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LE Magazine July 2003

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Male Fertility

Economics of treatments for male infertility.

Economic factors play a major role in the consideration of treatment options for male reproduction. This article has summarized the data and provided new insight into how patients, insurers and populations evaluate competing therapies for male infertility. Many studies are difficult to interpret because of differing success rates and monetary bias. Future studies comparing line-by-line costs and reimbursements by independent sources may be the best way to evaluate different treatments. Urol Clin North Am 2002 Nov;29(4):841-53 Effects of testosterone plus medroxyprogesterone acetate on semen quality, reproductive hormones and germ cell populations in normal young men. Testosterone (T) treatment suppresses gonadotropin levels and sperm counts in normal men, but the addition of a progestin may improve the efficacy of hormonal contraception. This study aimed to investigate the speed and extent of suppression of testicular germ cell number induced by T plus or minus progestin treatment and correlate these changes with serum gonadotropins and inhibin B levels, testicular androgens and sperm output. Thirty normal fertile men (31-46 yr) received either testosterone enanthate (TE, 200 mg im weekly) alone or TE plus depot medroxyprogesterone acetate (DMPA, 300 mg im once) for 2, 6, or 12 wk (n = 5 per group) before vasectomy and testis biopsy. Five men (controls) proceeded directly to surgery. The inclusion of DMPA led to a more rapid fall in serum FSH/LH levels (time to 10% baseline: FSH; 12.6 +/- 2.6 vs. 7.9 +/- 1.4 d; LH, 9.9 +/- 3.4 vs. 3.4 +/- 1.7 d, TE vs. TE+DMPA, respectively, mean +/- SD, both P < 0.0001), yet the mean time to reach a sperm count 10% of baseline was not different (23.7 +/- 7.3 vs. 25.3 +/- 13.9 d, NS). The maximum extent of FSH/LH suppression was identical at 12 wk (mean serum FSH 1.2 and 1.6%, and mean LH 0.3 and 0.2% of baseline: TE vs. TE+ DMPA, respectively) as was sperm count suppression (5 of 5 and 4 of 5 men, respectively, with sperm counts < or =0.1 x 10(6)/ml). Serum inhibin decreased to 55% control at 12 wk in the TE+DMPA group (P < 0.05) but was unchanged by TE treatment (86% control, NS). Testicular T levels declined to approximately 2% of control levels, but testicular dihydrotestosterone and 5alpha-androstane-3alpha,17beta-diol (Adiol) levels were not different to control. Germ cell numbers as determined by stereological methods did not differ between TE and TE+DMPA except at 2 wk when type B spermatogonia and early spermatocytes were significantly lower in the TE+DMPA group (P < 0.05). In all groups, a marked inhibition of Apale->B spermatogonial maturation was seen along with a striking inhibition of spermiation. We conclude that: 1) the addition of DMPA hastens the onset of FSH/LH suppression, correlating with a more rapid impairment of spermatogonial development, but in the longer term, neither germ cell number nor sperm count differed; 2) testicular dihydrotestosterone and Adiol levels are maintained during FSH/LH suppression despite markedly reduced T levels suggesting up-regulation of testicular 5alpha-reductase activity; and 3) spermatogonial inhibition is a consistent feature, but spermiation inhibition is also striking and is an important determinant of sperm output.

J Clin Endocrinol Metab 2002 Feb;87(2):546-56

Comprehensive office evaluation in the new millennium.

The success of a comprehensive office-based evaluation of male-factor infertility depends on the physician's thorough understanding of risk assessment in the history, identification of pertinent physical examination findings and correct assessment of laboratory data. Office-based ultrasonographic techniques have already increased the urologist's ability to visualize suspected anatomic abnormalities, and the use of functional tests of sperm has given greater depth to the limited, but essential, prognostic capabilities of the routine semen analysis.

Urol Clin North Am 2002 Nov;29(4):873-94

The effect of coenzyme Q10 on sperm motility and function.

In sperm cells, the majority of coenzyme Q10 (CoQ10) an energy promoting agent and antioxidant, is concentrated in the mitochondria of the midpiece, so that the energy for movement and all other energy-dependent processes in the sperm cell also depend on the availability of CoQ10. The reduced form of CoQ10-ubiquinol also acts as an antioxidant, preventing lipid peroxidation in sperm membranes. The objective of the study was to evaluate the effect of CoQ10 on sperm motility in vitro, after incubation with 38 samples of asthenospermic and normal motility sperm, and to evaluate the effect of CoQ10 administration in vivo in 17 patients with low fertilization rates after in vitro fertilization with intracytoplasmic sperm injection (ICSI) for male factor infertility. All 38 sperm samples from patients registered in our infertility clinic had normal concentrations and morphology. Of these, 16 patients had normal motility (mean 47.5%) and 22 patients were asthenospermic (mean motility 19.1%). Sperm samples were divided into four equal parts and incubated for 24 h in: HAM's medium alone, in HAM's medium with 1% DMSO and HAM's with 5 microM or 50 microM CoQ10. While no significant change in motility after incubation was observed in the samples with initial normal motility, a significant increase in motility was observed in the 50 microM CoQ10 subgroup of sperm from asthenospermic men, with a motility rate of 35.7 +/- 19.5%, as compared to 19.1 +/- 9.3% in the controls (P < 0.05). The 17 patients with low fertilization rates after ICSI were treated with oral CoQ10, 60 mg/day, for a mean of 103 days before the next ICSI treatment. No significant change was noted in most sperm parameters, but a significant improvement was noted in fertilization rates, from a mean of 10.3 +/- 10.5% in their previous cycles, to 26.3 +/- 22.8% after CoQ10 (P < 0.05). In conclusion, the administration of CoQ10 may result in improvement in sperm functions in selective patients. Further investigation into the mechanisms related to these effects is needed.

Mol Aspects Med 1997;18 Suppl:S213-9

Lipid peroxidation and human sperm motility: protective role of vitamin E.

Asthenospermia is the main factor of male infertility among patients consulting the Asir Infertility Center in Abha, Saudi Arabia. Lipid peroxidation occurring in both the seminal plasma and spermatozoa was estimated by malondialdehyde (MDA) concentration. Spermatozoal MDA concentration was higher in men with decreased sperm motility. The MDA concentration in the seminal plasma exhibited no relationship with sperm concentration, sperm motility, the number of immotile spermatozoa, or even the absence of spermatozoa. The MDA concentration in sperm pellet suspensions of asthenospermic and oligoasthenospermic patients was almost twice that of the normospermic males. The MDA concentration in the sperm pellet suspension from normospermic or oligospermic patients was about 10% that in the seminal plasma. However, the MDA concentration in the sperm pellet suspension of asthenospermic or oligoasthenospermic patients was about 15% that in the seminal plasma. Treatment of asthenospermic patients with oral Vitamin E significantly decreased the MDA concentration in spermatozoa and improved sperm motility. Eleven out of the 52 treated patients (21%) impregnated their spouses; nine of the spouses successfully ended with normal term deliveries, whereas the other two aborted in the first trimester. No pregnancies were reported in the spouses of the placebo-treated patients.

J Androl 1996 Sep-Oct;17(5):530-7

Testicular function in asymptomatic chronic alcoholics: relation to ethanol intake.

To evaluate the effect of ethanol on testicular function in chronic alcoholics without chronic liver disease, we studied 38 asymptomatic chronic alcoholics and 19 age-matched controls. Detailed clinical history, nutritional status, hormonal analysis, and seminal studies were conducted in each case and control. Alcoholic patients had an average of 39 +/- 2 years old (range: 26 to 60) and reported a daily ethanol consumption from 100 to 350 g (mean: 198 +/- 15) over a period of 18.0 +/- 1.2 years. Alcoholics exhibited a significant increase of the luteinizing hormone (p < 0.001) and a decrease of the Free Androgen Index, compared with controls (p < 0.05) that related significantly with the total lifetime dose of ethanol (p < 0.01, both). Seminal studies indicate that 39.4% of alcoholics had significantly reduced their spermatozoa count (p < 0.01), whereas significant morphological abnormalities were observed in 44.7% of the alcoholics (p < 0.01). Spermatozoa motility from alcoholics was also found to be altered in half of the patients (p < 0.01). A significant increase of serum luteinizing hormone, follicle-stimulating hormone, and sex hormone binding globulin levels, and a decrease of Free Androgen Index were observed in alcoholics with morphology and motility abnormalities (p < 0.05, all). In multivariate analysis, the only independent factor that determined the alterations in sperm (count, morphology abnormalities, and motility alterations) was the total lifetime of ethanol intake (p < 0.001, all). We conclude that alcoholics frequently develop a situation of primary hypogonadism related to a lifetime of ethanol consumption.

Alcohol Clin Exp Res 1997 Feb;21(1):128-33

The effect of smoking and varicocele on human sperm acrosin activity and acrosome reaction.

Smoking and varicocele are frequent findings in the medical history and physical examination of patients attending andrological outpatient departments. However, data about their influence on human semen parameters, such as sperm concentration and motility, are contradictory. Therefore, the purpose of this study was to examine sperm function (acrosin activity and induction of the acrosome reaction) in smokers (n = 30) and varicocele patients (n = 30) compared with normal fertile donors (n = 20). The acrosome reaction was detected by triple staining after 3 h of incubation at 37 degrees C, followed by treatment with 0.1% dimethylsulphoxide (spontaneous acrosome reaction) and 10 microM calcium ionophore A23187 (induced acrosome reaction) for 1 h at 37 degrees C. Acrosin activity was measured by gelatinolysis. The diameters around the sperm heads after gelatinolysis and the percentages of spermatozoa showing halo formations were evaluated. The inducibility of the acrosome reaction was significantly lower in semen samples from smokers than in those from the fertile group (7.1 +/- 3.2 versus 11.2 +/- 4.0%, P < 0.01), whereas no statistically significant difference was demonstrated in spermatozoa from patients with varicocele (9.3 +/- 4.3%). Both the percentages of spermatozoa with halo formation (53.3 +/- 20.0 versus 76.6 +/- 13.6%, P < 0.05) and the halo diameters (16.1 +/- 6.6 versus 31.0 +/- 14.5 microns, P < 0.001) were significantly lower in the varicocele group than in the samples from fertile men. These data suggest that smoking and varicocele affect sperm function, and that the standard semen parameters alone are insufficient to evaluate the influence of both factors on human male fertility.

Hum Reprod 1995 Dec;10(12):3190-4

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