Here we review in a general way the non-surgical male infertility treatments that continue to withstand the test of time either because they make good medical sense or have been shown to be cost-effective in the era of assisted reproduction.
My biggest concern when evaluating men for infertility is to make sure that they do not have an underlying medical problem as a cause of the infertility”. – Dr. Paul Turek
Male Infertility Causes and Solutions
Only about 20% of young men actually know the exact time to have sex during the female cycle to achieve a pregnancy. The critical period can be assessed by either basal body temperature charting or home kits that detect the LH surge in the urine immediately (24 hours) prior to ovulation. Since sperm reside in the cervical mucus for 48 hours and are released continuously, it is not necessary that coitus and ovulation occur at the exact same time. Another issue is how often to have sex to conceive. Ejaculation has to occur frequently enough to bracket the ovulatory period. Sex every other day around this period is recommended. Recent evidence also suggests that most couples become pregnant from intercourse before ovulation rather than after ovulation. The level of sexual stimulation prior to ejaculation is important to the quality of ejaculation.
Medications and Toxins
Medications are usually extensively tested for their potential as reproductive hazards before marketing. Despite this, it is wise to discontinue any unnecessary medications that can be safely stopped during attempts to conceive. A list of gonadotoxic medications is found in Table 1.
Table 1. Medications to avoid while trying to conceive.
Lubricants should also be avoided if possible; Surgilube, K-Y jelly and saliva should definitely not be used as they may contain antiseptics that hurt sperm. If necessary, vegetable oils such as olive oil appear to be the safest. Other toxins include heat exposure from regular saunas, hot tubs or jet tubs or baths, cigarettes, cocaine and alcohol. Marijuana can also lead to reversible depression of spermatogenesis.
Hormonal Treatments – Specific
The normal role of prolactin in men is not clear, but it may keep testosterone levels high in the testis and help the growth and secretions of the sex glands. Normal prolactin levels are important for normal sex drive and fertility as well. Hyperprolactinemia occurs when prolactin levels rise above normal and this is a medical condition that is routinely treated. Other reasons for elevated prolactin include stress during the blood draw, obtaining the blood test too soon after awakening (prolactin levels rise during sleep), illness in the body and medications.
Both high and low levels of thyroid hormone can affect sperm production. Thyroid issues account for < 0.5% of infertility but are very treatable. Because of their rarity, routine thyroid screening is not recommended for infertility patients.
Congenital Adrenal Hyperplasia
Most commonly, the 21-hydroxylase enzyme is deficient and there is low cortisol production. The testes fail to mature because of this. The diagnosis is rare and classically presents as early puberty; careful laboratory evaluation is essential. The condition and the infertility associated with it are both treated with corticosteriods.
There are conditions in which no or low testosterone is present due to abnormal hormone signaling in the brain (Kallman Syndrome). Infertility associated with these conditions can be effectively treated by replacing pituitary hormones. On the contrary, anabolic steroid use, commonly taken by college and professional athletes, impairs sperm production and leads to zero sperm counts in most men. In this case, the steroids should be discontinued to reverse the problem.
Other Specific Medical Treatments
Elevated white blood cells in semen (>1 million/mL) is termed pyospermia or leukocytospermia and is associated with (a) silent genital tract infection, (b) elevated reactive oxygen species, and (c) poor sperm function and infertility. Sperm can be damaged by oxidative stress from leukocytes because the sperm have little inherent protective antioxidant activity. The treatment of leukocytospermia is controversial without an obvious bacterial infection. When appropriate, the use of broad-spectrum antibiotics such as doxycycline and trimethoprim-sulfamethoxazole in combination with frequent ejaculation has been shown to durably reduce seminal leukocyte concentrations. Generally, the female partner is also treated.
Hormonal Treatments – Empirical
Empirical therapy can also be offered to men with infertility. These treatments are not necessarily disease-based, but tend to push the hormone axis harder than normal to make more sperm or add something that infertile men may be missing to improve fertility. As a rule, empirical therapy does not work as well as specific therapy in the treatment of infertility. Several examples of empirical therapy include:
This is a synthetic, nonsteroidal drug that acts as an antiestrogen and binds to estrogen receptors in the brain. This blocks the action of the normally low levels of estrogen on the male hormone axis and causes increased output of reproductive hormones that increases testosterone production and (hopefully) sperm production.
Clomiphene is given for low sperm counts and is much less effective as a treatment for low motility. After starting, testosterone and FSH levels should be monitored at 2-4 weeks and the dose adjusted to keep the testosterone level within the normal range. Higher than normal testosterone levels may result in a decrease in semen quality. A semen analysis is obtained at 3 months and at regular intervals thereafter. Therapy should be discontinued if no semen quality response is observed in 6 months. Clomiphene therapy is relatively safe with the following side effects occurring in less than 5% of patients: breast tenderness, upset stomach, weight gain, dizziness, visual complaints, change in sex drive (more) and skin reactions.
Gonadotropins (hCG, FSH)
This treatment concept is simply the idea that “if some is good, more is better.” Human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG) or pure forms of FSH are most commonly used. They tend to increase the hormonal drive to the testicle to make testosterone (hCG or LH) or sperm (FSH). Serum testosterone levels and semen analyses are monitored and drug doses adjusted accordingly. These medications are safe, but can be very expensive and are all taken as injections. Therefore, there is a risk of scarring and infection at injection sites. Mood and libido changes and acne can occur. There is evidence to suggest that sperm concentration may rise with treatment. From an evidence-based viewpoint, this therapy is useful in limited situations.
There is evidence that up to 40% of infertile men have increased levels of reactive oxygen species (“oxidants”) in the reproductive tract. These are reactive molecules (OH, 02 radicals and hydrogen peroxide) that are thought to cause damage to sperm membranes and hurt fertility. Treatment with scavengers of these radicals may protect sperm from oxidative damage. This kind of treatment may be useful for cases of unexplained low motility on the semen analysis. They are also used to reduce levels of fragmented DNA in sperm. Generally, antioxidants are found in vitamins and other nutritional supplements, which, although expensive, have minimal side effects. The best-studied fertility supplements are vitamins E and C, acetylcysteine and glutathione. Folic acid is an important micronutrient well studied for its effects on preventing neurologic problems in the embryo. It is involved with RNA and DNA synthesis during spermatogenesis and has antioxidant properties. Folic acid supplementation may benefit certain groups of infertile men, especially tobacco users. The trace element zinc plays an important role in testicular development, sperm production, and sperm motility. In fact, the zinc level in male genital organs is considerably higher than that in other tissues. It is made by the prostate and is also found in maturing sperm. Zinc deficiency has been linked to low sperm counts in men, but large randomized studies of zinc supplementation in infertile men are lacking. L-Carnitine and acetyl-L-carnitine are highly concentrated in the epididymis and are important for sperm maturation. In studies of infertile men, there have been significant improvements in sperm quality (sperm concentration and forward motility) in men taking this supplement relative to men taking sugar pills. What has not been significant are improvements in pregnancy rates.
Chinese and Japanese herbal therapy has been used for centuries for a variety of maladies, including female infertility. Their application to treat male infertility, however, is very recent. There have been recent attempts to study these medications more scientifically to demonstrate exactly how they might improve male fertility. In China, infertility is recognized as Kidney Yin Deficiency-Hyperactivity of Fire Syndrome, or too little Yin per unit of Yang. Herbs that have been used to treat infertility are listed in Table 2. Dose regimens are not standardized, but are tradition-dependent.
Table 2. Established traditional herbs for male infertility.