Unrecognized pelvic inflammatory disease (PID) may be a major factor in the pathogenesis of tubal factor infertility. This is supported by the presence of serologic evidence of prior sexually transmitted diseases (STD's) in a large proportion of women with tubal factor infertility, yet most of these women do not recall a history of STD's or PID. In addition, many women with lower genital tract infection associated with STD's (gonorrhea, chlamydia, bacterial vaginosis) have histologic evidence of endometritis even though they do not have symptoms of PID. Our hypothesis is that unrecognized PID due to STD's is associated with tubal obstruction. We propose to test this hypothesis in a cohort of 1500 women aged 15-30 with lower genital tract STD associated infection. A group of 200 women with acute symptomatic PID will be evaluated for comparison. Specimens will be obtained from the vagina and cervix for microbiologic analysis and measurement of defensins (neutrophil granule products). An endometrial biopsy will be obtained for histologic and microbiologic analysis. The primary outcome of this study is tubal impatency, therefore all women will undergo a hysterosalpingogram 12 weeks from enrollment. Other outcomes include infertility and ectopic pregnancy formation, which will be determined using regular telephone contact for at least one year to determine the rate of adverse reproductive sequelae. The frequency of tubal impatency will be compared between women with acute symptomatic PID, women with unrecognized PID, and uninfected women. The risk of unrecognized PID will be compared between women testing positive for an STD and uninfected women. As the diagnostic accuracy for the diagnosis of PID is currently suboptimal, risk factors for unrecognized PID will be established, a clinical prediction model will be devised, and defensins from the lower genital tract will be evaluated as less-invasive markers of PID. The microbiology and histology of unrecognized PID will be compared to these findings in acute PID, in an effort to understand the pathogenesis of PID. Information obtained from this study will: i) determine the role of unrecognized PID in subsequent tubal damage ii) establish risk factors and predictors of PID iii)improve the understanding of the pathogenesis of PID. Earlier detection of unrecognized PID will enable more timely treatment, with the intent on reducing the rate of tubal impatency and resultant adverse reproductive sequelae.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Bacteriology and Mycology Subcommittee 2 (BM)
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Magee-Women's Hospital of Upmc
United States
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Austin, Michele N; Rabe, Lorna K; Srinivasan, Sujatha et al. (2015) Mageeibacillus indolicus gen. nov., sp. nov.: a novel bacterium isolated from the female genital tract. Anaerobe 32:37-42
Wiesenfeld, Harold C; Hillier, Sharon L; Meyn, Leslie A et al. (2012) Subclinical pelvic inflammatory disease and infertility. Obstet Gynecol 120:37-43
Gursahaney, Priya R; Meyn, Leslie A; Hillier, Sharon L et al. (2010) Combined hormonal contraception may be protective against Neisseria gonorrhoeae infection. Sex Transm Dis 37:356-60
Cherpes, Thomas L; Wiesenfeld, Harold C; Melan, Melissa A et al. (2006) The associations between pelvic inflammatory disease, Trichomonas vaginalis infection, and positive herpes simplex virus type 2 serology. Sex Transm Dis 33:747-52
Wiesenfeld, Harold C; Sweet, Richard L; Ness, Roberta B et al. (2005) Comparison of acute and subclinical pelvic inflammatory disease. Sex Transm Dis 32:400-5
Cherpes, Thomas L; Meyn, Leslie A; Hillier, Sharon L (2003) Plasma versus serum for detection of herpes simplex virus type 2-specific immunoglobulin G antibodies with a glycoprotein G2-based enzyme immunoassay. J Clin Microbiol 41:2758-9
Yudin, Mark H; Hillier, Sharon L; Wiesenfeld, Harold C et al. (2003) Vaginal polymorphonuclear leukocytes and bacterial vaginosis as markers for histologic endometritis among women without symptoms of pelvic inflammatory disease. Am J Obstet Gynecol 188:318-23
Wiesenfeld, Harold C; Hillier, Sharon L; Krohn, Marijane A et al. (2003) Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis 36:663-8
Wiesenfeld, Harold C; Hillier, Sharon L; Krohn, Marijane A et al. (2002) Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Obstet Gynecol 100:456-63
Wiesenfeld, Harold C; Heine, R Phillip; Krohn, Marijane A et al. (2002) Association between elevated neutrophil defensin levels and endometritis. J Infect Dis 186:792-7