June 19, 2020
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By Stanton Honig, MD
June is Men’s Health Month and we want to heighten awareness of preventable health problems and encourage early detection and treatment of disease among men and boys. We are highlighting men’s infertility.
Male factor infertility accounts for approximately 50% of all infertility. For this reason, the evaluation and treatment of the male are critical to a comprehensive program for the infertile couple. Because there are many treatable, reversible, and preventable causes of male factor infertility, early evaluation and treatment are very important. While in-office visits are returning, we have developed a telehealth program for patients who are not ready to come to the office for a consultation.
In 1994, Drs. Honig, Jarow, and Lipshultz reported the incidence of significant medical conditions 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, or spinal cord tumor) caused male infertility. Subsequent studies have shown a significantly higher incidence of testis cancer in infertile men despite variable semen quality. Early intervention was crucial to treat the life-threatening condition and improve the couple’s overall chance of conceiving.
Early evaluation of the male should include a semen analysis. If this is abnormal, an early consultation with a urologist well-trained in male infertility disorders should follow. This should occur before or in conjunction with assisted reproductive technologies.
What can be done as “preventive medicine” for male factor infertility?
Prevention starts with avoiding lifestyle issues that may be detrimental to sperm quality. Acquired causes of male infertility include exposure to substances that can be toxic to sperm such as illicit drugs (marijuana, cocaine, anabolic steroids), heavy alcohol use, cigarette smoking, medications, and excessive heat to the scrotal area.
It is becoming increasingly 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. This has become more of a problem since laws requiring marijuana use have loosened. Cocaine has been shown to have direct effects on the testis and may affect sperm concentration, motility, and DNA of the sperm. Anabolic steroids used for bodybuilding clearly have direct effects on the testis by lowering the body’s ability to make its own testosterone. It also decreases spermatogenesis and may cause temporarily no sperm in the ejaculate, which is sometimes irreversible. Education of high school and college students regarding the negative impact of anabolic steroids and other recreational drugs is critical to prevent male fertility problems down the road.
Cigarette smoking and heavy alcohol use have been shown in clinical and research studies to affect hormone levels, as well as direct toxic effects on the testicle. Basic science data has shown increased testicular injury when exposed to environmental toxins.
Many medications used for the treatment of unrelated medical conditions may have negative effects on sperm quality, as well. It is the job of the reproductive specialist to educate physicians and the public on these effects. Some medications that may affect sperm quality are testosterone, calcium channel blockers for high blood pressure, sulfasalazine (Crohn’s disease-bowel disease), cyclosporine (organ transplants), and chemotherapy for cancers or rheumatologic disease and anti-virals utilized for severe COVID disease.
Many of these medications can be interchanged with similar drugs that have less toxic side effects. For example, we have seen a MAJOR increase in the use of testosterone in men of reproductive age. This has been driven by the sense that testosterone will bring “the fountain of youth”. Unfortunately, this “overuse” in men has resulted in the lowering of sperm counts, in some cases to zero. Luckily, most of the time, this is reversible. In addition, there are other medications that can increase testosterone via the hypothalamic pituitary axis that can be utilized instead to improve libido, sexual function, energy level, etc. With high blood pressure, it appears that calcium channel blocker medication may directly affect the sperm’s ability to bind to egg receptors. Switching to a different medication may remove this risk. In irritable bowel disease, mesalazone may be substituted for sulfasalazine having less reproductive side effects with similarly good disease control results.
Chemotherapy for cancer and other chronic diseases (like rheumatoid arthritis, renal disease, autoimmune illnesses) can also affect sperm quality. Important considerations include freezing sperm prior to starting any toxic drug regimens and using the least toxic chemotherapy regime with equal survival results. Younger males with prostate cancer should be asked about future fertility interests prior to definitive therapy. Radical prostatectomy, radiation therapy, and hormone deprivation therapy have specific deleterious effects on sperm and/or sperm transport.
Occupational exposure to toxins may also affect sperm quality. Agents like pesticides, cadmium, lead, and manganese may interfere with male reproduction, so checking and removing work exposures is important.
Direct heat to the testis can be a major cause of diminished sperm quality and male infertility. Varicoceles are one of the most common, treatable, and reversible causes of male factor infertility. Although the exact mechanism of how varicoceles affect sperm quality is not known, 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. Varicocele repair has been shown to improve sperm concentration, motility, morphology, and the DNA of sperm. Minimally invasive ligation of varicoceles can significantly improve the chances of pregnancy as compared to natural intercourse. In varicocele-associated infertility, multiple studies have shown that it is more cost-effective to perform varicocele repair as compared to going directly to IVF/ICSI in moderate male factor infertility cases. In addition, varicocele repair may upgrade semen quality to allow couples to proceed with less invasive/less costly hyperstimulation/IUI as opposed to going directly to IVF/ICSI.
External heat effects on the testis may affect semen quality as well. We recommend abstinence from hot tub use or lowering the temperature to 97 degrees (same as scrotal temperature). It is unclear if the illness-related effects of COVID-19 will have a temporary or permanent effect of sperm but one study did show a drop in sperm quality in patients with severe effects of COVID-19. On a lighter note, wear whatever underwear you want. Conventional lay information regarding types of underwear is vastly overplayed. Scientific studies have shown that there is no difference in sperm quality between boxer shorts and briefs.
Coital factors are extremely important in achieving pregnancy. Although timing intercourse with ovulation may be tedious, it is critical with male factor patients. Timing with basal body temperature or ovulation predictor kits is extremely useful. Intercourse every 24-48 hours around the time of ovulation is critical to achieving pregnancy naturally. 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 spermatoxic lubricants such as K-Y jelly, surgilube and lubrifax, is important. A natural lubricant, such as “Replens” or “Pre-seed”, may be substituted and is not sperm toxic.
Are vitamins and supplements helpful? The answer is… sometimes.
Scientific data is quite mixed. Some supplements used for other reasons (depression, memory loss, “prostate health”) may affect semen quality in a negative way, while others have been studied to determine if they’ll improve semen quality in patients with male infertility. Below are vitamins and supplements that are recommended:
Vitamin C 500-1000 mg/daily
Carnitine and/or L-acetyl carnitine 3gms/daily
Vitamin E 400 -800 iu/daily
There is a large amount of literature evaluating the effects of antioxidant vitamins (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 “reactive oxygen species” or oxidants in their semen. Reactive oxygen species may have effects both directly on the sperm and indirectly on the sperm environment. Vitamins C and E are antioxidants and may serve to lower the level of reactive oxygen species and, therefore, negate its negative effects.
Carnitine appears to play an important role in both the function of the epididymis and possibly in sperm energy/motility. Some studies from Italy have suggested some benefit in using this supplement (mostly with improvement in sperm motility), with no significant side effects. We recommend 3gms of carnitine and L-acetyl carnitine. Be careful with supplements that claim they are “Male Fertility Supplements”, as they may contain only tiny amounts of the recommended supplements.
Most other supplements (such as zinc, selenium, folate, coenzyme Q-10) are not necessary if a balanced diet is maintained since most are present in healthy foods. Not all nutritional supplements are good for sperm. Saw palmetto may have a negative effect on sperm production and ejaculate volume. It is thought that saw palmetto lowers levels of dihydrotestosterone (DHT), which is thought to be important for sperm production and ejaculation. Studies on the effects of 1 mg of finasteride (Propecia-for male pattern baldness) showed no negative effects on sperm quality. Saw palmetto may work similarly 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.
Summary
Preventive medicine has an important role in male factor infertility. A thorough evaluation and physical examination by a physician familiar with male infertility are important to identify treatable, reversible, and potentially life-threatening conditions. In addition, modification of behaviors, and avoiding toxic recreational drugs such as anabolic steroids may improve the chances of pregnancy. Avoiding supplements that may negatively affect male infertility and using other vitamins and supplements that may positively impact male fertility-related disorders are important to consider, as well.
Patients should ask their physicians and seek out organizations like RESOLVE, the American Society for Reproductive Medicine (www.asrm.org), The Society for the Study of Male Reproduction (www.ssmr.org), American Urological Association (www.urologyhealth.org/urologic-conditions/male-infertility).
The Clara study was suspended by our sponsor, Ferring Pharmaceuticals, at the start of the COVID-19 pandemic. At the same time, cycle starts for non-study patients were also suspended. Based on recent favorable indicators, we are able to begin procedures the first and second weeks of May for non-study patients. Although currently at a reduced capacity, these scheduled procedures will be increased over the coming weeks. While we have not yet received approval to resume the Clara study, we anticipate recruitment and screening to resume in late June or early July.