title: Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients.
abstract: OBJECTIVE
  What is the diagnostic performance of qPCR assays compared with Nugent scoring for abnormal vaginal microbiota and for predicting the success rate of IVF treatment?
  
  
  CONCLUSIONS
  The vaginal microbiota of IVF patients can be characterized with qPCR tests which may be promising tools for diagnosing abnormal vaginal microbiota and for prediction of clinical pregnancy in IVF treatment.
  
  
  BACKGROUND
  Bacterial vaginosis (BV) is a common genital disorder with a prevalence of approximately 19% in the infertile population. BV is often sub-clinical with a change of the vaginal microbiota from being Lactobacillus spp. dominated to a more heterogeneous environment with anaerobic bacteria, such as Gardnerella vaginalis and Atopobium vaginae. Few studies have been conducted in infertile women, and some have suggested a negative impact on fecundity in the presence of BV.
  
  
  METHODS
  A cohort of 130 infertile patients, 90% Caucasians, attending two Danish fertility clinics for in vitro fertilization (IVF) treatment from April 2014-December 2014 were prospectively enrolled in the trial.
  
  
  METHODS
  Vaginal swabs from IVF patients were obtained from the posterior fornix. Gram stained slides were assessed according to Nugent's criteria. PCR primers were specific for four common Lactobacillus spp., G. vaginalis and A. vaginae. Threshold levels were established using ROC curve analysis.
  
  
  RESULTS
  The prevalence of BV defined by Nugent score was 21% (27/130), whereas the prevalence of an abnormal vaginal microbiota was 28% (36/130) defined by qPCR with high concentrations of Gardnerella vaginalis and/or Atopobium vaginae. The qPCR diagnostic approach had a sensitivity and specificity of respectively 93% and 93% for Nugent-defined BV. Furthermore, qPCR enabled the stratification of Nugent intermediate flora. Eighty-four patients completed IVF treatment. The overall clinical pregnancy rate was 35% (29/84). Interestingly, only 9% (2/22) with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (P = 0.004).
  
  
  CONCLUSIONS
  Although a total of 130 IVF patients were included in the study, a larger sample size is needed to draw firm conclusions regarding the possible adverse effect of an abnormal vaginal microbiota in relation to the clinical pregnancy rate and other reproductive outcomes.
  
  
  CONCLUSIONS
  Abnormal vaginal microbiota may negatively affect the clinical pregnancy rate in IVF patients. If a negative correlation between abnormal vaginal microbiota and the clinical pregnancy rate is corroborated, patients could be screened and subsequently treated for abnormal vaginal microbiota prior to fertility treatment.
  
  
  BACKGROUND
  This study was funded by The AP Møller Maersk Foundation for the advancement of Medical Science and Hospital of Central Jutland Research Fund, Denmark. No competing interests.
  
  
  BACKGROUND
  The project was registered at clinicaltrials.gov (file number NCT02042352).
authors.affiliation: Faculty of Health, Aarhus University and the Fertility Clinic, Skive Regional Hospital, Skive, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Haahr
authors.affiliation: Statens Serum Institute, Copenhagen, Denmark.
authors.forename: J S
authors.initials: JS
authors.lastname: Jensen
authors.affiliation: Faculty of Health, Aarhus University and the Fertility Clinic, Skive Regional Hospital, Skive, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Thomsen
authors.affiliation: Department of Clinical Microbiology, Regional Hospital Central and West Jutland, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Duus
authors.affiliation: Trianglen Fertility Clinic, Copenhagen, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Rygaard
authors.affiliation: Faculty of Health, Aarhus University and the Fertility Clinic, Skive Regional Hospital, Skive, Denmark peter.humaidan@midt.rm.dk.
authors.forename: P
authors.initials: P
authors.lastname: Humaidan
mesh_terms: D039903:Actinobacteria / Q000145:classification / Q000302:isolation & purification*; D000328:Adult; D058345:Asymptomatic Infections; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005191:Family Characteristics; D005260:Female; D005307:Fertilization in Vitro; D006194:Gardnerella vaginalis / Q000145:classification / Q000302:isolation & purification; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000628:therapy*; D007248:Infertility, Male; D007778:Lactobacillus / Q000145:classification / Q000302:isolation & purification*; D008297:Male; D058889:Molecular Typing; D011247:Pregnancy; D018873:Pregnancy Rate; D015995:Prevalence; D011446:Prospective Studies; D012372:ROC Curve; D014621:Vagina / Q000382:microbiology*; D016585:Vaginosis, Bacterial / Q000175:diagnosis / Q000382:microbiology / Q000503:physiopathology*
keywords: Atopobium vaginae; Gardnerella vaginalis; IVF; Nugent score; bacterial vaginosis; clinical pregnancy; prevalence; vaginal microbiota