Diagnosis of pelvic inflammatory disease: time for a rethink.

OBJECTIVES: To critically evaluate the available evidence base concerned with the diagnosis of pelvic inflammatory disease (PID) based on clinical presentation, and to investigate the relation between signs and symptoms and the presence of laparoscopically diagnosed PID using the largest available dataset. METHODS: The evidence base was critically evaluated and data collected by Lund University between 1960 and 1969 were used to compare clinical presentation with the results of laparoscopic investigation. Three techniques were used in this investigation-sensitivity and specificity, likelihood ratios, and discriminant analysis. RESULTS: None of the variables (abnormal vaginal discharge, fever >38 degrees C, vomiting, menstrual irregularity, ongoing bleeding, symptoms of urethritis, rectal temperature >38 degrees C, marked tenderness of pelvic organs on bimanual examination, adnexal mass, and erythrocyte sedimentation rate >or=15 mm in the first hour) had both high specificity and sensitivity-most had low specificity and sensitivity. There was little variation in either the likelihood ratios or the post-test probabilities between the variables. The lowest likelihood ratio (0.97) produced a post-test probability of 78% (95% CI: 74% to 81%) whereas the highest (1.73) had a post-test probability of 84% (95% CI: 81% to 87%). The pretest probability of having PID based on the presence of lower abdominal pain was 79% (95% CI: 76% to 82%). The discriminant analysis indicated that three variables significantly influenced the prediction of the presence of PID: erythrocyte sedimentation rate (p<0.0001), fever (p<0.0001), and adnexal tenderness (p<0.0001). These variables correctly classified 65% of patients with laparoscopically diagnosed PID (95% CI: 61% to 69%). CONCLUSION: There is insufficient evidence to support existing diagnostic criteria, which have been based on a combination of empirical data and expert opinion. A new evidence base is urgently needed but this will require either a new investigation of the association between clinical presentation and PID based on a laparoscopic "gold standard" or the development of new diagnostic techniques.

Severity of pelvic inflammatory disease as a predictor of the probability of live birth.

OBJECTIVE: Our aim was to study the association between severity of pelvic inflammatory disease at laparoscopy and the probability of achieving a live birth, while accounting for subsequent episodes of pelvic inflammatory disease. STUDY DESIGN: Beginning in 1960 a cohort of 1288 women in Lund, Sweden, who had clinical symptoms of acute pelvic inflammatory disease and who desired pregnancy was followed for up to 24 years. All participants underwent laparoscopy and were categorized by degree of salpingitis: mild (n = 371), moderate (n = 580), or severe (n = 337) pelvic inflammatory disease. Cumulative live birth rates, obtained by life-table analysis, and proportional hazards ratios were compared among women by severity of pelvic inflammatory disease, while accounting for subsequent episodes. RESULTS: The cumulative proportion of women achieving a live birth after 12 years was 90% for women with mild, 82% for women with moderate, and 57% for women with severe pelvic inflammatory disease. The occurrence of subsequent episodes in women with mild pelvic inflammatory disease did not diminish their long-term probability of live birth, whereas it significantly lowered the probability of live birth in women with severe pelvic inflammatory disease. Women with severe disease and subsequent episodes were eight times more likely to fail to achieve live birth compared with women with a single pelvic inflammatory disease episode with mild disease (relative risk 8.1; 95% confidence interval 3.0 to 22.2). CONCLUSIONS: Increasing severity of pelvic inflammatory disease correlates with a lower long-term probability of live birth. Subsequent episodes have a greater impact on women with severe pelvic inflammatory disease at the index episode compared with those with milder disease.

Vestibular nerve fiber proliferation in vulvar vestibulitis syndrome.

OBJECTIVE: To evaluate nerve fiber density in vestibular specimens from women operated upon for vulvar vestibulitis. METHODS: Forty-seven women with vulvar vestibulitis syndrome underwent modified posterior vestibulectomies. Vestibular specimens were analyzed after being stained for S-100 neural tissue protein. Women were followed up for 2 years. RESULTS: In specimens from 44 of 47 patients, the densities and numbers of nerve fibers per square unit in the preparations were greater than those in specimens from six control women. In the patients, a statistically significant linear correlation was found between inflammation and nerve bundle density in the preparations (Spearman rank correlation coefficient rs=.41; P=.005). There were no signs of infectious etiology in any preparation. No or slight postoperative dyspareunia was reported by 38 of 42 women after 6 months, 36 of 39 after 12 months, and 26 of 28 after 24 months. CONCLUSION: Vestibular neural hyperplasia may provide a morphologic explanation of the pain in vulvar vestibulitis syndrome.

Analysis of ectopic pregnancy data using marginal and conditional models.

This work is motivated by a longitudinal study of women and their ectopic pregnancy outcomes in Lund, Sweden. In this article, we review and apply the Liang-Zeger methodology to the Lund ectopic pregnancy data set. We further analyse the ectopic pregnancy data using conditional modelling approaches suggested by Rosner and Bonney. From the Lund ectopic pregnancy data, we learned that PID is the strongest predictor of subsequent development of ectopic pregnancy and that there is a monotone relationship between PID severity and ectopic pregnancy. We also learned that the presence of mycoplasma from lower or upper genital tract sites at index laparoscopy is also a strong predictor of ectopic pregnancy. Other correlates of ectopic pregnancy include age at pregnancy and history of gynaecologic surgery.

Chlamydia and its effect on reproduction.

PIP: Epididymitis in the male and salpingitis in the female may cause permanent functional damage to the reproductive tract, resulting in infertility. Agents with proven connection to post-infection infertility are Neisseria gonorrhoeae and Chlamydia trachomatis. In men, infertility after chlamydia-associated epididymitis is uncommon, whereas in women sequelae after salpingitis--including chlamydia-associated disease--are the most common cause of acquired infertility. In a prospectively followed cohort of women who all sought pregnancy after one episode of laparoscopically verified acute salpingitis, 79/1025 (7.8%) were infertile because of post-salpingitic tubal occlusion, compared with 4/448 control women (0.9%). Important factors in post-salpingitic infertility were: number of episodes [relative risk (RR) after none, 1, 2, and 3 or more episodes were 1.0, 5.2, 11.3, and 19.8, respectively, amounting to a total infertility rate after salpingitis of 15%]; in women with only one episode, the severity of infection (mild, moderate, and severe; RR, 1.0, 1.8, and 5.6, respectively) and delayed care (less than 3 days and 3 or more days; RR, 1.0 and 3.0, respectively); use of contraceptives (non-contraceptors, pill users, IUD users, and 'other'; RR, 1.0, 0.3, 0.5, and 0.8, respectively); and non-chlamydial and chlamydial infection (RR, 1.0 and 1.7, respectively). Observations in infertile women suggest that an equally large number of women may have post-infectious tubal infertility also after asymptomatic salpingitis; in the majority of cases with serologic evidence of a passed genital chlamydial infection. Recently, a hypothesis has been presented that antigen-antibody reactions to chlamydial heat-shock proteins might be an important factor for the morphological tissue damage and scarring leading to impaired fertility. Post-pelvic inflammatory disease associated with sexually transmitted disease infertility is acquired and, hence, preventable.^ieng

Effect of pelvic inflammatory disease on fertility.

Genital infections, in both men and women, may cause permanent functional damage to the reproductive tract resulting in infertility. In men, post-infection infertility is uncommon, whereas in women sequelae after pelvic inflammatory disease (PID) are the most common cause of acquired infertility. In a prospective cohort study of women who all sought pregnancy after laparoscopically verified acute (non-tuberculous) salpingitis, 141/1309 (10.8%) were infertile because of proven post-PID tubal occlusion. In 448 control women, the corresponding figures were 4/448 (0.9%). Of independent and significant importance for post-PID infertility were the numbers of PID episodes (0/1/2 or= 3: RRs 1.0/7.0/16.2/28.3), and in women with only one PID episode, the severity of infection (mild/moderate/severe; RRs 1/1.8/5.6), delayed care (3 days/3 or more days; RR 1/2.8), use of contraceptives (none/pills/IUDs/other; RRs 1/0.3/0.5/0.8). Similar influences of the same variables were also demonstrated for subfertility, i.e. ectopic pregnancy, and time between index laparoscopy and pregnancy in those women who conceived after PID.

Sexually transmitted diseases and infertility.

In both men and women, STD-associated genital infections may cause permanent damage to the reproductive tract resulting in sub- or infertility. In men, the wide zone between sterility and normal fertility makes it difficult to demarcate the precise role of infection on post-infection fecundity, but it seems less important than in women. The reproductive events were studied in a cohort of 1,309 pregnancy-seeking women, < or = 35 years of age, after laparoscopically verified acute salpingitis, and 451 women with normal laparoscopy. Tubal factor infertility (TFI) was diagnosed in 12.1% of the patients and 0.9% of the controls, and the first pregnancy was ectopic in 7.8% and 1.3%, respectively. Of independent importance for infertility, ectopic pregnancy, and time between PID and first intrauterine pregnancy were number of infections, severity of the infections, contraception at the index laparoscopy, age, and delayed treatment. STD-associated in-subfertility is acquired and, hence, preventable.

Delayed care of pelvic inflammatory disease as a risk factor for impaired fertility.

OBJECTIVE: We evaluated the relationship between delayed care of symptomatic pelvic inflammatory disease and impaired fertility. STUDY DESIGN: We used data from a cohort of women with clinically recognized pelvic inflammatory disease. Case patients were women with either ectopic pregnancy or infertility (n = 76); controls were women with intrauterine pregnancies (n = 367). RESULTS: Women who delayed seeking care for pelvic inflammatory disease were three times more likely to experience infertility or ectopic pregnancy than women who sought care promptly after adjustment for age, organism, year of diagnosis, and history of recent gynecologic events (95% confidence interval = 1.27, 6.11). This association was strongest for women with chlamydia; 17.8% (18/101) of those who delayed seeking care had impaired fertility, whereas 0.0% (0/13) of those who sought care promptly suffered known sequelae. CONCLUSIONS: Women with pelvic inflammatory disease who delay seeking care are at increased risk for infertility and ectopic pregnancy. Furthermore, our data suggest that prompt evaluation and treatment of chlamydial pelvic inflammatory disease can prevent these sequelae.

Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results.

From 1960 10 1984, 2,501 women underwent diagnostic laparoscopy (index laparoscopy) because of a clinical suspicion of acute pelvic inflammatory disease (PID). Of these women, 1,844 had abnormal laparoscopic findings (patients) and 657 had normal findings (control subjects). The reproductive events after index laparoscopy of 1,732 patients and 601 control subjects were followed. The patients and control subjects were followed for a total of 13,400 and 3,958 woman-years, respectively. During the follow-up period, 1,309 (75.6%) of the patients and 451 (75.0%) of the control subjects attempted to conceive. Of these women, 209 (16.0%) of the patients and 12 (2.7%) of the control subjects failed to conceive. A total of 141 (10.8%) of the patients and 0 (0%) of the control subjects had confirmed tubal factor infertility, 21 (1.6%) of the patients and 3 (0.7%) control subjects had other causes of infertility, and 47 (3.6%) patients and 9 (2.0%) control subjects did not have a complete infertility evaluation. Additional information on tubal morphology (hysterosalpingography, laparoscopy, or laparotomy) in women from couples for whom evaluation was incomplete indicated that 165 (12.2%) patients and 4 (0.9%) of the control subjects had abnormal tubal function or morphology after index laparoscopy. Tubal factor infertility after PID was associated with number and severity of PID episodes. The ectopic pregnancy rate for first pregnancy after index laparoscopy was 9.1% among the patients and 1.4% among control subjects.

Recurrence of ectopic pregnancy: the role of salpingitis.

We evaluated the role of salpingitis on the recurrence of ectopic pregnancy from a historical cohort of 2501 women who had undergone laparoscopic examination for acute salpingitis. We used pregnancy (N = 2899) as the unit of analysis and a modified conditional logistic regression to estimate a pairwise odds ratio as a measure of the recurrence of ectopic pregnancy. Among the second or higher order of pregnancy, the recurrence was 21.7%. For pregnancies with a prior uterine pregnancy, the ectopic pregnancy rate increased with prior salpingitis scores constructed from a combination of prior salpingitis episodes and severity (0 score, 2.7%; 1 to 2 scores, 4.8%; and greater than or equal to 3 scores, 12.1%). For those with a prior ectopic pregnancy, the rate did not increase with prior salpingitis scores (score 0, 20.0%; score 1 or 2, 19.2%; and score greater than or equal to 3, 26.9%). The adjusted pairwise odds ratio was 2.2 and was practically unchanged (2.1) after additional adjustment with prior salpingitis scores. These findings confirm salpingitis as a risk factor for first ectopic pregnancy, but once a woman had an ectopic pregnancy, previous salpingitis might not add any incremental risk.

Treatment of candidal vaginitis. A prospective randomized investigator-blind multicenter study comparing topically applied econazole with oral fluconazole.

Two hundred and thirty-five women with clinically and microbiologically proven candidal vaginitis were randomly allocated for treatment with either one topically applied vaginal tablet of 150 mg econazole (114 women) or one orally administered capsule of 150 mg fluconazole (121 women). The women returned for follow-up visits 7-10, 28-35, and 80-100 days after the recruitment visit. Women with clinical and/or mycological failures and/or a recurrence were successively excluded from the follow-up. At the 28-35-day follow-up visit, the women treated with fluconazole had a significantly higher clinical/microbiological cure rate than those given econazole (P = 0.022; Fisher's exact 2-tail test). No significant such differences were observed at the 7-10 and the 80-100-day follow-up visits, although fluconazole tended to be more efficacious. Nine women administered fluconazole, and 2 women given econazole reported minor systemic side effects of the treatment. Three women out of 4 preferred oral to local therapy of candidal vaginitis.

Chlamydia trachomatis--clinical significance and strategies of intervention.

Chlamydia trachomatis is currently the most common sexually transmitted bacterial infection in the industrialized countries. In sexually active persons less than or equal to 25 years of age, prevalences up to 20% have been noted; urethritis/epididymitis in men and cervicitis/endometritis/salpingitis in women being the most common clinical expressions. Despite uncomplicated genital chlamydial infections often being asymptomatic or clinically indolent, sequelae to their complications are of importance in constituting the most common cause of acquired infertility in humans. Their commonness, high proportion of asymptomatic disease, and their serious postcomplication sequelae, make the genital chlamydial infections a major health problem; active search for genital chlamydial infections seems to be the most important means of intervention.

Reduced rate of postoperative infections in emergency cesarean section after two doses of cefuroxim perioperatively. A placebo-controlled study.

The rate of postoperative infections after cesarean section was studied in a prospective double-blind randomized study to compare cefuroxim with a placebo. Intravenous bolus injections were given at the beginning of, and 12h after the operation. Eighty patients received cefuroxim and 80 received placebo. Endometritis or wound infection, or both, was diagnosed in 2/80 (2.5%) patients receiving cefuroxim and in 23/80 (29%) patients receiving placebo. No side effects were demonstrated or reported by the patients. Thus, two bolus injections of 1.5 g of cefuroxim given perioperatively significantly reduced postoperative infectious morbidity after emergency cesarean section.