A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Effects of pentoxifylline on sperm motility in normogonadotropic asthenozoospermic men. Pentoxifyllin treatment of oligoasthenospermic men. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Comparison of the effectiveness of placebo, clomiphene citrate, mesterolone, pentoxifylline, and testosterone rebound therapy for the treatment of idiopathic oligospermia. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. Treatment of asthenozoospermia with zinc sulphate: andrological, immunological and obstetric outcome. Indications of the mechanisms involved in improved sperm parameters by zinc therapy. Lipid peroxidation and human sperm motility: protective role of vitamin E. Carnitine for the treatment of idiopathic asthenospermia: a randomized, double-blind, placebo-controlled trial. Relationship between ascorbic acid and male fertility. Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status. [In vivo scavenging effect of ethylcysteine on reactive oxygen species in human semen]. Magnesium-orotate supplementation for idiopathic infertile male patients: a randomized, placebo-controlled clinical pilot study. A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia. [A controlled randomized trial of the use of combined L-carnitine and acetyl-L-carnitine treatment in men with oligoasthenozoospermia]. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. Effect of DHA supplementation on DHA status and sperm motility in asthenozoospermic males. May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrograde embolization for varicocele? Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia. A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial. The effect of oral selenium supplementation on human sperm motility.
To determine the effectiveness of the in vivo administration of vitamin E as treatment for reactive oxygen species-associated male infertility.
                University-based center for reproductive medicine.
                Double-blind randomized placebo cross-over controlled trial.
                Thirty healthy men with high levels of reactive oxygen species generation in semen and a normal female partner.
                Patients were allocated to two groups according to the blinded randomization. Each patient received either 600 mg/d of vitamin E (Ephynal, 300 mg tablets; F. Hoffman-La Roche Ltd., Basle, Switzerland) (order A) or identical placebo tablets (order B) for 3 months. Then after a 1-month wash-out period the patients were crossed-over to the other treatment.
                Improvement in the in vitro function of the spermatozoa measured by conventional semen analysis, computerized motility assessment, determination of reactive oxygen species generation, binding to the zona pellucida of the unfertilized human oocyte in a competitive zona binding assay, development of hyperactivated motility (both spontaneous and in the presence of 20% of the natural agonist, human follicular fluid) and pregnancy.
                Rise in the blood serum vitamin E levels after treatment accompanied by improvement in one of the sperm function tests: the zona binding assay. The zona binding ratio for order A improved from 0.2 (range 0 to 0.5) before treatment to 0.5 (range 0.1 to 1.0) after treatment, the corresponding values for order B were 0.2 (range 0 to 1.0) before treatment and 0.3 (range 0.1 to 0.7) after treatment.
                Oral administration of vitamin E significantly improves the in vitro function of human spermatozoa as assessed by the zona binding test. Forty-seven normogonadotropic men with idiopatic asthenozoospermic were divided at random: group I (N = 22) received placebo and group II (N = 25) received 1200 mg of pentoxifylline/day during 6 months. Semen analysis was performed basal and at 3 and 6 months of the study period. No statistical changes in serum hormone concentration were found, nor in volume, sperm counts, viability, and morphology before and after treatment. Sperm motility increased following pentoxifylline treatment after 3 and 6 months from 25.5 (21.0-30.0) to 35.5 (31.5-39.0) (p < .00001) and to 42.0 (38.0-46.0) (p < .00001), respectively. Although in the placebo control cases some changes were observed in the sperm motility, they were less significant. Furthermore, progressive motility only in grade A increased with pentoxifylline from 2.5 (0.0-6.0) to 12.0 (6.0-19.5) (p < .001) at 3 months and to 22.5 (17.0-26.0) at 6 months (p < .00001). In conclusion, pentoxifylline had an additional effect rather than placebo and was useful treatment in these cases of male factor infertility. A randomised group of 90 men with idiopathic oligoasthenozoospermia was subjected to control study with pentoxifyllin. Pentoxifyllin was given to 51 men 1200 mg daily for 3 months. The other group of 39 infertile men was followed during the same period of time. Significant improvement was observed, in treated group, in percentage of motile sperms and normal shaped sperms after 3 months treatment. This study emphasizes that pentoxifyllin is a relatively good drug for restoring sperm motility and morphology in oligoasthenozoospermic men. To evaluate the effectiveness of coenzyme Q(10) treatment in improving semen quality in men with idiopathic infertility.
                Placebo-controlled, double-blind randomized trial.
                Andrology Unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.
                Sixty infertile patients (27-39 years of age) with the following baseline sperm selection criteria: concentration >20 x 10(6)/mL, sperm forward motility <50%, and normal sperm morphology >30%; 55 patients completed the study.
                Patients underwent double-blind therapy with coenzyme Q(10), 200 mg/day, or placebo; the study design was 1 month of run-in, 6 months of therapy or placebo, and 3 months of follow-up.
                Variations in semen parameters used for patient selection and variations of coenzyme Q(10) and ubiquinol concentrations in seminal plasma and spermatozoa.
                Coenzyme Q(10) and ubiquinol increased significantly in both seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, baseline and after treatment, of seminal plasma or intracellular coenzyme Q(10) and ubiquinol levels and kinetic parameters was found in the treated group. Patients with a lower baseline value of motility and levels of coenzyme Q(10) had a statistically significant higher probability to be responders to the treatment.
                The exogenous administration of coenzyme Q(10) increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia. To study the effects of folic acid and zinc sulfate treatment on semen variables in fertile and subfertile men.
                Double-blind, placebo-controlled interventional study.
                Two outpatient fertility clinics and nine midwifery practices in The Netherlands.
                One hundred eight fertile and 103 subfertile men.
                Both groups were randomly assigned to receive one of four treatments for 26 weeks: folic acid and placebo, zinc sulfate and placebo, zinc sulfate and folic acid, and two placebos. Folic acid was given at a daily dose of 5 mg, and zinc sulfate was given at a daily dose of 66 mg.
                Before and after treatment, standardized semen and blood samples were obtained for determinations of sperm concentration, motility, and morphology according to World Health Organization guidelines; semen morphology according to strict criteria; and blood folate and zinc concentrations. Effects of the four interventions were evaluated separately in subfertile and fertile men.
                Subfertile men demonstrated a significant 74% increase in total normal sperm count and a minor increase of 4% abnormal spermatozoa. A similar trend was observed in fertile men. Pre-intervention concentrations of folate and zinc in blood and seminal plasma did not significantly differ between fertile and subfertile men.
                Total normal sperm count increases after combined zinc sulfate and folic acid treatment in both subfertile and fertile men. Although the beneficial effect on fertility remains to be established, this finding opens avenues of future fertility research and treatment and may affect public health. Forty-six subfertile men with idiopathic oligospermia were randomly assigned to 6 months of treatment with a placebo, clomiphene citrate (25 or 50 mg/day), mesterolone (100 mg/day), or pentoxifylline (1200 mg/day) or 4 months of testosterone enanthate treatment (100 or 250 mg on alternate weeks). Treatment with the placebo, mesterolone, pentoxifylline, and testosterone rebound therapy did not result in a significant increase in the mean sperm concentration or pregnancy in the partners. Clomiphene citrate at both dosages significantly increased the mean sperm concentration without improving sperm motility or morphology during the 6-month treatment period. Pregnancy rates of 36.4% and 22.2% were observed in partners of men receiving clomiphene citrate 25 mg/day and 50 mg/day, respectively. This study also illustrates the difficulties in identifying suitable patients for and assessing the efficacy of different treatment regimens. We determined the efficacy of coenzyme Q10 supplementation on semen parameters, sperm function and reproductive hormone profiles in infertile men.
                A total of 212 infertile men with idiopathic oligoasthenoteratospermia were randomly assigned to receive 300 mg coenzyme Q10 (Kaneka, Osaka, Japan) orally daily (106 in group 1) or a similar placebo regimen (106 in group 2) during a 26-week period, followed by a 30-week treatment-free phase. Two semen analyses, acrosome reaction test, immunobead test for antisperm antibody, and determination of resting levels of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone and inhibin B were done in all participants. Blood and seminal plasma total coenzyme Q10 was also assessed.
                Significant improvement in sperm density and motility was evident with coenzyme Q10 therapy (each p = 0.01). Using the Kruger classification sperm morphology evaluation revealed an increase in the percent of normal forms in the coenzyme Q10 group (p = 0.07). A positive correlation was found between treatment duration with coenzyme Q10 and sperm count (r = 0.46, p = 0.03) as well as with sperm motility (r = 0.45, p = 0.04) and sperm morphology (r = 0.34, p = 0.04). The coenzyme Q10 group had a significant decrease in serum follicle-stimulating hormone and luteinizing hormone at the 26-week treatment phase (each p = 0.03). By the end of the treatment phase the mean +/- SD acrosome reaction had increased from 14% +/- 8% and 15% +/- 8% to 31% +/- 11% and 16% +/- 10% in the coenzyme Q10 and placebo groups, respectively (p = 0.01).
                Coenzyme Q10 supplementation resulted in a statistically significant improvement in certain semen parameters. However, further studies are needed to draw a final conclusion and evaluate the effect of coenzyme Q10 supplementation on the pregnancy rate. The role of zinc therapy on infertility caused by defective sperm quality is examined.
                In this study, 100 men with asthenozoospermia were randomised into two groups--250 mg twice daily zinc therapy for 3 months and no therapy. The patients were followed up for another 6 months. Sperm parameters, circulating antisperm antibodies, sex hormones and T helper cytokines were evaluated before and after treatment for the two groups.
                There was significant improvement in the sperm quality; sperm count (P<.02), progressive motility (P<.05), fertilising capacity (P<.01) and a reduction in the incidence of antisperm antibodies (P<.01). Zinc/cadmium was higher in the zinc therapy group (P<.02). T helper cytokine, interleukin-4 level was significantly higher after zinc therapy (P<.02) while TNFalpha showed a significant decrease (P<.05).
                Zinc therapy has a role in improving sperm parameters in men with asthenozoospermia, probably through its membrane stabilising effect as an antioxidant and its effect on cellular and humoral immunity by reducing the levels of antisperm antibodies and TNFalpha and increasing that of IL-4. To determine possible indications of the mechanisms involved in improved sperm parameters by zinc therapy in asthenozoospermic men.
                Forty-five men with asthenozoospermia (>or=40% immotile sperm) were randomized into four therapy groups: zinc only: n = 11; zinc + vitamin E: n = 12 and zinc + vitamins E + C: n = 14 for 3 months, and non-therapy control group: n = 8. Semen analysis was done according to WHO guidelines. Malone dialdehyde, tumour necrosis factor-alpha (TNF-alpha), total antioxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase were determined in the semen and serum. Antisperm antibodies IgG, IgM and IgA were evaluated by immunobeads. Sperm chromatin integrity was determined by acid denaturation by acridine orange and sperm apoptosis by light and electron microscopy. The effect of zinc on in vitro induced sperm oxidative stress by NADH was evaluated.
                Asthenozoospermia was significantly associated with oxidative stress with higher seminal malone dialdehyde (8.8 vs. 1.8 mmol/l, p < 0.001) and TNF-alpha (60 vs. 12 pg/l, p < 0.001), and low total antioxidant capacity (1.8 vs. 8.4, p < 0.01), SOD (0.8 vs. 3.1, p < 0.01) and glutathione peroxidase (1.6 vs. 4.2, p < 0.05), compared to normozoospermia. Zinc therapy alone, in combination with vitamin E or with vitamin E + C were associated with comparably improved sperm parameters with less oxidative stress, sperm apoptosis and sperm DNA fragmentation index (DFI). On the whole, there was no difference in the outcome measures between zinc only and zinc with vitamin E and combination of vitamins E + C. In the in vitro experiment zinc supplementation resulted in significantly lower DFI (14-29%, p < 0.05) compared to zinc deficiency.
                Zinc therapy reduces asthenozoospermia through several mechanisms such as prevention of oxidative stress, apoptosis and sperm DNA fragmentation.
                (c) 2008 S. Karger AG, Basel. 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. To determine the effect of oral carnitine supplementation on the semen parameters of men with idiopathic asthenospermia.
                Prospective, randomized, double-blind placebo-controlled study.
                Academic tertiary referral centers.
                Male patients presenting with infertility and with sperm motility of 10%-50% were selected.
                Patients were randomized to 24-week treatment arms of oral carnitine (2,000 mg L-carnitine and 1,000 mg L-acetyl-carnitine per day) or placebo.
                Sperm motility and total motile sperm counts at baseline, 12 weeks, and 24 weeks. Seminal plasma and sperm free, acetyl, and total L-carnitine levels at baseline and at week 24.
                Twenty-one patients entered the study, with 12 patients in the carnitine arm and 9 in the placebo arm. There were no significant differences in baseline semen parameters between the carnitine and placebo arms. There was no statistically significant or clinically significant increase in motility or total motile sperm counts between baseline, 12 week, or 24 weeks in the carnitine or placebo arms.
                Carnitine supplementation demonstrated no clinically or statistically significant effect on sperm motility or total motile sperm counts in men with idiopathic asthenospermia. nan In a randomized, placebo-controlled, double-blind study we investigated whether high-dose oral treatment with vitamins C and E for 56 days was able to improve semen parameters of infertile men. Ejaculate parameters included semen volume, sperm concentration and motility, and sperm count and viability. Thirty-one patients without genital infection but with asthenozoospermia (< 50% motile spermatozoa) and normal or only moderately reduced sperm concentration (> 7 x 10(6) spermatozoa/ml) (according to WHO criteria) were examined. To investigate the influence of the epididymal storage period on semen parameters, the patients were asked to deliver two semen samples with abstinence times of 2 and 7 days both before and at the end of vitamin treatment. After randomization, the patients received either 1000 mg vitamin C and 800 mg vitamin E (n = 15) or identical placebo capsules (n = 16). No changes in semen parameters were observed during treatment, and no pregnancies were initiated during the treatment period. Combined high-dose antioxidative treatment with vitamins C and E did not improve conventional semen parameters or the 24-h sperm survival rate. Prolonged abstinence time increased ejaculate volume (P < 0.05), sperm count (P < 0.05), sperm concentration (P < 0.05) and the total number of motile spermatozoa (P < 0.05). Numerous studies have reported beneficial effects of antioxidant drugs on semen quality, but there is no well-defined therapeutical protocol in male infertility. This study aimed to test the effects of vitamin E and selenium supplementation on lipid peroxidation and on sperm parameters. The study included 54 voluntary and infertile men who produced semen samples for spermiogram and for spectrophotometric measurement of a lipid peroxidation marker, the malondialdehyde (MDA), and produced blood samples for high-performance liquid chromatography assessment of serum vitamin E level. The trial was randomized and open. Twenty-eight men were supplemented daily by vitamin E (400 mg) and selenium (225 microg), during 3 months. The remaining 26 patients received vitamin B (4,5 g/day) for the same duration. Only 20 patients achieved their treatment and returned for control analysis. MDA concentrations in sperm were much less than in seminal plasma and motility and viability were inversely correlated with semen MDA levels. In contrast to vitamin B supplementation, vitamin E and selenium supplementation produced a significant decrease in MDA concentrations and an improvement of sperm motility. The results confirm the protective and beneficial effects of vitamin E and selenium on semen quality and advocate their use in male infertility treatment. To examine whether a beneficial effect of N-acetylcysteine (NAC) on semen parameters and oxidative/antioxidant status in idiopathic male infertility exists. The production of reactive oxygen species is a normal physiologic event in various organs. However, overproduction of reactive oxygen species can be detrimental to sperm and has been associated with male infertility.
                Our study included 120 patients who had attended our clinic and were diagnosed with idiopathic infertility according to medical history and physical and seminal examination findings, as initial evaluations. The patients were divided randomly into 2 groups. Those in the study group (60 men) were given NAC (600 mg/d orally) for 3 months; the control group (60 men) received a placebo. The oxidative status was determined by measuring the total antioxidant capacity, total peroxide and oxidative stress index in plasma samples. The sperm parameters were evaluated after NAC treatment and were compared with those in the control group.
                NAC had significant improving effects on the volume, motility, and viscosity of semen. After NAC treatment, the serum total antioxidant capacity was greater and the total peroxide and oxidative stress index were lower in the NAC-treated group compared with the control group. These beneficial effects resulted from reduced reactive oxygen species in the serum and reduced viscosity of the semen. No significant differences were found in the number or morphology of the sperm between the 2 groups.
                We believe that NAC could improve some semen parameters and the oxidative/antioxidant status in patients with male infertility. The production of reactive oxygen species (ROS) is a normal physiological event in various organs including the testis. Overproduction of ROS, however, can be detrimental to sperm, being associated with male infertility. In vivo experiments using vitamin E (Vit. E), one of the major membrane protectants against ROS and lipid peroxidation, have shown its significant potential in treating ROS-associated male infertility. There has been no study that the scavenging drugs reduce the level of ROS in human semen. Previously we reported the in vitro scavenging effectiveness of ethylcysteine (EC) against ROS in human semen. The present study was performed in order to determine the effectiveness of the in vivo administration of EC as treatment for ROS-associated male infertility.
                Ten cases of male infertility, with the exceptions of azoospermia and pyospermia, were chosen. Patients were divided randomly into two groups. Each group received either 600 mg/day of EC (Group A) or Vit. E 600 mg/day (Group B) for 3 months. Then, after a 1-month wash-out period, the patients were switched to another treatment. Conventional semen analysis, computerized motility assessment, measurement of ROS generation and sperm function assessment by triple stain were performed before and after administration of EC and Vit. E. The levels of EC and Vit. E were also assessed in patients' blood serum and seminal plasma before and after administration of EC and Vit. E.
                Sperm density and sperm motility did not improve but sperm function had a significant tendency toward improvement after administration of EC and Vit. E. ROS levels significantly decreased only after administration of EC After administration of EC and Vit. E, their levels significantly increased in patients' blood serum but were unchanged in patients' seminal plasma.
                Since our study showed that oral administration of EC produced results similar to those of Vit. E, we conclude that EC is an effective treatment agent for ROS-associated male infertility. A randomized, placebo-controlled clinical pilot study was performed in order to examine the effect of magnesium-orotate in male idiopathic infertility. Ten males were treated daily for 90 consecutive days with 3000 mg magnesium-orotate (Magnerot) tablets (Group M). As a control, ten other males were treated in the same way with placebo (Group P). Conventional microscopic sperm characteristics (sperm concentration, motility ratio, total number of motile sperm cells, normal morphology ratio), plus total and ionized magnesium levels in seminal plasma and blood serum were evaluated both prior to treatment and on day 90, at the conclusion of the study. No significant changes in sperm characteristics, blood ionized or total Mg, or ejaculate total Mg levels were detected. However, ejaculate ionized Mg levels increased in Group M from 0.18 +/- 0.05 to 0.30 +/- 0.05 (mmol/l; mean +/- SD, p < 0.05). Within the observation period of 3 months, one pregnancy occurred in the partner of a male from Group M. In conclusion, magnesium-orotate treatment at a dose of 3000 mg/day leads neither to a significant improvement of sperm variables nor does it increase the pregnancy rates of female partners of treated males as compared to those of controls. Thus, magnesium-orotate treatment was not shown to be effective therapy for idiopathic male infertility. Evidence has accumulated supporting the role of reactive oxygen species (ROS) in the pathogenesis of sperm dysfunction among men with infertility. Damage to sperm DNA by ROS can lead to failure of conception, miscarriage or potentially even childhood cancer. The objective of this study was to examine the effect of male antioxidant treatment on embryo quality and pregnancy outcome during in vitro fertilisation-intracytoplasmic sperm injection (IVF-ICSI) treatment.
                Sixty couples with severe male factor infertility were enrolled in a prospective randomised double-blind placebo-controlled trial. Male participants were randomly assigned to take either one capsule per day of the Menevit antioxidant or an identical in appearance placebo for three months prior to their partner's IVF cycle. The primary outcome was cleavage stage embryo quality and the secondary outcomes were oocyte fertilisation rate, pregnancy rates and treatment side-effects. Approval by the local Human Research Ethics Committee was obtained prior to the commencement of this study.
                The antioxidant group recorded a statistically significant improvement in viable pregnancy rate (38.5% of transferred embryos resulting in a viable fetus at 13 weeks gestation) compared to the control group (16% viable pregnancy). No significant changes in oocyte fertilisation rate or embryo quality were detected between the antioxidant and the placebo groups. Side-effects on the Menevit antioxidant were rare (8%) and mild in nature.
                The Menevit antioxidant appears to be a useful ancillary treatment that significantly improves pregnancy rates in couples undergoing IVF-ICSI treatment for severe male factor infertility. The objective of this study was to detect a therapy for idiopathic and varicocele-associated oligoasthenospermia (OAT). Idiopathic and varicocele OAT patients were randomized into 3 groups. Each group was composed of varying degrees of left varicoceles (graded into 5 grades with echo-color Doppler) and of idiopathic OATs. Group 1 used a placebo, group 2 used oral L-carnitine (2 g/d) + acetyl-L-carnitine (1 g/d), group 3 used L-carnitine/acetyl-L-carnitine + 1 x 30-mg cinnoxicam suppository every 4 days. Drugs were administered for 6 months. The groups were composed as follows: group 1, 71 varicoceles and 47 idiopathic OATs; group 2, 62 varicoceles and 39 idiopathic OATs; group 3, 62 varicoceles and 44 idiopathic OATs. Sperm concentration, motility, and morphology before during and after treatments were assessed. Pregnancy rates and side effects were recorded. Group 1 did not have modified sperm patterns during treatment. Group 2 had significantly increased sperm patterns at 3 and 6 months into therapy in idiopathic patients and in patients with grades I, II, and III varicocele, but not in grades IV and V. Group 3 had significantly increased sperm parameters in all patients, with the exception of grade V varicocele. Group 3 sperm patterns proved significantly higher during therapy than group 2. All sperm patterns fell to baseline after therapy suspension. Minor side effects occurred. Pregnancy rates were 1.7% (group 1), 21.8% (group 2), and 38.0% (group 3) (P <.01). L-carnitine/acetyl-L-carnitine + cinnoxicam suppositories proved a reliable treatment for low-grade varicoceles and idiopathic OATs. To determine the efficacy and safety of combined L-carnitine and acetyl-L-carnitine therapy in infertile males with oligoasthenozoospermia.
                One hundred fifty patients with oligoasthenozoospermia were randomized selected into treatment and control groups. The treatment group with 90 patients were given L-carnitine (2 g/d) and acetyl-L-carnitine (1 g/d) orally, twice a day. The patients in control group were given Vitamin E 100 mg plus Vitamin C 100 mg, tid. The oral therapy lasted three months and patients accepted sperm analysis every one month. The L-carnitine level in seminal plasma was examined by high performance liquid chromatography (HPC). Side effects as well as pregnant rate were observed.
                In the treatment group, 85 patients out of 90 finished the three month treatment. Female spouses of 10 patients (11.6%) achieved pregnancy. Moreover, their forward motile sperm per ejaculation, total motile sperm, as well as the concentration of L-carnitine in seminal plasma were increased significantly (P < 0.01). In control group, 53 patients out of 60 completed three months therapy. Two pregnancy (3.7%) was observed. Though some increase was seen in number of forward motile sperm and total motile sperm per ejaculation, the changes were not statistically significant (P > 0.05). The difference of the pregnant rate between two groups was statistically significant. No side effects were found.
                Combined treatment with L-carnitine and acetyl-L-calmitine can be an effective and safe option for treating oligoasthenozoospermia by means of significantly improving forward motile sperm and total motile sperm per ejaculation, as well as increasing pregnant rates. Sperm DNA fragmentation is known to compromise male fertility. Previous findings have suggested the implication of oxidative stress in the etiology of this pathological condition. The present study was conducted to find out if the pathologically increased incidence of DNA fragmentation in ejaculated spermatozoa can be reduced by oral treatment with two antioxidants, vitamins C and E. Sixty-four men with unexplained infertility and an elevated (> or = 15%) percentage of DNA-fragmented spermatozoa in the ejaculate were randomized between an antioxidant treatment (1 g vitamin C and 1 g vitamin E daily for 2 months) group and a placebo group. Sperm DNA fragmentation was evaluated by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assay before and after treatment. No differences in basic sperm parameters were found between the antioxidant treatment and the placebo group before or after treatment. However, the percentage of DNA-fragmented spermatozoa was markedly reduced (P < .001) in the antioxidant treatment group after the treatment (9.1 +/- 7.2) as compared with the pretreatment values (22.1 +/- 7.7). No difference in the pretreatment and posttreatment incidence of sperm DNA fragmentation was observed in the placebo group. These data show that sperm DNA damage can be efficiently treated with oral antioxidants administered during a relatively short time period. The effects of supplementation with docosahexaenoic acid (DHA) on DHA levels in serum, seminal plasma, and sperm of asthenozoospermic men as well as on sperm motility were examined in a randomized, double-blind, placebo-controlled manner. Asthenozoospermic men (n = 28; < or =50% motility) were supplemented with 0, 400, or 800 mg DHA/d for 3 mon. Sperm motility and the fatty acid composition of serum, seminal plasma, and sperm phospholipid were determined before and after supplementation. In serum, DHA supplementation resulted in decreases in 22:4n-6 (-30% in the 800-mg DHA group only) and total n-6 (-6 and -12% in the 400- and 800-mg DHA groups, respectively) fatty acids. Increases were noted in DHA (71 and 131% in the 400- and 800-mg DHA groups, respectively), total n-3 fatty acids (42 and 67% in the 400- and 800-mg DHA groups, respectively), and the n-3/n-6 ratio (50 and 93% in the 400- and 800-mg DHA groups, respectively). In seminal plasma, DHA supplementation resulted in a decrease in 22:4n-6 (-31% in the 800-mg DHA group only) and an increase in the ratio of n-3 to n-6 (35 and 33% in the 400- and 800-mg DHA groups, respectively). There were insignificant increases in DHA and total n-3 fatty acids. In sperm, decreases were noted in 22:4n-6 (-37 and -31% in the 400- and 800-mg DHA groups, respectively). There were no other changes. There was no effect of DHA supplementation on sperm motility. The results show that dietary DHA supplementation results in increased serum--and possibly seminal plasma--phospholipid DHA levels, without affecting the incorporation of DHA into the spermatozoa phospholipid in asthenozoospermic men. This inability of DHA to be incorporated into sperm phospholipid is most likely responsible for the observed lack of effect of DHA supplementation on sperm motility. We performed a randomized, prospective, controlled, intention to treat study in order to determine the effectiveness of an antioxidant therapy in improve the quality of seminal fluid parameters and the natural pregnancies in men with persistent oligospermia (5-20 million/ml) 6 months after retrograde embolization. Forty-two subjects were enrolled and randomized in the study. Treated group (20 subjects) was assigned to receive antioxidant therapy (NAC 600 mg and vitamins-minerals). Untreated group (22 subjects) received no adjunctive medical therapy and was used as controls. Our data were analyzed with an intention to treat strategy. A statistically significant increase in sperm count after antioxidant therapy was recorded (P=0.009). After this therapy, no statistical differences in percentage of WHO class A motile sperm (P=0.752) and typical forms (P=0.926) were found. The univariate logistic regression analysis showed that a man treated with antioxidant therapy presented a probability to have a normal sperm count 20-fold (OR=20.1; CI 95%=1.05-43.2; P=0.014) higher than a man who was untreated. No significant impact on spontaneous pregnancies was found after antioxidant therapy. Despite this preliminary data, we show that antioxidant therapy based on a combination of NAC and micronutrient supplementation can be helpful in improve the sperm count at least in a subset of oligospermic males. However, this improving in sperm count is not associated with a significant increase in spontaneous pregnancies after 12 months. To evaluate the effectiveness of L-carnitine (LC) or L-acetyl-carnitine (LAC) or combined LC and LAC treatment in improving semen kinetic parameters and the total oxyradical scavenging capacity in semen.
                Placebo-controlled, double-blind, randomized trial.
                Andrology unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.
                Sixty infertile men, ages 20 to 40 years, with the following baseline sperm selection criteria: concentration > 20 x 10(6)/mL, sperm forward motility < 50%, and normal sperm morphology > 30%; 59 patients completed the study.
                Patients underwent a double-blind therapy of LC 3 g/d, LAC 3 g/d, a combination of LC 2 g/d and LAC 1 g/d, or placebo. The study design was 1 month of run in, 6 months of therapy or placebo, and 3 months of follow-up evaluation.
                Variations in semen parameters used for patient selection, and variations in total oxyradical scavenging capacity of the seminal fluid.
                Sperm cell motility (total and forward, including kinetic features determined by computer-assisted sperm analysis) increased in patients to whom LAC was administered both alone or in combination with LC; combined LC + LAC therapy led to a significant improvement of straight progressive velocity after 3 months. The total oxyradical scavenging capacity of the semen toward hydroxyl and peroxyl radicals also increased and was positively correlated with the improvement of kinetic features. Patients with lower baseline values of motility and total oxyradical scavenging capacity of the seminal fluid had a significantly higher probability of responding to the treatment.
                The administration of LC and LAC is effective in increasing sperm kinetic features in patients affected by idiopathic asthenozoospemia and improves the total oxyradical scavenging capacity of the seminal fluid in the same population. To determine the efficacy of combined l-carnitine and l-acetyl-carnitine therapy in infertile males with oligo-astheno-teratozoospermia.
                Placebo-controlled double-blind randomized trial.
                University tertiary referral center.
                Sixty infertile patients (aged 20-40 years) with the following baseline sperm selection criteria: concentration, 10 to 40 x 10(6)/mL; forward motility, <15%; total motility, 10% to 40%; and atypical forms, <80%. Fifty-six patients completed the study.
                Patients were submitted to a combined treatment of l-carnitine (2 g/d) and l-acetyl-carnitine (1 g/d) or of placebo; the study design was 2 months' wash-out, 6 months of therapy or of placebo, and 2 months' follow-up.
                Variation in the semen parameters that were used for patient selection.
                Even though increases were seen in all sperm parameters after combined carnitine treatment, the most significant improvement in sperm motility (both forward and total) was present in patients who had lower initial absolute values of motile sperm (<4 x 10(6) forward or <5 x 10(6) total motile spermatozoa per ejaculate).
                Combined treatment with l-carnitine and l-acetyl-carnitine in a controlled study of efficacy was effective in increasing sperm motility, especially in groups with lower baseline levels. To determine the efficacy of L-carnitine therapy in selected cases of male factor infertility.
                Placebo-controlled, double-blind, crossover trial.
                University tertiary referral center.
                One hundred infertile patients (ages 20-40 years) with the following baseline sperm selection criteria: concentration, 10-20 x 10(6)/mL; total motility, 10%-30%; forward motility, <15%; atypical forms, <70%; velocity, 10-30 micro/s; linearity, <4. Eighty-six patients completed the study.
                Patients underwent L-carnitine therapy 2 g/day or placebo; the study design was 2 months of washout, 2 months of therapy/placebo, 2 months of washout, and 2 months placebo/therapy.
                Variation in sperm parameters used in the patients selection criteria, in particular, sperm motility. Excluding outliers, a statistically significant improvement in semen quality, greater than after the placebo cycle, was seen after the L-carnitine therapy for sperm concentration and total and forward sperm motility. The increase in forward sperm motility was more significant in those patients with lower initial values, i.e., <5 x 10(6) or <2 x 10(6) of forward motile sperm/ejaculate or sperm/mL.
                Based on a controlled study of efficacy, L-carnitine therapy was effective in increasing semen quality, especially in groups with lower baseline levels. However, these results need to be confirmed by larger clinical trials and in vitro studies. To determine whether the decline in selenium intake and selenium status in men in the West of Scotland might be a contributory factor to male subfertility.
                Two semen samples were collected from patients attending a subfertility clinic and those patients with samples showing reduced motility were invited to participate in an ethically approved double-blind clinically controlled trial with informed consent. Sixty-nine patients were recruited and received either placebo, selenium alone or selenium plus vitamins A, C and E daily for 3 months. A further semen sample was collected at the end of the trial. Plasma selenium status was determined at the beginning and end of the trial period, as was total sperm density and motility.
                Plasma selenium concentrations were significantly (P < 0.001) higher in both selenium-treated groups than in controls. No significant effect of treatment on sperm density was recorded. Sperm motility increased in both selenium-treated groups, in contrast to a slight decline in the placebo group, but the difference was not significant. However, as the provision of additional vitamins had no effect on any variable measured it was considered justified to combine the two selenium-treated groups and compare them with the placebo treatment. On this basis, selenium treatment significantly (P < 0.002) increased plasma selenium concentrations and sperm motility (P = 0.023) but sperm density was again unaffected. Five men (11%) achieved paternity in the treatment group, in contrast to none in the placebo group.
                This trial confirms the result of an earlier study, that selenium supplementation in subfertile men with low selenium status can improve sperm motility and the chance of successful conception. However, not all patients responded; 56% showed a positive response to treatment. The low selenium status of patients not supplemented again highlights the inadequate provision of this essential element in the Scottish diet.
Preliminary evidence from three small randomised controlled trials suggests that antioxidant supplementation in subfertile males may improve live birth rates for subfertile couples undergoing ART cycles. However, further large well-designed randomised placebo-controlled trials are needed to confirm this.