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 frequently occur; this is thought to be secondary to the scarring and adhesion formation that accompany healing of infection-damaged tissues. These sequelae (chronic pelvic pain, infertility, and ectopic pregnancy) account for much of the morbidity, suffering, and cost of PID [2]. One group estimated that a cohort of 100,000 females acquiring PID between 20 and 24 years of age would go on to have 18,600 cases of chronic pelvic pain; 16,800 cases of infertility; and 8550 ectopic pregnancies [3].
Long-term complications of PID will be reviewed here; other issues related to this disorder 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".)
RECURRENT PELVIC INFLAMMATORY DISEASE — Women with a history of PID are at increased risk of recurrence. As an example, a study of primarily low income African American women with mild-moderate PID found that 15 percent reported a recurrence within 35 months and 21 percent reported a recurrence within 84 months. In the adjusted analysis, adolescents were 50 percent more likely than adult women to experience a recurrence [4]. Other populations may have lower or higher recurrence risks.
HYDROSALPINX — After PID resolves, the damaged fallopian tube can become blocked, fill with sterile fluid, and become enlarged. 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 except for tubal factor infertility.
Hydrosalpinx in patients undergoing in vitro fertilization (IVF) has negative consequences on the rates of pregnancy, implantation, early pregnancy loss, preterm birth, and live delivery [5,6].
CHRONIC PELVIC PAIN — Chronic pelvic pain is defined as menstrual or nonmenstrual pain of at least six months' duration that occurs below the umbilicus and is severe enough to cause functional disability. As many as one-third of women with PID develop chronic pelvic pain [7,8]. 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'.)
A study of risk factors for chronic pelvic pain in women with symptoms and signs of PID found recurrent PID was the strongest predictor for the development of this type of pain (odds ratio [OR] 2.84, 95% CI 1.07-7.54) [9]. Other risk factors included non-Black race, married status, smoking, and poor mental health score.
A case-control study identified a correlation between a history of PID and painful bladder syndrome (OR 3.69, 95% CI 2.89-4.71), suggesting that painful bladder syndrome may be a sequelae of PID [10]. (See "Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis", section on 'Pathogenesis'.)
INFERTILITY — Both symptomatic and asymptomatic 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, lead to tubal infertility [11]. There may be additional mechanisms of infertility, as well.
Subclinical PID, defined as histologic endometritis with no symptoms of acute PID, appears to decrease subsequent fertility, even in patients who are treated for chlamydia, gonorrhea, and bacterial vaginosis [12]. Treatment of cervicitis without endometritis does not appear to have this effect.
The prevalence of infertility after acute PID depends upon multiple factors (discussed below), but appears to be increased severalfold. This was illustrated by a prospective cohort study of 2501 Swedish women with suspected PID who underwent diagnostic laparoscopy and were followed for as long as 25 years [13]. Among women desiring pregnancy, 16 percent of those with laparoscopically-confirmed PID (group 1) and 2.7 percent of those with normal laparoscopic findings (group 2) failed to conceive. Tubal factor accounted for 67.6 percent of infertility diagnoses, but was not a cause of infertility in any woman in group 2.
Risk factors
●Chlamydial infection – Among the microorganisms that cause PID, Chlamydia trachomatis appears to carry the greatest risk of infertility. Approximately one in four women with tubal factor infertility seeking care in an infertility clinic has serum antibodies to C. trachomatis [14] and serum titers of C. trachomatis antibodies correlate inversely with pregnancy rates [14,15]. In one study, the pregnancy rates in women with the highest and lowest titers were 59 and 73 percent, respectively, seven years postinfection [16].
These data suggest that infertility after PID may result, at least in part, from the host's immune response to chlamydial infection. A high titer may be associated with a greater inflammatory response.
●Delay in seeking care for PID – In one study, women with PID who delayed seeking treatment for three or more days were threefold more likely to be diagnosed with infertility than women who sought care in a timely manner [17]. In women with chlamydial infection, 17.8 percent of those who delayed seeking care had impaired fertility, whereas none of those who sought care promptly suffered sequelae.
●Increasing number of PID episodes – A classic review found that pregnancy rates after one, two, or three or more episodes of PID were 89, 77, and 46 percent, respectively [18].
●Severity of infection – The cumulative proportions of women achieving a livebirth after mild, moderate, and severe PID were 90, 82, and 57 percent, respectively [19].
ECTOPIC PREGNANCY — Tubal damage caused by PID increases the risk of tubal pregnancy, as well as infertility. The increased expression of certain proteins involved in implantation may play a role in the pathophysiology [20]. (See "Ectopic pregnancy: Epidemiology, risk factors, and anatomic sites".)
In the prospective Swedish cohort study discussed above [13], the incidence of ectopic pregnancy in the first pregnancy after laparoscopically-confirmed PID was 7.8 percent versus 1.3 percent in women without PID at laparoscopy. The risk of ectopic pregnancy increased with the number of episodes and severity of PID:
●After one, two, and three episodes of PID, the ratio of ectopic pregnancy to intrauterine pregnancy was 1:15, 1:6, and 1:3, respectively.
●In women 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. A meta-analysis of 16 studies investigating PID and ovarian cancer risk reported a positive association (hazard ratio [HR] 1.18, 95% CI 1.13-1.22) [21]. One of the included studies looked at the effect of number of PID episodes and found that women with multiple episodes of PID had a particularly high risk (HR 2.46, 95% CI 1.48-4.09 for women who had at least five episodes of PID) [22]. Although a pooled analysis of 13 case-control studies found an association between PID and increased risk of borderline ovarian tumors (pooled odds ratio [OR] 1.32, 95% CI 1.10-1.58), it found no increased risk for ovarian cancer overall (pooled OR 0.99, 95% CI 0.83-1.19) [23].
It is not known whether PID is an independent risk factor for ovarian cancer since PID increases the risk of low parity, nulliparity, nulligravidity, and infertility, which are also risk factors for ovarian cancer [24].
PREDICTION AND PREVENTION OF LONG-TERM SEQUELAE — Signs and symptoms associated with acute PID are poor predictors of the eventual development of chronic sequelae [25]. Furthermore, clinical and/or microbiologic cure of acute disease does not preclude development of the long-term complications described above. Therefore, clinicians should not assume that women with a complete recovery from PID have avoided the increased risk of long-term complications.
As discussed above, recurrent PID is associated with an almost twofold increase in infertility and more than fourfold increase in chronic pelvic pain; therefore, prevention of recurrent disease is important [9,18,26]. Options to reduce the risk of recurrence include:
●Condoms – Women whose partners consistently use condoms are less likely to develop recurrent PID or infertility [27]. In addition, condom use protects against acquisition of sexually transmitted infections, and in the PEACH trial, women 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 2.3, 95% CI 1.2-3.2) [26].
●Progestins – Progestin-based contraceptives may decrease the risk of PID because progestin thickens cervical mucus, thereby possibly providing an enhanced barrier against ascending infection.
●Oral contraceptive pills – The protective role of oral contraceptives in the acquisition of PID is controversial; some studies found the use of oral contraceptives conferred a protective effect against the development of chlamydial PID [28,29], while others did not [30].
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
●The major long-term complications of pelvic inflammatory disease (PID) are chronic pelvic pain, infertility, ectopic pregnancy, and possibly ovarian cancer. Treatment of PID may not prevent long-term sequelae because of the scarring and adhesion formation that accompany healing of infection-damaged tissues. (See 'Introduction' above.)
●The risk of complications increases with the number of episodes and severity of PID. (See 'Chronic pelvic pain' above and 'Infertility' above and 'Ectopic pregnancy' above.)
●Risk factors for infertility after PID include the number of infections, the severity of infection, presence of chlamydial infection, and delay in initiating treatment. (See 'Infertility' above.)
