The diagnostic performance of the ductus venosus for the detection of cardiac defects in the first trimester: a systematic review and diagnostic test accuracy meta-analysis.

PURPOSE: Abnormal flow in the ductus venosus (DV) has been reported to be associated with adverse perinatal outcome, chromosomal abnormalities, and congenital heart defects (CHD). Aneuploid fetuses have increased risk of CHD, but there are discrepancies on the performance of this markers in euploid fetuses. The aim of this meta-analysis was to establish the predictive accuracy of DV for CHD. METHODS: MEDLINE, EMBASE, and CINAHL were searched from inception to February 2022. No language or geographical restrictions were applied. Inclusion criteria regarded observational and randomized studies concerning first-trimester DV flow as CHD marker. Random effect meta-analyses to calculate risk ratio (RR) with 95% confidence interval (CI), hierarchical summary receiver-operating characteristics (HSROC), and bivariate models to evaluate diagnostic accuracy were used. Primary outcome was the diagnostic performance of DV in detecting prenatal CHD by means of area under the curve (AUROC). Subgroup analysis for euploid, high-risk, and normal NT fetuses was performed. Quality assessment of included papers was performed using QUADAS-2. RESULTS: Twenty two studies, with a total of 204.829 fetuses undergoing first trimester scan with DV Doppler evaluation, fulfilled the inclusion criteria for this systematic review. Overall, abnormal DV flow at the time of first trimester screening was associated to an increased risk of CHD (RR 6.9, 95% CI 3.7-12.6; I2 = 95.2%) as well in unselected (RR: 6.4, 95% CI 2.5-16.4; I2 = 93.3%) and in euploid (RR: 6.45, 95% CI 3.3-12.6; I2 = 95.8%) fetuses. The overall diagnostic accuracy of abnormal DV in detecting CHD was good in euploid fetuses with an AUROC of 0.81 (95% CI 0.78-0.84), but it was poor in the high-risk group with an AUROC of 0.66 (95% CI 0.62-0.70) and in the unselected population with an AUROC of 0.44 (95% CI 0.40-0.49). CONCLUSIONS: Abnormal DV in the first trimester increases the risk of CHD with a moderate sensitivity for euploid fetuses. In combination with other markers (NT, TV regurgitation) could be helpful to identify fetuses otherwise considered to be at low risk for CHD. In addition to the improvement of the fetal heart examination in the first trimester, this strategy can increase the detection of major CHD at earlier stage of pregnancy.

Pre- versus Post-Menopausal Onset of Overactive Bladder and the Response to Vaginal Estrogen Therapy: A Prospective Study.

Background and Objectives: This study examined the utility of local estrogen therapy for improving urinary symptoms in women diagnosed with Overactive Bladder allied to the time of onset of urinary symptoms whether pre- or post-menopausal. Materials and Methods: Subject to informed consent, menopausal women diagnosed with Overactive Bladder (OAB) and Genitourinary Syndrome of Menopause (GSM) were enrolled at three urogynecological units. OAB symptoms were scored using the Global Pelvic Floor Symptoms Bother Questionnaire (GPFSBQ), with explicit attention to question number 3 that specifically addresses the presence or absence of urgency and the Patient Perception of Intensity of Urgency Scale (PPIUS). The Vaginal Health Index (VHI) was used to assess the vaginal mucosa trophism. Exclusion criteria included: Pelvic organ prolapse (POP) ≥ stage II, urinary tract infection or disease, diabetes, inflammatory diseases, use of diuretics, alcohol or drug addictions, neurological and/or psychiatric disorders, and other precluding conditions. Women were treated with local estrogens for 3 months and re-evaluated. Results: Forty-three post-menopausal women were enrolled. Of these, ten women developed OAB symptoms before menopause (Group I) and 33 developed symptoms after menopause (Group II). Following local estrogen therapy, based on the Global Pelvic Floor Symptoms Bother Questionnaire, improvement of OAB symptoms was reported by 20% of patients in Group I (p = 0.414) and 64% of patients in Group II, (p = 0.002). Based on the PPIUS scale, diminution in urinary urgency was experienced by 20% of patients in Group I (p = 0.68) and 66% of patients in Group II (p = 0.036). Improved VHI scores were graded statisticaly significant in both groups (Group I in 100% of women, p = 0.005 vs. 76% in Group II, p = 0.004). Conclusions: Our results indicate that local estrogen therapy is more effective in women who develop OAB after menopause.

Microbiota and HPV: The role of viral infection on vaginal microbiota.

The World Health Organization (WHO) estimates that the prevalence of human papillomaviruses (HPV) infection is between 9% and 13% of the world population and only in the United States, more than 6.2 million are positive every year. There are more than 100 types of HPV, among them, two serotypes (16 and 18) are related to 70% of cervical cancers and precancerous cervical lesions. The vaginal microbiota could play a considerable role in HPV infection and the genesis of cervical tumors caused by HPV. Moreover, bacteria are strongly associated with vaginal inflammation and oncogenic mutations in human cells. We aim to investigate whether HPV infection could influence the bacterial microbiota composition in the uterine cervix. A total of 31 women were enrolled in this study. The vaginal swabs were collected; the HPV-DNA was extracted with QIAamp DNA Microbiome. The V3-V4-V6 region of the 16S rDNA gene was amplified by polymerase chain reaction (PCR) followed by sequencing with MiSeq Illumina. The main phylum identified in the vaginal microbiota were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. The phylum of Actinobacteria, Proteobacteria, and Bacteroides was more represented in HPV-positive patients. Lactobacilli represented the dominant genus, with a high percentage of Lactobacilli iners, Lactobacilli jensenii, and Lactobacilli crispatus as species. Gardnerella vaginalis, Enterococcus spp., Staphylococcus spp., Proteus spp., and Atopobium were the most represented in HPV-positive patients. An altered vaginal microbiota might play a functional role in HPV cervical infection, progression, and clearance. The relationship between infection and microbiota could spur the development of new probiotics. However, further studies are needed to clarify the role of the vaginal microbiota in HPV infection.

Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: A Problem with a Thousand Nuances-A Systematic Review of Oncological Outcomes.

BACKGROUND: Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC). The guidelines have recognized various approaches, depending on the tumor stage and other risk factors such as histotype and lymphovascular positivity. Much more debate has centered around the boundary within which these treatments should be considered. Indeed, these are methods to be reserved for ECC, but tumor size may represent the most significant limitation. In particular, there is no consensus on the strategy to be adopted in the case of ECC ≥ 2 cm. Therefore, this systematic review was to collect the literature evidence regarding the management of these patients. METHODS: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the Pubmed and Scopus databases was conducted in April 2022, from the date of the first publication. We made no limitation on the country. We included all studies containing data on disease-free survival, overall survival, recurrence rate (RR), or complete response rate (CRR) to chemotherapy. RESULTS: Twenty-six studies fulfilled the inclusion criteria, and 691 patients were analyzed regarding FST. Surgery-based FST showed an RR of between 0 and 42.9%, which drops to 12.9% after excluding the vaginal or minimally invasive approaches. Furthermore, papers regarding FST based on the neoadjuvant chemotherapy (NACT) approach showed a CRR of between 21.4 and 84.5%, and an RR of between 0 and 22.2% CONCLUSION: This paper focused on the significant heterogeneity present in the clinical management of FST of ECC ≥ 2 cm. Nevertheless, from an oncological point of view, approaches limited to the minimally invasive or vaginal techniques showed the highest RR. Vice versa, the lack of standardization of NACT schemes and the wealth of confounders to be attributed to the histological features of the tumor make it difficult, if not impossible, to set a standard of treatment.

Laparo-assisted vaginal radical hysterectomy as a safe option for minimal invasive surgery in early stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: Radical hysterectomy and pelvic lymphadenectomy are considered the standard treatment for early-stage cervical cancer (ECC). Minimal Invasive approach to this surgery has been debated after the publication of a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC trial). It demonstrated poorer oncological outcomes for Minimal Invasive Surgery in ECC. However, the reasons are still an open debate. Laparo-Assisted Vaginal Hysterectomy (LAVRH) seems to be a logical option to Abdominal Radical Hysterectomy (ARH). This meta-analysis has the aim to prove it. METHODS: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the Pubmed database and Scopus database were systematically searched in January 2022 since early first publications. No limitation of the country was made. Only English article were considered. The studies containing data about Disease-free Survival (DFS) and/or Overall Survival (OS) and/or Recurrence Rate (RcR) were included. RESULTS: 18 studies fulfilled inclusion criteria. 8 comparative studies were enrolled in meta-analysis. Patients were analyzed concerning surgical approach (Laparo-Assisted Vaginal Radical Hysterectomy) and compared with ARH Oncological outcomes such as DFS and OS were considered. 3033 patiets were included. Meta-analysis highlighted a non-statistic significant difference between LARVH and ARH (RR 0.82 [95% CI 0.55-1.23] p = 0.34; I2 = 0%; p = 0.96). OS was feasible only for 3 studies (RR 1.14 [95% CI 0.28-4.67] p = 0.43; I2 = 0 p = 0.86). Data about the type of recurrences (loco-regional vs distant) were collected. CONCLUSION: LARVH does not appear to affect DFS and OS in ECC patients. The proposed results seem to be comparable with the open approach group of the LACC trial, which today represents the reference standard for the treatment of this pathology. More studies will be needed to test the safety and efficacy of LARVH in the ECC.

Laparo-assisted vaginal radical hysterectomy as a safe option for Minimal Invasive Surgery in early stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: Radical hysterectomy and pelvic lymphadenectomy are considered the standard treatment for early-stage cervical cancer (ECC). Minimal Invasive approach to this surgery has been debated after the publication of a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC trial). It demonstrated poorer oncological outcomes for Minimal Invasive Surgery in ECC. However, the reasons are still an open debate. Laparo-Assisted Vaginal Hysterectomy (LAVRH) seems to be a logical option to Abdominal Radical Hysterectomy (ARH). This meta-analysis has the aim to prove it. METHODS: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the Pubmed database and Scopus database were systematically searched in January 2022 since early first publications. No limitation of the country was made. Only English article were considered. The studies containing data about Disease-free Survival (DFS) and/or Overall Survival (OS) and/or Recurrence Rate (RcR) were included. RESULTS: 19 studies fulfilled inclusion criteria. 9 comparative studies were enrolled in meta-analysis. Patients were analyzed concerning surgical approach (Laparo-Assisted Vaginal Radical Hysterectomy) and compared with ARH Oncological outcomes such as DFS and OS were considered. 3196 patiets were included for the review. Meta-analysis of 1988 0f them highlighted a non-statistic significant difference between LARVH and ARH (RR 0.8 [95% CI 0.55-1.16] p = 0.24; I2 = 0%; p = 0.98). OS was feasible only for 4 studies (RR 0.84 [95% CI 0.23-3.02] p = 0.79; I2 = 0 p = 0.44). Sub-analysis for tumor with a maximum diameter greater than 2 cm was performed. Data about the type of recurrences (loco-regional vs distant) were collected. CONCLUSION: LARVH does not appear to affect DFS and OS in ECC patients. The proposed results seem to be comparable with the open approach group of the LACC trial, which today represents the reference standard for the treatment of this pathology. More studies will be needed to test the safety and efficacy of LARVH in the ECC.

Incidence of gestational diabetes mellitus before and after the Covid-19 lockdown: A retrospective cohort study.

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/m2 , 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.

Impact of Braxton-Hicks contractions on fetal wellbeing; a prospective analysis through computerised cardiotocography.

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.

Aberrant right subclavian artery: the association with chromosomal defects and the related post-natal outcomes in a third level referral centre.

Aberrant right subclavian artery (ARSA) is the most common embryologic abnormality of the aortic arch. The presence of ARSA has been previously associated with an increased risk of Down syndrome. ARSA at birth may be associated with dysphagia, respiratory distress and stridor and there is no clear evidence-based management. The aim of this study was to describe the associations with chromosomal abnormalities and the postnatal outcome of fetuses diagnosed with ARSA. We analysed fetuses diagnosed antenatally with ARSA between January 2013 and September 2019 in the fetal echocardiography unit of the Hospital Monaldi, University 'Vanvitelli' of Naples, Italy. The results showed fifty fetuses diagnosed with ARSA, all confirmed after birth. The ARSA was an isolated finding in 46 fetuses (92%), while in 4 fetuses the ARSA was associated with other cardiac and/or extra-cardiac anomalies. Only one fetus was diagnosed with trisomy 21 (2%). In this fetus the ARSA was the only ultrasound anomaly identified. There were no cases necessitating referral due to the presence of compression symptoms at birth. The presence of ARSA was associated with trisomy 21 in the 2% of cases in our series and there were no neonatal complications due to airway compression at birth.IMPACT STATEMENTWhat is already known on this subject? Aberrant right subclavian artery (ARSA) is the most common embryologic abnormality of the aortich arch. ARSA at birth could be associated with dysphagia, respiratory distress and stridor and no evidence-based management of these fetuses has been described yet. The presence of ARSA has been previously associated with an increased risk of Down syndrome.What do the results of this study add? This study confirms known data on association with chromosomal defects and provides some original data on the absence of symptomatology due to tracheal compression with a postnatal follow-up up to three years of age.What are the implications of these findings for clinical practice and/or further research? Our findings suggest that in cases with adequate prenatal assessment performed by experienced clinicians, delivery can safely take place at local hospitals, with no need of referral soon after birth. The use of transthoracic echocardiography to confirm the diagnoses of ARSA after birth and to plan the next follow-up appointments can be supported.

The Oncological Implication of Sentinel Lymph Node in Early Cervical Cancer: A Meta-Analysis of Oncological Outcomes and Type of Recurrences.

Background and Objectives: Pelvic lymphadenectomy has been associated with radical hysterectomy for the treatment of early Cervical Cancer (ECC) since 1905. However, some complications are related to this technique, such as lymphedema and nerve damage. In addition, its clinical role is controversial. For this reason, the sentinel lymph node (SLN) has found increasing use in clinical practice over time. Oncologic safety, however, is debated, and there is no clear evidence in the literature regarding this. Therefore, our meta-analysis aims to schematically analyze the current scientific evidence to investigate the non-inferiority of SLN versus PLND regarding oncologic outcomes. Materials and Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in June 2022 since their early first publications. We made no restrictions on the country. We considered only studies entirely published in English. We included studies containing Disease-Free Survival (DFS), Overall Survival (OS), Recurrence Rate (RR), and site of recurrence data. We used comparative studies for meta-analysis. We registered this meta-analysis to the PROSPERO site for meta-analysis with protocol number CRD42022316650. Results: Twelve studies fulfilled inclusion criteria. The four comparative studies were enrolled in meta-analysis. Patients were analyzed concerning Sentinel Lymph Node Biopsy (SLN) and compared with Bilateral Pelvic Systematic Lymphadenectomy (PLND) in early-stage Cervical Cancer (ECC). Meta-analysis highlighted no differences in oncological safety between these two techniques, both in DFS and OS. Moreover, most of the sites of recurrences in the SLN group seemed not to be correlated with missed lymphadenectomy. Conclusions: Data in the literature do not seem to show clear oncologic inferiority of SLN over PLND. On the contrary, the higher detection rate of positive lymph nodes and the predominance of no lymph node recurrences give hope that this technique may equal PLND in oncologic terms, improving its morbidity profile.

Hysteroscopic and ultrasonographic evaluation of ulipristal acetate treatment for symptomatic myomas in premenopausal women: a prospective study.

OBJECTIVE: This study aimed to analyze the effects of a six-month therapy with ulipristal acetate (UPA) on myoma size and endometrial thickness in premenopausal women. MATERIAL AND METHODS: Seventy-four women undergoing conservative therapy with UPA were enrolled for this study. All women underwent transvaginal ultrasound evaluation to assess the endometrial thickness, and the number and size of myomas at the beginning and after six months. Hysteroscopy and biopsy were performed after six months, if necessary. RESULTS: After six months of treatment, sonographic examination showed a statistically significant (p < .05) reduction of the size of the largest myoma (56.3 ± 5.1 vs. 31.7 ± 10.1 mm) and a statistically significant (p < .05) increase in endometrial thickness (5.9 ± 2.1 vs. 9.7 ± 3.4 mm). Twenty-two patients with endometrial thickness >10 mm or nonhomogeneous pattern and ten patients with metrorrhagia underwent hysteroscopy: the most frequent finding was the combination of endometrial hypotrophy, floating surface, and chicken-wire vascular pattern aspect (14 cases, 43.7%). Histologic findings showed no case of complex hyperplasia. CONCLUSION: UPA is a safe, effective and assured method to decrease symptoms, reduce the need for surgery in premenopausal women suitable for the treatment.

Reproductive and pregnancy outcomes following embryo transfer in women with previous cesarean section: A systematic review and meta-analysis.

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 13 696 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.

Flow Cytometry Characterization of Pluripotent Transmembrane Glycoproteins on Resident Cervix Uteri Cells in Patients Screened for Cervical Cancer.

The aim of this study was to characterize both by flow cytometry analysis and immunohistochemistry cervix uteri cells of nulliparous women screened for cervical intraepithelial neoplasia (CIN) in comparison to a group without CIN by using mesenchymal stem cell-like and hematopoietic lineage markers. A significant expression for CD29, CD38, HLA-I, and HLA-II was correlated positively to the CIN degree and it was more relevant in patients positive for human papilloma virus (HPV). Thus, identification and detailed characterization of pluripotent resident in uteri cells could be a promising therapeutic target.

Integrated pre-surgical diagnostic algorithm to define extent of disease in cervical cancer.

OBJECTIVES: Survival of patients with cervical cancer is strongly associated with the local extent of the primary disease. The aim of the study was to develop an integrated diagnostic algorithm, including ultrasonography (USG), magnetic resonance imaging (MRI), and examination under anesthesia, to define the local extent of disease in patients with newly diagnosed cervical cancer. METHODS: Patients with biopsy proven cervical cancer who underwent primary surgery from January 2013 to December 2018 in four participating centers were recruited. Patients who underwent USG, MRI, and examination under anesthesia prior to surgery were included in the study. Those for whom complete data were not available were excluded. Data regarding tumor size, parametrial invasion, and vaginal involvement obtained by USG, MRI, and examination under anesthesia were retrieved and compared with final histology. Specificity and sensitivity of the three methods were calculated for each parameter and the methods were compared with each other. An integrated pre-surgical algorithm was constructed considering the accuracy of each diagnostic method for each parameter. RESULTS: A total of 79 consecutive patients were included in the study. Median age was 53 years (range 28-87) and median body mass index was 24.6 kg/m2 (range 16-43). Fifty-five (69.6%) patients had squamous carcinoma, 18 (22.8%) patients had adenocarcinoma, and six (7.6%) patients had other histological subtypes. A statistically significant difference among the three methods was found for detecting tumor size (p=0.002 for tumors >2 cm and p=0.006 for tumors >4 cm) and vaginal involvement (p=0.01). There was no difference in detection of parametrial invasion between USG, MRI, and examination under anesthesia (p=0.26). Furthermore, regarding tumor size assessment, USG was found to be the significantly better method (p<0.01 for tumors >2 cm and p=0.02 for tumors >4 cm). Examination under anesthesia was the most accurate method for detection of vaginal involvement (p=0.01). Examination under anesthesia and MRI had higher accuracy than USG for identification of parametrial invasion. Application of the algorithm provided the correct definition of local extent of disease in 77.2% of patients (p=0.04). USG was the most accurate method to determine tumor size, while examination under anesthesia was found to be more accurate in prediction of vaginal involvement. CONCLUSION: Our integrated diagnostic algorithm allows a higher accuracy in defining the local extent of disease and may be used as a tool to determine the therapeutic approach in women with cervical cancer.

Reproductive outcome after cesarean scar pregnancy: A systematic review and meta-analysis.

INTRODUCTION: To evaluate subsequent reproductive among women with a prior cesarean scar pregnancy (CSP). MATERIAL AND METHODS: MEDLINE, Embase and ClinicalTrials.gov databases were searched. Inclusion criteria were women with a prior CSP, defined as the gestational sac or trophoblast within the dehiscence/niche of the previous cesarean section scar or implanted on top of it. The primary outcome was the recurrence of CSP; secondary outcomes were the chance of achieving a pregnancy after CSP, miscarriage, preterm birth, uterine rupture and the occurrence of placenta accreta spectrum disorders. Subgroup analysis according to the management of CSP (surgical vs non-surgical) was also performed. Random effect meta-analyses of proportions were used to analyze the data. RESULTS: Forty-four studies (3598 women with CSP) were included. CSP recurred in 17.6% of women. Miscarriage, preterm birth and placenta accreta spectrum disorders complicated 19.1% (65/341), 10.3% (25/243) and 4.0% of pregnancies, and 67.0% were uncomplicated. When stratifying the analysis according to the type of management, CSP recurred in 21% of women undergoing surgical and in 15.2% of those undergoing non-surgical management. Placenta accreta spectrum disorders complicated 4.0% and 12.0% of cases, respectively. CONCLUSIONS: Women with a prior CSP are at high risk of recurrence, miscarriage, preterm birth and placenta accreta spectrum. There is still insufficient evidence to elucidate whether the type of management adopted (surgical vs non-surgical) can impact reproductive outcome after CSP. Further large, prospective studies sharing an objective protocol of prenatal management and long-term follow up are needed to establish the optimal management of CSP and to elucidate whether it may affect its risk of recurrence and pregnancy outcome in subsequent gestations.

In vitro genotoxic effects of titanium dioxide nanoparticles (n-TiO2 ) in human sperm cells.

Titanium dioxide nanoparticles (TiO2 -NPs) are one of the most widely engineered nanoparticles used. The study has been focused on TiO 2 -NPs genotoxic effects on human spermatozoa in vitro. TiO 2 -NPs are able to cross the blood-testis barrier induced inflammation, cytotoxicity, and gene expression changes that lead to impairment of the male reproductive system. This study presents new data about DNA damage in human sperms exposed in vitro to two n-TiO 2 concentrations (1 µg/L and 10 µg/L) for different times and the putative role of reactive oxygen species (ROS) as mediators of n-TiO 2 genotoxicity. Primary n-TiO 2 characterization was performed by transmission electron microscopy. The dispersed state of the n-TiO 2 in media was spectrophotometrically determined at 0, 24, 48, and 72 hr from the initial exposure. The genotoxicity has been highlighted by different experimental approaches (comet assay, terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL] test, DCF assay, random amplification of polymorphic DNA polymerase chain reaction [RAPD-PCR]). The comet assay showed a statistically significant loss of sperm DNA integrity after 30 min of exposure. Increased threshold of sperm DNA fragmentation was highlighted after 30 min of exposure by the TUNEL Test. Also, the RAPD-PCR analysis showed a variation in the polymorphic profiles of the sperm DNA exposed to n-TiO 2 . The evidence from the DCF assay showed a statistically significant increase in intracellular ROS linked to n-TiO 2 exposure. This research provides the evaluation of n-TiO 2 potential genotoxicity on human sperm that probably occurs through the production of intracellular ROS.

A Nutraceutical Approach to Menopausal Complaints.

The menopausal transition, or perimenopause, is characterized by menstrual irregularities, vasomotor symptoms, sleep disturbances, mood symptoms, and urogenital tract atrophy. These changes can also affect the quality of life and one's self-esteem. Hormone replacement therapy (HRT) is considered the best option to achieve therapeutic relief of different menopausal symptoms but is usually restricted to moderate or severe symptoms. Moreover, many women refuse HRT for a variety of reasons concerning the fear of cancer and other adverse effects. According to these considerations, new topics are emerging: Dissatisfaction with drug costs and conventional healthcare, desire for personalized medicines, and the public perception that "natural is good". In this context, nonhormonal therapies are mostly evolving, and it is not unusual that women often request a "natural" approach for their symptoms. The aim of this study is to investigate nonhormonal therapies that have been identified to reduce the menopausal symptoms.

Oocyte polarized light microscopy, assay of specific follicular fluid metabolites, and gene expression in cumulus cells as different approaches to predict fertilization efficiency after ICSI.

BACKGROUND: The complex relationship between oocyte morphology, specific follicular fluid metabolites, gene expression in cumulus granulosa cells, and oocyte competence toward fertilization and embryo development still needs further clarification. METHODS: Forty-six oocytes retrieved from the largest pre-ovulatory follicle of patients undergoing intra-cytoplasmic sperm injection (ICSI) were considered assessing: (a) oocyte morphological characteristics at polarized light microscopy (PLM), (b) specific follicular fluid (FF) metabolites previously suggested to influence oocyte competence (AMH, markers of redox status and of cytotoxicity), (c) transcription of AMH and AMH type II receptor genes in cumulus cells. Data were analyzed using mono-parametric tests and multivariable logistic analysis in order to correlate morphological and biochemical data with fertilization. RESULTS: Comparing normally fertilized oocytes (n = 29, F group) with unfertilized (n = 17, nF group) we observed that: (a) the meiotic spindle area and major axis were significantly higher in nF group and in fertilized oocytes undergoing an early embryo development arrest; (b) AMH level in FF was comparable in F and nF groups; (c) the FF of nF group contained significantly higher levels of cytotoxicity (lactate dehydrogenase) and oxidative stress (Cu,Zn-superoxide dismutase, catalase, 4-hydroxynonenal-protein conjugates) markers; (d) cumulus cells of nF group showed significantly higher AMH receptor type II gene expression. CONCLUSIONS: Taken together, these observations suggest that an excessive cytotoxicity level can alter AMH signal transduction within cumulus cells, in turn leading to partial inhibition of aromatase activity, altered cytoplasmic maturation and increased oxidative stress, factors able to impair oocyte fertilization competence and embryo growth.