BACKGROUND Semen quality is taken as a surrogate measure of male fecundity in clinical andrology, male fertility, reproductive toxicology, epidemiology and pregnancy risk assessments. Reference intervals for values of semen parameters from a fertile population could provide data from which prognosis of fertility or diagnosis of infertility can be extrapolated. METHODS Semen samples from over 4500 men in 14 countries on four continents were obtained from retrospective and prospective analyses on fertile men, men of unknown fertility status and men selected as normozoospermic. Men whose partners had a time-to-pregnancy (TTP) of < or =12 months were chosen as individuals to provide reference distributions for semen parameters. Distributions were also generated for a population assumed to represent the general population. RESULTS The following one-sided lower reference limits, the fifth centiles (with 95th percent confidence intervals), were generated from men whose partners had TTP < or = 12 months: semen volume, 1.5 ml (1.4-1.7); total sperm number, 39 million per ejaculate (33-46); sperm concentration, 15 million per ml (12-16); vitality, 58% live (55-63); progressive motility, 32% (31-34); total (progressive + non-progressive) motility, 40% (38-42); morphologically normal forms, 4.0% (3.0-4.0). Semen quality of the reference population was superior to that of the men from the general population and normozoospermic men. CONCLUSIONS The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.

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World Health Organization reference values for human semen characteristics

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently growing demand for assisted reproduction. Due to specialization in medicine and different ages at presentation of symptoms, reproductive problems used to be analysed separately by various professional groups, e.g. paediatric endocrinologists, urologists, andrologists and oncologists. This article summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. Experimental and epidemiological studies suggest that TDS is a result of disruption of embryonal programming and gonadal development during fetal life. Therefore, we recommend that future epidemiological studies on trends in male reproductive health should not focus on one symptom only, but be more comprehensive and take all aspects of TDS into account. Otherwise, important biological information may be lost.

Testicular dysgenesis syndrome ; an increasingly common developmental disorder with environmental aspects

Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.

Male reproductive health and environmental xenoestrogens

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.

This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter.

Environmental endocrine disruption: an effects assessment and analysis.

Objective: To determine whether the quality of semen has changed in a group of over 500 Scottish men born between 1951 and 1973. Design: Retrospective review of data on semen quality collected in a single laboratory over 11 years and according to World Health Organisation guidelines. Setting: Programme of gamete biology research funded by Medical Research Council. Subjects: 577 volunteer semen donors. Of these, 171 were born before 1959, 120 were born in 1960-4, 171 in 1965-9, and 115 in 1970-4. Main outcome measures: Conventional criteria of semen quality including semen volume (ml), sperm concentration (106/ml), overall motility (% motile), total number of sperm in the ejaculate (106), and total number of motile sperm in the ejaculate (106). Results: When the four birth cohort groups were compared a later year of birth was associated with a lower sperm concentration, a lower total number of sperm in the ejaculate, and a lower number of motile sperm in the ejaculate. The median sperm concentration fell from 98x106/ml among donors born before 1959 to 78x106/ml among donors born after 1970 (P=0.002). The total number of sperm in the ejaculate fell from 301x106 to 214x106 (P=0.0005), and the total number of motile sperm in the ejaculate fell from 169.7x106 to 129.0x106 (P=0.0065). Conclusion: This study provides direct evidence that semen quality is deteriorating, with a later year of birth being significantly associated with a reduced number of sperm in adult life. Key messages Key messages When men born in the 1970s were compared with men born in the 1950s, the total number of motile sperm in the ejaculate was reduced by almost 25% These data confirm previously published data from other countries that semen quality is changing, declining by about 2.1% per year Research is urgently required to examine the function as well as the number of sperm and to assess whether these changes are affecting human health and male fertility

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Evidence of deteriorating semen quality in the United Kingdom: birth cohort study in 577 men in Scotland over 11 years

anaemia from carcinoma at the cardiac orifice of the ,stomach. Here there were occasional enormous red corpuscles that would have done credit to any case of per-nicious anaemia, and others that were distinctly above the normal size. But these were exceptions, and the average -size was much below normal, in keeping with a haemo-globin percentage of 18, a red count of 1,560,000, and a haemoglobin index of only 57 per cent. Even in a typical case of chlorosis I have come across large numbers of macrocytes, which at first sight strongly suggested pernicious anaemia, but the other corpuscles were small, and, in spite of the number of large corpuscles, the average size was below normal, as shown by the low haemoglobin index of 64.

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Pernicious anaemia with pigmentation of the skin and buccal mucous membrane

Declining sperm count

• VA loses the majority of trainees to private sector competitors • Hiring current or former VA health professions trainees into Hybrid or Title 38 positions can be quick and easy • Once internal employee job posting requirements in local bargaining unit agreements are met, current or former trainees can be appointed to Hybrid and Title 38 vacancies without posting any type of vacancy announcement • Title 38/Hybrid Title 38 allows selection of current trainees who will meet qualification standards at the time of appointment as well as former graduates • Trainees may be selected and tentatively offered positions prior to graduation o Offers may be made contingent upon meeting qualifications at the time of appointment o Graduates who still have pending credentials (licensure, certification, etc.) may be hired as graduate technicians in their occupations, in accordance with VA Handbook 5005 procedures for the occupation • The VAOIG has designated 5 critical shortage occupations for FY16: o Physicians (all specialties) o Nurses (RN, CRNA, NP) o Physician Assistants o Physical Therapists o Psychologists Note: During FY16, Hybrid Title 38 Veterans’ Preference rules do not apply to Physical Therapists and Psychologistsnormal Title 38 Veterans’ Preference procedures should be followed for the 38 U.S.C. 7401(1) occupations – Physicians, Nurses and Physician Assistants • Trainee hiring flexibilities apply to all Title 38 and Hybrid Title 38 occupations and are not limited just to the VAOIG top 5 critical shortage occupations

John Aitken

Papers

Evidence of deteriorating semen quality in the United Kingdom: birth cohort study in 577 men in Scotland over 11 years

Pernicious anaemia with pigmentation of the skin and buccal mucous membrane

Declining sperm count

Urgent action needed