Miscarriage: Is vaginal dysbiosis a suspect?

Fertility

Miscarriages that are not genetic in origin appear to be associated with vaginal dysbiosis and local inflammation. These results could open up new avenues for prevention in women with a vaginal microbiota low in lactobacilli.

About this article

Created 04 May 2022

Updated 10 May 2022

One in 5 pregnancies ends in an early miscarriage (before 12 weeks), and half are caused by chromosomal abnormalities (aneuploid miscarriages). Late euploid miscarriages can occur between 12 and 24 weeks, usually in connection with an infection (2 in 3 cases). Little is currently known about the mechanisms involved, but it is thought that the vaginal microbiota may play a role.

Hence the following hypothesis:

might these late euploid miscarriages be caused by inflammatory signals linked with the composition of vaginal microbiota?

1/5 One in 5 pregnancies ends in an early miscarriage

1/2 half are caused by chromosomal abnormalities

Miscarriages: a question of lactobacilli?

To answer this question, researchers monitored 167 pregnancies: 74 full-term pregnancies, 54 non-genetic miscarriages (euploid pregnancies) and 39 genetic miscarriages (aneuploid). Analysis of their microbiota (16S RNA) revealed the existence of 2 types of vaginal microbiota: the first is 94.2% dominated by Lactobacillus spp. (75% of samples); the second is characterized by a depletion of lactobacilli, with an average concentration of just 18.5% (25% of samples).

At the same time, compared to aneuploid miscarriages, euploid miscarriages have been shown to be associated with a vaginal microbiota that is:

richer in bacteria and diversity
low in Lactobacillus spp.
rich in Streptococcus spp. (60% of cases) and Prevotella spp. (40%).

Vaginal microbiota and inflammation

In terms of inflammation, low levels of lactobacilli are associated with high concentrations of cytokines in the vaginal/cervical fluid, regardless of pregnancy outcome. Above all, subgroups dominated by Prevotella or Streptococcus spp. have significantly higher concentrations of TNF-α and of some proinflammatory interleukins (IL-6, IL-8, IL-1β). A depletion in Lactobacillus spp. may therefore be associated with a proinflammatory environment detrimental to the smooth progress of pregnancy. This would be consistent with the higher frequency of miscarriages observed in cases of low levels of vaginal microbiota lactobacilli.

In addition, a high concentration of streptococci is thought to be the most significant risk factor for euploid miscarriages, and the main factor responsible for the increase in proinflammatory mediators in such patients.

Sources

^{Grewal K, Lee YS, Smith A et al. Chromosomally normal miscarriage is associated with vaginal dysbiosis and local inflammation. BMC Med. 2022 Jan 28;20(1):38.}