Treatment of the Intermediate Vaginal Microbiota With Vaginal Probiotics Containing Lactobacillus Casei Rhamnosus (Lcr Regenerans) to Improve Pregnancy Outcomes

Despite recent achievements in perinatal care, the prevention of preterm delivery (PTD) remains a major challenge in modern obstetrics. Healthy vaginal flora, dominated by Lactobacillus species (spp.), plays an important role in the protection against genital infections, which are considered a frequent cause of PTD. Imbalances of the vaginal flora caused by a reduction in the proportion of Lactobacillus spp. can lead to an overgrowth of mixed anaerobic bacteria, which can ultimately result in bacterial vaginosis (BV). Since the effect of treating pregnant women with an abnormal vaginal flora was introduced, BV has gained interest and is now a well-known risk factor for ascending infections and subsequent PTD. However, the overall risk reduction of PTD through antibiotic treatment of an abnormal flora was disproved by large and well-designed studies in a general obstetrical population.

At present, little is known about the role of the intermediate vaginal flora, which can either be regarded as the transition from a healthy to an abnormal flora or as the transition from abnormal flora back to a healthy vaginal microbiota. The intermediate vaginal flora constitutes a highly heterogeneous group that may or may not include vaginal Lactobacillus spp. and that may or may not be characterised by the presence of anaerobic bacteria. In 2007, a meta-analysis reported that the presence of intermediate vaginal flora was not associated with PTD, late miscarriage, maternal or neonatal infection, or perinatal mortality. In contrast, an observational study by Hay et al.reported a high rate of late miscarriage (16-24 gestational weeks) in women with intermediate vaginal flora at an examination before 16 gestational weeks. Additionally, another study reported an association of PTD with partial BV, which is defined as streaks of BV flora in a smear that has areas of normal flora.

Latest research reported that there is an association between the intermediate vaginal flora and PTD. In one of our previous studies, intermediate flora was identified on the examined screening smears of 529/8421 (6.3%) women. In this group, 349/529 (66%) women had a Nugent score of 4, 94/529 (17.8%) had a Nugent score of 5, and 86/529 (16.2%) had a Nugent score of 6. In women with a Nugent score of 4, 232/349 (66.5%) women were assigned to the Lactobacilli group. The Non-Lactobacilli group consisted of 117/349 (33.5%) women with a Nugent score of 4 due to the total absence of any bacterial colonisation, including Lactobacillus spp. The preterm delivery rate was significantly lower in the Lactobacilli than in the Non-Lactobacilli group On follow-up smears, bacterial vaginosis rates were 9% in the Lactobacilli and 7.8% in the Non-Lactobacilli group. Hence, according to this retrospective study, the absence of vaginal Lactobacillus species and any bacterial colonisation increases the risks of preterm delivery and low birth weight in women with intermediate vaginal flora in early pregnancy.

In the currently presented trial, investigators aim to evaluate the treatment of the intermediate vaginal flora during the first trimester of pregnancy with vaginal lactobacilli to restore the normal vaginal microbiota and therewith reduce the rate of PTD.

At investigators Department, pregnancy care includes a prenatal consultation, where women registered for a planned delivery at our department between 10 + 0 (10 weeks plus 0 days) and 16 + 0 (16 weeks plus 0 days) gestational weeks. Women underwent routine screening for asymptomatic vaginal infections and characterization due to Nugent score. All women except those with a normal flora (Nugent score 0 to 3) will be asked to undergo a follow-up smear between 14 + 0 (14 weeks plus 0 days) and 22 + 0 (22 weeks plus 0 days) gestational weeks at our department. Vaginal smears will be obtained after vaginal fluid collection with sterile swabs from the lateral vaginal wall and posterior fornix vaginae. Both at first and control smear. All smears will be Gram-stained and microscopically analyzed by one of four biomedical laboratory assistants, specialized in gynecological cytopathology, at a laboratory that is certified according to DIN EN ISO 9001:2008. Nugent scores of 0 to 3 will be considered to indicate normal vaginal flora, 4 to 6 to indicate intermediate vaginal flora, and 7 to 10 to indicate BV.