inorganic phosphorus were significantly decreased in samples with absent or poor coagulation (p 120 min (p=0.003) and pH > 8.0 (p 5.0 mL (p=0.007, p=0.034 and p=0.011) and pH > 8.0 (p<0.001). Also, calcium and zinc were significantly increased in hypoviscous samples (p=0.012 and p=0.003), whereas the zinc concentration was significantly lower in hyperviscous samples (p=0.026). Using receiver operating characteristic (ROC) curve analysis, pH showed the highest predictive power to identify prostate dysfunction (83.6%) and simultaneous prostate and seminal vesicle dysfunction (98.8%). Physical analysis of ejaculate was also found to be clinically useful for evaluating the secretory activity of the seminal vesicles and prostate. Abnormal coagulation, liquefaction, volume, viscosity and pH strongly suggest gland dysfunction.

Physical analysis of ejaculate to evaluate the secretory activity of the seminal vesicles and prostate.

Semen analysis is a basic step in the investigation of several disturbances affecting the male genital tract. Analysis of seminal parameters provides important clinical information on the spermatogenesis and functional competence of spermatozoa, as well as on the secretory pattern of the accessory genital glands. Semen analysis is particularly useful in the evaluation of couples requiring fertility investigation (to detect genital infections and pathologies) and in verifying the influence of environmental factors, drugs, lifestyle, chemical products, and professional activities on several diseases affecting male reproductive health. Measure of semen quality is of substantial interest for diagnoses in clinical urology, andrology, and gynecology. Currently, basic requirements for semen analysis are standardized by World Health Organization (WHO) guidelines that describe several procedures for an objective evaluation of the semen quality with diagnostic purposes. These guidelines include: parameters for the physical and biochemical evaluation of semen; parameters for the analysis of sperm characteristics; and other seminal parameters that can be easily adopted in any laboratory. This report summarizes current concepts on semen analysis and the significance of the seminal parameters for reaching a diagnosis based on the procedures recommended by WHO guidelines.

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Semen analysis in laboratory practice: an overview of routine tests.

Objective To determine the distribution of sperm abnormalities in a population of suspected infertile men presenting for the initial investigation of male factor infertility. Study design Results obtained in the analysis of sperm viability, motility, conventional morphology (including 12 sperm anomalies), strict criteria sperm morphology analysis (SCSMA) and hypoosmotic swelling test (HOST) were compared in oligozoospermic ( 250.0 x 10(6)/mL) semen samples from 233 suspected infertile men. Results Percentage of sperm viability, category a and categories a plus b of sperm motility, oval-headed sperm, and normal-headed sperm according to SCSMA and HOST had a direct relationship with sperm counts (P 40.0 x 10(6)/mL (P = .003) and of neck/midpiece defects was lowest in semen with 250.0 x 10(6)/mL (viability and motility), > 100.0 x 10(6)/mL (conventional morphology) and > 40.0 x 10(6)/mL (SCSMA and HOST). Conclusion The incidence of defective spermatozoa is lowest in semen with the highest sperm count. However, sperm abnormalities that affect male fertility may be detected at any level of sperm density. The data indicate that an increase in any sperm abnormality should be regarded as a possible cause of decreased fertility.

Sperm parameters in men with suspected infertility. Sperm characteristics, strict criteria sperm morphology analysis and hypoosmotic swelling test.

The relationship between seminal fructose concentration and sperm characteristics was investigated in semens of 187 suspected infertile men without evidence of disturbances in the seminal vesicular function. Sperm density, viability, motility, morphologically oval sperm, and 10 categories of defective spermatozoa (small, large, amorphous, round-head, double-head, pin-head, tapering, mid-piece defects, tail defects, and combined defects) were assessed in 6 levels of seminal fructose concentration, as follows: (1) 0 to 1.0 mg/ml; (2) 1.1 to 2.0 mg/ml; (3) 2.1 to 3.0 mg/ml; (4) 3.1 to 4.0 mg/ml; (5) 4.1 to 5.0 mg/ml; (6) >5.0 mg/ml. None of the sperm characteristics analyzed had shown statistically significant differences among the study groups. It is concluded that seminal fructose levels detected in the routine of semen analysis give no information on the clinical usefulness in defective sperm formation.

Fernando Tadeu Andrade-Rocha

Papers

Ureaplasma urealyticum and Mycoplasma hominis in men attending for routine semen analysis. Prevalence, incidence by age and clinical settings, influence on sperm characteristics, relationship with the leukocyte count and clinical value.

Physical analysis of ejaculate to evaluate the secretory activity of the seminal vesicles and prostate.

Semen analysis in laboratory practice: an overview of routine tests.

Sperm parameters in men with suspected infertility. Sperm characteristics, strict criteria sperm morphology analysis and hypoosmotic swelling test.

Seminal fructose levels in male infertility: relationship with sperm characteristics.