**3. Infections and male infertility**

Tubal and peritoneal pathology is among the most common causes of infertility and the primary diagnosis in approximately 30-35% of infertile couples. A history of pelvic inflam‐ matory disease (PID), septic abortion, ruptured appendix, tubal surgery, or ectopic pregnancy suggests the possibility of tubal damage. PID is unquestionably the major cause of tubal factor infertility and ectopic pregnancies. Classic studies in women with PID diagnosed by laparo‐ scopy have revealed that the risk of subsequent tubal infertility increases with the number and severity of pelvic infections; overall, the incidence is approximately 10-12% after one episode, 23-35% after two, and 54-75% after three episodes of acute PID.[1] The most frequent causes for pelvic infections are sexually transmitted pathogens and intrauterine manipulations like

Approximately 35% of women with an infertility problem are afflicted with post-inflammatory changes of the oviduct or surrounding peritoneum that interfere with tubo-ovarian function. Most of these alterations result from infection. Salpingitis occurs in an estimated 15% of reproductive-age women, and 2.5% of all women become infertile as a result of salpingitis by age 35.[2] Because in most cases, especially those caused by *Chlamydia trachomatis*, signs and symptoms are often minimal or non-existent, the actual percentage of women with upper

Unfortunately, the impact of infectious sequelae on human reproduction continues to increase as a consequence of sexual promiscuity and the popularity of non-barrier methods of contra‐ ception. *C. trachomatis* and gonorrheal infections, as well as mixed anaerobic infections, are the most prevalent causes of upper genital tract infections resulting in pelvic inflammatory disease (PID). Bacterial vaginosis, *Trichomonas vaginalis*, and *Candida albicans* are the most prevalent bacterial, protozoan, and fungal causes of lower genital tract infections. Although gonorrheal infections have been on the decline in the last decade, chlamydial infections of the male and female genital tract continue to be an increasing problem, and *C. trachomatis* is the major cause of tubal factor infertility.[3] *C. trachomatis* is usually recovered three to five times more frequently than *Neisseria gonorrhoeae* from the reproductive tracts of infected individuals.

Women are twice as likely as men to acquire gonorrhea or *Chlamydia* during a single act of unprotected intercourse with an infected partner. Many newly infected women have no symptoms and so do not seek medical intervention and continue to spread the infection to other sexual partners. An estimated 10% to 20% of untreated women with endocervical gonorrhea or chlamydial infection eventually develop salpingitis.[4] Scholes et al[5] recom‐ mended routine testing of sexually active women to prevent sequelae like pelvic inflammatory disease and consequently infertility. Despite the current focus on sexually transmitted diseases (STDs), infertility may also follow blood-borne infections such as tuberculosis, mixed aerobic and anaerobic infections of other pelvic sites, inflammatory complications of surgical trauma,

curettage, evacuation, etc.

4 Genital Infections and Infertility

genital tract infections is probably underestimated.

post-abortal and puerperal sepsis, and appendicular rupture.

**2. Epidemiology**

Acute and chronic genital tract infections are well-known causes of infertility in men (Table 1). Episodes of acute orchitis or epididymitis may result in permanent damage to the testis or to obstruction in the efferent ejaculatory ducts. *C. trachomatis* causes approximately 50% of epididymitis in sexually active men under age 35. Unilateral epididymal obstruction is seldom diagnosed, and its effect on fertility is largely unknown. However, 80% of men with unilateral ductal obstruction have antibodies to sperm, a potential cause of male infertility.[6] Appro‐ priate assessment of a semen sample including tests like presence of seminal Fructose, neutral alpha-glucosidase and pH go a long way in differentiating between obstructive and nonobstructive azoospermia.


**Table 1.** Male Genital Tract Infections That May Cause Infertility

Most men do not develop antibodies to their own spermatozoa because the male genital tract is essentially a closed tube, and sperm are isolated from the immune system. Genital tract infections, even those without symptoms, can weaken this barrier, leading to sperm leakage and the influx of immunologically competent cells. Genital tract infections are a major cause of anti-sperm antibody formation in men.[7] Similarly, genital tract infections and anti-sperm antibody formation in men can lead to immune-mediated infertility in women.[8]

Mumps orchitis is a well-known testicular infection resulting in damage to the germinal epithelium. Systemic infections, whether bacterial or viral, may also cause depression of sperm production for variable periods. Between 2 and 6 months may be required for normal seminal cytology to reappear after a severe febrile illness. Urethral stricture is an occasional compli‐ cation of untreated gonorrhea. Although the stricture does not in itself interfere with sperm motility, it may cause recurring urinary tract infection or prostatitis and epididymitis.

The fertility of a couple may be impaired if the man has a chronic bacterial prostatitis. Chronic prostatitis is presumed to be caused by a pathogenic organism and in most cases is associated with leukocytes in the semen. The prevalence of leukocytospermia among male infertility patients is about 10% to 20%. Although the exact role of WBCs in semen and its importance with respect to fertility is not clearly elucidated, there is some evidence that treating such patients with long term antibiotics does have a favourable impact on the semen parameters.[9] According to a study the presence in semen of counts more than 10,000 colony-forming units/ ml had a negative effect on IVF pregnancy rates when *E. coli, Proteus,* or *S. aureus* organisms were isolated.[10] Again, there is some evidence that the occurrence of leucocytes in semen yields abnormal sperm function tests, possibly because of the damaging effects of free radicles of WBCs to the sperms in their journey through the epididymis.[11] There is also substantial evidence that infection contributes to the development of sperm antibodies. Sperm antibodies have been detected in 48% of men with culture-positive asymptomatic infections, 47% of men with a history of urethritis or prostatitis, and in only 5% of men with no infection and a normal semen analysis.

The presence of IgA antibodies was associated with reduced fertility.[12] High concentrations of sperm antibodies can interfere with fertility by several mechanisms. Antibodies on sperm heads or tails may cause sperm to agglutinate. Tail-bound antibodies also interfere with sperm motility. Antibodies anywhere on spermatozoa can lead to sperm phagocytosis through binding to Fc or complement receptors on phagocytic cells. Similarly, antibody-bound sperm react with cervical mucus leading to sperm immobilization and expulsion from the female genital tract. Antibodies on sperm can interfere with sperm binding and penetration of the oocyte.[13] Similar to the situation in women, *C. trachomatis* infection of the male genital tract is often asymptomatic and therefore may persist for a long time. One study using PCR analysis of semen specimens suggested that an asymptomatic unsuspected *C. trachomatis* male genital tract infection may be the cause of previously unexplained infertility.[14] In response to a persistent asymptomatic chlamydial infection and HSP60 production, γδ T cells may be induced in the male genital tract; γδ T cells are capable of releasing proinflammatory cytokines and could therefore initiate an antisperm immune response within the genital tract.
