Chronic endometritis and altered embryo implantation: a unified pathophysiological theory from a literature systematic review

Purpose: Chronic endometritis (CE) is a frequent hysteroscopic and histological finding which affects embryo transfer implantation during IVF-ICSI cycles. In particular, CE impairs proper decidualization and, subsequently, implantation. Although this correlation has been clearly clarified, a pathophysiological explanation assembling all the studies performed has not been elucidated yet. For this reason, we have structured a systematic review considering all the original articles that evaluated a pathological element involved in CE and implantation impairment. Methods: The authors searched electronic databases and, after screening, collected 15 original articles. These were fully scanned and used to create a summary pathway. Results: CE is primarily caused by infections, which lead to a specific cytokine and leukocyte pattern in order to prepare the uterus to fight the noxa. In particular, the immunosuppression requested for a proper semi-allogenic embryo transfer implantation is converted into an immunoreaction, which hampers correct embryo implantation. Moreover, endometrial vascularization is affected and both irregular vessel density and luminal thickening and thrombosis reduce what we have first identified as endometrial flow reserve. Finally, incorrect uterine wave propagation could affect embryo contact with decidua. Conclusion: This is the first summary of evidence on CE pathophysiology and its relationship with infertility. Understanding the CE pathophysiology could improve our knowledge in embryo transfer success

Peri-Conceptional Intake of Folic Acid Supplement to Date: A Medical-Legal Issue

Folic Acid (FA) supplementation during pregnancy represents a so widespread and established recommendation all over the world, to be taken for granted sometimes. As a matter of fact, this vitamin supplement is worldwide recommended mostly during peri-conceptional period for its proved preventive effect on Neural Tubal Defects (NTDs), like spina bifida. However, The biological and clinical potential of FA is reassessing and this represents a hot topic in scientific community, mostly in consideration of the possible medical-legal implications. An overview is mandatory in order to keep in mind FA-related possibl

Alterazioni endocrine e metaboliche della donna diabetica in menopausa.

Hormonal and metabolic disorders in menopause play a key role in hyperinsulinemia, insulin resistance and visceral obesity, contributing to dyslipidemia, oxidative stress, inflammation, clotting and atherosclerosis. These conditions all constitute risk factors for cardiovascular disease. In menopausal women estrogen deficiency and the relative hyperandrogenism promote metabolic dysfunction, predisposing to obesity, metabolic syndrome and type 2 diabetes. This review focuses on the role of estradiol (E2) and its receptors (ERs) in the control of energy homeostasis and glucose metabolism. E2 in the hypothalamic nuclei separately controls food intake, energy expenditure and fat distribution. In skeletal muscle, liver, adipose tissue and immune cells, E2 is involved in insulin sensitivity and prevents obesity and inflammation. E2 regulates insulin secretion in pancreatic β-cells. In menopausal women with pre-existing Type 1 and Type 2 diabetes mellitus, climacteric symptoms, metabolic disorders and diabetic complicationsare more severe. Hormone therapy (HRT) is not recommended for the prevention of metabolic disorders in menopausal women, but can be considered part of a tailored global strategy to improve the perception of menopausal symptoms and prevent diabetes complications. For the future, new selective estrogen receptor modulators - SERMs - are undergoing testing; they act only on ERs involved in energy balance and glucose homeostasis which activate cellular pathways, with beneficial metabolic effects by blocking ERs in the breast and uterus. New synthesis peptides (GLP-1 + E2) can transport E2 directly to pancreatic β-cells

Unusual and severe peripartum cardiomyopathy: A case report

Peripartum cardiomyopathy (PPCM) is a relatively rare cardiac disease that manifests in the final stage of pregnancy and in the first months after delivery in women with no preexisting heart disease. Many etiological processes have been suggested: viral myocarditis, abnormal immune response to pregnancy, excessive prolactin excretion, prolonged tocolysis and a familiar predisposition to PPCM. Its diagnosis is often delayed because its symptoms, which include fatigue, dyspnea and palpitations are nonspecific. For this reason the diagnosis of PPCM is still made by exclusion of other etiologies. The long-term prognosis, once the acute phase is over, is a function of myocardial damage, this varies from complete functional recovery to chronic HF. The outcome of PPCM is highly variable with an alevated risk of fetomaternal morbidity and mortality. We report a serious case of a 40 years old female with biamniotic bicorionic twin pregnancy (PMA) who delivered by caesarean section and developed acute PPCM on post-operative. Symptoms occurred two hours after an intramuscular injection of two vials of methylergonovine the same day of cesarean delivery. These manifested in sudden tachypnoe, tachycardia and the appearance itchy maculopapular rash on her chest. On further evaluation, ECHO revealed cardiomegaly with reduced ejection fraction (< 15%). The case was successfully managed by a multidisciplinary team, using drugs like levosimendan and cabergoline, which rapresent emerging strategy in this clinical context

Persistent or Recurrent Diabetic Macular Edema After Fluocinolone Acetonide 0.19 mg Implant: Risk Factors and Management

Purpose: To investigate baseline characteristics of patients undergoing additional antivascular endothelial growth factor (VEGF) injections for residual or recurrent diabetic macular edema (DME) in the first year after 0.19-mg fluocinolone acetonide (FAc) implant. Design: Prospective cohort study. Methods: Ninety-four eyes of 66 patients received an FAc implant. Eyes with persistent or recurrent DME were managed with pro re nata anti-VEGF agents. Demographic data and medical history were collected at baseline. Best-corrected visual acuity and central macular thickness were measured every 2 months. The 3 outcomes explored were 1) the risk factors for administration of additional anti-VEGF agents, 2) the interval from FAc to first anti-VEGF injection; and 3) the number of anti-VEGF doses required to maintain regression of DME. Results: Eighteen eyes (19.1%) of 13 patients received 1.3 ± 0.6 anti-VEGF injections. These eyes had significantly thicker central macular thickness at baseline and over the entire follow-up period (P < .001); best-corrected visual acuity was similar at every time point to eyes that were not receiving extra DME treatments. Eyes without preexistent panretinal photocoagulation (PRP) had a higher risk to undergo supplemental treatments (hazard ratio 1.5 [95% confidence interval 1.1-2.5, P = .03). The interval between FAc implant and the first anti-VEGF had a significant linear positive relationship with the number of dexamethasone implants before FAc implant (P = .002, R2 = 0.47). No association was found between baseline factors and the number of injections given. Conclusion: Anti-VEGF agents are efficient treatment to maintain visual acuity in residual/recurrent DME after FAc. Patients with higher baseline central macular thickness and with no previous central macular thickness are more likely to require additional treatments to control DME

Liquid biopsy in cervical cancer: Hopes and pitfalls

Cervical cancer (CC) is the fourth most common cancer in women worldwide, with about 90% of cancer-related deaths occurring in developing countries. The geographical influence on disease evolution reflects differences in the prevalence of human papilloma virus (HPV) infection, which is the main cause of CC, as well as in the access and quality of services for CC prevention and diagnosis. At present, the most diffused screening and diagnostic tools for CC are Papanicolaou test and the more sensitive HPV-DNA test, even if both methods require gynecological practices whose acceptance relies on the woman’s cultural and religious background. An alternative (or complimen-tary) tool for CC screening, diagnosis, and follow-up might be represented by liquid biopsy. Here, we summarize the main methodologies developed in this context, including circulating tumor cell detection and isolation, cell tumor DNA sequencing, coding and non-coding RNA detection, and exosomal miRNA identification. Moreover, the pros and cons of each method are discussed, and their potential applications in diagnosis and prognosis of CC, as well as their role in treatment mon-itoring, are explored. In conclusion, it is evident that despite many advances obtained in this field, further effort is needed to validate and standardize the proposed methodologies before any clinical use

Chronic Endometritis Due to Common Bacteria Is Prevalent in Women With Recurrent Miscarriage as Confirmed by Improved Pregnancy Outcome After Antibiotic Treatment

Recurrent miscarriage (RM) is defined as 3 or more miscarriages before 20 weeks' pregnancy. In recent years, interest has been focused on chronic endometritis (CE), a subtle inflammation thought to be associated with RM. We aimed to evaluate the relationships between CE and RM. The records of 360 women with unexplained RM were retrospectively analyzed. Data from hysteroscopy, endometrial histology, endometrial culture, and polymerase chain reaction for chlamydia, performed before and after antibiotic treatment for CE, were analyzed. The occurrence of successful pregnancies within 1 year after treatment was also evaluated. Results showed that 208 (57.8%) women with RM showed CE at hysteroscopy; 190 (91.3%), positive at hysteroscopy, were also positive at histology, and 142 (68.3%) had positive cultures. Common bacteria were found in 110 (77.5%) patients. Mycoplasma and Ureaplasma were found in 36 (25.3%) patients and Chlamydia in 18 patients (12.7%). In 102 (71%) women, antibiogram-based antibiotic treatment normalized hysteroscopy, histology, and cultures (group 1); while in 40 (28.2%) patients, CE was still present at hysteroscopy (group 2). In 16 of the 66 patients positive at hysteroscopy, but not at cultures, the hysteroscopy becomes normal (group 3) after a Centers for Disease Control and Prevention-based therapy; while in 50 women, CE was still present (group 4). One year after treatment, group 1 showed a significantly higher number of pregnancies (78.4%) compared to group 2 (17.5%; P < .001) and group 4 (15.3%; P = .005). The CE is frequent in women with RM. Antibiotic treatment seems to be associated with an improved reproductive outcome

Interleukin-6, interleukin-1β, and tumor necrosis factor α in menstrual effluents as biomarkers of chronic endometritis.

Objective: To assess the relationship between chronic endometritis (CE) and proin␣ammatory cytokine levels in menstrual ef␣uents and to develop a simple noninvasive test for screening CE. Design: Case-control study. Setting: Academic center. Patient(s): Sixty-four women referred to our center for infertility. Intervention(s): Of␣ce hysteroscopy; endometrial biopsy; collection of menstrual blood at subsequent cycle. Main Outcome Measure(s): Interleukin (IL) 6, IL-1b, and tumor necrosis factor (TNF) a concentrations in menstrual ef␣uents. Result(s): Thirty-sixoutof64infertilewomenhadhistologicallyprovenCE.Theremaining28womenwereincludedascontrols.IL-6, IL-1b, and TNF-a levels were markedly higher in menstrual ef␣uents of women with CE compared with control subjects. Receiver operating characteristic curve analysis revealed a good CE screening capacity for all of the cytokines. The combined evaluation of either IL-6/TNF-a or IL-6/IL-1b increased the diagnostic capacity of the test, which reached a 100% sensitivity and a negative predictive value of 100 when at least one cytokine was found to exceed its cutoff value; it also reached a 100% speci␣city and a positive predictive value of 100 in cases of positivity of both cytokines. Logistic regression analysis con␣rmed the IL-6/TNF-a– based model as a signi␣cant predictor of CE. Conclusion(s): Proin␣ammatorycytokinelevelsareincreasedinmenstrualef␣uentsofwomen with CE. A test dosing IL-6 and TNF-a seems to have a high screening capacity for CE. (Fertil Steril! 2014;101:242–7. !2014 by American Society for Reproductive Medicine.

Comparison of endometrial polyp recurrence in fertile women after office hysteroscopic endometrial polypectomy using two widely spread techniques

Aim: To compare the recurrence of benign endometrial polyps after office hysteroscopic polypectomy performed with a bipolar electrode (BE) or a small diameter hysteroscopic tissue removal system (HTRs). Methods: From July 2018 to December 2019 we evaluated the charts of 114 asymptomatic fertile women who underwent office hysteroscopic polypectomy, 1 year before, for a single large benign endometrial polyp (size between 10 and 20 mm) using a 4 mm continuous flow hysteroscope with a BE or a 5 mm HTRs. Patients, divided into two groups according to surgical procedure, each performed exclusively by one expert gynecologist, were scheduled for a 12-month postoperative transvaginal sonography to evaluate the recurrence of endometrial polyps. Results: Forty-eight women of the BE group and 42 of the HTRs group were considered for the 1-year transvaginal sonography follow-up. Five polyps were identified in the BE group and three in the HTRs group (5/48 vs 3/42, P = n.s.). All polyps were removed hysteroscopically (in three out of five and in two out of three cases, respectively, in the same places of the previous polypectomy) and evaluated as ‘benign’ by the pathologist. Conclusion: Office hysteroscopic endometrial polypectomy with small HTRs compared to BE revealed at a 1-year follow-up no difference in terms of complete removal and recurrence of polyps. HTRs polypectomy resulted in less pain and significantly quicker time of procedure compared to BE. This data should be kept in mind for patient comfort any time hysteroscopic polypectomy is planned in an office setting