Vaginal Microbiota in Short Cervix Pregnancy: Secondary Analysis of Pessary vs. Progesterone Trial.

BACKGROUND/OBJECTIVES: Preterm birth (PTB) is a leading cause of neonatal mortality, particularly in women with a short cervix. Vaginal dysbiosis has been associated with increased PTB risk. Progesterone (PR) and Arabin pessary (PE) are commonly used for PTB prevention, but their impact on vaginal microbiome composition is unclear. This study aimed to compare the effects of these interventions on the vaginal microbiome in women at risk of PTB. METHODS: In a secondary analysis of a randomized trial at Hospital das Clínicas, Universidade de São Paulo, 203 women with singleton pregnancies and cervical length ≤ 25 mm at the second trimester were assigned to daily vaginal PR (200 mg) or PE. Vaginal swabs from 44 participants (n = 22 per group) were collected at baseline and 4 weeks post-treatment and analyzed via 16S rRNA gene sequencing. RESULTS: From 88 samples analyzed, 80 showed a low-diversity, Lactobacillus-dominated microbiota, 42 classified into Lactobacillus iners-dominated community state type (CST-III), and 38 presented other Lactobacillus species dominance (termed CST-I/II/V). The remaining eight samples presented non-Lactobacillus dominance (CST-IV). Comparing the two groups, no significant changes in CST were observed between sampling timepoints (PE group, p = 0.368; PR group, p = 0.223). Similarly, Shannon alpha diversity did not change (PE group, p = 0.62; PR group, p = 0.30), and Bray-Curtis dissimilarity also did not change after treatment (p = 0.96, before; p = 0.87, after treatment). CONCLUSIONS: Arabin pessary and vaginal progesterone maintain vaginal microbiome stability in women at high PTB risk, supporting the microbiological safety of both interventions.