G. vaginalis sustain a proinflammatory response in the fetal membranes in vitro, while genital mycoplasmas induce a strong control of the inflammatory response. The ability of genital mycoplasmas to control the proinflammatory response may favor their survival in the upper genital tract.

Genital mycoplasmas (GM), such as Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma parvum, and Ureaplasma urealyticum are commonly associated with spontaneous preterm labor (SPTL), spontaneous preterm birth (PTB), and preterm prelabor rupture of membranes (PPROM). This study determined the association between GM and such adverse pregnancy outcomes. We searched for studies published 1980–2019 in MEDLINE, EMBASE, and Web of Science. Studies were eligible when GM was detected during pregnancy. We included 93 and 51 studies in determining the prevalence and the inflammatory biomarkers associated with GM, respectively, using the “metafor” package within R. The protocol was registered with PROSPERO (registration no. CRD42016047297). Women with the studied adverse pregnancy outcomes had significantly higher odds of presence with GM compared to women who delivered at term. For PTB, the odds ratios were: M. hominis (OR: 2.25; CI: 1.35–3.75; I2: 44%), M. genitalium (OR: 2.04; CIL 1.18–3.53; I2: 20%), U. parvum (OR: 1.75; CI: 1.47–2.07; I2: 0%), U. urealyticum (OR: 1.50; CI: 1.08–2.07; I2: 58%). SPTL had significantly higher odds with M. hominis (OR: 1.96; CI: 1.19–3.23; I2: 1%) or U. urealyticum (OR: 2.37; CI: 1.20–4.70; I2: 76%) compared to women without SPTL. Women with PPROM had significantly higher odds with M. hominis (OR: 2.09; CI: 1.42–3.08; I2: 0%) than women without PPROM. However, our subgroup analysis based on the diagnostic test and the sample used for detecting GM showed a higher prevalence of GM in maternal samples than in fetal samples. GM presence of the cervix and vagina was associated with lower odds of PTB and preterm labor (PTL). In contrast, GM presence in the AF, fetal membrane, and placenta was associated with increased odds of PTB and PTL. However, genital mycoplasmas may not elicit the massive inflammation required to trigger PTB. In conclusion, GM presence in the fetal tissues was associated with significantly increased odds of PTB and PTL.

The polybacterial invasion of the amniotic cavity and risk of preterm birth is often due to cervicovaginal bacteria such as genital mycoplasmas (Mycoplasma hominis and Ureaplasma urealyticum) and Gardnerella vaginalis. The most studied biomarker associated with preterm birth is interleukin-6 (IL-6), a pleiotropic cytokine that performs different functions based on classical or trans-signaling mechanisms. This study evaluated the changes in IL-6 and IL-6 function associated accessory molecules by human fetal membranes to determine the functional availability of IL-6 assessment in an in vitro model of polybacterial infection. Fetal membranes were treated with LPS or heat-inactivated genital mycoplasmas and G. vaginalis alone or in combination. IL-6 and its soluble receptors (sgp130, sIL-6R) were assessed in conditioned medium by immunoassays and membrane-bound receptors were evaluated in the tissue using immunohistochemistry and RT-PCR. Data from protein and gene expression were evaluated using linear mixed effects models. Data from immunohistochemistry were evaluated using one-way analysis of variance followed by the Tukey test. Genital mycoplasmas alone, or in combination, inhibited IL-6 trans-signaling with increased sgp130 production. G. vaginalis activated the classical IL-6 signaling pathway, as did LPS. Polybacterial treatment resulted in a balanced response with neither pathway being favored. The increase in IL-6 production by fetal membranes in response to infection is likely a non-specific innate response and not an indicator of a functional mediator of any labor-inducing pathways. This suggests that correlating the risk of adverse pregnancy outcomes and designing interventions based on IL-6 levels without considering soluble receptors may be an ineffective strategy.

Lower levels of hBD-1, hBD-2, and hBD-3 in cervicovaginal fluid were detected in the presence of C. trachomatis infection.

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Aims To compare the cervicovaginal levels of human beta defensin (hBD)-1, 2 and 3 of women according to the status of Nugent-defined bacterial vaginosis (BV). Methods A total of 634 women of reproductive age were included in the study. Participants were equally distributed in two groups: according to the classification of vaginal smears according to Nugent criteria in normal (scores 0 to 3) and BV (scores ≥7). Cervicovaginal fluid samples were used for measurements of hBDs1, 2 and 3 levels by enzyme-linked immunosorbent assay (ELISA). Levels of each hBD were compared between the two study groups using Mann-Whitney test, with p-value <0.05 considered as significant. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for sociodemographic variables and hBD1-3 levels associated with BV a multivariable analysis. Correlation between Nugent score and measured levels of hBDs1-3 were calculated using Spearman’s test. Results Cervicovaginal fluids from women with BV showed lower levels of hBD-1 [median 2,400.00 pg/mL (0–27,800.00); p<0.0001], hBD-2 [5,600.00 pg/mL (0–45,800.00); p<0.0001] and hBD-3 [1,600.00 pg/mL (0–81,700.00); p = 0.012] when compared to optimal microbiota [hBD-1: [median 3,400.00 pg/mL (0–35,600.00), hBD-2: 12,300.00 pg/mL (0–95,300.00) and hBD-3: 3,000.00 pg/mL (0–64,300.00), respectively]. Multivariable analysis showed that lower levels of hBD-1 (OR: 2.05; 95% CI: 1.46–2.87), hBD-2 (OR: 1.85; 95% CI: 1.32–2.60) and hBD-3 (OR: 1.90; 95% CI: 1.37–2.64) were independently associated BV. Significant negative correlations were observed between Nugent scores and cervicovaginal levels of hBD-1 (Spearman’s rho = -0.2118; p = 0.0001) and hBD-2 (*Spearman’s rho = -0.2117; p = 0.0001). Conclusions Bacterial vaginosis is associated with lower cervicovaginal levels of hBDs1-3 in reproductive-aged women.

Amniochorion membranes were collected from 25 pregnant women at preterm labor, in the presence or not of Preterm Premature Rupture of Membranes (PPROM) and 27 pregnant women at term in the presence at labor, in order to quantify the expression and to evaluate the immunoreactivity of human beta defensins (HBD)1, HBD2, HBD3 and HBD4 in amniochorion membranes from pregnancies complicated by spontaneous prematurity. The HBDs were evaluated by immunohistochemistry, real time quantitative PCR and ELISA. Statistical analyses were performed using Chi-squared and Mann Whitney tests. There was no significant difference in HBDs expression between study and