Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients.

STUDY QUESTION: 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? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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. PARTICIPANTS/MATERIALS, SETTING AND 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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). LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTERESTS: 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. TRIAL REGISTRATION NUMBER: The project was registered at clinicaltrials.gov (file number NCT02042352).