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Background: Transversus abdominis plane (TAP) block and wound infiltration (WI) with local anesthetics are used for postoperative analgesia after cesarean section (CS), reducing the need for administration of opioids. Objective: To compare the analgesic effect of TAP block related to WI. Search strategy: MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Cochrane Library, and CINAHL were searched from inception until April 2020. Selection criteria: Randomized controlled trials (RCTs) about women who underwent TAP block or WI after CS. Data collection and analysis: Relevant data were extracted and tabulated. Review Manager 5.3 was used for data analysis. Primary outcome was cumulative opioid consumption (COC) 24 and 48 h after CS. Main results: Five RCTs, enrolling 268 women, were included. There were no significant differences between the interventions regarding COC at 24 (mean difference [MD] -1.68, 95% confidence interval [CI] -6.29 to 2.93) and 48 hours (MD 1.28, 95% CI -10.44 to 13.00). Adverse effects (relative risk [RR] 0.93, 95% CI 0.75-1.16), gastrointestinal reactions (RR 1.30, 95% CI 0.46-3.68), or mild-moderate sedation (RR 1.12, 95% CI 0.72-1.74), pain scores, satisfaction of women, and withdrawals were similar between groups. Conclusions: There might be no significant advantages selecting TAP block over WI for post-CS analgesia.

Introduction Prolonged labor increases the risk of maternal and fetal complications. The active management of labor has been proven effective in lowering neonatal and maternal morbidity by shortening the duration of labor. Several pharmaceutical and non-pharmaceutical approaches are currently being used in the active management of labor. Hyoscine Butyl-bromide (HBB) is an antispasmodic and anticholinergic drug that acts as a cervical spasmolytic agent. It has been widely used in everyday practice for shortening the active phase of labor. Nonetheless, only a few trials have been conducted on the topic. Objective This review aimed to evaluate whether HBB is effective in decreasing the mean duration of the active phase of labor. Study design An electronic search was conducted on Medline (through PubMed), Scopus, ClinicalTrials.gov, EMBASE, PROSPERO, and Cochrane Library from the beginning of all databases to December 2019. Results were limited to randomized trials. Restriction for English language was applied. Inclusion criteria were: randomized clinical trials regarding primiparae or multiparae women with a singleton vertex pregnancy at term who were randomized to HBB versus placebo or other drugs. Primary outcome evaluated was the mean reduction of the active phase of labor. Data collection and analysis Eight randomized clinical trials, including 1159 pregnant women, were analyzed. Significant heterogeneity (I2 = 99 %) between studies was noted for the primary outcome. The active phase of labor duration was significantly reduced in the treatment arm compared to controls [mean difference (MD) −83.93 min (95 % confidence interval (CI) −163.61, −4.25)]. Achieved reduction in primiparae women was −55.09 min [95 % CI −68.83, −41.35; I2 = 37 %]. Conclusion HBB is an effective treatment to shorten the duration of the active phase of labor in primiparae and multiparae women.

Human Papillomavirus is the main cause of cervical cancer, including squamous cell carcinoma of the oropharynx, anus, rectum, penis, vagina, and vulva. In recent years, considerable effort has been made to control HPV-induced diseases using either prophylactic or therapeutic approaches. A critical review of the literature about the therapeutic Human Papillomavirus vaccine was performed to analyze its efficacy in the treatment of female lower genital tract lesions and its possible perspective application in clinical practice. The most important medical databases were consulted, and all papers published from 2000 until 2021 were considered. We retrieved a group of seven papers, reporting the role of anti HPV therapeutic vaccines against the L2 protein in the order of their efficacy and safety in female lower genital tract disease. In addition, the immune response due to vaccine administration was evaluated. The development of therapeutic vaccines represents an interesting challenge for the treatment of HPV infection of the lower genital tract. Literature data underline that the L2 protein may be an interesting and promising target in the development of therapeutic HPV vaccines, but the possible strengths and the unclear longevity of L2 immune responses are factors to be considered before clinical use.

Background and Objectives: The human brain presents a functional asymmetry for every cognitive function, and it is possible that sexual hormones could have an impact on it. Visual–spatial attention, one of the most lateralized functions and one that is mainly dependent on the right hemisphere, represents a sentinel for functional cerebral asymmetry (FCA). The aim of this study was to evaluate whether menopausal hormone therapy (MHT) or phytoestrogens could modulate FCA in postmenopausal women. Materials and Methods: We enrolled postmenopausal women who were taking MHT or soy isoflavones or receiving no therapy and asked them to perform the line bisection test at study enrollment and after 18 and 36 months. Results: Ninety women completed the follow-up. At zero time, women who had not been subjected to therapy showed a leftward deviation (F = −3.0), whereas, after 36 months, the test results showed a rightward deviation (F = 4.5; p < 0.01). Women taking MHT showed a leftward deviation at the start (F = −3.0) and a persistent leftward deviation after 36 months (F = −4.0; p = 0.08). Conversely, women taking soy isoflavones started with a leftward deviation (F = −3.0) that became rightward (F = 3.0), with a significant difference shown after 36 months (p < 0.01). Conclusions: Our data suggest that hormonal modulation improves the interplay between the two hemispheres and reduces FCA. We propose, therefore, that the functions of the right hemisphere are mainly affected by aging and that this could be one of the reasons why the right hemisphere is more susceptible to the effects of MHT.

Aim To evaluate whether the first Covid-19 lockdown for Italian citizens (March to July 2021) might have altered the incidence of gestational diabetes mellitus (GDM). Methods A retrospective single-center study in a tertiary referral center. Primary outcome was the incidence of GDM among pregnant women. GDM incidence, from June 11, 2019 to December 4, 2020, was compared by dividing the study time as follows: from the beginning of the study to before Covid-19 lockdown (from June 11, 2019, to March 9, 2020) and lockdown period (from March 10, 2020, to December 4, 2020). GDM was diagnosed with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 gestational weeks. Results Concerning 1295 women, GDM incidence increased during the lockdown period (9.3% vs. 3.4%, p < 0.001). Higher pregnancy weight gain with an increased body mass index (BMI) at the delivery was reported during the lockdown (31.3 vs. 28.4 kg/m(2), p = 0.02 and mean weight gain of 9.3 vs. 6.6 kg, p = 0.007). There was no difference in other comorbidity incidence and OGTT values between the two groups. Conclusions Pregnant women during the Covid-19 lockdown might have experienced higher BMI and pregnancy weight gain with increased GDM diagnoses. This may be related to physical limitations and emotional distress experienced during the lockdown. However, evidence is limited due to restricted study duration and random variations of outcomes across time. More studies are needed to understand the dietary patterns and the physical activity changes during the Covid-19 lockdown and its impact on fetal outcomes.

Objectives: The main goal of our research was to explore correlations between a history of uterine myomectomy and maternal-fetal outcomes, throughout a comparison between vaginal deliveries in patients with or without a history of uterine myoma excision. Materials and methods: A prospective study was carried out at two tertiary care hospitals between January 2019 and January 2020. Women were assigned into two groups according to the history of laparoscopic or laparotomic myomectomy (Group 1) or without myomectomy (Group 2). Results: 80 women successfully delivered after myomectomy. Pregnancies with previous laparoscopic or laparotomic myomectomy were associated with a minor rate of spontaneous labor onset (RR 1.17; 95% CI 1.04 − 1.31) and with an increased rate of emergency cesarean section (RR 1.22; 95% CI 1.09 − 1.36). Moreover, myomectomy group had a significant number of indications to emergency cesarean section correlated to suspected uterine rupture (RR 1.19; 95% CI 1.02–1.39). There were no uterine ruptures or neonatal deaths recorded. First stage of labor was longer in the myomectomy group (316 vs 204 mins, p = 0.01). No differences in the rates of the prolonged first and second stage of labor, postpartum hemorrhage and vaginal laceration, and no neonatal adverse outcomes were found between groups. Conclusions: Pregnancies after myomectomy might be associated with an elevated rate of emergency cesarean section only due to a higher percentage of suspected uterine rupture, without a real hazard of adverse obstetric or neonatal outcomes.

Background and Objectives: Uterine sarcomas represents only 3% of all the female genital tract ones. The tumoral stage is the most significant prognostic factor. The role of the bilateral salpingo-oophorectomy (BSO) in the surgical management of FIGO stage IA and IB appears still controversial. This review aims to investigate the impact of bilateral adnexectomy in the treatment of uterine sarcoma. Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed, Scopus, Cochrane, Medline, and Medscape databases in February 2022. We applied no language or geographical restrictions, but we considered only English studies. We included the studies containing data about Recurrence Rate (RR), Disease-free Survival (DFS), and Overall Survival (OS). We used comparative studies for meta-analysis. Results: Seventeen studies fulfilled the inclusion criteria; 2 retrospective observational studies, and 15 retrospective comparative studies, And 14 out of the 15 comparative studies were enrolled in meta-analysis. A total of 3743 patients were analyzed concerning the use of adnexectomy with hysterectomy in patients with uterine sarcoma and compared with those who did not. Meta-analysis highlighted a non-significant worsening of the OS in the BSO group compared to the OP group and showed that adnexectomy does not improve the DFS (BSO OR 1.23 (95% CI 0.81–1.85) p = 0.34; I2 = 24% p = 0.22). Conclusions: Most studies selected for our review showed that adnexectomy does not significantly affect the RR, OS, and PFS in treating FIGO stage I uterine sarcomas. Therefore, even if there is a unanimous consensus about bilateral adnexectomy in menopausal patients, preservation of ovarian tissue may be considered in premenopausal women. Nonetheless, there are not enough cases in the literature to recommend this procedure.

During the last decades, the number of couples with reproductive issues has substantially increased. Many different factors are implicated in reproductive failure, including uterine factors. Endometrial pathologies, such as endometrial polyps, hyperplasia, endometritis, and Mullerian anomalies, can also hinder embryo implantation. Hysteroscopy remains the gold standard for the evaluation and treatment of intrauterine pathology. Over the last few years, advances in hysteroscopic instrumentations and surgical techniques have significantly evolved, the refinement in technology, miniaturization of instruments, and improved image quality have rendered hysteroscopy a more patient and user-friendly procedure that has enhanced its use in reproductive medicine. Nowadays, hysteroscopy is essential in the evaluation and treatment of women with infertility. This article underscores the major technological breakthroughs achieved over the last few years with emphasis on the role of artificial intelligence, augmented reality, and 3D hysteroscopy, which can set new benchmarks in hysteroscopy applied to reproductive medicine.

Background. Diabetes in pregnancy is associated with an increased risk to the woman and to the developing fetus. Currently, there is no consensus on the optimal management strategies for the follow-up and the timing of delivery of pregnancies affected by gestational and pregestational diabetes, with different international guidelines suggesting different management options. Materials and Methods. We conducted a retrospective cohort study from January 2017 to January 2021, to compare maternal and neonatal outcomes of pregnancies complicated by gestational and pregestational diabetes, followed-up and delivered in a third level referral center before and after the introduction of a standardized multidisciplinary management protocol including diagnostic, screening, and management criteria. Results. Of the 131 women included, 55 were managed before the introduction of the multidisciplinary management protocol and included in group 1 (preprotocol), while 76 were managed according to the newly introduced multidisciplinary protocol and included in group 2 (after protocol). We observed an increase in the rates of vaginal delivery, rising from 32.7% to 64.5% ( P < 0.001 ). No differences were found in neonatal outcomes, and the only significant difference was demonstrated for the rates of fetal macrosomia (20% versus 5.3%, P : 0.012). Therefore, the improvements observed in the maternal outcomes did not impact negatively on fetal and neonatal outcomes. Conclusion. The introduction of a standardized multidisciplinary management protocol led to an improvement in the rates of vaginal delivery and in the rate of successful induction of labor in our center. A strong cooperation between obstetricians, diabetologists, and neonatologists is crucial to obtain a successful outcome in women with diabetes in pregnancy.

To estimate the correlation between the maternal perception of Braxton-Hicks contractions (BHC) and foetal wellbeing throughout antepartum computerised cardiotocography (cCTG) parameters, we performed a prospective observational study between April 2019 and March 2020. Non-labouring women with a term pregnancy were recruited. We collected data regarding maternal perception of BHC in the last two weeks before delivery. For each patient, an external computerised cardiotocography (cCTG) was registered. Women were subdivided in accordance with perception or non-perception of BHC. Fifty women were recruited. Women who felt BHC showed higher foetal heart rate (135 bpm vs 128 bpm, p = .008), lower long-term variability (47.2 ms vs 57.7 ms, p = .02) and reduced number of accelerations (7.8 vs 11.4, p = .04). In conclusion, the absence of mother's perception of BHC showed lower baseline foetal heart rate, increased number of accelerations and higher long-term variability related to mothers who perceived BHC.IMPACT STATEMENTWhat is already known on this subject? BHC are common painful contractions that start in the third trimester. They are random spots of uterine action that happen in the absence of sufficient gap-junction connectivity. BHC have a significant impact on foetal wellbeing.What do the results of this study add? BHC are associated with reduced long-term variability during cCTG examination. Moreover, baseline foetal heart rate seems lower, and accelerations are less frequent when BHC are felt by pregnant women.What are the implications of these findings for clinical practice and/or further research? These findings could be related to a cumulative effect on the uterine flow mediated by BHC. Further researches are needed to state the impact of BHC on the foetal wellbeing. What is already known on this subject? BHC are common painful contractions that start in the third trimester. They are random spots of uterine action that happen in the absence of sufficient gap-junction connectivity. BHC have a significant impact on foetal wellbeing. What do the results of this study add? BHC are associated with reduced long-term variability during cCTG examination. Moreover, baseline foetal heart rate seems lower, and accelerations are less frequent when BHC are felt by pregnant women. What are the implications of these findings for clinical practice and/or further research? These findings could be related to a cumulative effect on the uterine flow mediated by BHC. Further researches are needed to state the impact of BHC on the foetal wellbeing.

Background: Besides reducing the quality of obstetric care, the direct impact of COVID-19 on pregnancy and postpartum is uncertain. Objective: To evaluate the characteristics of pregnant women who died due to COVID-19. Search strategy: Cochrane Library, Embase, MEDLINE, Scopus, and Google Scholar were searched from inception to February 2021. Selection criteria: Studies that compared deceased and survived pregnant women with COVID-19. Data collection and analysis: Relevant data were extracted and tabulated. The primary outcome was maternal co-morbidity. Main results: Thirteen studies with 154 deceased patients were included. Obesity doubled the risk of death (relative risk [RR] 2.48, 95% confidence interval [CI] 1.41–4.36, I2=0%). No differences were found for gestational diabetes (RR 5.71; 95% CI 0.77–42.44, I2=94%) or asthma (RR 2.05, 95% CI 0.81–5.15, I2=0%). Overall, at least one severe co-morbidity showed a twofold increased risk of death (RR 2.26, 95% CI 1.77–2.89, I2=76%). Admission to intensive care was related to a fivefold increased risk of death (RR 5.09, 95% CI 2.00–12.98, I2=56%), with no difference in need for respiratory support (RR 0.53, 95% CI 0.23–1.48, I2=95%) or mechanical ventilation (RR 4.34, 95% CI 0.96–19.60, I2=58%). Conclusion: COVID-19 with at least one co-morbidity increases risk of intensive care and mortality.

Introduction: Cesarean section affects subsequent spontaneous pregnancies because of implantation issues. However, its impact on post-embryo transfer pregnancies is still debated. This review aimed to evaluate the impact of a previous cesarean section on fertility and pregnancy outcomes of women undergoing fresh or frozen embryo transfer. Material and methods: MEDLINE, Scopus, ClinicalTrials.gov, Scielo, EMBASE, Cochrane Library at the CENTRAL, and LILACS were searched from inception to February 2021. Studies were included if they evaluated reproductive or pregnancy outcomes after fresh or frozen embryo transfer in infertile women with a previous cesarean section relative to women with a previous vaginal delivery. Random-effect meta-analyses to calculate risk ratio (RR) or mean differences with 95% confidence intervals (CI) followed by subgroup analysis for fresh and frozen embryo transfer were performed. Risk of bias and quality assessment were conducted using Newcastle–Ottawa scale and GRADE criteria. The review was registered in the International Prospective Register of Systematic Reviews (CRD42021226297). Results: Ten studies, with data provided for 13696 participants, were eligible. For embryo transfers after cesarean section, compared with vaginal delivery, there was a significant reduction of the live birth rate (RR 0.88, 95% CI 0.79–0.99) and biochemical pregnancy rate (RR 0.89, 95% CI 0.82–0.96). No statistically significant differences were found for clinical pregnancy rate (RR 0.92, 95% CI 0.84–1.02), ectopic pregnancies (RR 1.00, 95% CI 0.68–1.46), pregnancy loss (RR 1.05, 95% CI 0.94–1.18), multiple pregnancies (RR 0.80, 95% CI 0.63–1.02), stillbirths (RR 0.86, 95% CI 0.27–2.69), birth defects (RR 1.71, 95% CI 0.49–5.96) or birthweight (mean difference 46.82, 95% CI −40.16 to 133.80). Subgroup analysis revealed an increased risk for preterm birth in post-cesarean section fresh embryo transfer pregnancies (RR 1.59, 95% CI 1.16–2.19). Conclusions: Low-grade evidence shows that post-embryo transfer pregnancies in infertile women who had a previous cesarean delivery result in reduced biochemical pregnancy and live birth rates relative to women with a previous vaginal delivery. An increased risk for preterm birth is notable in post-fresh embryo transfer pregnancies.

Introduction Breech/transverse presentation is responsible for about 30–50 % of cesarean sections in the world. Cesarean section carries a five-fold greater morbidity than vaginal delivery, deeply impacting on women’s health. External Cephalic Version (ECV) is an external manipulation used to convert a non-cephalic to a cephalic presentation. The use of tocolysis might facilitate this procedure; however, it is still controversial which drug should be considered as first choice. Objective To assess the effectiveness of tocolysis with atosiban, a competitive oxytocin receptor antagonist, in order to increase the rate of successful ECV. Study design Nine databases (including MEDLINE, CINAHL, LILACS, EMBASE, Scopus, ClinicalTrials.gov, Scielo, PROSPERO, Cochrane at CENTRAL) were searched from the inception to August 2020 using a combination of MeSH terms and keywords regarding “atosiban” and “external cephalic version”. We included trials of women with a singleton pregnancy who reached at least 36 weeks of gestation and were scheduled to ECV and tocolysis with atosiban (intervention group) compared to beta-agonists or other drugs (control group). The primary outcome was the incidence of successful ECV. Summary measures were reported as relative risk (RR) with 95 % confidence interval (CI). Data collection and analysis Four studies (1534 women) were eligible for analysis. ECV success rate was significantly lower in women randomized to atosiban (36.7 % vs 45.3 %; RR 0.78 [95 % CI 0.6 to 0.98]). Cesarean section and vaginal delivery rates did not differ between intervention and control group ((59.8 % vs 52.6 %; RR 1.17 [0.98–1.38] and (38.6 % vs 45.0 %; RR 0.83 [95 % CI 0.69–1.01] respectively). Cephalic (36.9 % vs 44.6 %; RR 0.81 [95 % CI 0.65 to 1.01], or breech/transverse presentation at labor (63.4 % vs 55.1 %; RR 1.18 [95 % CI 0.99–1.40]), APGAR score less than 7 at 5 min (1.6 % vs 2.0 %; RR 1.14 [95 % CI 0.27–4.73], NICU admissions (44.2 % vs 48.1 %; RR 0.92 [95 % CI 0.58–1.46] and Umbilical cord pH were similar in both groups. Drug-related side effects were lower in women randomized to atosiban, compared with control group (16.0 % vs 42.9 %; RR 0.38 [95 % CI 0.31 to 0.47]. Conclusion The use of atosiban for tocolysis does not improve the rate of successful ECVs when compared to beta-agonists. However, atosiban was associated with a significantly lower incidence of side effects and comparable cesarean section rates.

Background and Objectives: Echinacea angustifolia and purpurea have known immunomodulatory effects which boost viral clearance, including HPV infection. However, evidence regarding the improvement due to Echinacea-based supplements of cervical HPV-related pathologies is still lacking. The aim of this study is to evaluate the efficacy of Echinacea supplementation on the remission of cervical low-grade squamous intraepithelial lesions (L-SIL). Materials and Methods: A single-blind 1:1:1 parallel randomized controlled trial was conducted at the Colposcopy Unit of a tertiary care referral center. Reproductive-aged women were allocated either to (a) an oral supplement based on Echinacea extracts plus vaginal hyaluronic acid-based soft gel capsules, (b) the Echinacea supplement alone, or (c) vaginal hyaluronic acid-based soft gel capsules alone for 3 months. The primary outcome was the regression of cervical intraepithelial neoplasia (CIN)-1 for each treatment arm at 3, 6 and 12 months after the diagnosis. Secondary outcomes included changes in the epithelialization, pap smear, colposcopic parameters, histological reports, and vaginal health indexes (VHI) in the study groups. Results: 153 women (52 for arm A, 50 for arm B and 51 for arm C) completed the follow-up and were included in the analysis. There were no significant differences in both primary and secondary outcomes for the three groups after 3 months. At the 6-month follow-up, the number of persistent CIN-1 diagnoses was significantly lower in arm A (15/51), rather than in arm B (23/48, p = 0.03) and C (27/49, p = 0.03). Similarly, the same effect was seen after 12 months for treatment A (5/51) relative to B (15/48, p = 0.03) and C (14/48, p = 0.03). Colposcopic, histological and vaginal parameters were all significantly improved at 6 and 12 months for arm A relative to B and C, while no beneficial effects were seen after 3 months. Conclusions: Echinacea extracts supplementation in women with L-SIL/CIN-1 significantly boosts HPV lesion clearance, reducing the overall amount of diagnosis, histological, colposcopic and vaginal parameters after 6 and 12 months. However, a limited sample size reduces the quality of evaluated evidence, emphasizing the need for additional studies to validate these findings.

Background: Spontaneous pneumomediastinum (SPM) during pregnancy or labor is a rare event. We presented a case report and a systematic review of the literature to provide comprehensive symptoms, treatments, and complications analysis in the pregnant population affected by SPM. Methods: We conducted a comprehensive search of four databases for published papers in all languages from the beginning to 1 September 2021; Results: We included 76 papers with a total of 80 patients. A total of 76% patients were young primiparous, with a median age of 24 ± 5.4 years. The median gestational age was 40 ± 2.4 weeks, with a median duration of labor of 7.4 ± 4.2 h. In 86%, the ethnic origin was not specified. SPM develops in 55% of cases during the second stage of labor. Subcutaneous swelling and subcutaneous emphysema were present in 91.4%. Chest pain and dyspnea were present in 51.4% and 50% of the patients, respectively. We found that 32.9% patients had crepitus, and less common symptoms were dysphonia and tachycardia (14.3% and 14.3%, respectively). Oxygen and bronchodilators were used in 37.7% of the cases. Analgesics or sedatives were administered in 27.1%. Conservative management or the observation was performed in 21.4% and 28.6%, respectively. Antibiotics treatment was offered in 14.3%, whereas invasive procedures such as chest-tube drainage were used in just 5.7% of patients. There were no complications documented in most SPM (70.0%). We found that 16.7% of the SPM developed a pneumothorax and 5% developed a pneumopericardium.; Conclusions: In pregnancy, SPM occurs as subcutaneous swelling or emphysema during the second stage of labor. The treatment is usually conservative, with oxygen and bronchodilators and a low sequela rate. A universal consensus on therapy of spontaneous pneumomediastinum in pregnancy is necessary to reduce the risk of complications.

The aim of this systematic literature review and meta-analysis is to assess the impact of hysteroscopic metroplasty for dysmorphic uteri on reproductive outcomes in women with recurrent miscarriages. Available studies were identified through a PubMed, Scopus, and Cochrane search until June 2019. Live-birth rate, clinical pregnancy and miscarriage rate after hysteroscopic metroplasty was evaluated. DerSimonian and Laird’s random-effect model was used for relative risks, Freeman-Tukey Double Arcsine for pooled estimates and exact method to stabilize variances and CIs. Heterogeneity was quantified using I2-statistics. Six out of 164 published studies met the inclusion criteria. All (n = 221) women underwent metroplasty, using 5Fr-hysteroscope with bipolar electrodes or 26Fr/28Fr-resectoscope in outpatient or inpatient settings. After 6 to 60-month follow-up, reported live-birth rate was 50% (0.37-0.63 95% CI) from a clinical pregnancy rate of 73% (0.51-0.91 95% CI) and miscarriage rate was 23% (0.15-0.30 95% CI). Hysteroscopic metroplasty for dysmorphic uteri led half of the women who experienced recurrent miscarriages at least one live birth and is correlated to few surgical and obstetric complications. However, randomized clinical trials and case-control studies are unavailable due to ethical constrains; inhomogenity of follow-up durations and standardized protocols regarding preoperative diagnosis and post-surgical management resrict our conclusions.

Background: Ion channels play a crucial role in many physiological processes. Several subtypes are expressed in the endometrium. Endometriosis is strictly correlated to estrogens and it is evident that expression and functionality of different ion channels are estrogen-dependent, fluctuating between the menstrual phases. However, their relationship with endometriosis is still unclear. Objective: To summarize the available literature data about the role of ion channels in the etiopathogenesis of endometriosis. Methods: A search on PubMed and Medline databases was performed from inception to November 2019. Results: Cystic fibrosis transmembrane conductance regulator (CFTR), transient receptor potentials (TRPs), aquaporins (AQPs), and chloride channel (ClC)-3 expression and activity were analyzed. CFTR expression changed during the menstrual phases and was enhanced in endometriosis samples; its overexpression promoted endometrial cell proliferation, migration, and invasion throughout nuclear factor kappa-light-chain-enhancer of activated B cells-urokinase plasminogen activator receptor (NFκB-uPAR) signaling pathway. No connection between TRPs and the pathogenesis of endometriosis was found. AQP5 activity was estrogen-increased and, through phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT), helped in vivo implantation of ectopic endometrium. In vitro, AQP9 participated in extracellular signal-regulated kinases/p38 mitogen-activated protein kinase (ERK/p38 MAPK) pathway and helped migration and invasion stimulating matrix metalloproteinase (MMP)2 and MMP9. ClC-3 was also overexpressed in ectopic endometrium and upregulated MMP9. Conclusion: Available evidence suggests a pivotal role of CFTR, AQPs, and ClC-3 in endometriosis etiopathogenesis. However, data obtained are not sufficient to establish a direct role of ion channels in the etiology of the disease. Further studies are needed to clarify this relationship.

Background and Objectives: Hot flushes and sleep disturbances are the most common vasomotor symptoms (VMS) reported by postmenopausal women. Hormonal treatment is to date referred to as the gold standard approach but not suitable for all the patients. Alternative treatments are needed in case of a contraindication to menopausal hormone therapy (MHT), adverse side effects, and poor compliance. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS. Nonetheless, few trials with low consensus are available about this topic. In this review, we aimed to evaluate the efficacy of low-dose paroxetine therapy in the treatment of vasomotor hot flushes and night sleep disturbances in postmenopausal women. Materials and Methods: We performed an electronic search from the beginning of all databases to July 2019. All results were then limited to a randomized trial. Restrictions for language or geographic location were not utilized. Inclusion criteria were randomized clinical trials of physiological or surgical postmenopausal women experiencing hot flushes and sleep disturbances who were randomized to either low-dose paroxetine or placebo (i.e., formulations without active ingredients). The primary outcome evaluated was the mean weekly reduction of hot flushes. Results: Five randomized clinical trials, including 1482 postmenopausal women, were analyzed. Significant heterogeneity (I2 = 90%) between studies was noted. Hot flushes episodes were significantly reduced in the treatment arm compared to placebo (mean difference (MD) −7.97 [−10.51, −5.92] episodes/week). Results on the improvement on sleep were limited by being reported in only two studies; however, no significant reduction of night-time awakenings was observed (MD, −0.40 awakenings/night [−1.38, 0.58 CI]). Conclusions: Low-dose paroxetine is an effective treatment for vasomotor menopause symptoms, including hot flushes.