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PurposeChronic 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.MethodsThe authors searched electronic databases and, after screening, collected 15 original articles. These were fully scanned and used to create a summary pathway.ResultsCE 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.ConclusionThis 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.

Polycystic ovary syndrome (PCOS) is a heterogenous disorder characterized by chronic ovulation dysfunction and hyperandrogenism. It is considered the most common endocrinological disorder, affecting up to 25% of women of reproductive age, and associated with long-term metabolic abnormalities predisposing to cardiovascular risk, such as insulin resistance (IR), dyslipidemia, endothelial dysfunction, and systemic inflammation. PCOS is also characterized by elevated serum levels of luteinizing hormone (LH), causing a condition of hyperandrogenism and a consequent altered ratio between LH and the follicle stimulating hormone (FSH). Over the years, several different approaches have been proposed to alleviate PCOS symptoms. Supplementation with natural molecules such as inositols, resveratrol, flavonoids and flavones, vitamin C, vitamin E and vitamin D, and omega-3 fatty acids may contribute to overcoming PCOS pathological features, including the presence of immature oocyte, IR, hyperandrogenism, oxidative stress and inflammation. This review provides a comprehensive overview of the current knowledge about the efficacy of natural molecule supplementation in the management of PCOS.

Pregnancy is a complex process, featuring several necessary changes in women’s physiology. Most women undergo healthy pregnancies; even so, several women experience reduced fertility or pathologies related to the pregnancy. In the last years, researchers investigated several molecules as promoters of fertility. Among all, myo-inositol (myo-ins) represents a safe compound that proved useful in issues related to fertility and pregnancy. In fact, myo-ins participates in several signaling processes, including the pathways of insulin and gonadotropins, and, therefore, it is likely to positively affect fertility. In particular, several clinical trials demonstrate that its administration can have therapeutic effects in infertile women, and that it can also be useful as a preventive treatment during pregnancy. Particularly, myo-ins could prevent the onset of neural tube defects and the occurrence of gestational diabetes mellitus, promoting a trouble-free gestation. Due to the safety and efficiency of myo-ins, such a treatment may also substitute several pharmaceuticals, which are contraindicated in pregnancy.

The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence. Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433 ).

The paths of medically assisted reproduction represent the most important scientific progress to cope with the inability to achieve spontaneous conception (SC) and to reach desired parenthood. Couples undergoing assisted reproductive technology (ART) and couples not facing ovulation induction and artificial fertilization show sufficient levels of well-being and psychological adjustment. However, in some cases couples undergoing ART show lower perceived quality of life than couples with SC.Our aim is to investigate the main psychological variables involved in the special risk condition of medically assisted reproduction and how they could direct specific guidelines to enhance mental wellbeing in dealing with infertility. In this regard, we performed a systematic review following the PRISMA guidelines. From all the studies included, the considered outcome measures were psychological, social, and relational variables and are presented in a systematic approach. A total of 14 studies were included in this article, according to our strict inclusion criteria. Conflicting results have been proven by this systematic review. Even though all underlined the importance of taking charge of the psychological variables in infertility, few studies monitored and evaluated the effectiveness of these interventions. Moreover, none of the selected studies monitored the evolutionary implications of parental competence on the development of children born from ART.

Background and Objectives: Hysteroscopy is a reliable technique which is highly useful for the evaluation and management of intrauterine pathology. Recently, the widespread nature of in-office procedures without the need for anesthesia has been requesting validation of practical approach in order to reduce procedure-related pain. In this regard, we performed a comprehensive review of literature regarding pain management in office hysteroscopic procedures. Materials and Methods: MEDLINE, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), Global Health, Health Technology Assessment Database and Web of Science, other research registers (for example Clinical Trials database) were searched. We searched for all original articles regarding pain relief strategy during office hysteroscopy, without date restriction. Results have been collected and recommendations have been summarized according to the Appraisal of Guidelines for Research and Evaluation (AGREE) tool. Moreover, the strength of each recommendation was scored following the Grading of Recommendations Assessment (GRADE) system, in order to present the best available evidence. Results: Both pharmacological and non-pharmacological strategies for pain management are feasible and can be applied in office setting for hysteroscopic procedures. The selection of strategy should be modulated according to the characteristics of the patient and difficulty of the procedure. Conclusions: Accumulating evidence support the use of pharmacological and other pharmacological-free strategies for reducing pain during office hysteroscopy. Nevertheless, future research priorities should aim to identify the recommended approach (or combined approaches) according to the characteristics of the patient and difficulty of the procedure.

PurposeThe current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138.MethodsThis is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC.ResultsSensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761–0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138.ConclusionIHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE.

This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success.

Endometriosis is a chronic inflammatory disorder with a prevalence of six to ten percent in women of childbearing age. As long as the aetiology of endometriosis is not fully understood and the disease has no definitive treatment, an examination of the environmental factors or interventions that could modify or cure endometriosis would greatly benefit women suffering from this chronic condition. This literature review utilized the electronic databases PubMed, EMBASE, and MEDLINE until February 2021. Studies indicate that fish oil may have a positive effect on reducing endometriosis-related pain due to the effects of pro-inflammatory prostaglandins derived from omega-3 fatty acids. The same effect was seen with the introduction of antioxidant vitamins C, D, and E. There is clinical viability of a low fermentable oligo-, di-, and mono-saccharides and polyols diet to successfully reduce the symptoms of patients who suffer from both endometriosis and irritable bowel syndrome. Despite the low level of evidence, there are frequent associations between endometriosis and gastrointestinal conditions in addition to the influence of various nutritional factors on the disease. The management of endometriosis requires a holistic approach focused on reducing overall inflammation, increasing detoxification, and attenuating troublesome symptoms. A dietician may provide great benefit in the management of these patients, especially at younger ages and in early stages. High-level evidence and well-designed randomized studies are lacking when it comes to studying the effect of lifestyle and dietary intake on endometriosis. Inarguably, further research with a more extensive focus is needed.

Background: Chronic endometritis (CE) and endometrial polyps (EPs) are common conditions in reproductive age women. CE is an infectious disorder of the endometrium characterized by signs of chronic inflammation at hysteroscopic and histological analyses. EPs are abnormal endometrial growths containing glands, stroma and blood vessels projecting from the lining of the uterus. During the last years, different authors have investigated the correlation between CE and EPs, with controversial results. The aim of this study was to summarize available evidence on the potential correlation between CE and EPs. Design: Systematic literature review and meta-analysis. Methods: Observational-studies were identified by searching electronic databases from their inception to September 2021. Only studies on pre-menopausal women were included. Statistical analysis was performed using MedCalc 16.4.3 (Ostend, Belgium) and Review Manager version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration). The summary measures were reported as pooled proportion or odds ratio (OR) with 95% confidence interval (CI). The primary outcome was to evaluate the prevalence of CE in women with EPs. The secondary outcome was to determine the prevalence of CD-138-positive EPs among EPs. Tertiary outcomes were to compare the prevalence of CE in women with EPs versus women with a non-polypoid endometrium and to compare the prevalence of CE in women with a single EP versus women with multiple EPs. Results: Eight observational studies (n = 3225 patients) were included in quantitative synthesis. Pooled prevalence of CE among women with EPs was 51.35% (95% CI, 27.24–75.13%). Pooled proportion of CD-138-positive EPs among EPs was 70.73% (95% CI, 55.73–83.68%). Women with EPs showed higher prevalence of CE compared to women without EPs (OR 3.07, 95% CI 1.59–5.95). Women with ≥3 EPs had higher prevalence of CE then women with a single EP (OR 3.43, 95% CI 1.83–6.46). Conclusions: In pre-menopausal women, CE and EPs may have a dependent relationship and may represent two consequent steps of a common pathological process.