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Treatment of idiopathic oligozoospermia with tamoxifen--a randomized controlled study.

There is no conclusive evidence of the usefulness of tamoxifen in the treatment of idiopathic oligozoospermia (OAT-syndrome), as it has been used mostly in uncontrolled studies. We herein report on the controlled treatment of OAT-syndrome with tamoxifen versus placebo following a randomized design. Seventy-six men with sperm counts of 2-20 x 10(6) ml-1, sperm motility of 20-50%, and sperm morphology (abnormal cells) between 50 and 80% were involved in the study. Patients with varicocele, a history of testicular maldescent or genital inflammation were excluded. Thirty-nine patients received tamoxifen (30 mg daily), 37 patients placebo. There was a statistically significant increase in the mean serum testosterone level after treatment in the tamoxifen-treated group (from 4.9 +/- 1.9 to 7.9 +/- 3.6 ng ml-1) in comparison to the placebo group (5.3 +/- 2.0 and 5.6 +/- 2.0 ng ml-1). Serum FSH levels increased slightly in the tamoxifen group (from 6.8 +/- 4.1 to 7.3 +/- 4.8 mU ml-1), but this was not statistically significant in comparison to the placebo group (from 5.9 +/- 3.9 to 5.2 +/- 3.5 mU ml-1). Serum levels of LH did not show any differences between groups. The sperm count increased during treatment from 9.3 +/- 11.7 to 11.4 +/- 13.7 x 10(6) ml-1 in the tamoxifen group and from 9.1 +/- 7.1 to 9.3 +/- 8.8 x 10(6) ml-1 in the placebo group; this difference did not reach statistical significance. The percentage of motile and abnormal sperm was not different between the two treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Results of the American Association of Bioanalysts national proficiency testing programme in andrology.

Proficiency testing samples for antisperm antibodies (ASAB), sperm count, morphology and vitality were mailed to participating laboratories. The majority participating utilized Immunobead ASAB procedures (81 versus 14% mixed antiglobulin reaction and 5% 'other'), and there was 95.6 +/- 1.2% agreement on the presence or absence of ASAB. The majority of laboratories utilized manual (79%) versus computer assisted semen analysis (CASA; 15%) methods. Approximately 64% used the haemocytometer and 26% used the Makler counting chambers for manual counts. Coefficients of variation (CV) in sperm counts ranged from 24 to 138%, with CASA displaying lower overall CV (53 +/- 8%) than manual methods (80 +/- 9%). A wide variation in the reports of percent normal morphology was noted (CVs calculated from arc sin transformed means ranged from 15 to 93%). Participants using American Society of Clinical Pathologists (ASCP) criteria reported sperm morphology values that were clustered in the 'normal' range (11 out of 12 samples), while those using strict criteria were clustered in the 'abnormal' range (10 out of 12 samples). Good agreement was observed in sperm vitality (overall mean CV = 18%). These data highlight the urgent need for improvement in overall quality of andrology testing and indicate that practical proficiency testing programmes can be made available on a large scale.

Data Collection↗

Effects of maternal 4-tert-octylphenol exposure on the reproductive tract of male rats at adulthood.

Increases in human male reproductive disorders (testicular cancer, cryptorchidism, hypospadias, and low sperm counts) might stem from increased exposure of the developing male to environmental estrogens. In the present study, we investigated the effects of octylphenol (OP), an estrogenic compound, exposure on the male reproductive system during the fetal period in which the development of reproductive organs and sexual differentiation occurs. Male rats were treated with OP in utero at doses of control (vehicle), 100 or 250 mg/kg/day. After birth, male rats were allowed to grow until adulthood, and then testes, epididymides, and prostate glands were investigated histopathologically. Sperm counts and percentage of abnormal sperm were determined. Seminiferous and epididymal round tubules were evaluated for tubule diameter, lumen diameter, and height of tubule epithelium. Treatment with OP caused abnormalities in the histology of the testis and epididymis and induced atrophy of prostate glands tubules. Although there were no differences in sperm counts among treatment groups, abnormal sperm percentages in the high dose group increased significantly. The results of this study demonstrate that maternally injected OP causes adverse effects on male reproductive tract at adulthood, especially on sperm structure.

Animals↗

Testosterone and dihydrotestosterone seminal plasma levels in varicocele patients.

Testosterone (T) and Dihydrotestosterone (DHT) were measured in seminal plasma levels of forty-four varicocele patients and in seventeen normal men. T values were not significantly different from controls, while DHT values were significantly lower in varicocele patients. When we grouped the patients according to the sperm count, we observed a decrease of DHT similar to that reported by other authors in oligozoospermic patients. However in the patients with normal sperm count, where the motility was the only parameter significantly lower, DHT in the ejaculate showed again a marked decrease. In contrast to that observed in the normal subjects, in the latter group, with normal sperm count, we observed a negative correlation between the age of the patients and DHT in the ejaculate. This suggests that the duration of varicocele per se could affect DHT seminal plasma levels.

Adolescent↗

Testosterone and dihydrotestosterone seminal plasma levels in varicocele patients.

Testosterone (T) and 5-a-Dihydrotestosterone (DHT) was measured in seminal plasma levels of forty-four varicocele patients and in seventeen normal men. T values were not significantly different from controls, while DHT values were significantly lower in varicocele patients. When grouped the patients according to the sperm count, we observed a decrease of DHT similar to that reported by other authors in oligozoospermic patients. However in the patients with normal sperm count, where the motility was the only parameter significantly lower, DHT in the ejaculate showed again a marked decrease. In contrast to that observed in the normal subjects, in the latter group, with normal sperm count, we observed a negative correlation between the age of the patients and DHT in the ejaculate. This suggests that the duration of varicocele per se could affect DHT seminal plasma levels.

Adolescent↗

[Effect of late motility on the fertilization of ova in the IVF program].

In the course of the IVF programme at our department we made the observation that even with primarily normal sperm counts late motility often varies widely. The impression that late sperm motility might be related to successful fertilisation caused us to study the influence of late sperm motility on fertilisation rates in a series of 80 patients. Sperm was capacitated with B2 medium (Menezo INRA). Even in the presence of an originally normal sperm count, reduced late motility was associated with lower fertilisation and embryo transfer rates. It seems that late sperm motility will have to be considered as an important parameter in evaluating the prognosis for successful IVF and ET.

Adult↗

Reproductive disorders in pubertal and adult phase of the male rats exposed to vinclozolin during puberty.

Vinclozolin (VCZ) is a systemic dicarboximide fungicide with antiandrogenic activity. Reproductive toxicity of VCZ was investigated in male rats exposed to VCZ during puberty. Sprague-Dawley male rats aged with 35 days were assigned to six different groups; negative control, positive control receiving flutamide (100 mg/kg), VCZ (100, 200 and 400 mg/kg), and a combination of VCZ (200 mg/kg) + methyltestosterone (100 mg/kg). The animals were treated with test compounds by oral gavage daily during 35 to 44 days of age. In pubertal rats sacrificed on the next day after final treatment, VCZ or flutamide-treated group showed a decrease in weights of prostate, epididymis, and seminal vesicle, hypertrophy of Leydig cells in the testis, detached debris and sloughed cells in the tubules of the caput epididymis, and an increase in serum testosterone levels. On the other hand, combined treatment of VCZ + methyltestosterone decreased testicular weight, increased seminal vesicle weight, and induced degeneration of spermatocytes. In adult rats sacrificed at five weeks after final treatment, flutamide decreased testicular sperm counts, and VCZ, flutamide and VCZ + methyltestosterone also decreased epididymal sperm counts. In addition, treatment of VCZ (400 mg) or VCZ + methyltestosterone decreased some motion kinematic parameters of sperms including curvilinear velocity, mean angular displacement and lateral head displacement. Flutamide treatment also decreased lateral head displacement. These results indicate that VCZ exposure during pubertal period in male rats causes reproductive disorders in puberty and adulthood.

Administration, Oral↗

Male infertility: possible association with valproate exposure.

PURPOSE: To describe a potential association between male infertility and valproate (VPA) exposure. VPA has been implicated in the development of polycystic ovarian disease and subsequent menstrual and infertility problems in women with epilepsy. Infertility has been well described in population-based studies of persons with epilepsy. The low marital rates for men with epilepsy have previously been thought to play a major contributing role. METHODS: We report a case of a 32-year-old man whose wife and he were able to bear a child before the development of his epilepsy. With VPA monotherapy, the family were unable to conceive despite 4 years of unprotected intercourse. An infertility evaluation of the man revealed a very low sperm count of < 50,000/ml, no motile sperm, < 10% viability, and 100% with abnormal structure. Follicle-stimulating hormone, luteinizing hormone, and testosterone levels were normal. RESULTS: Felbamate (FBM) was initiated and VPA discontinued for improved seizure control. Within 4 months, the couple conceived their second child. A seminal analysis revealed a sperm count of > 16 million, 50% motility, 78% viability, and 72% with abnormal structure. CONCLUSIONS: One must be cautious in extrapolating from a case report, but these findings strongly suggest a direct effect of VPA on spermatic structure and function.

Adult↗

Coenzyme Q10 levels in human seminal fluid: diagnostic and clinical implications.

The levels of Coenzyme Q10 (CoQ10) were determined by HPLC in seminal fluid samples obtained from 77 patients who performed a standard semen analysis for infertility, previous phlogosis or varicocele. CoQ10 was determined in total seminal fluid (n = 60), in seminal plasma (n = 44) and in the cell pellet (n = 37). The molecule, in total fluid, showed a linear correlation with sperm count and motility. In the pellet of spermatozoa, a trend toward an inverse correlation between CoQ10 (expressed as ng/10(6) cells) and semen parameters could be observed. A different pattern was shown in varicocele patients, in whom, in total fluid, the correlation between CoQ10 and sperm count was preserved, but the one between CoQ10 and sperm motility was lacking; moreover, a higher proportion of CoQ10 was present in seminal plasma, and the inverse trend between cellular CoQ10 and sperm count and motility was not observed. These data suggest a pathophysiological role of ubiquinone in human seminal fluid and a molecular defect in the spermatozoa of varicocele patients.

Adult↗

Effects of bisphenol A on adult male mouse fertility.

The aim of this investigation was to evaluate the effect of bisphenol A (BPA), a contaminant of resin-based dental composites and sealants, on the fertility of male mice. Forty adult male Swiss mice were divided into four groups of 10. BPA (5, 25 and 100 micro g kg(-1) [corrected] was administered intragastrically daily to the mice in the test groups and distilled water to the control group for 28 d. Male fertility was assessed by mating each mouse with two untreated females. Females mated with male mice having ingested 25 and 100 micro g kg(-1) [corrected] BPA showed a significant reduction in pregnancy rates. Furthermore, the total number of resorptions out of the total number of implantations was significantly increased in females impregnated with males having ingested all three doses of BPA. Males having ingested 25 and 100 micro g kg(-1) [corrected] BPA showed a significant reduction in testicular sperm counts and in the efficiency of sperm production. Epididymal sperm counts were also significantly reduced in males that had ingested BPA. There were significant reductions in the absolute weights of the testes and seminal vesicles. These results suggest that male fertility and reproduction is impaired by bisphenol A.

Animals↗

Comparison of semen analysis between the two Hamilton-Thorn semen analysers.

This study was designed to assess the reproducibility of the computer-assisted semen analysis (CASA) system. Semen specimens from 41 suspected subfertile patients were analysed on two identical Hamilton-Thorn Motility analysers (HTM, model 2030, version 7). Specimens were analysed after liquefaction at 37 degrees C for 30 min on two HTMs adjusted to the same gate settings and by using the same semen droplet loaded on a Makler counting chamber prewarmed at 37 degrees C. Significant differences were seen in the total sperm count (P < 0.0004), motile sperm count (P < 0.004), amplitude of lateral head displacement (P < 0.0001), linearity (P < 0.01), and beat cross frequency (P < 0.0001) between the two HTMs. No significant differences between the two machines was seen in the case of other sperm motion parameters: percentage motility, average path velocity, straightline velocity, curvilinear velocity, straightness, and progressive motility. Our results indicate that the reproducibility of several semen parameters analysed by HTM is poor, and steps to remedy this problem are necessary.

Autoanalysis↗

[Clinical studies of varicocele. 1: Clinical statistical analysis of varicocele].

A clinical statistical analysis was conducted of the patients with varicocele who visited the Department of Urology, Osaka City University, and its related hospitals. Regarding the age distribution, patients younger than 50 years old were predominant; this age group included 20 of 24 cases, or 83%. An overwhelming majority of the cases, 75%, had the main complaint of infertility; they had not been able to have children even after 2 to 3 years of marriage. The next most common complaint was swelling and/or an uncomfortable feeling of the contents of the scrotum. In all of the cases, the lesion was seen in the left side of the scrotum. When the patients were classified on the basis of the sperm count, oligospermia was predominant; it was seen in 15 cases (62.5%). A study on the relationship between the sperm count and the grade of varicocele revealed a tendency for the sperm count to show an inverse relationship with the grade. Testicular atrophy showed a direct correlation with the grade. Of the patients with varicocele, 5 patients had one or more children, while 8 patients (61.5%) complained of their inability to have a child. No particular relationship could be identified between the age at the time of visiting our Department as outpatients and the degree of testicular atrophy.

Adolescent↗

[Varicocele in children and adolescents. Is surgery justified?].

Varicocele, a disease essentially observed in adults, is under-estimated in children and adolescents, in whom, for the majority of authors, the therapeutic management is surgical although the benefits in terms of fertility are unknown. Forty-eight children and adolescents, seen between 1978 and 1983, were followed by clinical examination and subsequent sperm count with a mean follow-up of 5.20 years. The presence at the first examination of the subsequent development of testicular atrophy is a pejorative element in the disease: 12% of children managed expectantly developed left testicular atrophy at puberty associated with severe anomalies of the sperm count. Persistent testicular atrophy after surgery was synonymous with anomalies of the sperm count in all of these children. Regression of moderate atrophy was observed in three children after surgical cure, but the pre and post-treatment sperm counts were normal.

Adolescent↗

Evaluation of the effect of experimental cyclosporine toxicity on male reproduction and renal function. Reversal by concomitant human chorionic gonadotropin administration.

Administration of cyclosporine to rats has been shown to impair testicular function, resulting in a decrease in sperm counts and fertility. In order to determine whether or not the deleterious effects of CsA could be reversed by hormonal therapy, mature male Sprague Dawley rats were treated with CsA (40 mg/kg/day, s.c.) alone or in combination with human chorionic gonadotropin (hCG) (5 micrograms/day/r; s.c.) for 14 days. Cyclosporine administration decreased the body weight (290 +/- 5.30 vs. 339 +/- 8.7 g; P less than 0.05) and reproductive organ weights (testis 1.49 +/- 0.42 vs. 1.60 +/- 0.03 g; epididymis 0.41 +/- 0.02 vs. 0.49 +/- 0.002 g; seminal vesicle 0.61 +/- 0.09 vs. 1.60 +/- 0.05 g; prostate 0.28 +/- 0.04 vs. 0.60 +/- 0.06 g; P less than 0.05) testicular sperm counts (5.80 +/- 0.42 vs. 8.49 +/- 0.48 x 10(7)/100 mg tissue; P less than 0.05) and epididymal sperm counts, (28.2 +/- 0.95 vs. 51 51.62 +/- 2.17 x 10(7)/100 mg tissue; P less than 0.05) and fertility (25% vs. 100%). Serum levels of LH were elevated (101.98 +/- 21.48 vs. 25.6 +/- 5.18 ng/ml; P less than 0.05) and testosterone was decreased (0.48 +/- 0.07 vs. 2.06 +/- 0.56 ng/ml; P less than 0.05). The administration of hCG to the CsA-treated rats restored the reproductive organ weights (testis 1.56 +/- 0.043 g; seminal vesicle 1.04 +/- 0.05 g; prostate 0.70 +/- 0.06 g) and sperm counts (testicular 7.88 +/- 1.0 x 10(7)/100 mg tissue; epididymal 59.86 +/- 4.16 x 10(7)/100 mg tissue; P less than 0.05) Serum levels of testosterone (18.63 +/- 4.45 ng/ml) and LH (431.65 +/- 31.41 ng/ml) were significantly elevated, as compared with control and CsA-treated groups (P less than 0.05). All the rats in the gonadotropin-treated group were fertile, as compared with 25% in the CsA-treated group. CsA reduced the kidney weight (1.17 +/- 0.02 vs. 1.27 +/- 0.03 g; P less than 0.05) and increased the levels of serum creatinine (0.97 +/- 0.07 vs. 0.59 +/- 0.03 mg/dl; P less than 0.05): these changes were ameliorated by the administration of hCG (kidney weight 1.35 +/- 0.03 g; creatinine 0.76 +/- 0.09 mg/dl).

Animals↗

Separate mechanisms for procarbazine spermatotoxicity and anticancer activity.

Procarbazine causes dose-dependent decreases in sperm count after a single i.p. injection in (C57BL/6 X DBA/2)F1 male mice. Two antioxidants, N-acetylcysteine and sodium ascorbate, administered with equimolar doses of procarbazine decreased the spermatotoxicity of procarbazine. At the highest doses of procarbazine (400 mg/kg) that caused a 56% decrease in sperm count, equimolar doses of N-acetylcysteine coadministered with procarbazine caused only a 17% decrease in sperm count, and equimolar doses of ascorbate coadministered with procarbazine caused only a 13% decrease in sperm count. Thus, protection against the spermatotoxic effects of procarbazine was demonstrated with either antioxidant. The effect of the antioxidants on the chemotherapeutic efficacy of procarbazine against murine L1210 leukemia was also assessed. Procarbazine at the highest dose (600 mg/kg) increased mean survival time of mice inoculated i.p. with 1 X 10(5) L1210 leukemia cells by 31%. Simultaneous administration of equimolar doses of either N-acetylcysteine or ascorbate given with procarbazine caused no change in the increased mean survival time of tumor-bearing mice. These results indicate a decrease in the toxicity of procarbazine when coadministered with antioxidants, via decreased spermatotoxicity without changing anticancer efficacy. The results also indicate that different mechanisms are involved in the spermatotoxicity and anticancer activity of procarbazine.

Acetylcysteine↗

Effect of testosterone enanthate on testis size.

We treated chronically 39 normal men with a depot androgen, testosterone enanthate (200 mg. intramuscularly), to assess its potential as a male contraceptive agent. Careful examination and quantification of testicular volume were done before, during and after several dose regimens of androgen therapy. After 4 months of weekly or bimonthly treatment with testosterone enanthate testicular volume decreased by 19.0 plus or minus 2.1 and 16.5 plus or minus 3.4 per cent, respectively. Decrease in testicular volume was related directly to decrease in sperm count. A total of 17 subjects on either weekly or bimonthly injections failed to suppress sperm counts to less than 5 million per cc after 16 weeks; testicular volume was not significantly less than control at this time. Four to 12 weeks of additional weekly injections decreased sperm counts to less than 5 million per cc in 13 of the 17 patients and decreased testicular volume by 23.0 plus or minus 4.8 per cent. The 16 additional weeks of less frequent injections (every 3 or 4 weeks) resulted in an increase in testicular volume with a return to normal size after treatment was discontinued.

Adult↗

[Effects of hachimijiohgan and ninjintoh on fertility in males with sterility].

The effects of TSUMURA HACHIMIJIOHGAN (TJ-7) and TSUMURA NINJINTOH (TJ-32) on patients with the complaint of male sterility due to both or either oligozoospermia or asthenozoospermia were evaluated in comparison with the effects of clomiphene citrate. TJ-7 was administered in 7.5 g doses three times a day for 4 months to 23 patients with oligozoospermia and 20 patients with asthenozoospermia. Sperm count was improved in 5 of the patients (21%) with oligozoospermia and sperm motility was improved in 10 of the patients (50%) with asthenozoospermia. TJ-32 was administered in 5.1 g doses three times a day for 4 months to 26 patients with oligozoospermia and 20 of the patients with asthenozoospermia. Sperm count was improved in 8 of the patients (31%) with oligozoospermia and sperm motility was improved in 9 of the patients (45%) with asthenozoospermia. Both TJ-7 and TJ-32 were more effective in sperm count and motility than clomiphene citrate. No side effects or abnormal laboratory data including serum LH, FSH, testosterone, estradiol and prolactin were observed in any cases.

Adult↗

Effect of short-term and long-term treatments with three ecotypes of Lepidium meyenii (MACA) on spermatogenesis in rats.

Lepidium meyenii (Brassicaceae), known as Maca, is a Peruvian hypocotyl that grows exclusively between 4000 and 4500 m above sea level in the central Andes. Maca is traditionally employed in the Andean region for its supposed fertility-enhancing properties. The study aimed to test the hypothesis that different ecotypes of Maca (Red, Yellow and Black) after short-term (7 days) and long-term (42 days) treatment affects differentially spermatogenesis adult rats. After 7 days of treatment with Yellow and Red Maca, the length of stage VIII was increased (P<0.05), whereas with Black Maca stages II-VI and VIII were increased (P<0.05). Daily sperm production (DSP) was increased in the group treated with Black Maca compared with control values (P<0.05). Red or Yellow Maca did not alter DSP and epididymal sperm motility was not affected by treatment with any ecotype of Maca. After 42 days of treatment, Black Maca was the only ecotype that enhanced DSP (P<0.05). Moreover, Black Maca was the only that increased epididymal sperm motility (P<0.05). In relation to the control group, Red Maca did not affect testicular and epididymal weight nor epididymal sperm motility and sperm count; however, prostate weight was reduced (P<0.05). Black or Yellow Maca did not affect prostate weight. In conclusion, there were differences in the biological response of the three ecotypes of Maca (Yellow, Red and Black). Black Maca appeared to have more beneficial effect on sperm counts and epididymal sperm motility.

Administration, Oral↗