The Impact of Vaginal Probiotics on Pessary Use: A Randomized Controlled Trial.

Importance: Pessary-related adverse effects are common, and treatment options are limited. Probiotics may improve pessary-related adverse effects by altering the vaginal microenvironment.

Objective: This study aimed to evaluate the effect of a vaginal probiotic suppository on the vaginal microenvironment among pessary users.

Vaginal pH measured in vivo: lactobacilli determine pH and lactic acid concentration.

Background: Lactic acid (protonated lactate) has broad antimicrobial activity. Vaginal lactobacilli produce lactic acid, and are known to confer protection against reproductive tract infections when they are predominant in the vaginal microbiota. Using novel ex vivo methods, we showed that cervicovaginal fluid (CVF) from women with a predominantly lactobacilli-morphotype microbiota contains significantly more lactic acid than previously thought, sufficient to inactivate reproductive tract pathogens.

The implausible "in vivo" role of hydrogen peroxide as an antimicrobial factor produced by vaginal microbiota.

In the cervicovaginal environment, the production of hydrogen peroxide (HO) by vaginal Lactobacillus spp. is often mentioned as a critical factor to the in vivo vaginal microbiota antimicrobial properties. We present several lines of evidence that support the implausibility of HO as an "in vivo" contributor to the cervicovaginal milieu antimicrobial properties.

Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota.

Lactic acid at sufficiently acidic pH is a potent microbicide, and lactic acid produced by vaginal lactobacilli may help protect against reproductive tract infections. However, previous observations likely underestimated healthy vaginal acidity and total lactate concentration since they failed to exclude women without a lactobacillus-dominated vaginal microbiota, and also did not account for the high carbon dioxide, low oxygen environment of the vagina. Fifty-six women with low (0-3) Nugent scores (indicating a lactobacillus-dominated vaginal microbiota) and no symptoms of reproductive tract disease or infection, provided a total of 64 cervicovaginal fluid samples using a collection method that avoided the need for sample dilution and rigorously minimized aerobic exposure.

Evaluation of microbicide gel adherence monitoring methods.

Background: An objective and accurate method that measures adherence to vaginal microbicide gel regimens during clinical trials could provide more accurate estimates of microbicide efficacy, aid in targeting adherence promotion resources, and enable objective assessment of adherence promotion strategies.

Methods: We evaluated 4 methods to assess whether or not gel applicators had been vaginally inserted. At the study site, 50 women inserted hydroxyethylcellulose universal placebo gel through a polypropylene vaginal applicator and handled, but did not insert a second "sham-inserted" applicator.

In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide.

Background: Hydrogen peroxide (H2O2) produced by vaginal lactobacilli is generally believed to protect against bacteria associated with bacterial vaginosis (BV), and strains of lactobacilli that can produce H2O2 are being developed as vaginal probiotics. However, evidence that led to this belief was based in part on non-physiological conditions, antioxidant-free aerobic conditions selected to maximize both production and microbicidal activity of H2O2. Here we used conditions more like those in vivo to compare the effects of physiologically plausible concentrations of H2O2 and lactic acid on a broad range of BV-associated bacteria and vaginal lactobacilli.

Cervicovaginal fluid and semen block the microbicidal activity of hydrogen peroxide produced by vaginal lactobacilli.

Background: H2O2 produced by vaginal lactobacilli is believed to protect against infection, and H2O2-producing lactobacilli inactivate pathogens in vitro in protein-free salt solution. However, cervicovaginal fluid (CVF) and semen have significant H2O2-blocking activity.

Methods: We measured the H2O2 concentration of CVF and the H2O2-blocking activity of CVF and semen using fluorescence and in vitro bacterial-exposure experiments.