Semen Analysis

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.

TABLE 180-2 Interpretation of Semen Analysis

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.)

A semen analysis can be conducted by a number of assessments, including the following:

Scrotal Temperature

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.

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).

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.

There are reports that estrogens have been detected in drinking water.^17,19 Presumably they are recycled from excreted synthetic estrogens (birth control pills) at water treatment plants. These estrogens may be harmful to male sexual vitality because they are more potent—they do not bind to sex hormone–binding globulin (SHBG). Purified or spring water may be a suitable option to prevent exposure. It is also important to ensure that bottled water is avoided owing to the bisphenol A content of plastic bottles.

Other sources of estrogen in the environment (food, water, and air) can weaken male sexual vitality. For example, many of the chemicals with which we have contaminated our environment in the past 50 years are weakly estrogenic. Most of these chemicals, like polychlorinated biphenyls (PCBs), dioxin, and dichlorodiphenyltrichloroethane (DDT), are resistant to biodegradation and are recycled in our environment until they find a safe haven in our bodies. For example, even though DDT has been banned for nearly 30 years, it is still often found in the soil and in root vegetables such as carrots and potatoes. These toxic chemicals are known to interfere with spermatogenesis, but their effects during sexual development may be even more important.

All of the estrogenic factors previously discussed are thought to have their greatest impact during fetal development. On the basis of animal studies, these estrogens inhibit multiplication of the Sertoli cells. The number of Sertoli cells is directly proportional to the number of sperm that can be produced, because each Sertoli cell can support only a fixed number of germ cells that will develop into sperm. Sertoli cell multiplication occurs primarily during fetal life and before puberty and is controlled by follicle-stimulating hormone (FSH). In animal studies, estrogens administered early in life have been found to inhibit FSH secretion, resulting in a reduced number of Sertoli cells and, in adult life, diminished sperm counts.

One example of the impairment of male sexual development by environmental estrogens is the ability of vinclozolin, a fungicide used in the wine industry, to disrupt the fertility of male rats.²⁰ Alarmingly, just one exposure of a pregnant female rat to this fungicide was found to disrupt spermatogenesis in more than 90% of the male offspring for at least four generations via an effect exclusively transmitted through the male germ line.

Environmental toxins are also linked to increasing testicular cancer rates, testicular dysgenesis syndrome (TDS), cryptorchidism, and hypospadias.^3,21 Whether the outcome is impaired spermatogenesis, TDS, testicular cancer, or any other disturbance may depend on the timing and nature of the xenobiotic attack and the genetic background on which these factors are acting. As such, a determination of the outcome will have to take into account the patient’s polymorphism profile for proteins involved in detoxification, such as the cytochrome P450s and glutathione-S-transferases. The bottom line is that the environmental impact on spermatogenesis cannot be underestimated. Industrial growth since the end of World War II has introduced many complex chemicals into the environment that are novel to biological detoxification systems. Some of these molecules are reproductive toxicants, capable of impairing fertility and inducing developmental abnormalities in the embryo, including errors in normal sexual differentiation.

The power of reproductive toxicants that target the germ line lies in their capacity to generate damage that can be passed down the generations via genetic or epigenetic means. A prime example is the effect of paternal smoking. Men who smoke heavily generate spermatozoa that may have high levels of DNA damage, largely as a result of oxidative stress. One of the consequences of this DNA damage is that the children of such men exhibit an increased incidence of childhood cancer.²² Although we have traditionally focused on the ability of cigarette smoke to induce lung cancer, a far more sinister effect is its ability to induce DNA damage in the germ line and thereby influence the health and well-being of future generations.

It is therefore advisable to discourage exposure to cigarette smoke in all male fertility patients and, in those with suspected heavy exposure, to initiate further investigations and specialized treatments to chelate and support detoxification.