Role of the vaginal microbiome in miscarriage: exploring the relationship

Abstract

Miscarriage is a devastating pregnancy loss that affects many women worldwide. It is characterized as a spontaneous miscarriage that occurs before 20 weeks of gestation which affects more than 25% of pregnancies. While the causes of miscarriage are complex and multifactorial, recent research has suggested a potential role of the vaginal microbiota. The vaginal microbiome is a dynamic ecosystem of microbes that are essential for preserving vaginal health and avoiding infections. Vaginal dysbiosis has been accompanied with numerous adverse pregnancy complications, such as preterm birth. However, the effect of the vaginal microbiome in miscarriage is not fully understood. This review aims to investigate the link between vaginal microbiota and miscarriage. Also, we investigate the various mechanisms through which the vaginal microbiota may affect miscarriage. Additionally, we examine the implications of these research findings, specifically the possibility of vaginal microbiome screening and targeted interventions to prevent miscarriage.

Keywords: inflammation; pregnancy complications; pregnancy loss; vaginal dysbiosis; vaginal microbiota.

Figure 1

Factors leading to miscarriage: There are several factors that may increase the risk of miscarriage, including maternal age, the vaginal microbiome, immunological factors, hormonal changes, genetic factors, epigenetic factors, lifestyle, endocrines factors, pregnancy history and improper embryo selection. The figure was created with BioRender.com.

Figure 2

The vaginal microbiome may affect the risk of miscarriage. The composition of the vaginal microbiota plays a crucial role in conception and pregnancy. Indeed, the high diversity increased the risk of pathogen colonization and ascending infection that can activate the immune and inflammatory pathway, consequently, the uterine contractions and fetal membrane remodeling that increase the risk of miscarriage, in contrast, the dominance of Lactobacillus spp inhibit the pathogen colonization so the risk of pregnancy complication such as miscarriage is low ( Figure 2 ). The figure was created with BioRender.com.

Figure 3

Predominance of non-commensal bacteria and miscarriage: The overabundance of non-commensal bacteria has the potential to disrupt the tight connections of the epithelium and compromise the integrity of the endometrial mucosal barrier. If the host’s defense mechanisms become compromised, pathogens may enter the endometrial stroma and activate an immune response in antigen-presenting cells and other immune cells that express Pattern-recognition receptors (PRRs). Bacterial products that are ingested or infections that penetrate and rupture the mucosal barrier may activate T cells. An imbalance in cytokine production may favor the production of pro-inflammatory T helper 1 cells (Th1) that generate tumor necrosis factor (TNF), interferon (IFN), and interleukin-2 (IL-2). The figure was created with BioRender.com.