Chapter 180 Infertility, Male
Diagnostic Summary
• Inability to conceive a child after 12 months of regular unprotected intercourse (at least twice weekly) with the same female partner and in the absence of female causes.
• Sperm abnormalities confirmed by two properly performed semen analyses of sperm count, morphology, motility, or other aspects.
General Considerations
Infertility affects about 7.3 million women and their partners in the United States, which equates to approximately 12% of the reproductive-age population.1 One out of seven couples will experience difficulty conceiving. Infertility affects men and women equally, with approximately one third of cases being due to male factors, one third to female factors, and the remaining one third to joint issues. In the United States, it is estimated that about 6% of men between the ages of 15 and 50 years are infertile.2
Throughout the world there has been a recent and dramatic decline in fertility that appears to be unrelated to the socioeconomic status of any given country; however, deferred childbearing and improved contraception are undoubtedly major factors. Population growth is below the replacement rate in several countries—such as Sri Lanka, Denmark, and Spain—where there have been no obvious increases in abortion rates or contraceptive use. This loss of fertility has affected Denmark to the point where approximately 7% of all newborn babies are now being conceived by assisted methods.3 In the United States, some patients will require assisted reproductive technologies (ARTs) in order to conceive. Statistics indicate that in vitro fertilization (IVF) and similar treatments account for less than 3% of infertility services and approximately 0.07% of U.S. health care costs.
Fertility is a reflection of general health and well-being and can also indicate latent or undiagnosed genetic abnormalities or other etiologic considerations. These considerations are many and varied; thus, a comprehensive, holistic review is essential. An overview of the causes of male infertility is given in Table 180-1.
Aspermia | An absence of semen despite male orgasm |
Azoospermia | A complete absence of sperm (spermatozoa) in the semen. |
Oligozoospermia | Reduced number of normal motile sperm cells (spermatozoa) in the ejaculate (compared with azoospermia, which means no sperm in the ejaculate). It includes laborious terms such as asthenozoospermia, teratozoospermia, and oligoasthenoteratozoospermia |
Teratozoospermia | Sperm with abnormal morphology |
Necrospermia | Death of sperm |
Oligoasthenoteratozoospermia | An unnecessarily long name that indicates low count, weak motility, and abnormal morphology |
If a sperm deviates from normal, it is defined by the terminology given in Table 180-1.
Diagnostic Considerations
Andrology Assessments
Semen Analysis
An individual’s semen quality can vary considerably between samples, even in males with normal semen parameters. In interpreting the assessment, it is imperative that the clinician acknowledge the important fact that a diagnosis is not achieved until an abnormality is confirmed by two separate investigations. As a result, at least two and occasionally three semen analyses are needed, each several weeks apart, in order to gain an accurate picture of an individual’s average semen quality. It is well recognized that sperm count can be adversely affected by illness, especially fevers, which may temporarily suppress sperm count in normal males for several months. In this case, the semen analysis should of course be delayed. Additionally, general recommendations such as in-clinic collection (versus at-home collection), careful consideration of laboratory guidelines (abstinence timing, lubricant usage), and the standard of the andrology laboratory facility must be considered in reviewing results. Table 180-2 outlines the World Health Organization’s (WHO’s) guidelines for assessing a semen analysis.
SEMEN PARAMETER | LOWEST REFERENCE (REFERENCE RANGE) | INTERPRETATION AND TREATMENT OBJECTIVE |
---|---|---|
Standard Components of a Semen Analysis | ||
Abstinence | Parameters are defined based on abstinence of 3 days. | It is essential to ensure that males ejaculate and then count the required 3 days’ abstinence. |
Collection method | Optimal collection is via masturbation; however, specialized condoms can be provided for males with religious restrictions. Additionally, standard lubricants can interfere with the accuracy of the reading and must be avoided. Andrology laboratories are able to supply alternatives. | |
Specimen | Semen sample must be complete. | Incomplete samples are frequent and will distort readings. Assessment can be determined only by reviewing a full sample owing to variations in prostatic secretion vs. epididymal involvement. |
Analysis time | Sample must be analyzed within 60 min and is best collected in the clinic environment to prevent complications. | |
Appearance | Nil debris, nil clumping, or viscosity changes, liquefaction complete. | Debris, clumping, viscosity, or liquefaction issues can suggest systemic congestion, poor hydration, poor elimination, or immune reactions (clumping especially). It can also indicate poor ejaculation frequency. |
pH | >7.2 (7.2-7.8) | pH control is essential for sperm survival. An abnormally high or low semen pH can kill sperm or affect their ability to move or to penetrate an egg. The pH of the sample will be affected if there was a delay between sample collection and analysis. If the pH is <7.0 and the sample is azoospermic, there may be an obstruction of the ejaculatory ducts or bilateral congenital absence of the vas deferens (CBAVD). pH irregularities can relate to dietary intake and hydration level. Very acidic samples can indicate obstruction and require referral. |
Volume | >1.5 mL (1.4-1.7 mL) | Volume can be affected by the period of abstinence (3 days are recommended), incomplete ejaculation, and retrograde ejaculation. It generally indicates dehydration; treatment should consist of hydration calculation based on weight and energy expenditure. |
Concentration | ||
Sperm concentration | > 15 million/mL (12-16 million/mL) | Concentration can be affected by a number of factors, including:
The finding of no sperm in the ejaculate suggests either an absence of sperm production or obstruction to sperm outflow. It is most important that an azoospermic semen sample be spun down to carefully examine whether the ejaculate contains even a few sperm. |
(>25% rapid, >40% progressive, >50% motile)
There are other important conditions that predominantly affect sperm motility, such as sperm autoimmunity, a condition that accounts for about 6% of male infertility. No movement (immotile sperm) may be due to structural problems in the sperm’s tail or to death of sperm.
The percentage of sperm that are alive (sperm vitality) is noted because this declines in association with genital tract infections and disorders of sperm transport through the genital tract. The proportion of live sperm is assessed if total motility is <50%. Low motility and high vitality could indicate a disturbance of the motility apparatus. If >75% of sperm are dead, immobilizing antisperm antibodies might be present and testing is encouraged.
Poor motility can often indicate autoimmune processes; infection; lack of mitochondrial energy to propel the sperm; or medication, alcohol or other toxins that affect semen quality.
Note: A trial wash can provide specificities of morphologic abnormalities (i.e., head, neck, tail).
Morphology is often a direct reflection of generalized toxicity, because semen is a by-product of the body and is a major eliminatory channel. Detoxification, avoidance of environmental toxins, and immaculate dietary practices are essential. Key nutrients in sperm structure must be considered, including protein, essential fatty acids (DHA), all antioxidants including coenzyme Q10, zinc, vitamins C and E, and selenium.
Ascertaining the type of infection is the primary objective, with subsequent targeted treatment to eradicate it. It is essential to assess the female partner to prevent cross-infection.
Abstinence or a barrier method until the immune system is regulated is essential, along with concurrent autoimmune treatment with herbal medicines, dietary modifications, lifestyle modifications, and nutritional supplementation.
>50% pathologically significant (except tail tip binding)
High green stain (HG):
DNA fragmentation can be attributed to various pathologic conditions including cryptorchidism, cancer, varicocele, fever, age, infection, leukocytospermia, and others. Many environmental conditions can also affect DNA fragmentation, such as chemotherapy, radiation, prescribed medicines, air pollution, smoking, pesticides, chemicals, heat and ART preparation protocols.
Research indicates that sperm with high levels of DNA fragmentation have a lower probability of producing a successful pregnancy. Samples with a DNA fragmentation level greater than 29% are likely to have significantly reduced fertility potential, including a significant reduction in term pregnancies and an increased miscarriage rate. Sperm that appears to be normal by traditional semen analysis parameters may have extensive DNA fragmentation.
It is normal for up to 1:5 sperm (20%) to have some DNA fragmentation. Mature sperm are protected from damage, because 85% of the chromosome are bound by protamines into a condensed, compact structure. If more than 20% of sperm have DNA damage, there is an increased risk of infertility, poor oocyte fertilization, defective/impaired embryo development, increased probability of implantation failure, miscarriage and recurrent miscarriage (up to 3-4 times higher) and genetic disease or childhood cancer in the next generation.
Once male germ cells have completed meiosis, they lose their capacity for DNA repair, discard their cytoplasm (containing the defensive enzymes that protect most cell types from oxidative stress), and eventually become separated from the Sertoli cells that have nursed and protected them throughout their differentiation into spermatozoa. In this isolated state spermatozoa must spend a week or so journeying through the male reproductive tract and, uniquely in our species, a further period (up to 3 or 4 days) in the female tract waiting for an egg. During this period of isolation, sperm DNA is vulnerable to damage by both xenobiotics and electromagnetic radiation. Such DNA damage is associated with male infertility; its aberrant repair in the fertilized egg may result in mutations in the embryo with the potential to either induce abortion or impair the health and fertility of the offspring.134,135
Treatment consists of environmental review and modification as well as exceptionally high doses of antioxidant prescription.
Data from World Health Organization. WHO Laboratory Manual for the Examination and Processing of Human Semen, 5th ed. Geneva, Switzerland: 2010, cited in Hechtman L. Clinical Naturopathic Medicine. Chatswood, Australia: Elsevier Australia.
A semen analysis can be conducted by a number of assessments, including the following:
• General semen analysis (SA): To assess motility, morphology, concentration, volume, appearance, and so forth.
• Sperm chromatin integrity test: To determine the level of DNA damage to sperm
• Immunobead test: To assess for antibodies against sperm
• Semen culture: To assess for infection
• Retrograde ejaculatory testing: To assess for retrograde semen flow or obstruction if semen analysis yields an extremely low count
• Trial wash: To assess sperm factors and determine whether IVF or intracytoplasmic sperm injection (ICSI) is more appropriate, conducted prior to IVF and/or ICSI procedures
• MESA/TESE/PESE (microsurgical epididymal sperm aspiration/testicular sperm extraction/percutaneous epididymal sperm aspiration): To extract sperm from the testicles by a specialized procedure when sperm count is low/absent or if ejaculation is not possible
Male Reproductive Assessment
A thorough assessment of the male patient is crucial to accurately determine his general and fertility health. Some of these assessments may require referral to a fertility specialist, urologist, or endocrinologist; however, thorough questioning should be conducted by the naturopath to elucidate a full history and assess causative or contributing factors. Tables 180-3 through 180-6 highlight the most relevant assessments required in a fertility workup.
ASSESSMENT | ELABORATION AND EXPLANATION |
---|---|
Age | What ages are the couple? |
Fertility history | How long have they been trying to conceive, and have they ever conceived previously (together/separately)? Do they have any idea why they have not been able to conceive? |
Sexual history | STI screen: Potential sexually transmitted disease exposure, symptoms of genital inflammation (e.g., urethral discharge, dysuria) |
Medication history | Such as sulfasalazine (Azulfidine), methotrexate, colchicine, cimetidine (Tagamet), spironolactone (Aldactone) |
Surgical history | Such as previous genitourinary surgery |
Contraception | When it was ceased and the likely speed of its reversibility |
Fertile times | Whether the couple engage in regular intercourse during fertile times |
Lifestyle factors | Diet, exercise, alcohol, smoking cessation, recreational drug use, environmental toxin screen |
Prior paternity | Previous fertility |
Psychosexual issues (erectile, ejaculatory) | Interference with conception |
Pubertal development | Poor progression suggests underlying reproductive issue |
A history of undescended testes | Risk factor for infertility and testicular cancer |
Previous genital infection (STI) or trauma | Risk of testis damage or obstructive azoospermia |
Symptoms of androgen deficiency | Indicative of hypogonadism |
Previous inguinal, genital, or pelvic surgery | Testicular vascular impairments, damage to vasa, ejaculatory ducts, ejaculation mechanisms |
Medications, drug use | Transient or permanent damage to spermatogenesis |
General health (diet, exercise, smoking) | General health screen |
Modified from Hechtman L. Clinical Naturopathic Medicine. Chatswood, Australia: Elsevier Australia, 2011.
ASSESSMENT | ELABORATION AND EXPLANATION |
---|---|
General examination | Acute/chronic illness, nutritional status |
Genital examination | Assess for varicocele, testicular size, and other genital factors Testes: Small testes suggest spermatogenic failure Presence of vas deferens: may be congenitally absent Epididymides: thickening or cysts may suggest previous infection and resultant obstructive problems Varicoceles: detected when standing, coughing, or performing Vaslsalva maneuver Penis: assessed for abnormalities (e.g., Peyronie’s disease) that may interfere with intercourse |
Degree of virilization assessment | Assess for signs of virility Signs of androgen deficiency (e.g., increased body fat, decreased muscle mass, decreased facial and body hair, small testes, Tanner stage <5) |
Prostate examination | Assess if history suggests prostatitis or a sexually transmitted infection |
Modified from Hechtman L. Clinical Naturopathic Medicine. Chatswood, Australia: Elsevier Australia, 2011.
ASSESSMENT | JUSTIFICATION FOR ASSESSMENT |
---|---|
Follicle stimulating hormone (FSH) | Assessment to ensure that hormonal status is optimal to eliminate hormonal abnormalities
Testosterone Testosterone is often normal (8-27 nmol/L) even in men with significant spermatogenic defects. Some men with severe testicular problems display a fall in testosterone levels and rise in serum LH. These men should undergo evaluation for androgen deficiency. The finding of low serum testosterone and low LH suggests a hypothalamic–pituitary problem (e.g., prolactinoma; serum prolactin levels required). Elevated levels are seen when spermatogenesis is poor (primary in testicular failure); in normal men, the upper reference value is approximately 8 IU/L. In azoospermic men, 14 IU/L strongly suggests spermatogenic failure, 5 IU/L suggests obstructive azoospermia; a testis biopsy may be required to confirm that diagnosis. |
Progesterone (P4) | |
Prolactin (PRL) | |
Luteinizing hormone (LH) | |
Total testosterone, free testosterone | |
Sex hormone–binding globulin (SHBG) | Evaluates if concentration of SHBG is affecting the amount of testosterone available to body tissues. |
DHEA-S, cortisol | Additional hormone levels should be reviewed on an individual basis, including a full adrenal profile if the impact of stress is considered relevant. |
Modified from Hechtman L. Clinical Naturopathic Medicine. Chatswood, Australia: Elsevier Australia, 2011.
ASSESSMENT | JUSTIFICATION |
---|---|
General Health Assessments | |
FBC, blood type Standard blood chemistries 25[OH]D3 Fasting glucose Cholesterol profile General sexually transmitted infection (STI) screen |
General health assessments to eliminate other abnormalities |
TSH and urinary iodine (24-hour or morning spot) | Query thyroid function and iodine status |
Urinalysis/swab | |
Infection screen | General urinalysis to eliminate underlying infection or abnormality. Urogenital infections have been found to play a part in the genesis of miscarriage136,137 and infertility.138 Most patients are unaware of their presence owing to the asymptomatic nature of these infections. The most common infections that require screening include Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and Neisseria gonorrhoeae. |
Advanced Fertility Assessments | |
Karyotyping and subsequent genetic testing | Advanced fertility assessments if previous results show no abnormality or if infertility remains unexplained. WHO guidelines suggest that peripheral blood karyotyping analysis can be diagnostically helpful. Abnormal genotype may be present in up to 12% of azoospermic men and 4% of oligospermic men. Cystic fibrosis screening is recommended for azoospermia if due to CBAVD. Optional screening for Y-chromosome microdeletion if sperm count is <5 million/mL. |
Scrotal (testicular) ultrasonography | History of undescended testes or concern regarding testicular cancer. |
Transrectal ultrasonography | If ejaculatory duct obstruction suspected. |
MTHFR C677T MTHFR 1298C Prothrombin G20210A Factor V Lieden Selenium assay Fasting homocysteine |
Indicated in instances of miscarriage, unexplained infertility, marked sperm abnormalities, or implantation issues. |
Other Considerations | |
Nutrient and toxic element screening | Assessments of toxic elements, including aluminum, arsenic, cadmium, lead, and mercury are crucial so as to eliminate them as causative or contributing factors. It is widely accepted that excessive exposure to heavy metals has a detrimental effects on fertility139,140 and must therefore be assessed and remedied during the preconception period. |
Environmental impact | Other environmental assessments, including those that assess porphyrins, PCBs, chlorinated pesticides, volatile solvents, phthalates, parabens, and other toxins. These should additionally be considered due to their deranging effects on reproductive function, endocrinology, gamete development, and thus embryologic potential. |
Modified from Hechtman L. Clinical Naturopathic Medicine. Chatswood, Australia: Elsevier Australia, 2011.
Therapeutic Considerations
• Treatable conditions: One in eight infertile men has a treatable condition that can be overcome, so that natural conception may become possible.
• Untreatable subfertility: Three quarters of infertile men have sperm present in the semen, but in lower numbers than normal. In these cases the problem cannot be solved without intervention. These men are often defined as subfertile, since pregnancies may occur but at lower rates than usual. On average, more months of trying are needed to achieve conception, or conception may simply not occur. Following naturopathic intervention, it may be possible to address infertility factors or, alternatively, offer a referral for ARTs/IVF.
• Untreatable male sterility: About one in nine infertile men has no sperm in his semen or testes and cannot be treated. Sperm-producing cells in the testes either have not developed or have been irreversibly destroyed. Adoption or donor insemination are the only possibilities for couples in this group who wish to have families.
Of importance, acknowledging and addressing nutritional status throughout this developmental stage can significantly influence the prospective outcome. The concept of nutrient repletion is highly applicable within a fertility context. Optimal fertility is best achieved when prime health is realized. The repletion model indicates that prescriptions are required for a minimum of 3 months to properly address any deficiencies present and to ensure that all nutrients are used within each required pathway in the body. For example, zinc is involved in hundreds of pathways, including those that affect reproductive health and function. To rectify all possible deficiencies, sufficient zinc supplementation at a repletion dose (typically higher than in general prescriptions) for an extended time (at least 3 months) can enable optimal correction. At lower doses or doses of insufficient duration, zinc treatment may address only those health concerns that have the highest priority (i.e., immune function vs. sperm production).
Improving Sperm-Controlling and Sperm-Damaging Factors
Scrotal Temperature
Infertile men should wear boxer-type underwear and periodically apply a cold shower or ice to the scrotum. They can also choose to use a device called a testicular hypothermia device or “testicle cooler” to reduce scrotal temperatures. The testicle cooler looks like a jock strap from which long, thin tubes have been extended. The tubes are attached to a small fluid reservoir filled with cold water that attaches to a belt around the waist. The fluid reservoir is also a pump that causes the water to circulate. When the water reaches the surface of the scrotum, it evaporates and keeps the scrotum cool. Because of evaporation, the reservoir must be filled every 6 hours or so. It is recommended that the testicle cooler be worn daily during waking hours. Most users claim that it is fairly comfortable and easy to conceal.15
Estrogen and Xenoestrogen Exposure
According to experts on the impact of the environment and diet on fetal development, we now live in an environment that can be viewed as “a virtual sea of estrogens.”16,17 Increased exposure to environmental estrogens and other environmental pollutants during fetal development as well as during the reproductive years is suggested to be a major cause of the tremendous rise in the incidence of disorders of development and function of the male sexual system18 (see Box 180-1).
BOX 180-1 Compounds that Exert Estrogenic Activity
• Alkylphenols (intermediate chemicals used in the manufacture of other chemicals)
• 4-Methylbenzylidene camphor (4-MBC) (sunscreen lotions)
• Butylated hydroxyanisole, BHA (food preservative)
• Bisphenol A (monomer for polycarbonate plastic and epoxy resin; antioxidant in plasticizers)
• Dichlorodiphenyldichloroethylene (one of the breakdown products of DDT)
• Dieldrin (banned insecticide)
• Endosulfan (widely banned insecticide)
• Ethinylestradiol (released into the environment as a xenoestrogen)
• Heptachlor (restricted insecticide)
• Lindane, hexachlorocyclohexane (restricted insecticide)
• Metalloestrogens (a class of inorganic xenoestrogens)
• Methoxychlor (banned insecticide)
• Nonylphenol and derivatives (industrial surfactants; emulsifiers for emulsion polymerization; laboratory detergents; pesticides)
• Pentachlorophenol (restricted general biocide and wood preservative)
• Polychlorinated biphenyls, PCBs (banned; formerly used in electrical oils, lubricants, adhesives, paints)
• Phenosulfothiazine (a red dye)
• Propyl gallate (used to protect oils and fats in products from oxidation)
One can best view the relationship between estrogens and male sexual development by examining the effects of the synthetic estrogen diethylstilbestrol (DES). Between 1945 and 1971, several million women were treated with DES. By 1970, the side effects of DES became better known. DES is now recognized to have led to substantial increases in the number of men suffering from developmental problems of the reproductive tract as well as decreased semen volume and sperm count.16 Apart from having been used in humans, DES and other synthetic estrogens were used for 20 to 30 years in the livestock industry to fatten the animals and make them grow faster.
There are reports that estrogens have been detected in drinking water.17,19