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Factors affecting sperm yield during swim-up.

PURPOSE: The migration of sperm (expressed as the percentage of the total motile cells in the ejaculate aliquot) from seminal plasma into overlying medium (swim-up) was increased with time, temperature, and increasing the surface area of contact between the two phases by increasing the angle of tube inclination. RESULTS: The proportion of sperm migrating into the medium was relatively constant with varying sperm count. Stimulation of the progressive motility of spermatozoa in vitro using a motility enhancing drug (2-deoxyadenosine) increased sperm migration initially but no more than the maximum reached by controls after extended incubation. CONCLUSION: Sperm yield from normozoospermic men and men with borderline asthenoteratozoospermia represented approximately 40 and 15% of the total motile cells in the ejaculate aliquots, respectively. In general, in both groups spermatozoa in the swim-up fraction exhibited superior motility, vitality, and morphology compared to the original ejaculates. Tail abnormalities were reduced more than head abnormalities and subjects with borderline sperm qualities exhibited less dramatic improvements in quality than the normozoospermic individuals.

Cell Separation↗

New treatment of idiopathic severe oligozoospermia with mast cell blocker: results of a single-blind study.

OBJECTIVE: To determine whether mast cell blocker (tranilast) improves fertility and/or semen parameters in severe oligozoospermia. DESIGN: Placebo-controlled single-blind clinical study. SETTING: Nagoya University Hospital Andrology Clinic, Nagoya, Japan. PATIENTS: Fifty men with sperm density < 5 x 10(6) sperm/mL, normal serum gonadotropins, and T, and a fertile partner were enrolled in this study. INTERVENTIONS: Patients were prescribed randomly 300 mg/d tranilast or a placebo, three tablets per day, for 3 months. Semen and blood samples were collected before and after therapy. Semen parameters, serum gonadotropins, T, and PRL were evaluated before and after therapy. RESULTS: The pregnancy rate (PR) in the mast cell blocker group was 28.6% compared with 0% in the placebo group. There was a statistical difference in the PR between groups. The mast cell blocker group had significantly higher levels of sperm density, sperm motility, and total motile sperm count. There were no differences between the mast cell blocker and placebo groups in seminal volume and normal sperm morphology. CONCLUSIONS: The authors conclude that mast cell blocker is clinically useful for the treatment of idiopathic severe oligozoospermic men.

Adult↗

Trends in semen parameters in the northeast of Scotland.

The data on trends in semen quality are conflicting and sensitive to geographical variations. Although previous British surveys on semen quality indicate a decline, the northeast of Scotland has never been included in these surveys. This is an area with low out migration rates where andrology services for a population of 500 000 are centralized within a single laboratory, thus providing a unique opportunity to study population-based trends in semen quality over time. We investigated trends in semen parameters between 1994-2005, in a cohort of 4832 men attending for routine semen analysis at the Aberdeen Fertility Centre who had a sperm density of greater than 20 million per mL. The main outcome measures were trends in sperm density, sperm motility and motile density in the first semen sample. Linear regression and time series analysis were used to examine trends over time in the semen parameters. The mean and standard deviation (SD) age of all men (n=5204) in the study was 34(6) years. The median (inter quartile range) for sperm density and motile density for the study population were 61 (40-91) million/mL and 99 (47-181) million. The mean (SD) sperm motility was 49 (19)%. Among 4832 men (with sperm count >20 million per mL), data adjusted for age and period of abstinence showed a decreasing trend for sperm density over time, R2=0.45 (P=.017). There was no such trend in sperm motility and motile density. However, this trend has to be interpreted with caution due to fluctuations in semen parameters, population bias and the retrospective nature of the analysis.

Adolescent↗

Tumor-associated trypsin inhibitor as a possible marker in male infertility.

The concentrations of tumor-associated trypsin inhibitor (TATI) in the seminal plasma of infertile males was studied. The TATI levels in seminal plasma were not correlated with either sperm count or ejaculate volume. High levels were observed in some men with unexplained infertility and high or normal sperm counts, whereas normal levels were observed in males with antisperm antibodies. The concentrations in seminal plasma were stable in the same subjects. These results suggest that TATI may be an important marker of reproductive pathology in men.

Adult↗

[Effects of perfluorooctane sulfonate on spermiogenesis function of male rats].

OBJECTIVE: To evaluate the effects of administration of perfluorooctane sulfonate(PFOS) on spermiogenesis function of male rats. METHODS: 36 male rats were randomly divided into 4 groups, which received 0, 0.5, 1.5, 4.5 mg x kg(-1) PFOS by food intake per day for 65 days. The testicular and epididymal viscera coefficients, the number, motility and deformity of sperm were examined. The activities of lactate dehydrogenase isoenzyme-x (LDHx), sorbitol dehydrogenase (SDH) and the generation of malonyldialdehyde (MDA) in the testes were also measured. RESULTS: The viscera coefficients did not show any significant change ( P > 0.05) while the body weight and weight of testis decreased ( P < 0.05) in treated rats compared with the corresponding control group animals. In 1.5,4.5 mg x kg(-1) PFOS treated rats there were significant decreases in the sperm count (P < 0.05) and the mean activities of LDHx and SDH whereas obvious increases in the rate of sperm deformity ( P < 0.05). In 4.5 mg x kg(-1) PFOS group the generation of MDA increased (P < 0.05) while the motility of sperm reduced (P < 0.05) with respect to the control value. CONCLUSION: It suggested that PFOS could elicit the impairment of sperm production and maturation of male rats.

Alkanesulfonic Acids↗

Effects of delivering different amounts of dihydrotestosterone by ceramic implants on the reproductive system of male rats.

Administration of drugs or hormones to patients, orally or by injections, results in a pulsatile delivery of the drug. The purpose of this study was to determine whether dihydrotestosterone (DHT), delivered in a sustained manner by ALCAP ceramic capsules, can regulate fertility in male rats. Sixty rats were distributed equally into 4 groups. Each of the 15 capsules (1.60 +/- 0.01 gm/cm3) in groups I, II and III was loaded with 30, 60, and 90 mg DHT, respectively and implanted in rats. Rats in group IV served as controls and were implanted with empty capsules. Five rats from each group were euthanized at the end of 1, 2, and 3 months. The data obtained showed that the weights of vital organs of rats in all groups did not differ significantly. At the end of 3 months, accessory reproductive organs (ARO) in group I and group II rats showed significantly lower sperm counts, but maintained the weights of ARO. Group III rats did not show a significant decrease in the sperm counts or weights of ARO in comparison to values obtained for control rats. The data obtained suggest that DHT, delivered in appropriate amounts by ceramic capsules, can be used to regulate fertility in mammals.

Animals↗

Measurement of seminal LDH-X and transferrin in normal and infertile men.

LDH-X, an isoenzyme of lactate dehydrogenase specific for germinal epithelium activity, has been measured in the seminal plasma of infertile subjects whose infertility had different origins. In the same samples, seminal transferrin, an index of Sertoli cell function, was also measured. In this investigation, seminal LDH-X was not detectable in the vasectomized subjects, in patients with azoospermia due to seminiferous tubular damage, nor in patients who showed a marked decrease in sperm concentration (less than 1 X 10(6)/ml). In oligozoospermic patients (sperm concentration less than 20 X 10(6)/ml) seminal LDH-X levels were reduced to about one-third of those found in normal controls. Seminal LDH-X levels correlated (r = 0.7237) with total sperm count better than seminal transferrin levels (r = 0.5511), while no correlation was found between these two biochemical parameters and sperm motility, viability and morphology. To study their spontaneous variations with time, LDH-X and transferrin were also measured in semen specimens collected monthly from five healthy men, over 1 year. In these samples (N = 60), sperm count variability (43.1%, calculated in terms of the coefficient of variation), was similar to that of LDH-X (40.4%) and higher than for transferrin (23.0%).

Adult↗

Fertility treatment and reproductive health of male offspring: a study of 1,925 young men from the general population.

Little is known the about the reproductive health of offspring after fertility treatment. In 2001-2005, the authors approached young Danish men attending a compulsory physical examination to determine their fitness for military service. A total of 1,925 men volunteered, delivered a semen sample, had a physical examination performed and a blood sample drawn, and responded to a questionnaire. Their mothers were questioned about whether they had received fertility treatment in order to conceive their sons. Forty-seven mothers reported having received fertility treatment to conceive the index subject. After control for confounders, men whose mothers had received fertility treatment to conceive them had a 46% lower sperm concentration (95% confidence interval (CI): -63, -20) and a 45% lower total sperm count (95% CI: -64, -16). They had a smaller testis size (-0.9 ml, 95% CI: -2.2, 0.4), fewer motile sperm (-4.0%, 95% CI: -8.0, -0.1), and fewer morphologically normal spermatozoa (-2.0%, 95% CI: -4.1, 0.0). They also had a lower serum testosterone level and free androgen index (results not statistically significant). These findings should be viewed in light of the increasing use of fertility treatments. Although the cause of these findings is unknown, they raise concern about possible late effects of fertility treatment. Larger-scale studies of children born after fertility treatment should be performed.

Adult↗

Pregnancy course and health of children born after ICSI depending on parameters of male factor infertility.

BACKGROUND: There is an ongoing debate as to whether the outcome of ICSI is affected by the origin of sperm used or by the severity of male factor infertility. METHODS: Data from a multicentric prospective, controlled cohort study in Germany were analysed to look for differences in pregnancy course and outcome following the use of either ejaculated, epididymal or testicular sperm. Pregnancies were recruited before the 16th week of gestation and included only when they were still ongoing in the 16th week of gestation. A total of 2809 pregnancies was originally included in the study. For 2545 pregnancies with 3199 fetuses/children, data of sperm count and origin were available. RESULTS: Regarding pregnancy course and complications, there was no influence of the origin of sperm. No higher risk of pre-eclampsia was associated with the use of surgically obtained sperm. The birth data of children were similar between the three groups (ejaculated, epididymal, testicular sperm). The risk of major malformation in abortions, stillbirths, livebirths and induced abortions was not significantly different between the three groups, but these results must be treated with caution because of the low numbers in some groups. Major malformation rates did not depend on the number of sperm in the ejaculate. CONCLUSIONS: The course of pregnancy as well as the outcome after ICSI is neither affected by the origin of sperm nor by the number of sperm in the ejaculate.

Child Welfare↗

Low dose gossypol for male contraception.

AIM: To ascertain whether the side effects of gossypol, hypokalemia and irreversibility, could be avoided on dose reduction. METHODS: Seventy-seven male volunteers were divided into 3 groups: control (22 cases), 10 mg gossypol (29 cases) and 12.5 mg (26 cases). Serum levels of testosterone, FSH and LH were measured by RIA and potassium by flame photometry. Sperm counts and motility were examined before and regularly after treatment for the evaluation of contraceptive efficacy. RESULTS: The average sperm density and motility started to decrease significantly by the end of month 2 of medication and gradually reached the infertility levels (< 4 million/mL) in both treated groups. After that the 10 mg group was asked to take the same dose every other day for up to a total observation period of 16-18 months for the maintenance of infertility. Subjects in the 12.5 mg group did not take gossypol any more so as to observe the length of the loading dose required, but in a few, a maintenance dose of 12.5 mg every other day was instituted for a few more months. In both treated groups, none of the spouses was pregnant during the maintenance dose period. Serum levels of potassium, FSH, LH and testosterone were not significantly changed and not a single volunteer complained of myoasthenia. After cessation of drug administration, the semen data returned to pretreatment levels. CONCLUSION: A regimen with 10 or 12.5 mg of gossypol as the daily loading dose and 35 or 43.75 mg as the weekly maintenance dose could induce infertility in male volunteers without developing hypokalemia or irreversibility.

Contraceptive Agents, Male↗

Effects of low doses of cyproterone acetate on sperm morphology and some other parameters of reproduction in normal men.

Cyproterone acetate was given to three healthy men in a dosage of 10 mg per day for 8-14 weeks. The effects on sperm count, morphology, motility and vitality was followed weekly and compared with the effects of 25 mg daily in another case. Sperm morphology included the study of live spermatozoa separately. The effects on serum levels of FSH, LH, testosterone and oestrogens was also studied. With respect to sperm count and morphology a dose-effect relationship is indicated. Abnormalities within tails and midpieces of live spermatozoa appear early and may predict sterility before azoospermia develops. FSH and oestrogens were comparatively more depressed than LH and testosterone. The results indicate that cyproterone acetate may have an androgenic (or gestagenic) effect on the hypophyseo-hypothalamic level in addition to an antiandrogenic effect on gonads and their accessory organs.

Adult↗

Effect of bisphenol A and co-administration of bisphenol A and vitamin C on epididymis of adult rats: a histological and biochemical study.

AIM: To study the effect of bisphenol A on the epididymis and epididymal sperm of rats and the possible amelioration action of co-administration with vitamin C. METHODS: Male Wistar rats were orally administered bisphenol A (0.2 microg x kg (-1) x day(-1), 2 microg x kg(-1) x day(-1) and 20 microg x kg(-1) x day(-1)) and 0.2 microg, 2 microg and 20 microg bisphenol A + 40 mg vitamin C x kg(-1) x day(-1) for 60 days. On day 61, rats were killed with anesthetic ether and sperm collected from epididymis were used or assessment of sperm count, motility and viability and biochemical studies. A 1 % homogenate of epididymis was prepared and used for biochemical estimations. Caput, corpus and cauda epididymis were fixed in Bouin's fixative for histological studies. RESULTS: Administration of bisphenol A caused a reduction in the epididymal sperm motility and count and the sperm viability remained unchanged. The activities of superoxide dismutase and glutathione peroxidase decreased, while the levels of lipid peroxidation increased in epididymal sperm and epididymis at all doses. Co-administration with vitamin C reversed the effect of bisphenol A-induced oxidative stress in epididymal sperm and epididymis. A complete degeneration of epididymal epithelium in caput, corpus and cauda regions with reduction in the number of sperms were observed at all doses of bisphenol A-treated rats. CONCLUSION: Bisphenol A induced oxidative stress in epididymis and caused degeneration of the epididymal epithelium of rats. Co-administration with vitamin C had a protective effect against the bisphenol A-induced toxicity in epididymal sperm and epididymis.

Air Pollutants, Occupational↗

Assessment of in vivo mutagenic potency of ethylenediaminetetraacetic acid in albino mice.

Ethylenediaminetetraacetic acid (EDTA) disodium salt, a widely used metal chelator, was studied for its potency to induce bone marrow micronuclei, dominant lethal mutations and sperm-head abnormalities in albino mice. The acute oral LD50 dose computed by probit regression was 30 mg/kg body weight in the strain used. Preliminary studies showed that oral administration of EDTA disodium salt at doses of 5, 10 and 15 mg/kg body weight/day on 5 consecutive days did not induce any obvious signs of toxicity. In the bone marrow micronucleus assay acute doses of EDTA disodium salt (5-20 mg/kg body weight) induced a dose-dependent increase in the incidence of micronucleated polychromatic erythrocytes at a 24-hr sampling. However, administration at doses of 5, 10 and 15 mg/kg for 5 consecutive days did not produce any observable effect on either the testicular or epididymal weights and histology. No appreciable alterations were observed in the caudal sperm counts at any of the sampling intervals and there was no treatment-related increase in the incidence of sperm-head abnormalities. Furthermore, treatment of male mice with EDTA disodium salt (10 mg/kg body weight/day for 5 consecutive days) induced no increase in the incidence of post-implantation embryonic deaths, except for a marginal but statistically insignificant increase during wk 2 and 3 of mating.

Animals↗

Postnatal exposure of the male mouse to 2,2',3,3',4,4',5,5',6,6'-decabrominated diphenyl ether: decreased epididymal sperm functions without alterations in DNA content and histology in testis.

2,2',3,3',4,4',5,5',6,6'-Decabrominated diphenyl ether (PBDE 209) is the second most used brominated flame retardant (BFRs) in constructed materials because it is considered less toxic than others, though other fire retardants, some congeners of PBDE 209, are reported to be toxic. This combined the fact that PBDE 209 has been found in high levels in human milk, blood, indoor environments as well as in foodstuffs has led us in this study attempt to find out whether PBDE 209, also known as decaBDE and decabrominated diphenyl oxide (DBDPO), has an adverse effect on this histology of testes and sperm in CD-1 male mice. The mice we studied were divided into groups and gavaged with 10, 100, 500 and 1500 mg/kg PBDE 209 in corn oil per day between postnatal Days 21 and 70. On Day 71, the mice were anesthetized and sperm function, testis DNA content, and histopathology were studied. We found in the 500- and 1500-mg/kg/day groups that neonatal exposure to PBDE 209 reduced sperm epididymal sperm mitochondrial membrane potential (MMP), reduced amplitude of the lateral head displacement (ALH) and induced the generation of hydrogen peroxide (H2O2) in the sperm of sexually mature male mice, without affecting the sperm count, motility, morphology, curvilinear velocity (VCL), angular progressive velocity (VAP), straight-line velocity (VSL), beat-cross frequency (BCF), sperm chromatin structure assay (SCSA), superoxide anion (O2-*) generation, DNA content in testis cells, or testicular histopathology. ALH was positively associated with an increase in MMP and negatively associated with generation of sperm H2O2. The reduction of MMP was negatively associated with an increase in generation of sperm H2O2. The presence of the relationships between sperm ALH, MMP, and generation of H2O2 indicate toxic action possibly resulting from PBDE 209-induced oxidative stress. In conclusion, this is the first study to report the lowest-observed-adverse-effect level (LOAEL) for sperm function to be 500 mg/kg of PBDE 209 in male mice. Decreased epididymal sperm MMP and ALH as well as induced generation of sperm H2O2 were some of the most serious effects of postnatal PBDE 209 exposure. Future investigations should be performed to study the effects of prenatal exposure of PBDE 209 and the mechanism behind PBDE 209-related oxidative stress in the fetal and pubertal stages of development.

Animals↗

Comparison of the effectiveness of placebo and alpha-blocker therapy for the treatment of idiopathic oligozoospermia.

OBJECTIVE: To determine whether alpha-blocker (bunazosin) improves fertility and/or semen parameters DESIGN: Placebo-controlled, double-blind clinical study. SETTING: Nagoya University Hospital Andrology Clinic, Nagoya, Japan. PATIENTS: Thirty-four men with sperm density between 5 and 20 x 10(6) sperm/mL, normal serum gonadotropins and T, and a fertile partner were enrolled in this study. INTERVENTIONS: After a 3-month control period, patients randomly were prescribed bunazosin 2 mg/d or a placebo, two tablets per day, for 6 months. Semen and blood samples were collected before and after therapy. Semen parameters, serum gonadotropins, T, PRL, and E2 were evaluated before and after therapy. RESULTS: The pregnancy rate (PR) in the alpha-blocker group was 25%, compared with 6.7% in the placebo group. There was no statistical difference in the PR between groups. The alpha-blocker group had significantly higher levels of sperm density and total motile sperm count. There were no differences between the placebo and alpha-blocker groups in seminal volume, the percentage of motile sperm, and normal morphology or hormone levels. CONCLUSIONS: The authors conclude that alpha-blocker is a useful drug in the treatment of idiopathic moderate oligozoospermic men.

Adrenergic alpha-Antagonists↗

Gonadal effects of chlorambucil given to prepubertal and pubertal boys for nephrotic syndrome.

To assess the gonadal effects of chlorambucil given to prepubertal and pubertal boys, testicular function of 21 adolescents or young men, treated with chlorambucil for nephrotic syndrome before or during puberty, have been evaluated. Evaluations have been based on penis and testicular size, serum FSH, LH and testosterone values, and sperm count. Nine patients have testicular hypotrophy, 13 have significantly elevated FSH, 17 have azoospermia, two have severe oligospermia, and repetitive sperm counts show no improvement. A quiescent state of the epithelium of the seminiferous tubules does not protect against chlorambucil toxicity, which seems to be related to the cumulative dose. Chlorambucil should be used with caution, even in children.

Adolescent↗

A practicable immunological approach to block spermatogenesis without loss of androgens.

The intrinsic capacity of the immune system to elicit immune response selectively against late developing sperm proteins has been mobilized to intercept spermatogenesis. Bacillus Calmette-Guérin given in appropriate doses intratesticularly is effective in bringing about this effect. In dogs and rhesus monkeys, the sperm count in the semen declined precipitously, and almost complete azospermia was attained in 4-6 weeks after immunization. The few sperm cells that were present were immotile. Examination of serial sections of testes in immunized rats showed about 98% of the tubules to be devoid of sperm. The tubules were partially or fully atrophied. The basement membrane was, however, intact and the pertubular cell layer was normal. Sertoli cell nuclei were apparently normal but the cytoplasm was vacuolated and, in most cells, partially disintegrated. The lumen of the tubules was exhausted of formed elements and at times filled with eosinophilic debris. Leydig cells were present and hyperplasia of interstitial cells was seen, with massive infiltration of leukocytes. Blood testosterone levels were in the normal range and Leydig cells were responsive to gonadotropins. Libido was intact. The method was applicable to a variety of mammalian species. The implications of the results are discussed.

Adjuvants, Immunologic↗

Does seminal fluid viscosity influence sperm chromatin integrity?

A retrospective study was undertaken to investigate whether viscosity alters sperm chromatin integrity. Semen samples were obtained from 269 men attending the infertility clinic. The viscosity was measured quantitatively by needle and syringe method and the viscosity ratio was calculated against distilled water. The chromatin integrity was evaluated by in vitro decondensation test using 1% SDS and 6 mM EDTA. According to the viscosity ratios the samples were divided into 2 groups: I, normal (ratio < 9, n = 239): and II, abnormal (ratio > 9, n = 30) viscosity. Chromatin integrity was significantly lower in the group with higher viscosity. Significant decrease in sperm count and motility were seen in group II as compared to group I. Thus, hyperviscosity of seminal fluid alters the sperm chromatin integrity.

Chromatin↗