Preventive Medicine Fact and Fiction

Male factor infertility accounts for approximately 50% of all problems with infertility. It is for this reason that evaluation and treatment of the male is critical to a thorough comprehensive program for the infertile couple. Because there are many treatable, reversible, and preventable causes of male factor infertility, early evaluation and treatment is very important.

In 1994, Drs. Honig, Jarow and Lipshultz reported the incidence of significant medical pathology associated with the evaluation and treatment of male factor infertility. In 1% of patients, a significant medical condition, sometimes life-threatening (such as a cancer of the testis, brain tumor, or spinal cord tumor) was the cause of the male infertility. Early intervention in these cases was important for treatment of the life-threatening medical condition and improvement in the couples overall chance of getting pregnant. It is for this reason, we believe that early evaluation of the male should include a semen analysis and, if abnormal, an early consultation with a urologist well-trained in male fertility-related disorders. This should occur before a treatment plan (such as intrauterine insemination, in vitro fertilization or other assisted reproductive technologies) for the couple is instituted.

What can be done as "preventive medicine" for male factor infertility?

It starts with avoidance of lifestyle issues that may be detrimental to sperm quality. Acquired causes of male factor infertility include exposure to toxins such as illicit drugs (marijuana, cocaine, etc.), heavy alcohol use, cigarette smoking, medications, and excessive heat to the scrotal area.

It is becoming increasing clear that recreational drugs can have an adverse effect on the testes and sperm quality. Chronic marijuana use may lower testosterone levels and affect sperm quality. Cocaine has been shown to have direct effects of killing testis cells (apoptosis), and may affect sperm concentration and motility. Anabolic steroids used for body building clearly will have direct effects on the testis through lowering the body's ability to make its own testosterone. This is not always reversible. Cigarette smoking has been shown in both clinical studies and research studies to have effects on hormone levels as well as direct toxic effects on the testicle. Heavy alcohol use will cause lowering of hormone levels and affect sperm quality.

Many medications used for treatment for unrelated conditions may have negative effects on sperm quality. It is the job of the reproductive specialist to educate physicians and the general public on the effects of certain medications on sperm quality. Some of the medications that may have an effect on sperm quality is listed below in table 1.

Table 1 -Medications
Calcium channel blockers for high blood pressure
Sulfasalazine, mercaptopurine (Crohn's disease-bowel disease)
Colchicine/allopurinol (gout)
Cimetidine (peptic ulcers)
Cyclosporine (organ transplants)
Chemotherapy for cancers

Many of these medications can be interchanged with other similar drugs with less toxic side effects on reproduction. For example, with high blood pressure, it appears that calcium channel blocker medication may have direct effects on the ability for sperm to bind to egg receptors. Switching to a different medication may remove this risk. In irritable bowel disease, mesalazone may be substituted for sulfasalazine with less reproductive side effects with similarly good disease control results.

Chemotherapy for cancer and other related diseases (such as rheumatoid arthritis, renal disease, etc) can affect sperm quality. Important considerations include freezing sperm prior to starting any toxic drugs regimens and asking your physician about using the least toxic chemotherapy regimen that can be used with equal survival results.

Occupational exposure to toxins may also affect sperm quality. Agents such as pesticides, cadmium, lead and manganese may interfere with reproductive function. Therefore, checking with your employer regarding exposures at work and subsequent protection is important.

Heat can be a major cause of direct effects on sperm quality. Most of these effects are seen with internal heat such as varicose veins around the testes(varicoceles) or high fevers as opposed to external heat effects. Varicoceles are one of the most common, treatable and reversible causes of male factor infertility. Although the exact mechanism of how varicose veins around the testis affects sperm quality, it is believed that this is usually through an increased heat effect. Multiple studies have shown that scrotal temperature is increased in patients with varicoceles. Simple repair of these veins with minimally invasive procedures can significantly improve the chances of pregnancy as compared to natural intercourse. External heat effects on the testis have not been well documented. However, hot tubs greater in temperature than 96 degrees on a regular basis should be avoided. Regarding types of underwear, a recent study has shown that there is no difference in sperm quality between boxer shorts and briefs.

Couples factors are extremely important to achieving pregnancy. Although timing intercourse with ovulation may sometimes be tedious, with male factor patients, this may be critical. Either timing with basal body temperature, or use of ovulation predictor kits are extremely useful to determine approximate timing of intercourse. Intercourse every 24-48 hours around the time of ovulation is critical to achieving pregnancy through natural intercourse. Some patients maintain good semen parameters despite frequent ejaculation, and in these patients, intercourse every 24 hours or so, may be beneficial. In addition, avoidance of spermatotoxic lubricants such as K-Y jelly, surgilube and lubrifax are important. A natural lubricant such as "Replens," may be substituted, is not sperm toxic.

Another area of preventive medicine addresses the use of vitamins, minerals and natural supplements on male factor infertility. But what are the affects of these substances on male infertility? Do some improve sperm quality while others unknowingly lower sperm quality? Scientific data is quite mixed regarding these issues. Some supplements are used for other reasons (depression, memory loss, "prostate health"), but may affect semen quality as a side effect. Other supplements have been studied to determine if they will improve semen quality in patients with male infertility. Listed below in Table 2 are vitamins and supplements that have undergone some scientific testing.

Table 2 - Vitamin Supplements
Vitamin C
Carnitine, l-acetyl carnitine
Vitamin E
Zinc

There is a large amount of literature evaluating the effects of antioxidant vitamins (vitamin C and E) on sperm. These studies have been performed on patients taking these vitamins by mouth as well as mixing them with semen. It appears clear that some male factor patients have an increase in the amount of "reactive oxygen species" or oxidants in their semen. Reactive oxygen species may affect sperm through both direct effects on the sperm and indirect effect of the sperm environment. Vitamin C and E are thought to be anti-oxidants and may serve to lower the level of these toxic agents and therefore negate its deleterious effects.

Carnitine appears to play an important role in both function of the epididymis and possibly sperm energy/motility. Some studies from overseas have suggested some benefit in using this supplement (mostly with improvement in sperm motility), with no significant side effects. Formal studies are underway in this country to assess its overall value to male infertility patients. Table 3 lists nutritional supplements that may affect sperm, but are generally used for other reasons.

Table 3 - Herbs
Saw palmetto
Ginkgo biloba
St. John's wort
Echinacea

A recent paper published in Fertility and Sterility has suggested that some of the nutritional supplements listed in Table 3 may have adverse effects on male infertility through direct effects on sperm. This paper has received a significant amount of national press. Unfortunately, the studies looked at mixing the supplements in a dish directly with semen. It is not known what the effects might be when these supplements are taken by mouth since it is not known if they even enter the semen. At this point, there is no clear evidence that these supplements affect sperm in a negative fashion.

Of all the supplements listed above, saw palmetto would appear to be mostly likely to have a negative effect on sperm production and ejaculate volume. It is thought that saw palmetto lowers levels of male hormone, dihydrotestosterone, which is thought to be important for sperm production and ejaculation. A recent paper studying the effects of 1 mg of finasteride (propecia- for male pattern baldness) showed no negative effects on sperm quality. It is thought that saw palmetto may work similar to a higher dose of this drug used for benign prostate enlargement. It would be my recommendation that any patient trying to achieve a pregnancy stop using saw palmetto until further studies show that there are no deleterious effects on male infertility and pregnancy.

In summary, preventive medicine has an important role in male factor infertility. A thorough evaluation and physical examination by a physician familiar with male infertility is important to rule out treatable, reversible and potentially life threatening medical conditions. Patients should ask their physicians and seek-out organizations such as RESOLVE, the American Society for Reproductive Medicine, the Society for the Study of Male Reproduction, American Urological Association, etc. for information regarding qualified physicians. This information is available on the Internet through these organizations. In addition, modification of lifestyle behaviors, and avoiding toxic recreational drugs and vices may improve chances of pregnancy. Preventive medicine with avoidance of supplements that may affect male infertility in a negative way and use of other vitamins and supplements that may positively impact male fertility related disorders are important to consider as well.

Stanton Honig, MD, is Assistant Clinical Professor of Surgery/Urology at the University of Connecticut School of Medicine in Farmington, Connecticut, and Staff Urologist at Yale New Haven Hospital and Hospital of St. Raphael in New Haven Connecticut.

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Preventive Medicine Fact and Fiction
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Monday, January 7, 2013