Machine learning endometrial cancer risk prediction model: integrating guidelines of European Society for Medical Oncology with the tumor immune framework.

OBJECTIVE: Current prognostic factors for endometrial cancer are not sufficient to predict recurrence in early stages. Treatment choices are based on the prognostic factors included in the risk classes defined by the ESMO-ESGO-ESTRO (European Society for Medical Oncology-European Society of Gynaecological Oncology-European Society for Radiotherapy and Oncology) consensus conference with the new biomolecular classification based on POLE, TP53, and microsatellite instability status. However, a minority of early stage cases relapse regardless of their low risk profiles. Integration of the immune context status to existing molecular based models has not been fully evaluated. This study aims to investigate whether the integration of the immune landscape in the tumor microenvironment could improve clinical risk prediction models and allow better profiling of early stages. METHODS: Leveraging the potential of in silico deconvolution tools, we estimated the relative abundances of immune populations in public data and then applied feature selection methods to generate a machine learning based model for disease free survival probability prediction. RESULTS: We included information on International Federation of Gynecology and Obstetrics (FIGO) stage, tumor mutational burden, microsatellite instability, POLEmut status, interferon γ signature, and relative abundances of monocytes, natural killer cells, and CD4+T cells to build a relapse prediction model and obtained a balanced accuracy of 69%. We further identified two novel early stage profiles that undergo different pathways of recurrence. CONCLUSION: This study presents an extension of current prognostic factors for endometrial cancer by exploiting machine learning models and deconvolution techniques on available public biomolecular data. Prospective clinical trials are advisable to validate the early stage stratification.

Vaccine hesitancy and knowledge regarding maternal immunization among reproductive age women in central Italy: a cross sectional study.

Background: Vaccination in pregnancy offers protection to the mother and the newborn. In Italy, influenza, pertussis, and COVID-19 vaccinations are recommended in pregnancy, but vaccination coverage is still far from the National Immunization Plan goals. We aimed to assess knowledge and attitude on maternal immunization in two groups of Italian women, in pregnancy and in reproductive age (non pregnant). Methods: A cross sectional study on Italian childbearing age women gathering information on their knowledge on maternal immunization and attitudes to receiving influenza and pertussis vaccines in pregnancy was carried out at the University of Rome Tor Vergata, between September 2019 and February 2020. Logistic and multinomial regressions were chosen as statistical tests for our analysis. Results: 1,031 women participated in the survey by answering the questionnaire. Out of these, 553 (53.6%) women were pregnant, and 478 (46.4%) were in the reproductive age. 37% (204/553) of pregnant women and 41% (198/476) of non pregnant women are aware of the existence of an immunization plan for pregnant women in Italy. The group with age between 20 and 30, for both pregnant women and women in the reproductive age, has a better knowledge of vaccination in pregnancy. Working status is a variable associated with more awareness about vaccination during pregnancy only for pregnant women (OR = 2.34, p < 0.00001). Educational status, trimester of pregnancy and knowledge on the topic are associated with vaccine hesitancy in our multivariate analysis for pregnant women. In the reproductive age group women who had a previous pregnancy are more likely to be hesitant towards vaccination in pregnancy, on the other hand the one with a higher knowledge and educational status are more likely to get vaccinated. Conclusions: The study highlights the persistent vaccine hesitancy among Italian women of reproductive age and pregnant women. Despite healthcare providers being identified as a reliable source of information, their recommendations alone are insufficient to overcome vaccine hesitancy. Factors such as employment status, educational level, pregnancy trimester, and knowledge about vaccinations during pregnancy influence vaccine hesitancy. Tailored educational interventions and communication campaigns targeting these areas can help reduce vaccine hesitancy and promote maternal immunization.

Towards reproducible research in recurrent pregnancy loss immunology: Learning from cancer microenvironment deconvolution.

The most recent international guidelines regarding recurrent pregnancy loss (RPL) exclude most of the immunological tests recommended for RPL since they do not reach an evidence-based level. Comparisons for metanalysis and systematic reviews are limited by the ambiguity in terms of RPL definition, etiological and risk factors, diagnostic work-up, and treatments applied. Therefore, cohort heterogeneity, the inadequacy of numerosity, and the quality of data confirm a not standardized research quality in the RPL field, especially for immunological background, for which potential research application remains confined in a separate single biological layer. Innovative sequencing technologies and databases have proved to play a significant role in the exploration and validation of cancer research in the context of dataset quality and bioinformatics tools. In this article, we will investigate how bioinformatics tools born for large-scale cancer immunological research could revolutionize RPL immunological research but are limited by the nature of current RPL datasets.

Diagnostic factors for recurrent pregnancy loss: an expanded workup.

PURPOSE: There is limited information on the risk factors for recurrent pregnancy loss (RPL). METHODS: In this study, a patient-based approach was used to investigate the possible involvement and relative relevance of a large number of diagnostic factors in 843 women with RPL who underwent an extensive diagnostic workup including 44 diagnostic factors divided into 7 major categories. RESULTS: The rates of abnormalities found were: (1) genital infections: 11.74%; (2) uterine anatomic defects: 23.72%; (3) endocrine disorders: 29.42%; (4) thrombophilias: 62%; (5) autoimmune abnormalities: 39.2%; (6) parental karyotype abnormalities 2.25%; (7) clinical factors: 87.78%. Six hundred and fifty-nine out of eight hundred and forty-three women (78.17%) had more than one abnormality. The mean number of pregnancy losses increased by increasing the number of the abnormalities found (r = 0.86949, P < 0.02). The factors associated with the highest mean number of pregnancy losses were cervical isthmic incompetence, anti-beta-2-glycoprotein-1 antibodies, unicornuate uterus, anti-prothrombin A antibodies, protein C deficiency, and lupus anticoagulant. The majority of the considered abnormalities had similar, non-significant prevalence between women with 2 versus ≥ 3 pregnancy losses with the exception of age ≥ 35 years and MTHFR A1298C heterozygote mutation. No difference was found between women with primary and secondary RPL stratified according to the number of abnormalities detected (Chi-square: 8.55, P = 0.07). In these women, the only factors found to be present with statistically different rates were age ≥ 35 years, cigarette smoking, and genital infection by Ureaplasma. CONCLUSION: A patient-based diagnostic approach in women with RPL could be clinically useful and could represent a basis for future research.

Transvaginal Ultrasound Findings After Laparoscopic Rectosigmoid Segmental Resection for Deep Infiltrating Endometriosis.

OBJECTIVES: To evaluate transvaginal ultrasound (TVUS) findings in patients who underwent segmental rectosigmoid resection for deep infiltrating endometriosis (DIE) and to correlate postsurgical ultrasound findings with symptoms. METHODS: A retrospective study including 50 premenopausal women with bowel endometriosis who underwent segmental rectosigmoid resection was conducted. Within 12 months after surgery, a TVUS examination was conducted in all patients to evaluate the presence of postsurgical endometriosis locations and symptoms, including dysmenorrhea, dyspareunia, dysuria, dyschezia, and chronic pelvic pain. Pelvic pain was assessed in all women by a visual analog scale. RESULTS: At the follow-up 32 of 50 patients were receiving medical treatment, whereas 18 women declined postsurgical medical therapy and tried to conceive. A high percentage of adhesions (90%) was found. A negative sliding sign (a simple diagnostic sign that can be performed during a TVUS examination, consisting of gentle pressure applied by both the vaginal transducer and the examiner's hand on the abdomen; if the uterus does not glide freely along with the rectum and posterior fornix, the sign is considered negative, and adhesions can be suspected) was found in 29 (58%) women and was associated with bowel symptoms. Recurrence of posterior DIE was found in 9 cases (18%) and endometriomas in 8 cases (16%). Adenomyosis was observed in 80% of women and was present in all symptomatic patients. CONCLUSIONS: After rectosigmoid segmental resection patients with DIE may continue to be symptomatic, and postoperative TVUS may reveal foci of disease or pelvic adhesions. Moreover, adenomyosis could be linked to symptoms experienced during follow up. Women should be aware that painful symptoms and alterations of pelvic organs could still be present after surgery and be detectable by TVUS.

Adolescence and endometriosis: symptoms, ultrasound signs and early diagnosis.

OBJECTIVE: To evaluate the ultrasonographic presence of different forms of endometriosis and the associated clinical symptoms in adolescent women. DESIGN: Retrospective observational study. SETTING: University hospital. PATIENT(S): Two hundred and seventy women aged 12-20 years referred to the gynecologic ultrasound unit from January 2014 to June 2019. INTERVENTION(S): Two-dimensional, three-dimensional, and power Doppler ultrasound (US) pelvic examination (transvaginal or transrectal in pre-sexually active adolescents) were performed in all included adolescents. Medical history was collected for each patient before the scan. MAIN OUTCOME MEASURE(S): All possible locations of endometriosis evaluated and recorded using a dedicated ultrasound mapping sheet and severity of painful symptoms evaluated through a visual analogue scale (VAS). RESULT(S): Dysmenorrhea was detected in 147 (54.4%) of 270 patients and heavy menstrual bleeding in 76 (28.1%) of 270. At least one ultrasound feature of endometriosis was identified in 36 (13.3%) of 270 cases. Ovarian endometriomas were found in 22 (11%) patients, adenomyosis in 16 (5.2%), and deep infiltrating endometriosis (DIE) in 10 (3.7%). Ultrasound signs of endometriosis were found in 21% of adolescents who reported dysmenorrhea and 33% with dyspareunia. The presence of DIE at ultrasound was associated with bowel symptoms in 33% of patients and associated with dyspareunia in 25% of patients. CONCLUSION(S): The detection rate of pelvic endometriotic lesions at ultrasound was 13%. The rates of dysmenorrhea, dyspareunia and heavy menstrual bleeding in adolescents with endometriosis ultrasound signs were statistically significantly higher compared with those without. In patients with dysmenorrhea, the detection rate of pelvic endometriosis at ultrasound increased to 20%. Professionals involved with teens should be aware of the clinical presentation of endometriosis to reduce the delay between the onset of symptoms and the diagnosis, referring these young women to dedicated centers.

Erratum to "Uterine Tumor Resembling Ovarian Sex Cord Tumors Type II with Vaginal Vault Recurrence".

[This corrects the article DOI: 10.1155/2019/5231219.].

Pregnancy-Related Complications in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study.

The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and 661 in normal healthy women. The prevalence of the following complications was observed: threatened miscarriage, miscarriage, cervical insufficiency, chromosomal/genetic abnormalities, fetal anomalies, oligohydramnios, polyhydramnios, fetal growth restriction, intrauterine fetal death, gestational diabetes mellitus (GDM), preeclampsia, placenta previa, abruptio placentae, pregnancy-related liver disorders, and preterm premature rupture of the membranes. The odds ratio and 95% CI for each pregnancy complication considered were determined by comparing women with RPL and normal healthy women. Women with RPL had an overall rate of pregnancy complications higher than normal women (OR = 4.37; 95% CI: 3.353-5.714; p < 0.0001). Their risk was increased for nearly all the conditions considered. They also had an increased risk of multiple concomitant pregnancy complications (OR = 4.64; 95% CI: 3.10-6.94, p < 0.0001). Considering only women with RPL, women with ≥3 losses had a higher risk of pregnancy complications than women with two losses (OR = 1.269; 95% CI: 1.112-2.386, p < 0.02). No differences were found in the overall risk of pregnancy complications according to the type, explained or unexplained, of RPL. Women with secondary RPL had an increased risk of GDM than women with primary RPL. Pregnancy in women with RPL should be considered at high risk.

First-trimester trophoblasts obtained by chorionic villus sampling maintain tolerogenic and proteomic features in successful pregnancies despite a history of unexplained recurrent pregnancy loss.

PROBLEM: While there are several known causes for recurrent pregnancy loss (RPL), about 50% are unexplained (uRPL), and in these cases, an aberrant immune regulation seems to be involved. Although fetally derived trophoblast cells have a key role in immune regulation, it is difficult to study their immune function during pregnancy, and it is not known whether trophoblast function may be an inherent aberration in uRPL or whether it is associated with the outcome of the current pregnancy. METHOD OF STUDY: Chorionic villus sampling (CVS) was performed for clinical indications at 12 weeks of gestation. Superfluous materials, divided in small explants, were cultured for 20-24 hours, and supernatants (conditioned medium) were collected from 36 women with singleton normal pregnancies, of whom 9 women had a history of RPL. The secreted immune protein profile was measured by proximity extension assay, and the conditioned medium was further used in functional ex vivo models to assess ability to polarize blood monocytes and CD4+ T cells into immune regulatory phenotypes, as detected by flow cytometry. RESULTS: Conditioned medium from chorionic villi, human fetally derived placental tissue, was able to induce a decidual-type of M2-like macrophages, as well as an expansion of Treg cells ex vivo, both in women with uRPL and in control women. The preserved immunological properties were confirmed by a maintained immune protein profile in RPL compared with controls. CONCLUSION: Trophoblasts in an ex vivo model maintain tolerogenic and proteomic profile features in successful pregnancies, despite a previous history of RPL.

Time-to-Pregnancy in Women with Unexplained Recurrent Pregnancy Loss: A Controlled Study.

To determine whether differences are present in the time-to-pregnancy (TTP) between women with unexplained recurrent pregnancy loss (uRPL) and control women, in this case-control, retrospective study, carried out in tertiary university hospitals, the TTP, defined as the months needed to reach pregnancy from when the woman started to try to conceive, was determined in 512 women, 207 of which were diagnosed as having uRPL and 305 were normal healthy control women. The specific TTPs for each pregnancy, stratified by order of pregnancy occurrence, were also determined. Pregnancy rates by time were calculated by using the Kaplan-Meier method to construct the survival curves. The age at which the pregnancies occurred was determined. Comparisons were carried out between women with uRPL and controls. Overall, 1192 pregnancies occurred and were analyzed. Mean TTP in uRPL women was shorter than in controls (P < 0.001) when all the pregnancies were considered. Similarly, it was shorter in the first, second, third, and fifth pregnancy. The pregnancy rates of uRPL women were shorter than that of control women for the first three pregnancies, for which the numbers of subjects allowed the comparisons to be made. These findings were observed despite maternal age of uRPL women was higher than that of control women. TTP is shorter in uRPL than in normal women. This finding clinically supports to the hypothesis that women with uRPL could be, at least in early stages of pregnancy, more fertile or receptive toward the implanting embryo than healthy women.

Uterine and placental blood flow indexes and antinuclear autoantibodies in unexplained recurrent pregnancy loss: should they be investigated in pregnancy as correlated potential factors? A retrospective study.

BACKGROUND: The potential role of antinuclear antibodies (ANA) in recurrent pregnancy loss (RPL) pathogenesis is still debated, although some evidences suggest that they could affect pregnancy outcome, leading to a higher miscarriage rate in these patients. A hypothesized mechanism is through changes in uterine flow in pre-conceptional stage, by modifying endometrial receptivity in RPL. However, scant data are available, in pregnancy, about their role in RPL placental perfusion, also in relation to its potential treatments, such as low molecular weight heparin (LMWH). The aim of this study is to retrospectively further investigate the correlation between two-dimensional (2D) and three-dimensional (3D) uterine and placental flow indexes and the presence or the absence of ANA in women with unexplained RPL (uRPL), treated or not treated with LMWH. METHODS: 2D Doppler measurement of pulsatility index (PI) of the uterine arteries and 3D ultrasonography determination of vascularization index (VI), flow index (FI) and vascularization flow index (VFI) was carried out with the aid of the virtual organ computer-aided analysis (VOCAL) technique in LMWH treated (n 24) and not treated-uRPL patients (n 20) and in the relative control group (n 27), each group divided in ANA+ and ANA- subgroups. Serum assay for the presence of ANA was performed in all women. RESULTS: No differences were found in PI, VFI and VI values, by comparing the different groups. A difference in VI values was found for ANA- patients between RPL women not treated with LMWH and the treated ones (p = 0,01), which have lower VI values and similar to controls. By considering only ANA- treated and not treated RPL patients, the ROC curve shows an area of 0,80 and at the VI cut-off of 11,08 a sensitivity of 85% and a specificity of 67%. CONCLUSIONS: LMWH could exert a potential beneficial effect in restoring the physiological blood flow supply in terms of VI in uRPL ANA- status, suggesting to include ANA and VI investigations in the RPL diagnostic algorithm in a research context, since further studies are needed to clarify this challenging hypothesis in order to try to ameliorate ANA and abnormal placental vascularization negative influence on RPL pregnancy outcome .

Effect of chorionic villus sampling on placental volume and vascularization in the first trimester of pregnancy.

Objective: To evaluate the effects of chorionic villus sampling (CVS) on placental volume (PV), perfusion, and vasculature in the first trimester of pregnancy.Method: Uterine artery pulsatility index (PI), PV, vascularization index (VI), flow index (FI), and Vascularization Flow Index (VFI) were serially measured in 38 pregnant women who underwent CVS. Thirty-eight women who did not undergo invasive prenatal diagnosis were recruited as controls.Results: CVS was associated with a mild reduction of PI, a reduction of placental VI, FI, and VFI and with an increase in PV detected one week after the procedure. The outcome of pregnancy was similar between women of the two groups.Conclusion: Our findings showed that CVS is associated with mild placental vascular and morphological changes. However, these changes do not seem to be associated with adverse outcome.

Longitudinal Changes of Subpubic Arch Angle throughout Pregnancy.

OBJECTIVE: The objective of this study is to assess whether the subpubic arch angle (SPA) changes throughout pregnancy. MATERIALS AND METHODS: We recruited a group of nulliparous women in the first trimester of pregnancy. Each woman was assessed 3 times throughout pregnancy, once per each trimester, by measuring SPA using a recently described highly reproducible three-dimensional transperineal ultrasound (linear reconstruction with contrast enhancement technique; OmniView-volume contrast imaging). Repeated measures analysis of variance was used to study SPA changes during pregnancy. RESULTS: Overall, 97 women were included in the final analysis. SPA increased progressively and significantly (F = 27.824, p < 0.001) from the first to the second trimester (121.8 ± 8.7 vs. 123.5 ± 8.4°, p = 0.01) and from the second to the third trimester (123.5 ± 8.4 vs. 125.3 ± 8.1°, p = 0.01). CONCLUSION: SPA width increases progressively but slightly during pregnancy. Although this finding is interesting, the extremely small difference detected is unlikely to be clinically significant.

Endometrial Immune Dysfunction in Recurrent Pregnancy Loss.

Recurrent pregnancy loss (RPL) represents an unresolved problem for contemporary gynecology and obstetrics. In fact, it is not only a relevant complication of pregnancy, but is also a significant reproductive disorder affecting around 5% of couples desiring a child. The current knowledge on RPL is largely incomplete, since nearly 50% of RPL cases are still classified as unexplained. Emerging evidence indicates that the endometrium is a key tissue involved in the correct immunologic dialogue between the mother and the conceptus, which is a condition essential for the proper establishment and maintenance of a successful pregnancy. The immunologic events occurring at the maternal-fetal interface within the endometrium in early pregnancy are extremely complex and involve a large array of immune cells and molecules with immunoregulatory properties. A growing body of experimental studies suggests that endometrial immune dysregulation could be responsible for several, if not many, cases of RPL of unknown origin. The present article reviews the major immunologic pathways, cells, and molecular determinants involved in the endometrial dysfunction observed with specific application to RPL.

Amniotic fluid antiphospholipid antibodies: potential role in antiphospholipid syndrome-independent aberrant implantation process.

BACKGROUND: The direct role of antiphospholipid antibodies (aPL) at maternal-fetal interface has not been fully investigated, especially whether they are involved in physiological and pathological implantation conditions, in an antiphospholipid syndrome (APS)-independent manner. In fact, trophoblast cells and placental endothelial cells at the implantation site express potential aPL targeted-phospholipid antigens (PL Ags); thus, the local production and presence of their specific antibodies, not related to APS (characterized by aPL presence in the peripheral blood), could be a potential marker of aberrant invasion, implantation and fetal-maternal immune tolerance processes. METHODS: Anti-Beta2glycoprotein I (anti-ß2GPI) and anticardiolipin (aCL Ab) antibodies (the most clinically relevant aPL) were detected by immunoenzymatic assay (ELISA), in the amniotic fluid (AF) of 167 women with physiological and complicated common pregnancy conditions, sharing an aberrant implantation process, such as recurrent pregnancy loss (RPL), autoimmune hypothyroidism (ahT) and smoking. All women included in the study were negative to peripheral blood aPL. RESULTS: aCL and anti-ß2GPI antibodies were detectable in all the AF samples. RPL, ahT and smoking patients had higher level of anti-ß2GPI Abs (IgM) compared to women with physiological pregnancies (p < 0.0001). Since IgM cannot cross the placenta, their local production in response to maternal-fetal interface stimuli, could be hypothesized. CONCLUSIONS: The presence of aPL in the AF (not related to APS) could reveal a potential clinical significance at maternal-fetal interface in selected pregnancy complications, in which an aberrant implantation process, and in turn an impaired fetal-maternal immune tolerance cross-talk, could occur.

Significant relationship of combined ACP1/PTPN22 genotype variants with the growth of uterine leiomyomas.

OBJECTIVE: To analyze the interaction between ACP1 and PTPN22 concerning their effects on the growth of the tumor. In previous paper we have shown (i) that ACP1*B/*B genotype of ACP1 is negatively associated with the growth of leiomyomas and (ii) that there is a negative association of *C/*C genotype of PTPN22 with tumor growth. MATERIALS AND METHODS: Two hundred and three White women from the population of Rome with symptomatic leiomyomas were recruited in the University of Rome Tor Vergata. All subjects gave consent for the participation in the study that was approved by the Council of Department. ACP1 and PTPN22 genotypes were determined by DNA analysis. RESULTS: The proportion of women with small leiomyomas decreases with the decrease of the number of protective factors and it is 37.2% in women carrying the joint genotype ACP1*B/*B-PTPN22 *C/*C (two protective factors) and 0% in women carrying no protective factors. Three way contingency table analysis by a log linear model has shown no evidence of epistatic interaction between the two genetic systems but a highly significant cooperative effect on the dimension of leiomyomas. There is a highly significant negative correlation between the number of protective factors and the dimension of leiomyomas with a minimum (cm 4.74) in women carrying the joint genotype ACP1*B/B-PTPN22 *C/*C and a maximum (cm 7.25) in women carrying no protective factors. CONCLUSION: The present study suggests a cooperative interaction between ACP1 and PTPN22 concerning their effects on the growth of uterine leiomyomas. The determination of the genotype of the two systems may help to evaluate the risk of clinical manifestations of this common benign tumor.

Hysteroscopic polypectomy: a comparison between 22 Fr and 26 Fr resectoscopes under paracervical block anesthesia, a randomized controlled study.

Objective: The aim of this study was to compare 22 Fr unipolar resectoscope with the traditional 26 Fr unipolar resectoscope in endometrial polypectomy performed under paracervical block anesthesia. Methods: The trial took place in Gynecologic Unit, Department of Surgery, Tor Vergata University Hospital, Rome. Inclusion criteria were: diagnosis of endometrial polyps <3 cm at office hysteroscopy; agreement of patients to perform surgery under paracervical block anesthesia but not in office setting. Patients with ASA physical status classes III or more and with contraindication to operative hysteroscopy were excluded. Before the procedure, the recruited patients were randomly assigned to two groups, 35 to the 22 Fr unipolar resectoscope group (group A) and 35 to the 26 Fr unipolar resectoscope group (group B). Primary endpoint was the time spent for cervical dilatation and resection. Secondary endpoints were pain during and after surgery, efficacy of paracervical block, use of analgesic drugs during and after the procedure, patients' satisfaction, correlation between pain and menopause or parity. Statistical analysis was performed by the SPSS software, and the tests used were Pearson Chi-Square, One-way ANOVA and Mann-Whitney test. A p value <.05 was considered significant. Results: The mean time for cervical dilatation was two minutes in group A (26 Fr) and five minutes in group B (22 Fr, p = .001). Operative mean time was four minutes in group A and seven minutes in group B (p = .001). Pain during dilatation was analogous (VAS = 6, p = .054), while during the procedure it was higher in group B (VAS = 1 vs VAS = 2, p = .003). Sufentanil was administered during resection in 19 patients of group A and in 22 patients of group B (p = .754). General anesthesia was never necessary. Postoperative pain was higher in group B (p = .01). Nine patients of group B needed analgesics, as opposed to no patient of group A (p = .002). Conclusions: The 22 Fr unipolar resectoscope appears advantageous compared to the 26 Fr resectoscope in the resection of endometrial polyps <3 cm, in terms of cervical dilatation and operative time, pain and need of postoperative analgesics. Paracervical block is useful and safe in compliant patients at high risk for general anesthesia.

hCG and Its Disruption by Environmental Contaminants during Human Pregnancy.

Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para-Nonylphenol (p-NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances.

Ectopic pregnancy in women with recurrent miscarriage.

AIM: The aim of this study was to investigate the possible association between recurrent miscarriage (RM) and ectopic pregnancy (EP). METHODS: In this case-control retrospective study, the clinical cards of women followed as outpatients in the RM and low-risk pregnancy offices of the Obstetrics and Gynecology Unit at the Policlinico Tor Vergata University Hospital were carefully reviewed for the occurrence of EP. RESULTS: Overall, 598 women with RM and 2043 normal women without RM (controls) were included in the study. Among these women, 4974 pregnancies were analyzed, in which 2028 miscarriages occurred. The EP rate (3.51%) was significantly higher in RM than in control women (1.51%) [odds ratio = 2.31 (95% confidence interval: 2.3-2.4)]; it was particularly high in women with primary RM (5.11%). However, when EP rates were calculated not by women but by overall pregnancies, no differences could be found between RM and control women. In control women, the absence of a miscarriage in the reproductive history was associated with a lower rate of EP. CONCLUSIONS: Women with RM, particularly primary RM, are at increased risk of EP. This increased risk seems to be dependent on the high number of pregnancies occurring in women with RM rather than to specific characteristics of these women.