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SPERM ANALYSIS

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A normal semen sample should have a volume of 1.5-5.0 ml, with greater than 20 million sperm/ml. The number of abnormal sperm should be less than 40 percent, with greater than 30 percent of the sperm sample demonstrating proper motility. Unfortunately, conventional semen analysis is not a highly accurate predictor of fertility. Purvis et al reported, after surveying infertility clinics, that 52 percent of men with a sperm count below 20 million/ml were able to impregnate their partners and 40 percent of men with a sperm count below 10 million/ml were also able to conceive. Conventional semen analysis often fails to identify infertile males with "normal" samples and conversely fails to identify fertile males with subnormal semen parameters. Another confounding factor is variations in sperm density, motility, and morphology among multiple samples from the same subject.

More sensitive tests are available, including the post-coital test, which measures the ability of sperm to penetrate cervical mucus, and the hamster-egg penetration test, which measures the in vitro ability of sperm to penetrate hamster eggs. This test predicts fertility in an estimated 66% of cases, in comparison to 30 percent with conventional sperm analysis.


Nutritional Therapies

Carnitine

The main function of carnitine in the epididymis is to provide an energetic substrate for spermatozoa. Carnitine contributes directly to sperm motility and may be involved in the successful maturation of sperm. This is especially important since epididymal sperm use fatty acid oxidation as their main source of energy metabolism, and thus tend to concentrate carnitine while in the epididymis, as carnitine is necessary for transport of fatty acids into the mitochondria. Low levels of carnitine reduce fatty acid concentrations within the mitochondria, leading to decreased energy production and potential alterations in sperm motility.

In a study involving 124 infertile patients, a direct correlation between semen carnitine content and sperm motility was found. The results also show a positive correlation between free L-carnitine and both sperm count and the number of motile sperm per milliliter (P<0.01).

In one multi-center trial, 100 patients received 3 g/day of oral L-carnitine for four months. Sperm parameters were assessed before, during, and after the study. Motility was determined by computer-assisted sperm analysis. The results clearly demonstrate carnitine has a positive effect on sperm motility. The percentage of motile spermatozoa increased from 26.9 ± 1.1 to 37.7 ± 1.1 percent. The percent of sperm with rapid linear progression increased from a baseline of 10.8 percent to 18.0 percent. Not only did carnitine significantly affect sperm motility, but the total number of spermatozoa per ejaculate also increased.

Another clinical study reported similar results with 3 g carnitine given daily for three months. Thirty-seven of the 47 participants had increases in sperm motility, rapid linear progression, and total number of sperm.

In a related study, 20 men with idiopathic asthenospermia (defective sperm motility) were given acetylcarnitine, 4 g/day for 60 days. While acetylcarnitine did not affect sperm density or total motility, it did significantly increase progressive linear sperm motility. It is interesting to note that gains in sperm motility were sustained in 12 of the subjects during the four-month follow-up period. Five pregnancies occurred during treatment, with two more occurring during the four months following the trial.
Nutritional Therapies

Carnitine

The main function of carnitine in the epididymis is to provide an energetic substrate for spermatozoa. Carnitine contributes directly to sperm motility and may be involved in the successful maturation of sperm. This is especially important since epididymal sperm use fatty acid oxidation as their main source of energy metabolism, and thus tend to concentrate carnitine while in the epididymis, as carnitine is necessary for transport of fatty acids into the mitochondria. Low levels of carnitine reduce fatty acid concentrations within the mitochondria, leading to decreased energy production and potential alterations in sperm motility.

In a study involving 124 infertile patients, a direct correlation between semen carnitine content and sperm motility was found. The results also show a positive correlation between free L-carnitine and both sperm count and the number of motile sperm per milliliter (P<0.01).

In one multi-center trial, 100 patients received 3 g/day of oral L-carnitine for four months. Sperm parameters were assessed before, during, and after the study. Motility was determined by computer-assisted sperm analysis. The results clearly demonstrate carnitine has a positive effect on sperm motility. The percentage of motile spermatozoa increased from 26.9 ± 1.1 to 37.7 ± 1.1 percent. The percent of sperm with rapid linear progression increased from a baseline of 10.8 percent to 18.0 percent. Not only did carnitine significantly affect sperm motility, but the total number of spermatozoa per ejaculate also increased.

Another clinical study reported similar results with 3 g carnitine given daily for three months. Thirty-seven of the 47 participants had increases in sperm motility, rapid linear progression, and total number of sperm.

In a related study, 20 men with idiopathic asthenospermia (defective sperm motility) were given acetylcarnitine, 4 g/day for 60 days. While acetylcarnitine did not affect sperm density or total motility, it did significantly increase progressive linear sperm motility. It is interesting to note that gains in sperm motility were sustained in 12 of the subjects during the four-month follow-up period. Five pregnancies occurred during treatment, with two more occurring during the four months following the trial.
Arginine

The amino acid arginine is a biochemical precursor in the synthesis of putrescine, spermidine, and spermine, which are thought to be essential to sperm motility. In 1973, Schachter et al published a study in which arginine was given to 178 men with low sperm count. Seventy-four percent of the subjects had significant improvement in sperm count and motility after taking 4 g/day for three months.

More recently, researchers in Italy evaluated the clinical efficacy of arginine in 40 infertile men. All the men had a normal number of sperm ( > 20 million/ml) but had decreased motility which was not due to immunological disorders or infections. Subjects were given 80 ml of a 10-percent arginine HCl solution for six months. Arginine supplementation significantly improved sperm motility without any side effects.


Zinc

Zinc is a trace mineral essential for normal functioning of the male reproductive system. Numerous biochemical mechanisms are zinc dependent, including more than 200 enzymes in the body. Zinc deficiency is associated with decreased testosterone levels and sperm count. An adequate amount of zinc ensures proper sperm motility and production. Zinc levels are generally lower in infertile men with diminished sperm count, and several studies have found supplemental zinc may prove helpful in treating male infertility.

In one trial, the effect of zinc supplementation on testosterone, dihydrotestosterone, and sperm count was studied. Thirty-seven patients with idiopathic infertility of more than five-years duration and diminished sperm count received 24 mg elemental zinc from zinc sulfate for 45-50 days. The results were dramatic in the 22 subjects with initially low testosterone levels; a significant increase in testosterone levels and sperm count (from 8 to 20 million/ml) was noted, along with nine resulting pregnancies.

Fourteen infertile males with idiopathic oligospermia were supplemented with 89 mg zinc from oral zinc sulfate for four months. Serum zinc levels were unaffected, but seminal zinc levels significantly increased. There were also improvements in sperm count and in the number of progressively motile and normal sperm. Three pregnancies occurred during the study.

Zinc supplementation appears warranted in the treatment of male infertility, especially in cases of low sperm count or decreased testosterone levels.

Antioxidants

Polyunsaturated fatty acids and phospholipids are key constituents in the sperm cell membrane and are highly susceptible to oxidative damage. Sperm produce controlled concentrations of reactive oxygen species, such as the superoxide anion, hydrogen peroxide, and nitric oxide, which are needed for fertilization; however, high concentrations of these free radicals can directly damage sperm cells. Disruption of this delicate balance has been proposed as one of the possible etiologies of idiopathic male infertility.

Vitamin C

Studies have shown the concentration of ascorbic acid in seminal plasma directly reflects dietary intake, and lower levels of vitamin C may lead to infertility and increased damage to the sperm's genetic material. Fraga et al demonstrated this by reducing ascorbic acid intake in healthy men from 250 mg to 5 mg per day. Seminal plasma levels of vitamin C decreased by 50 percent, with a concomitant 91-percent increase in sperm with DNA damage.

Cigarette smoking has been documented as having deleterious effects on sperm quality. In a University of Texas study on vitamin C and sperm quality in heavy smokers, 75 men were divided into three supplementation groups; one was given placebo, the other groups received 200 mg or 1000 mg ascorbic acid. While the placebo group showed no improvement, the ascorbic acid groups showed significant improvement in sperm quality, with the greatest improvement occurring in the 1000 mg group.

In perhaps one of the best studies on vitamin C and male infertility, 30 infertile but otherwise healthy men were given a placebo, 200 mg, or 1000 mg vitamin C daily. After one week, the group receiving 1000 mg/day had a 140-percent increase in sperm count, while there was no change in the placebo group. The 200 mg/day group had a 112-percent increase in sperm count, while both groups demonstrated significant reductions in the number of agglutinated sperm. Most importantly, by the end of the 60-day study every participant in the vitamin C group had impregnated their partner, while no pregnancies occurred in the placebo group.

Vitamin E
Vitamin E is a well-documented antioxidant and has been shown to inhibit free-radical-induced damage to sensitive cell membranes. In one study, lipid peroxidation in the seminal plasma and spermatozoa was estimated by malondialdehyde (MDA) concentrations. Oral supplementation with vitamin E significantly decreased MDA concentration and improved sperm motility, resulting in a 21-percent pregnancy occurrence during the study.

In one randomized, cross-over, controlled trial, 600 mg/day vitamin E improved sperm function in the zona binding assay, therefore enhancing the ability of the sperm to penetrate the egg in vitro.

Nine men with low sperm count and alterations in sperm motility were given vitamin E with the antioxidant trace mineral selenium for six months. Compared to the baseline pre-supplementation period of four months, the combination of vitamin E and selenium significantly increased sperm motility and the overall percentage of normal spermatozoa.

Glutathione/Selenium

Glutathione is vital to sperm antioxidant defenses and has demonstrated a positive effect on sperm motility. Selenium and glutathione are essential to the formation of phospholipid hydroperoxide glutathione peroxidase, an enzyme present in spermatids which becomes a structural protein comprising over 50 percent of the mitochondrial capsule in the mid-piece of mature spermatozoa. Deficiencies of either substance can lead to instability of the mid-piece, resulting in defective motility.

Glutathione therapy was used in a two-month, placebo-controlled, double-blind, cross-over trial of 20 infertile men. The subjects were given either a daily 600 mg intramuscular injection of glutathione or an equal volume of placebo. Glutathione demonstrated a statistically significant effect on sperm motility, especially increasing the percentage of forward motility.

Sixty-nine infertile Scottish men were given either placebo, selenium, or selenium in combination with vitamins A, C, and E for three months. At the end of the trial, both selenium-treated groups had significant improvements in sperm motility; however, sperm density was unaffected. Eleven percent of the participants in the treatment groups impregnated their partner during the course of the study.

Another study compared the effects of selenium supplementation in 33 infertile men. They were given either a 200 mcg/day dose of selenium from sodium selenite or a selenium-rich yeast for 12 weeks. While selenium concentration in seminal fluid was increased in both groups, it was markedly higher in the yeast-Se group. Yeast-Se significantly increased glutathione peroxidase activity in the seminal fluid, but failed to produce any improvements in sperm count, motility, or morphology.

Coenzyme Q-10
In sperm cells, coenzyme Q10 (CoQ10) is concentrated in the mitochondrial mid-piece, where it is involved in energy production. It also functions as an antioxidant, preventing lipid peroxidation of sperm membranes. When sperm samples from 22 asthenospermic men were incubated in vitro with 50 microM CoQ10, significant increases in motility were observed. CoQ10 (60 mg) was given to 17 infertile patients for a mean 103 days, and although there were no significant changes in standard sperm parameters, there was a significant improvement in fertilization rate (p<.0.05).

In another study, 10 mg/day of coenzyme Q7 (an analog of CoQ10) was given to infertile men, with resulting increases in sperm count and motility.

Clearly, additional studies will be needed to evaluate the possible role of coenzyme Q10 in the treatment of male infertility.

Vitamin B12

Vitamin B12, in its various forms, has been studied for its effect on male infertility. Vitamin B12 is important in cellular replication, especially for the synthesis of RNA and DNA, and deficiency states have been associated with decreased sperm count and motility.

Methylcobalamin (1,500 mcg/day) was given to a group of infertile men for a period of 8-60 weeks. They were evaluated periodically by semen analysis, and standard sperm parameters were increased by 60 percent. In another methylcobalamin study, 1,500 mcg/ day was given to 26 infertile men for a period of 4-24 weeks. Sperm analysis was conducted eight weeks into the study. Sperm concentration increased in 38.4 percent of the cases and total sperm count increased in 53.8 percent of the men. Sperm motility increased in 50 percent of the participants. Serum LH, FSH, and testosterone levels were unchanged. When 6000 mcg/day was given to men with low sperm count, it resulted in a 57-percent improvement. Vitamin B-12 (1000 mcg/day) was administered to men with a sperm count less than 20 million/ml. By the end of the study, 27 percent of the men had a sperm count over 100 million/ml.

Acupuncture and Botanical Medicine

Several studies have investigated the use of acupuncture as a therapy for male infertility. In one prospective controlled study, 16 infertile males were treated with acupuncture twice per week for five weeks. Compared to the control group, patients receiving acupuncture had increases in total functional sperm fraction, percentage of viability, total motile sperm per ejaculation, and overall integrity of the axonema (p<0.05).

An additional study reported when acupuncture was performed on 28 infertile men, all sperm parameters significantly improved, with the exception of ejaculate volume.

Ginseng has historically been used in Chinese medicine as a male Qi tonic. Panax ginseng and Eleutherococcus senticosus (Siberian ginseng) have a long history of traditional use and were commonly prescribed to enhance male virility and fertility.

Ginseng, an adaptogenic herb, has a multitude of physiological effects within the body. Chen et al found extracts of Panax notoginseng were capable of significantly enhancing in vitro sperm motility. Other studies have shown that Panax ginseng promotes increased sperm formation and testosterone levels in animals.
Researchers in Korea have recently determined that administering Panax ginseng extract to animals can enhance erectile capacity and protect against atrophy and testicular damage induced by dioxin.

When 18 water extracts of Chinese medicinal herbs were evaluated for their effect on sperm motility, Astragalus was the only herb with a significant stimulatory effect. At 10 ml/mg, in vitro sperm motility was increased 146.6 ± 22.6 percent compared to control.

The herb Pygeum africanum may also be an effective therapy for male infertility, especially in cases of diminished prostatic secretions. Pygeum extracts have been shown to increase alkaline phosphatase activity, which helps maintain the appropriate pH of seminal fluid, and increases total prostatic secretions. Sperm motility is partly determined by the pH of the prostatic fluid. If Pygeum can raise the pH of prostatic fluid, it may have a role in promoting and maintaining optimal sperm motility.

SEMEN ANALYSIS MALE INFERTILITY

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