High-risk human papillomaviruses (hrHPVs) are causally related to cervical intraepithelial neoplasia (CIN) and subsequent cervical cancer (CC). The vaginal microbiome has been suggested to play a role in the development of CC, but the effect of conservative surgical treatment on the microbiome and hrHPV elimination has not been elucidated. In this study, we aimed to characterize the vaginal microbiome and inflammatory chemokine profile in 85 women treated for CIN2-CIN3 lesions, before and after surgical CIN removal. The results showed, as expected, a high prevalence of dysbiotic microbiomes and vaginal proinflammatory cytokines in the CIN cohort, correlated with disease severity, at the basal level. By contrast, surgical CIN removal induced significant vaginal microbiome variations, and specific microbiome/cytokine profiles were associated with hrHPV clearance/ persistence at 6-month follow-up. hrHPV-cleared patients, in fact, showed a specific increase of L. crispatus and decrease of dysbiosis and inflammatory cytokines compared to hrHPV-persistent patients. These data highlight the crosstalk between HPV and the local microbiome, and suggest that vaginal microbiome modulation might represent a novel approach to modifying the natural history of hrHPV-related CC. Study registration n. ISRCTN34437150 (https://www.isrctn.com/ISRCTN34437150).
Late-onset Intrauterine growth restriction (IUGR) refers to impaired growth and development of the fetus, characterized by placental morphological abnormalities that affect the fetus's supply of nutrients. Human leukocyte antigen-G (HLA-G) is physiologically expressed during pregnancy, but decreased in normal placenta during the last weeks of gestation possibly inducing childbirth. Several viruses involved in congenital infection, such as herpesviruses, exploit HLA-G expression as an immune-escape mechanism. To date, despite different congenital herpetic infections having been associated with late IUGR, no direct implication of Human herpesvirus 6 (HHV-6) infection has been reported. We evaluated HLA-G expression and HHV-6 infection in 11 placentas from late-onset IUGR newborns and 11 placentas from uncomplicated pregnancies by histopathological and immunohistochemistry analysis. We found higher levels of HLA-G expression and HHV-6 presence in IUGR placenta samples compared with control placenta samples.We report HHV-6 staining in IUGR placenta samples, characterized by high HLA-G expression. These preliminary data suggest a possible involvement of HHV-6 infection in HLA-G deregulation that might affect vessel remodeling and prevent the correct pregnancy outcome in the IUGR condition.
Key message Even though assisted reproductive techniques represent one of the greatest achievements in modern medicine, the risk of preterm birth related to these pregnancies is about twice as high. This must be highlighted and further investigated to optimize the management of both mothers and newborns. Purpose The purpose of this study was to compare adverse pregnancy outcomes after assisted reproductive techniques (ART) and spontaneous conceptions, focusing on the incidence of preterm births (PTB) and distinguishing between iatrogenic and spontaneous events. Methods This retrospective cohort study analyzed single births of one Italian hospital. The incidence of PTBs in ART pregnancies, divided into iatrogenic procedures, spontaneous preterm labors and preterm premature ruptures of the membranes (pPROMs), was compared with the non-ART control group. The incidence of other adverse pregnancy outcomes and the types of delivery were also reported and compared. Results Of the 11,769 single births included, 2.39% were conceived by ART. The incidence of PTBs was 4.74% for spontaneous pregnancies and 12.8% for ART pregnancies (aOR 1.93; 95% CI 1.29-2.88). The percentage of iatrogenic procedures was 27.78% in the ART-PTBs' group and 30.88% in the non-ART-PTBs' controls. ART pregnancies showed an increased incidence of pPROMs (6.40% versus 2.41%), preterm labors (2.85% versus 0.93%), hypertensive disorders of the pregnancy (8.19% versus 2.32%), placenta previa (3.20% versus 0.59%), cesarean sections (28.47% versus 16.27%) and vacuum extractions (10.32% versus 5.19%). Conclusions Singleton ART pregnancies have a higher risk of PTB which is mostly linked to a higher incidence of pPROMs and spontaneous preterm labor. The concurrency of a demonstrated higher risk of hypertensive gestational disorders and placenta previa suggests that placental development plays an important role in the pathogenesis of PTB.
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