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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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