DOCSLIB.ORG

205223Orig1s000

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
205223Orig1s000 CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 205223Orig1s000 MEDICAL REVIEW(S) Clinical Investigator Financial Disclosure Review Template Application Number: 205223 Submission Date(s): May 24, 2013 Applicant: Valeant Pharmaceuticals North America LLC Product: Metronidazole Vaginal Gel 1.3% Reviewer: Hala Shamsuddin, M.D. Date of Review: February 24, 2014 Covered Clinical Study (Name and/or Number): Study GW05-0904 Study MP-1601-01 Was a list of clinical investigators provided: Yes X No (Request list from applicant) Total number of investigators identified: 52 (fifty-two) Number of investigators who are sponsor employees (including both full-time and part-time employees): None Number of investigators with disclosable financial interests/arrangements (Form FDA 3455): 52 (fifty-two) If there are investigators with disclosable financial interests/arrangements, identify the number of investigators with interests/arrangements in each category (as defined in 21 CFR 54.2(a), (b), (c) and (f)): Compensation to the investigator for conducting the study where the value could be influenced by the outcome of the study: None Significant payments of other sorts: None Proprietary interest in the product tested held by investigator: None Significant equity interest held by investigator in sponsor of covered study: None Is an attachment provided with details Yes X No (Request details from of the disclosable financial applicant) interests/arrangements: Is a description of the steps taken to Yes X No (Request information minimize potential bias provided: from applicant) Number of investigators with certification of due diligence (Form FDA 3454, box 3) None Is an attachment provided with the NA No (Request explanation reason: Reference ID: 3464175 from applicant) Discuss whether the applicant has adequately disclosed financial interests/arrangements with clinical investigators as recommended in the guidance for industry Financial Disclosure by Clinical Investigators.1 Also discuss whether these interests/arrangements, investigators who are sponsor employees, or lack of disclosure despite due diligence raise questions about the integrity of the data: - If not, why not (e.g., study design (randomized, blinded, objective endpoints), clinical investigator provided minimal contribution to study data) - If yes, what steps were taken to address the financial interests/arrangements (e.g., statistical analysis excluding data from clinical investigators with such interests/arrangements) Briefly summarize whether the disclosed financial interests/arrangements, the inclusion of investigators who are sponsor employees, or lack of disclosure despite due diligence affect the approvability of the application. Reviewer’s Comments Certification was submitted that the sponsor had not entered into any financial arrangements with any of the clinical investigators whereby the value of compensation to the investigator could be affected by the outcome of the study as defined in 21CFR 54.2(a). Certification was provided that none of the listed investigator disclosed a proprietary interest in the product or significant equity in the sponsor as defined in 21 CFR 54.2(b) and (c), and that no listed investigator received significant payments of other sorts 21CFR (f). The applicant for NDA 205223 has adequately disclosed financial interests/arrangements with the clinical investigators. 1 See [web address]. Reference ID: 3464175 --------------------------------------------------------------------------------------------------------- This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature. --------------------------------------------------------------------------------------------------------- /s/ ---------------------------------------------------- HALA H SHAMSUDDIN 03/04/2014 Reference ID: 3464175 NDA 205223 SN000 Metronidazole Vaginal Gel 1.3% for the Treatment of Bacterial Vaginosis Clinical Review NDA 205223 SN 000 Type of Review Standard Submit Date May 24, 2103 PDUFA Goal Date March 24, 2014 Division of Anti-Infective Products (DAIP) Division/Office Office of Anti-microbial Products (OAP) Reviewer Hala Shamsuddin MD Team Leader Thomas Smith MD Product Metronidazole Vaginal Gel 1.3% Proposed Trade Name Metronidazole Vaginal Gel 1.3% Sponsor Valeant Pharmaceuticals Indication Treatment of Bacterial Vaginosis in Non-Pregnant Women 1 Reference ID: 3436511 NDA 205223 SN000 Metronidazole Vaginal Gel 1.3% for the Treatment of Bacterial Vaginosis Contents Recommendation on Regulatory Action ............................................................................. 5 Risk Benefit Assessment..................................................................................................... 5 Recommendations for Post-Market Risk Evaluation and Mitigation Strategies ................ 5 Recommendations for Post-Market Requirements and Commitments ............................... 5 Executive Summary ............................................................................................................ 5 Introduction ..................................................................................................................... 5 Efficacy ........................................................................................................................... 6 Safety .............................................................................................................................. 8 Pregnancy ........................................................................................................................ 9 Introduction ......................................................................................................................... 9 Bacterial Vaginosis ......................................................................................................... 9 Currently Available Treatments for BV ........................................................................... 10 Regulatory Background .................................................................................................... 10 Ethics................................................................................................................................. 11 Issues Related to Other Review Disciplines ..................................................................... 11 CMC .............................................................................................................................. 11 Microbiology................................................................................................................. 11 Toxicology .................................................................................................................... 12 Clinical Pharmacology .................................................................................................. 12 Sources of Clinical Data ................................................................................................... 12 PK Study MP-1601-02 ...................................................................................................... 13 Phase 2 Dose Ranging Study - Study GW05-904 ............................................................ 13 Study Design ................................................................................................................. 13 Subject Disposition ....................................................................................................... 15 Analysis Populations ..................................................................................................... 15 Demographics and Disease Characteristics .................................................................. 16 Primary Efficacy Endpoint ........................................................................................... 16 Secondary Efficacy Endpoints ...................................................................................... 17 Safety Evaluation .......................................................................................................... 18 Extent of Exposure .................................................................................................... 18 Concomitant Medications ......................................................................................... 18 Adverse Events ......................................................................................................... 18 2 Reference ID: 3436511 NDA 205223 SN000 Metronidazole Vaginal Gel 1.3% for the Treatment of Bacterial Vaginosis SAE ........................................................................................................................... 20 Pregnancies ............................................................................................................... 20 Phase 3 Placebo-Controlled Study - MP-1601-01 ............................................................ 21 Study Design ................................................................................................................. 21 Protocol Amendments ................................................................................................... 22 Subject Disposition ....................................................................................................... 22 Protocol Deviations ....................................................................................................... 23 Analysis Populations ....................................................................................................
Load more

Recommended publications
  • Pelvic Inflammatory Disease (PID) Brown Health Services Patient Education Series
    Pelvic Inflammatory Disease (PID) Brown Health Services Patient Education Series the uterine lining to treat abnormal What is PID? bleeding) PID (pelvic inflammatory disease) is ● PID risk from insertion of an IUD inflammation caused by infections ascending (intrauterine device) – occurs in the first 3 weeks post insertion from the vagina or cervix to the upper genital ● Abortion tract. This includes the lining of the uterus, the ovaries, the fallopian tubes, the uterine wall Why is it important to treat PID? and the uterine ligaments that hold these ● structures in place. PID is the most common serious infection of women aged 16 to 25 years What causes it? of age ● Untreated pelvic infections may cause Most cases of PID are caused by sexually adhesions in the fallopian tubes, which transmitted infections (STIs). The disease can be may lead to infertility caused by many different organisms or ● 1 in 4 women with acute PID develop combinations of organisms, but is frequently future problems such as ectopic caused by gonorrhea and chlamydia. Although pregnancy or chronic pelvic pain from Bacterial Vaginosis (BV) is associated with PID, adhesions whether the incidence of PID can be reduced by What are the symptoms? identifying and treating people with vaginas with BV is unclear. If you notice abnormal ● Painful intercourse could be the first discharge and a fishy vaginal odor (signs of BV) sign of infection ● you should be evaluated at Health Services. Pain and tenderness involving the lower abdomen, cervix, uterus and ovaries PID may also occur following procedures that ● Fever and chills create an open wound where infectious ● Nausea and/or diarrhea organisms can more easily enter, such as: ● Abnormal vaginal bleeding or discharge ● Biopsy from the lining of the uterus Early treatment can usually prevent these ● D & C (dilation and curettage – a problems.
    [Show full text]
  • Vaginitis and Abnormal Vaginal Bleeding
    UCSF Family Medicine Board Review 2013 Vaginitis and Abnormal • There are no relevant financial relationships with any commercial Vaginal Bleeding interests to disclose Michael Policar, MD, MPH Professor of Ob, Gyn, and Repro Sciences UCSF School of Medicine [email protected] Vulvovaginal Symptoms: CDC 2010: Trichomoniasis Differential Diagnosis Screening and Testing Category Condition • Screening indications – Infections Vaginal trichomoniasis (VT) HIV positive women: annually – Bacterial vaginosis (BV) Consider if “at risk”: new/multiple sex partners, history of STI, inconsistent condom use, sex work, IDU Vulvovaginal candidiasis (VVC) • Newer assays Skin Conditions Fungal vulvitis (candida, tinea) – Rapid antigen test: sensitivity, specificity vs. wet mount Contact dermatitis (irritant, allergic) – Aptima TMA T. vaginalis Analyte Specific Reagent (ASR) Vulvar dermatoses (LS, LP, LSC) • Other testing situations – Vulvar intraepithelial neoplasia (VIN) Suspect trich but NaCl slide neg culture or newer assays – Psychogenic Physiologic, psychogenic Pap with trich confirm if low risk • Consider retesting 3 months after treatment Trichomoniasis: Laboratory Tests CDC 2010: Vaginal Trichomoniasis Treatment Test Sensitivity Specificity Cost Comment Aptima TMA +4 (98%) +3 (98%) $$$ NAAT (like GC/Ct) • Recommended regimen Culture +3 (83%) +4 (100%) $$$ Not in most labs – Metronidazole 2 grams PO single dose Point of care – Tinidazole 2 grams PO single dose •Affirm VP III +3 +4 $$$ DNA probe • Alternative regimen (preferred for HIV infected
    [Show full text]
  • Original Article
    ORIGINAL ARTICLE ASSOCIATION OF BACTERIAL VAGINOSIS WITH PRETERM LABOUR Shilpa M.N1, A.P. Chandrashekar2, G.S. Vijay Kumar3, Rashmi P. Mahale4 HOW TO CITE THIS ARTICLE: Shilpa M.N, A.P Chandrashekar, G.S. Vijay Kumar, Rashmi P. Mahale. “Association of bacterial vaginosis with preterm labour”. Journal of Evolution of Medical and Dental Sciences 2013; Vol2, Issue 32, August 12; Page: 6104-6110. ABSTRACT: OBJECTIVES: To study the prevalence of bacterial vaginosis (BV) in preterm labour and to investigate its association as one of the causative factors of preterm labour. MATERIALS AND METHODS: Fifty women who presented with preterm labour (study group) and fifty women in labour at term (control group) admitted to a teaching hospital from November 2009 to May 2011 were examined for bacterial vaginosis using Nugent score. All the statistical methods were carried out through SPSS for windows (version 16.0), STUDY DESIGN: A comparative study. RESULTS: The prevalence of bacterial vaginosis among preterm labour group was 22% and its prevalence among full term group was 4%. There was statistically significant association of BV with preterm labor when compared to term labor (p=.007). Bacterial Vaginosis was strongly associated with very preterm delivery (<34 weeks) (p=.050). Bacterial vaginosis was significantly associated with lesser gestational age at delivery and low birth weight. CONCLUSION: Bacterial vaginosis is significantly associated with preterm labour and is one of the probable causative factors of preterm labour. KEYWORDS: Bacterial vaginosis, Nugent score, Preterm labor. INTRODUCTION: Preterm labour is defined as onset of labour prior to completion of 37 weeks gestation after period of viability.1,2 Though only 7-10% of all deliveries are preterm, prematurity alone accounts for more than 80% of perinatal morbidity and mortality in India.1,2,3,4 The etiology for preterm labour is multifactorial and in many of the cases is obscure.
    [Show full text]
  • Women's Health: a Guide to Preventing Infections, Bacterial
    Women’s Health: A Guide to Preventing Infections Bacterial vaginosis, or BV, is a common vaginal infection in women. It is the most common vaginal infection in women of childbearing age, including pregnant women. Bacterial Vaginosis (BV) While it is not a sexually transmitted disease (STD), The risk of BV is higher if you: some sexual behaviors increase the chances for BV. u Have a new sex partner or multiple sex partners. Women who have never had sex can also have BV. u Douche. u Do not use condoms. How is it spread? u Have a female sexual partner with BV. The vagina contains many different types of bacteria. Normally, there are large numbers of “good” bacteria that keep the number of “harmful” bacteria very low. BV is more common in lesbian Bacterial vaginosis occurs when this balance is upset and bisexual women than in and there are more “harmful” bacteria than “good” other women. The reason for bacteria. The cause of BV is not fully understood. this is unknown. Veterans Health Administration 2012 Women’s Health: Bacterial Vaginosis (BV) What are signs of BV in women? Women with BV may have few or no signs of infection. Some women with BV have: u Increased vaginal discharge: Often watery. Gray or white in color. Sometimes has an unpleasant, fish-like odor, especially after sex. u Itching or irritation in the vaginal area. u Burning during urination. How do you know if you have BV? BV can be diagnosed during a medical exam. To check for BV, your health care provider looks for signs of infection and collects a sample of vaginal fluid for lab tests.
    [Show full text]
  • Evaluation of Different Diagnostic Methods of Bacterial Vaginosis
    IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-ISSN: 2279-0853, p-ISSN: 2279-0861. Volume 13, Issue 1, Ver. VIII (Feb. 2014), PP 15-23 www.iosrjournals.org Evaluation of different diagnostic methods of bacterial vaginosis Gamal F. M. Gad¹, Ahmed R. El-Adawy², Mohammed S. Mohammed3, Abobakr F. Ahmed1, Heba A. Mohamed¹ ¹ Microbiology department, Faculty of Pharmacy, Minia University 2 Gynecology and Obstetrics department, Faculty of Medicine, Minia University 3 Microbiology department, Faculty of Medicine, Minia University Abstract: Bacterial vaginosis (BV) is an ecological disorder of the vaginal microbiota that affects millions of women annually, and is associated with numerous adverse health outcomes including pre-term birth and the acquisition of sexually transmitted infections. This study aimed to determine the incidence rate of bacterial vaginosis among women and examine the effect of some risk factors and demographic features on BV incidence. Also aimed to compare between the different methods of BV diagnosis. The results revealed that from the 100 patients, 33% were diagnosed as bacterial vaginosis, 23% were having candidiasis, 8% aerobic vaginitis, 3% trichomoniasis and 33% were normal. The highest number of BV positive cases was in the age group of (26-35)Yrs, 94% of the 33 BV positive cases were using vaginal douches and 94% were married. BV positive cases using IUD were equal to BV positive cases using hormonal contraceptives including injection and tablets (12/33, 36.4%). BV was diagnosed in 33%, 38%, 36%, 30% and 34% of patients using Gram stain, culture, Amsel criteria, BV Blue test® and qPCR respectively.
    [Show full text]
  • Bacterial Vaginosis
    Bacterial Vaginosis What is bacterial vaginosis? Bacterial vaginosis (BV) is a change in the normal balance of bacteria in the vagina with overgrowth of bad bacteria. It is the most common cause of vaginal discharge and odor. What bacteria are supposed to be in the vagina? Lactobacilli are the good bacteria of the vagina (probiotics). They produce lactic acid keeping the vaginal mildly acidic thereby preventing overgrowth of bad bacteria. How common is bacterial vaginosis? Bacterial vaginosis is the most common vaginal infection in women ages 15-44. 29% of women age 15-49 have had bacterial vaginosis. How is bacterial vaginosis spread? Researchers do not know the cause of BV or how some women get it, but we do know the infection is more common in sexually active women. How can I avoid getting bacterial vaginosis? The following basic prevention steps may help lower your risk of developing BV: use condoms with sex, limit your number of sex partners, stop douching, increase probiotics in your diet or take oral probiotic capsules containing Lactobacilli. How do I know if I have bacterial vaginosis? Many women (84%) with BV do not have symptoms. If you do have symptoms, you may notice a thin white or gray vaginal discharge, odor, pain, itching, urinary urgency and frequency or burning in the vagina or with urination. How is bacterial vaginosis treated? Traditional treatment is with vaginal or oral antibiotics such as metronidazole or clindamycin. Male sex partners of women diagnosed with BV do not need to be treated. Are there any natural remedies for BV? In addition to probiotics, studies have shown effective treatment with garlic tablets by mouth for seven days, boric acid vaginal suppositories nightly for two weeks and hydrogen peroxide 3% 30ml vaginal washings nightly for seven days.
    [Show full text]
  • The Microbiota Continuum Along the Female Reproductive Tract and Its Relation to Uterine-Related Diseases
    ARTICLE DOI: 10.1038/s41467-017-00901-0 OPEN The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases Chen Chen1,2, Xiaolei Song1,3, Weixia Wei4,5, Huanzi Zhong 1,2,6, Juanjuan Dai4,5, Zhou Lan1, Fei Li1,2,3, Xinlei Yu1,2, Qiang Feng1,7, Zirong Wang1, Hailiang Xie1, Xiaomin Chen1, Chunwei Zeng1, Bo Wen1,2, Liping Zeng4,5, Hui Du4,5, Huiru Tang4,5, Changlu Xu1,8, Yan Xia1,3, Huihua Xia1,2,9, Huanming Yang1,10, Jian Wang1,10, Jun Wang1,11, Lise Madsen 1,6,12, Susanne Brix 13, Karsten Kristiansen1,6, Xun Xu1,2, Junhua Li 1,2,9,14, Ruifang Wu4,5 & Huijue Jia 1,2,9,11 Reports on bacteria detected in maternal fluids during pregnancy are typically associated with adverse consequences, and whether the female reproductive tract harbours distinct microbial communities beyond the vagina has been a matter of debate. Here we systematically sample the microbiota within the female reproductive tract in 110 women of reproductive age, and examine the nature of colonisation by 16S rRNA gene amplicon sequencing and cultivation. We find distinct microbial communities in cervical canal, uterus, fallopian tubes and perito- neal fluid, differing from that of the vagina. The results reflect a microbiota continuum along the female reproductive tract, indicative of a non-sterile environment. We also identify microbial taxa and potential functions that correlate with the menstrual cycle or are over- represented in subjects with adenomyosis or infertility due to endometriosis. The study provides insight into the nature of the vagino-uterine microbiome, and suggests that sur- veying the vaginal or cervical microbiota might be useful for detection of common diseases in the upper reproductive tract.
    [Show full text]
  • Diagnosing Bacterial Vaginosis with a Novel, Clinically-Actionable Molecular Diagnostic Tool
    ISSN: 2581-7566 Volume 1: 2 J Appl Microb Res 2018 Journal of Applied Microbiological Research Diagnosing Bacterial Vaginosis with a Novel, Clinically-Actionable Molecular Diagnostic Tool Joseph P Jarvis1 Doug Rains2 1Coriell Life Sciences, Pennsylvania, USA Steven J Kradel1 2Quantigen Genomics, Indiana, USA James Elliott2 3ThermoFisher Scientific, USA Evan E Diamond3 4Primex Clinical Laboratories, California, USA Erik Avaniss-Aghajani4 5Maternity & Infertility Institute, California, USA Farid Yasharpour5 Jeffrey A Shaman1* Abstract Article Information Bacterial vaginosis is a common condition among women of Article Type: Research reproductive age and is associated with potentially serious side-effects, Article Number: JAMBR109 including an increased risk of preterm birth. Recent advancements in Received Date: 15 June, 2018 microbiome sequencing technologies have produced novel insights Accepted Date: 11 July, 2018 into the complicated mechanisms underlying bacterial vaginosis and Published Date: 18 July, 2018 have given rise to new methods of diagnosis. Here we report on the validation of a quantitative, molecular diagnostic algorithm based on *Corresponding author: Dr. Jeffrey A Shaman, Coriell the relative abundances of ten potentially pathogenic bacteria and four Life Sciences, Philadelphia, Pennsylvania, USA. Tel: + 609 357 0578; Email: jshaman(at)coriell.com as symptomatic (n=149) or asymptomatic (n=23). We observe a clear #These Authors are Joint First Authors on this Work. commensal Lactobacillus species in research subjects (n=172) classified and reinforcing pattern among patients diagnosed by the algorithm that Citation: Jarvis JP, Rains D, Kradel SJ, Elliott J, Diamond is consistent with the current understanding of biological dynamics EE, Avaniss-Aghajani E, Yasharpour F, Shaman JA (2018) and dysregulation of the vaginal microbiome during infection.
    [Show full text]
  • Prevalence of Bacterial Vaginosis Among Patients with Vulvovaginitis in a Tertiary Hospital in Port Harcourt, Rivers State, Nigeria
    Asian Journal of Medicine and Health 7(4): 1-7, 2017; Article no.AJMAH.36736 ISSN: 2456-8414 Prevalence of Bacterial Vaginosis among Patients with Vulvovaginitis in a Tertiary Hospital in Port Harcourt, Rivers State, Nigeria 1 1* 1 1 1 K. T. Wariso , J. A. Igunma , I. L. Oboro , F. A. Olonipili and N. Robinson 1Department of Medical Microbiology and Parasitology, University of Port Harcourt Teaching Hospital, Nigeria. Authors’ contributions This work was carried out in collaboration between the authors. Author KTW designed the study and wrote the protocol. Author FAO wrote the first draft of the manuscript. Authors JAI and NR managed the literature search and performed statistical analysis. Author ILO managed the analysis of the study. All authors read and approved the final manuscript. Article Information DOI: 10.9734/AJMAH/2017/36736 Editor(s): (1) Jaffu Othniel Chilongola, Department of Biochemistry & Molecular Biology, Kilimanjaro Christian Medical University College, Tumaini University, Tanzania. Reviewers: (1) Olorunjuwon Omolaja Bello, College of Natural and Applied Sciences, Wesley University Ondo, Nigeria. (2) Ronald Bartzatt, University of Nebraska, USA. Complete Peer review History: http://www.sciencedomain.org/review-history/21561 Received 12th September 2017 Accepted 12th October 2017 Original Research Article Published 25th October 2017 ABSTRACT Background: Bacterial vaginosis (BV) is one of the three common causes of vulvovaginitis in women of child bearing age, usually resulting from alteration the normal vaginal microbiota and PH. Common clinical presentation includes abnormal vaginal discharge, pruritus, dysuria and dyspareunia. Aims: To determine the prevalence of bacterial vaginosis among symptomatic women of child bearing age that attended various outpatient clinics in the university of Port Harcourt teaching Hospital.
    [Show full text]
  • Women's Health
    Women’s Health Kristen Jones, DO Osteopathic Faculty St. Luke’s Family Medicine Residency Bethlehem, PA ACOFP exam • Women’s Issues (4% of test – OB/GYN = 4%) between 4-6% • Common Topics • Vaginal Discharge • Pelvic Pain • Cancer risk factors • Menstrual disorders • Breast Discharge • Eang disorders • Osteoporosis • HRT • 23 yo with vaginal discharge. Sexually ac[ve. Pelvic exam reveals: • Thin gray-white discharge, pH 5, a strong fishy odor is present when KoH is added to the discharge. • A)Bacterial Vaginosis • B)Gonorrhea • C)Chlamydia • D)Candida • E)Physiologic Discharge • 23 yo with vaginal discharge. Sexually ac[ve. Pelvic exam reveals: • Thin gray-white discharge, pH 5, a strong fishy odor is present when KoH is added to the discharge. • A)Bacterial Vaginosis • B)Gonorrhea • C)Chlamydia • D)Candida • E)Physiologic Discharge Bacterial Vaginosis • pH >4.5 • +Whiff Test • +Clue cells – epithelial cells with adherent bacteria. • Caused by Gardnerella • Treat with Flagyl 500mg po q12hx7 days (safe in pregnancy) • 23 yo with vaginal discharge. Sexually ac[ve. Pelvic exam reveals: • pH <4, vulvar erythema, thick white discharge • Most likely cause is: • A)Bacterial Vaginosis • B)Trichomonas • C)Chlamydia • D)Candida • E)Physiologic Discharge • 23 yo with vaginal discharge. Sexually ac[ve. Pelvic exam reveals: • pH <4.5, vulvar erythema, thick white discharge • Most likely cause is: • A)Bacterial Vaginosis • B)Trichomonas • C)Chlamydia • D)Candida • E)Physiologic Discharge Vaginal Candidiasis • pH <4.5 • Budding yeast and hyphae on KOH • Thick white, chunky discharge • Vulvar erythema and pruri[s • Treat with PO fluconazole 150mg po x1 • Treat with PV clotrimazole or miconazole for 7 days during pregnancy • 23 yo with vaginal discharge.
    [Show full text]
  • Intricate Connections Between the Microbiota and Endometriosis
    International Journal of Molecular Sciences Review Intricate Connections between the Microbiota and Endometriosis Irene Jiang, Paul J. Yong, Catherine Allaire and Mohamed A. Bedaiwy * Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of British Columbia, D415A-4500 Oak Street, Vancouver, BC V6H 3N1, Canada; [email protected] (I.J.); [email protected] (P.J.Y.); [email protected] (C.A.) * Correspondence: [email protected]; Tel.: +604-875-2000 (ext. 4310) Abstract: Imbalances in gut and reproductive tract microbiota composition, known as dysbiosis, disrupt normal immune function, leading to the elevation of proinflammatory cytokines, compro- mised immunosurveillance and altered immune cell profiles, all of which may contribute to the pathogenesis of endometriosis. Over time, this immune dysregulation can progress into a chronic state of inflammation, creating an environment conducive to increased adhesion and angiogenesis, which may drive the vicious cycle of endometriosis onset and progression. Recent studies have demonstrated both the ability of endometriosis to induce microbiota changes, and the ability of antibiotics to treat endometriosis. Endometriotic microbiotas have been consistently associated with diminished Lactobacillus dominance, as well as the elevated abundance of bacterial vaginosis-related bacteria and other opportunistic pathogens. Possible explanations for the implications of dysbiosis in endometriosis include the Bacterial Contamination Theory and immune activation, cytokine- impaired gut function, altered estrogen metabolism and signaling, and aberrant progenitor and stem-cell homeostasis. Although preliminary, antibiotic and probiotic treatments have demonstrated efficacy in treating endometriosis, and female reproductive tract (FRT) microbiota sampling has Citation: Jiang, I.; Yong, P.J.; Allaire, successfully predicted disease risk and stage.
    [Show full text]
  • Bacterial Vaginosis in Pregnancy and Risk of Spontaneous Preterm
    Bacterial vaginosis in pregnancy and risk of spontaneous preterm delivery Approved at the obstetrical guideline-meeting January 2015 Danish Society of Obstetrics and Gynecology (DSOG) Update February 2019 The Lancet has now published reference 31b, by Subtil et al. (2018). The 2015 version of the DSOG guideline included this reference as a congress presentation (ref. 31a), i.e. the risk of bias was high. However, the DSOG working group finds that this publication supports the DSOG recommenda- tions from 2015 (see “Update February 2019” for details). Apart from the “Update February 2019” paper, we did not make any other changes to the original guideline from 2015 . Members of the working group • DSOG: Niels Uldbjerg (chairman, [email protected], +4520679420), Anne Ersbøll, Jens Svare, Kirstine Sneider, Rikke Bek Helmig, Thor Haahr, Mona Aarenstrup Karlsen, Lene Hee Christensen. • Midwife: Louise Weile (MHSc) • Clinical Pharmacology: Agnes Ziobrowska Bech, MD (Department of Clinical Pharmacology, Aarhus University Hospital) • Clinical Microbiology: Claus Østergaard MD, consultant (Department of Clinical Microbiology, Vejle, Denmark) • External reviewers: Bo Jacobsson MD, professor & Ronald Lamont MD, professor. • Advisor concerning diagnostic criteria: Jørgen Skov Jensen (Statens Seruminstitut) Objective The objective of this guideline is to evaluate bacterial vaginosis in pregnancy concerning • Different treatments for prevention of preterm delivery. • Screening of pregnant women with low as well as high risk of sPTD. • Stratification into gestational ages below and above 16 weeks. • Diagnostic methods. Key words Bacterial vaginosis, vaginal pH, pH-glove, vaginal discharge, Nugent score, Amsel score, Gardnerella vaginalis, Mobiluncus species, preterm delivery, preterm birth, GRADE, clindamycin, metronidazole, screening, treatment, probiotics, antibiotics, dysbiosis, abnormal vaginal flora.
    [Show full text]