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OBJECTIVES: Preterm birth (PTB) is a major public health problem worldwide. It can occur spontaneously or be medically indicated for obstetric complications, such as pre-eclampsia (PE) or fetal growth restriction. The main objective of this study was to investigate whether there is a shared uteroplacental etiology in the first trimester of pregnancy across PTB subtypes. METHODS: This was a retrospective cohort study of singleton pregnancies that underwent screening for preterm PE as part of their routine first-trimester ultrasound assessment at a tertiary center in London, UK, between March 2018 and December 2020. Screening for preterm PE was performed using the Fetal Medicine Foundation algorithm, which includes maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and pregnancy-associated plasma protein-A (PAPP-A). Women with a risk of ≥ 1 in 50 for preterm PE were classified as high risk and offered prophylactic aspirin (150 mg once a day) and serial ultrasound assessments. The following delivery outcomes were evaluated: PTB

Objective\ud The use of twin-specific vs singleton growth charts in the assessment of twin pregnancy has been controversial. The aim of this study was to assess whether a diagnosis of small-for-gestational age (SGA) made using twin-specific estimated-fetal-weight (EFW) and birth-weight (BW) charts is associated more strongly with adverse neonatal outcomes in twin pregnancies, compared with when the diagnosis is made using singleton charts.\ud \ud Methods\ud This was a cohort study of twin pregnancies delivered at St George's Hospital, London, between January 2007 and May 2020. Twin pregnancies complicated by intrauterine death of one or both twins, fetal aneuploidy or major abnormality, twin–twin transfusion syndrome or twin anemia–polycythemia sequence and those delivered before 32 weeks' gestation, were excluded. SGA was defined as EFW or BW below the 10th centile, and was assessed using both twin-specific and singleton EFW and BW charts. The main study outcome was composite adverse neonatal outcome. Mixed-effects logistic regression analysis with random pregnancy-level intercepts was used to test the association between SGA classified using the different charts and adverse neonatal outcome.\ud \ud Results\ud A total of 1329 twin pregnancies were identified, of which 913 (1826 infants) were included in the analysis. Of these pregnancies, 723 (79.2%) were dichorionic and 190 (20.8%) were monochorionic. Using the singleton charts, 33.3% and 35.7% of pregnancies were classified as SGA based on EFW and BW, respectively. The corresponding values were 5.9% and 5.6% when using the twin-specific charts. Classification as SGA based on EFW using the twin charts was associated significantly with composite adverse neonatal outcome (odds ratio (OR), 4.78 (95% CI, 1.47–14.7); P = 0.007), as compared with classification as appropriate-for-gestational age (AGA). However, classification as SGA based on EFW using the singleton standard was not associated significantly with composite adverse neonatal outcome (OR, 1.36 (95% CI, 0.63–2.88); P = 0.424). Classification as SGA based on EFW using twin-specific standards provided a significantly better model fit than did using the singleton standard (likelihood ratio test, P

OBJECTIVES: Women with hypertensive disorders of pregnancy (HDP) present with evidence of significant myocardial dysfunction on echocardiographic assessment at the time of diagnosis. Birth not only cures the syndrome of HDP, but is also associated with a reduction in cardiovascular (CV) volume and resistance load in the mother due to the delivery of the fetoplacental unit. The impact of this physiological change on maternal myocardial function in women with HDP has not been systematically evaluated. The aim of this study is to compare echocardiographic findings immediately before and after childbirth in women with HDP. METHODS: In this prospective longitudinal study, 30 women with a diagnosis of HDP underwent two consecutive transthoracic echocardiography (TTE) examinations: the first prepartum and the second in the early postpartum period. Paired comparisons of these assessments were performed. RESULTS: Left ventricular (LV) concentric remodelling or hypertrophy were found in 21 (70%) patients and there were no significant differences in cardiac morphology indices: LV mass index (78.9±16.3 g/m2 vs 77.9 ±15.4 g/m2 , p=0.611) and relative wall thickness (0.45±0.1 vs 0.44±0.1, p=0.453). LV diastolic function did not demonstrate any peripartum variation: left atrial volume (52.40±15.3 vs 50.97±15.6, p=0.433); lateral E' (0.12±0.03 vs 0.12±0.03, p=0.307) and E/E' ratio (7.88±2.19 vs 7.91±1.74, p=0.934). Systolic function indices such as LV ejection fraction (57.5±4.4% vs 56.4±2.1%, p=0.295) and global longitudinal strain (-15.3±2.6% vs -15.1±3.1%, p=0.715) also remained unchanged. CONCLUSIONS: Maternal hemodynamic changes associated with birth did not significantly influence peripartum TTE indices in women with HDP. Suboptimal maternal echocardiographic findings in HDP are likely to be the consequence of chronic pregnancy CV load changes or pre-existing maternal CV impairment. Severity and persistence of myocardial dysfunction into the postpartum period may be related to the long-term maternal CV disease legacy of HDP. This article is protected by copyright. All rights reserved.

BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are at increased long-term risk of cardiovascular disease. However, there has been increasing evidence on the same risks in the months following birth. OBJECTIVES: This review aims to estimate the incidence of hypertension in the first 2 years after HDP. SEARCH STRATEGY: MEDLINE, Embase and Cochrane databases were systematically searched in October 2019. SELECTION CRITERIA: Observational studies comparing hypertension rate following HDP and normotensive pregnancies up to 2 years. DATA COLLECTION AND ANALYSIS: A meta-analysis to calculate the odds ratio (OR) with a 95% confidence interval (CI) and a sub-group analysis excluding women with chronic hypertension were performed. MAIN RESULTS: Hypertension was diagnosed within the first 2 years following pregnancy in 468/1646 (28.4%) and 584/6395 (9.1%) of the HDP and control groups, respectively (OR 6.28; 95% CI 4.18-9.43; I2 = 56%). The risk of hypertension in HDP group was significantly higher in the first 6 months following delivery (OR 18.33; 95% CI 1.35-249.48; I2 = 84%) than at 6-12 months (OR 4.36; 95% CI 2.81-6.76; I2 = 56%) or between 1-2 years postpartum (OR 7.24; 95% CI 4.44-11.80; I2 = 9%). A sub-group analysis demonstrated a similar increase in the risk of developing postpartum hypertension after HDP (OR 5.75; 95% CI 3.92-8.44; I2 = 49%) and pre-eclampsia (OR 6.83; 95% CI 4.25-10.96; I2 = 53%). CONCLUSIONS: The augmented risk of hypertension after HDP is highest in the early postpartum period, suggesting that diagnosis and targeted interventions to improve maternal cardiovascular health may need to be commenced in the immediate postpartum period. TWEETABLE ABSTRACT: The risk of hypertension within 2 years of birth is six-fold higher in women who experienced pre-eclampsia.

Global longitudinal strain (GLS) is becoming routinely used to direct the medical management of various cardiac diseases, but its application in pregnancy is unclear. Our objective was to perform a meta-analysis and pool multiple study data to consolidate the evidence base for the role of GLS in the assessment of women with hypertensive disorders of pregnancy (HDP). Electronic database searches were performed in PubMed/Medline and EMBASE for research articles reporting GLS in pregnancies complicated by HDP and normotensive pregnancies that have been published up to September 2021. The meta-analysis included 17 studies with a pooled sample size of 1723 participants, which included 951 women with HDP, of which 680 were preeclamptic, and 772 controls. The primary random-effects pooled analysis demonstrated a statistically significant weighted mean difference in GLS between the HDP and control group (mean difference: 3.08% [CI, 2.33–3.82], P

Objective\ud The placental development has been shown to be compromised in pregnancies affected by fetal congenital heart defects (CHD). This study aimed to investigate the frequency of complications related to utero‐placental insufficiency in pregnancies with and without major CHD.\ud \ud Method\ud This retrospective case‐control study was conducted at a Fetal Echocardiography Center in Milan. The following outcomes were compared between the two groups: preeclampsia (PE), small for gestational age (SGA), placental disorders and preterm birth (PTB). The logistic regression analysis was adjusted for maternal age, parity, co‐morbidities and mode of conception.\ud \ud Results\ud The CHD group (n = 480) showed significantly increased incidence of PE (2.9% vs 0.9%; aOR, 6.50; 95% CI, 1.39‐30.41; P = .017) as compared to the control group (n = 456). Placental disorders occurred more frequently in the CHD than in controls, but the increased risk showed only a borderline significance (4.5% vs 3.3%; aOR, 2.56; 95% CI, 0.99‐1.02; P = .046). There was a significantly higher risk of SGA in CHD than in controls (8.7% vs 3.9%; aOR, 3.37; 95% CI, 1.51‐7.51; P = .003). PTB occurred in 65/477 (13.6%) cases and in 39/447 (8.7%) controls (P = .022) (aOR, 2.17; 95% CI, 1.24‐3.81; P = .007).\ud \ud Conclusion\ud Major CHD are significantly associated with the risk of PE, SGA and PTB.

Le malattie del trofoblasto di origine gestazionale (GTD) rappresentano una complicanza rara della gravidanza. Esse si dividono in forme benigne (mola idatiforme parziale e completa) e maligne (tumori del trofoblasto, GTN). Nonostante la prognosi favorevole che attualmente accompagna tale diagnosi, la natura stessa di queste malattie costituisce una considerevole fonte di stress per le pazienti che ne sono affette. Metodi. Trentuno pazienti affette da GTD hanno completato una batteria di questionari autosomministrati volti a valutare il ruolo dei meccanismi di difesa nell’influenzare l’adattamento psicologico alla malattia, in particolare la presenza di sintomi ansiosi e depressivi e lo stress legato all’infertilità. Risultati. Le pazienti affette da tumori del trofoblasto riportano un maggiore utilizzo di meccanismi di difesa maturi rispetto alle pazienti con mola idatiforme. Le analisi di regressione evidenziano che, al netto di variabili demografiche e mediche correlate alla patologia, i meccanismi di difesa immaturi mantengono una relazione specifica con l’ansia di stato e con lo stress legato all’infertilità riportato dalle pazienti. Conclusioni. I risultati suggeriscono l’importanza di considerare, nella progettazione di interventi clinici, gli specifici meccanismi di difesa messi in atto dalle pazienti, in quanto significativamente coinvolti nel modulare l’adattamento psicologico alle GTD Gestational Trophoblastic Disease (GTD) is a group of disorders that derive from the placenta and arise after a rare gestational event. They can be divided into pre-malignant forms (partial and complete hydatidiform mole) and malignant forms called Gestational Trophoblastic Neoplasia (GTN). Despite a favourable prognosis, the nature of this group of disorders can be a source of stress for patients who are affected by this disease. Methods. Thirty-one patients diagnosed with GTD completed a battery of self-administered questionnaires aimed at analysing the psychological adaptation of the patients to the disease. The variables analysed were the following: defense mechanisms, anxiety, depression and infertility-related stress. Results. Patients with GTN use mature defense mechanisms significantly more than patients with hydatidiform mole. Regression analyses highlight that, considering demographic and clinical variables, immature defense mechanisms are significantly related to state anxiety. Immature defence mechanisms also significantly predict infertility-related global stress. Conclusions. The results show the importance of taking into consideration defense mechanisms used by patients, as they are involved in the modulation of psychological adaptation to GTD.

Gestational Trophoblastic Disease (GTD) is a group of disorders that derive from the placenta and arise after a rare gestational event. They can be divided into pre-malignant forms (partial and complete hydatidiform mole) and malignant forms called Gestational Trophoblastic Neoplasia (GTN). Despite a favourable prognosis, the nature of this group of disorders can be a source of stress for patients who are affected by this disease. Methods. Thirty-one patients diagnosed with GTD completed a battery of self-administered questionnaires aimed at analysing the psychological adaptation of the patients to the disease. The variables analysed were the following: defense mechanisms, anxiety, depression and infertility-related stress. Results. Patients with GTN use mature defense mechanisms significantly more than patients with hydatidiform mole. Regression analyses highlight that, considering demographic and clinical variables, immature defense mechanisms are significantly related to state anxiety. Immature defence mechanisms also significantly predict infertility-related global stress. Conclusions. The results show the importance of taking into consideration defense mechanisms used by patients, as they are involved in the modulation of psychological adaptation to GTD.

Purpose: To compare the performance of the algorithms proposed by the Fetal Medicine Foundation in 2012 and BCNatal in 2013 in an Italian population. Methods: A multicentric prospective study was carried out which included pregnancies at 11–13weeks’ gestation from Jan 2014 through May 2017. Two previously published algorithms were used for the calculation of the “a priori” risk of preeclampsia (based on risk factors from medical history) in each individual. Results: In a study population of 11,632 cases, 67 (0.6%) developed early preeclampsia and 211 (1.8%) developed late preeclampsia. The detection rates (95% CI) for early and late preeclampsia were 58.2% (45.5–70.2) vs. 41.8% (29.6–54.5) (p value < 0.05) and 44.1% (37.3–51.1) vs. 38% (31.3–44.8) (p value < 0.05) for the Fetal Medicine Foundation and BCNatal, respectively (at a 10% false positive rate). The associated risk was 1:226 and 1:198 (p value ns) for early PE, and 1:17 and 1:24 (p value ns) for late PE for the Fetal Medicine Foundation and BCNatal, respectively. Conclusions: The Fetal Medicine Foundation screening for preeclampsia at 11–13weeks’ gestation scored the highest detection rate for both early and late PE. At a fixed 10% false positive rate, the estimated “a priori” risks of both the Fetal Medicine Foundation and the BCNatal algorithms in an Italian population were quite similar, and both were reliable and consistent.

Objective: the use of twin-specific versus singleton charts in the assessment of twin pregnancies has been controversial. The aim of the study was to assess whether a diagnosis of small for gestational age (SGA) made using twin specific estimated fetal weight (EFW) and birthweight (BW) charts is more strongly associated with adverse neonatal outcomes compared to singleton charts in twin pregnancies. Methods: this was a cohort study of twin pregnancies delivered at St George's Hospital in London between January 2007 and May 2020. Twin pregnancies complicated by intrauterine demise of one or both twins; aneuploidy or major fetal abnormality, twin-to-twin transfusion syndrome or twin anemia polycythemia sequence (TAPS); and those delivered before 32 weeks' gestation, were excluded. SGA was defined as EFW or BW below the 10th centile. The main study outcome was composite neonatal morbidity, which was stratified to mild or severe for sensitivity analysis. Mixed-effects logistic regression analysis with random pregnancy level intercepts was used to test the association between different SGA classifications and adverse neonatal outcomes. Results: a total of 1329 twin pregnancies were identified, and 913 twin pregnancies (1826 infants) included in the analysis. Of these, 723 (79.2%) were dichorionic and 190 (20.8%) monochorionic. Using the singleton charts, 33.3% and 35.7% were classified as SGA by the singleton chart when using EFW and BW, respectively. The corresponding figures were 5.9% and 5.8% when using the twin specific charts. EFW SGA according to the twin charts, had a significant association with neonatal morbidity (OR 4.78, 95% CI 1.47-14.7, P=0.007), when compared to AGA twins. However, EFW below the 10th percentile according to singleton standards did not have a significant association with neonatal morbidity (OR 1.36, 95% CI 0.63-2.88, P=0.424). SGA classification of EFW using twin specific standards significantly better model fit than using singleton standard (P, NA

Objective: Preterm birth (PTB) is more common in pregnancies conceived by in-vitro fertilization (IVF) as compared with those conceived naturally. However, the extent to which this is attributed to spontaneous labor or to iatrogenic indications has not been determined. The aim of this study was to quantify the risk of spontaneous PTB (sPTB) in singleton pregnancies resulting from IVF or intracytoplasmic sperm injection (ICSI) treatment as compared with that in spontaneously conceived pregnancies. Methods: An electronic search of PubMed/MEDLINE, Scopus and Web of Science to September 2017 and manual search of reference lists identified articles comparing the risk of sPTB in IVF/ICSI vs spontaneously conceived singleton pregnancies. Inclusion criteria were singleton conception with IVF/ICSI, PTB defined as delivery before 37 weeks' gestation and cohort design with clear distinction between spontaneous and indicated PTB. The primary outcome was sPTB < 37 weeks. Relevant secondary outcomes were also analyzed, including sPTB < 34 and < 32 weeks, preterm prelabor rupture of membranes, stillbirth, perinatal mortality, neonatal sepsis, respiratory distress syndrome and gastrointestinal morbidity. A meta-analysis provided the estimation of risk of sPTB in IVF/ICSI pregnancies. Results: In total, 674 records were identified from the search, of which 15 met the inclusion criteria and were included in the meta-analysis. A pooled crude analysis of the primary outcome generated a total sample size of 61 677 births, including 8044 singletons conceived after IVF/ICSI and 53 633 conceived spontaneously. A pooled crude data analysis showed a significant increase in the incidence of sPTB < 37 weeks in singleton IVF/ICSI pregnancies compared with those conceived spontaneously (810/8044 (10.1%) vs 2932/53 633 (5.5%); odds ratio (OR), 1.75; 95% CI, 1.50–2.03; I2= 39%). A subgroup analysis of studies matching for maternal age and parity confirmed the finding (OR, 1.63; 95% CI, 1.30–2.05; I2= 33%). A pooled crude analysis of secondary outcomes showed a significant increase in the incidence of sPTB < 34 weeks in pregnancies conceived after IVF/ICSI compared with those conceived spontaneously (37/1012 (3.6%) vs 24/1107 (2.2%); OR, 1.78; 95% CI, 1.03–3.08; I2= 6%) and did not show any significant difference for any of the other secondary outcomes analyzed. The quality of evidence, rated using the GRADE criteria, was low for the outcome sPTB < 37 weeks and very low for sPTB < 34 weeks. Conclusions: The risk of sPTB in singleton pregnancies resulting from IVF/ICSI is significantly greater than that in spontaneously conceived singletons. These findings should be interpreted with caution given the low quality of the available evidence. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Aim: The study aimed to describe prenatal diagnosis and the outcome of complete hydatidiform mole and coexistent normal fetus (CHMCF). Methods: This was a retrospective case series of 13 patients with CHMCF. Prenatal diagnosis, outcome and development of gestational trophoblastic neoplasia (GTN) were reviewed. Results: Ultrasound diagnosis was carried out in 12 of 13 cases at 17 ± 2.7 weeks of gestation (mean ± SD). Six patients showed abnormalities suggestive of subchorionic hematoma on first trimester ultrasonography (US). Prenatal invasive procedures were performed in 8 of 13 cases (62%). Two women decided to terminate their pregnancies. Four ended in late miscarriages (36%, 4 of 11) between 13 and 21 weeks, and early neonatal death occurred in 1 case (9%, 1 of 11); 5 women delivered a live baby with a mean gestational age of 31 weeks (range 26-37 weeks) with an overall neonatal survival of 45% (5 of 11). GTN occurred in 31% of cases (4 of 13). Conclusions: The first trimester US features of CHMCF are not well-documented. Our series showed that abnormalities of CHMCF could be misdiagnosed as subchorionic hematoma in the early first trimester. When CHMCF is confirmed by expert US, prenatal invasive procedures should be carefully evaluated depending on the associated US findings and exhaustive counseling should be performed.

Background Traditionally, pregnancy was considered to have a positive effect on endometriosis and its painful symptoms due not only to blockage of ovulation preventing bleeding of endometriotic tissue but also to different metabolic, hormonal, immune and angiogenesis changes related to pregnancy. However, a growing literature is emerging on the role of endometriosis in affecting the development of pregnancy and its outcomes and also on the impact of pregnancy on endometriosis. The present article aims to underline the difficulty in diagnosing endometriotic lesions during pregnancy and discuss the options for the treatment of decidualized endometriosis in relation to imaging and symptomatology; to describe all the possible acute complications of pregnancy caused by pre-existing endometriosis and evaluate potential treatments of these complications; to assess whether endometriosis affects pregnancy outcome and hypothesize mechanisms to explain the underlying relationships. Methods This systematic review is based on material searched and obtained via Pubmed and Medline between January 1950 and March 2015. Peer-reviewed, English-language journal articles examining the impact of endometriosis on pregnancy and vice versa were included in this article. Results Changes of the endometriotic lesions may occur during pregnancy caused by the modifications of the hormonal milieu, posing a clinical dilemma due to their atypical appearance. The management of these events is actually challenging as only few cases have been described and the review of available literature evidenced a lack of formal estimates of their incidence. Acute complications of endometriosis during pregnancy, such as spontaneous hemoperitoneum, bowel and ovarian complications, represent rare but life-threatening conditions that require, in most of the cases, surgical operations to be managed. Due to the unpredictability of these complications, no specific recommendation for additional interventions to the routinely monitoring of pregnancy of women with known history of endometriosis is advisable. Even if the results of the published studies are controversial, some evidence is suggestive of an association of endometriosis with spontaneous miscarriage, preterm birth and small for gestational age babies. A correlation of endometriosis with placenta previa (odds ratio from 1.67 to 15.1 according to various studies) has been demonstrated, possibly linked to the abnormal frequency and amplitude of uterine contractions observed in women affected. Finally, there is no evidence that prophylactic surgery would prevent the negative impact of endometriosis itself on pregnancy outcome. Conclusions Complications of endometriosis during pregnancy are rare and there is no evidence that the disease has a major detrimental effect on pregnancy outcome. Therefore, pregnant women with endometriosis can be reassured on the course of their pregnancies although the physicians should be aware of the potential increased risk of placenta previa. Current evidence does not support any modification of conventional monitoring of pregnancy in patients with endometriosis.

Objective: There is no consensus in current practice guidelines on whether conception by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) techniques is an indication for performing a fetal echocardiogram. The aim of the study was to assess whether congenital heart defects (CHD) occur more often in pregnancies conceived after IVF/ICSI as compared with those conceived spontaneously. Methods: A systematic search for studies was conducted of PubMed/MEDLINE, EMBASE and Scopus from inception to September 2017. The search included the following medical subject heading (MeSH) terms alone or in different combinations: ‘IVF’, ‘IVF/ICSI’, ‘ART pregnancy’, ‘assisted conception’, ‘birth defect’, ‘congenital heart defects’ and ‘congenital malformation or abnormalities’. Studies comparing neonatal incidence of CHD in pregnancies conceived after IVF/ICSI and those conceived spontaneously were included. Studies reporting on other types of assisted reproductive technology (ART) or lacking information concerning termination of pregnancy were excluded. Chromosomal abnormalities were excluded in all analyzed studies. A meta-analysis of selected cohort studies was conducted to estimate the pooled odds ratio (OR) with 95% CI using a random-effects model. Statistical heterogeneity among the studies was evaluated with the I2 statistic and Q-test. Results: Forty-one studies were identified for review including six case–control and 35 cohort studies. Data of eight selected cohort studies were used for meta-analysis. A total of 25 856 children conceived from IVF/ICSI techniques and 287 995 children conceived spontaneously, involving both singleton and multiple gestations, were included in the analysis. Total CHD events were 337/25 856 (1.30%) and 1952/287 995 (0.68%) in the IVF/ICSI and spontaneous conception groups, respectively. The risk of CHD was significantly increased in the IVF/ICSI group as compared with the spontaneous conception group (pooled OR, 1.45; 95% CI, 1.20–1.76; P = 0.0001; I2 = 44%; P = 0.08). In the subgroup of singleton IVF pregnancies, a significant difference was also obtained (OR, 1.55; 95% CI, 1.21–1.99; P = 0.0005; I2 = 36%; P = 0.18) and also multiple confounding factors adjusted ORs showed statistical significance (pooled OR, 1.29; 95% CI, 1.03–1.60; P = 0.02; I2 = 0%; P = 0.43). Conclusion: Fetuses conceived with IVF/ICSI methods are at an increased risk of developing CHD compared with those conceived spontaneously. However, this finding deserves further investigation due to heterogeneity of both ART procedures and cardiac defects. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Chemotherapy has been associated with premature ovarian failure and infertility in women with cancer. It is well known that anticancer drugs reduce the primordial follicle pool and harm the ovarian blood vascularization leading to ovarian atrophy. However, their mechanism of injury still remains unclear. The aim of this study was to identify the cellular mechanisms involved in the toxicity of chemotherapy drugs belonging to different classes on human ovarian luteinized granulosa cells (LGCs). Treatment with doxorubicin (DXR), paclitaxel (PC), and cisplatin (CP) affected LGCs viability by inducing apoptosis and downregulating both estrogen receptor β and follicle-stimulating hormone receptor in a dose-dependent manner. Several members of the WNT signaling pathway are expressed in granulosa cells where they regulate follicle development, ovulation, and luteinization. Here we show that treatment with DXR, PC, and CP induced upregulation of WNT4 expression, whereas WNT3 expression was downregulated by DXR and PC and upregulated by CP. Analysis of the WNT3 downstream signaling pathway showed that total β-catenin protein levels were reduced upon treatment with DXR and PC. Additionally, restoration of β-catenin signaling by lithium chloride protected LGCs from the injury induced by chemotherapy. The in vitro LGC toxicity model described might represent a tool to identify components of specific signaling pathways, such as the Wnt pathway, that can be targeted in order to limit the follicular damage caused by chemotherapy.

PURPOSE: Gestational trophoblastic neoplasia (GTN) is a rare and aggressive tumour that is usually sensitive to chemotherapy. The usefulness of conventional imaging modalities in evaluating treatment response is limited, mainly due to the difficulty in differentiating between residual tumour tissue and necrosis. The aim of the present study was to evaluate the role of FDG PET or PET/CT in primary staging and in monitoring treatment efficacy. The effect of FDG PET and combined PET/CT on the management of patients with GTN was also evaluated comparing the differences between standard treatments based on conventional imaging and alternative treatments based on PET. METHODS: This retrospective study included 41 patients with GTN referred to San Raffaele Hospital between 2002 and 2010. All patients were studied by either PET or PET/CT in addition to conventional imaging. Of the 41 patients, 38 were evaluated for primary staging of GTN and 3 patients for chemotherapy resistance after first-line chemotherapy performed in other Institutions. To validate the PET data, PET and PET/CT findings were compared with those from conventional imaging, including transvaginal ultrasonography (TV-US) in those with uterine disease, CT and chest plain radiography in those with lung disease and whole-body CT in those with systemic metastases. Conventional imaging was considered positive for the presence of uterine disease and/or metastases when abnormal findings relating to GTN were reported. PET and PET/CT were considered concordant with conventional imaging when metabolic active disease was detected at the sites corresponding to the pathological findings on conventional imaging. In addition, in 12 of the 41 patients showing extrauterine disease, FDG PET/CT was repeated to monitor treatment efficacy, in 8 after normalization of beta human chorionic gonadotropin (?HCG) and in 4 with ?HCG resistance. In some patients, PET or PET/CT findings led to an alternative nonconventional treatment, and this was considered a change in patient management for the study analysis. RESULTS: When compared to TV-US, chest radiography and CT for staging, PET showed a concordance in 91 %, 84 % and 81 % of patients, respectively. In 8 of the 41 patients with extrauterine disease during staging, PET/CT showed a complete response to therapy after ?HCG normalization. PET and PET/CT identified the sites of persistent disease in all seven high-risk patients with ?HCG resistance, of whom four underwent second-line chemotherapy, two surgical removal of resistant disease instead of additional chemotherapy, and one surgical removal of resistant disease and second-line chemotherapy with subsequent negative ?HCG. CONCLUSION: In staging, PET cannot replace conventional imaging and does not show any information in addition to that shown by conventional imaging. The additional value of PET/CT in GTN with respect to conventional imaging is found in patients with high-risk disease. PET can identify the sites of primary and/or metastatic disease in patients with persistent high levels of ?HCG after first-line chemotherapy and may be of additional value in patient management for guiding alternative treatment.

Arteriovenous malformations (AVMs) of the uterus are rare vascular lesions that may be congenital or more commonly acquired after medical or surgical abortion, spontaneous miscarriage, dilation and...

Objectives Gestational Trophoblastic Disease (GTD) comprises a group of disorders that derive from the placenta. Even if full recovery is generally expected, women diagnosed with GTD have to confront: the loss of a pregnancy, a potentially life-threatening diagnosis and delays in future pregnancies. The aim of the study is to evaluate the psychological impact of GTD, focusing on perceived fertility, depression and anxiety. Methods 37 patients treated for GTD at San Raffaele Hospital, Milan, took part in the study. The STAI-Y (State-Trait Anxiety Inventory), the BDI-SF (Beck Depression Scale-Short Form) and the FPI (Fertility Problem Inventory) were used. Patients were grouped on the basis of presence of children (with or without), age (< or >= 35) and type of diagnosis (Hydatidiform Mole, HM, or Gestational Trophoblastic Neoplasia, GTN). Differences in the values between variables were assessed by a t-type test statistic. Three-way ANOVAs were also carried out considering the same block factors. Results The study highlights that women suffering from GTN had higher depression scores compared to women suffering from HM. A significant correlation was found between anxiety (state and trait) and depression. Younger women presented higher Global Stress scores on the FPI, especially tied to Need for Parenthood and Relationship Concern subscales. Need for Parenthood mean scores significantly varied between women with and without children too. Conclusions We can conclude that fertility perception seems to be negatively affected by GTD diagnosis, particularly in younger women and in those without children. Patients should be followed by a multidisciplinary team so as to be supported in the disease's psychological aspects too.