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I commend the effort required to undertake a modestly large trial to alter the vaginal microbiome.[1] Its aim was to reduce preterm birth, the single most important and unsolved issue in obstetrics. Very early preterm birth, before 34 weeks of gestation, is strongly linked to an ascending chorioamnionitis infection with resulting inflammation from vaginal bacteria, particularly with bacterial vaginosis (BV). Hence, it may be more efficient to attempt BV prevention after treatment among those shown to have a propensity to develop BV than to use a I Lactobacillus i probiotic in those with and without BV. [Extracted from the article]

Many cases of mucopurulent cervicitis (MPC) are idiopathic and cannot be attributed to the known cervical pathogens Neisseria gonorrhoeae, Chlamydia trachomatis, or herpes simplex virus. Because Mycoplasma genitalium is associated with nongonoccocal urethritis in men, its role in MPC, the corresponding syndrome in women, was investigated. Archived cervical specimens from women recruited in the Harborview Sexually Transmitted Disease Clinic in Seattle from 1984 to 1986 were tested, using polymerase chain reaction, in a study that identified other causes of and risk factors for MPC. M. genitalium was detected in 50 (7.0%) of 719 women. Young age, multiple recent partners, prior miscarriage, smoking, menstrual cycle, and douching were positively associated with M. genitalium, whereas bacterial vaginosis and cunnilingus were negatively associated. After adjustment for age, phase of menstrual cycle, and presence of known cervical pathogens, women with M. genitalium had a 3.3-fold greater risk (95% confidence interval, 1.7-6.4) of MPC, which suggests that this organism may be a cause of MPC. [ABSTRACT FROM AUTHOR]

Abstract Background Gingivitis has been linked to adverse pregnancy outcome (APO). Bacterial vaginosis (BV) has been associated with APO. We assessed if bacterial counts in BV is associated with gingivitis suggesting a systemic infectious susceptibilty. Methods Vaginal samples were collected from 180 women (mean age 29.4 years, SD ± 6.8, range: 18 to 46), and at least six months after delivery, and assessed by semi-quantitative DNA-DNA checkerboard hybridization assay (74 bacterial species). BV was defined by Gram stain (Nugent criteria). Gingivitis was defined as bleeding on probing at ≥ 20% of tooth sites. Results A Nugent score of 0–3 (normal vaginal microflora) was found in 83 women (46.1%), and a score of > 7 (BV) in 49 women (27.2%). Gingivitis was diagnosed in 114 women (63.3%). Women with a diagnosis of BV were more likely to have gingivitis (p = 0.01). Independent of gingival conditions, vaginal bacterial counts were higher (p < 0.001) for 38/74 species in BV+ in comparison to BV- women. Counts of four lactobacilli species were higher in BV- women (p < 0.001). Independent of BV diagnosis, women with gingivitis had higher counts of Prevotella bivia (p < 0.001), and Prevotella disiens (p < 0.001). P. bivia, P. disiens, M. curtisii and M. mulieris (all at the p < 0.01 level) were found at higher levels in the BV+/G+ group than in the BV+/G- group. The sum of bacterial load (74 species) was higher in the BV+/G+ group than in the BV+/G- group (p < 0.05). The highest odds ratio for the presence of bacteria in vaginal samples (> 1.0 × 104 cells) and a diagnosis of gingivitis was 3.9 for P. bivia (95% CI 1.5–5.7, p < 0.001) and 3.6 for P. disiens (95%CI: 1.8–7.5, p < 0.001), and a diagnosis of BV for P. bivia (odds ratio: 5.3, 95%CI: 2.6 to 10.4, p < 0.001) and P. disiens (odds ratio: 4.4, 95% CI: 2.2 to 8.8, p < 0.001). Conclusion Higher vaginal bacterial counts can be found in women with BV and gingivitis in comparison to women with BV but not gingivitis. P. bivia and P. disiens may be of specific significance in a relationship between vaginal and gingival infections.

Background: Bacterial vaginosis is believed to be a risk factor for preterm delivery. We undertook a study of the association between bacterial vaginosis and the preterm delivery of infants with low birth weight after accounting for other known risk factors.Methods: In this cohort study, we enrolled 10,397 pregnant women from seven medical centers who had no known medical risk factors for preterm delivery. At 23 to 26 weeks' gestation, bacterial vaginosis was determined to be present or absent on the basis of the vaginal pH and the results of Gram's staining. The principal outcome variable was the delivery at less than 37 weeks' gestation of an infant with a birth weight below 2500 g.Results: Bacterial vaginosis was detected in 16 percent of the 10,397 women. The women with bacterial vaginosis were more likely to be unmarried, to be black, to have low incomes, and to have previously delivered low-birth-weight infants. In a multivariate analysis, the presence of bacterial vaginosis was related to preterm delivery of a low-birth-weight infant (odds ratio, 1.4; 95 percent confidence interval, 1.1 to 1.8). Other risk factors that were significantly associated with such a delivery in this population were the previous delivery of a low-birth-weight infant (odds ratio, 6.2; 95 percent confidence interval, 4.6 to 8.4), the loss of an earlier pregnancy (odds ratio, 1.7; 1.3 to 2.2), primigravidity (odds ratio, 1.6; 1.1 to 1.9), smoking (odds ratio, 1.4; 1.1 to 1.7); and black race (odds ratio, 1.4; 1.1 to 1.7). Among women with bacterial vaginosis, the highest risk of preterm delivery of a low-birth-weight infant was found among those with both vaginal bacteroides and Mycoplasma hominis (odds ratio, 2.1; 95 percent confidence interval, 1.5 to 3.0).Conclusions: Bacterial vaginosis was associated with the preterm delivery of low-birth-weight infants independently of other recognized risk factors. [ABSTRACT FROM AUTHOR]

Localized provoked vulvodynia (LPV) causes dyspareunia among reproductive aged women. We review the pathogenesis of LPV and suggest that LPV is an inflammatory pain syndrome of the vestibular mucosa triggered by microbial antigens in a susceptible host. Tissue inflammation and hyperinnervation are characteristic findings which explain symptoms and clinical signs. Education of health care providers of LPV is important since this condition is common, often unrecognized, and patients often become frustrated users of health care. Research is needed on the antigen triggers of the syndrome. Randomized clinical trials are needed to evaluate treatment modalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Paavonen and Eschenbach.)

Importance: Genital lichen planus is a debilitating disorder that lacks definitive recommendations regarding diagnosis and treatment., Objective: The aim of this study was to present best practices from available evidence for the diagnosis and treatment of genital lichen planus., Evidence Acquisition: We conducted a narrative review of the literature on genital lichen planus by searching PubMed using the following search terms: "vulvar lichen planus" OR (vulvar diseases[mesh] OR vulva[mesh]) AND lichen planus[mesh] OR vulvar[ti] AND "lichen planus"[ti]. We included all languages and years in the search., Results: The search resulted in 273 citations that we reviewed for relevancy and selected 60 as the foundation for this review that focuses on genital sites. Diagnosis can be made without biopsy, and when a biopsy is taken, the pathologic findings may be nonspecific. Topical ultrapotent corticosteroids are most commonly used as first-line treatment of genital lichen planus., Conclusions and Relevance: When patients present with genital lichen planus, a complete review of systems and a thorough physical examination should be performed because of the prevalence of extragenital sites. Treatment of genital disease should start with a topical, ultrapotent steroid, and follow-up visits should occur to ensure improvement and to monitor for adverse drug reactions and malignancy.

Objective: Microbial invasion of the amniotic cavity is associated with spontaneous preterm labor and adverse pregnancy outcome, and Mycoplasma hominis often is present. However, the pathogenic process by which M hominis invades the amniotic cavity and gestational tissues, often resulting in chorioamnionitis and preterm birth, remains unknown. We hypothesized that strains of M hominis vary genetically with regards to their potential to invade and colonize the amniotic cavity and placenta., Study Design: We sequenced the entire genomes of 2 amniotic fluid isolates and a placental isolate of M hominis from pregnancies that resulted in preterm births and compared them with the previously sequenced genome of the type strain PG21. We identified genes that were specific to the amniotic fluid/placental isolates. We then determined the microbial burden and the presence of these genes in another set of subjects from whom samples of amniotic fluid had been collected and were positive for M hominis., Results: We identified 2 genes that encode surface-located membrane proteins (Lmp1 and Lmp-like) in the sequenced amniotic fluid/placental isolates that were truncated severely in PG21. We also identified, for the first time, a microbial gene of unknown function that is referred to in this study as gene of interest C that was associated significantly with bacterial burden in amniotic fluid and the risk of preterm delivery in patients with preterm labor., Conclusion: A gene in M hominis was identified that is associated significantly with colonization and/or infection of the upper reproductive tract during pregnancy and with preterm birth., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Worldwide, abortion accounts for approximately 14% of pregnancy-related deaths, and septic abortion is a major cause of the deaths from abortion. Today, septic abortion is an uncommon event in the United States. The most critical treatment of septic abortion remains the prompt removal of infected tissue. Antibiotic administration and fluid resuscitation provide necessary secondary levels of treatment. Most young physicians have never treated septic abortion. Many obstetrician-gynecologists experience, or plan to experience, global health activities and will likely care for women with septic abortion. Thus, updated knowledge of the pathophysiology, clinical presentation, microbes, and proper treatment is needed to optimally treat this emergency condition when it exists. The pathophysiology of septic abortion involves infection of the placenta, especially the maternal villous space that leads to a high frequency of bacteremia. Symptoms and signs range from mild to severe. The microbes involved are usually common vaginal bacteria, including anaerobes, but occasionally potentially very serious and lethal infection is caused by bacteria that produce toxins. The primary treatment is early curettage to remove infected and devitalized tissue even in the face of continued fetal heart tones. Important secondary treatments are the administration of fluids and antibiotics. Updated references of sepsis and septic shock are reviewed.

Preterm premature rupture of membranes (PPROM) occurs in 1% to 2% of births. Impact of PPROM is greatest in low- and middle-income countries where prematurity-related deaths are most common. Recent investigations identify cytokine and matrix metalloproteinase activation, oxidative stress, and apoptosis as primary pathways to PPROM. These biological processes are initiated by heterogeneous etiologies including infection/inflammation, placental bleeding, uterine overdistention, and genetic polymorphisms. We hypothesize that pathways to PPROM overlap and act synergistically to weaken membranes. We focus our discussion on membrane composition and strength, pathways linking risk factors to membrane weakening, and future research directions to reduce the global burden of PPROM., (© The Author(s) 2014.)

Group A streptococcal (GAS) infections continue to be an infrequent, but potentially lethal infections in women despite the victory over childbed fever in the 1800s. Invasive group A streptococcal infection still causes 40% of septic deaths among patients with postpartum endometritis, necrotizing fasciitis, and toxic shock syndrome. Many times symptoms and signs of this infection are nonspecific, but laboratory evaluation can suggest serious infection. The prudent combination of antibiotic and surgical therapy can be lifesaving.

Background: Preterm birth is a major societal and economic problem accounting for 80 to 90% of neonatal morbidity and mortality worldwide. It is recognized as a complex multifactorial condition comprising several distinct clinical phenotypes with different underlying etiologies. As animal models are expensive and fail to mimic the biology of spontaneous preterm birth in humans, understanding the pathophysiology requires detailed clinical studies. Meta-analyses and clinical translation of data, however, are limited by heterogeneity of study design and size, publication and reporting biases, definition of patient groups, and a lack of standard universal definitions. This article provides a harmonized open-source template for designing clinical studies addressing preterm birth., Methods: Recommendations are made for clinical definitions, choice and assignment to preterm birth phenotypes, selection of enriched populations and control pregnancies, and potential confounding factors. In addition, recommendations are made for study design, sample size and power calculations, the minimal data sets needed for any study of preterm birth, and the optimal data set of an ideal study., Results: Recommended patient phenotypes are infection, uterine overdistension, hemorrhage, stress (either maternal or fetal), and idiopathic. Confounding factors include medical conditions, obesity, antenatal glucocorticoids, multifetal pregnancies, and fetal sex. Guidelines regarding study design, sample size, and clinical data acquisition are provided to serve as a universal template for preterm birth studies., Conclusions: Adoption of a harmonized template will allow generation of protocols and studies with a basic degree of compatibility and will allow data to be compared, and samples and data sets to be combined for meaningful meta-analyses.

Background: We evaluated predictors of consistent condom use among female sex workers (FSWs), a core group for controlling the spread of HIV., Methods: In an analysis of data collected in 2004-2005 from 140 Kenyan FSWs who completed questionnaires administered during a baseline study visit and three bimonthly follow-up visits, we used a case-crossover design to identify predictors of consistent condom use during all coital acts in the preceding 2 weeks, overall and by partner type., Results: Participants (n=140) completed the baseline visit and 390 bimonthly follow-up visits. Alcohol use during sex was negatively associated with consistent condom use with helping partners (defined as regular sex partners to whom the woman could go for help or support if needed) (adjusted odds ratio [AOR], 2.6, 95% confidence interval [CI] 1.0-6.5) but not associated with condom use with other partners. Coital frequency was associated with condom use with other partners only. Women who reported 1-5 (AOR 11.0, 95% CI 4.3-28.3) or 6-9 recent coital acts (AOR 3.8, 95% CI 1.7-8.8) with other partners were more likely to report consistent condom use with those partners than were women who reported ≥10 acts. Having a recent partner delay payment was inversely associated with consistent condom use with helping, other, or all partners., Conclusions: Correlates of consistent condom use differed by partner type. By using a case-crossover design, we were able to identify potentially modifiable factors associated with consistent condom use by FSWs who used condoms consistently with a given partner type during some periods but not others.

Objective: An outbreak of 20 peripartum Clostridium difficile infections (CDI) occurred on the obstetrical service at the University of Washington Medical Center (UWMC) between April 2006 and June 2007. In this report, we characterize the clinical manifestations, describe interventions that appeared to reduce CDI, and determine potential risk factors for peripartum CDI., Methods: An investigation was initiated after the first three peripartum CDI cases. Based on the findings, enhanced infection control measures and a modified antibiotic regimen were implemented. We conducted a case-control study of peripartum cases and unmatched controls., Results: During the outbreak, there was an overall incidence of 7.5 CDI cases per 1000 deliveries. Peripartum CDI infection compared to controls was significantly associated with cesarean delivery (70% versus 34%; P=0.03), antibiotic use (95% versus 56%; P=0.001), chorioamnionitis (35% versus 5%; P=0.001), and the use of the combination of ampicillin, gentamicin, and clindamycin (50% versus 3%; P<0.001). Use of combination antibiotics remained a significant independent risk factor for CDI in the multivariate analysis., Conclusions: The outbreak was reduced after the implementation of multiple infection control measures and modification of antibiotic use. However, sporadic CDI continued for 8 months after these measures slowed the outbreak. Peripartum women appear to be another population susceptible to CDI.

Changes in the rates of condom use and number of sexual partners were evaluated among 140 female sex workers in Kibera, Kenya, participating in a 6-month study of diaphragm safety and acceptability for prevention of sexually transmitted infections conducted in 2004-2005. Analyses were stratified by partner type. Multivariable Tobit regression modeling was used to assess the association between study visit and proportion of acts protected. Participants completed 140 baseline visits and 390 bimonthly follow-up visits. The mean percentage of coital acts reported as protected by a condom increased from 56% at baseline to 68% at the 6-month visit (P < 0.01). Similar increases were observed for condom use by all partner types. Additionally, the mean number of sexual partners decreased over the study. Furthermore, consistent (i.e., 100%) diaphragm use during follow-up was associated with a higher proportion of coital acts protected by a condom in analyses adjusted for study visit and coital frequency. These findings suggest that, despite concerns that introduction of the diaphragm would result in more risky sexual behaviors, reported condom use increased and number of partners decreased.

Objectives: To assess vaginal cleansing and lubricant use among female sex workers (FSW) in Kenya participating in a 6-month, prospective study of the acceptability of the use of the diaphragm., Methods: The study is based on 140 FSW in Nairobi, who completed 140 baseline visits and 390 bi-monthly follow-up visits. Participants were instructed to wear the diaphragm for all coital acts during follow-up and to refrain from vaginal cleansing while wearing the diaphragm. Logistic regression was used to identify predictors of recent vaginal cleansing to 'tighten' the vagina reported at baseline; recent vaginal cleansing to prevent infection reported at baseline; recent vaginal cleansing with the diaphragm in place reported during follow-up; and recent use of oil-based lubricant during coitus reported at baseline., Results: At baseline, 99% of women reported vaginal cleansing in the previous 2 weeks for purposes of hygiene or to remove evidence of past coitus. Approximately 41% of women also reported cleansing in the past 2 weeks to 'tighten' the vagina. Women reported vaginal cleansing with the diaphragm in place in the past 2 weeks at 14% of follow-up visits in which the diaphragm was used. Predictors of such cleansing included young age, 6-month study visit, being divorced or widowed and higher educational level., Conclusions: While vaginal cleansing is a modifiable behaviour, given that cleansing for hygiene was almost universal among this study population at baseline and that more women reported cleansing while wearing the diaphragm as the study progressed, the complete eradication of the practice would probably be difficult.

Objective: We analyzed the vaginal fluid proteome to identify biomarkers of intraamniotic infection among women in preterm labor., Study Design: Proteome analysis was performed on vaginal fluid specimens from women with preterm labor, using multidimensional liquid chromatography, tandem mass spectrometry, and label-free quantification. Enzyme immunoassays were used to quantify candidate proteins. Classification accuracy for intraamniotic infection (positive amniotic fluid bacterial culture and/or interleukin-6 >2 ng/mL) was evaluated using receiver-operator characteristic curves obtained by logistic regression., Results: Of 170 subjects, 30 (18%) had intraamniotic infection. Vaginal fluid proteome analysis revealed 338 unique proteins. Label-free quantification identified 15 proteins differentially expressed in intraamniotic infection, including acute-phase reactants, immune modulators, high-abundance amniotic fluid proteins and extracellular matrix-signaling factors; these findings were confirmed by enzyme immunoassay. A multi-analyte algorithm showed accurate classification of intraamniotic infection., Conclusion: Vaginal fluid proteome analyses identified proteins capable of discriminating between patients with and without intraamniotic infection., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Female sex workers (n = 140) were enrolled in a 6-month acceptability trial of the diaphragm. We randomized a subset (n = 40) to receive colposcopies after 1 month of diaphragm use or after 1 month of observation before commencing diaphragm use. Adverse events were mild in nature. Frequency of colposcopic findings did not differ between women randomized to immediate versus delayed diaphragm use (P = 0.25).

Objective: To assess adherence to and acceptability of the diaphragm among 140 female sex workers in Kenya in a 6-month prospective study., Methods: At baseline and bimonthly visits, participants were interviewed on diaphragm knowledge, attitude, and practices. We used principal component analysis and logistic regression to identify predictors of consistent use., Results: At 50% of 386 bimonthly visits, women reported consistently using a diaphragm with all partners during the preceding 2 weeks. Consistent use was significantly higher at the 6-month than the 2-month visit. Women reported less covert use with "helping" (regular sex partners to whom she could go for help or support) than with "other" partners. Perceptions that diaphragms are easier to use than condoms and that their lack of coital interruption is important were associated with consistent diaphragm use with both partner types. Partner support of diaphragm use is correlated with consistent use with "helping" partners only while higher parity, consistent condom use, and perceived lack of need of condoms as a benefit of diaphragms were associated with consistent use with "other" partners., Conclusions: Diaphragm acceptance among female sex workers in Nairobi was high. Future studies should distinguish between partner types when evaluating diaphragm adherence.

The objective of this study was to examine the associations between lower genital tract infection, racial group and preterm birth in the Vaginal Infections and Prematurity Study, a large prospective cohort study conducted between 1984 and 1989. This analysis included 11 910 women enrolled at 23-26 weeks' gestation with equal representation from self-identified African American, Hispanic and white women. Subjects were screened for Chlamydia trachomatis, Trichomonas vaginalis and bacterial vaginosis at study entry, and their pregnancy outcomes were ascertained after delivery. The primary outcome of interest was preterm delivery of a low-birthweight infant (<37 weeks and <2500 g). The associations between lower genital tract infection and preterm delivery of a low-birthweight infant were examined within each racial group, with adjustment for potential confounders using multivariable logistic regression. In this cohort, 6.4% of African Americans, 3.8% of Hispanics, and 4.4% of whites had a preterm delivery of a low-birthweight infant (P < 0.001). Lower genital tract infection was significantly associated with preterm delivery of a low-birthweight infant among African Americans, but not among other racial groups. The proportion of preterm birth associated with lower genital tract infection was 21% among African Americans and 5% among whites. The increase in infection-associated preterm birth among African Americans appears to be related both to an increased prevalence of lower genital tract infection, and also to an increased risk of preterm delivery of a low-birthweight infant in the context of lower genital tract infection.

Indirect evidence supports a possible genetic predisposition towards preterm birth. The recurrence of spontaneous preterm delivery in individual women, families and ethnic groups suggests a long-acting aetiology, consistent with a genetic factor. Genetic contributions from both mother and fetus probably play a role in determining gestational length. Preliminary genetic association studies implicate gene variants of tumor necrosis factor-alpha (TNF-alpha) in preterm birth. Further understanding of a genetic predisposition begins with investigation of the pathogenesis of preterm delivery. Technological advances in the study of the human genome (genomics) and protein complement (proteomics) will allow identification of novel genes and proteins involved in preterm delivery. Insight into the complex gene regulation and protein production in preterm delivery may contribute to an understanding of a genetic basis. A discovered genetic factor may lead to medical breakthroughs and reductions in prematurity, neonatal morbidity and mortality.

Objective: Two single-base polymorphisms of the tumor necrosis factor-alpha gene (TNF-alpha) at positions -863 and -308 are associated with variation in production of TNF-alpha (TNF-alpha). TNF-alpha genotypes were tested for association with adverse outcomes in mother-infant pairs with preterm labor., Study Design: We analyzed a cohort of 118 mother-infant pairs with preterm labor before 34 weeks' gestation. Polymerase chain reaction was used on extracted deoxyribonucleic acid for polymorphism assay. Outcomes included amniotic fluid TNF-alpha concentration, histologic chorioamnionitis, delivery gestational age, and composite neonatal morbidity. Statistical significance was determined by chi 2 and Kruskal-Wallis analysis of variance., Results: Mothers homozygous for the -863 polymorphism (AA) had significantly earlier deliveries ( P = .02), more chorioamnionitis ( P = .03), and greater composite neonatal morbidity ( P = .03). Neither maternal nor fetal carriage of the -308 polymorphism was associated with adverse outcome., Conclusion: In women with preterm labor before 34 weeks' gestation, maternal homozygous carriage of the -863 polymorphism may be associated with preterm delivery and adverse neonatal outcome.

Objective: To evaluate the efficacy of metronidazole to reduce post-abortion complications among women with bacterial vaginosis., Design: A randomised, double-blind placebo-controlled trial., Setting: An American outpatient abortion facility between April 1999 and June 2000., Sample: Women presenting for surgical abortion were screened for bacterial vaginosis using a pH and amines card test., Methods: Women positive for elevated pH and amines on a self-collected vaginal discharge sample were randomised to 1000 mg oral metronidazole before abortion followed by 500 mg twice daily or placebo. All randomised women were also dispensed 100 mg doxycycline to take twice daily for seven days., Main Outcome Measures: Data were collected by phone, daily diary or visit and scored from 0 to 7 for post-abortion complications. Intention-to-treat analyses were completed prior to unblinding., Results: Of 1764 women screened by card test, 638 (36%) were positive. Of these, 393 were randomised. Follow up data were available for 253 (64%) of these women. A complication score of 3 or more occurred in 21% of women assigned to metronidazole, compared with 19% in those assigned placebo (RR 1.1, 95% CI 0.7-1.9). Among 153 women with Gram stain confirmation for bacterial vaginosis, there was a similar lack of benefit with treatment (RR 1.6, 95% CI 0.9-3.0). No individual symptom or sign was statistically different between groups even for second trimester procedures., Conclusion: Among women undergoing abortion and diagnosed with bacterial vaginosis, oral metronidazole, in conjunction with doxycycline, did not reduce post-abortion complications.

Context: Intra-amniotic infection (IAI) is commonly associated with preterm birth and adverse neonatal sequelae. Early diagnosis of IAI, however, has been hindered by insensitive or nonspecific tests., Objective: To identify unique protein signatures in rhesus monkeys with experimental IAI, a proteomics-based analysis of amniotic fluid was used to develop diagnostic biomarkers for subclinical IAI in amniotic fluid and blood of women with preterm labor., Design, Setting, and Participants: Surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry, gel electrophoresis, and tandem mass spectrometry were used to characterize amniotic fluid peptides in 19 chronically instrumented pregnant rhesus monkeys before and after experimental IAI. Candidate biomarkers were determined by liquid chromatography-tandem mass spectrometry. Polyclonal antibodies were generated from synthetic peptides for validation of biomarkers of IAI. Amniotic fluid peptide profiles identified in experimental IAI were subsequently tested in a cohort of 33 women admitted to Seattle, Wash, hospitals between June 25, 1991, and June 30, 1997, with preterm delivery at 35 weeks or earlier associated with subclinical IAI (n = 11), preterm delivery at 35 weeks or earlier without IAI (n = 11), and preterm contractions with subsequent term delivery at later than 35 weeks (n = 11)., Main Outcome Measures: Identification of peptide biomarkers for occult IAI., Results: Protein expression profiles in amniotic fluid showed unique signatures of overexpression of polypeptides in the 3- to 5-kDa and 10- to 12-kDa molecular weight ranges in all animals after infection and in no animal prior to infection. In women, the 10- to 12-kDa signature was identified in all 11 patients with subclinical IAI, in 2 of 11 with preterm delivery without IAI, and in 0 of 11 with preterm labor and term delivery without infection (P<.001). Peptide fragment analysis of the diagnostic peak in amniotic fluid identified calgranulin B and a unique fragment of insulinlike growth factor binding protein 1, which were also expressed in maternal serum. Mapping of other amniotic fluid proteins differentially expressed in IAI identified several immunoregulators not previously described in amniotic fluid., Conclusions: This proteomics-based characterization of the differential expression of amniotic fluid proteins in IAI identified a distinct proteomic profile in an experimental primate chorioamnionitis model that detected subclinical IAI in a human cohort with preterm labor. These diagnostic protein expression signatures, complemented by immunodetection of specific biomarkers in amniotic fluid and in maternal serum, might have application in the early detection of IAI.

Objective: Our purpose was to evaluate the antimicrobial therapy effect on clinical and laboratory findings among women at risk for endometritis., Study Design: A prospective antimicrobial treatment trial of 153 women was performed to characterize subacute endometritis and to determine the treatment effect on endometritis resolution., Results: After antimicrobial treatment, significant reductions occurred in abnormal bleeding (60% vs 29%), mucopurulent cervicitis (20% vs 6%), uterine tenderness (20% vs 6%), and histologic endometritis (38% vs 4%), all P<.001. In women with prior pelvic inflammatory disease (PID), endometritis was present in 43% with and 28% without current Chlamydia trachomatis or Neisseria gonorrhoeae. In women without prior PID, endometritis was present in 23% with and 12% without current C trachomatis or N gonorrhoeae (P=.002 for trend)., Conclusions: In women without a clinical diagnosis of PID, antimicrobial therapy decreased abnormal clinical findings and histologic endometritis. Prior PID is additive with current cervical infection as a risk for endometritis.

Objective: The aim of this study was investigate the impact of vaginal flora and vaginal inflammation on conception and early pregnancy loss following in-vitro fertilization (IVF)., Methods: We enrolled 91 women who were undergoing IVF. At embryo transfer (ET), all of the women had quantitative vaginal culture, ET catheter-tip culture, and vaginal Gram stain scored for bacterial vaginosis and quantitated for polymorphonuclear leukocytes (PMNs). Conception and early pregnancy loss were compared with culture and Gram stain results. Statistical analyses included the Chi-square test, Fisher's exact test and the Mann-Whitney U-test., Results: The overall live birth rate (LBR) was 30% (27/91), and the rate of early pregnancy loss was 34% (14/41). In women with bacterial vaginosis, intermediate flora and normal flora, the conception rates were 30% (3/10), 39% (12/31) and 52% (26/50), respectively (p = 0.06 for trend). Early pregnancy loss occurred in 33% (1/3), 42% (5/12) and 31% (8/26) of women, respectively (p = 0.06, comparing intermediate and normal flora). The vaginal log concentration of hydrogen peroxide-producing lactobacilli was 7.3 +/- 1.7 in women with a live birth (n = 27) and 4.9 +/- 2.5 in those with early pregnancy loss (n = 14) (p = 0.1)., Conclusions: IVF patients with bacterial vaginosis and with a decreased vaginal log concentration of hydrogen peroxide-producing lactobacilli may have decreased conception rates and increased rates of early pregnancy loss. A larger prospective treatment trial designed to evaluate the impact on IVF outcomes of optimizing the vaginal flora prior to IVF may be warranted.

Objective: The purpose of this study was to determine whether the microbial hydrolytic enzymes, sialidase and prolidase, and immunoglobulin A against the Gardnerella vaginalis cytolysin (anti-Gvh IgA) increase the risk for early preterm birth (< or =34 weeks of gestation) among women with bacterial vaginosis or intermediate flora., Study Design: Two hundred eighteen afebrile women in preterm labor with intact membranes had a vaginal Gram stain performed, and sialidase, prolidase, and anti-Gvh IgA concentrations were determined., Results: Women with bacterial vaginosis or intermediate flora had significantly higher sialidase and prolidase concentrations than women with normal flora. Among women with bacterial vaginosis or intermediate flora, the women with sialidase had a higher rate of early preterm birth (P =.05). Sialidase had a sensitivity of 43% and specificity of 77% for early preterm birth. Prolidase and anti-Gvh IgA did not predict early preterm birth., Conclusion: Women in preterm labor with bacterial vaginosis or intermediate flora and detectable sialidase are at increased risk of early preterm birth.