Reference Library

Am J Epidemiol. 1992 Jun 1;135(11):1208-19.

Fertility of male workers exposed to cadmium, lead, or manganese.

Gennart JP1, Buchet JP, Roels H, Ghyselen P, Ceulemans E, Lauwerys R.


The effect of exposure to cadmium, lead, or manganese on male reproductive function was examined in 1988-1989 in Belgian blue-collar workers. The workers were exposed to cadmium in two smelters (n = 83; geometric mean urinary cadmium level = 6.94 micrograms/g of creatinine; mean duration of exposure = 24 years), to lead in a battery factory (n = 74; mean blood lead level = 46.3 micrograms/dl; mean duration of exposure = 10.7 years), or to manganese (manganese dioxide) in a dry alkaline battery plant (n = 70; median atmospheric concentration of total manganese dust = 0.71 mg/m3; mean duration of exposure = 6.2 years). Fertility in these workers and in an unexposed population (n = 138) was assessed by examining the birth experiences of their wives through a logistic regression model. The probability of a live birth was not different between the unexposed workers and the cadmium- or manganese-exposed workers before or after the onset of exposure. While the fertility of the lead-exposed workers was somewhat greater than that of the unexposed before the onset of exposure, a significant decrease in fertility was observed during the period of exposure to the metal (odds ratio = 0.65, 95% confidence interval 0.43-0.98).

Int J Fertil Menopausal Stud. 1994 Jul-Aug;39(4):208-14.

Dietary exposure to aflatoxin in human male infertility in Benin City, Nigeria.

Ibeh IN1, Uraih N, Ogonar JI.



To discover the relationship between aflatoxin levels, if any, in serum of infertile men in comparison with random controls from the community. In a parallel experiment, adult male rats were given an aflatoxin-contaminated diet.


100 adult males, yielding 50 semen samples, from men attending Infertility Clinics at a university teaching hospital and 50 normal men in the same community.


The staple foods of the men were assayed for aflatoxin content. The rats were given the aflatoxin-rich diet, and their spermatozoa were examined and their ability to reproduce assessed.


A random sampling of semen from 100 adult males comprising 50 samples drawn from infertile men and 50 drawn from normal individuals within the same community revealed the presence of aflatoxins in 20 semen samples from the infertile group (40.0%) and four samples from the fertile group (8.0%). The mean aflatoxin concentrations were 1.660 +/- 0.04 micrograms/mL (infertile men) and 1.041 +/- 0.01 micrograms/mL (fertile men). Infertile men with aflatoxin in their semen showed a higher percentage of spermatozoal abnormality (50.0%) than the fertile men (10.0-15.0%). Dietary exposure of adult male Albino rats to aflatoxin (8.5 micrograms AF1/g of Guinea growers feed for 14 days) produced deleterious effects on the spermatozoa of the affected rats, producing features that resemble those seen in semen of infertile men exposed to aflatoxin.

Bull Environ Contam Toxicol. 1975 Aug;14(2):171-9.

The effect of DDT on spermatogenesis of the juvenile rat.

Krause W, Hamm K, Weissmüller J.


Juvenile male rats of Wistar/Han strain were fed DDT suspended in olive oil. They received either 500 mg/kg at the 4th and 5th or 300 mg/kg daily at the 4th till 23rd day of life. After certain interval the testes were examined histologically, and at the 60th and 90th day of life fertility was proved. The spermatogenetic cells showed an increase of the physiological degeneration in the course of spermatogenesis and a decrease of their total number. The number of Leydig cells was diminished. In parallel, the litters of normal female rats mated to treated males were smaller than those of controls. The hypothesis is suggested that the damage of the seminiferous epithelium can be explained by a lack of local testosterone.

Arch Androl. 1996 Nov-Dec;37(3):201-18.

Toxicology of male reproduction in animals and humans.

De Celis R1, Pedrón-Nuevo N, Feria-Velasco A.


Environmental contaminants can interfere with the male reproduction function. A review is presented of those pollutants with adverse effects on human reproduction. The possible effects of occupational and environmental exposure to various substances on male reproductive health are evaluated. This analysis considers studies showing damage of men exposed to halogenated hydrocarbons, other organic compounds, heavy metals and some physical agents, and some lifestyles, such as continuous stress, alcohol consumption, cigarette and marijuana smoking, and other addictions. Possible influences of these agents on the neuroendocrine system with the decrease of male fertility during the last decades are also discussed.

Hum Reprod. 1998 Aug;13(8):2122-5.

Occupational heat exposure and male fertility: a review.

Thonneau P1, Bujan L, Multigner L, Mieusset R.


In humans, as in most mammals, spermatogenesis is temperature dependent. This temperature dependence has been clearly demonstrated by several experimental studies showing that artificial increases in scrotum or testicle temperature in fertile men reduce both sperm output and quality. Our knowledge of the effects of occupational heat exposure on male fertility comes mostly from a small number of epidemiological studies. We conducted an extensive review of these published reports, focusing on methodology and design (retrospective or prospective; reference group; number of subjects) and principal results (using several indicators such as the time taken to obtain a pregnancy or sperm characteristics). We concluded that occupational heat exposure is a significant risk factor for male infertility, affecting sperm morphology and resulting in delayed conception. The limits and biases involved in this type of research are also discussed.

J Occup Environ Med. 1995 Aug;37(8):922-30.

Occupation- and exposure-related studies on human sperm.

Lähdetie J1.


Many kinds of exposures and chemicals have been shown to affect human sperm quantity and quality. This review focuses first on the best known occupational testicular toxin, dibromochloropropane. Prolonged heat is clearly detrimental to spermatogenesis. Studies on occupational heat, radiation, and chemical exposures and their effects on sperm are reviewed. The evaluation of human sperm studies is hampered by inconsistencies in biological analytical methods, in control for confounders, and in weaknesses of study design. Still, there is reason to suggest that human semen parameters can serve as valuable indicators of toxic and, in future, even genotoxic effects of occupational and environmental factors.

Verh K Acad Geneeskd Belg. 1999;61(3):441-52; discussion 453-5.

A strategy for the prevention of male infertility.

[Article in Dutch]

Comhaire FH1, Dhooge W, Mahmoud A, Depuydt C.


Since 1990 there has been a simultaneous reduction of natality in Flanders (by approximately 12%) with increased demand for assisted reproduction, while sperm quality, mostly motility and morphology, have clearly deteriorated over recent decades. This evolution has been ascribed to the deleterious effects of hormone disrupting substances in the environment, synergistically enhancing unfavorable influences from life style and possible genito urinary diseases that can impair the function of the testes and accessory sex glands. It is probable that this synergistic effect is exerted through the intermediate of free oxygen radicals (also called reactive oxygen species) that damage both the sperm membrane and sperm DNA, which could allow certain minimal inborn genetic defects (such as point lesions) to come to expression. Both pseudo- or xeno-estrogens (such as certain organo chlorides, alkyl phenols, phthalates, etc.) and anti-androgens are held responsible for prenatal testicular damage and increased prevalence of testicular carcinoma and oligozoospermia, for anatomical malformations, as well as postnatal depression of testicular function and spermatogenesis. However, methods presently available to detect hormone disrupters are tedious and not fully adequate. A first strategic goal is to develop a simple method for the detection of these substances so that environmental pollution can be mapped. Fazing out the production and application of hormone disrupters, and removing them from the environment are the second strategic step. Also, a health food is being developed that will inhibit the absorption of these chemicals from the intestinal tract. In addition it is projected to detect and treat common genital diseases that can cause infertility, such as varicocele and infection of the urinary tract and accessory sex glands. The first could be organized to take place during medical examinations at school, whereas the second requires correct medical treatment of any cysto urethritis in adolescents. Non surgical treatment of varicocele by means of transcatheter embolization offers a cost effective approach, with minimal risk and complications, and high level of efficacy. Improving food quality and educational efforts aimed at a healthier life style should score high priority. The suggested strategy uses several entries in order to address the multifactorial mechanisms involved in the pathogenesis of male infertility. Preliminary epidemiological and biological data suggest that the proposed strategy can, indeed, be successful within a relatively short lapse of time.

Hum Reprod. 1996 Feb;11(2):325-9.

Deterioration of sperm quality in young healthy Belgian men.

Van Waeleghem K1, De Clercq N, Vermeulen L, Schoonjans F, Comhaire F.


We have retrospectively analysed the sperm characteristics of 416 consecutive healthy young men who presented themselves in the past 19 years as candidate sperm donors. Ejaculate volume increased slightly (P = 0.067), and average sperm concentration decreased (P = 0.035) by 12.4 x 10(6)/ml over the observation period, so that sperm count per ejaculate remained unchanged (P = 0.91). In contrast, sperm morphology (r = - 0.23, P < 0.0001), rapid progressive motility (r = - 0.42, P < 0.0001) and total motility (r = - 0.33, P < 0.0001) presented an important and time-related decrease. When a quadratic model was used rather than a linear one to analyse the data on rapid progressive motility, there appeared to have been no further decline since 1990. The average proportion of spermatozoa with normal morphology decreased from 39.2% in the period 1977-1980 to 26.6% in 1990-1995 (P < 0.0001), and the mean percentage of spermatozoa with rapid progressive motility decreased from 52.7 to 31.7% (P < 0.0001). The percentage of candidate donors with sperm characteristics below the 5th percentile cut-off value of a normal fertile population increased from 13 to 54% during the observation period (P < 0.0001). Since the technique of semen analysis has remained essentially unchanged in-so-far as has been practically possible, as has the method of recruitment of candidate sperm donors, the observed deterioration of sperm characteristics is considered to reflect degeneration of sperm production among men aged between 20 and 40 years.

Environ Health Perspect. 1995 Oct;103 Suppl 7:137-9.

Declining semen quality and increasing incidence of testicular cancer: is there a common cause?

Carlsen E1, Giwercman A, Keiding N, Skakkebaek NE.


Male reproduction has been given little attention in science and in medical practice. However, a recent metaanalysis on semen quality, which clearly pointed to a decrease over the past 50 years, has been repeatedly quoted. Three recent reports have found that semen quality has declined among candidate semen donors during the past 20 years. The evidence of decline in the quality of semen is not the only indicator that the human testis is at risk. During the past 50 years, cancer of the testis has also become more common. This is a disorder of young men, and it is associated with a high rate of other abnormalities of the testis including undescended testis and poor semen quality. Furthermore, the incidence of both hypospadias and undescended testis has been reported to be rising in the general population. We believe that the evidence of declining semen quality should be seen in the light of these trends in other reproductive disorders of men. However, the etiology is unknown. A recent hypothesis that links the trends in the health of the male reproductive system to xenoestrogens in the environment is discussed.

BMJ. 1992 Sep 12;305(6854):609-13.

Evidence for decreasing quality of semen during past 50 years.

Carlsen E1, Giwercman A, Keiding N, Skakkebaek NE.



To investigate whether semen quality has changed during the past 50 years.


Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991).


14,947 men included in a total of 61 papers published between 1938 and 1991.


Mean sperm density and mean seminal volume.


Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density.


There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.

Ugeskr Laeger. 1993 Aug 16;155(33):2530-5.

Decline in semen quality from 1930 to 1991.

[Article in Danish]

Carlsen E1, Giwercman AJ, Keiding N, Skakkebaek NE.


It has been suspected for years that semen quality has declined. However, the issue is still controversial since previous studies were criticized for methodological errors. We therefore attempted to systematically review the complete international literature on semen quality since 1930 with rigorous selection criteria and statistical analysis. Based on a literature search using Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-august 1991), we identified 61 papers concerning sperm density in a total of 14,957 males without a history of infertility. A significant decline in mean sperm density from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in mean seminal volume from 3.40 ml to 2.75 ml (p = 0.027) was noted. The incidence of testis cancer and possibly also that of cryptorchidism and hypospadias has increased during the same relatively short time period. Such a remarkable deterioration in male genitourinary function is more likely to be due to environmental rather than genetic factors.

Arch Androl. 1996 Mar-Apr;36(2):139-43.

Changes in various antioxidant levels in human seminal plasma related to immunoinfertility.

Palan P1, Naz R.


The present study was designed (1) to determine levels of antioxidant micronutrients in human seminal plasma, and (2) to evaluate the association between the concentrations of these antioxidants and the antisperm antibody titers in immunoinfertile men. To investigate this, the seminal plasma concentrations of antioxidant beta-carotene, lycopene, retinol, and alpha-tocopherol were measured by high-pressure liquid chromatography in 37 men (22 fertile and 15 immunoinfertile), aged 27 to 35 years. The SIT (sperm-immobilization technique), TAT (tray-agglutination technique), and IBT (indirect immunobead test) were used to evaluate the antisperm antibody titers. The levels of three antioxidants, namely, beta-carotene, lycopene, and retinol, were significantly (p = .01) decreased and the concentration of alpha-tocopherol was significantly (p = .002) increased in seminal plasma of immunoinfertile men as compared to the levels in fertile men. There was a significant linear correlation between the antisperm antibody titer and beta-carotene level measured by IBT (r = .561, p = .002), whereas no significant correlation was found with the other three seminal plasma antioxidants, namely, lycopene, retinol, and alpha-tocopherol levels. These results indicate, for perhaps the first time, the presence of antioxidants in local genital tract secretions of men. Modulation of their concentrations in immunoinfertile men and their correlation with the antisperm antibody titers strongly suggest the involvement of dietary antioxidants in male infertility, especially mediated through immunologic factors.

Int J Androl. 1993 Feb;16(1):1-13.

Infection in the male reproductive tract. Impact, diagnosis and treatment in relation to male infertility.

Purvis K1, Christiansen E.


The following are the conclusions that can be derived from a review of the literature regarding the role of infection in the aetiology of male infertility. (i) Temporary inflammatory episodes in the male reproductive tract which are self-limiting are probably common. (ii) Caution should be exercised in the use of leukospermia or bacteriospermia as parameters for glandular infection. (iii) There is a need for alternative techniques for detecting non-symptomatic deep pelvic infections in the male; one technique of great promise is rectal ultrasound. (iv) Rectal ultrasound indicates that a large number of men with poor sperm quality have a non-symptomatic, chronic prostatovesiculitis. (v) Increasing evidence implicates Chlamydia trachomatis as being a major cause of chronic non-bacterial prostatitis. (vi) An important aspect of chlamydial infections in men may be that the male accessory sex glands may function as reservoirs for the organism, increasing the probability of infection in the female. (vii) Ureaplasma urealyticum may also play an important aetiological role in male infertility but its significance is confounded by its acknowledged function as a commensal in the reproductive tract. (viii) One of the manifestations of male reproductive tract infection is the induction of sperm autoantibodies. (ix) There is a need for more systematic controlled studies of the effects of antibiotic treatment on sperm quality with different preparations for extended periods using patient groups in which a glandular infection has been verified, e.g. by rectal ultrasonography.

Arch Androl. 1990;25(3):199-211.

Evaluation and treatment of a male factor component to unexplained infertility.

Check JH1, Nowroozi K, Lee M, Adelson H, Katsoff D.


The standard semen analysis frequently fails to identify subfertile males even when findings are normal and conversely often fails to identify fertile males with subnormal semen analyses. This has created the need to produce other tests of sperm physiology that will better distinguish a fertile from a subfertile specimen. Understanding more about the nature of the sperm defect should lead to the establishment of more specific and effective therapies. Until that time, it would still be reasonable to try some of the available empirical therapies even though they may work merely by a placebo mechanism.

Ann Med. 1992 Aug;24(4):259-72.

Male infertility: current concepts.

Purvis K1, Christiansen E.



The purpose of the article is to review the current concepts regarding the etiology and treatment of male-factor infertility. The following general conclusions can be drawn: (a) conventional parameters for sperm quality and male fertility are inadequate and any assessment should involve several different tests of sperm cell function to increase the fertility prognosis; (b) the causes of disturbed sperm quality are still poorly understood; (c) the role of the varicocele is still controversial but some of the discrepancies reported in the literature may be explained by the negative influence of other factors such as smoking, epididymal pathology or glandular infections operating either in conjunction or independent of the varicocele; (d) the role of chronic inflammatory processes in the reproductive organs, in particular the involvement of chronic chlamydial infections, has been underestimated, largely because it is often asymptomatic and difficult to demonstrate objectively; (e) partial androgen insensitivity may account for a significant number of cases of severe oligozoospermia; (f) no major advances have been made in the medical treatment of poor sperm quality; (g) assisted fertilization techniques such as IVF and GIFT offer encouraging possibilities for the treatment of male-factor infertility; and (h) recent advances in microsurgical techniques are increasing the treatment possibilities for certain forms of obstructive azoospermia and severe oligozoospermia.