Mannose-binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis.

Precis: Women with recurrent vulvovaginal candidiasis (RVC) due to a polymorphism in codon 54 of the MBL2 gene respond better to fluconazole maintenance therapy than do women with other underlying causes.

Objective: To explain differences in response rates to maintenance therapy with fluconazole in women suffering from RVC by evaluating associations with a polymorphism in the gene coding for mannose-binding lectin (MBL).

Design: Follow-up study, neted case-control group.

Relationship between clinical diagnosis of recurrent vulvovaginal candidiasis and detection of Candida species by culture and polymerase chain reaction.

Background: Recurring vulvovaginal candidiasis (RVVC) is a common vaginal discharge affecting 75% of all women at least once in their life. In 5% of these women, infection is recurring. Aim of the study was to determine the sensitivity of detecting Candida species by culture and polymerase chain reaction (PCR) in women with a clinical diagnosis of RVVC.

Circulating antibodies to a conserved epitope of the Chlamydia trachomatis 60-kDa heat shock protein is associated with decreased spontaneous fertility rate in ectopic pregnant women treated by salpingectomy.

Problem: This prospective study was aimed to evaluate whether non-invasive clinical and serologic parameters of tubal disease are predictive for subsequent spontaneous conception and pregnancy outcome after first episode of ectopic pregnancy (EP).

Method Of Study: Overall, 144 women aged <35 years were enrolled. Outcome of subsequent spontaneous conception was analyzed after 3 years and compared with clinical parameters and antibody responses to Chlamydia trachomatis and epitopes of the 60-kDa chlamydial heat shock protein (CHSP-60).

Association between primary vulvar vestibulitis syndrome, defective induction of tumor necrosis factor-alpha, and carriage of the mannose-binding lectin codon 54 gene polymorphism.

Objective: We evaluated whether women with vulvar vestibulitis syndrome (VVS) could be subdivided on the basis of genotyping the polymorphic mannose-binding lectin (MBL) gene.

Study Design: DNA from 123 women with VVS was tested for a single nucleotide polymorphism at codon 54 of the MBL gene. Blood samples from 86 of the women were evaluated for ex vivo tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 receptor antagonist (IL-1ra) production in response to Candida albicans, gram-positive peptidoglycan, and gram-negative lipopolysaccharide.

Fetal polymorphisms in anti-inflammatory cytokine and beta-adrenergic receptor genes associated with placental pathological lesions.

Prematurity is the leading cause of infant morbidity and mortality. Altered intra-amniotic levels of anti-inflammatory cytokines, interleukin (IL) 1ra and IL-4, and beta2-adrenergic receptor (beta2AR) production have been associated with preterm labor and delivery. The aim of this study was to evaluate potential associations of polymorphisms in these genes with specific placental pathological findings.

Antibody to the Chlamydia trachomatis 60 kDa heat shock protein in follicular fluid and in vitro fertilization outcome.

Problem: The association between 60 kDa Chlamydia trachomatis heat shock protein (CHSP60) antibodies and the etiology and outcomes of in vitro fertilization (IVF) outcomes is not well known.

Method Of Study: A retrospective study with a double-blind analysis of follicular fluid from 253 IVF patients for IgG antibodies to CHSP60.

Results: The CHSP60 antibodies were detected in 74.

Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model.

Objective: The purpose of this study was to determine whether treatment with ampicillin together with dexamethasone and indomethacin delays preterm birth that is induced by intraamniotic group B Streptococcus in a nonhuman primate model.

Study Design: After contraction onset that was induced by group B Streptococcus (10(6) colony-forming units/mL), chronically instrumented rhesus macaques received either no treatment (controls; n = 6); ampicillin (n = 4); or ampicillin + dexamethasone + indomethacin (n = 5). Outcomes included the interval from contraction onset until delivery and concentrations of amniotic fluid inflammatory mediators.

Ex vivo cytokine production by whole mid-trimester amniotic fluid.

We hypothesized that ex vivo measurement of intraamniotic production of immune mediators differed from analysis of these mediators within unincubated amniotic fluid. Mid-trimester amniotic fluid from 72 women were incubated ex vivo with or without 50 ng/ml lipopolysaccharide (LPS). Supernatants and the corresponding unincubated amniotic fluids were tested for interleukin (IL)-6, IL-1 receptor antagonist (IL-1ra), IL-10 and nitric oxide.

Antibodies to the 70 kDa heat shock protein in midtrimester amniotic fluid and intraamniotic immunity.

Objective: Antibodies to the 70 kDa heat shock protein (hsp70) immunoglobulin (Ig) G are markers for exposure to adverse or nonphysiological stimuli. In addition, these antibodies cross-link hsp-70 microbial antigen complexes and enhance development of antimicrobial immunity. The association between intraamniotic hsp70 IgG concentrations and intraamniotic immune responses were evaluated.

A fetal cyclooxygenase-2 gene polymorphism is associated with placental malperfusion.

Prostaglandin levels vary during pregnancy, mostly under the control of the inducible enzyme cyclooxygenase-2 (COX-2). The expression of COX-2 has been associated with ischemic events in the heart and brain, but its direct effect on human placental perfusion has not been previously examined. The purpose of this study was to investigate whether a functional polymorphism in the COX-2 gene that controls enzyme expression levels is associated with placental histopathologic lesions.

Chlamydia trachomatis infection, Fallopian tube damage and a mannose-binding lectin codon 54 gene polymorphism.

Background: Mannose-binding lectin (MBL), a component of the innate immune system, provides a first-line defense against invading microorganisms. Polymorphisms in the MBL gene have been associated with increased risk of infection. Chlamydia trachomatis genital tract infections are a major cause of Fallopian tube occlusion.

Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis, and bacterial vaginosis.

Objective: To evaluate associations between polymorphisms in the gene coding for mannose-binding lectin (MBL) and the diagnosis of acute or recurrent vulvovaginal candidiasis and bacterial vaginosis

Methods: Women at two outpatient clinics in Brazil filled out a questionnaire and were examined for the presence of vulvovaginal candidiasis or bacterial vaginosis. A buccal swab was blindly tested for codons 54 and 57 MBL2 gene polymorphisms by polymerase chain reaction and endonuclease digestion.

Results: A total of 177 women were enrolled.

Fetal MMP2/MMP9 polymorphisms and intrauterine growth restriction risk.

Poor embryo implantation can lead to poor feto-maternal exchanges and intrauterine growth restriction. Matrix metalloproteinase-2 (MMP-2) and MMP-9 are highly involved in early embryo implantation and three functional polymorphisms have been described for these genes: MMP2 C-1306T, MMP9 C-1562T and MMP9 (CA)n repeat. We evaluated therefore the association between fetal genotype for these mutations and intrauterine growth retardation (IUGR).

Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) in IVF patients with polycystic ovary syndrome: correlations with outcome.

Objective: To evaluate serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) levels during stimulation in polycystic ovary syndrome (PCOS) and control populations as factors predictive of IVF outcome.

Design: Observational study.

Setting: Academic medical center-based IVF practice.

Mannose-binding lectin (MBL) codon 54 gene polymorphism protects against development of pre-eclampsia, HELLP syndrome and pre-eclampsia-associated intrauterine growth restriction.

Insufficient invasion of the spiral arteries by trophoblast cells is associated with the etiology of pre-eclampsia, the syndrome of hemolysis, elevated liver enzymes and low platelet counts (HELLP) and pre-eclampsia-associated intrauterine growth restriction (IUGR). Mannose-binding lectin (MBL) is a component of the innate immune system. MBL-mediated activation of the complement cascade is an important event in the destruction of invading trophoblasts.

An altered immunity hypothesis for the development of symptomatic bacterial vaginosis.

The hypothesis is advanced that the transition from a Lactobacillus-dominated vaginal microflora to a microflora characteristic of bacterial vaginosis (BV), as well as development of the adverse consequences of BV in some women but not in others, are due to alterations in innate immunity. A microbial-induced inhibition of Toll-like receptor expression and/or activity may block induction of proinflammatory immunity and lead to the proliferation of atypical vaginal bacteria. A lack of 70-kDa heat-shock protein production and release in response to abnormal flora would compound this failure to activate antimicrobial immune responses.

Bacterial flora of the female genital tract: function and immune regulation.

The use of non-culture gene amplification techniques has improved our understanding of the composition of the vaginal bacterial ecosystem. In most healthy women in the reproductive period the predominant vaginal bacteria are one or more of the following species of Lactobacillus: L. crispatus, L.

Preterm labor is induced by intraamniotic infusions of interleukin-1beta and tumor necrosis factor-alpha but not by interleukin-6 or interleukin-8 in a nonhuman primate model.

Objectives: The purpose of this study was to determine the relative contributions of individual proinflammatory cytokines and chemokines to the triggering of preterm labor.

Study Design: Eighteen chronically instrumented pregnant rhesus monkeys at 135 +/- 3 days gestation (term = 167 days) received 1 of 5 intraamniotic infusions: (1) interleukin-1beta (IL-1beta) (10 microg; n = 5), (2) tumor necrosis factor-alpha (TNF-alpha) (10-100 microg; n = 5), (3) IL-6 (20 microg twice a day; n = 2), (4) IL-8 (20 microg twice a day; n = 2), and (5) saline control (n = 4). Primary study outcomes were the mean uterine hourly contraction area (mm Hg x s/h) in 24 hours during peak response to cytokine infusion (all groups) and the interval from cytokine infusion until labor onset (IL-1beta, IL-6, and IL-8 groups).

TNFA-308G>A polymorphism influences the TNF-alpha response to altered vaginal flora.

Objective: To investigate the association between a tumor necrosis factor-alpha (TNF-alpha) gene polymorphism, vaginal TNF-alpha level, and microbial flora in pregnant women.

Methods: Vaginal samples from 203 women at 18-22 weeks' gestation were analyzed for microflora. TNFA-308G>A polymorphism was analyzed by polymerase chain reaction and restriction endonuclease analysis and TNF-alpha concentration was determined by ELISA.

Vulvodynia: a state-of-the-art consensus on definitions, diagnosis and management.

Vulvodynia is a chronic pain syndrome affecting up to 18% of the female population. Despite its high prevalence and associated distress, the etiology, diagnosis and clinical management of the disorder have not been clearly delineated. This "white paper" describes the findings and recommendations of a consensus conference panel based on a comprehensive review of the published literature on vulvodynia in addition to expert presentations on research findings and clinical management approaches.

Vaginal nitric oxide in pregnant women with bacterial vaginosis.

Problem: To evaluate vaginal nitric oxide (NO) production in response to alterations in the vaginal microbial flora.

Method Of Study: Cervicovaginal lavage samples from 206 women at 18-22 weeks of gestation were tested for NO, interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1ra), tumor necrosis factor-alpha and the inducible 70 kDa heat shock protein (hsp70). Bacterial vaginosis (BV) was diagnosed based on gram staining of vaginal smears.

Chlamydia heat shock protein 60 induces trophoblast apoptosis through TLR4.

Intrauterine infection affects placental development and function, and subsequently may lead to complications such as preterm delivery, intrauterine growth retardation, and preeclampsia; however, the molecular mechanisms are not clearly known. TLRs mediate innate immune responses in placenta, and recently, TLR2-induced trophoblast apoptosis has been suggested to play a role in infection-induced preterm delivery. Chlamydia trachomatis is the etiological agent of the most prevalent sexually transmitted bacterial infection in the United States.

Prevalence of cervical human papillomavirus in women undergoing in vitro fertilization and association with outcome.

Human papillomavirus (HPV) was detected in 17 (16.0%) of 106 patients undergoing treatment for IVF. Human papillomavirus-positive women had a decreased pregnancy rate (4 of 17, 23.

Are you a lumper or a splitter?

The current goal of evidence-based medicine, prospective therapeutic interventions in large numbers of patients, may not always reach an accurate conclusion. Individual variations in genetic characteristics need to be acknowledged and taken into account in the analysis. Some women with recurrent vulvo-vaginal candiosis (RVVC) have polymorphisms in genes that directly contribute to their increased susceptibility to these infections.