Clinical Relevance of Vaginal and Endometrial Microbiome Investigation in Women with Repeated Implantation Failure and Recurrent Pregnancy Loss

Abstract

Recent studies have investigated if and how the vaginal and endometrial microbiome might affect endometrial receptivity and reproductive health. Although there is no consensus on the existence of a core uterine microbiome yet, evidence shows that the dominance of Lactobacillus spp. in the female reproductive tract is generally associated with eubiosis and improved chances of successful implantation and an ongoing pregnancy. Conversely, vaginal and endometrial dysbiosis can cause local inflammation and an increase of pro-inflammatory cytokines, compromising the integrity and receptivity of the endometrial mucosa and potentially hampering successful embryonic implantation. This review provides a critical appraisal of the influence of the vaginal and endometrial microbiome as parts of the female reproductive tract on fertility outcomes, focusing on repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It seems that RIF as well as RPL are both associated with an increase in microbiome diversity and a loss of Lactobacillus dominance in the lower female reproductive system.

Understanding the Role of Female Genital Tract Microbiome in Recurrent Implantation Failure

“…As mentioned above, the uterine cavity harbors far fewer microorganisms and specifically, about 10,000 times fewer microorganisms in comparison to the vagina [ 45 ]. This significantly smaller biomass and the relative inaccessibility of the uterine cavity without risking the contamination of the specimen is the reason why no consensus has been reached regarding the composition of the healthy uterine microbiome [ 77 , 78 ]. In a study of 141 women with RIF, 121 individuals had Lactobacillus non-dominant microbiomes, and high numbers of Streptococcus , Staphylococcus , Neisseria , and Klebsiella were reported [ 2 ] which are known to disrupt the normal endometrium [ 11 ].…”

“…Another set of studies has shown a drastic decrease in Lactobacilli and an abundance of Dialister , Prevotella , Gardnerella , and Anaeroccus in women with chronic endometritis [ 28 , 67 ]. The disruption of the healthy uterine microbiome is thought to result in chronic endometritis [ 77 ] and triggers a pro-inflammatory response that renders the endometrium unfavorable for implantation [ 22 , 32 , 80 ]. What we need to mention, however, is the fact that there are studies that failed to report a difference between the women with dysbiotic and eubiotic communities as far as the IVF success rates are concerned [ 55 , 81 ].…”