Exercise-Induced Male Factor Infertility
By Laura E.A. Cook, Whitney E. Mayberry, and William E. Roudebush
Department of Biomedical Sciences
University of South Carolina School of Medicine Greenville
Greenville, South Carolina, USA
E.N. is a 32 year-old male who presents to his primary care provider with his wife with a complaint of infertility. He and his wife, a 30 year-old female, have been unsuccessful at conceiving for the past 15 months. His wife has been having normal monthly menstrual cycles, has been evaluated by her gynecologist and had normal fertility testing. Edward was instructed by his wife’s doctor to seek out fertility testing of his own. He and his wife are concerned about their ability to conceive.
E.N. was referred to an urologist specializing in male infertility. Upon further questioning by the urologist, Edward admits to difficulty obtaining an erection for the past 2 years. He has also noticed a decrease in the size of his testicles. He has not had any changes in medications. He currently takes only a multivitamin. He states that he does not smoke any tobacco products, rarely consumes any alcohol, and does no recreational drugs. He reports being healthy eater and is strict about his diet in order to maintain adequate fitness level. He exercises frequently, as he is an amateur cyclist. He cycles over 400 miles a week and competes in races. He reports no vision changes or headaches. He denies any nutritional supplement use. He has a family history positive for high blood pressure in his father, but his parents are both still living. He thinks his dad has some prostate problems, but there is no history of infertility or testicular cancer.
On physical exam, E.N. is a well-nourished man who appears slightly anxious due to the subject material of today’s visit. He is physically fit. His height is 6’2” and he weighs 143 pounds, with a calculated BMI of 18.4 and. He appears to have very little body fat. His vital signs are stable. His cardiovascular, pulmonary and abdominal exams are normal. On urogenital examination it is noted that he has bilateral testicular atrophy, with a right and left testicular volume of 9 and 8cc’s, respectively. There is no sign of hydrocele or varicocele. His spermatic cords are palpable and benign. No masses are palpated. There is no sign of penile abnormality or discharge.
E.N. had laboratory studies completed, with results as follows:
Free Testosterone: 150ng/dL (N: 270-1070ng/dL)
Follicular stimulating hormone (FSH): 0.50 mIU/mL (N: 1.6-8.0 mIU/mL)
Luteinizing Hormone (LH): 0.38 mIU/mL (N: 1.5-9.3 mIU/mL)
A semen analysis was completed. Through proper protocols, E.N. gave two semen samples two weeks apart by masturbation after sexual abstinence for at least seven days. The following were the average findings of his analysis:
Volume: 2.4 mL (N > 1.5 mL)
Sperm concentration: 12.9 spermatozoa million/mL (N >15 million/mL)
Total sperm count: 31 million spermatozoa / ejaculate
Morphology: Length, width, width ratio, acrosomal area, neck and tail all within normal limits
Total Motility: 74% total motility; 41% progressively motile, 32% nonprogressively motile
Vitality: 72% live spermatozoa
A body composition study was completed using Cosmed Bod Pod technology. The following results were obtained:
Body mass: 143.5 lb
Fat free mass: 134.603 lb
Fat mass: 8.897 lb
Percent fat: 6.2%
Percent fat free mass: 93.8%
Body volume: 61.4 L
Body density: 1.06 kg/L
Thoracic gas volume: 4.500 L
Pathophysiology of Infertility
Infertility is defined as the inability to conceive after twelve months or more of unprotected intercourse. (Zegers-Hochschild, 2009). Infertility may be due to irregularities within the female or male reproductive system. Irregularities of the male reproductive system may be due to the male’s ejaculate. When infertility is due to poor semen quality, several factors contribute to the inability of sperm to fertilize the female’s egg. If the number of sperm which are present within the ejaculate is low, there exists a decreased probability of fertilization. The morphology of the sperm also plays a role in its ability to reach and fertilize the female ova. If spermatozoa are not produced appropriately, they may be unable to reach the female’s egg or interact as appropriately when the egg is encountered. Research has shown that poor sperm morphology negatively impacts the likelihood of natural (Swerdloff, 2016). In addition to morphology and concentration, the motility of sperm affects success in conception. According to the World Health Organization, spermatozoa are now classified as progressively motile, non-progressively motile, or immobile. At least 40% of sperm should be mobile, while at least 32% of sperm should be progressively mobile for normal male fertility (Organization, 2010). These abnormalities of spermatozoa and semen can be related to intrinsic production deficiencies or as the result of external factors.
Sperm production is regulated by hormones produced within the body, specifically, gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and inhibin interact to produce viable sperm for fertilization. LH and FSH are produced within the pituitary gland of the brain and subsequently act locally within the testis. GnRH controls the release of LH and FSH into the bloodstream. In the testis, LH directs the secretion of testosterone while FSH produces a protein called androgen-binding protein which binds testosterone. This permits a high concentration of testosterone within the testis. Spermatogenesis, the production of sperm, is regulated by testosterone, which provides the signals necessary for the body to produce spermatozoa, or sperm cells (Walker, 2016). The production of this sex hormone is dependent upon cholesterol which is obtained from the diet and stored within the body (Turek, 2011). If the body does not have enough nutrients to successfully produce sperm, a hormone known as inhibin lowers the release of FSH and GnRH, thereby lowering the concentration of testosterone within the testis, a method of negative feedback (Boundless, 2016). Optimal sperm production necessitates an appropriate relationship of these hormones in addition to an environment in which sperm cells can thrive. Factors altering this balance may lead to suboptimal sperm production and infertility.
Even when appropriate hormonal balance exists, external factors may prohibit fertile ejaculate production. Sperm, like all living cells, must have an appropriate environment in which they can grow and develop. This environment can be altered by changes in temperature, stress placed on the body, and other factors. The nervous system allows for appropriate ejaculation of developed sperm. Injuries, to the nervous system, whether temporary or permanent, uniquely impact male fertility.
Special populations are at risk for alterations in the fertility cycle based on physiological changes in spermatogenesis. In male cyclists it has been theorized that the incidence of infertility is higher than that of the general population (Leibovitch I., 2005). The cause of infertility in cyclists has been the focus of much research in recent years. Results have shown several reproductive changes consistently exhibited by cyclists which may negatively impact semen quality.
Cycling is distinguished from many alternative forms of aerobic exercise in that much time is spent in a seated position. This position places reproductive organs within the genital region under increased mechanical pressure (Gebreegziabher Y., 2004). The nerves and vessels which supply this region are also compressed. In fact, pressures applied to the saddle region of cyclists by the bicycle seat are double the threshold value known to cause nerve injury as a result of diminished oxygen delivery (Schrader S.M., 2002). This injury may be the cause of genital numbness and erectile dysfunction experienced by many long distance cyclists (Sommer F., 2001). Although causality has not been confirmed systematically, it is likely this mechanism may be one cause of changes in the process of sperm production.
The impact of changes in sperm production have been demonstrated by several differences in sperm characteristics in cyclists as compared the overall population. The percentage of sperm with normal shape and morphology is lower in cyclists. Although the number of normal sperm has been shown to be lower in cyclists, the value falls within the normal range (Gebreegziabher Y., 2004). Furthermore, studies have indicated that the total sperm count and the number of total motile sperm (TMS, the number of sperm who are able to move appropriately) is lower in cyclists who spend five or more hours cycling per week than that of men who participate in other forms of exercise (Gebreegziabher Y., 2004).
Other elements may also play a role in cyclists’ infertility. As in the case of E.N., many cyclists prefer to maintain a low body mass index (BMI) to ensure they are able to achieve peak performance. BMI is determined by dividing weight (in kilograms) by the square of height (in meters) and is used to assess healthy weight parameters (Control, 2015).
Research has shown that a low BMI can impact fertility status. Those considered underweight (BMI less than 18.5) have decreased total sperm counts, lower sperm concentration (percentage of the ejaculate that is made up by sperm), and a decreased percentage of normal sperm within semen (Qin, 2007). These decreases in fertility markers may be due to a lack of precursor nutrients such as cholesterol, which is utilized in the production of testosterone. Universally high levels of cholesterol lead to a decrease in testosterone levels. One study of a group of men with cardiovascular disease indicated that higher levels of high-density lipoprotein, known as the “healthy” cholesterol, correlated with higher testosterone levels (Page, 2008). More research is necessary to delineate the precise cause for decrease in testosterone within populations with extremely low BMI’s. Despite unknown causality, variations in semen quality related to low BMI can lead to suboptimal sperm production and can be augmented by compression of nerves and vessels experienced in cyclists.
Although variations in cyclists’ semen quality have been shown by recent research, there is still much to learn regarding the true impact of these changes. A recent observational study based on self-reported data indicated that time spent cycling did not influence male infertility (Hollingworth, 2015). These results contradict prior research findings. Although changes in male ejaculate have been shown, this may indicate that these deviations may not be enough to significantly affect the rate of male fertility when compared to non-cyclists. Moreover, advantages of cycling have the potential to outweigh disadvantages. Obesity negatively impacts fertility in many ways beyond the scope of this report. If a cyclist were to lose weight or maintain a healthy body weight, health benefits exist in favor of fertility. Additional studies will continue to enhance our understanding of the impact of cycling on the male reproductive system.
Given the results of E. N. semen analysis and laboratory studies, the likely cause of E.N.’s infertility was due to secondary hypogonadism caused by low levels of FSH and LH leading to low testosterone. His low BMI and percent body fat likely caused low cholesterol levels and contributes to his abnormal hormone levels. Sperm concentration in his semen was significantly decreased, negatively impacting his chances of conception. Given that he had no previous health problems, takes no medications, and does not use any recreational drugs and little to no alcohol, it was suspected that E.N.’s abnormal hormone levels were due to his strict dietary habits, intensive exercise patterns, and low body fat percentage and body mass index.
E.N. was recommended to alter his lifestyle in order to increase his body fat percentage to a healthier level. He was told to decrease the number of miles cycling, as well as alter his training methods. He was recommended to participate in high intensity interval training with lower mileage in order maintain strength and cardiovascular stamina. He was instructed to keep a food diary and record his meals daily, as well as log his activity in order to monitor calorie intake versus calorie burn. He was told to increase his caloric intake in order to exceed his calories burned to put on weight, with a goal BMI of over 18.5. He was recommended to see a licensed nutritionist in order to develop a more balanced diet, and instructed to incorporate more healthy carbohydrates into his diet.
Six months later E.N. returns to the office for follow up. He has been compliant with the recommendations for alteration in his activity level, been seeing a nutritionist and keeping a food diary. He reports a weight gain of fifteen pounds over the past 6 months. His BMI is now 20.3. He cannot report successful conception at this time, but he and his wife are still trying to conceive. He had repeat laboratory tests completed before his appointment, which show improvement with increased testosterone, FSH and LH. He is instructed to continue his food diary, activity and dietary changes. He will follow up again in six months’ time.
Free Testosterone: 450 ng/dL (N: 270-1070ng/dL)
Follicular stimulating hormone (FSH): 3.2 mIU/mL (N: 1.6-8.0 mIU/mL)
Lutenizing Hormone (LH): 2.42 mIU/mL (N: 1.5-9.3 mIU/mL)
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