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Desogestrel plus testosterone effectively suppresses spermatogenesis but also causes modest weight gain and high-density lipoprotein suppression.

OBJECTIVE: To test the hypothesis that oral desogestrel (DSG) plus testosterone would uniformly and rapidly suppress sperm concentrations in young men as effectively as levonorgestrel (LNG) plus testosterone and cause less high-density lipoprotein (HDL) suppression and weight gain. DESIGN: Single-blind, randomized trial. SETTING: VA Puget Sound and University of Washington, Seattle, Washington. PATIENT(S): Twenty-four healthy young men, aged 20-49. INTERVENTION(S): Subjects were randomized to three groups of men who were administered 6 months of therapy with oral DSG plus im testosterone enanthate: 150 microg of DSG plus 50 mg of testosterone (DSG 150-T 50), 150 microg of DSG plus 100 mg of testosterone (DSG 150-T 100) or 300 microg of DSG plus 100 mg of testosterone (DSG 300-T 100). We compared these three groups to two groups of historical controls of 100 mg of im testosterone alone or 150 microg of oral LNG plus 100 mg of im testosterone (LNG 125-T 100 group) enrolled in similar studies. MAIN OUTCOME MEASURE(S): Suppression of sperm counts to severe oligoazoospermia (sperm counts <1 x 10(6)/mL) and azoospermia, weight gain, and serum high-density cholesterol (HDL) suppression. RESULT(S): Azoospermia was achieved in all eight men receiving DSG 150-T 100 and seven of the eight men in the DSG 300-T 100 group. DSG 150 or 300 plus T 100 suppressed spermatogenesis as effectively as LNG 125-T 100 and more effectively than DSG 50-T 100 or testosterone alone. All groups tended to gain weight compared with their baseline, but the weight gain was greatest (and statistically significant) in the DSG 150-T 100, DSG 300-T 100, and LNG 125-T 100 groups. Serum HDL levels were modestly suppressed in all groups, and this effect was greatest in the DSG 300-T 100 and LNG 125-T 100 groups. CONCLUSION(S): The combination of DSG plus testosterone is a very effective regimen for suppression of spermatogenesis and has acceptably low side effects.

Acne Vulgaris↗

Use of synthetic luteinizing hormone-releasing hormone in treatment of oligospermic men: a preliminary report.

Synthetic luteinizing hormone-releasing hormone (LH-RH) was administered to four normogonadotropic, oligospermic men (24 to 39 years of age) who had no endocrinologic, urologic, or associated vascular disease, to assess its possible therapeutic value in male infertility. Previous testicular biopsies of these subjects indicated alteration of spermiogenesis only. LH-RH (mean dose, 500 mug/day) was administered intramuscularly for 100 to 135 days. Each patient had at least two sperm count before starting therapy and had one every 20 to 30 days during and for two to five months after treatment. The sperm count, semen volume, sperm motility and morphology, and seminal plasma concentrations of fructose and citric acid were studied in each semen sample. In three of the four patients, urinary LH and FSH excretion and plasma testosterone levels were also measured. The sperm count increased clearly in two subjects 30 to 80 days after therapy started; the response was small in the third subject and negative in the fourth. The remaining parameters followed variable courses. Libido increased in all subjects. In the post-treatment period, the two patients who had shown the best response during treatment experienced a new and abrupt increase in the sperm count which remained well above initial values at the end of follow-up. LH-RH appears to be of value in the treatment of certain types of oligospermia, but several issues remain unsettled.

Adult↗

Intrauterine insemination after ovarian stimulation with clomiphene citrate: predictive potential of inseminating motile count and sperm morphology.

This retrospective study aimed to evaluate the prognostic value of the inseminating motile count (IMC) and sperm morphology (using strict criteria) on success rates after homologous intrauterine insemination (IUI) combined with clomiphene citrate (CC) stimulation. A total of 373 couples underwent 792 IUI cycles in a predominantly (87.4%) male subfertility group. The overall cycle fecundity (CF) and baby take-home rate (BTH) was 14.6 and 9.9% respectively. The cumulative CF and BTH (per couple) after three cycles were 30.6 and 21.1% respectively. Overall, sperm morphology and IMC were of no prognostic value using receiver operating characteristic (ROC) curve analysis, but after classifying the study population into different subgroups according to IMC, sperm morphology turned out to be a valuable prognostic parameter in subgroup 1, i.e. IMC <1 x 10(6). In this subgroup, no pregnancies were seen when the morphology score was <4% and the mean value of sperm morphology was significantly different in the pregnant (8.3%) versus non-pregnant group (5.0%; P <0.05). The cumulative CF and BTH after three IUI cycles were comparable for all couples with the exception of those cases in which the IMC was <1 x 10(6) with a morphology score of <4% normal forms. We recorded only two twin pregnancies (2.5%) and no moderate or severe ovarian hyperstimulation syndrome. We conclude that in a selected group of patients without CC resistance and normal ovarian response following CC stimulation [maximum of three follicles with a diameter of >16 mm at the time of administration of human chorionic gonadotrophin (HCG)], IUI combined with CC-HCG can be offered as a very safe and non-expensive first-line treatment, at least with an IMC of >1 x 10(6) spermatozoa. In cases with <1 x 10(6) spermatozoa, CC-IUI remains important as a first-choice therapy provided the morphology score is > or =4%.

Adult↗

[Is today's man really less fertile?].

In 1992, a statistical analysis of data from 61 studies of semen quality among normal men led to the conclusion that human sperm count fell of 40% from 1940 to 1990. This meta-analysis has since been invalidated for methodological reasons as well as for statistical reasons, but it caused enormous concern to both the scientific community and to the international media. A decline of human fertility was speculated. To date, the most popular hypothesis offered to explain this alleged decline has been increasing exposure to environmental estrogen mimicking chemicals. However, there is no evidence that male or mammal fertility is declining. Moreover, the sperm count of breeding mammals did not declined in the meanwhile. Since 1992, numerous papers reported on men investigated during the last 20 years have shown conflicting results, from sperm count improvement to sperm count decline. However, several publications included methodological and analytical biases. In fact, the techniques used for semen analysis have to be questioned. It is a subjective exam, lacking laboratory standards and quality control procedures. This induces very important variations between laboratories and between biologists. For the sperm count itself, numerous errors can occur, provoked by the technique, the equipment and the reader: for the same sperm, the coefficient of variation can exceed 40% between two technicians. Therefore, the current techniques of semen analysis cannot warrant epidemiological studies. It is indispensable to admit the limits of the semen analysis in order to improve as much as possible its quality and its reliability.

Adult↗

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 5). Effects of repeated doses of flutamide for 2 and 4 weeks.

Flutamide, a nonsteroidal antiandrogen, was administered orally to 8-week (for the 2 week study) and 6-week-old (for the 4 week study) male Crj:CD(SD) rats at dose levels of 0 mg/kg, 60 mg/kg and 200 mg/kg daily for 2 weeks or 4 weeks in order to determine whether a 2 week treatment period is sufficient for detection of drug effects on the male reproductive system. Flutamide treatment for 4 weeks resulted in decreased organ weights of the epididymides and prostate, decreased sperm counts and Leydig cell proliferation in the testes at 60 mg/kg and 200 mg/kg. Decreased sperm motility and histological lesions in the seminiferous tubules were observed at 200 mg/kg. Flutamide treatment for 2 weeks decreased organ weight of epididymides and prostate and caused Leydig cell proliferation in the testes at 60 mg/kg and 200 mg/kg. Decreased sperm counts and sperm motility, and histological lesions in seminiferous tubules were observed at 200 mg/kg. The results of this study showed that 2 weeks treatment with flutamide causes histological lesions of testes and disorders of sperm parameters similar to those observed with 4 weeks treatment, indicating that 2 weeks treatment is sufficient for detection of effects of flutamide on the male reproductive system.

Administration, Oral↗

Efficacy of kallikrein in the treatment of oligozoospermia and asthenozoospermia: a double-blind trial.

OBJECTIVE: To assess the effect of kallikrein on sperm motility and sperm count in infertile oligozoospermic and asthenozoospermic men. DESIGN: Double-blind placebo-controlled clinical trial. SETTING: Multicenter trial in three andrologic clinics. PATIENTS: Infertile men with < 20 x 10(6) total sperm count and > 3 x 10(6) sperm cells/mL and/or sperm motility of < 30%. INTERVENTIONS: One hundred fourteen men received either placebo or 600 kallikrein units of kallidinogenase by mouth daily for 12 weeks. Semen analyses were performed before and at 6-week intervals during the trial. Compliance and incidence of adverse effects were assessed. RESULTS: The incidence of adverse effects was similar under placebo and under kallidinogenase treatment, usually mild, transient, and did not require the cessation of treatment in any patient. Kallidinogenase was not superior to placebo in improving sperm count and sperm motility. CONCLUSIONS: At the doses and for the duration given, our results were disappointing. The absence of a therapeutical effect, as evidenced in the present study may be due to the very low absorption rate of kallidinogenase after oral administration. Probably a much higher dose of kallidinogenase should be used to achieve a therapeutic affect.

Adult↗

Computer-aided semen analysis: sperm concentration assessment by the Strömberg-Mika system.

The scope of this study was to evaluate the accuracy, precision and specificity of the sperm concentration measurements by the Strömberg-Mika Cell Motion Analyser (SM-CMA). Our data show that the instrument generally underscores the sperm concentration and therefore the uncorrected measurements must be corrected by the operator using the 'mouse'-driven option. In terms of precision, the system appears to have an excellent internal precision whereas its repeatability is influenced by the sperm concentration, the sample's homogeneity and the correction of the raw data. In order to increase the system's repeatability, we suggest that sperm counts should be carried out in various fields of the counting chamber, and the mean of the corrected values be taken as representative of the sperm concentration in the ejaculate if the various measurements show a homogeneous (poissonian) distribution. The correction of the raw data with the 'mouse'-driven correction option was also shown to improve the system's reproducibility. Concerning specificity, our data evidenced that, without technical correction, the instrument failed to correctly classify certain spermatozoa as such, thereby grossly underscoring sperm counts. This finding was more evident at low sperm counts. Overall, the SM-CMA requires additional laboratory time but the corrected sperm counts are comparable to manual counts and semi-automated counts with the added option that it provides the andrologists with various motility characteristics not possible with the latter methodologies.

Autoanalysis↗

[Fertility after treatment with HCG for undescended testes (author's tranls)].

151 out of 212 adolescents having had been treated by human chorionic gonadotrophin (HCG) before puberty because of undescended testes, were re-examined 7 to 12 years later at an individual age of at least 17 years. In 121 of them a semen specimen for sperm counts could be obtained. In 10 patients, however, no ejaculate could be collected because of their hypogonadism. 78 of these 121 patients examined by sperm count had a sufficient testicular descensus after HCG treatment. In 43 adolescents HCG therapy failed, therefore subsequent orchidopexy was performed. A normal sperm count was seen in only 39 per cent of the 121 patients. After unilateral testicular maldescensus 18%, after bilateral maldescensus 43% of the patients had to be evaluated as prospectively infertile. Maier and Spann reported sperm counts below 10(6)/ml in 9 out of 17 patients with bilateral maldescensus who had been treated by surgery alone. In the present study, however, only 9 out of 35 individuals treated for bilateral maldescensus by HCG alone showed sperm counts below 10(6)/ml. Plasma LH and FSH concentrations were determined in 93 patients, 6 out of which showed hypergonadotrophic values of FSH and sperm counts below 10(7)/ml. Subsequently, 3 cases of Klinefelter's syndrome could be diagnosed among the total group of 121 patients. The etiology of testicular maldescensus is by no means uniform since anatomical, endocrine and/or chromosomal factors are involved.

Adolescent↗

Time to pregnancy in relation to semen quality assessed by CASA before and after sperm separation.

BACKGROUND: In order to provide a reference for infertile men, we defined normal values of semen quality in a population of fertile men, using computer-assisted semen analysis (CASA) before and after sperm separation. Additionally, we investigated the relationship between semen quality and time to pregnancy (TTP). METHODS AND RESULTS: Semen samples were obtained from 315 proven fertile men. The median sperm concentration in fresh samples was 107 x 10(6)/ml (5-95 percentiles: 16-322 x 10(6)/ml), the median percentage of motile sperm cells was 65% (14-87%) and the median percentage of progressively motile cells was 37% (5-64%). After density gradient sperm separation, the median total sperm count was 46 x 10(6) (4-350 x 10(6)), the median percentage of motile sperm cells was 77% (16-95%) and the median percentage of progressively motile cells was 63% (11-84%). No significant associations were found between TTP and sperm counts or sperm motility, either before or after sperm separation. This may be due in part to the fact that the study comprised couples with proven fertility. CONCLUSION: We have defined semen parameters, including the results of density gradient separation, in a population of normal fertile men which may be of interest in the evaluation of semen samples from infertile men.

Adult↗

Factors associated with the quality before freezing and after thawing of sperm obtained by microsurgical epididymal aspiration.

OBJECTIVE: To identify whether the cause, site of ductal obstruction, and characteristics of fluid aspirates are associated with the cryosurvival and fertility after thawing of sperm obtained during reconstruction of the excurrent ducts with microsurgical epididymal sperm aspiration, vasal sperm aspiration, or both. DESIGN: Prospective study. SETTING: Andrology center at a tertiary care institution. PATIENT(S): Men undergoing reconstruction of the excurrent duct and sperm aspiration (n = 42) or microsurgical epididymal sperm aspiration (n = 11). INTERVENTION(S): Sperm were tested for an association with the cause and site of obstruction. Fertilization and pregnancy rates after sperm aspiration and intracytoplasmic sperm injection (ICSI) were evaluated for fresh and frozen aspirates. MAIN OUTCOME MEASURE(S): Motile sperm count and percentage motility after thawing. RESULT(S): The motile sperm count before freezing was significantly higher in the caput epididymis than in the corpus. The motile sperm count before freezing was related inversely to the distance from the caput where the sperm were aspirated. Sperm from clear and opaque fluid aspirates had better percent motility than those from cloudy and creamy fluid aspirates. High fertilization and pregnancy rates were achieved using both fresh and frozen epididymal sperm. CONCLUSION(S): None of the factors studied was associated with cryosurvival of aspirated epididymal or vasal spermatozoa. Because motility is low after thawing, these specimens are best used with ICSI.

Adult↗

The impact of ofloxacin on rat testicular DNA: application of image analysis.

Ofloxacin induces its antibacterial action mainly by inhibition of DNA gyrase which is equivalent to topoisomerase II in mammalian cells. The present study was focused on the impact of ofloxacin on rat testicular DNA ploidy in a dose-response relationship using an image analysis technique on testicular sections following Fuelgen DNA staining. Sperm count and motility as well as sperm head abnormality tests were also investigated. Ofloxacin was given p.o. in doses of 36, 72 and 360 mg kg(-1) day(-1) for 15 consecutive days. The animals were then left to live safely to day 60 from starting the experiment to give them a chance to complete the cycle of spermatogenesis. Results revealed that ofloxacin significantly decreased the percentage of haploid cells in a dose-dependent manner with concomitant increase in the percentage of diploid cells. Sperm count and motility was also markedly decreased in a dose-dependent fashion. Sperm head abnormality showed no marked change following ofloxacin treatment. In conclusion, ofloxacin induced a marked disturbance in rat testicular DNA ploidy, which may be explained on the basis of cross-reactivity to topoisomerase II.

Animals↗

Azoospermia in testicular sarcoidosis is an indication for corticosteroid therapy.

OBJECTIVE: To report improvement of azoospermia and hypogonadism after high-dose corticosteroid therapy in a patient with testicular sarcoidosis. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 27-year-old man with testicular sarcoidosis and azoospermia. INTERVENTION(S): High-dose corticosteroid therapy was commenced in an attempt to improve sperm count and restore gonadal function. MAIN OUTCOME MEASURE(S): Analysis of sperm count, T, and gonadotropin response to steroid therapy. RESULT(S): FSH and LH concentrations decreased and T levels increased in parallel with control of disease activity with steroid therapy. Repeat semen analysis demonstrated a significant increase in sperm count, allowing sperm banking to take place. CONCLUSION(S): High-dose corticosteroid therapy may be indicated in testicular sarcoidosis, not only for control of systemic disease activity but also for recovery of gonadal function and spermatogenesis.

Adrenal Cortex Hormones↗

Exposure to different spectra of light, continuous light and treatment with melatonin affect reproduction in the Indian desert gerbil Meriones hurrianae (Jerdon).

In two separate experiments, the gonadal response to melatonin treatment and exposure to continuous white light (LL) and different spectra of light (blue, green, yellow and red) was investigated in the Indian desert gerbil Meriones hurrianae. In experiment 1, exposure to green light for 8 weeks increased (p < 0.01) the gonadosomatic index (GSI) and sperm count, whereas exposure to red light decreased (p < 0.01) the GSI and sperm count. The response of accessory organs to the treatment varied. In experiment 2, exposure to LL for 5 weeks decreased the GSI and sperm count, and treatment with melatonin (in the late-light period) not only increased the GSI and sperm count, but also counteracted the inhibitory action of LL and red light. Melatonin treatment stimulated accessory sex organs and the scent gland surface area. The inhibition or stimulation of the reproductive parameters correlated with an increase or decrease in pinealocytes and pinealocyte nuclear diameters. Therefore, the influence of light and its spectra on reproduction may be mediated by the pineal gland, though extrapineal mechanisms cannot be ruled out.

Animals↗

Effect of Black maca (Lepidium meyenii) on one spermatogenic cycle in rats.

Lepidium meyenii (Maca) grows exclusively between 4000 and 4500 m above sea level in the Peruvian central Andes. The hypocotyls of this plant are traditionally used in the Andean region for their supposed fertility-enhancing properties. The hypocotyls have different colours. Of these, Black maca has better effects on spermatogenesis. The present study aimed to test the hypothesis that Black maca has early effects during a spermatogenic cycle (12 days) of male rats. For this, testicular spermatid, epididymal sperm and vas deferens sperm counts were measured after 1, 3, 5, 7 and 12 days of treatment with Black maca. Aqueous extract of Black maca was given orally by daily gavage at a dose of 2 g kg(-1). In a spermatogenic cycle, compared with day 1, daily sperm production (DSP) was lower at day 7 (control), whereas with Black maca, the difference was observed at day 12. Epididymal sperm count was higher in rats treated with Black maca at days 1, 3 and 7, but similar to controls at days 5 and 12; similarly sperm counts in vas deferens was higher in rats treated with Black maca in days 3, 5 and 7, but similar to controls at days 1 and 12. From this, it is suggested that first action of Black maca was at epididymal level increasing sperm count after 1 day of treatment, whereas an increase in sperm count was observed in vas deferens at day 3 of treatment. Finally, an increase in DSP was observed after 7 days of treatment with Black maca. Testicular testosterone was not affected after 7 days treatment with Black maca. In conclusion, Black maca affects sperm count as early as 1 day after beginning of treatment.

Animals↗

Automation of semen analysis using flow cytometer in comparison with manual methods.

In order to standardize techniques and limit the effect of human factors on the results of analyses of biological fluids, automation seems to be mandatory. In an attempt to automate semen analysis, computer assisted sperm analysis (CASA) system has been developed, however its use is still limited and its practical applications have many criticisms. In a trial to automate semen analysis, this study aimed to evaluate the usefulness of flow cytometer in the detection of some seminal parameters in comparison with the traditional manual methods. Isolated spermatogenic cells and isolated sperms from semen and EDTA blood of volunteers were analyzed by flow cytometer in order to define their respective regions. Ejaculates of 28 male patients were subjected to routine semen analyses, leucocytes detection by peroxidase test and monoclonal antibody CD53 using flow cytometer after preparation of the patients' semen samples for flow cytometeric analysis. A highly significant correlation (r=0.96, p= 0.001) of absolute neutrophils (pus cells) detected by peroxidase versus flow cytometer using CD53 monoclonal antibody. A poor correlation (r=0.39, p=0.035) of sperm counts assessed by manual technique and flow cytometer and a spurious sperm counts of 1.08 million/ml detected by flow cytometery in azoospermic patients. Flow cytometer could be used for the assessment of pus cells in semen but seems to be non reliable for the assessment of sperm count if gating depend on sperm size and granularity alone.

Adult↗

The evaluation of routine andrological parameters in human serum.

A study was carried out to evaluate the andrological parameters in 540 human semen specimens divided into groups according to sperm counts. The parameters were: motility percentage and grade, percentage of viability and of morphologically normal sperm and immature cells. The Duncan multiple range test and the Kruskal-Wallis test with multiple comparison of ranks were used in the statistical analyses. Of particular interest, among other our findings, were the significant differences obtained by comparing the group with sperm counts up to 5 x 10(6) per ml semen and that with counts ranging from 5.1 to 10 x 10(6) per ml semen. This was true for all parameters with the exception of semen volume. Comparison of the oligozoospermic groups (up to 20 x 10(6)/ml) with those having higher sperm counts also showed significant differences. There was a trend towards improvement of the examined parameters with the increase in sperm density, but with a remarkable heterogeneity particularly within the oligozoospermic groups. In all groups motility, viability and morphological normality of sperm showed a positive correlation with each other. "Normal values" of the parameters studied could be derived from scatterplot charts over the entire range of sperm counts and from the statistical evaluation of the grouped material.

Humans↗

Effect of Prograf (FK506) on spermatogenesis in rats.

Prograf (FK506) was given to male mature rats in a daily subcutaneous dose of 1 or 3 mg/kg/day for 2 weeks to investigate its effect on spermatogenesis. Prograf dose-dependently sperm counts and motility, but did not affect testosterone level in the serum of rats. Histopathologically, there were no abnormal changes in the testis, seminal vesicle or prostate in any rats dosed with Prograf, but intra-ductal eosinophilic globules, probably degeneration of the sperm cells, were observed in the epididymis of the 3 mg/kg/day group. Sperm counts and motility returned to the control levels after stopping of the drug. The results indicate that Prograf decreased sperm counts and motility through direct action on the sperm in the epididymis, but not the production of sperm in the testis. Cyclosporine A (CsA) was used as the reference drug in the present study. Thirty mg/kg/day of CsA also decreased sperm counts and motility, and stopping of the drug led to the recovery of these changes. The males dosed with Prograf for 2 weeks were mated with non-dosed females to investigate its effect on the fertility potential of the males. Prograf did not affect copulation or fertility index, but a decrease in the number of live fetuses associated with implantation loss was observed in the 3 mg/kg/day group. The changes were considered to be due to the decrease of sperm counts and motility, although 1 mg/kg/day of Prograf, 5-10 times the clinical dose, did not affect any fertility parameters including implantation index.

Animals↗

Simultaneous treatment of the wife in infertile couples with oligospermia.

Poor ovulation was found to be common in infertile couples with oligospermia. When the sperm count was less than 5 x 10(6)/ml, 33% of wives had poor ovulation. When the sperm count was between 5 x 10(6)/ml and 20 x 10(6)/ml, 78% of wives had poor ovulation. Improvement in sperm count was most likely to increase the chances of conception when the pretreatment sperm count was less than 5 x 10(6)/ml. Pregnancy in infertile couples with oligospermia cannot be related simply to treatment or improvement in the husband's oligospermia but can only be viewed in the context of the wife's fertility, which is quite frequently also impaired in infertile couples with male factor problems.

Clomiphene↗