Infertility and chronic inflammation from subclinical pelvic inflammatory disease

Key points: (1) Subclinical (without apparent symptoms) pelvic inflammatory disease (PID) can cause infertility. (2) Pelvic inflammation can persist after PID has been treated. (3) Pelvic inflammation causing infertility can have an autoimmune component.A study just published in the journal Obstetrics & Gynecology brings to light that undetected pelvic inflammatory disease is common and a cause of infertility.The authors state:

"...a large proportion of PID leading to infertility may be undetected. Subclinical PID is common in women with uncomplicated chlamydial or gonococcal cervicitis or with bacterial vaginosis. We assessed whether women with subclinical PID are at an increased risk for infertility."

They examined 418 women with or at risk for gonorrhea or chlamydia or with bacterial vaginosis by endometrial biopsy to identify endometritis (subclinical PID). Anyone with acute PID was excluded. After any necessary treatment for gonorrhea, chlamydia or bacterial vaginosis was rendered, the subjects were followed-up for fertility outcomes. Their data showed the link between subclinical PID and infertility:

"There were 146 incident pregnancies during follow-up, 50 pregnancies in 120 (42%) women with subclinical PID and 96 in 187 (51%) women without subclinical PID. Women with subclinical PID diagnosed at enrollment had a 40% reduced incidence of pregnancy compared with women without subclinical PID. Women with Neisseria gonorrhoeae or Chlamydia trachomatis, in the absence of subclinical PID, were not at increased risk for infertility."

In other words, the persistent inflammation (endometritis) of subclinical PID was strongly associated with infertility with or without infection. The authors note an important point in their conclusion:

"Subclinical PID decreases subsequent fertility despite provision of treatment for sexually transmitted diseases. These findings suggest that a proportion of female infertility is attributable to subclinical PID and indicate that current therapies for sexually transmitted diseases are inadequate for prevention of infertility."

Perusal of the literature yields a multitude of scientific papers that address the topics of autoimmune oopheritis (inflammation of the ovary) and autoimmune disruption of the pituitary-ovarion axis, both causing premature ovarian failure (POF); and the autoimmune dimension of endometriosis and chronic pelvic pain in both sexes. This amounts to a wealth of data demonstrating autoimmune inflammation of the pelvic and reproductive tissues. In light of this and the association of subclinical PID and infertility it is of great interest to consider a paper published in Current Topics in Microbiology and Immunology in which the authors how chlamydia infections can trigger autoimmune diseases through molecular mimicry. The authors observe:

"Chlamydial infections are among the most common human infections...Chlamydia infections often precede the initiation of autoimmune diseases, and Chlamydiae are often found within autoimmune lesions. Thus, they have been suspected in the etiology and pathogenesis of autoimmune diseases."

In fact there is a wealth of evidence implicating infections as triggers of autoimmune disease. They discuss mechanisms specific to chlamydia:

"One mechanism by which infection is linked to the initiation of autoimmunity is termed molecular mimicry. Molecular mimicry describes the phenomenon of protein products from dissimilar genes sharing similar structures that elicit an immune response to both self and microbial proteins...we will focus on chlamydial proteins that mimic host self-proteins and thus contribute to initiation and maintenance of autoimmune diseases. Thus far, the strongest cases for molecular mimicry seem to have been made for chlamydial heat shock proteins 60, the DNA primase of Chlamydia trachomatis, and chlamydial OmcB proteins."

Clinical significance: It would be prudent for practitioners to bear in mind that subclinical, asymptomatic pelvic inflammatory disease with an autoimmune component can persist after pathogen elimination and be a cause of infertility.