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Background: Intrauterine fetal death and perinatal death represent one of the most relevant medical scientific problems since, in many cases, even after extensive investigation, the causes remain unknown. The considerable increase in medical legal litigation in the obstetrical field that has witnessed in recent years, especially in cases of stillborn births, has simultaneously involved the figure of the forensic pathologist in scientific research aimed at clarifying the pathophysiological processes underlying stillbirth. Methods: our study aims to analyze cases of sudden intrauterine unexplained death syndrome (SIUD) to evaluate the role of oxidative stress in the complex pathogenetic process of stillbirth. In particular, the immunohistochemical expression of specific oxidative stress markers (NOX2, NT, iNOS, 8-HODG, IL-6) was evaluated in tissue samples of placentas of SIUDs belonging to the extensive case series (20 cases), collected from autopsy cases of the University of Ferrara and Politecnica delle Marche between 2017 and 2023. Results: The study demonstrated the involvement of oxidative stress in intrauterine fetal deaths in the placenta of the cases examined. In SIUD, the most expressed oxidative stress markers were NOX2 and 8-HODG. Conclusions: The study contributes to investigating the role of oxidative stress in modulating different pathways in unexplained intrauterine fetal death (SIUD) tissues.

AbstractObjective The objective of this study was to evaluate the attitude of obstetricians/gynecologists toward indicating an elective cesarean delivery in pregnant patients with a previous myomectomy.Materials and Methods Web-based multiple-choice questions survey evaluating the attitude to indicate a cesarean with a composite summated score (range 56–280) from a 56-item Likert scale: score 56–112: weak attitude, 113–168: moderate, 169–224: strong, and 225–280: very strong. The reliability of the score (internal consistency) was evaluated with Cronbach’s alpha coefficient. The association between the score and participants’ characteristics was determined with a bivariate analysis followed by linear regression analysis. The “global importance” of each risk factor was defined as the prevalence of the answers: “moderately important”, “very important”, and “extremely important” on the Likert scale. Factors with a “global importance” >75% were considered “crucial” in influencing the choice to indicate a cesarean.Results One-hundred-twenty obstetricians/gynecologists responded (response rate 70.6%). The mean ± SD composite summated score was 137 ± 31; 30 (25.0%) participants presented a "weak attitude to cesarean", 68 (56.7%) a "moderate attitude", 22 (18.3%) a "strong attitude", and none a "very strong attitude". The Cronbach’s alpha was 0.934 (high internal consistency). A self-reported number of myomectomies performed per year >50 was associated with a lower score (-25 points, 95% CI −50 to −1, p = 0.04). Eight criteria resulted “crucial” in indicating a cesarean: opening of the endometrial cavity, monopolar electrosurgery, time surgery-pregnancy

The 2022 Delphi revision of the MUSA (Morphological Uterus Sonographic Assessment) criteria for the ultrasound diagnosis of adenomyosis divides the ultrasound signs for diagnosis into direct and indirect ones, considering the presence of at least one direct sign as a mandatory criterion. This study aimed to reclassify the patients referred to the Pelvic Pain specialist outpatient clinic of the Gynecological Clinic of Udine according to the new criteria, evaluating the number of overdiagnoses and the possible correlation between the direct and indirect signs and the patients’ symptoms. 62 patients affected by adenomyosis were retrospectively recruited. The patients were then re-evaluated by ultrasound and clinically. At least one direct sign of adenomyosis was found in 52 patients, while 16% of the population examined did not present any. There was no statistically significant difference between patients presenting direct signs and those presenting none for the symptoms considered. According to the new criteria, 16% of the patients examined were not affected by adenomyosis; applying the new consensus to symptomatic patients could increase false negatives. In a population of symptomatic patients, the diagnosis of adenomyosis is still highly probable even without direct ultrasound signs, given the clinical symptoms and having ruled out other causes of such symptoms.

Soft markers are sonographic structural, nonspecific signs with little pathological significance, often transient, usually considered as normal variants. However, they may also be associated with chromosomal abnormalities. The most widely examined soft markers include absent or hypoplastic nasal bone (NB), intracardiac echogenic focus (IEF), ventriculomegaly (VM), thickened nuchal fold (NF), choroid plexus cyst (CPC), echogenic bowel, short long bones, and urinary tract dilation (UTD). Although the use of noninvasive prenatal testing (NIPT) has been spreading quickly in maternal–fetal medicine, it is not a diagnostic test and it still remains unavailable or cost-prohibitive for most of the population in many countries. After normal screening test results in the first trimester, there is no uniform consensus regarding the clinical significance of isolated soft markers for aneuploidy. Nowadays, the search for soft markers in an ultrasound is still part of clinical evaluation, and the interpretation of these findings is often a matter of debate. In the present review, we summarize the recent literature about the role of soft markers in the era of NIPT and propose an overview of the different clinical guidelines.

Infectious diseases during pregnancy are still a major cause of fetal mortality and morbidity worldwide. The most common teratogenic pathogens are cytomegalovirus (CMV), varicella-zoster virus (VZV), rubeovirus, parvovirus B19, herpes simplex virus (HSV), Toxoplasma gondii, Treponema pallidum and the emergent Zika virus (ZIKV). Ultrasound findings include cerebral anomalies, orbital defects, micrognathia, cardiac defects, hepatosplenomegaly, liver calcifications, abdominal anomalies, skin and limb anomalies, edema, placental and amniotic fluid anomalies and altered Doppler analyses. The classification of ultrasound markers of congenital infections by anatomical region is reported to guide differential diagnosis and prenatal care.

Intrauterine transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) is still matter of debate among scientists and there is limited information concerning this aspect of research. This could lead to severe complications of the growing fetus and, theoretically, of the newborn as well. We report the case of a male infant of 1,100 grams, born at 27th week of gestation to a SARS-CoV-2 mother, tested negative for viral detection at delivery. He was immediately admitted to neonatal Intensive Care Unit (ICU) for severe complications, where he died after 37 days by pulmonary embolism and thrombosis of the superior vena cava. After autopsy, SARS-CoV-2 N-protein and Spike RBD were detected in several tissues, particularly in the esophagus, stomach, spleen, and heart, with a significantly higher H-Score than the placenta. In conclusion, immunohistochemical analysis demonstrated SARS-CoV-2 NP and Spike RBD positivity in different tissues suggesting a possible intrauterine transmission. Newborn thrombo-embolism could be a complication of SARS-CoV-2 infection as observed in adult patients.

Abstract Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic-ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate-to-severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third-level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic-ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life.

Abstract Miscarriage is the spontaneous termination of a pregnancy before 24 weeks of gestation. We studied the genome of euploid miscarried embryos from mothers in the range of healthy adult individuals to understand genetic susceptibility to miscarriage not caused by chromosomal aneuploidies. We developed gp , a pipeline that we used to prioritize 439 unique variants in 399 genes, including genes known to be associated with miscarriages. Among the prioritized genes we found STAG2 coding for the cohesin complex subunit, for which inactivation in mouse is lethal, and TLE4 a target of Notch and Wnt, physically interacting with a region on chromosome 9 associated to miscarriages.

Abstract Laparoscopic rectosigmoid resection for endometriosis is usually performed with the section of the inferior mesenteric artery (IMA) distal to the left colic artery (low-tie ligation). This study was to determine outcomes in IMA-sparing surgery in endometriosis cases. A single-center retrospective study based on the analysis of clinical notes of women who underwent laparoscopic rectosigmoid segmental resection and IMA-sparing surgery for deep infiltrating endometriosis with bowel involvement between March the 1st, 2018 and February the 29th, 2020 in a referral hospital. During the study period, 1497 patients had major gynecological surgery in our referral center, of whom 253 (17%) for endometriosis. Of the 100 patients (39%) who had bowel endometriosis, 56 underwent laparoscopic nerve-sparing rectosigmoid segmental resection and IMA-sparing surgery was performed in 53 cases (95%). Short-term complications occurred in 4 cases (7%) without any case of anastomotic leak. Preservation of the IMA in colorectal surgery for endometriosis is feasible, safe and enables a tension-free anastomosis without an increase of postoperative complication rates.

Background: Assessing outcomes of birth in induced patients (full-term and premature) in relation with symphysis-fundal height (SFH) measurement. Methods: A prospective enrollment of induced patients was performed at the Obstetrics and Gynecology Unit of Arcispedale Sant’Anna of Ferrara. Reasons for induction, Bishop’s score, body mass index, gestational age, parity, mode of induction, number of induction cycles, time of active labor phase, Cesarean section, operative vaginal birth, post-partum hemorrhage, arterial cord pH, neonatal intensive care admission, size at birth were recorded. Correspondence analysis was applied to analyze independent relationships. These relationships were converted into probabilities. Probabilities for outcomes variables were plotted along with values of SFH and trends were tested. Results: Significant trends of increasing probability of adverse birth and labor outcomes were observed for SFH from 34 cm or less to over 37 cm: two cycles of induction (best fit p = 0.002); three cycles of induction (best fit p = 0.002); Cesarean section (best fit p = 0.027); higher length of active phase of labor (best fit p = 0.002); operative vaginal birth (best fit p = 0.002); arterial blood pH below or equal to 7.15 (best fit p = 0.006); post-partum minor hemorrhage (best fit p = 0.002), post-partum major hemorrhage (best fit p = 0.006). Conclusion: In induced pregnancies, SFH over 34 cm increased the probability of both neonatal and labor adverse outcomes, independently of gestational age.

Coronavirus disease (COVID-19) has emerged as a very serious pandemic caused by the rapidly evolving transmission of the coronavirus SARS-CoV-2. Since its outbreak in 2020, the SARS CoV-2 has represented an important challenge for the physicians due to its well known respiratory sequelae. To date, the role of SARS-CoV-2 infection on organs and systems other than lungs and respiratory tract remains less clear. In particular, it remains to be investigated whether the reproductive system can be affected by the SARS-CoV-2 in the long term-period or, in alternative, drugs used to treat COVID-19 might impact the reproductive systems and, in turn, fertility. What is known is that SARS-Cov-2 binds to target cells of host through different receptors including angiotensin-converting enzyme 2 (ACE2), neuropilin-1, AXL and antibody-FcɣR complexes. ACE2 physiologically regulates both the expression of angiotensin II (Ang II) as well as Ang-(1-7) to exerts its physiological functions. The reproductive system abundantly expresses ACE2 and produces Ang-(1-7), starting from precursors which are locally generated or derived from systemic circulation. Ang-(1-7) plays an important role of stimulus to the growth and maturation of ovarian follicle as well as to ovulation. Also human endometrium expresses Ang-(1-7), mainly during the post-ovulatory phase. Animal and human observational studies demonstrated that Ang-(1-7) is involved in the maternal immune response to pregnancy and its deficiency is associated with a defective placenta development. In our manuscript, we review the current knowledge about whether SARS-CoV-2 may impact the female reproductive system. We further explain the possible molecular mechanism by which SARS-CoV-2 might affect ovarian, endometrial and female genital tract cells.

In the last few years, there have been significant evolutions in the understanding of the hormone melatonin in terms of its physiology, regulatory role, and potential utility in various domains of clinical medicine. Melatonin’s properties include, among others, the regulation of mitochondrial function, anti-inflammatory, anti-oxidative and neuro-protective effects, sleep promotion and immune enhancement. As it is also bioavailable and has little or no toxicity, it has been proposed as safe and effective for the treatment of numerous diseases and to preserve human health. In this manuscript, we tried to evaluate the role of melatonin at the beginning of human life, in pregnancy, in the fetus and in newborns through newly published literature studies.

This systematic review aims to evaluate the effectiveness of pharmacological and non-pharmacological strategies for pain relief in women during contrast-enhanced ultrasound for the assessment of tubal patency and uterine disease, compared with placebo or no intervention. In December 2021, we searched the electronic databases (Pubmed, Embase, Sciencedirect, the Cochrane library and Clinicaltrials.gov) without date restriction: We identified 10 randomized control trials (RCTs) (2098 women) eligible for this systematic review, after applying our inclusion and exclusion criteria. Among these, five studies compared the use of painkillers with the placebo, two studies compared different catheter positions in the cervix or in the uterine cavity, and two others considered different temperatures of the contrast medium, as a method to reduce pain. Topical lidocaine applied before the procedure may be associated with effective pain relief during hysterosonography, though the quality of this evidence is low. New echogenic contrast agents and their temperature at 37 °C ensure a less painful procedure. There is insufficient evidence to draw conclusions on the efficacy of other analgesics or strategies.

Objective: To review the literature on the impact on female quality of life and sexual function of orthotopic reconstruction after radical cystectomy for non-malignant bladder conditions. Radical cystectomy is commonly required to treat malignant conditions but may also be considered for the treatment of non-malignant diseases. These heterogeneous group of disorders includes interstitial cystitis, painful bladder syndrome, neurogenic bladder, haemorrhagic/ radiation cystitis, endometriosis and refractory genitourinary fistula. Treatment begins with non-invasive medical therapies but, in non-responder cases, a surgical solution should be considered. Such invasive techniques include urinary diversion and reconstructive procedures that have an impact on healthrelated quality of life, physical, social, and mental status. Materials and methods: This narrative review research was done using the PubMed database up until 2020, July. All papers referring to cystectomy for benign indication were considered. Results: In comparison to other reconstructive options, orthotopic neobladder allows the restoration of a normal self-image and consequently it is the most suitable procedure when a surgical reconstruction is necessary for non-malignant conditions. However, women can face many disorders that impact on everyday life, such as voiding dysfunction or sexual activity problems. Conclusions: Scant data is available about quality of life, sexual life and self-perception in women treated by cystectomy for benign conditions and most literature is dedicated to those indicators in cancer patients. More research is needed to understand the tolerability and the quality of life results of the female population affected by benign conditions undergoing this kind of surgical approach.

Abstract Objective The aim of the present study was to perform a comprehensive review of the literature to provide a complete and clear picture of isthmocele-a hypoechoic area within themyometriumat the site of the uterine scar of a previous cesarean section-by exploring in depth every aspect of this condition. Methods A comprehensive review of the literature was performed to identify the most relevant studies about this topic. Results Every aspect of isthmocele has been studied and described: pathophysiology, clinical symptoms, classification, and diagnosis. Its treatment, both medical and surgical, has also been reported according to the actual literature data. Conclusion Cesarean section is the most common surgical procedure performed worldwide, and one of the consequences of this technique is isthmocele. A single and systematic classification of isthmocele is needed to improve its diagnosis and management. Further studies should be performed to better understand its pathogenesis.

High-risk human papillomaviruses (hrHPVs) are causally related to cervical intraepithelial neoplasia (CIN) and subsequent cervical cancer (CC). The vaginal microbiome has been suggested to play a role in the development of CC, but the effect of conservative surgical treatment on the microbiome and hrHPV elimination has not been elucidated. In this study, we aimed to characterize the vaginal microbiome and inflammatory chemokine profile in 85 women treated for CIN2-CIN3 lesions, before and after surgical CIN removal. The results showed, as expected, a high prevalence of dysbiotic microbiomes and vaginal pro-inflammatory cytokines in the CIN cohort, correlated with disease severity, at the basal level. By contrast, surgical CIN removal induced significant vaginal microbiome variations, and specific microbiome/cytokine profiles were associated with hrHPV clearance/persistence at 6-month follow-up. hrHPV-cleared patients, in fact, showed a specific increase of L. crispatus and decrease of dysbiosis and inflammatory cytokines compared to hrHPV-persistent patients. These data highlight the crosstalk between HPV and the local microbiome, and suggest that vaginal microbiome modulation might represent a novel approach to modifying the natural history of hrHPV-related CC.Study registration n. ISRCTN34437150 (https://www.isrctn.com/ISRCTN34437150).

Background: Oxidative stress (OxS) has been linked to several pregnancy-related complications. Previous studies demonstrated that lactoferrin (LF) has the ability to modulate inflammation, OxS and the immune function. Therefore, we aimed to observe whether vaginal LF administration was able to decrease OxS in the amniotic fluid (AF) of pregnant women undergoing mid-trimester genetic amniocentesis.Methods: In this open-label clinical study, 60 pregnant women were divided into three groups: CONTROLS (n = 20), not treated with LF; LACTO 4HRS (n = 20), treated with LF 4 h prior to amniocentesis; LACTO 12HRS (n = 20), treated with LF 12 h prior to amniocentesis. Thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS) and oxidative stress index (OSI) were measured in AF samples. In addition, the in vitro antioxidant activity of LF on a cell line was tested.Results: LF decreased the concentration of TBARS in the AF, with LACTO 4HRS demonstrating the lowest value compared with CONTROLS (P < 0.0001). LACTO 4HRS had higher TAS and lower OSI than CONTROLS (P < 0.0001 for both). In vitro, LF was effective against the oxidative challenge regardless of the time of pretreatment.Conclusion: In conclusion, LF decreased both in vivo and in vitro OxS. LF administration may represent an intriguing clinical solution as an adjuvant to treat complications of pregnancy related to inflammation and OxS.Trial Registration:Clinicaltrials.gov, NCT02695563. Registered 01 March 2016—Retrospectively registered, https://clinicaltrials.gov/show/NCT02695563.

Background: Endometrial hyperplasia (EH) is considered a heterogeneous pre-neoplastic clinical entity characterized by an abnormal glandular proliferation, with less than half of the tissue area occupied by the stroma. The aim of this retrospective study was to evaluate the correlation between the histological diagnosis of atypical endometrial hyperplasia (AEH) obtained through office hysteroscopy (OH) or uterine dilation and curettage (D&C) and the definitive histological evaluation after hysterectomy. Methods: Among 112 patients with atypical EH, 45 (40%) underwent hysteroscopy and 67 (60%) curettage. Results: The diagnostic accuracy of OH was very high: in particular, it showed a diagnostic coincidence in 87% of cases with the definitive histological diagnosis through hysteroscopy. The curettage, instead, had diagnostic coincidence only in 14% of cases. Conclusion: Office hysteroscopy is the ideal procedure for both diagnosis and follow-up of endometrial hyperplasia.

Abstract Noncompaction cardiomyopathy (NCCM) and left ventricular noncompaction (LVNC), in their isolated form, are rare cardiomyopathies. They are characterized by a thickened myocardium due to the presence of deep trabeculae recesses, and to thick trabeculae. This condition is associated with a variable clinical phenotype including heart failure, thromboembolism, and sudden death. We report a case of LVNC at 26 weeks and 4 days of gestation revised on the basis of what is currently reported in the literature. A review of the literature was performed to better describe this rare condition. Left ventricular noncompaction is a rare fetal condition and it should be suspected in case of cardiomyopathy.

Abstract Transverse vaginal septum is a rare female genital tract anomaly, and little is described about its surgical treatment. We report the case of a patient who wished to preserve hymenal integrity due to social and cultural beliefs. We performed a vaginoscopic resection of the septum under laparoscopic view, followed by the introduction of a Foley catheter in the vagina, thus preserving the hymen. After 12 months of follow-up, no septal closure was present, and the menstrual flow was effective. Vaginoscopic hysteroscopy is an effectivemethod of vaginal septum resection, even in cases in which hymenal integrity must be preserved due to social and cultural beliefs.

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.

This DIB article provides additional data on laparoscopic lateral suspension with mesh for correcting pelvic organ prolapse. Data come from a multicentric sample of Italian women (https://doi.org/10.1016/j.ejogrb.2019.07.025). Data are collected retrospectively. Descriptive and raw data on surgery and descriptive and raw data on symptoms of pelvic organ prolapse pre-surgery and post-surgery are provided. Kaplan-Meier curves and scores of 7-items King's Health Questionnaire for quality of life assessment are also reported. Keywords: Pelvic organ prolapse, Laparoscopic lateral suspension, Surgical treatment, Mesh

AimWomen with adenomyosis are at higher risk of endometriosis recurrence after surgery. This study was to assess if the lymphatic vessel network drained from the uterus to near organs where endometriosis foci lied.MethodsA prospective, observational study, Canadian Task Force Classification II-2, was conducted at Sacro Cuore Don Calabria Hospital, Negrar, Italy. 104 white women aged 18-43 years were enrolled consecutively for this study. All patients underwent laparoscopy for endometriosis and a tubal dye test was carried out.ResultsEvidence of dye dissemination through the uterine wall and outside the uterus was noted in 27 patients (26%) with adenomyosis as it permeated the uterine wall and a clear passage of the dye was shown in the pelvic lymphatic vessels regardless whether the tubes were unobstructed. Histological assessment of the uterine biopsies confirmed adenomyosis.ConclusionAdenomyosis is characterized by ectatic lymphatics that allow the drainage of intrauterine fluids (the dye and, perhaps, menstrual blood) at minimal intrauterine pressure from the uterine cavity though the lymphatic network to extrauterine organs. Certainly, this may not be the only explanation for endometriosis dissemination but the correlation between the routes of the dye drainage and location of endometriosis foci is highly suggestive.

ABSTRACT Objective: Analyzing if the sonographic evaluation of the cervix (cervical shortening) is a prognostic marker for vaginal delivery. Methods: Women who underwent labor induction by using dinoprostone were enrolled. Before the induction and three hours after it, the cervical length was measured by ultrasonography to obtain the cervical shortening. The cervical shortening was introduced in logistic regression models among independent variables and for calculating receiver operating characteristic (ROC) curves. Results: Each centimeter in the cervical shortening increases the odds of vaginal delivery in 24.4% within 6 hours; in 16.1% within 24 hours; and in 10.5% within 48 hours. The best predictions for vaginal delivery are achieved for births within 6 and 24 hours, while the cervical shortening poorly predicts vaginal delivery within 48 hours. Conclusion: The greater the cervical shortening 3 hours after labor induction, the higher the likelihood of vaginal delivery within 6, 24 and 48 hours.

Objectives. To deepen the knowledge in obstetrics on a very rare pregnancy complication: umbilical cord hematoma. Methods. A review of the case reports described in the last ten years in the literature was conducted in order to evaluate epidemiology, predisposing factors, potential outcomes, prenatal diagnosis, and clinical management. Results. Spontaneous umbilical cord hematoma is a rare complication of pregnancy which represents a serious cause of fetal morbidity and mortality. There are many risk factors such as morphologic anomalies, infections, vessel wall abnormalities, iatrogenic causes, and traction or torsion of the cord, but the exact etiology is still unknown. Conclusions. Due to the rarity of this condition, every new case of umbilical cord hematoma should be reported in order to improve the knowledge of predisposing factors, prenatal diagnosis, and clinical management.

BACKGROUND: Cesarean section on maternal request (CSMR) could represent an avoidable quota of cesareans. In Italy, this is a topical problem of health-policy, involving ethical, juridical and medical issues. AIM AND METHODS: A 5-questions questionnaire to quantitatively assess the perspectives of medical, juridical and ethical issues of planned CSMR was administered to obstetricians and gynecologists, midwives, lawyers and pregnant women. It was assessed to what extent those issues matter on the final decision of planning a CSMR. RESULTS: Non-homogeneous answers of stakeholders suggest different perspectives about issues on CSMR. The juridical issue seems to have the greatest impact on the final decision. CONCLUSION: Planning a CSMR associates overall with juridical issues in each group of respondents. Therefore, an obstetrician and gynecologist is unable to counsel a patient on CSMR from a medical point of view. The most direct way for reducing cesareans in Italy could be the formal prohibition of CSMR.

Simian virus 40 (SV40) large T antigen (LT) coding sequences were revealed in different human samples, whereas SV40 antibodies (Ab) were detected in human sera of cancer patients and healthy individuals, although with a lower prevalence. Previous studies carried out by the neutralization assay gave a SV40 seroprevalence, in the general population, up to 8%, although higher rates, 12%, were detected in kidney transplant children, in a group of HIV-positive patients, and in healthy females. In this study, serum samples from pregnant women, together with those from non-pregnant women, were analyzed to check the prevalence of IgG Ab reacting to SV40 LT antigens. Serum samples were collected from pregnant and non-pregnant women, with the same mean age. Women were in the range of 15–48 years old. Samples were assayed by an indirect ELISA employing specific SV40 LT mimotopes as antigens, whereas functional analysis was performed by neutralization of the viral infectivity in cell cultures. As a control, sera were analyzed for Ab against BK polyomavirus (BKPyV), which is a human polyomavirus homologous to SV40. Statistical analyses employed chi-square with Yates’ correction, and Student’s t tests. Indirect ELISAs indicated that pregnant women tested SV40 LT-positive with a prevalence of 17% (23/134), whereas non-pregnant women had a prevalence of 20% (36/180) (P > 0.05). Ab against BKPyV were detected with a prevalence of 80% in pregnant women and with a prevalence of 78% in non-pregnant women. These data indicate that SV40 infects at a low prevalence pregnant women. We may speculate that SV40, or a close human polyomavirus still undetected, could be transmitted from mother to fetus.

BACKGROUND AND OBJECTIVE:Preeclampsia is a systemic disorder, affecting 2-10% of pregnancies, characterized by a deregulated pro- and anti-angiogenic balance. Semaphorin 3F is an angiogenesis inhibitor. We aimed to investigate whether semaphorin 3F expression is modulated in preeclampsia. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS:We performed two observational single center cohort studies between March 2013 and August 2014. In the first we enrolled 110 consecutive women, undergoing an elective cesarean section; in the second we included 150 consecutive women undergoing amniocentesis for routine clinical indications at 16-18 week of gestation. Semaphorin 3F concentration was evaluated in maternal peripheral blood, venous umbilical blood and amniotic fluid, along with its placenta protein expression at the time of delivery in the first study group and in the amniotic fluid at 16-18 weeks of gestation in the second study group. RESULTS:In the first study 19 patients presented at delivery with preeclampsia. Semaphorin 3F placenta tissue expression was significantly reduced in preeclampsia. In addition, semaphorin 3F level at delivery was significantly lower in serum, amniotic fluid and venous umbilical blood of preeclamptic patients compared with normal pregnant women. In the prospective cohort study 14 women developed preeclampsia. In this setting, semaphorin 3F amniotic level at 16-18 weeks of gestation was reduced in women who subsequently developed preeclampsia compared to women with a normal pregnancy. ROC curve analysis showed that semaphorin 3F amniotic levels could identify women at higher risk of preeclampsia. CONCLUSIONS:Semaphorin 3F might represent a predictive biomarker of preeclampsia.

Objective. Tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) is attracting attention for its role in the physiopathology of metabolic disease/diabetes. Evidence suggests that it might protect against metabolic abnormalities driven by obesity-induced dysregulated secretion of adipokines, but this role of TRAIL has not yet been fully established. On this basis, we aimed to investigate the potential association between TRAIL and adipokine levels in a cohort of subjects in which age/gender/hormonal interferences were excluded. Methods. Serum levels of TRAIL and a panel of adipokines were measured in postmenopausal women (n=147) stratified according to waist circumference measures as normal, overweight, or obese. The panel of adipokines included interleukin- (IL-) 6, IL-8, IL-1β, adipsin, lipocalin-2/neutrophil gelatinase-associated lipocalin (ngal), TNF-alpha, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, hepatocyte growth factor, resistin, leptin, adiponectin, and nerve growth factor. Results. Low serum TRAIL concentration (deciles I–IV) was significantly and inversely correlated with resistin and lipocalin 2/ngal levels (r=−0.502 and p

Background. Experimental evidence suggests a relationship between the vasodilatory effect of hCG and the NOS system in the testis. The influence of hCG administration on testicular vascular NOS gene expression has not been fully investigated. Objective: This study aimed to evaluate the presence of the nitric oxide syntheses gene in ram testicular arteries and the influence of hCG administration on its expression. Materials and methods: Both testicular arteries of sixteen rams were extracted before and after i.v. administration of 5000 IU of hCG or placebo. The expression of the iNOS gene was investigated by real time PCR. Data were analyzed by means of Wilcoxon and Mann-Whitney tests. A p value of < 0.05 was considered statistically significant. Results: PCR revealed the presence of iNOS mRNA in all basal samples but the expression of the iNOS gene was significantly reduced in all arteries obtained 24 h after the administration of either hCG or placebo. A significant reduction in the expression of iNOS gene was observed in the testicular arteries extracted after 24 h in both treated and placebo groups. On the other hand hCG stimulation did not significantly influence iNOS expression following its administration compared to a placebo. Conclusion: Ram testicular arteries express the iNOS gene but hCG stimulation did not significantly influence iNOS expression. A significant reduction in the expression of this gene was observed in the testicular arteries extracted after 24 h in both treated and placebo groups, suggesting that iNOS expression on the testicular artery could be influenced by the spermatic vessel ligation of the controlateral testis.

PURPOSE: To assess if arylsulfatase A activity (ASA) and sulfatide (SL) concentration in the human endometrium can be predictive of the development of endometrial polyps over the years, since ASA activity reflects the endometrial sensitivity to hormones. METHODS: ASA activity and SL concentration were determined by biochemical procedures on endometrial samples collected between 1990 and 1994 in non-menopausal women. These women underwent a new endometrial sampling following the clinical indication some years after the first endometrial sampling. The histological assessment of the second endometrial specimens found four patients with normal endometrial pattern and 10 patients with one or more endometrial polyps. ASA activity/years elapsed and SL concentration/years elapsed were compared using two tailed Mann-Whitney test for unpaired data between patients with normal pattern and patients with endometrial polyps. RESULTS: Median ASA activities were 2.62 (normal pattern) versus 1.85 (endometrial polyps) nmol hydrolized substrate/min. Median activity/years elapsed is higher in patients with second endometrial sample presenting normal pattern (p=0.006) and median SL concentration/years elapsed does not differ significantly among groups, even if median SL concentration seems to be higher in patients who subsequently developed polyps (1031 µg/g of fresh tissue versus 341,5 µg/g of fresh tissue). CONCLUSIONS: ASA activity can predict the onset of endometrial polyps over the years.OBJETIVO: Avaliar se a atividade da arilsulfatase A (ASA) e a concentração de sulfatida (SL) no endométrio humano pode ser preditivo em relação ao desenvolvimento de pólipos endometriais ao longo dos anos, posto que atividade da ASA reflete a sensibilidade do endométrio aos hormônios. MÉTODOS: A atividade da ASA, assim como a concentração de SL, foi determinada por meio de procedimentos bioquímicos em amostras de endométrio coletadas entre 1990 e 1994, em mulheres que não se encontravam na menopausa. Essas mulheres foram submetidas a uma nova amostragem endometrial após indicação clínica alguns anos depois da primeira amostragem endometrial. A avaliação histológica dos segundos espécimes endometriais permitiu identificar quatro pacientes com padrão endometrial normal e 10 com um ou mais pólipos endometriais. A atividade da ASA/anos depois e a concentração de SL/anos depois foram comparadas, utilizando o teste bilateral U de Mann-Whitney para dados não pareados entre as pacientes com padrão normal e as pacientes com pólipos endometriais. RESULTADOS: A ativitade da ASA foi 2,62 (padrão normal) em comparação com 1,85 (endometrial pólipos) de substrato hidrolisado/min. A atividade da ASA/anos depois é maior em pacientes com segunda amostra endometrial a apresentarem um padrão normal (p=0,006), e a concentração mediana de SL/anos depois não difere de forma significativa entre os grupos, apesar de a concentração mediana de SL parecer maior em pacientes que posteriormente desenvolveram pólipos (1031 µg/g de tecido fresco em comparação com 341,5 µg/g de tecido fresco). CONCLUSÕES: A atividade da ASA pode prever a aparição de pólipos endometriais ao longo dos anos.

Objective: Ovarian senescence affects many tissues and produces a variety of symptoms and signs. We hypothesized that estrogens may also influence circulating redox balance by regulating activity of the cellular antioxidative enzyme system. We aimed to explore the impact of surgical estrogen deprivation and replacement (ERT) on the glutathione balance and antioxidant enzymes expression in fertile women. Study design: Nineteen healthy premenopausal women who underwent total hysterectomy with bilateral salpingo-oophorectomy were evaluated at baseline, 30 days after surgery without ERT and 30 days after ERT. Redox balance was determined by measuring blood reduced (GSH) and oxidized (GSSG) glutathione, as well as the GSSG/GSH ratio. Antioxidant status was evaluated by measuring serum estrogen (E2) levels and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) in peripheral blood mononuclear cells. Results: Serum E2 significantly lowered after surgery, and increased in 12 out of 19 patients after 30 days of ERT (Responders). In such patients, an increase in oxidative stress was observed after surgery that resolved after ERT. Oxidative stress was sustained by reduction in the mRNA expression of both SOD and GSH-Px, that recovered after 30 days of therapy in responders. CAT and GST mRNA expression were not modified by surgery and replacement therapy. Conclusions: Menopause is associated with significant change in antioxidant gene expression that in turn affects circulating redox state. Estrogens replacement therapy is able to prevent and counteract such modifications by acting as regulators of key antioxidant gene expression. These findings suggest that antioxidant genes are, almost in part, under the control of sex hormones, and that pathophysiology of the difference in gender disease may depend on the redox biology.

Inflammation plays an important role in pregnancy, and cytokine and matrix metalloproteases (MMPs) imbalance has been associated with premature rupture of membranes and increased risk of preterm delivery. Previous studies have demonstrated that lactoferrin (LF), an iron-binding protein with anti-inflammatory properties, is able to decrease amniotic fluid (AF) levels of IL-6. Therefore, we aimed to evaluate the effect of vaginal LF administration on amniotic fluid PGE2 level and MMP-TIMP system in women undergoing genetic amniocentesis. One hundred and eleven women were randomly divided into controls (n=57) or treated with LF 4 hours before amniocentesis (n=54). Amniotic fluid PGE2, active MMP-9 and MMP-2, and TIMP-1 and TIMP-2 concentrations were determined by commercially available assays and the values were normalized by AF creatinine concentration. PGE2, active MMP-9, and its inhibitor TIMP-1 were lower in LF-treated group than in controls (p

Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women.