Vaginal Microbiota and Biofilms in a Clinical Trial of the NuvaRing® in Rwanda
Crucitti T1, Hardy L1, van de Wijgert J2, Agaba S3, Buyze J1, Kestelyn E2, 3, Delvaux T1, Mwambarangwe L3, De Baetselier I1, Jespers V1, the Ring Plus study group
1 Insititute of Tropical Medicine, Antwerp, Belgium; 2 University of Liverpool, Liverpool, United Kingdom; 3 Rinda Ubuzima, Kigali, Rwanda
The impact of NuvaRing®, a commonly used estrogen/progestin-containing contraceptive vaginal ring, on the vaginal microbiota has been inadequately studied.
We randomized 120 women 1:1 to intermittent use (three rings with one week off between rings) or continuous use (four rings without ring-free weeks) of the NuvaRing® in Kigali, Rwanda. Quantitative PCR was used to assess the vaginal microbiota at baseline and follow-up, as well as the ring deposits at follow-up. Vaginal slides were Nugent scored and cell-adherent bacteria were visualized using fluorescent in situ hybridization (FISH). One-third pieces of the removed rings were assessed for biomass deposit by crystal violet staining and by scanning electron microscopy.
The baseline prevalence of bacterial vaginosis (BV) by Nugent scoring was high (48%) and BV persisted or recurred during the study in 67% of the cases. The mean Nugent score decreased, and the presence and concentration of lactobacilli in vaginal secretions increased significantly over time. A polymicrobial biofilm containing BV-associated bacteria was detected by FISH in half of the vaginal slides and the presence did not significantly change over time. All ring pieces were coated with an adherent biomass composed of accumulated vaginal epithelial cells covered by either loose or dense structures of bacteria.
NuvaRing® use promoted a lactobacilli-dominated vaginal microbiota in a study population characterized by high BV prevalence. The presence of a polymicrobial vaginal biofilm did not change significantly over time. In addition, biomass deposit on rings, consisting of vaginal epithelial cells covered by vaginal bacteria, was common.
This study was funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) through a project entitled 'Preparing for clinical trials with vaginal rings that protect women from HIV and unintended pregnancy' (grant code SOP.2011.41304.043) with contributions from the Institute of Tropical Medicine in Antwerp and the University of Liverpool.