A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium

Abstract

PurposeThe present study aimed to analyze the pregnancy outcomes of IVF patients presenting Lactobacillus‐dominated microbiota (LDM) or non‐Lactobacillus‐dominated microbiota (NLDM) of their endometrium and to report cases who were treated for NLDM concurrently with antibiotics and prebiotic/probiotic supplements in a Japanese infertile population.MethodsNinety‐two IVF patients were recruited from August 2017 to March 2018. Endometrial fluid samples for sequencing were collected using an IUI catheter. The bacterial status of the endometrium and the pregnancy outcomes were analyzed. For cases with NLDM, antibiotics and prebiotics/probiotics were administered according to their individual microbial conditions.ResultsForty‐seven cases (51.1%) presented LDM and 45 cases (48.9%) presented NLDM at initial analysis. Nine Patients with NLDM were treated by antibiotics and prebiotics/probiotics, and successfully became Lactobacillus‐dominant. Pregnancy rates by single vitrified‐warmed blastocyst transfers were higher in the LDM group (58.9% per patient and 36.3% per FBT) than in the NLDM group (47.2% per patient and 34.7% per FBT) but not significantly different.ConclusionThe results of this study could not necessarily prove the clear benefit of establishing Lactobacillus‐dominated endometrium in terms of pregnancy outcome, but there is significance in searching for endometrial microbial status of infertile patients and recovering Lactobacillus‐dominated endometrium might benefit implantation.

New Opportunities for Endometrial Health by Modifying Uterine Microbial Composition: Present or Future?

“…Atopobium [6,[8][9][10], Bacteroides [12], Betaproteobacteria [12], Bifidobacterium [5,[8][9][10][11]13,104], Burkholderia [7], Chitinophagaceae [12], Corynebacterium [104], Escherichia/Shigella [10,12], Flavobacterium [4], Gardnerella [5][6][7][8][9][10][11]13], Lactobacillus [4][5][6][7][8][9][10][11]13,104], Megasphaera [9,10], Pelomonas [12], Prevotella [8][9][10][11]13], Pseudoalteromonas [5], Rhodanobacter [5], Sneathia [8,9], Staphylococcus [8]…”

“…The initial studies of endometrial microbiome suggest its association with reproductive outcomes in assisted reproduction [4][5][6][7][8][9][10][11][12][13] and with different gynaecological pathologies such as chronic endometritis (CE) [14][15][16], endometriosis [13,[17][18][19][20][21], dysfunctional endometrial bleeding [22], endometrial polyps [16], and endometrial cancer or hyperplasia [23][24][25]. Nevertheless, causality has been difficult to prove because the reproductive tract represents a polymicrobial niche [26], and it is not clear whether dysbiosis within the uterus is a cause or a consequence of a pathology.…”

The Impact Of The Vaginal And Endometrial Microbiome Pattern On Assisted Reproduction Outcomes

“…When we analyzed the taxonomic characterization, we also implantation (18). In this preliminary study, the predominance of Lactobacillus was favorable in terms of the pregnancy rate; however, the results were not as significant as in the previous pilot study (17); the reasons for this may be due to the limited number of cases, short follow-up period, or ethnic differences. In an other study also concluded that women with an abnormal vaginal microbiota are approximately 1.4 times less likely to become pregnant after in vitro fertilization treatment, compared to women with a normal microbiota pattern (19).…”

“…The ability of lactobacilli to inhibit infection without inducing inflammation can maximize fertility and favour pregnancy outcomes(16). The presence of a non-Lactobacillus-dominated microbiome (NLDM) is associated with a lower rate of implantation, pregnancy rate, pregnancy progression and live birth(17). Moreno et al reported that a relative abundance of lactobacilli of less than 90% in endometrial fluid was predictive of adverse pregnancy outcomes.…”

“…In this study, patients classified as NLDM and showing a relative abundance of more than 80% Lactobacillus spp. in the endometrium showed good pregnancy outcomes, suggesting that this threshold could be considered sufficient for embryo implantation(17). In addition, even if classified as NLDM, the endometrium with a dominant quantity of Bifidobacteria could also be an acceptable environment for implantation(18).Another pilot study aimed to analyze both the endometrial and vaginal microbiome in the infertile Japanese population via sequencing and to assess the impact of the endometrial and vaginal environment on embryo implantation.…”