Infectious Diseases in Obstetrics and Gynecology 1:51-57 (1993) (C) 1993 Wiley-Liss, Inc. Infection and Infertility Sebastian Faro Department of Gynecology and Obstetrics, University of Kansas School of Medicine, Kansas City, KS ABSTRACT Asymptomatic infection appears to be a common cause of fallopian tube damage resulting in ectopic pregnancy or infertility. (C) 1993 Wiley-Liss, Inc. KEY WORDS Bacterial vaginosis, Mycoplasma, Ureaplasma, asymptomatic infection he role of serious pelvic infection in female bacteria, gram-positive aerobes, facultative gram- infertility is well recognized. However, the negative bacteria, anaerobic gram-negative bac- role of asymptomatic infection caused by Neisseria teria, and gram-positive bacteria. The presence of gonorrhoeae and Chlamydia trachomatis, although of Lactobacillus appears to be pivotal in maintaining great concern, has not been well established. Sig- the equilibrium and preventing potentially patho- nificant research efforts have been made to define genic bacteria from gaining dominance. The cur- these asymptomatic sexually transmitted diseases rent theory is that the production of lactic acid by (STDs) and their role in infertility. In conjunction lactobacilli maintains the appropriate pH. In addi- with much of the theorizing on the infectious etiol- tion, these bacteria produce hydrogen peroxide that ogy of infertility, the role of the vaginal microflora is toxic to anaerobic bacteria, which do not produce has also been implicated in these infections. Cur- peroxidase. When the balance is upset, the com- rently, the initial infection is thought to be due to mensal bacteria decrease in number, reducing the the gonococcus and/or chlamydia. This initial in- hydrogen ion concentration and hydrogen peroxide fection is then followed by ascension of potentially and allowing the growth of facultative and anaero- destructive microbes endogenous to the lower fe- bic bacteria, thereby resulting in an unhealthy state. male genital tract. Important to remember is that, despite the many forms of vaginitis, certain types are more conduc- THE VAGINAL MICROFLORA tive to the production of" upper genital tract infec- The lower female genital tract is a delicate ecosys- tion, such as endometritis and salpingitis. The most tem maintained in dynamic equilibrium. This bal- common types of vaginitis are bacterial vaginitis ance can be tipped by any number of factors, both (30% to 35% of cases), yeast vaginitis (20%-25%), endogenous and exogenous. The bacteriologic and trichomoniasis (10%-15%). 2-4 Trichomonia- make-up of the lower genital tract includes both sis should serve as a marker organism for the possi- synergistic bacteria and antagonistic organisms. The ble existence of other infections, as it is commonly healthy vaginal ecosystem is characterized by a pI--I found in association with gonorrhea and chlamy- of 3.8 to 4.2; a slate-grey to white, odorless dis- dia. 5-7 charge; and the presence of other gram-positive The unhealthy or abnormal vaginal flora is char- commensal bacteria, with the dominant bacterium acterized by a pH >4.5. A discharge is also char- being Lactobacillus. Also present are many other acteristic; it is usually dirty-grey but may be colors Address reprint requests to Sebastian Faro, M.D., Ph.D., Department of Gynecology and Obstetrics, The University of Kansas School of Medicine, 3901 Rainbow Blvd., Kansas City, KS 66160-7316. Received January 20, 1993 Review Article Accepted April 7, 1993 INFECTION AND INFERTILITY FARO other than white. It may or may not be frothy and of patients all demonstrated Gardnerella vaginalis, may or may not be homogenous. Typically, it emits but in high colony counts of 3 l0 s to 9 10 9 an amine odor when mixed with 10% potassium cfu/ml of vaginal fluid. The vaginal fluid of the hydroxide (KOH). Microscopic examination usu- patients in this second group revealed clue cells, ally reveals the squamous epithelial cells to be cov- rare WBCs, and bacteria floating in clumps, not ered by adherent bacteria, obliterating the cytoplas- individually. The finding of varieties of bacterial mic membrane and nucleus. In the case of bacterial infections raises the concern regarding not the par- vaginosis (BV), white blood cells (WBCs) are usu- ticular type of vaginitis, but the possibility that the ally absent, thus the use of the suffix "-osis" to bacteria present may ascend to the upper genital indicate the absence of an inflammatory reaction, tract and act synergistically in causing a progressive but numerous individually free-floating bacteria infection. are present. Important to remember is that the individual Microbiologic evaluation of this type of lower with bacterial vaginitis or BV is at greater risk for genital tract will reveal the presence of large num- having an accompanying STD. This epidemiologic bers of facultative and obligate anaerobes. With information is important for two reasons. First, it BV, the patient is more likely to have an STD. In implies that the patient's behavior pattern may cur- one study, 54% of the women with BV reported rently place her at risk for upper genital tract infec- having had an STD. Other bacterial derangements tion. Second, it encourages the physician to obtain a of the vaginal microflora may exist, especially in detailed sexual history to determine if the patient patients who have been repeatedly treated for has been at risk for a prolonged time, making the vaginitis but whose flora has not regained the com- possibility of" a past or present upper genital tract position of a healthy state. Gardnerella vaginalis infection more of a reality. vaginitis, originally described by Gardner and Dukes, consists of a vaginal discharge resembling EVALUATION OF THE PATIENT that of BV, but differing in that the free-floating FOR INFECTION bacteria found in the vaginal fluid are not individ- The physician should encounter little difficulty in ually distributed but in aggregates. Rarely, if ever, evaluating the patient with an acute symptomatic are WBCs present. 9 Some patients present with genital tract infection. However, the goal should bacterial vaginitis consisting predominantly of be the prevention of damage of the fallopian tubes Gardnerella vaginalis with few, if any, other types which might result in abnormal function or infer- of bacteria and, rarely, anaerobes. Whereas other tility. The annual ectopic pregnancy rate from 1970 types of vaginitis may have clinical parameters sim- through 1989 has risen four-fold from 4.5 to 16.1/ ilar to those found with BV, 30% of patients with a 1000 pregnancies. 12 Hospital admissions for ec- discharge that liberates a foul odor will have BV topic pregnancy in 1991 were 88,400, a 10% in- and 17 % of patients with clue cells but no dominant crease over 1988. This rise in the ectopic pregnancy anaerobic bacteria will have BV. 1 In one study, rate is believed to be due to the rise in the number patients with persistent vaginitis who had been re- of cases of pelvic inflammatory disease (PID). Al- peatedly treated with antibiotics were enrolled. 1' though obtaining data with regard to infertility and All patients had a vaginal pH of > 4.5 and the infection is difficult, the estimation has been made liberation of amines when the discharge was mixed that, after a single episode of PID, approximately with 10% KOI-I. These patients were divided into 12% of the women will be infertile; after two epi- two groups. The first group consisted of 48 pa- sodes, 25% will be infertile; and, after three or tients. Microscopic analysis of the vaginal fluid of more episodes, more than 50% will be infertile. 3 all patients in the first group demonstrated numer- The Centers for Disease Control has estimated that ous individually free-floating bacteria and numer- four million initial visits to physicians for PID ous WBCs. Half of the patients in this first group were made in 1991, generating approximately did not demonstrate Gardnerella vaginalis as part of 250,000 hospital admissions. 14 the microflora, and half demonstrated Gardnerella To prevent fallopian tube damage, the physician vaginalis in counts of <103 colony-forming units must recognize the earliest stage of the disease pro- per ml (cfu/ml) of vaginal fluid. The second group cess. The initial site of infection in the female pa- 2 INFECTIOUS DISEASES IN OBSTETRICS AND GYNECOLOGY INFECTION AND INFERTILITY FARO tient is the cervix. However, the difficulty lies in the uterine fundus and obtaining a tissue specimen. the fact that the greatest percentage of infected The pipette should be carefully withdrawn without women are asymptomatic. The physician may be touching the vaginal walls. The specimen should be clued in by asking the patient the appropriate ques- divided into two portions. One should be sent for tions indicating historical evidence for the possible histologic evaluation and the other one sent in an existence of an STD: anaerobic transport vessel for the culture of N. gonorrhoeae, C. trachomatis, aerobic, facultative, 1. Have you noticed a change in your vaginal and obligate anaerobic bacteria. The presence of discharge? plasma cells, especially if C. trachomatis is the in- 2. Do you have spotting following sexual inter- fecting organism, is highly correlated with salpin- course? gitis. 18,19 Endometritis, frequently asymptomatic, 3. Have you noticed a sudden onset of pain with has been reported to occur in approximately 40% of sexual intercourse? women with cervicitis. 18 It has also been reported that women clinically diagnosed as having salpingi- Close attention should be paid to the endocervi- tis, but laparoscopically found to have normal fallo- cal epithelium, specifically noting the presence of pian tubes, had endometritis by biopsy. 2 hypertrophy. A dacron swab should be passed into the endocervical canal and rotated for 5 to 10 sec- RISK FACTORS onds to determine if any endocervical mucus is The first line of intervention is prevention; how- present.