Version May 2024
INTRODUCTION — Pelvic inflammatory disease (PID) refers to infection of the female upper genital tract leading to one or more of the following: endometritis, salpingitis, oophoritis, pelvic peritonitis, and perihepatitis [1]. Prompt diagnosis and treatment are important to reduce the risk of both short- and long-term complications. However, even with timely treatment and clinical improvement in symptoms, long-term sequelae (eg, chronic pelvic pain, infertility, ectopic pregnancy) frequently occur. The mechanism by which this occurs is thought to be secondary to scarring and adhesion formation that accompanies healing of infection-damaged tissues.
Long-term complications of PID will be reviewed here; other issues related to PID are discussed separately:
●(See "Pelvic inflammatory disease: Pathogenesis, microbiology, and risk factors".)
●(See "Pelvic inflammatory disease: Clinical manifestations and diagnosis".)
●(See "Pelvic inflammatory disease: Treatment in adults and adolescents".)
PREDICTORS AND DISEASE RECURRENCE — Signs and symptoms associated with acute PID (eg, pelvic pain, documented infection, endometritis) are poor predictors of the eventual development of chronic sequelae [2]. Furthermore, clinical and/or microbiologic cure of acute disease does not preclude development of the long-term complications (eg, chronic pain, infertility, ectopic pregnancy). Therefore, clinicians should not assume that patients with a complete recovery from PID have avoided the increased risk of long-term complications.
Patients with a history of PID are also at increased risk of recurrence. In a secondary analysis of over 800 patients with mild to moderate PID from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) randomized trial, recurrent PID at 35 and 84 months occurred in 15 and 21 percent of patients, respectively [3]. Adolescents compared with adults were 50 percent more likely to experience a recurrence and had shorter times to recurrence (hazard ratio [HR] 1.54, 95% CI 1.03-2.3]). Limitations of this study include that recurrent PID was self-reported (although verified with medical records when available) and most patients in this study were uninsured or had public insurance; other populations may have different rates of recurrence.
CHRONIC PELVIC PAIN — As many as one-third of patients with PID develop chronic pelvic pain, defined as menstrual or non-menstrual pain of at least six months' duration that occurs below the umbilicus and is severe enough to cause functional disability [4-6]. While the precise etiology is unknown, the pain may result from scarring and adhesions that develop from inflammation related to the infectious process. (See "Chronic pelvic pain in nonpregnant adult females: Causes", section on 'Common'.)
In studies using data from the PID evaluation and clinical health (PEACH) randomized trial, recurrent PID was the strongest predictor for the development of chronic pelvic pain (odds ratio [OR] 2.84, 95% CI 1.07-7.54) [7]. Other predictors included smoking (OR 1.65, 95% CI 1.01–2.71) and a lower (worse) mental health score (OR 2.71, 95% 1.69–4.34). Similarly, in a subsequent study, patients with versus without recurrent PID were over four times more likely to report chronic pelvic pain (adjusted OR 4.2, 95% CI 2.8-6.2) [8].
PID may result in painful bladder syndrome. In a case-control study evaluating the correlation between painful bladder syndrome and PID, patients with bladder pain syndrome/interstitial cystitis (449 patients) compared with controls were more likely to have a history of PID (41.7 versus 15.4 percent, OR 3.69, 95% CI 2.89-4.71) [9]. (See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis", section on 'Pathogenesis'.)
TUBAL DAMAGE — PID can cause permanent injury to the fallopian tube, especially the endosalpinx. Changes to the fallopian tube, including loss of ciliary action, fibrosis, and occlusion can lead to hydrosalpinx, tubal infertility, and ectopic pregnancy [10].
Hydrosalpinx — Patients with PID may develop a hydrosalpinx, a postinflammatory process in which the damaged fallopian tube can become blocked, fill with sterile fluid, and become enlarged. Even after PID resolves, the hydrosalpinx remains. Damage to the fallopian tube from previous surgery or adhesions can also result in hydrosalpinx.
Hydrosalpinx may be associated with pain or may be asymptomatic; some asymptomatic patients present with tubal factor infertility.
In patients undergoing in vitro fertilization (IVF), hydrosalpinx has negative consequences on the rates of pregnancy, implantation, early pregnancy loss, preterm birth, and live delivery [11,12]. Thus, salpingectomy with removal of the hydrosalpinx is often performed prior to IVF to improve outcomes. This is discussed in detail separately. (See "Female infertility: Treatments", section on 'Salpingectomy for hydrosalpinx'.)
Imaging findings of hydrosalpinx and the progression to pyosalpinx are discussed separately. (See "Hysterosalpingography", section on 'Hydrosalpinx' and "Epidemiology, clinical manifestations, and diagnosis of tubo-ovarian abscess", section on 'Progression of infection'.)
Infertility — Tubal damage caused by PID increases the risk of infertility, the prevalence of which appears to be increased severalfold. In a study using data from the PID evaluation and clinical health (PEACH) randomized trial, recurrent PID was associated with an almost twofold increase in infertility (adjusted OR 1.8, 95% CI 1.2-2.8) [8]. Similarly, in a prospective study of 1760 Swedish patients with suspected PID who underwent diagnostic laparoscopy and desired pregnancy, more patients with laparoscopically-confirmed PID (group 1) compared with normal laparoscopic findings (group 2) failed to conceive (16 versus 2.7 percent); patients were followed for up to 25 years [13]. Tubal factor accounted for 68 percent of infertility diagnoses; no patients in group 2 had tubal factor infertility.
Subclinical PID, defined as histologic endometritis with no symptoms of acute PID, also appears to decrease subsequent fertility, even in patients who are treated for chlamydia, gonorrhea, and bacterial vaginosis [14]. Treatment of cervicitis without endometritis does not appear to have this effect.
Infertility after acute PID depends upon multiple factors:
●Chlamydial infection – Infection with Chlamydia trachomatis increases the risk of tubal factor infertility. In one prospective study including 194 patients with tubal factor infertility seeking care in an infertility clinic, approximately one in four patients had serum antibodies to C. trachomatis [15].
Furthermore, serum titers of C. trachomatis antibodies correlate inversely with pregnancy rates [15,16]. In one study of 443 patients with symptoms and signs of PID in whom blood samples were available, patients with the highest and lowest antibody titers had pregnancy rates of 59.6 and 73 percent, respectively, at seven years postinfection [17]. These data suggest that infertility after PID may result, at least in part, from the hostꞌs immune response to chlamydial infection, and a high titer may be associated with a greater inflammatory response.
●Mycoplasma genitalium – Infection with Mycoplasma genitalium, a bacteria associated with non-specific urethritis in males and acute cervicitis and PID in females, also increases the risk of infertility. In a prospective study of over 460 females attempting conception after discontinuation of contraception, those with positive compared with negative M. genitalium serology had longer times to conception (8.5 versus 4.8 months [median]) and higher rates of infertility (31.7 versus 20 percent) at 12 months [18]. M. genitalium also appeared to be a better predictor of infertility than C. trachomatis serology.
●Delay in initiating treatment – Patients with PID who delay seeking care are at increased risk for infertility. In one cohort study including patients with PID, patients who delayed seeking treatment for ≥3 days compared with seeking care in a timely manner were more likely to be diagnosed with infertility (19.2 versus 8.3 percent) [19]. This association was highest in patients with chlamydial infection (17.8 percent); no patients with chlamydia who sought care promptly had impaired fertility.
●Increasing number of PID episodes – Increasing number of PID episodes is also associated with increased infertility. In a classic review of PID in resource-abundant countries, pregnancy rates after one, two, or three or more episodes of PID were 89, 77, and 46 percent, respectively [20].
●More severe infection – More severe PID is also inversely related to the probability of live birth. In another classic review of patients with PID and who desired pregnancy, the cumulative proportions of patients achieving a livebirth after mild, moderate, and severe PID were 90, 82, and 57 percent, respectively [21].
In patients with chronic PID, infertility may also result from diminished ovarian reserve, as reported in at least one study [22].
Ectopic pregnancy — Tubal damage caused by PID increases the risk of tubal pregnancy. The increased expression of certain proteins involved in implantation may also play a role in the pathophysiology [23]. This is discussed in detail separately. (See "Ectopic pregnancy: Epidemiology, risk factors, and anatomic sites", section on 'Pelvic inflammatory disease and other genital infections'.)
In the prospective study of Swedish patients discussed above (see 'Infertility' above), patients with laparoscopically-confirmed PID compared with normal laparoscopic findings had a higher incidence of ectopic pregnancy for the first pregnancy after laparoscopy (7.8 versus 1.3 percent) [13]. The risk of ectopic pregnancy also increased with the number of episodes and severity of PID. For patients with one, two, and three episodes of PID, the ratio of ectopic pregnancy to intrauterine pregnancy was 1:15, 1:6, and 1:3, respectively. Similarly, for patients with a single episode of mild, moderate, or severe PID, the ratio of ectopic pregnancy to intrauterine pregnancy was 1:35, 1:25, and 1:5, respectively.
OVARIAN CANCER — The association between PID and ovarian cancer is unclear. In a meta-analysis of 16 cohort and case-control studies, PID was associated with an increased risk of ovarian cancer (hazard ratio [HR] 1.18, 95% CI 1.13-1.22) [24]. In one study included in this meta-analysis, patients with at least five episodes of PID had a particularly high risk (HR 2.46, 95% CI 1.48-4.09) [25]. Subanalyses also showed an increase in borderline ovarian tumors (HR 1.28, 1.19–1.37; two studies) and both serous and nonserous types. In a subsequent case-control study using data from several Swedish nationwide registries, patients with ovarian cancer compared with controls had higher rates of prior PID (adjusted odds ratio [OR] 1.39, 95% CI 1.17-1.66) [26].
However, it is not known whether PID is an independent risk factor for ovarian cancer as PID increases the risk of low parity and infertility, both of which are also risk factors for ovarian cancer [27]. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Incidence and risk factors", section on 'Nulliparity' and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Incidence and risk factors", section on 'Infertility and infertility treatment'.)
If PID increases the risk of ovarian cancer, management with salpingectomy likely decreases this risk. In a subsequent cohort using nationwide registry-based data and including almost 100,000 patients with PID, those managed without salpingectomy compared with controls had a higher risk of developing ovarian cancer (HR 1.44, 95% CI 1.31-1.59) [28]. By contrast, patients managed with salpingectomy compared with controls had a lower risk of ovarian cancer (HR 0.55, 95% CI 0.36-0.83). The latter finding is consistent with an abundance of data demonstrating that the fallopian tubes, rather than the ovaries, are the primary site of most epithelial ovarian, fallopian tube, and peritoneal carcinomas. (See "Opportunistic salpingectomy for ovarian, fallopian tube, and peritoneal carcinoma risk reduction", section on 'Role of the fallopian tube in carcinogenesis'.)
ENDOMETRIOSIS — A history of PID may be associated with endometriosis. In a meta-analysis of 14 studies (over 740,000 patients) evaluating the association between PID and endometriosis, those with versus without a history of PID had an increased risk of endometriosis (pooled odds ratio [OR] 2.7, 95% CI 1.87–3.9); the risk was also increased in a subgroup of patients with endometritis (OR 1.63, 95% CI 1.53-1.74; six studies) [29]. However, this analysis was limited by the heterogeneity of the included studies as well as a lack of consistent use of laparoscopy to confirm endometriosis. Given both PID and endometriosis cause pelvic pain, there is also the potential for misclassification.
PREVENTION — Prevention of PID and disease recurrence is important in reducing long-term sequelae [7,8,20].
●Condoms – Patients whose male partners consistently use condoms are less likely to acquire sexually transmitted infections (STIs), and develop recurrent PID or infertility [30]. In the PID evaluation and clinical health (PEACH) randomized trial, patients with PID who subsequently acquired a lower genital tract infection were 2.3 times more likely to develop chronic pelvic pain than those who did not (adjusted odds ratio [OR] 2.3, 95% CI 1.2-3.2) [8].
The use of male condoms for the prevention of STIs is discussed separately. (See "Prevention of sexually transmitted infections", section on 'Male condom use'.)
Other contraceptives may also reduce the risk of PID, but the evidence is less certain:
●Progestins – While progestin-based contraceptives do not protect from acquiring sexually transmitted infections, they may decrease the risk of PID. Progestin-induced thickening and increased viscosity of cervical mucus has been hypothesized to inhibit ascent of bacteria, thereby possibly providing an enhanced barrier against ascending infection. (See "Contraception: Progestin-only pills (POPs)", section on 'Impact on sexually transmitted infection acquisition'.)
●Intrauterine Devices – The risk of PID in intrauterine device (IUD) users is low, and the risk of PID in patients with chlamydia or gonorrhea using an IUD is similar to the risk of PID in patients with chlamydia or gonorrhea who are not using an IUD. While there is some evidence that the risk of STI acquisition is lower in copper IUD users compared to hormonal IUD users (OR 0.34, 95% CI 0.14-0.86), this finding was no longer statistically significant in the adjusted analysis [31].
The risks of PID in patients with an IUD, as well as management of patients with PID and an IUD, are discussed in detail separately. (See "Intrauterine contraception: Management of side effects and complications", section on 'Infection and/or pelvic inflammatory disease'.)
●Oral contraceptive pills – The protective role of oral contraceptives in the acquisition of PID is controversial, with some studies reporting that use of oral contraceptives confers a protective effect against the development of chlamydial PID [32,33], while others do not [34]. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Impact on STI acquisition'.)
Other prevention strategies to reduce STIs are discussed separately. (See "Prevention of sexually transmitted infections".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gynecologic infectious diseases (non-sexually transmitted)".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Pelvic inflammatory disease (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Clinical significance – Pelvic inflammatory disease (PID) refers to infection of the female upper genital tract leading to one or more of the following: endometritis, salpingitis, oophoritis, pelvic peritonitis, and perihepatitis. While prompt diagnosis and treatment are important to reduce the risk of both short- and long-term complications, long-term sequelae frequently occur. (See 'Introduction' above and 'Predictors and disease recurrence' above.)
●Recurrence – Patients with a history of PID are at increased risk of recurrence. Adolescents are more likely than adults to experience recurrence and have shorter times to recurrence. (See 'Predictors and disease recurrence' above.)
●Long-term sequalae – Major long-term complications of PID include:
•Chronic pelvic pain – As many as one-third of patients with PID develop chronic pelvic pain, defined as menstrual or non-menstrual pain of at least six months' duration that occurs below the umbilicus and is severe enough to cause functional disability. (See 'Chronic pelvic pain' above.)
•Tubal damage
-Hydrosalpinx – Patients with PID may develop a hydrosalpinx, a postinflammatory process in which the damaged fallopian tube can become blocked, fill with sterile fluid, and become enlarged. Even after PID resolves, the hydrosalpinx remains. (See 'Hydrosalpinx' above.)
-Infertility – PID can cause permanent injury to the fallopian tube, especially the endosalpinx. Risk factors for infertility after PID include presence of chlamydial or Mycoplasma genitalium infection, delay in initiating treatment, increased number of PID infections, and severity of infection. (See 'Infertility' above.)
-Ectopic pregnancy – Tubal damage caused by PID increases the risk of tubal pregnancy. (See 'Ectopic pregnancy' above.)
•Ovarian cancer – The association between PID and ovarian cancer is unclear; PID increases the risk of low parity and infertility, which are also risk factors for ovarian cancer. (See 'Ovarian cancer' above.)
•Endometriosis – A history of PID may be associated with endometriosis, however studies are limited, and both can cause chronic pelvic pain. (See 'Endometriosis' above.)
●Prevention – Patients whose male partners consistently use condoms are less likely to acquire sexually transmitted infections (STIs) and develop recurrent PID or infertility. Other contraceptives (eg, progestin-only, combined oral contraceptives) may also play a protective role in the acquisition of PID, but the evidence is less certain. (See 'Prevention' above.)
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