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This prospective cohort study aimed to evaluate the performance of Flora select™ (FS), a newly developed real-time PCR test, for the assessment of the vaginal microbiome during early pregnancy. Five hundred and fifty-six pregnant women underwent examinations of FS, Nugent score—a Gram-staining scoring system for the diagnosis of bacterial vaginosis (BV)—and conventional bacterial culture between 8 weeks and 12 gestational weeks. Nugent scores of 0–3, 4–6, and ≥7 were found in 469 (84.2%), 41 (7.4%), and 47 (8.5%) of the women, respectively. Relative dominance rates of Lactobacillus species of high (≥80% medium (50%≤, <80%), and low (0.1≤, <50%), and no detection (<0.1%) were 63.0%, 8.8%, 17.1%, and 11.2%, respectively. Gardnerella, Prevotella, Atopobium, Streptococcus, Ureaplasma, and Mycoplasma species were detected in 23.9%, 17.6%, 17.1%, 7.0%, 23.0%, and 4.9% of the women, respectively. Gardnerella species were detected in all women with Nugent scores ≥7 and Ureaplasma were detected in 40.4% of them. BV-associated bacterial species were also detected in 70.7% of women with Nugent scores of 4–6. Gardnerella, Prevotella, Atopobium, Streptococcus, Ureaplasma, and Mycoplasma species were highly prevalent in women with Nugent scores ≥4 or Lactobacillus species <50%. FS detected Gardnerella, Prevotella, and Atopobium species more effectively than conventional bacterial culture. FS could determine relative dominance rates of Lactobacillus species in the vaginal microbiome, and simultaneously detect four kinds of BV-associated bacteria, Ureaplasma and Mycoplasma species. Therefore, FS may be clinically useful for the screening of the vaginal microbiome during pregnancy to prevent preterm birth and for the assessment of the vaginal microbiome after BV treatments. [ABSTRACT FROM AUTHOR]

Objectives: This prospective study evaluated whether endometriosis is associated with chronic endometritis (CE) and affects the uterine endometrium microbiome (UEM) in women with repeated implantation failure (RIF). Methods: Forty-three women with RIF were divided into 12 with endometriosis (EM) and 31 without endometriosis (non-EM). The UEM was examined by 16S ribosomal RNA (rRNA) sequencing, and CE was determined by CD 138 staining (plasma cells > 5.15/10 mm2) simultaneously. Results: The EM group had a higher bacterial number (EM vs. non-EM; median [range], 6.5 vs. 3 [3–11, 1–16], p = 0.009), while the frequency of Lactobacillus species did not change. The rates of presence of Dialister (41.7% [5/12] vs. 3.3% [1/31], p = 0.004) and Streptococcus species (58.3% [7/12] vs. 16.1% [5/31], p = 0.017) were higher in the EM group. The prevalence of CE did not differ between the two groups. Multivariable logistic regression analysis revealed that the presence of Dialister species (odds ratio, 10.97, 95% confidence interval, 1.17–249.37, p = 0.036) was associated with endometriosis. In the EM group, five women with Dialister species had a higher number of bacterial species (10 vs. 5 [6–11, 3–7], p = 0.021) and higher Shannon diversity index (0.50 vs. 0.20 [0.19–1.39, 0.03–0.46], p = 0.026) than seven without Dialister species. Conclusions: Dialister and Streptococcus species, and the increased number of bacterial species in UEM may be related to the pathogenesis of RIF complicated by endometriosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether chronic endometritis (CE) and uterine endometrium microbiota were associated with repeated implantation failures (RIFs) and recurrent pregnancy losses (RPLs). In this prospective study, uterine endometrial specimens were obtained from 24 women with RIF, 27 with RPL, and 29 fertile control women. Immunohistochemical staining of CD138 for CE and 16S ribosomal RNA (rRNA) sequencing analysis for uterine endometrium microbiota were performed simultaneously. To assess CE, Liu's method, McQueen scores and plasma cell count/10 mm2 were used. The frequency of CE (plasma cells > 5.15/10 mm2) was higher in women with RPL (29.6%) than in fertile controls (6.8%, p < 0.05). The plasma cell count/10 mm2 in women with RPL (median 1.53, range 0–252.6, p < 0.01) and women with RIF (median 0.6, range 0–6.98, p < 0.05) was higher than in fertile controls (median 0, range 0–29). The uterine endometrium microbiota in women with RPL or RIF was not significantly different from that in fertile controls. However, the relative dominance rate of Lactobacillus iners (median 4.7%, range 0–99.9 vs. median 0%, range 0–100, p < 0.001) and the positive rate of Ureaplasma species (36.3% vs. 8.6%, p < 0.05) were higher in 11 women with CE than in 69 women without CE. The results suggest that CE may be involved in the pathophysiology of RPL and RIF. Lactobacillus iners and Ureaplasma species may be associated with the etiology of CE. [ABSTRACT FROM AUTHOR]

Anti-β2-glycoprotein I/HLA-DR (anti-β2GPI/HLA-DR) antibody has been reported to be associated with antiphospholipid syndrome and recurrent pregnancy loss (RPL). We conducted a prospective multicenter cross-sectional study aimed at evaluating whether the anti-β2GPI/HLA-DR antibody is associated with adverse obstetric outcomes and RPL. From 2019 to 2021, serum anti-β2GPI/HLA-DR antibody levels (normal, <73.3 U) were measured in 462 women with RPL, 124 with fetal growth restriction (FGR), 138 with hypertensive disorders of pregnancy (HDP), 71 with preterm delivery before 34 gestational weeks (preterm delivery (PD) ≤ 34 GWs), and 488 control women who experienced normal delivery, by flow cytometry analysis. The adjusted odds ratios (aORs) of anti-β2GPI/HLA-DR antibody positivity for adverse obstetric outcomes and RPL were evaluated on the basis of comparisons between the control and each patient group, using multivariable logistic regression analysis. The following were the positivity rates for the anti-β2GPI/HLA-DR antibody in the patient and control groups: RPL, 16.9%; FGR, 15.3%; HDP, 17.4%; PD ≤ 34 GWs, 11.3%; and the control, 5.5%. It was demonstrated that anti-β2GPI/HLA-DR antibody positivity was a significant risk factor for RPL (aOR, 3.3 [95% confidence interval {CI} 1.9–5.6], p < 0.001), FGR (2.7 [1.3–5.3], p < 0.01), and HDP (2.7 [1.4–5.3], p < 0.01) although not for PD ≤ 34 GWs. For the first time, our study demonstrated that the anti-β2GPI/HLA-DR antibody is involved in the pathophysiology underlying FGR and HDP, as well as RPL. [ABSTRACT FROM AUTHOR]

Sphingosine 1-phosphate (S1P), an inflammatory mediator, is abundantly contained in red blood cells and platelets. We hypothesized that the S1P concentration in the peritoneal cavity would increase especially during the menstrual phase due to the reflux of menstrual blood, and investigated the S1P concentration in the human peritoneal fluid (PF) from 14 non-endometriosis and 19 endometriosis patients. Although the relatively small number of samples requires caution in interpreting the results, S1P concentration in the PF during the menstrual phase was predominantly increased compared to the non-menstrual phase, regardless of the presence or absence of endometriosis. During the non-menstrual phase, patients with endometriosis showed a significant increase in S1P concentration compared to controls. In vitro experiments using human intra-peritoneal macrophages (MΦ) showed that S1P stimulation biased them toward an M2MΦ-dominant condition and increased the expression of IL-6 and COX-2. An in vivo study showed that administration of S1P increased the size of the endometriotic-like lesion in a mouse model of endometriosis. [ABSTRACT FROM AUTHOR]

Background: Relaxin (RLX)-2, produced by the corpus luteum and placenta, is known to be potentially effective in fibrotic diseases of the heart, lungs, kidneys, and bladder; however, its effectiveness in endometriosis has not yet been investigated. In the present study, we conducted a comprehensive study on the effect of RLX-2 on endometriosis. We checked the expressions of LGR-7, a primary receptor of RLX-2, in endometriomas using immunohistochemistry. Endometriotic stromal cells (ESCs) purified from surgical specimens were used in in vitro experiments. The effects of RLX-2 on ESCs were evaluated by quantitative-PCR, ELISA, and Western blotting. Gel contraction assay was used to assess the contraction suppressive effect of RLX-2. The effect of RLX-2 was also examined in the endometriosis mouse model. LGR-7 was expressed in endometriotic lesions. In ESCs, RLX-2 increased the production of cAMP and suppressed the secretion of interleukin-8, an inflammatory cytokine, by 15% and mRNA expression of fibrosis-related molecules, plasminogen activator inhibitor-1 (PAI-1), and collagen-I by approximately 50% (p < 0.05). In the gel contraction assay, RLX-2 significantly suppressed the contraction of ESCs, which was cancelled by removing RLX-2 from the medium or by adding H89, a Protein Kinase A (PKA) inhibitor. In ESCs stimulated with RLX-2, p38 MAPK phosphorylation was significantly suppressed. In the endometriosis mouse model, administration of RLX-2 significantly decreased the area of the endometriotic-like lesion with decreasing fibrotic component compared to non-treated control (p = 0.01). RLX-2 may contribute to the control of endometriotic lesion by suppressing fibrosis, scar formation, and inflammation. [ABSTRACT FROM AUTHOR]