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.

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.

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 .

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.

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.

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.

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.

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.

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.

Three-hour analysis of non-invasive foetal sex determination: application of Plexor chemistry.

BACKGROUND: The knowledge of the individual genetic "status" in the prenatal era is particularly relevant in the case of positive family history for genetic diseases, in advanced maternal age and in the general screening for foetal abnormalities. In this context, here, we report an innovative molecular assay which utilizes the cell-free foetal DNA (cffDNA) as a source for the early and fast detection of the foetal sex. The study involved 132 pregnant women in their first 3 months of pregnancy, who agreed to give a blood sample. All the collected samples were immediately subjected to the separation of the plasma, which was utilized for the extraction of the cffDNA. Successively, the extracted cffDNA was analysed by a quantitative PCR (qPCR) method based on Plexor-HY chemistry, which is able to simultaneously identify, quantify and discriminate the autosomal DNA from the sex-linked DNA. RESULTS: Overall, the Plexor-HY assay demonstrated to be sensitive and specific for the determination of low-template DNA, such as the cffDNA. In fact, the Plexor-HY assay has been successfully performed in all the samples, identifying 70 males and 62 females. As the foetal sex can be provided in 120 min just by utilizing a maternal blood sample as cffDNA source, the assay represents a very fast, safe and non-invasive prenatal method. CONCLUSIONS: The possibility of determining the foetal sex in the early prenatal life consents the application of our assay as a helpful screening test for subjects and families at risk of sex-linked disorders. Moreover, the early knowledge of the foetal sex may be of great help even for the specialist, who might promptly advise the patients concerning the foetal risk of inheriting sex-linked disorders and the clinical utility of performing an invasive prenatal diagnosis.

Three-Dimensional Hysterosalpingo Contrast Sonography with Gel Foam: Methodology and Feasibility to Obtain 3-Dimensional Volumes of Tubal Shape.

OBJECTIVES: To investigate the feasibility of hysterosalpingo foam sonography (HyFoSy) with automated 3-dimensional (3D) software in the evaluation of tubal patency and visualization of the tubal course by obtaining a 3D volume acquisition of tubes. DESIGN: Prospective observational study (Canadian Task Force classification III). SETTING: University hospital. PATIENTS: A total of 132 infertile females evaluated between October 2013 and February 2015. INTERVENTIONS: All patients underwent HyFoSy with the new automated 3D coded contrast imaging (CCI) followed by 2-dimensional (2D) real-time HyFoSy. To evaluate the feasibility of 3D visualization of the tubal course, consecutive volume acquisitions were performed during gel foam contrast agent injection. Conventional 2D real-time hysterosalpingo contrast sonography (HyCoSy) by detection of gel foam moving through the tubes and around the ovaries was finally performed and considered to indicate the final results of tubal status. MEASUREMENTS AND MAIN RESULTS: All the patients underwent 3D CCI HyFoSy, followed by 2D real-time HyFoSy. After both procedures, we observed 108 patients (81.8%) with bilateral tubal patency, 22 patients (16.6%) with unilateral tubal patency, and 2 patients (1.5%) with bilateral tubal occlusion. The concordance rate for tubal status between the first and second 3D volume acquisitions and the final 2D real-time evaluation was 84.8% and 97.0%, respectively. CONCLUSIONS: Transvaginal ultrasound HyFoSy with 3D volume reconstruction of the uterus and tubes is an accurate and safe technique that allows complete visualization of tubal shape and patency with high patient compliance.

Gestational age of pregnancy loss in women with unexplained recurrent miscarriage.

AIM: The aim of this study was to investigate the gestational age (GA) of pregnancy loss in women with unexplained recurrent miscarriage (RM) and to determine whether the miscarriages occur at similar GA in RM women. MATERIAL AND METHODS: This retrospective study was carried out in a university hospital and included 288 women with unexplained RM. The GA at which each miscarriage occurred was carefully determined. Overall, 739 miscarriages were analyzed. RESULTS: RM women had miscarriages at a median GA of 7 weeks (range: 3-20). In RM women, 47.2% (n = 136) experienced miscarriages within a 1-week range of GA and 53.4% (n = 154) had miscarriages in the same period of fetal development (pre-embryonic, embryonic or fetal). CONCLUSION: Women with unexplained RM tend to have miscarriages at the same GA, which is characteristic for each patient.

Randomized comparison of total laparoscopic, laparoscopically assisted vaginal and vaginal hysterectomies for myomatous uteri.

PURPOSE: To compare the operative data and early postoperative outcomes of total laparoscopic hysterectomy (TLH), laparoscopically assisted vaginal hysterectomy (LAVH) and vaginal hysterectomy (VH). METHODS: One hundred and eight women requiring hysterectomy for enlarged myomatous uterus were randomly allocated into three treatment arms: TLH (n = 36); LAVH (n = 36); VH (n = 36). Randomization procedure was based on a computer-generated list. The primary outcome was the discharge time comparison. The secondary outcomes were operating time, blood loss, paralytic ileus time, intraoperative complications, postoperative pain, and early postoperative complications. RESULTS: The mean discharge time was shorter after VH than after LAVH and TLH (P = 0.001). Operating time significantly influenced the discharge time, considered as a dependent variable in general linear model analysis (P = 0.006). In contrast, blood loss did not influence the discharge time (P = 0.55).The mean operating time was significantly shorter in VH than in TLH and LAVH groups (P = 0.000).The intraoperative blood loss was greater during LAVH than during TLH and VH (P = 0.000).Paralytic ileus time was shorter after VH than after TLH and LAVH (P = 0.000). No intraoperative complications or conversion to laparotomy occurred. CONCLUSIONS: VH was the faster operative technique with smaller blood loss and shorter discharge time compared with the others two techniques. So, VH should be considered the preferred approach in patients with enlarged myomatous uteri. When VH is not feasible or salpingo-oophorectomy is required, LAVH or TLH should be considered as valid alternatives. It is necessary to continue prospective comparative studies between the various surgical options to identify the best approach for hysterectomy in each single woman.

Estrogen replacement therapy and asthma.

A growing body of clinical and experimental evidence indicates that female sex hormones, particularly estrogen, have significant effects on normal airway function as well as on respiratory disorders, such as asthma. These effects are very complex and are exerted at several levels, directly on airway reactivity or indirectly through regulation of the immune and inflammatory responses in the lung. They can have relevant clinical implications not only according to the phases of the reproductive life in women, but also in relation to the therapeutical administration of estrogen, as in the case of menopausal hormone therapy. Clinical evidence suggests that administration of estrogen to menopausal women is associated with increased rates of newly diagnosed asthma. Conversely, functional studies show that estrogen can improve objective indexes of respiratory functionality.

Uterine myomectomy: role of gasless laparoscopy in comparison with other minimally invasive approaches.

INTRODUCTION: The aim of this review was to assess the role of gasless laparoscopy (GLM) in comparison with two other minimally invasive approaches to myomectomy, CO(2) laparoscopy (LM) and minilaparotomy (MM), focusing on the most recent randomized or prospective controlled studies. MATERIAL AND METHODS: A computerized search was made of the Medline, Science Citation Index, Current Contents, Embase, and PubMed databases for English language publications from the first reports of GLM, LM, and MM in 1995 to 2010. The fifteen most recent randomized or prospective controlled studies were selected and analyzed considering the operative and postoperative parameters. RESULTS: One randomized controlled, one multicenter controlled, three prospective studies about GLM, four randomized controlled studies and one prospective study about LM, four randomized controlled trials and one prospective study about MM were reviewed and analyzed. DISCUSSION: GLM offers some advantages eliminating the adverse effects and potential risks of CO(2) insufflation, particularly when large myomas have to be removed. The advantages of LM are the tamponade effect generated by the gas on the small vessels and the more precise myoma enucleation by using the endoscopic instruments, thus reducing intraoperative bleeding. MM can be a suitable option being associated with a lower overall level of surgical skill, even if it is desirable to have a standard universally accepted definition of "minilaparotomy" in order to correctly compare the results of the different studies. Lastly, the surgical outcomes of the three minimally invasive approaches to myomectomy are influenced by size, site, and number of the myomas, as well as by the skill and preference of the surgeon.All these criteria should be considered in the choice of the best minimally invasive approach to myomectomy.

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.

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.

Adenylate kinase genetic polymorphism and spontaneous abortion.

OBJECTIVE: Recent studies on healthy puerperae suggest that Adenylate kinase locus 1 (Ak(1)) genetic polymorphism could be involved in intrauterine selection. In this article, we have searched for a possible relationship between Ak(1) polymorphism and spontaneous abortion. METHODS: 178 women with primary repeated spontaneous abortion (RSA), 487 healthy consecutive puerperae, 251 puerperae with diabetes, and 361 consecutive healthy female newborns from the White Caucasian population of Central Italy delivered at the Maternal Department have been studied. In these subjects, Ak(1) phenotype was determined to study the relationship between this enzyme and spontaneous abortion. RESULTS: The proportion of Ak(1)2-1 phenotype is higher in women with history of two or more spontaneous abortion than in puerperae with a negative history of spontaneous abortion and in female newborns infants (O.R. 1.930; 95%C.I. 1.113-3.280). Moreover, RSA women carrying the Ak(1)2-1 phenotype have a reduced probability of having live-born infants. CONCLUSIONS: Our findings suggest a reduced reproductive efficiency of women carrying the Ak(1)2-1 phenotype: this observation could have practical importance in predicting the probability of reproductive success in couples with RSA and in the practice of in vitro fertilization.