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Reversible azoospermia induced by an androgen-progestin combination regimen in Indonesian men.

The suppression of spermatogenesis by a combination of depot medroxyprogesterone acetate (DMPA) and testosterone enanthate (TE) was studied in Indonesian men. Twenty healthy, fertile volunteers were allocated randomly to either of two treatments each consisting of four intramuscular injections at monthly intervals. Group I (n = 10 men) received 100 mg DMPA plus 100 mg TE monthly while group II (n = 10 men) received 200 mg DMPA plus 250 mg TE monthly. Sperm concentration was suppressed markedly, with all men attaining azoospermia between the third and fourth month after the start of treatment. There was no significant difference in the suppression of spermatogenesis between the two dosage regimens. The median time to reaching azoospermia was 2.5 months from the onset of injections and the median time to recovery of sperm in the ejaculate was 2.0 months after cessation of treatment. Both steroid regimens were equally effective in suppressing LH, FSH and testosterone levels. Testosterone levels returned to baseline by the fourth post-treatment month while LH and FSH demonstrated significant rebound above baseline levels from 3 to 5 months after cessation of treatment. No serious clinical side effects were observed. Weight gain and increases in libido were reported during treatment by most volunteers. A transient decrease in libido was noted in 5/20 (25%) men between 1-2 months after cessation of injections, presumably due to the prolonged effects of DMPA relative to TE. These results indicate that uniform induction of reversible azoospermia with minimal side effects can be achieved in a non-Caucasian population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Residual sperm function in oligozoospermia induced by testosterone enanthate administered as a potential steroid male contraceptive.

To investigate the fertility of men who remain oligozoospermic despite sex steroid suppression, the in-vitro fertilizing capacity of residual spermatozoa was assessed in 30 men receiving intramuscular testosterone enanthate (TE). Spermatozoa were prepared by either Percoll or repetitive centrifugation/washing. Although the mean (+/- SEM) pretreatment zona-free hamster oocyte penetration (HOP) rates were similar (59.4 +/- 10.1 and 63.8 +/- 10.8%), following the induction of oligozoospermia the Percoll-prepared spermatozoa exhibited a penetration rate (26.9 +/- 10.2%) which was markedly greater than that obtained for sperm prepared by repetitive washing (0 +/- 0%). In addition, the partners of two men exhibiting a HOP test with Percoll-prepared spermatozoa, conceived despite a sperm concentration of 3 x 10(6) ml-1 and a negative HOP test with spermatozoa prepared by repetitive washing. These results suggest that Percoll preparation optimizes the assessment of in-vitro sperm function and that the fertility of men with TE-induced severe oligozoospermia is suppressed but not abolished.

Adult↗

Effect of androgen on different biochemical constituents of human semen.

Changes in the levels of fructose, sialic acid, ascorbic acid, cholesterol and acid and alkaline phosphatases in the semen were studied in eight azoospermic volunteers during administration of testosterone propionate over a four week period. In order of responsiveness, elevations were observed in the levels of acid phosphatase, fructose, sialic acid and alkaline phosphatase during androgen therapy. No changes were seen in the levels of cholesterol and ascorbic acid.

Acid Phosphatase↗

Effect of administration of a single dose of testosterone oenanthate on constituents of human seminal plasma and serum gonadotropins.

Testosterone oenanthate was administered intramuscularly in six infertile men with oligozoospermia and its effects on serum gonadotropins and some constituents in the seminal plasma were studied. One week after injection the mean serum FSH level was decreased to about 50%. Serum LH levels did not change. The mean ornithine decarboxylase activity in human semen was increased by 100% after the testosterone administration. The androgen dependent nature of ODC, fructose and sialic acid have been demonstrated.

Citrates↗

The effect of a combination of prostatic massage and antibiotic plus anticongestive drugs on human semen quality and fertility.

A total of 123 patients suffering from chronic prostatitis and infertility were included in this study. No significant improvement in sperm quality was found following prostatic massage with (90 patients) or without (33) antiobiotic plus anticongestive therapy. There was no apparent change in the relative contribution on the prostate and seminal vesicle of the ejaculate, as judged by the concentration of calcium and fructose. Nor was the pregnancy rate increased. It is concluded that prostatic massage is of little or no therapeutic value in treatment of infertility.

Adult↗

The effects of vasectomy on viscosity, pH and volume of semen in man.

The effects of vasectomy on seminal viscosity, volume and pH have been investigated in freshly emitted semen of 21 healthy men before operation and three months later. Viscosity and the pH range were decreased significantly, but the decrease of the seminal volume was not significant. Reasons of changes have been discussed.

Adult↗

The effect of temperature on the motility and viability of sperm.

In specimens of semen kept at 37 degrees C sperm lose their motility and viability. If kept at 4 degrees C they retain their viability but lose their motility from so-called thermal shock. The best temperature to keep semen in order to preserve sperm motility is 20 degrees C. Loss of motility at 37 degrees C is not entirely prevented by prevention of bacterial contamination with antibiotics.

Anti-Bacterial Agents↗

Improvement of semen and pregnancy rate after ligation and division of the internal spermatic vein: fact or fiction?

Male partners with left-sided varicoceles of 96 infertile couples were studied. Fifty-one patients were submitted to ligation of the testicular veins and 45 individuals were randomised as controls. During an observation period of 53 months (range 36 to 74 months) we found no statiscally significant improvement in the semen crude variables, the morphology or the progressive motility in the series of men submitted to surgery. The pregnancy rate was lower in those who had an excision of varicocelle.

Adult↗

Germ cell alkaline phosphatase in human seminal plasma following vasectomy.

Germ cell alkaline phosphatase (also termed placental-like alkaline phosphatase or Nagao isoenzyme) was assayed in seminal plasma using monoclonal antibody-based enzyme immunoassays in samples obtained both before and after vasectomy. In all cases, germ cell alkaline phosphatase fell to undetectable levels within 14 days of operation. A fall in seminal plasma germ cell alkaline phosphatase may thus be an early indication of successful vasectomy.

Alkaline Phosphatase↗

Gonadotropin-releasing hormone antagonist plus testosterone: a potential male contraceptive.

No effective hormonal contraceptive has yet been devised for men. Through their suppressive effect on gonadotropin secretion, GnRH antagonists inhibit both testosterone (T) production and spermatogenesis in animals. Long term administration of an antagonist alone would result in androgen deficiency; this would cause unacceptable physiological and behavioral sequellae in men. Therefore, androgen replacement must be included in any GnRH antagonist regimen used in human male contraception. We tested the hypothesis that the combination of a GnRH antagonist plus T would suppress spermatogenesis in the male primate to azoospermic levels while maintaining normal serum T levels. We examined the effects of the GnRH antagonist Deterelix [N-Ac-DNal(2)1-DpCl-Phe2-DTrp3-DhArg(Et2)6 -DAla10-GnRH], alone and with simultaneous T replacement, on sperm production and serum T levels in adult male monkeys (n = 22). After 12 weeks of daily sc antagonist injection, all animals that received antagonist alone (n = 5) and those that 750 micrograms/kg.day antagonist plus T (n = 5) were azoospermic. After 16 weeks, four of five animals that received 250 micrograms/kg.day antagonist plus T became azoospermic. Control animals (n = 7) received daily injections of vehicle; sperm counts increased somewhat during the study period in that group. Castrate range T levels were achieved in animals receiving antagonist alone. T levels in the groups that received T supplementation and in the control group were in the normal male range throughout the treatment period. Sperm counts returned to the pretreatment range in all animals during the recovery period. We conclude that the combination of a GnRH antagonist plus T can induce azoospermia reversibly in this nonhuman primates species, and that a similar combination may be an effective contraceptive regimen in men. The GnRH antagonist alone may be an effective treatment for androgen-dependent neoplasia.

Animals↗

Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido.

GnRH antagonists suppress pituitary and gonadal function by competing with endogenous GnRH for binding to receptors on pituitary gonadotrophs. We studied the effects of GnRH antagonist administration to men in a protocol simulating a likely male contraceptive regimen combined with a low dose of testosterone. The GnRH antagonist Nal-Glu was given daily (10 mg, sc) for 20 weeks to eight normal men, and a low dose of testosterone enanthate (25 mg, sc) was given every week. Sperm counts started declining during week 4, and complete azoospermia was reached within 6-12 weeks in six of the eight subjects. Subjects 7 and 8, whose sperm counts and serum gonadotropin levels were not suppressed after 10 weeks, were given 20 mg Nal-Glu starting at week 10. One became azoospermic at week 16, while the other's total sperm counts continued declining and reached a nadir of 1.4 million by week 20. Sperm motility and viability in this subject were completely suppressed after week 14. Sperm counts returned to baseline levels 12-14 weeks after the end of Nal-Glu administration. The mean serum LH level of the first six subjects decreased from 3 +/- 03. U/L at baseline to less than 0.1 U/L until week 20, and then levels returned to baseline. FSH levels similarly decreased from a combined mean of 3.6 +/- 0.9 U/L at baseline to below 0.3 U/L after 4 weeks of Nal-Glu administration. Serum mean testosterone levels between weekly injections of testosterone enanthate ranged from 27.4 +/- 5.9 to 4.8 +/- 1.4 nmol/L, but remained in the hypogonadal range (less than 10 nmol/L) for 4 of the 7 days. None of the subjects, however, complained of decreased libido or potency, as assessed by a questionnaire. No systemic or significant local side-effects were observed, other than a minimal reaction at the injection site. These data suggest that complete sustained azoospermia can be achieved in man, without loss of libido, by chronic administration of a GnRH antagonist plus testosterone.

Adult↗

The removal of the seminal vesicles from the boar and the effects on the semen characteristics.

A technique is described for the removal of the seminal vesicles from the boar. The operation was carried out on twelve animals and six of the animals were subsequently trained for semen collection. The seminal plasma from the boars after surgery compared with normal litter mates had a more watery consistency and did not form the characteristic gelduring ejaculation. The sperm concentration was 49% lower while the total reduction of sperm number ejaculate was 78% in the experimental animals, but the ratio of living to dead spermatozoa remained unchanged. The concentrations of citrate and protein were significantly depressed in the seminal plasma of the animals after surgery and the pH increased; the osmolarity remained unchanged. In semination of gilts with the semen from experimental boars revealed no significant loss of fertility compared with the normal controls. Animals slaughtered up to 17 months after surgery showed no regeneration of the seminal vesicles.

Animals↗

Combined effects of urine exposure and cryopreservation on sperm quality: an in vitro study of retrograde ejaculation.

Sperm quality influences fertility and offspring health through both genomic inheritance and epigenetic inheritance. Thus, for use in clinical-assisted reproductive technology (ART), spermatozoa must have optimal genomic and epigenetic structures. In patients with retrograde ejaculation, spermatozoa are usually recovered from urine and then cryopreserved for ART. However, the effects of urine exposure and subsequent freeze-thaw cycles on sperm quality remain unclear. This is particularly true for epigenetic changes and their underlying mechanisms. In this study, we examined how different durations of urine exposure (10 min and 40 min) followed by freeze-thaw cycles affected sperm motility, DNA integrity, and methylation levels of imprinting genes (H19-imprinted maternally expressed transcript [ H19 ], mesoderm-specific transcript [ MEST ], and the transposable element Alu [ Alu ]). As the duration of urine exposure increased, sperm motility (median [interquartile range]) decreased from 48.0% (39.0%-52.5%) to 1.0% (1.0%-5.0%), the DNA fragmentation index (DFI; median [interquartile range]) increased from 12.0% (9.3%-19.9%) to 23.5% (13.9%-33.9%), the MEST methylation level (mean ± standard deviation [s.d.]) increased from 3.8% ± 1.5% to 11.5 ± 1.2%, and the H19 methylation level (mean ± s.d.) decreased from 86.9% ± 0.9% to 82.1% ± 0.5%. The freeze-thaw process further reduced sperm motility, while the DFI and methylation levels of MEST and H19 did not significantly change. The Alu methylation level remained stable. These findings demonstrate that urine exposure affects sperm motility, DNA integrity, and methylation levels of some imprinting genes. These effects intensify over time. In contrast, the freeze-thaw process impacts only sperm motility. In clinical practice, minimizing exposure to urine might improve sperm quality.

Humans↗

Effects of vasectomy on fructose levels in the ejaculate of rams.

Fructose concentration was studied in the ejaculates of 20 intact and 19 vasectomised rams over a two year period. In intact rams the concentration ranged from 222-740 mg/100 ml of seminal plasma during the breeding season (October to December), with lower values (0-300 mg/100) during the rest of the year. In vasectomised rams the seasonal pattern was less marked with very high values (800-1260 mg/100 ml) as well as low values (0-20 mg/100 ml) being encountered during both the breeding and non-breeding seasons, indicating changes in accessory gland function.

Animals↗

Determinantion of testosterone concentration in semen of men with normal or subnormal sperm counts and after vasectomy.

Semen from 58 male subjects, aged 22 to 50, was assayed on an individual basis to determine whether T was present in it. Of the subjects examined 23 were normospermic, 14 oligospermic and 9 azoospermic; 12 men had undergone vasectomy were also included in the study. In 39 of the subjects plasma testosterone was estimated. A competitive protein binding technique was employed for T assays while dried extracts of semen were examined by combined gas-chromatography-mass spectrometry and mass fragmentography. Measurable amounts of T were detected in all seminal specimens assayed. This was confirmed by gas chromatography-mass spectrometry which showed a spectrum suggestive of T. The ratio of unconjugated to conjugated steroid in semen was found to be approximately 1:10. Levels of unconjgated T were similar to those found in plasma of normally menstruating women. The mean seminal concentration of unconjugated T (+/-SD) in the specimens assayed was 0.71 ng/ml+/-0.08 for the normospermic, 0.79+/-0.14 for the ezoospermic, 0.69+/-0.09 for the oligospermic, but only 0.38+/-0.04 for the vasectomized subjects. Plasma levels for this androgen were within the range found in normal men of comparable age. Significant correlation between plasma and seminal T concentration could not be demonstrated and there was no correlation between either of the above parameters and the seminal volume, the number, abnormal form percentage and the motility of spermatozooa in the normo--or oligospermic group. However, when the two groups were pooled into one, significant correlations were found between plasma, (but not seminal T concentration) and the seminal characters examined, perhaps suggesting the number of specimens from the groups should be increased to obtain valid data. Administration of human chorionic gonadotropin produced a marked plasma response as well as a rise of seminal T levels in 3 normospermic subjects whereas cyproterone acetate caused reduction of plasm T levels but had no consistent effect on the seminal concentration of ts steroid although the sensitivity of the seminal method may not have detected smaller changes at this level.

Adult↗

Ureaplasma urealyticum (T. mycoplasma) and male infertility in topical countries.

In view of the potential role of ureaplasma urealyticum in reproductive failure, sample of semen from 100 Nigerian males was cultured in oxoid mycoplasma broth. In 39% of the patients, Uraeplasma uraelyticum was cultured. Of those with positive culture, 92.3% were infertile patients. Five subfertile males achieved pregnancy in their partners after eradication of the ureaplasma urealyticum by a course of tetracycline.

Humans↗

Effect of irrigation of vas deferens on sperm analyses after vasectomy.

70 men were operated for voluntary sterilisation by vasectomy alone and 20 men by vasectomy and irrigation of distal vasa with acid Kystosol solution. Postoperative semen analyses 2 weeks later showed azoospermia in only 2% of cases after vasectomy alone and in 25% of cases following vasectomy and irrigation, and 2 months postoperatively in 44% and 90%, respectively. Non-motile sperm cells in seminal analyses was the most common finding in both series 2 weeks after vasectomy. The problem whether the non motile sperm cells are viable or not is discussed. However, two azoospermic semen analyses must be obtained before sterility after vasectomy can be ascertained.

Cell Count↗