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PubMed2003

Testosterone undecanoate maintains spermatogenic suppression induced by cyproterone acetate plus testosterone undecanoate in normal men.

In this study we evaluated whether testosterone undecanoate (TU), alone or combined with low dose cyproterone acetate (CPA), can maintain spermatogenic suppression induced by higher doses of CPA plus TU. Twenty-four men received for 12 wk 20 mg/d CPA plus 1000 mg/6 wk TU and then 1000 mg/8 wk TU plus 20 mg/d CPA (n = 8), 2 mg/d CPA (n = 8), or plus placebo (n = 8) for 32 wk. Blood samples, physical examinations, hormones, chemistry, hematology, semen analysis, and sexual/behavioral assessments were performed throughout the study. Sperm counts decreased to less than 1 million/ml in all subjects by wk 12, and 54% of them achieved azoospermia. Suppression of sperm counts was maintained until wk 44. Serum LH and FSH levels were suppressed by wk 12 of hormone administration and remained suppressed until wk 44. No significant changes in any biochemical parameters were detected at wk 44 in any group. There was a slight increase in total prostate volume to within the normal range at wk 44 that returned to baseline 1 yr after stopping hormone administration. In conclusion, TU alone or combined with lower doses of CPA maintains sperm suppression induced by higher dose CPA plus TU for 32 wk. This prototype regimen represents a promising male contraceptive regimen.

Adult↗
PubMed1996

Suppression of mouse spermatogenesis by a gonadotropin-releasing hormone antagonist and antiandrogen: failure to protect against radiation-induced gonadal damage.

A combined GnRH antagonist (Nal-Glu) and antiandrogen (flutamide) treatment was used to suppress mouse spermatogenesis in an attempt to enhance recovery from stem cells after irradiation, as observed previously in the rat. Two weeks of treatment suppressed the intratesticular testosterone concentration to 10% of the control value, decreased testicular weight to 16% of the control value, and sperm count 2600-fold. Suppression was at least as great as that produced in the rat by Nal-Glu-flutamide. Testicular weights, sperm counts, and histology were indistinguishable from those in normal controls 45 days after the end of the treatment. Despite the suppression of spermatogenesis, the treatment did not enhance recovery of spermatogenesis after damage produced by a 10-Gray dose of radiation; 45 days after irradiation, testicular weight, sperm head counts, and repopulation indexes were as low as in the mice that received no hormone treatment. In contrast to the situation in the rat, after irradiation of mice, almost no A spermatogonia were found in the 80% non-repopulating tubules, indicating that nearly all A spermatogonia remaining after irradiation were capable of differentiation. This absence of A spermatogonia that fail to differentiate in the mouse is proposed as the reason for failure to protect against radiation-induced gonadal damage by hormone treatment.

Androgen Antagonists↗
PubMed1988

Human chorionic gonadotropin beta-subunit in human semen.

The level of human seminal chorionic gonadotropin beta-subunit (hCG beta) was determined by radioimmunoassay (RIA). The mean hCG beta level in 34 normal men was 3.7 +/- 1.6 ng/ml, which was much higher than that in serum. The mean hCG beta level for 20 patients with mild oligozoospermia (20-39 x 10(6) sperm/ml) was 2.5 +/- 0.8 ng/ml, that for 34 patients with severe oligozoospermia (1-19 x 10(6) sperm/ml) was 1.7 +/- 0.5 ng/ml, and that for 21 azoospermia was 1.5 +/- 0.6 ng/ml. Thus, the decrease of sperm count was correlated with the decrease of hCG beta. In 17 cases to which testicular biopsy was applied together with sperm counting, the seminal hCG beta level was found to positively correlate with the germinal cell index (the ratio germinal cell count/Sertoli cell count) and with the testicular volume. The level of seminal hCG beta was also found to correlate negatively with the levels of seminal LH and FSH and positively with the level of seminal testosterone. These findings suggest that the production of seminal hCG beta is a process of spermatogenesis and closely related to spermatogenesis. The level of hCG beta in serum was too low to detect, and no relation to that in seminal plasma could be investigated. However, in 6 cases with testicular tumor, the hCG beta level in serum was high, whereas that in seminal plasma was rather low probably because of unilateral secretion. Enhanced production of hCG beta by tumor tissues and the destruction of the blood-testis barrier by proliferation of tumor cells seemed to be one of the causes of this high hCG beta level in serum. The hCG beta levels in 13 vasectomized seminal plasma and the prostatic fluid samples collected from 3 normal men were 1.5 ng/ml, which was similar to those in azoospermic patients. These findings suggest that the seminal hCG beta level consists of the hCG beta secreted by the testis and about 1.5 ng/ml of hCG beta from the prostate. Based on these results, seminal hCG beta is thought to be secreted by the prostate and the process of spermatogenesis and the value of seminal hCG beta may serve as an effective index for the testicular function.

Adult↗
PubMed1999

Secular trends in sperm variables for groups of men in fertile and infertile couples.

OBJECTIVE: To assess possible secular trends in sperm variables in men according to previous or subsequent paternity. DESIGN: A comparison of secular trends in sperm variables 1975-1994 in men under investigation for infertility in groups according to previous and subsequent paternity, based on data from the Medical Birth Registry of Norway. SETTING: University hospital, Sperm laboratory and the Medical Birth Registry of Norway. MATERIAL: Samples were obtained from: 1108 men who had fathered at least one child before the analysis. 1786 men who had at least one child after the analysis, and 2286 men with no children registered. MAIN OUTCOME MEASURES: Sperm concentration, seminal fluid volume, total number of spermatozoa per ejaculate. RESULTS: Analyzed by year of evaluation, men with no child registered had a significant secular decrease of sperm concentration, total number of sperms per ejaculate and seminal volume. The group with subsequent children had significant secular decrease of sperm concentration and total sperm count per ejaculate, while no significant changes were found for the group with previous children. Analyzed by year of birth, a significant decrease of sperm concentration and total sperm count was found for the group without and for the group with subsequent children. CONCLUSION: The results are compatible with a cohort effect, exhibiting a trend of deteriorating sperm variables in consecutive birth cohorts.

Adult↗
PubMedDate not supplied

Heterogeneity of sperm density profiles following 16-week therapy with continuous infusion of high-dose LHRH analog plus testosterone.

LHRH agonist analogs have been investigated as potential male contraceptives. It has been shown that the LHRH agonistic analog [D-Trp6,Pro9-NEt] LHRH (LHRHA) given to men in single doses up to 500 micrograms daily for up to 20 weeks with the coadministration of testosterone enanthate produces reversible oligozoospermia. Individual responses to the treatment, however, were variable. In this study, we gave the same analog to eight normal male volunteers as a continuous infusion of 500 micrograms daily for 16 weeks. Testosterone enanthate, 100 mg, was given by injection every second week. Six of the subjects became oligozoospermic but the other two retained sperm counts that were greater than 20 million/ml, although their treatment continued for 20 weeks. The reasons for this variability of response are not clear. Serum immunoreactive LH values increased during the infusion period whereas testosterone declined. FSH values fell during treatment in all subjects except the two non-responders. The acute pituitary response to LHRHA during the treatment or shortly thereafter (48 h) was completely abolished, and bioactive LH values were suppressed totally. FSH, LH, testosterone and sperm counts returned to normal in all subjects following discontinuation of LHRHA infusion. Continuous infusion of 500 micrograms of LHRHA daily for 16 weeks with 100 mg of testosterone enanthate every 2 weeks induced desensitization of the pituitary, loss of LH bioactivity, and decreases of FSH and testosterone. This mode of administration, however, did not improve sperm density results obtained earlier by single daily injections of the analog. Heterogeneity of sperm density profiles still persists for reasons that are not yet clear.

Adult↗
PubMedDate not supplied

Predictive value of sperm chromatin condensation (aniline blue staining) in the assessment of male fertility.

A case control study was carried out to determine the value of sperm chromatin condensation in the assessment of male fertility. A total of 165 semen samples from 90 patients (cases) and 75 healthy donors (control) were examined for chromatin condensation (aniline blue staining), as well as conventional sperm parameters, notably sperm morphology, sperm count, and progressive motility. Whereas only 55 +/- 12.0% of the samples from the infertile patients were unstained by aniline blue (chromatin condensed), 78 +/- 19.0% of the samples in the control group did not take up the stain (chromatin condensed). A significant difference (p < .001) was observed between the two groups. Similarly, the difference between the mean percentage of morphologically normal spermatozoa for the infertile patients (12.1 +/- 1.2%) and the control (23.9 +/- 1.9%) was very significant (p < .001). In addition, only 50 out of the 90 patients (55.5%) had a normal sperm count, whereas all the 75 (100%) were normal in the control group. By comparing between the two groups a significant difference (p < .001) was also observed. Furthermore, a significant difference (p < .001) was also found between the cases and the control with regard to the percentage of spermatozoa illustrating linear progressive motility (40 +/- 9.7% vs. 70 +/- 12.3%). However, no correlation was found between sperm chromatin condensation and morphology, count, and motility. This study suggests that chromatin condensation constitutes a valuable parameter in the assessment of male fertility, completely independent of conventional sperm parameters. Consequently, the inclusion of chromatin condensation to routine laboratory investigations of semen prior to assisted reproduction is strongly recommended.

Adult↗
PubMed1994

Reproductive and nonreproductive responsiveness to photoperiod in laboratory rats.

Laboratory rats (Rattus norvegicus) have been traditionally considered nonphotoperiodic because reproductive function is unaffected by day length. However, at least three experimental manipulations of rats--perinatal androgen injection, peripubertal androgen implants, and peripubertal olfactory bulbectomy--have been reported to unmask reproductive responsiveness to photoperiod. The physiological means by which early testosterone treatment or olfactory bulbectomy affect the expression of photoperiodism were hypothesized to operate through similar underlying mechanism(s) that involved gonadotropin and prolactin blood levels. Short day lengths reduce blood levels of gonadotropins in so-called photoperiodic rodent species. Reduced prolactin levels result in virtually all reproductively photoperiodic species housed in short day lengths. In Experiment 1, male weanling rats either were olfactory-bulbectomized or received a sham-procedure and housed for 10 weeks in long (LD 16:8) or short (LD 8:16) days. Short-day rats reduced body mass, testicular sperm counts, and the size of their reproductive systems; olfactory bulbectomy amplified this inhibitory effect for some parameters including testicular and epididymal sperm counts. However, neither short days nor olfactory bulbectomy affected blood titers of follicle stimulating hormone (FSH) or prolactin. Pelage density was also unaffected by photoperiod, but rats retained their juvenile fur color; i.e., short-day rats remained white, but long-day rats became yellowish. In Experiment 2, male rats were injected with testosterone at 3 days of age, then housed in long or short days until 10 weeks of age. Day length alone did not affect any experimental parameter measured in Experiment 2 except fur color; again, short-day rats retained their juvenile fur color.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Relationship between hormone profiles and the restoration of spermatogenesis in men treated with gossypol.

Gossypol acetic acid was administered orally to 35 male volunteers at a dose of 20 mg once a day for 52-70 days in the loading phase and twice a week for 22 months in the maintenance phase. Sperm counts and the serum concentrations of LH, FSH, prolactin, testosterone and oestradiol were monitored regularly during treatment and for a follow-up period of 12 months. At around 90 days after treatment, all treated participants approached or attained azoospermia and remained at this level throughout the maintenance phase. By the end of the follow-up phase, eight treated men were still azoospermic, while sperm counts in the other 27 men were restored to normal levels. The only hormone that changed significantly during and after the treatment was FSH. From the 6th month of the treatment to the end of the follow-up phase, serum concentrations of FSH in the eight participants that reached irreversible azoospermia were significantly higher than in the other 27 men or in controls. It is suggested that monitoring of FSH levels might be of diagnostic use for identifying those participants with irreversible azoospermia during gossypol treatment.

Administration, Oral↗
PubMed1997

Effects of cancer on spermatozoa quality after cryopreservation: a 12-year experience.

OBJECTIVE: To determine whether type of cancer and response to treatment was related to prefreeze or post-thaw semen quality and to predict post-thaw sperm motility from prefreeze motility. DESIGN: Retrospective study. SETTING: Tertiary care institution. PATIENT(S): One hundred six cancer patients cryopreserving their semen specimens. INTERVENTION(S): Computer-assisted semen analysis was performed before and after cryopreservation on each patient specimen. MAIN OUTCOME MEASURE(S): The relationship of sperm motility and motion characteristics to type of cancer and patient's response to treatment. RESULT(S): Prefreeze and post-thaw semen quality did not differ between patients presenting with testicular cancer and Hodgkin's disease. Patients with leukemia or advanced soft tissue cancer had a higher prefreeze and post-thaw motility and higher total and motile sperm count than testicular and Hodgkin's disease patients. A prefreeze sperm motility of > or = 15% could predict a post-thaw motility of > 10%. CONCLUSION(S): Prefreeze or post-thaw semen quality in cancer patients is not affected (except the prefreeze motile sperm count within the testicular cancer patients) by the type of disease. Prefreeze motility can predict post-thaw motility. Cryopreservation of semen should be offered to cancer patients irrespective of the type of disease.

Adult↗
PubMed1986

Gonadotrophin induced effects on human testicular morphology.

Ten infertile men were treated with gonadotrophic hormones. The effects on serum hormone concentrations, sperm counts, in vitro conversion of progesterone in testicular biopsies and on testicular morphology, were studied. Gonadotrophin treatment increased serum testosterone concentrations and sperm counts in some patients. In the patients where the in vitro conversion of progesterone in testicular tissue was changed, the Leydig cells also increased in size. In some patients the thickness of the lamina propria decreased during therapy, and a thick lamina propria should not exclude a patient from gonadotrophin therapy. Gonadotrophin therapy may be beneficial in patients with understimulated progesterone conversion in vitro, even in cases without spermatogenesis, provided spermatogonia are present. No harmful effects of hCG/hMG treatment were observed.

Adult↗
PubMed1998

[Effects of varicocele therapy on spermatozoan function].

Men suffering from varicocele have lower mean sperm counts and "worse" seminal parameters than those without a varicocele. Also in those with a varicocele, who already fathered a child, the mean sperm count is lower than in other fertile men. The observations, however, do not refer specifically to an existing varicocele, but are common also in other spermatogenic defects. This holds also true for the frequency of tapering forms. Besides the classical parameters of the spermatozoa also novel parameters of the extended semen analysis were tested. As well in the rate of acrosome-reacting spermatozoa, in the rate of anilinblue stained cells, in the number of zona binding-spermatozoa as in the concentration of sperm antibodies no differences between men with and men without a varicocele were found. The grade of a varicocele does not account for the degree of the spermatogenic defect. The progressive damage to the spermatogenesis by an persisting varicocele is discussed controversely. It was suggested that an early treatment of a varicocele, in particular in the adolescence, might inhibit the later insufficiency of sperm production. Correction of a varicocele is followed by an improvement of seminal parameters, in particular of sperm motility. In controlled studies, however, this effect was also observed in the untreated group. This casts some doubt on the causative effect of the varicocele treatment. The improvement of seminal parameters is not always accompanied by an increase in fertility, although also some functional parameters showed an improvement after correction of the varicocele.

Adolescent↗
PubMed2001

Irrigation of the distal vas deferens during vasectomy: does it accelerate the post-vasectomy sperm-free rate?

A prospective, non-randomized, partially blinded, controlled trial was conducted to evaluate the efficacy of irrigation with normal saline solution (NSS) during no-scalpel vasectomy (NSV) compared with NSV alone in 62 men. In the NSS irrigation group, an Angiocath 24-gauge needle was inserted into the distal vas lumen, and 20 mL NSS solution was used to irrigate the vas manually on both sides. Post-operative follow-up included urine samples collected immediately and semen samples for sperm count at 2, 6 and 12 weeks post-vasectomy. The difference in the number of spermatozoa appearing in the post-vasectomy urine samples and the mean urine sperm count in both groups were significantly different ( p < 0.0001 and p < 0.01, respectively). The numbers of post-operative ejaculations, the mean sperm concentration, and the number of patients who achieved sterility (defined as no motile spermatozoa in the ejaculate) in both groups at 2, 6 and 12 weeks were similar ( p > 0.05). It is concluded that although irrigation of the distal vas with NSS was successful in removing a large number of spermatozoa from the tract, this procedure did not significantly accelerate the rate of achieving absence of motile spermatozoa in the ejaculate.

Adult↗
PubMed2003

Effect of sodium arsenite on spermatogenesis, plasma gonadotrophins and testosterone in rats.

AIM: To investigate the effect of arsenic on spermatogenesis. METHODS: Mature (4 months old) Wistar rats were intraperitoneally administered sodium arsenite at doses of 4, 5 or 6 mg.kg(-1).day(-1) for 26 days. Different varieties of germ cells at stage VII seminiferous epithelium cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7Sd) were quantitatively evaluated, along with radioimmunoassay of plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and assessment of the epididymal sperm count. RESULTS: In the 5 and 6 mg/kg groups, there were significant dose-dependent decreases in the accessory sex organ weights, epididymal sperm count and plasma concentrations of LH, FSH and testosterone with massive degeneration of all the germ cells at stage VII. The changes were insignificant in the 4 mg/kg group. CONCLUSION: Arsenite has a suppressive influence on spermatogenesis and gonadotrophin and testosterone release in rats.

Animals↗
PubMed1999

Paraoxonase polymorphism and its effect on male reproductive outcomes among Chinese pesticide factory workers.

BACKGROUND: Serum paraoxonase has been associated with the metabolism of organophosphate pesticides in humans. Molecular analysis of the human paraoxonase gene (PON1) has revealed that Arg192 homozygotes have a greater detoxifying capability than Gln192 homozygotes. We examined the effects of PON1 genotypes on male reproductive outcomes and its interaction with exposure to organophosphate pesticides. METHODS: We studied 60 Chinese pesticide-factory workers and 89 textile-factory workers who were unexposed to pesticides. The respective allele frequencies of Arg192 and Gln192 were 0.62 and 0.38. Pesticide exposure among 36 exposed subjects and 12 unexposed subjects, regardless of gender, was assessed by personal measurement of pesticide residues over an entire 8-hr shift and measurement of urinary p-nitrophenol level over a 24-hr period. We analyzed semen and hormone data collected from male subjects. RESULTS: When the three PON1 genotypes were analyzed separately, a gene dose effect was not detected. We used the unexposed Arg192 homo/heterozygotes as the reference group, and re-analyzed the data. Exposed Arg192 homo/heterozygotes had significantly lower sperm count (chi 2 = 9.01, P < 0.01) and lower percentage of sperm with normal morphology (chi 2 = 4.18, P < 0.05) than the reference group. Both unexposed Gln192 homozygotes (chi 2 = 4.90, P < 0.05) and exposed Arg192 homo/heterozygotes (chi 2 = 10.00, P < 0.01) showed significantly lower sperm concentrations than the reference group. In addition, exposed Arg192 homo/heterozygotes had significantly higher serum LH levels (chi 2 = 7.94, P < 0.01) than the reference group. CONCLUSIONS: Because of a small sample size, our findings are highly preliminary. Nevertheless, it calls for further investigation of the interaction between the PON1 genotype and organophosphate pesticide exposure on male reproductive outcomes.

Adult↗
PubMed1980

Surgical treatment of varicocelle in oligospermic patients: a re-evaluation.

Left varicocele ligation was performed in 64 infertile men seen at our clinic during 1974-1978. High ligation of the left internal spermatic vein was done in all cases. The ages of patients were 23--46 yr. The criteria for operation were: palpatory findings of varicocele, primary or secondary infertility, and abnormal sperm analysis. Statistical analysis of the 3 main sperm parameters before and after surgery shows a significant increase in sperm count (P < 0.005) and motility index (P < 0.005), while the sperm morphology was not improved (P = 0.2). The pregnancy rate was 43.8%.

Adult↗
PubMed2006

Sperm quality, birth rates and the environment in Flanders (Belgium).

The relationship between fertility and pollution is unclear. We evaluated sperm quality of 562 candidate donors (years 1977-2004), births rates (births), pollutants, and the number of females in reproductive age (NFRA, 20-39 years) in Flanders. Total sperm count did not change significantly with time. Births correlated with sperm morphology (r=0.60, P=0.0027). Continuing decline in sperm morphology with time is confirmed, statistically unrelated to pollutants. Grade A sperm motility declined (1977-1992) with gradual incomplete recovery thereafter. Multiple regression analysis (1995-2002) indicated dioxin (negative association) as the only independent variable for grade A motility (r-adjusted co-efficient of determination "r-adjusted"=0.76, P=0.008). Births and pollution were positively associated but births were only dependent on NFRA (r-adjusted=0.91, P<0.001). Our results suggest a relation between dioxin and sperm motility, partially reversible upon reduction of environmental dioxin. Though significantly correlated with sperm morphology, births are primarily associated with demographic factors.

Adult↗
PubMed2005

Chemoprotective effect of lipoic acid against cyclophosphamide-induced changes in the rat sperm.

Treatment with cyclophosphamide (CP), a commonly used anticancer and immunosuppressive agent, may result in oligospermia and azoospermia. CP administration induces oxidative stress and is cytotoxic to normal cells. In this context, we have studied the effect of an established antioxidant, lipoic acid on its influence on CP-induced oxidative injury in rat sperm. In this study, we have assessed the possible protective efficacy of lipoic acid on the sperm characteristics, peroxidative damages and abnormal antioxidant levels in the epididymal sperm of CP-administered rats. Male Wistar rats of 140+/-20 g were categorized into four groups. Two groups of rats were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce testicular toxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks; 24 h prior to CP administration). A vehicle treated control group and a lipoic acid drug control group were also included. CP-treated rats showed a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. The epididymal sperm of untreated CP-exposed rats showed 1.9-fold increase in lipid peroxidation, along with a significant increase in protein carbonyl level. These changes were associated with significant increase in DNA damage in the sperm as evidenced by increased single strand breaks in fluorimetric analysis of DNA unwinding (FADU). In rats treated with CP, abnormal changes in the activities/levels of enzymic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymic (reduced glutathione, ascorbate and alpha-tocopherol) antioxidants, were also observed. Pretreatment with lipoic acid improved the semen quality and reduced the oxidative stress and DNA damage induced by CP, thereby demonstrating the protection rendered by lipoic acid.

Animals↗
PubMed1984

Interrelations among the characteristics of human semen, and a new system for classification of male infertility.

The clinical fertility of 1077 men who underwent semen analysis during the years 1950 to 1952 was studied 20 years later using questionnaires returned by 785 men (72.9%). Decreasing fertility was correlated with decreasing sperm count (P less than 0.01), with increasing numbers of immobile sperm (P less than 0.01), with poorer motility (P less than 0.01), and with increasing numbers of morphologically abnormal sperm (P less than 0.01). The characteristics mentioned were all interrelated (P less than 0.01), with correlation coefficients from 0.36 to 0.67. A new system for classification of male fertility potential is elaborated, using a combination of the four characteristics. This system expresses the fertility of the man and the couple as a percentage of the chance of obtaining living children.

Humans↗