Immunologic Effects of Vasectomy

Vasectomy can be performed in a doctor’s office in around twenty minutes. Vasectomy is “pushed” as a completely safe, side-effect free procedure in advertisements on the Internet. It is pushed culturally and a suggestion is implicit that men should become more responsible for birth control. In fact, you will see references like this on the Internet, “…an estimated 20 to 30 women die in the United States each year from complications from tubal ligation surgery. Dr. Kennon, an urologist at Tripler Army Medical Center in Honolulu observes, “We [men] are subjecting our wives to a life-threatening procedure when we should be stepping up to the plate ourselves.”

The idea that men should “step up” to the plate and have a vasectomy may contribute to the estimated 500,000 vasectomies performed each year in the United States. Even with the vasectomy “push”, tubal ligations still outnumber vasectomies by about two to one. But this article is not about which procedure is best. I am not a fan of surgical treatment for infertility, but accept that each person must choose for themselves what to do about these matters.

The post-operative pain and swelling associated with vasectomy are fairly easy to mange with Tylenol, ice packs, and a few days rest. The acute complications of excess bleeding and infection are not common and usually respond to available treatments. This is the story you are meant to see. During the consent process, little is said about the long-term effects of vasectomy or effects on sexual function.

When a man has a vasectomy, his body continues to produce sperm. There is nowhere for this sperm to go and while some of it is reabsorbed, the amount produced can present some problems. In many men, this sperm builds up in the tail of the epididymis (a mushy sperm maturation organ connected to the testes). This leads to leaks in the epididymal lining. Sperm can then leak into areas they were never meant to be, and stimulate a different and stronger antibody response than is normal and seen during puberty.

You see, sperm is highly antigenic, meaning it stimulates a strong immune response. It is recognized by the man’s body as foreign. During puberty, some anti-sperm antibodies develop when the body is first exposed to sperm. Prior to this, the man’s immune system has never “seen” sperm. After puberty, the sperm are protected by a “blood-testes barrier”. When this barrier is broken by vasectomy and sperm are “presented” to the immune system, new anti-sperm antibodies are formed and the previous “normal” immune response becomes abnormal in strength, specific antibody types, and perseverance of response.

The fact that humans form some anti-sperm antibodies during puberty is known. Some people “poo poo” the anti-sperm issue based on this. However, it seems that the immune response to sperm after vasectomy is more robust, new antibody species appear that are not found in intact men. The response correlates with pre-vasectomy sperm count and continues to increase after vasectomy due to chronic sperm antigen presentation to the immune system.

See this reference: “In 1970, 50% of vasectomized men were found to have circulating spermatozoal antibodies. A more recent survey provides confirmation for this finding and presents an incidence of only 2% of agglutinating antibodies and 0% of immobilizing antibodies in a fertile control population. Some recent and convincing studies have shown sperm agglutinating and immobilizing antibodies to remain either at the same titer level or actually to increase 5-12 years postoperatively. Titers range from 2 to 2048 among different patients. The highest incidence of titers is 1 year after vasectomy, but titers can be found as early as 6 months or as late as 20 years postoperatively.

The wide range in titers can be explained in terms of technical problems in immune assays, since only immunoglobulins and not those antibodies part of immune complex systems can be measured. Since sperm antigens are in abundant supply in vasectomized men because of the continuous resorption of spermatozoa after vasectomy, possibly undetectable antibody titers actually reflect high levels of anti-sperm antibodies circulating in the form of immune complexes. Also it may be possible that the variety in measured titers of auto-antibodies, as well as the non-universal (70%) antibody response in a vasectomized population, is a variable dependent on genetic content and, therefore, an individual characteristic.” 

And this reference: “High antibody titer was also seen in 5 of 7 subjects who developed swelling at the ligation site. The results in this study yielded and 11% incidence of sperm agglutinating antibodies in nonvasectomized fertile males. 62% of those who had vasectomies developed these antibodies within the 1st few years. This indicates that the majority of vasectomized men are early responders to sperm antigens. This study also revealed that sperm immobilizing antibodies rise as the post-vasectomy period lengthens, even beyond 20 years.

Another study: “A comparative study of 69 vasectomized and 126 nonvasectomized men enrolled in the Portland (Oregon, US) Center for the Multiple Risk Factor Intervention Trial evaluated vasectomy as a risk factor for cardiovascular disease. In animal studies, atherosclerosis development has been linked to circulating anti-sperm antibodies and immune complexes formed in response to sperm breakdown products released in the body after vasectomy. Vasectomized men smoked more and had lower diastolic and systolic blood pressure than men in the control group.

As expected, both sperm immobilization and sperm agglutination assays were significantly higher among vasectomized men than controls; 29.4% of vasectomized men compared with only 2.5% of nonvasectomized men had sperm immobilization values of 0.3 or less, while 54.1% of vasectomized men compared with 12.5% of nonvasectomized men had sperm agglutination values of 20.0 or above. These significant differences persisted even when a variety of coronary heart disease risk factors and treatments were controlled. Multivariate analysis showed that antibody development tended to decrease with age at vasectomy and increase with time since vasectomy. In the case of sperm agglutination, the antibodies clearly increased with time since vasectomy.”

Why should you care?

In primate studies, there is an increase in atherosclerotic plaque formation after vasectomy even after controlling for dietary factors:

“We demonstrated previously that atherosclerosis develops more extensively in vasectomized cynomolgus macaques fed an atherogenic diet and speculated that the immunologic response to sperm antigens may have exacerbated the atherosclerosis. We report here that rhesus monkeys vasectomized for 9-14 yr and fed monkey chow (devoid of cholesterol and low in fat) rather than an atherogenic diet also had more extensive and severe atherosclerosis than did control animals of the same age. The extent of atherosclerosis was considered as the percentage of intimal surface with plaques. No control animals were found to have plaques in the thoracic aorta, but 7 of 10 vasectomized monkeys were affected. The plaques in the vasectomized monkeys occupied about 13% of the intimal surface. In 4 of 7 control monkeys and 7 of 10 vasectomized monkeys there were lesions in the abdominal aortas; the lesions were considerably more extensive and severe in the vasectomized animals.

This research finding has not been conclusively demonstrated in humans. It is concerning that a simple procedure could have unintended consequences on areas of the body far from the site of the surgery. The long-term effects of this immunologic experiment have yet to be fully discovered.

“In response to enquiries received by the World Health Organization (WHO) from several countries, the WHO Special Program of Research, Development and Research Training in Human Reproduction convened a meeting of experts in Geneva during August 1981 to review the available animal, clinical, and epidemiological data on vasectomy, with particular emphasis on clinical implications of long-term sequelae of vasectomy in cardiovascular disease. The occurrence of circulating antibodies to sperm antigens has been demonstrated after vasectomy in all animal species studied thus far by various techniques. Prospective clinical studies of vasectomized and nonvasectomized men have been conducted at 4 centers in the U.S. involving clinical and laboratory evaluation of subjects before surgery and at intervals thereafter. A total of 412 vasectomized men were enrolled in these studies; most were followed for 2, 3, or 4 years. The only significant finding was the development of antibody to sperm antigens. Alexander and Clarkson first reported that vasectomy increases the extent and severity of diet-induced atherosclerosis in cynomolgus monkeys. In a 2nd study, Clarkson and Alexander extended their previous findings to evaluate the effects of vasectomy on naturally occurring atherosclerosis in rhesus monkeys. The mechanism by which vasectomy exacerbates atherosclerosis in monkeys has not been defined. At present epidemiological data which have been published come from observations in the U.S. and United Kingdom and in particular from 2 studies involving 4830 and 1764 vasectomized men studied at about 5-6 years after surgery. No health risks of vasectomy were detected in these early years.” 

Another area of concern after vasectomy is Vasectomy Induced Testicular damage. Most people think of vasectomy as benign and safe. You are told that it will have no effect on you other than to stop sperm from getting in the ejaculate. What happens to all that sperm?

“When a patient elects to have a vasectomy, he must understand that pressure build-up proximal to the vasectomy site, congestion of the epididymis, and, indeed, epididymal blowouts are inevitable consequences of this surgical procedure. In more than 800 vasovasostomy (vasectomy reversal) patients whom we have seen, there is always some degree of epididymal engorgement and congestion. Indeed, after one explores these post-vasectomy patients microsurgically, it becomes difficult to understand why the vast majority of such patients have no pain or discomfort.” EI Shapiro and SJ Silber, Open-ended vasectomy, sperm granuloma, and post-vasectomy orchialgia., Fertility and Sterility, 32: 5, 546-550, November, 1979.

“The local effects of vasectomy on the reproductive tract are not fully determined. Distention of the epididymal duct occurs in most patients and granuloma formation is common. Vasectomy may also induce autoimmune orchitis. While many men develop structural changes in the reproductive tract after vasectomy, only a minority report discomfort.”  (Autoimmune orchitis is a chronic inflammatory condition that can lead to pain, low testosterone levels, and testicular shrinkage.)

And this: Germ cell differentiation, DNA synthesis, and apoptosis can be evaluated quantitatively. On the other hand, an interstitial (testicular) lesion is difficult to examine. We have focused on the quantitative analysis of testicular interstitial fibrosis after vasectomy. MATERIALS AND METHODS: Forty testicular biopsy specimens from twenty consecutive men were obtained at vasovasostomy. (Vasectomy reversal) Johnsen’s mean score was calculated from testicular biopsy specimens. Percent of interstitial fibrosis was determined quantitatively by the NIH-Image after Masson-trichrome staining. RESULTS: A significant increase in interstitial fibrosis was observed along with the obstructive interval (p < 0.001). Johnsen’s mean score count did not associate with the obstructive interval. CONCLUSION: Interstitial lesions of testicular physiology and pathophysiology can be evaluated using the NIH-Image. Interstitial fibrosis (permanent scarring), but not the intraseminiferous status, reflects the irreversible damage of vasectomized testes.

Clearly, the “party line” that vasectomy is safe is not justified for all cases. There are other consequences as listed on my website. The post-vasectomy incidence of chronic testicular pain in as many as 15% of patients is also of great concern. It does not seem to be of concern to the men that do fine after the procedure, but perhaps the known and unknown long-term immunologic issues will be of more interest to prospective vasectomy candidates.

I believe the testicular damage is related to back-pressure form closing off the system with vasectomy and also auto-immune (in some patients more than others, as the response is individual).

This may be person specific based on:

1. The degree of epididymal obstruction which may depend on the vigor of the auto-immune response
2. The length of the testicular segment of vas left after vasectomy for sperm reabsorption and the effect of this on sperm granuloma formation.
3. Individual variation in pre-vasectomy sperm count and thus post-vasectomy immune response which is genetically pre-determined
4. The continuing presence of soluble antigen presented to the immune system in sperm granulomas (the bodies response to immune cell contact with sperm and sperm components.)

It is easy to make a case for the back pressure effects on the testes based on the human studies and other mammalian studies I have read. The immune component is much more difficult to prove. Nonetheless, the issues presented here are cause for caution.

I believe that more research needs to be done on the effects of auto-immune phenomenon after vasectomy. Perhaps patients that develop problems are different in their response to chronic sperm antigen presentation. The immunologic experiment continues with the 500,000 men per year that choose vasectomy.