Diagnostic and prognostic value of Bcl-2 in uterine leiomyosarcoma.

BACKGROUND: Uterine leiomyosarcoma (uLMS) may show loss of expression of B-cell lymphoma-2 (Bcl-2) protein. It has been suggested that Bcl-2 loss may both be a diagnostic marker and an unfavorable prognostic marker in uLMS. OBJECTIVE: To define the diagnostic and prognostic value of Bcl-2 loss in uLMS through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to May 2020 for all studies assessing the diagnostic and prognostic value of Bcl-2 loss of immunohistochemical expression in uLMS. Data were extracted to calculate odds ratio (OR) for the association of Bcl-2 with uLMS vs leiomyoma variants and smooth-muscle tumors of uncertain malignant potential (STUMP), and hazard ratio (HR) for overall survival; a p value < 0.05 was considered significant. RESULTS: Eight studies with 388 patients were included. Loss of Bcl-2 expression in uLMS was not significantly associated with a diagnosis of uLMS vs leiomyoma variants and STUMP (OR = 2.981; p = 0.48). Bcl-2 loss was significantly associated with shorter overall survival in uLMS (HR = 3.722; p = 0.006). High statistical heterogeneity was observed in both analyses. CONCLUSION: Loss of Bcl-2 expression appears as a significant prognostic but not diagnostic marker in uLMS. The high heterogeneity observed highlights the need for further research and larger studies.

Prevalence and associated psychological risk factors of postpartum depression: a cross-sectional study.

This cross-sectional study aimed to evaluate the prevalence of postpartum depression and the associated risk factors in a sample of Italian women at three months after delivery. Eighty women were screened by completing the Edinburgh Postnatal Depression Scale (EPDS). Women with a score ≥10 were evaluated as positive and other variables were detected through the administration of the Postpartum Depression Predictors Inventory.The prevalence of postpartum depression in the sample was 11.25% (EPDS score >10). A statistically significant relationship was found between the predisposition to postnatal depression and various risk factors such as prenatal depression, stressful life experiences marital problems. Furthermore, strong emotional and instrumental support from the partner and a good economic status can represent protective factors. It is essential to promote an integrated approach to postpartum affective disorders in which psychosocial risk factors are taken into account, and adequate screening programs are implemented.Impact StatementWhat is already known on this subject? Pregnancy can cause emotional stress for women with consequent development, in some cases, of mood disorders such as postpartum depression.What do the results of this study add? According to this study, women suffering from postpartum depression showed a significant tendency to anxiety and depression, low perceived support from the partner, and low socio-economic status.What are the implications of these findings for clinical practice and/or further research? It would be desirable to promote an integrated approach to postpartum affective disorders in which psychosocial risk factors are taken into account and adequate screening programs are implemented.

Microbiome and PCOS: State-of-Art and Future Aspects.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

Hysteroscopic Intact Removal of an Angular Pregnancy with a 5Fr Electrode.

STUDY OBJECTIVE: Angular pregnancy is a rare and life-threatening condition in which the embryo is implanted in the lateral angle of the uterine cavity, medial to the uterotubal junction and round ligament. Angular pregnancy is associated with a high risk of uterine rupture of about 23% [1]. No consensus has been achieved regarding the diagnostic and therapeutic approach of angular pregnancy [2]. Thus, the aim of this study was to report a case of hysteroscopic treatment of an angular pregnancy in a 34-year-old women. DESIGN: Step-by-step video presentation of the surgical treatment (Canadian Task Force classification III). SETTING: Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy. PATIENT: A 34-year-old woman. Written informed consent was obtained from the patient. INTERVENTION: Hysteroscopy. MEASUREMENTS AND MAIN RESULTS: A 34-year-old woman was admitted to our Department with pelvic pain at 6 weeks of gestation. ß-Human chorionic gonadotropin (ß-hCG) was 5331 mIU/mL. The transvaginal ultrasound showed a gestational sac of 15 × 11 mm in the left uterine angle of an embryo without cardiac activity. The woman opted for a conservative approach with multiple-dose methotrexate [3]. Five days later the ß-hCG increased to 7589 mIU/mL with no regression of pregnancy at the transvaginal ultrasound. Therefore, a surgical approach was offered to the patient [4,5]. Laparoscopy showed normal salpinges, whereas hysteroscopy identified the gestational sac in the left uterine angle. A 5Fr bipolar electrode was used to open the gestational capsular decidua. The chorionic villi were progressively separated from the implantation site. Using grasping forceps we removed the specimen for histologic examination. Histologic examination confirmed the diagnosis of angular pregnancy. On the second postoperative day ß-hCG was 1131 mIU/mL, and the patient was discharged the day after. At the 1-month follow-up visit, ß-hCG and transvaginal ultrasound were negative for pregnancy. The office hysteroscopy showed an empty uterine cavity at 3-months' follow-up. CONCLUSION: Our case shows that hysteroscopy may be used as a diagnostic and therapeutic tool for angular pregnancy, providing a unique image of the intact removal of the gestational sac.

Low Interferon-γ Levels in Cord and Peripheral Blood of Pregnant Women Infected with SARS-CoV-2.

COVID-19 is characterized by the immune system's overreaction resulting in a 'cytokine storm', consisting in a massive release of cytokine into the bloodstream, leading to local and systemic inflammatory response. This clinical picture is further complicated in case of infection of patients with a peculiar immunological status, such as pregnancy. In this paper, we focused on Interferon-γ, which plays a pivotal immunomodulatory role in normal pregnancy and fetal development, as well as in defense against pathogens. In this study, we compared the levels of Interferon-γ and the Interferon autoantibodies of the peripheral and cord blood of pregnant women with confirmed mild COVID-19 and healthy pregnant women. The Interferon-γ was significantly lower both in the peripheral and cord blood of SARS-CoV-2-positive mothers, suggesting that infection can affect the fetal microenvironment even without severe maternal symptoms. In conclusion, further studies are needed to clarify whether lower levels of Interferon-γ due to SARS-CoV-2 infection affect the development or infection susceptibility of infants born to SARS-CoV-2-infected mothers.

Risk of unscheduled delivery in women with placenta accreta according to planned gestational age at delivery.

BACKGROUND: The optimal gestational age at delivery for stable women with suspected placenta accreta is still subject of debate. OBJECTIVE: To estimate the likelihood of vaginal bleeding necessitating expedited delivery in women with placenta accreta according to gestational age at planned cesarean hysterectomy. STUDY DESIGN: This was a multicenter cohort study. Singleton pregnancies at risk of placenta accreta because of placenta previa in the setting of prior cesarean delivery were included. Outcomes were compared in cohort of women who had planned cesarean hysterectomy at 34 0/7 - 34 6/7 weeks versus at 35 0/7 - 35 6/7 weeks. The primary outcome was incidence of vaginal bleeding severe enough to necessitate delivery. RESULTS: 118 singleton pregnancies with placenta previa in the setting of prior cesarean delivery, and confirmed placenta accreta at the time of delivery were included in the study. Women who had planned cesarean hysterectomy at 34 weeks had lower episodes of vaginal bleeding severe enough to necessitate immediate or emergency delivery (20.6% vs 38.0%; odds ratio (OR) 0.42, 95% confidence interval (CI) 0.19 to 0.96). Eight women (11.8%) in the 34 weeks group and 6 women (12.0%) in the 35 weeks group delivered before the planned date due to onset of spontaneous labor (OR 0.98, 95% CI 0.32 to 3.02). CONCLUSION: In singleton gestations with suspected placenta accreta, planned cesarean hysterectomy at 34 0/7 - 34 6/7 weeks was associated with a decreased chance of unscheduled delivery due to severe vaginal bleeding. CONDENSATION: In case of placenta accreta, planned cesarean hysterectomy at 34 weeks was associated with decreased chance of unscheduled delivery due to severe vaginal bleeding.

Trends in Caesarean Section Rate According to Robson Group Classification among Pregnant Women with SARS-CoV-2 Infection: A Single-Center Large Cohort Study in Italy.

BACKGROUND: Since there is no available data on temporal trends of caesarean section (CS) rates in pregnant women with COVID-19 through the pandemic, we aimed to analyze the trends in caesarean section rate in a large cohort of pregnant women with COVID-19, according to the Robson Ten Group Classification System of deliveries. METHODS: We prospectively enrolled pregnant women with a diagnosis of COVID-19 who delivered in our center between March 2020 and November 2021. Deliveries were classified, according to the Robson group classification, and according to three time periods: (1) deliveries from March 2020 to December 2020; (2) deliveries from January 2021 to April 2021; (3) deliveries from May 2021 to November 2021. We compared pregnancy characteristics and incidence of caesarean section, according to the Robson category in the total population, and according to the three time periods. RESULTS: We included 457 patients matching the inclusion criteria in our analysis. We found that overall CS rate significantly decreased over time from period 1 to period 3 (152/222, 68.5% vs. 81/134, 60.4% vs. 58/101, 57.4%, χ2 = 4.261, p = 0.039). CS rate significantly decreased over time in Robson category 1 (48/80, 60% vs. 27/47,57.4% vs. 8/24, 33.3%, χ2 = 4.097, p = 0.043) and Robson category 3 (13/42, 31% vs. 6/33, 18.2% vs. 2/22, 9.1%, χ2 = 4.335, p = 0.037). We also found that the incidence of induction of labor significantly increased over time (8/222, 3.6% vs. 12/134, 9% vs. 11/101, 10.9%, χ2 = 7.245, p = 0.027). CONCLUSION: Our data provide an overview of the temporal changes in the management and obstetric outcome of COVID-19 pregnant women through the pandemic, confirming that standards of obstetrical assistance for pregnancies complicated by SARS-CoV-2 infection improved over time.

Severe hypercalcemia associated with hypophosphatemia in very premature infants: a case report.

BACKGROUND: Severe hypercalcemia is rare in newborns; even though often asymptomatic, it may have important sequelae. Hypophosphatemia can occur in infants experiencing intrauterine malnutrition, sepsis and early high-energy parenteral nutrition (PN) and can cause severe hypercalcemia through an unknown mechanism. Monitoring and supplementation of phosphate (PO4) and calcium (Ca) in the first week of life in preterm infants are still debated. CASE PRESENTATION: We report on a female baby born at 29 weeks' gestation with intrauterine growth retardation (IUGR) experiencing sustained severe hypercalcemia (up to 24 mg/dl corrected Ca) due to hypophosphatemia while on phosphorus-free PN. Hypercalcemia did not improve after hyperhydration and furosemide but responded to infusion of PO4. Eventually, the infant experienced symptomatic hypocalcaemia (ionized Ca 3.4 mg/dl), likely exacerbated by contemporary infusion of albumin. Subsequently, a normalization of both parathyroid hormone (PTH) and alkaline phosphatase (ALP) was observed. CONCLUSIONS: Although severe hypercalcemia is extremely rare in neonates, clinicians should be aware of the possible occurrence of this life-threatening condition in infants with or at risk to develop hypophosphatemia. Hypophosphatemic hypercalcemia can only be managed with infusion of PO4, with strict monitoring of Ca and PO4 concentrations.

Robotic Hysterectomy as a Step of Gender Affirmative Surgery in Female-to-Male Patients.

INTRODUCTION: To evaluate the feasibility and safety of robotic hysterectomy in the "transgender male/non-conforming" population and the short and long-term surgical outcomes of robotic surgery in these patients. MATERIALS AND METHODS: A retrospective analysis was carried out from February 2016 to January 2018. Twenty female transgender patients with a previous psychiatric diagnosis of gender dysphoria who did not present genital pathologies were included in the study. The robotic hysterectomies were performed from June 2016 to March 2018 using a Da Vinci Xi Robot (Intuitive Surgical, Sunnyvale, CA, USA). RESULTS: No intraoperative or postoperative complications were recorded. The median duration of the intervention was of 90 minutes, including docking which lasted 16 minutes, while the median stay in the operating room was of 140 minutes. The median time of duration of intervention was of 90 minutes. The median blood loss was about 90 ml with a percentage decrease in hemoglobin between pre- and post-operative of about 8%. Postoperative pain was assessed using the VAS scale in the immediate postoperative period, on the first and second day, resulting of 3 and 2, respectively. The pathological examination of surgical specimens confirmed the absence of malignancy. CONCLUSIONS: The robotic approach represents a feasible, safe, and effective surgical option for hysterectomy for "transgender male" affected by gender dysphoria.

Risk of Recurrence in Uterine Leiomyoma with Bizarre Nuclei: a Systematic Review and Meta-Analysis.

Objective Leiomyoma with bizarre nuclei (LBN) is a variant of uterine leiomyoma, which has replaced the previous category of "atypical leiomyoma" and must be distinguished from smooth muscle tumors of uncertain malignant potential (STUMP). However, previously published series of "atypical leiomyoma" might have included both LBN and STUMP, due to the lack of strict diagnostic criteria. Based on such hypothesis, we aimed to define the risk of recurrence in LBN. Study Design A systematic review and meta-analysis was performed by searching 4 electronic databases for all studies assessing the outcome of patients with "atypical leiomyoma" or LBN. The pooled absolute risk of recurrence was calculated. The included studies were subdivided into two subgroups based on the criteria used: "LBN + STUMP" or "LBN-only". Results Twelve studies with 433 patients were included. The pooled risk of recurrence was 5.5% overall. The funnel plot showed two cluster of studies which superimposed to the two subgroups. In the LBN + STUMP cluster/subgroup, the pooled risk of recurrence was 7.7%. In the LBN-only cluster/subgroup, the pooled risk of recurrence was 1.9%. Statistical heterogeneity was null in all analyses. Conclusion Our results show a risk of recurrence of 1.9% for LBN; higher recurrence rates in older studies are likely due to the inclusion of STUMPs.

Role of ultrasonographic parameters for predicting tubal involvement in infertile patients affected by endometriosis: A retrospective cohort study.

INTRODUCTION: Transvaginal ultrasound is fundamental for the mapping of endometriosis, and the imaging criteria have been clearly described for different organs study. However, no specific ultrasonographic signs of tubal endometriosis have been reported, with the exception of hydrosalpinx, which is the expression of an extreme tubal damage and obstruction. The detection of tubal pathology in infertile patients is fundamental, therefore the aim of the study was to evaluate incidence of tubal endometriosis in infertile patients, and to analyze ultrasonographic signs useful for detection of this condition. MATERIAL AND METHODS: It is a single-center, retrospective cohort study. All 500 consecutive infertile women who underwent laparoscopic surgery for endometriosis were included. The preoperative workup included transvaginal ultrasound and was compared to intraoperative findings and histologic study. RESULTS: The incidence of tubal endometriosis in our study was 8%. Using hydrosalpinx as the ultrasonographic marker for tubal involvement the overall pooled, sensitivity and specificity of TVU were 12% (95%CI, 5-23%) and 99% (95%CI, 98-100%), respectively. If at least one ultrasonographic parameter like hydrosalpinx, periadnexal adhesions or ovarian cyst was considered as a sign of tubal endometriosis, a sensitivity, VPN and specificity were 94% (95% IC, 85-98%), 97% (95%IC, 93-99%) and 31% (95%CI, 27-36%), respectively. DISCUSSION: Hydrosalpinx as ultrasonographic sign alone is characterized by a high specificity but low sensitivity for detection of tubal endometriosis; its sensitivity can be improved by the addition of other markers such as endometrioma and/or periadnexal adhesions.

Use of routine ureteral stents in cesarean hysterectomy for placenta accreta.

Objective: To evaluate benefits of use of ureteral stents in association with cesarean hysterectomy in case of placenta accreta.Methods: This was a single center, cohort study. Clinical records of singleton pregnancies with placenta accreta who underwent cesarean hysterectomy were included in the study. For this study, pregnancies with diagnoses of placenta accreta, increta, or percreta were considered under the umbrella term of placenta accreta. For all women with placenta accreta, delivery was planned via cesarean hysterectomy at 340-356 weeks, without any attempt to remove the placenta. Reasons for earlier delivery included vaginal bleeding and spontaneous onset of labor. The primary outcome was the incidence of unintentional urinary tract injury. Outcomes were compared in a cohort of women who had planned the placement of ureteral stents and in those who did not.Results: Forty-four singleton gestations with confirmed placenta accreta at the time of cesarean hysterectomy were included in the study. Twenty-four (54.5%) of the included women had the placing of ureteral stents prior to cesarean, while 20 (45.5%) did not. At histological confirmation, most of them had placenta accreta (17/44, 38.6%), 14 placenta increta (31.8%), and 13 placenta percreta (29.6%). Urinary tract injuries occurred in eight cases (18.2%), six in the ureteral stents and two in the non-ureteral stents group (25 versus 10%; p = .21). All the injuries were bladder injuries, while no cases of ureteral injury were recorded. All injuries were recognized intraoperatively.Conclusion: In case of placenta accreta, the use of ureteral stents in association with cesarean hysterectomy does not reduce the risk of urinary tract injury.

The Genetics of Non-Syndromic Primary Ovarian Insufficiency: A Systematic Review.

Several causes for primary ovarian insufficiency (POI) have been described, including iatrogenic and environmental factor, viral infections, chronic disease as well as genetic alterations. The aim of this review was to collect all the genetic mutations associated with non-syndromic POI. All studies, including gene screening, genome-wide study and assessing genetic mutations associated with POI, were included and analyzed in this systematic review. Syndromic POI and chromosomal abnormalities were not evaluated. Single gene perturbations, including genes on the X chromosome (such as BMP15, PGRMC1 and FMR1) and genes on autosomal chromosomes (such as GDF9, FIGLA, NOBOX, ESR1, FSHR and NANOS3) have a positive correlation with non-syndromic POI. Future strategies include linkage analysis of families with multiple affected members, array comparative genomic hybridization (CGH) for analysis of copy number variations, next generation sequencing technology and genome-wide data analysis. This review showed variability of the genetic factors associated with POI. These findings may help future genetic screening studies on large cohort of women.