Chapter 180 Infertility, Male
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.
As a general rule, it is considered that 3 out of 5 couples conceive within 6 months of trying; 1 in 4 take between 6 months and a year. For the rest, conception takes more than a year, indicating that there may be a problem. Therefore, we can define primary infertility as existing when pregnancy has never occurred despite regular unprotected intercourse for a year or more. Secondary infertility is defined as existing if, despite having achieved a pregnancy in the past (which may or may not have resulted in the birth of a child), a couple is unable to conceive again after a year or more of regular unprotected intercourse.
Unexplained infertility occurs in approximately 5% to 10% of couples trying to conceive. Generally, assessments reveal limited information and find no apparent cause for infertility. The effort to determine whether unexplained infertility is a true diagnosis is often complicated by poor investigation or the lack of current assessment strategies. The naturopath can often elucidate answers in these situations by taking a holistic view in assessing the patients and thus producing positive outcomes.
Most causes of male infertility reflect abnormal sperm counts, morphology, or motility. Although it takes only one sperm to fertilize an egg, a male ejects nearly 200 million sperm in an average ejaculate. Because of the natural barriers in the female reproductive tract, only about 40 sperm ever reach the vicinity of an egg. There is a strong correlation between the number of sperm in an ejaculate and fertility.
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|
In healthy young men, sperm are produced by repeated divisions of cells in small, coiled tubules within the testes at an average rate of approximately 100 million per day. Each spermatogenic cycle consists of six stages, and approximately five cycles are required to produce one mature sperm. From the beginning of division of the stem cell to the appearance of mature sperm in the semen takes between 72 and 76 days. Therefore, anything that the male experiences during spermatogenesis can affect mature sperm regardless of his health at the time of examination. Factors to consider would include illness, toxicity, trauma, nutritional status, and others.
The sperm spend 2 to 10 days passing through the epididymis, during which time they mature and become capable of swimming and penetrating oocytes. At the beginning of ejaculation, sperm are transported from the tail of the epididymis via the vas deferens to the urethra. The seminal vesicles, prostate gland, and Cowper’s glands secrete most of the volume of semen; these secretions help deliver the sperm during ejaculation. The volume of liquid coming from the two epididymides is less than 5% of the total semen volume. Approximately 60% of the semen volume comes from the seminal vesicles and 30% from the prostate gland. The average semen volume for healthy men ejaculating every 2 days is 3 mL; the average sperm concentration is 85 million/mL (more specifics are given later). During ejaculation, the sperm and prostatic fluid are usually ejected first and the seminal vesicle fluid follows. The seminal vesicle fluid coagulates, giving the semen a lumpy, gel-like appearance. Liquefaction occurs after 20 minutes or so, when the gel disappears.
In a fertility context, the semen analysis forms the primary basis of assessment. It provides the clinician with a snapshot of the male’s fertility and reflects his general health in the preceding 72 to 76 days.
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.
|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.
In 2010, the WHO released updated guidelines for semen analysis. The fourth edition (released in 1999, with a review in 2003) had presented a more positive picture of male fertility. The 2010 guidelines suggest that, overall, male fertility is declining. (Note that all andrology laboratories have adopted the new guidelines. The greatest difference can be denoted by reviewing morphology, owing to differing criteria and percentage scales.)
• 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
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 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.
|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.
|General Health Assessments|
|FBC, blood type
Standard blood chemistries
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|
|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.|
Factor V Lieden
|Indicated in instances of miscarriage, unexplained infertility, marked sperm abnormalities, or implantation issues.|
|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.|
When the naturopath is presented with a male patient complaining of infertility, the first step is to determine whether he has been given a thorough, comprehensive assessment. Assessment results can help to determine whether the issue can be effectively treated, because genetic factors or overt physical impediments will require additional interventions.
• 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.
In treating males for infertility, the optimal approach is to adopt a preconception program for both prospective parents. Preconception treatment adheres to the philosophy that the final stages of gamete production can be modified and influenced. The final stages of spermatogenesis last between 72 and 76 days. By influencing the environment to which sperm are exposed and optimizing the general well-being of the host, practitioners may be able to influence sperm development positively and to address and deal with related health concerns.
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).
Within the naturopathic framework it is crucial to naturally support and attenuate all coexisting health conditions. Therefore, treatment should be structured to acknowledge all health concerns; that is, to optimize the general health of the male patient as an underlying position.
Finally, it is always important to acknowledge that the most favorable fertility occurs when the individual’s health is optimal. The body is primed to pass on genetic material only when the environment and other conditions are at their best. If survival from an evolutionary perspective is compromised, fertility will be hindered. Everything a person eats, drinks, experiences, or is exposed to can and will influence fertility. True naturopathic supports of fertility acknowledge and consider absolutely all variables of holistic health. Couples should be encouraged to participate in treatment for 3 to 4 months to properly address all genetic and epigenetic variables affecting the gamete.
The scrotal sac normally keeps the testes at a temperature of between 94° F and 96° F. At temperatures above 96° F, sperm production is greatly inhibited or stopped completely. Typically, the mean scrotal temperature of infertile men is significantly higher than that of fertile men. A reduction in the scrotal temperature in infertile men is often enough to make them fertile. This is best achieved by having them avoid tight-fitting underwear, tight jeans, and hot tubs.
In addition, the following exercise or exercise equipment can raise scrotal temperature, especially if a man is wearing synthetic fabrics, exceptionally tight shorts, or tight bikini underwear: rowing machines, simulated cross-country ski machines, treadmills, and jogging. After exercising, a man should allow his testicles to hang free to allow them to recover from heat buildup.
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
Increased scrotal temperature can be due to the presence of a varicocele. A large varicocele can lead to scrotal temperatures high enough to inhibit sperm production and motility. Surgical repair may be necessary, but scrotal cooling should be tried first.
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
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.
Although most synthetic estrogens like DES are now outlawed, many animals, both livestock and poultry, are still hormonally manipulated, especially dairy cows. Cow’s milk contains substantial amounts of estrogen because of modern farming techniques. The rise in dairy consumption since the 1940s inversely parallels the drop in sperm counts. Avoidance of hormone-fed animal products, including milk products, is important for male sexual vitality, especially in men with low sperm counts or low testosterone levels.