Online prediction tool for female pelvic floor dysfunction: development and validation.

INTRODUCTION AND HYPOTHESIS: The aim was to develop and validate (internally and externally) a prediction model for the presence and diagnosis of pelvic floor dysfunction (PFD) in women, including pelvic organ prolapse, stress urinary incontinence and/or overactive bladder via a patient-completed online tool. METHODS: Using a retrospective cohort of women aged >18 years, from multiple tertiary gynaecology units within Queensland, Australia (2014-2018), the prediction model was developed via penalized logistic regression with internal and external validation utilizing multiple clinical predictors (42 questions from the Australian Pelvic Floor Questionnaire and demographics: age, body mass index, parity and mode of delivery). The main outcome measures were the accuracy of the model in predicting a diagnosis of pelvic floor dysfunction and its specific conditions of prolapse and incontinence. RESULTS: A total of 3,501 women were utilized for model development and internal validation and 449 for external validation. On internal validation the model correctly identified those with PFD with 97% sensitivity, 74% specificity and a concordance index (C-index) of 0.96. Predictions of pelvic organ prolapse were also accurate, with 86% sensitivity, 83% specificity, C-index 0.83, as was stress urinary incontinence, 84% sensitivity, 87% specificity, C-index 0.87, and overactive bladder, 76% sensitivity, 77% specificity, C-index 0.77. External validation confirmed the model's accuracy with a similar C-index in all parameters. CONCLUSIONS: This model provides an accurate online tool to differentiate between those with and without PFD and diagnoses of common pelvic floor disorders. It serves as a valuable self-assessment for women and primary care providers.

A role for the endometrial microbiome in dysfunctional menstrual bleeding.

This study aimed to characterise the microbial community within the endometrial cavity and endocervix in women with menorrhagia or dysmenorrhea. Paired endocervical and endometrial biopsy samples were collected from women undergoing operative hysteroscopy and/or laparoscopy. Samples were cohorted based on pathology, indications for surgery, and histological dating of the endometrium. Samples were interrogated for the presence of microbial DNA using a two-step next generation sequencing technology approach to exploit the V5-V8 regions of the 16S rRNA gene. Pyrosequencing revealed that the endocervix and endometrium share a minor microbial community, but that each site harbours a separate and distinct microbial population (p = 0.024). This was also the case for women with menorrhagia and dysmenorrhea (p = 0.017). Lactobacillus spp. were the most abundant microbial taxa present in 50% of the cohorts, and across all endocervical groups. Members of the genera Prevotella, Fusobacterium and Jonquetella were the most abundant taxa identified in samples collected from nulliparous women. It can be concluded that the female upper genital tract is not sterile. Microbial community profiling revealed differences in the endometrial microbial community profiles for: (1) the endocervix compared to the endometrium, and (2), women with menorrhagia versus dysmenorrhea. The distinct microbial community profiles in these women may offer insight into the pathology and clinical management of dysfunctional menstrual bleeding.

Limitations of 16S rRNA Gene Sequencing to Characterize Lactobacillus Species in the Upper Genital Tract.

The endometrial cavity is an upper genital tract site previously thought as sterile, however, advances in culture-independent, next-generation sequencing technology have revealed that this low-biomass site harbors a rich microbial community which includes multiple Lactobacillus species. These bacteria are considered to be the most abundant non-pathogenic genital tract commensals. Next-generation sequencing of the female lower genital tract has revealed significant variation amongst microbial community composition with respect to Lactobacillus sp. in samples collected from healthy women and women with urogenital conditions. The aim of this study was to evaluate our ability to characterize members of the genital tract microbial community to species-level taxonomy using variable regions of the 16S rRNA gene. Samples were interrogated for the presence of microbial DNA using next-generation sequencing technology that targets the V5-V8 regions of the 16S rRNA gene and compared to speciation using qPCR. We also performed re-analysis of published data using alternate variable regions of the 16S rRNA gene. In this analysis, we explore next-generation sequencing of clinical genital tract isolates as a method for high throughput identification to species-level of key Lactobacillus sp. Data revealed that characterization of genital tract taxa is hindered by a lack of a consensus protocol and 16S rRNA gene region target allowing comparison between studies.

The effect of the levonorgestrel releasing intrauterine system on endometrial hyperplasia: an Australian study and systematic review.

BACKGROUND: The levonorgestrel intrauterine system (LNG-IUS) provides effective contraception and treatment for menorrhagia and is used to prevent endometrial hyperplasia (EH) in women taking unopposed oestrogens. AIMS: The aim of this study was to assess whether the LNG-IUS was also a safe and effective treatment for EH and to conduct a systematic review of the literature. METHODS: A retrospective record review was undertaken in a private gynaecology practice in Brisbane, Australia, and included all women with EH treated with hysterectomy, oral progestins or LNG-IUS between January 2004 and April 2007. Histopathological findings from hysterectomy specimens or endometrial biopsies were used to calculate rates of regression of the EH. RESULTS: Twenty-one women elected to have a hysterectomy and seven of those (33%) had no persisting hyperplasia at surgery. Twenty-six women had a LNG-IUS inserted at initial hysteroscopy dilatation and curettage or shortly afterwards; seven of those elected to proceed to hysterectomy when their diagnosis was known. Among ten women who used oral progestin treatment, 90% showed initial regression; two with recurrent EH were subsequently treated successfully with LNG-IUS. All 21 women (100%), including one with atypia, treated with LNG-IUS for more than seven weeks had normal endometrial histology on subsequent assessment. No women developed endometrial cancer. Pooled analysis of the published literature gave a 96% regression rate for non-atypical EH treated with LNG-IUS. CONCLUSIONS: These data contribute further evidence that LNG-IUS is a safe and effective method for treating non-atypical EH. Whether LNG-IUS could provide a safe and cost-effective alternative to hysterectomy for atypical EH warrants further examination.

The fallopian tube microbiome: implications for reproductive health.

OBJECTIVE: There is a paucity of data characterizing the microbiota of the female upper genital tract, which controversially is described as a sterile site. We examine whether the fallopian tube harbours an endogenous microbial community. DESIGN: This prospective study collected from women undergoing total hysterectomy or salpingectomy-oophorectomy. SETTING: Private hospital gynaecology department. PATIENTS: Fallopian tubes were collected from women diagnosed with benign disease or for prophylaxis. INTERVENTIONS: Samples were interrogated for the presence of microbial DNA using a next generation sequencing technology approach to exploit the V5 to V9 regions of the 16S rRNA gene. MAIN OUTCOME MEASURES: The fallopian tube microbiota was characterized using traditional culture techniques and next generation sequencing. RESULTS: Bacteria were isolated from 50% of cultured samples, and 100% of samples returned positive PCR results. Only 68% of the culture isolates could be confidently identified using automated diagnostic equipment in a clinical microbiology laboratory. Monomicrobial communities were identified only for cultured isolates (50%). Pyrosequencing revealed that all communities were polymicrobial. Lactobacillus spp. were not present in all groups, nor were they the most dominant isolates. Distinct differences in the microbial communities were evident for left compared to right fallopian tubes, ampulla versus isthmus, pre- and post- menopausal tissue, and in secretory phase fallopian tubes with and without Mirena intrauterine devices in situ (all p < 0.05). CONCLUSION: The female upper genital tract is not sterile. Distinct microbial community profiles in the fallopian tubes of healthy women suggest that this genital tract site supports an endogenous microbiota.

Fallopian tube microbiota: evidence beyond DNA.

AIM: To determine whether cultivation-dependent and -independent analyses identifying fallopian tube bacteria were associated with visually observable microbial cells in situ using scanning electron microscopy. PATIENTS: Fallopian tubes were collected from pre- and postmenopausal women undergoing salpingectomies for benign disease or as prophylaxis. MATERIALS & METHODS: Fresh fallopian tube samples were processed for scanning electron microscopy to characterize fallopian tube ultrastructure. Histopathology was used to exclude fallopian tube abnormalities and for menstrual cycle staging of the endometrium. RESULTS: Scanning electron microscopy revealed observable microbial cells in fallopian tube samples. CONCLUSION: In the absence of inflammatory pathology, the fallopian tube harbors a visually observable microbial population, which correlates with cultivation-dependent and -independent data, further refuting the sterility of this anatomical niche.