Higher Incidence of Colonization with Gardnerella Vaginalis in Patients with Recurrent Miscarriage and Elevated Peripheral Natural Killer Cells

Background: Screening of vaginal microbiota in recurrent miscarriage (RM) is not included in international guidelines. However, there are subgroups of RM patients with a history of obstetrical complications like preterm rupture of the membranes or late miscarriage that are associated with infections. Due to the small number of currently available studies no clear pathophysiological pathway can be conducted.

Objective: The aim of this study was to analyze the composition of the vaginal microbiota in RM patients and to correlate the findings to various immune parameters.

Methods: In total, n=243 RM patients with ≥3 consecutive miscarriages were recruited between 11/2011 and 03/2016. Vaginal swabs were taken and placed in a collection tube and send to the Department of Infectious Diseases, Medical Microbiology of the University of Heidelberg for analysis by microscopy and culture. Further, a cervical swab was taken in n=187 patients and the presence of Chlamydia trachomatis was evaluated by a molecular assay. Peripheral blood levels of CD45+CD3-CD56+CD16+ peripheral natural killer cells (pNK, determined by four-color fluorescence flow cytometry) and CD56+ uterine NK cells (uNK, uterine biopsy, determined by immunohistochemistry) were evaluated. The vaginal microbiota was analyzed in subgroups of RM patients.

Results: The frequency of RM patients positive for Gardnerella vaginalis was 18.9%, for Candida species 7.8%, for group B Streptococcus 11.1% and for Enterobacteriaceae 14.8%. Commensal lactobacilli were absent in 14.4% of the women. Chlamydia trachomatis was detected by molecular assay in only n=1 case (0.53%). The prevalence of Gardnerella vaginalis in RM patients with elevated pNK cells (> 280/ μl, n=69) was significantly higher (p=0.017) compared to patients with normal pNK cells (n=174).

Conclusion: RM patients with elevated pNK suffer more often from colonization by Gardnerella vaginalis. This might indicate an association between the vaginal microbiota, local inflammation, changes in immune parameters and miscarriage.