gen. nov., sp. nov., and sp. nov., gen. nov.: novel bacteria from the family isolated from the female genital tract.

Four obligately anaerobic Gram-positive bacteria representing one novel genus and two novel species were isolated from the female genital tract. Both novel species, designated UPII 610-J and KA00274, and an additional isolate of each species were characterized utilizing biochemical, genotypic and phylogenetic analyses. All strains were non-motile and non-spore forming, asaccharolytic, non-cellulolytic and indole-negative coccobacilli.

sp. nov., sp. nov., and sp. nov.: novel bacteria isolated from the female genital tract.

Six strictly anaerobic Gram-negative bacteria representing three novel species were isolated from the female reproductive tract. The proposed type strains for each species were designated UPII 199-6, KA00182 and BV3C16-1. Phylogenetic analyses based on 16S rRNA gene sequencing indicated that the bacterial isolates were members of the genus .

A phase 3, randomized, controlled trial of Astodrimer 1% Gel for preventing recurrent bacterial vaginosis.

Objective: The objective of the study was to confirm the efficacy and safety of Astodrimer 1% Gel to prevent recurrence of bacterial vaginosis.

Study Design: 864 women with a diagnosis of bacterial vaginosis and a history of recurrent bacterial vaginosis were enrolled in North America and first received oral metronidazole (500 mg twice daily for 7 days). Women successfully treated with metronidazole were randomly assigned 1:1 to Astodrimer 1% Gel (N = 295) or placebo (N = 291) at a dose of 5 g vaginally every second day for 16 weeks, and followed for a further 12 weeks off-treatment.

Bacterial Communities Associated With Abnormal Nugent Score in Postmenopausal Versus Premenopausal Women.

The Nugent score is the reference standard for bacterial vaginosis (BV) diagnosis but has not been validated in postmenopausal women. We compared relative abundances from 16S ribosomal RNA gene sequencing of vaginal microbiota with Nugent score in cohorts of premenopausal (n = 220) and postmenopausal (n = 144) women. In premenopausal women, 33 taxa were significantly correlated with Nugent score, including the classic BV-associated taxa Gardnerella, Atopobium, Sneathia, Megasphaera, and Prevotella.

Pathologic findings and clinical outcomes in women undergoing risk-reducing surgery to prevent ovarian and fallopian tube carcinoma: A large prospective single institution experience.

Objectives: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women at increased risk of ovarian, fallopian tube (FT), and peritoneal carcinoma (collectively OC). We describe rates of occult neoplasia in the largest single-institution prospective cohort of women undergoing RRSO, including those with mutations in non-BRCA homologous repair (HRR) genes.

Methods: Participants undergoing RRSO enrolled in a prospective tissue bank between 1999 and 2017.

Perceptions of risk and reward in BRCA1 and BRCA2 mutation carriers choosing salpingectomy for ovarian cancer prevention.

Salpingectomy with interval oophorectomy has gained traction as an ovarian cancer prevention strategy, but is not currently recommended for high risk women. Nevertheless, some choose this approach. We aimed to understand risk perception and plans for oophorectomy in BRCA1 and BRCA2 (BRCA) mutation carriers choosing salpingectomy for ovarian cancer prevention.

An Alternate Diagnostic Algorithm for the Diagnosis of Intraepithelial Fallopian Tube Lesions.

Intraepithelial fallopian tube neoplasia is thought to be a precursor lesion to high-grade serous carcinoma of the Müllerian adnexae, particularly in women with BRCA1 or BRCA2 mutations. This association has led to recommendations to assess fallopian tubes for intraepithelial atypia. However, the diagnostic reproducibility of a diagnosis of intraepithelial neoplasia is unclear.

Tumor infiltrating lymphocytes and homologous recombination deficiency are independently associated with improved survival in ovarian carcinoma.

Objective: The presence of tumor infiltrating lymphocytes (TIL) and defects in homologous recombination (HR) are each important prognostic factors in ovarian carcinoma (OC). We characterized the association between HR deficiency (HRD) and the presence of TILs in a cohort of OC patients and the relative contribution to overall survival.

Methods: Patients with carcinoma of the ovary, fallopian tube, or peritoneum were prospectively enrolled.

Combined symptom index and second-generation multivariate biomarker test for prediction of ovarian cancer in patients with an adnexal mass.

Objective: To assess the performance of a symptom index (SI) and multivariate biomarker panel in the identification of ovarian cancer in women presenting for surgery with an adnexal mass.

Study Design: Prospective study of patients seen at a tertiary medical center. Following consent, patients completed an SI and preoperative serum was collected for individual markers (CA 125) and a second-generation FDA-cleared biomarker test (MIA2G).

Parallel detection of lactobacillus and bacterial vaginosis-associated bacterial DNA in the chorioamnion and vagina of pregnant women at term.

Background: The majority of early preterm births are associated with intrauterine infections, which are thought to occur when microbes traffic into the uterus from the lower genital tract and seed the placenta. Bacterial vaginosis (BV) is associated with heterogeneous bacterial communities in the vagina and is linked to preterm birth. The extent to which trafficking into the uterus of normal and BV-associated vaginal bacteria occurs is unknown.

Clinical characteristics and outcomes of patients with BRCA1 or RAD51C methylated versus mutated ovarian carcinoma.

Objective: In ovarian carcinoma, mutations in homologous recombination DNA repair (HRR) genes, including BRCA1 and RAD51C, are associated with increased survival and specific clinical features. Promoter hypermethylation is another mechanism of reducing gene expression. We assessed whether BRCA1 and RAD51C promoter hypermethylation is associated with similar survival and clinical characteristics.

Combining a symptom index, CA125 and HE4 (triple screen) to detect ovarian cancer in women with a pelvic mass.

Objectives: To assess a simple algorithm of CA125, HE4 and Symptom Index to predict ovarian cancer in women with a pelvic mass.

Methods: This was a prospective study of women referred to a gynecologic oncology clinic for surgical evaluation of a pelvic mass. Preoperatively, women completed a SI and had serum markers drawn.

Evaluation of a Validated Biomarker Test in Combination With a Symptom Index to Predict Ovarian Malignancy.

Objective: This study aimed to evaluate the predictive ability of a multivariate biomarker test in combination with a symptom index (SI) to identify ovarian cancer in a cohort of women planning to undergo surgery for a pelvic mass.

Methods: This was a prospective study of patients seen at a tertiary care medical center. Following consent, patients completed an SI and preoperative serum was collected for a Food and Drug Administration-cleared multivariate biomarker test [multivariate index assay (MIA)].

More Easily Cultivated Than Identified: Classical Isolation With Molecular Identification of Vaginal Bacteria.

Background: Women with bacterial vaginosis (BV) have complex communities of anaerobic bacteria. There are no cultivated isolates of several bacteria identified using molecular methods and associated with BV. It is unclear whether this is due to the inability to adequately propagate these bacteria or to correctly identify them in culture.

Ultra-deep sequencing detects ovarian cancer cells in peritoneal fluid and reveals somatic TP53 mutations in noncancerous tissues.

Current sequencing methods are error-prone, which precludes the identification of low frequency mutations for early cancer detection. Duplex sequencing is a sequencing technology that decreases errors by scoring mutations present only in both strands of DNA. Our aim was to determine whether duplex sequencing could detect extremely rare cancer cells present in peritoneal fluid from women with high-grade serous ovarian carcinomas (HGSOCs).

Vaginal and Rectal Clostridium sordellii and Clostridium perfringens Presence Among Women in the United States.

Objective: To characterize the presence of Clostridium sordellii and Clostridium perfringens in the vagina and rectum, identify correlates of presence, and describe strain diversity and presence of key toxins.

Methods: We conducted an observational cohort study in which we screened a diverse cohort of reproductive-aged women in the United States up to three times using vaginal and rectal swabs analyzed by molecular and culture methods. We used multivariate regression models to explore predictors of presence.

Genetic characterization of early onset ovarian carcinoma.

Objective: Ovarian carcinoma (OC) is rare in young women and the fraction of early onset OC attributable to inherited mutations in known OC genes is uncertain. We sought to characterize the fraction of OC that is heritable in women diagnosed with ovarian, fallopian tube, or peritoneal carcinoma at forty years of age or younger.

Methods: We sequenced germline DNA from forty-seven women diagnosed with OC at age 40 or younger ascertained through a gynecologic oncology tissue bank or referred from outside providers using BROCA, a targeted capture and massively parallel sequencing platform that can detect all mutation classes.

Hydrogen Peroxide-Producing Lactobacilli Are Associated With Lower Levels of Vaginal Interleukin-1β, Independent of Bacterial Vaginosis.

Background: The presence of hydrogen peroxide (H2O2)-producing lactobacilli in the vagina is associated with decreased rates of preterm birth and HIV acquisition. We hypothesize that this is due to immunomodulatory effects of these species.

Methods: Concentrations of interleukin (IL)-1β, IL-6, IL-8, secretory leukocyte protease inhibitor, and human β-defensin 2 were quantified from vaginal swabs from 4 groups of women: women with and without bacterial vaginosis (BV) by Nugent score, further stratified by detection of H2O2-producing lactobacilli by semiquantitative culture.

Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms: Clinical correlates.

Objectives: To measure HE4 levels in urine from normal donors, patients with LMP tumors and ovarian cancer patients and to correlate levels with clinical factors in ovarian cancer patients.

Methods: Archived samples from controls, patients with LMP tumors and ovarian cancer were tested using commercial assays, including serially collected serum and urine samples from women treated for stage III/IV serous ovarian cancer.

Results: Five of 6 patients with stage I/II and 26 of 36 stage III/IV serous ovarian cancer patients had HE4-positive urines, similar to serum samples (4 of 5 stage I/II and 26 of 34 stage III/IV) when tested at the same level of specificity (95%).

Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women.

Objective: The objective of the study was to evaluate the upper genital tract (UGT) presence of vaginal bacterial species using sensitive molecular methods capable of detecting fastidious bacterial vaginosis (BV)-associated bacteria.

Study Design: Vaginal swabs were collected prior to hysterectomy. The excised uterus was sterilely opened and swabs collected from the endometrium and upper endocervix.

Long-term effect of depot medroxyprogesterone acetate on vaginal microbiota, epithelial thickness and HIV target cells.

Background: Depot medroxyprogesterone acetate (DMPA) has been linked to human immunodeficiency virus type 1 (HIV-1) acquisition.

Methods: Vaginal microbiota of women using DMPA for up to 2 years were cultured. Mucosal immune cell populations were measured by immunohistological staining.

More than meets the eye: associations of vaginal bacteria with gram stain morphotypes using molecular phylogenetic analysis.

Bacterial vaginosis (BV) is a highly prevalent condition associated with adverse health outcomes. Gram stain analysis of vaginal fluid is the standard for confirming the diagnosis of BV, wherein abundances of key bacterial morphotypes are assessed. These Lactobacillus, Gardnerella, Bacteroides, and Mobiluncus morphotypes were originally linked to particular bacterial species through cultivation studies, but no studies have systematically investigated associations between uncultivated bacteria detected by molecular methods and Gram stain findings.

Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas.

Purpose: Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination DNA repair genes is uncertain.

Experimental Design: Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic loss-of-function mutations in 30 genes, including BRCA1, BRCA2, and 11 other genes in the homologous recombination pathway.