Male Infertility: Natural Approaches to a Common Problem

Lisa Watson, ND

Infertility, or the inability to conceive after 12 months of unprotected sex, affects 1 in 6 couples worldwide.1,2 Male and female factor infertility are equally prevalent, with 40% ascribed to each male and female infertility, and 20% to either combined male and female infertility or idiopathic infertility.1,2

Male infertility is a multifactorial disease, with congenital factors, nutrition, environmental exposures, drugs, endocrine disturbances, varicocele, genetic abnormalities, and immunological factors all contributing to impairments in sperm production.1,3 Between 50% and 75% of men, however, have no clear explanation for their infertility.4

Diagnosis of Male Fertility

The majority of men seeking naturopathic care for infertility will have undergone a semen analysis and clinical intake. In some cases, additional laboratory testing or imaging studies may have been performed.

During the naturopathic intake, a clinical history should focus on identifying risk factors or lifestyle considerations that could negatively impact fertility. Systemic diseases, previous chemo/radiotherapy, alcohol abuse, intake of anabolic steroids, and toxic drugs should all be ruled out. Additionally, a history of testicular trauma, orchitis, inguinal surgery, sexually-transmitted diseases, diabetes, prostatitis, cryptorchidism, and varicocele should be elicited.3,4

Semen Analysis

The production of sperm (spermatogenesis) is a continuous process. Approximately 74 days are required to develop motile sperm, plus an additional 12 days to traverse the 6 meters of the epididymis.3

Semen analysis is integral to the diagnosis of male infertility and should be performed according to the World Health Organization (WHO) standards (see Table 1). If the results of semen analysis are normal according to WHO criteria, 1 test is considered to be sufficient. If results are abnormal, a second test should be performed at least 3 months following the initial test. If results are abnormal in at least 2 tests, further endocrine evaluation and imaging studies are indicated.3,4

Table 1. WHO Criteria for Semen Analysis5

Abnormality Finding
Oligozoospermia <15 million spermatozoa/mL
Asthenozoospermia <32% motile spermatozoa
Teratozoospermia <4% normal forms
Oligo-astheno-teratozoospermia (OAT syndrome) Disturbance of all 3 parameters
Azoospermia No spermatozoa in the ejaculate
Aspermia No ejaculate
Leukospermia >1 x 106 ml leukocytes in the ejaculate
pH 7.0-8.0

Medical Treatment of Male Fertility

Apart from a few exceptions, the only available treatments for male factor infertility are medically-assisted reproductive therapies (ART), including intrauterine insemination (IUI), in-vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI).4 ART does not address the underlying cause of male infertility and can potentially transmit genetic anomalies on to the offspring.4

Drug therapy, such as androgens, anti-estrogens, aromatase inhibitors, or gonadotropins, has been shown to have limited success in the treatment of idiopathic male infertility.3,6

Factors Influencing Male Fertility

Multiple research papers have highlighted the global decline in sperm counts. In fact, up to a 32% reduction in sperm counts has been found between 1989 and 2005.7 These findings are likely due to a variety of issues, including environmental, lifestyle and dietary factors (see Table 2).2,6

Table 2. Environmental and Lifestyle Factors Affecting Male Fertility

Environmental or Lifestyle Factor Effect on Fertility
Endocrine-disrupting chemicals Altered sperm parameters2,8,9

Altered steroidogenesis8

Underwear type No increase in scrotal temperature10

Unlikely to significantly impact fertility10

Cell phone use Exposure dependent changes in motility, viability, and morphology11
Alcohol Altered sperm parameters12,13

Increased reactive oxygen species (ROS) production2

Marijuana Altered sperm parameters

Reduced seminal volume13

Smoking Altered sperm morphology

Increased ROS production2,13,14

Coffee Altered sperm parameters with greater than 3 cups of coffee per day14
Age Decrease in semen volume, motility2

Increased DNA fragmentation2

Obesity Decreased testosterone levels

Increased ROS production2,14

Low body weight Lower sperm count and sperm concentration2,14
Psychological stress Altered sperm parameters and steroidogenesis

Increased ROS production15

Naturopathic Treatments

Nutritional Supplements

Prenatal vitamin supplementation has become a worldwide standard-of-care for all women. Despite growing evidence of the importance of nutrients in male factor fertility, there is no equivalent pre-conception nutritional counseling or recommendations available for men. Important nutrients for male factor fertility are discussed below.

Antioxidants

Sperm are highly susceptible to damage from reactive oxygen species (ROS). Male germ cells at various stages of differentiation generate ROS, and low physiologic levels are needed for healthy spermatogenesis. To maintain normal cell function, excess ROS must be continuously inactivated by antioxidants present in the seminal fluid, reflecting a delicate balance between physiological ROS and antioxidants.2,15 When this balance is disrupted, oxidative stress and cellular damage occurs.

Vitamin C is found in concentrations 10-fold higher in seminal plasma than in serum, protecting sperm against ROS damage.16 The concentration of vitamin C in seminal plasma is positively correlated with percentage of normal morphology of sperm. The impact of vitamin C is dose-dependent, with excess doses having damaging pro-oxidant effects that can reduce sperm motility.16,17 Suggested doses are 200-1000 mg daily.

Vitamin E deficiency in animals has been shown to result in infertility.17 Vitamin E is a lipid-soluble antioxidant that can prevent lipid peroxidation in sperm and enhance the activity of other antioxidants.16 Randomized controlled trials have reported vitamin E to be effective in treating infertile men with high ROS levels.18 Daily doses of vitamin E vary from 100 to 600 mg.

Selenium is required for normal spermatogenesis, motility, and morphology.18,19 A double-blind study of infertile men found supplementation with 100 µg of selenium over 3 months significantly increased sperm motility but had no effect on sperm count.20 Other studies have shown selenium to produce a dose-dependent increase in sperm counts, with toxicity reported at excessive doses.2,19 Selenium is best utilized in combination with other synergistic antioxidants such as vitamin E.16

N-acetylcysteine (NAC) acts as an antioxidant and replenishes levels of glutathione, the most abundant antioxidant in the body.16 Studies of NAC have shown improvements in sperm concentration,21 and NAC combined with selenium has additive beneficial effects on sperm concentration and morphology.22 Dosage is typically in the range of 600 mg/day.

Arginine

Arginine is necessary for the production of sperm and inhibition of seminal lipid peroxidation.23 Studies suggest that supplementing with 4 g per day for several months may increase sperm count and quality.24 Other studies have shown subjective improvements in sexual function in men with erectile dysfunction,25 as well as enhancements in sperm cell motility.24

Carnitines

Carnitine is a water-soluble antioxidant that provides the primary fuel for sperm motility. During the passage of sperm from the epididymis and development of motility, spermatozoa show increased levels of L-carnitine.16 Carnitines facilitate the entry and utilization of free fatty acids into the mitochondria and decrease fatty acid oxidation; they also protect sperm DNA from ROS-induced damage.16 Oral supplementation of L-carnitine, dosed at 2-4 g daily, can enhance both sperm motility and concentration over a period of 3 to 6 months.16

Carotenoids

Astaxanthin, a polar carotenoid extracted from the algae Hematococcus pluvialis, has a unique molecular structure enabling it to act as a free radical scavenger both within the cellular membrane’s hydrophobic interiors and along the hydrophilic boundaries.26,27 Astaxanthin is able to neutralize ROS without being destroyed or becoming a pro-oxidant in the process, and has been found to have antioxidant activity 10 times greater than other carotenoids.26,27 Astaxanthin studies in infertile men have shown decreases in ROS, increases in sperm concentration and testosterone, and decreased Inhibin B after 3 months of supplementation.28 This study also found a significant increase in total (54.5% vs 10.5%) and per-cycle (23.1% vs 3.6%) pregnancy rates, compared to a placebo group. Doses of astaxanthin have ranged in studies from 1 mg/day to 40 mg/day, with the majority in the 6-16 mg range.26

Lycopene is an apolar carotenoid found in the seminal fluid, with lower concentrations noted in infertile men.16 Lycopene is an integral part of the seminal fluid’s defense against ROS, and supplementation can improve motility and sperm concentration.16,29 Lycopene, dosed at 10 mg BID for 3 months, has also been shown in studies to improve polyunsaturated fatty acid ratios, including decreases in arachidonic acid (AA) and increases in docosahexaenoic acid (DHA), and a corresponding improvement in cellular integrity.30 This study resulted in a 51% conception rate, either spontaneously or assisted by IVF. Typical doses range from 4-10 mg BID.31

Coenzyme Q10

Coenzyme Q10 is a component of sperm, is involved in energy production, and supports the recycling of vitamin E, thereby controlling its pro-oxidant capability. Oral supplementation at 60 mg per day has been found to inhibit hydrogen peroxide formation in seminal fluid and improve fertilization rates.16 Other studies have shown improvements in sperm count and motility.32

Folic Acid

Folate is necessary for nucleotide synthesis, methylation, and maintenance and protection of DNA during spermatogenesis.33,34,35 Infertile men with low sperm counts often have low folate levels in seminal plasma.34 Increases in sperm count have been seen in different studies after supplementation with folic acid.36,37,38 Folic acid for male infertility is most often used in conjunction with zinc, a combination that has been shown to increase sperm counts, improve sperm motility, and reduce abnormal morphology.2,36,37 The synergy of zinc and folic acid likely results from the impairment of folic acid intestinal absorption in states of zinc deficiency.35 Doses of folic acid in studies range from 5 to15 mg daily.

Zinc

The impact of zinc on the function of the male reproductive tract is profound. Zinc is essential for folate absorption and metabolism, production of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone, formation and maturation of spermatozoa, and fertilization.23 Zinc also has anti-apoptotic and antioxidant properties.16,23 Supplementation with zinc has shown improvements in sperm concentration,38 progressive motility,16,23 sperm morphology,23 and pregnancy rates.16 It is important to note that excessive intake of trace metals such as zinc may have adverse, pro-oxidant effects that can lead to production of ROS.16 A starting dose of 30 mg BID, along with 1-2 mg of copper, has been recommended in the literature.39

Omega-3 Polyunsaturated Fatty Acids

Polyunsaturated fatty acids (PUFAs) have been shown to play critical roles in sperm maturation and membrane fluidity necessary for motility.40 Clinical studies have found lower levels of sperm DHA in men with oligoasthenozoospermia,41 and a higher omega-6/omega-3 ratio in infertile vs fertile men.42 The ratio of arachidonic acid (AA) to both EPA and DHA has been strongly negatively correlated to total sperm count, morphology, and motility.42 A 2011 double-blind, placebo-controlled, randomized study showed increases in sperm count with a combined EPA and DHA (total 1.84 g per day) fish oil supplement over 32 weeks in men with idiopathic oligoasthenoteratospermia (OAT).43 A study looking at a whole-food source of PUFAs found that 75 g of walnuts daily improved sperm motility and morphology in a group of healthy men, compared to a group consuming no nuts.44

Botanical Medicines

Botanical medicines also offer a unique approach to male factor fertility. Specifically, botanical medicines are able to influence endocrine function, balance the hypothalamus-pituitary-gonadal (HPG) axis, and act as adaptogens and antioxidants.

Mucuna puriens

Mucuna pruriens has a long history in the Ayurvedic tradition as a male aphrodisiac and general tonic.45 M pruriens impacts all of the major causes of male infertility, including hormonal disturbances, generation and removal of ROS, and altered spermatogenesis.45 The L-DOPA content of the seed accounts for much of the activity of M pruriens, including antioxidant action, enhancement of dopamine production, and increased release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. This process stimulates the pituitary to produce LH and FSH, leading to increased testosterone and spermatogenesis.45

Human and animal studies have shown improved sperm count and motility, improved antioxidant levels in seminal fluid, and increased testosterone.45,46,47 M pruriens may also be able to restore spermatogenesis after exposure to endocrine-disrupting chemicals. A 2013 study demonstrated an improved rate and magnitude of spermatogenic and endocrine recovery after exposure to ethinyl estradiol, a substance mimicked by many endocrine-disrupting chemicals.45 The adaptogenic properties of M pruriens were also explored in a 2010 study on infertile men with psychological stress.15 Daily supplementation with 5 g of M pruriens resulted in improved sperm parameters and decreased reports of stress and serum cortisol.

Panax ginseng

One of the oldest botanical medicines, Panax ginseng is still commonly used in traditional Chinese medicine as an adaptogen, to enhance libido and sexual behavior and to treat erectile dysfunction.48 Clinical studies have supported these indications, with demonstrations of improved erectile function and sexual satisfaction reported after doses of 900-1000 mg TID for 8-12 weeks.49,50 Improvements in sperm density and motility have also been demonstrated in asthenospermic patients.49,51 Panax ginseng is able to influence the HPG axis in both hormonal and neuronal ways, with increases in plasma total and free testosterone, FSH and LH, dopamine, and acetylcholine, which explains its beneficial effects on both sperm parameters and libido.49,51

Tongkat Ali

Eurycoma longifolia Jack, more popularly known as tongkat ali, is a traditional Malaysian botanical medicine with impacts on the male hormonal axis and spermatogenesis, thought to be related to the quassinoid, eurycomanone. Though the exact mechanism of action is not fully understood, animal models have demonstrated increased testosterone, LH and FSH, improved sperm concentration and motility, and increased copulatory behaviors.52,53 In a 2010 study of 75 men with idiopathic infertility, 100 mg BID of water-extracted tongkat ali root produced increases in semen volume, sperm concentration, percentage of normal sperm morphology, and sperm motility.54 A 14.7% rate of spontaneous pregnancy in the partners of men in the study was also noted.

Withania somnifera

Another herb with a long tradition in Ayurvedic medicine, Withania somnifera (ashwagandha) has shown promising results in clinical studies of men with oligospermia,55 and in normozoospermic but infertile men who heavily smoked, were under psychological stress, or had idiopathic infertility.56 In a 2013 study, men with oligospermia who used 225 mg TID of ashwagandha had a 167% increase in sperm count, a 53% increase in semen volume, and a 57% increase in sperm motility from baseline.55 Additionally, there was a 17% increase in serum testosterone and a 34% increase in LH. The influence of ashwagandha on cortisol levels likely explains one of its main therapeutic impacts on fertility. Cortisol elevations resulting from stress cause drops in LH production, leading to testicular involution and a significant drop in testosterone secretion.56

Other Herbs

Additional botanicals that have shown promise in research for male infertility and spermatogenesis include Lepidium meyenii (maca), Andrographis paniculata, Tribulus terrestris, and French maritime pine bark extract (pycnogenol).

Traditional Chinese Medicine and Acupuncture

In Traditional Chinese Medicine (TCM), male subfertility is known as bu ye, jue yu (male infertility), wu zi (childlessness) and nan zi nan ci (male difficulty in producing an heir).57 Three organ systems are thought to be responsible for healthy male reproduction – the Kidneys, Liver and Spleen.

Acupuncture has been found in multiple studies to positively influence male fertility. Improvements in motility, sperm count, semen quality, and normalization of hormones, including a 65.1% increase in testosterone, have been demonstrated.58 Enhanced blood flow in the testicular artery, resulting in decreased scrotal temperature and increased antioxidant supply to the testes has been demonstrated with acupuncture treatment.59,60 Acupuncture has also been shown to improve fertilization rates using intracytoplasmic sperm injection (ICSI) and resultant embryo quality, compared to pretreatment levels.61 The most commonly utilized acupuncture points in studies are UB32, UB35, REN4, ST30 and SP6, as well as points indicated for specific patterns of imbalance.57


Watson_Headshot_August_2014Lisa Watson, ND, is a graduate of the Canadian College of Naturopathic Medicine. She is in practice at the Integrative Health Institute in Toronto, Ontario. Her dynamic practice focuses on women’s health and adolescent health and she is a regular speaker throughout the Greater Toronto Area. Dr Watson enjoys writing about naturopathic medicine.

 

 

References

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