Gestational diabetes mellitus (GDM) is a metabolic complication associated with adverse outcomes for mother and fetus. Arsenic (As) exposure has been suggested as a possible risk factor for its development. The aim of this meta-analysis was to provide a comprehensive overview of published evidence on the association between As and GDM. The systematic search from PubMed, MEDLINE, and Scopus was limited to full-length manuscripts published in peer-reviewed journals up to April 2020, identifying fifty articles. Ten studies met the inclusion criteria, nine for quantitative synthesis with a total of n = 1984 GDM cases. The overall pooled risk was 1.56 (95% Confidence Interval - CI = 1.23, 1.99) with moderate heterogeneity (χ² = 21.95; I²% = 64). Several differences among the included studies that may account for heterogeneity were investigated. Stratification for exposure indicator confirmed a positive association for studies assessing urine As. A slightly higher risk was detected pooling studies based in Asia rather than in North America. Stratification for GDM diagnostic criteria showed higher risks when diagnosis was made according to the Canadian Diabetes Association (CDA-SOGC) or World Health Organization (WHO) criteria, whereas a lower risk was observed when adopting the American Diabetes Association (ADA) criteria. These results provide additional evidence for a possible association between As exposure and GDM, although the data need to be interpreted with caution due to heterogeneity.

Endometriosis and irritable bowel syndrome (IBS) are chronic conditions affecting up to 10% of the global population, imposing significant burdens on healthcare systems and patient quality of life. Interestingly, around 20% of endometriosis patients also present with symptoms indicative of IBS. The pathogenesis of both these multifactorial conditions remains to be fully elucidated, but connections to gut microbiota are becoming more apparent. Emerging research underscores significant differences in the gut microbiota composition between healthy individuals and those suffering from either endometriosis or IBS. Intestinal dysbiosis appears pivotal in both conditions, exerting an influence via similar mechanisms. It impacts intestinal permeability, triggers inflammatory reactions, and initiates immune responses. Furthermore, it is entwined in a bidirectional relationship with the brain, as part of the gut–brain axis, whereby dysbiosis influences and is influenced by mental health and pain perception. Recent years have witnessed the development of microbiota-focused therapies, such as low FODMAP diets, prebiotics, probiotics, antibiotics, and fecal microbiota transplantation, designed to tackle dysbiosis and relieve symptoms. While promising, these treatments present inconsistent data, highlighting the need for further research. This review explores the evidence of gut dysbiosis in IBS and endometriosis, underscoring the similar role of microbiota in both conditions. A deeper understanding of this common mechanism may enable enhanced diagnostics and therapeutic advancements.

The presence of endometriosis determines an inflammatory response locally. The objective of this validation study and systematic review was to assess systemic levels of coagulation and inflammatory parameters in women with or without the disease. We conducted a retrospective analysis of a database prospectively collected from January 2017 to February 2020 including n = 572 women who underwent laparoscopic surgery for endometriosis (cases, n = 324) or other benign gynecologic diseases (controls, n = 248). Inflammatory markers and coagulation parameters were determined. An advanced systematic search of the literature on the same parameters was conducted up to April 2020. A significantly higher neutrophil count was found in endometriosis patients. Patients with endometriomas and stage III–IV disease had a significantly lower absolute lymphocyte count and shortened activated partial thromboplastin time (aPTT) values. In the final regression model, aPTT retained significant predictive value for stage III–IV endometriosis (odds ratio (OR) = 0.002, 95% confidence interval (CI) = 0.00–0.445; p = 0.024). Results from the n = 14 included studies in the systematic review are characterized by a high variability, but some consistency has been found for alterations in thrombin time, platelet-to-lymphocyte ratio, and neutrophil count associated with endometriosis. Modest systemic changes of some inflammatory and coagulation parameters are associated with endometriosis. Indeed, all the modifications detected are still within the normal reference intervals, explaining the high heterogeneity among studies.

The aim of this study was to evaluate if moderate-severe endometriosis impairs uterine arteries pulsatility index (UtA-PI) during pregnancy when compared to unaffected controls. In this prospective cohort study, pregnant women with stage III–IV endometriosis according to the revised American Fertility Society (r-AFS) classification were matched for body mass index and parity in a 1:2 ratio with unaffected controls. UtA-PIs were assessed at 11–14, 19–22 and 26–34 weeks of gestation following major reference guidelines. A General Linear Model (GLM) was implemented to evaluate the association between endometriosis and UtA-PI Z-scores. Significantly higher third trimester UtA-PI Z-scores were observed in patients with r-AFS stage III–IV endometriosis when compared to controls (p = 0.024). In the GLM, endometriosis (p = 0.026) and maternal age (p = 0.007) were associated with increased third trimester UtA-PI Z-scores, whereas conception by in-vitro fertilization with frozen-thawed embryo transfer significantly decreased UtA-PI measures (p = 0.011). According to these results, r-AFS stage III–IV endometriosis is associated with a clinically measurable impaired late placental perfusion. Closer follow-up may be recommended in pregnant patients affected by moderate-severe endometriosis in order to attempt prediction and prevention of adverse pregnancy and perinatal outcomes due to a defective late placental perfusion.

The aim of this systematic review was to provide comprehensive and available data on the possible role of phytoestrogens (PE) for the treatment of endometriosis. We conducted an advanced, systematic search of online medical databases PubMed and Medline. Only full-length manuscripts written in English up to September 2020 were considered. A total of 60 studies were included in the systematic review. According to in vitro findings, 19 out of 22 studies reported the ability of PE in inducing anti-proliferative, anti-inflammatory and proapoptotic effects on cultured cells. Various mechanisms have been proposed to explain this in vitro action including the alteration of cell cycle proteins, the activation/inactivation of regulatory pathways, and modification of radical oxidative species levels. Thirty-eight articles on the effects of phytoestrogens on the development of endometriotic lesions in in vivo experimental animal models of endometriosis have been included. In line with in vitro findings, results also derived from animal models of endometriosis generally supported a beneficial effect of the compounds in reducing lesion growth and development. Finally, only seven studies investigated the effects of phytoestrogens intake on endometriosis in humans. The huge amount of in vitro and in vivo animal findings did not correspond to a consistent literature in the women affected. Therefore, whether the experimental findings can be translated in women is currently unknown.

Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed n = 40 studies eligible for inclusion in this systematic review. Of these, n = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.