Genetic Counseling and Management: The First Study to Report NIPT Findings in a Romanian Population.

Background and Objectives: Non-invasive prenatal testing (NIPT) has been confirmed as the most accurate screening test for trisomies 21, 18, 13, sex chromosomes aneuploidies and several microdeletions. This study aimed to assess the accuracy of cell free DNA testing based on low-level whole-genome sequencing to screen for these chromosomal abnormalities and to evaluate the clinical performance of NIPT. Materials and Methods: 380 consecutive cases from a single genetic center, from Western Romania were included in this retrospective study. Cell-free nucleic acid extraction from maternal blood, DNA sequencing and analysis of sequenced regions were performed by BGI Hong Kong and Invitae USA to determine the risk of specific fetal chromosomal abnormalities. In high-risk cases the results were checked by direct analysis of fetal cells obtained by invasive methods: 6 chorionic villus sampling and 10 amniocenteses followed by combinations of QF-PCR, karyotyping and aCGH. Results: NIPT results indicated low risk in 95.76% of cases and high risk in 4.23%. Seven aneuploidies and one microdeletion were confirmed, the other results were found to be a false-positive. A gestational age of up to 22 weeks had no influence on fetal fraction. There were no significant differences in fetal fraction across the high and low risk groups. Conclusions: This is the first study in Romania to report the NIPT results. The confirmation rate was higher for autosomal aneuploidies compared to sex chromosome aneuploidies and microdeletions. All cases at risk for trisomy 21 were confirmed. Only one large fetal microdeletion detected by NIPT has been confirmed. False positive NIPT results, not confirmed by invasive methods, led to the decision to continue the pregnancy. The main limitation of the study is the small number of patients included. NIPT can be used as a screening method for all pregnancies, but in high-risk cases, an invasive confirmation test was performed.

Analysis of the Impact of Comorbidities on Endometrial Lesions Using the Charlson Comorbidity Index in Western Romania.

Background and Objectives: This retrospective study aimed to identify the main comorbidities found in gynecological patients hospitalized for endometrial lesions and to analyze the relationships between these comorbidities and each type of endometrial lesion. The Charlson comorbidity index (CCI) was calculated, thus assessing the patient's probability of survival in relation to the underlying disease and the existing comorbidities. Materials and Methods: During 2015-2019, 594 cases hospitalized for vaginal bleeding outside of pregnancy were included in the research. For all cases, the frequency of comorbidities was calculated, applying the Cox proportional hazard model, considering the hospitalizations (from the following year after the first outpatient or hospital assessment) as a dependent variable; age and comorbidities were considered as independent variables. Results: Analysis of variance (ANOVA) for mean age of patients enrolled after diagnosis and multiple comparisons (via the Tukey post-hoc test) indicate significant differences (p < 0.05) between the average age for endometrial cancer (EC) and that for the typical endometrial hyperplasia or other diagnoses. The most common comorbidities were hypertension (62.28%), obesity (35.01%), and diabetes (22.89%), followed by cardiovascular disease. An intensely negative correlation (r = -0.715281634) was obtained between the percentage values of comorbidities present in EC and other endometrial lesions. The lowest chances of survival were calculated for 88 (14.81% of the total) patients over 50 years (the probability of survival in the next 10 years being between 0 and 21%). The chances of survival at 10 years are moderately negatively correlated with age (sample size = 594, r = -0.6706, p < 0.0001, 95% confidence interval (CI) for r having values from -0.7126 to -0.6238) and strongly negatively correlated with the CCI (r = -0.9359, p < 0.0001, 95% CI for r being in the range -0.9452 to -0.9251). Conclusions: Using CCI in endometrial lesions is necessary to compare the estimated risk of EC mortality with other medical conditions.

Female Romanian university students' attitudes and perceptions about contraception and motherhood.

OBJECTIVES: The aim of our study was to investigate the knowledge, perceptions and attitudes of female Romanian university students, as possible future opinion leaders, about contraception and motherhood, by assessing their level of contraceptive use, opinions and knowledge with regard to combined oral contraceptives (COCs). METHODS: A knowledge, attitudes and practice questionnaire was conducted among 1105 female university students aged 19 to 30 years. The participants were recruited from six faculties at universities in Iasi and Arad, Romania. The study protocol was approved by the university ethics committees. Statistical analyses included percentages, χ(2) tests and Fisher's exact test. RESULTS: Two-thirds of respondents were in a relationship or married. Average age at first sexual intercourse was 18.6 years. Two out of three (69%) students identified themselves as sexually active. The same percentage showed a positive attitude towards contraception and stated that they used it. The most commonly used contraceptive methods were condoms, COCs and withdrawal. The students' perceptions of the benefits and adverse effects of COCs were analysed. Half of the students had heard about extended COC regimens, but only 24% showed interest in using them regularly. A large proportion of pharmacy and non-medical students appeared to have poor knowledge about contraception and reproductive health, which generated misperceptions and negative attitudes. Two-thirds of the participants considered 25 to 29 years to be the optimal age for starting a family, and 85.5% intended to have children in the future. CONCLUSIONS: Medical students, but not pharmacy students, showed higher levels of knowledge. Improvement of students' knowledge, perceptions and attitudes towards general contraceptive use, COCs and childbearing is needed. Evidence-based information is required to address poor knowledge about the physiology of reproduction, misconceptions relating to COCs, and the possibility of menstrual suppression using hormonal contraceptive methods. Compulsory reproductive health education for students is desirable.

The Correlation of the IETA Ultrasound Score with the Histopathology Results for Women with Abnormal Bleeding in Western Romania.

In the early differential diagnosis of endometrial cancer (EC), decisive and mandatory histological aspects are considered, in addition to obvious clinical manifestations. In addition, sonographic aspects are characteristic in relation to the stage, degree, and histological types of identified cancer. This bi-center retrospective observational study included 594 women with abnormal uterine bleeding outside pregnancy, for which a biopsy was performed in the Obstetrics and Gynecology Departments of the Emergency County Hospitals of Arad and Timis Counties, Romania, between 2015 and 2019. Most of the cases were represented by EC or endometrial hyperplasia (EH). Of the 594 cases, 25.5% (n = 153) were EC at women aged between 41 and 85 years. High International Endometrial Tumor Analysis (IETA) scores (3, 4) were associated with a relative risk of 2.9335 compared with other endometrial lesions (95% CI 2.3046 to 3.734, p < 0.0001, NNT 1.805). Histological aspects and pelvic ultrasound using IETA scores represent valuable noninvasive assets in diagnosing and differentiating endometrial cancer from benign uterine pathology.

Defensive caesarean section: A reality and a recommended health care improvement for Romanian obstetrics.

RATIONALE: Defensive caesarean section (CS) has become one of the most common medical procedure worldwide. Additionally, performing CS in accordance with the patient's choice is an appropriate professional practice. AIMS AND OBJECTIVE: This paper reports a prospective, observational, multicenter study to quantify the use of this type of practice that is performed by obstetricians to avoid medico-legal complaints and decrease the frequency of malpractice litigations. METHODS: We interviewed 73 obstetricians from three distinct units of obstetrics and gynaecology, to assess their opinion regarding defensive caesarean delivery and caesarean delivery performed upon maternal request. We conducted an opinion-based survey using questionnaires based on nine, close-ended questions. RESULTS: Out of 73 respondents, 51 (69.9%) stated that they perform defensive CS; 63 (86.3%) declared that their choice of birth delivery is influenced by the risk of being accused of malpractice; 60 (82.2%) indicated that it is normal for the patient to be able to decide on the type of delivery; and 63 (86.3%) declared that they consult their patients regarding their delivery preferences. We found statistically significant differences between the respondents who declare that they perform defensive CS (69.9%) and those who said that they are influenced by the risk of malpractice when they choose the method of delivery for their patients (86.3%) (P < .001; McNemar Test). CONCLUSIONS: The results of our study indicate that defensive caesarean section is a widespread practice among obstetrics practitioners in Romania.

The Situation of Cervical Cancers in the Context of Female Genital Cancer Clustering and Burden of Disease in Arad County, Romania.

Romania has the highest incidence of cervical cancer morbidity and mortality in Europe. This study identifies the major clusters for genital cancers, observes the features of genital and cervical cancer, and determines the extent to which cancer is a contributor to total Disability-Adjusted Life Year (DALY). Spatial analysis used Besag and Newell's method for genital cancer distribution, prevalence considered Arad County patients records (2008⁻2017), and DALY was determined according to WHO methodology and GLOBOCAN 2013 data. Diagnosis was established by histopathological examination of diagnostic biopsies or tissues obtained by surgical procedures, followed by clinical staging. 1695 women were recorded with genital cancer. Of these, 14.9% of lesions were in situ (n = 252) and 74.20% of cases were recorded in stage III or IV (n = 1258) (p < 0.0001). Over 90% of cervical cancers were squamous cell carcinomas (n = 728), 33.76% of endometrial cancers were adenocarcinomas in situ (n = 131), 32.42% of ovarian cancers were serous adenocarcinomas (n = 131), and 70.58% of vulvar cancers were squamous cell carcinomas (n = 48) (p < 0.0001). DALY/1000 was 67.2 for genital cancers and 33 for cervical cancers. From the point of view of Romanian women, cervical cancer remains one of the major problems that need to be dealt with and access to optimal treatment proves to be extremely limited.

A rare case of synchronous ovarian tumors: clinical case report and literature review.

Epithelial ovarian carcinoma makes up 90-95% of all ovarian malignancies, taking into account also low-malignant-potential tumors. The Krukenberg tumor is a rare metastatic adenocarcinoma (ADK) in the ovary, representing 1-2% of ovarian tumors. Multiple primary malignant neoplasms may exist when more than one cancerous tumor is diagnosed in the same or a different organ. The incidence of multiple primary cancers among malignancies is between 2.4% to 8%. The aim of this paper is to report the case of a 47-year-old patient with two synchronous malignant tumors involving both ovaries, one diagnosed as primary papillary serous cystadenocarcinoma and the other one diagnosed as ovarian metastasis (Krukenberg tumor) of a synchronous colorectal ADK, and the complex diagnostic and therapeutic challenges that such a rare case poses. Histopathological (HP) examination and especially the immunohistochemical analysis had a determining role in differentiating between an ovarian primary tumor and a metastasis from a gastrointestinal tract cancer. The tumors examination for somatic mutations of Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) genes was performed in order to individualize the chemotherapic treatment in this difficult case. The conclusion of this case is that, although synchronous multiple primary cancers in a young patient are a rare condition, this situation should be taken into account in the differential diagnosis when we encounter clinical and HP diagnostic challenges.

De novo unbalanced translocation t(15;22)(q26.2;q12) with velo-cardio-facial syndrome: A case report and review of the literature.

The present study reports the case of a 3-h old male with a de novo unbalanced t(15;22) translocation and velo-cardio-facial syndrome (VCFS), with other abnormalities. The manifestations of the condition observed in the patient included cleft palate with feeding difficulties, respiratory infection, dysmorphic face with almond-shaped eyes, a long and wide nose, small and low-set ears, tetralogy of Fallot, cryptorchidism and varus equinus. Standard lymphocyte cytogenetic analysis using G-banding demonstrated a 45,XY,-22,der (15),t(15;22)(q26.2;q12) karyotype. Fluorescent in situ hybridization with DiGeorge/VCFS TUPLE 1 confirmed 22q11 deletions. These cytogenetic aspects appear to be rare in the etiology of VCFS, as >1% of all 22q11 deletions are the result of an unbalanced translocation, which involves chromosomes 22 and another chromosome. To the best of our knowledge, this is the second reported case where the clinical features associated with VCFS are combined with an unbalanced (15;22) translocation involving the critical 22q11.2 region.

Effects of the Hormone Replacement Therapy and of Soy Isoflavones on Bone Resorption in Postmenopause.

Postmenopausal osteoporosis is the most common form of osteoporosis and one of the major public health problems in developed countries. The prevalence of this condition, associated with the physiological stage of menopause, is continuously increasing. This study evaluated the effectiveness of soy isoflavones as compared to hormone replacement therapy (HRT) in low doses, on the prevention of postmenopausal osteoporosis, by determining bone mineral density (BMD) and urinary deoxypyridinoline (D-pyr) in physiological postmenopausal women. The study was conducted over a period of 12 months, on three parallel groups, which included a total of 325 postmenopausal women (HRT group: n = 95; phytoestrogens group: n = 124; control group: n = 106). At the one-year evaluation, we observed T-score normalization in a small number of cases (5.26%, 2.42% and 0.00%, respectively). The average values of D-Pyr decreased by 11.38% in the group treated with phytoestrogens (p < 0.05) and by 15.32% in the group that followed HRT (p < 0.05); it increased by 4.38% in the control group (p > 0.05). Both therapies have beneficial effects on bone metabolism, leading to a significant decrease in the evolution of bone resorption and there are no major differences between the efficacy of HRT and phytoestrogens in terms of the effects on BMD and bone resorption.

Somatic-vegetative Symptoms Evolution in Postmenopausal Women Treated with Phytoestrogens and Hormone Replacement Therapy.

BACKGROUND: The purpose of this study was to compare the effects of the phytoestrogens in relieving and/or suppressing the specific somatic-vegetative symptoms of menopause with those of the hormone therapy, administered in small doses. METHODS: The study was conducted in the County Clinical Emergency Hospital Oradea - Obstetric-Gynecological Ambulatory, and in private obstetrics-gynecology cabinets from Bihor County (NW Romania), from November 2011 to January 2014. Overall, 325 patients clinically diagnosed with specific postmenopausal symptomatology and not previously treated with phytoestrogens or hormone replacement therapy (HRT), were divided into 3 groups. Symptom assessment was performed with a standardized questionnaire named Menopause Rating Scale (MRS) in three phases: beginning of the treatment, after six months, and after one year. The administered doses for three different groups were as follows: 1 mg estradiol and 0.5 mg norethisterone acetate (NETA) p.o. daily (i.e. for the HRT group); 40 mg of isoflavones p.o. daily - i.e. 2 capsules of 40% standardized extract containing 20 mg of pure isoflavones: Genistein, Daidzein, and Glycitein (i.e. for the group with phytoestrogens); and no trreatment for the control group. RESULTS: The evolution of the somatic-vegetative symptoms was better in both groups treated either with phytoestrogens or HRT (P<0.001) as opposed to the higher percentage of patients with stationary symptoms in the control group (i.e. 37.74% for control group, 16.13% for the group treated with phytoestrogens, respectively 18.95% for the group treated with HRT). CONCLUSION: Twelve months treatment study is a favorable evidence for the use of soy derived phytoestrogens in the treatment of somatic-vegetative symptoms at postmenopausal women.

Uterine Artery Doppler Flow Indices in Pregnant Women During the 11 Weeks + 0 Days and 13 Weeks + 6 Days Gestational Ages: a Study of 168 Patients.

OBJECTIVES: Uterine artery Doppler flow studies during the 11th and 14th week of pregnancy are important in the prediction of preeclampsia and intrauterine growth restriction in pregnant women as well as in the prevention thereof. METHODS: Our study on Doppler flow indices of the uterine arteries involved 168 patients examined in our clinic, with pregnancies ranging from 11 weeks + 0 days to 13 weeks + 6 days. RESULTS: There were 72 patients from 11 weeks + 0 days to 11 weeks + 6 days (42.86%), 43 from 12 weeks + 0 days to 12 weeks + 6 days (25.60%), and 53 from 13 weeks + 0 days to 13 weeks + 6 days (31.55%). The mean values of the Doppler indices were PI 1.75±0.79, 1.88± 0.81, 1.71±0.81, and 1.58±0.72 and RI 0.72±0.14, 0.75±0.14, 0.71±0.14, and 0.70±0.14 for the entire group and for the three intervals, respectively. There were 71 (42.26%), 33 (19.64%, with 18 cases or 54.55% on the right side), and 64 (38.10%) patients with bilateral, unilateral and absent uterine artery notching, respectively. The mean Doppler indices for the three aforementioned groups were 2.18±0.79, 1.63±0.72, and 1.33±0.57 for the PI, and 0.79±0.11, 0.71±0.14, and 0.66±0.14 for the RI, respectively. The indices for the 175 arteries with and 161 without notching, taken separately, in all patients, as well as for the uterine arteries with and without notching in patients with unilateral notching only were 2.16±0.76, 1.30±0.54, 2.08±0.66, and 1.17±0.43 for the PI, and 0.79±0.11, 0.65±0.14, 0.79±0.11, and 0.63±0.12 for the RI, respectively. CONCLUSIONS: The mean uterine artery PI and RI decrease from 11 weeks + 0 days-11 weeks + 6 days to 13 weeks + 0 days-13 weeks + 6 days. They also decrease from patients with bilateral uterine artery notching to those without notching. The frequency of uterine artery notching decreases with increasing gestational age. Our results are similar to those in literature.

Synchronous bilateral primary ovarian carcinoma - case presentation.

Bilateral synchronous primary ovarian carcinoma, histopathologically identical or different is a rare entity encountered in clinical practice. We present the case of a 38-year-old patient who is admitted with the presence of a massive pelvic abdominal tumor formation of 45÷35÷25 cm occupying the lower pelvic and upper abdominal floor, reaching halfway distance between the umbilicus and sternum and lateral bilaterally in the two abdominal flanks until iliac wing. The mixed transabdominal÷transvaginal ultrasound and computed tomography (CT), establish the diagnosis of bilateral ovarian tumor. The CA-125 level is 1822 IU÷mL. The exploratory laparotomy identifies two distinct bilateral ovarian tumors, ascites liquid and pelvic and lumbo-aortic lymphadenopathy, thus the surgery involves hysterectomy with bilateral ovariectomy, pelvic and paraaortic lymphadenectomy and omentectomy. Histopathological and immunohistochemistry (IHC) diagnosis highlights a well-differentiated serous carcinoma on the left ovary and right ovary. The six-month check after surgery as well as the one-year check showed the efficiency of postsurgery chemotherapy and did not signal the presence of relapses. The particularity of this case lies in the presence of bilateral synchronous primary ovarian carcinoma, histopathologically and IHC indicated serous carcinoma present with a difficult differential diagnosis including clear cell carcinoma at a young patient.

Improvements in Cesarean Section Techniques: Arad's Obstetrics Department Experience on Adapting the Vejnovic Cesarean Section Technique.

OBJECTIVES: Cesarean section has become recently the first choice for delivery in many clinics in Romania and worldwide. The purpose of our study is to assess the benefits of introducing the adapted Vejnovic uterine suture technique into daily practice. MATERIAL AND METHODS: A total of 1703 out of the 1776 cesarean section performed in the period January, 2012 - March, 2013 in the Obstetric Department of the Emergency Clinical County Hospital of Arad were retrospectively analyzed based on the cesarean section registries, birth registries and patient's personal medical records. We compared results between the group of patients undergoing adapted Vejnovic cesarean section technique and the group of patients operated in a classic manner. OUTCOMES: The cesarean section rate in the studied period was 56.48%. Adapted Vejnovic cesarean section technique was performed in 548 cases (30.86% of the cases), furthermore in the last 3 months studied it reached 57.27%. Mean APGAR score was better in the adapted Vejnovic cesarean section group (8.43) compared with the reference group (8.34). No significant differences were seen between the two groups regarding maternal age, gestation, weeks of gestation, newborn weight, anesthesia and indications for cesarean section. Exteriorizing the uterus helped the incidental diagnosis of 35 uterine myoma, 22 adnexal masses and 13 uterine malformations. CONCLUSION: In a society with a constant growth of cesarean rate, the adapted Vejnovic cesarean section technique is becoming popular amongst clinicians for its advantages, but further studies need to be developed for its standardization.

Cervical intraepithelial neoplasia in the "dr. Salvator vuia" clinical obstetrics and gynecology hospital - arad during the 2000-2009 period.

OBJECTIVES: This study intends to analyze some statistical data concerning Cervical Intraepithelial Neoplasia diagnosed in our hospital. MATERIAL AND METHODS: Our study concerning the incidence of Cervical Intraepithelial Neoplasia (CIN) covers the 2000-2009 time-span, the data being collected from the Histopathology Exams (HPE) registers. RESULTS: During this period, CIN lesions were discovered in 1256 cases and Cervical Intraglandular Dysplasia (CIGD) in 53 cases. CIN I, CIN II and CIN III lesions represented 65.92%(828 cases), 19.67% (247 cases), and 14.41% (181 cases) of the total CIN cases, respectively. There were 26 cases combined with cervical carcinoma (2.07% of all CIN cases, 3.56% of the 731 cervical cancer cases). The mean patients' age was 44.65± 9.83 years for all cervical dysplasia cases, 44.58± 9.75 years for all CIN cases, 43.81±9.22, 46.50±10.17, and 45.46±11.05 years for CIN I, CIN II, and CIN III, respectively, and 46.45 ± 11.63 years for CIGD. The t-test revealed the following significant differences: all cases versus CIN I (p<0.05) and CIN II (p<0.01), CIGD versus CIN I (p<0.05), all cases versus CIN II (p<0.01), CIN I versus CIN II (p<0.0001) and versus CIN III (p<0.05). The mean age of the 731 cervical cancer cases diagnosed in our hospital during that same period was 52.94±12.96 years,and it was statistically significantly different from the mean ages of patients with CIN I, II and III (p <0.00000001) and with CIGD (p<0.0005). CONCLUSIONS: Early detection of CIN is of utmost importance for preventing cervical cancer, a serious and frequent health problem in Romania.

Gynecological Cancer Age Groups at the "Dr. Salvator Vuia" Clinical Obstetrics and Gynecology Hospital during the 2000-2009 Period.

OBJECTIVES: The purpose of this study is to statistically compare the mean ages of the patients with gynecologic cancer in our hospital during the 2000-2009 interval. MATERIAL AND METHODS: The data was collected from the Histopathology Exams (HPE) registers. RESULTS: Gynecologic cancer was discovered in 1244 cases: 731 cervical cancers, 392 uterine cancers, 82 ovarian cancers, 31 vulvar cancers and eight vaginal cancers.The mean ages were 52.94±12.96 years for cervical cancer (age range 22-87 years), 61.71±9.06 years for uterine cancer (age range 38-85 years), 51.46±14.28 years for ovarian cancer (age range 18-77 years), and 65.90±9.65 years for vulvar cancer (age range 39-81 years).After performing Student's test, the statistically significant differences were: cervical vs uterine (p<0.000001), cervical vs vulvar (<0.000001), uterine vs ovarian (<0.000001), uterine vs vulvar (<0.05), and ovarian vs vulvar (p=0.000001). Cervical and ovarian cancer mean ages were not significantly different (p=0.33). CONCLUSIONS: The mean ages of the patients from the groups with five gynecological cancer types from our study are similar to those in literature. Existing screening measures must be applied and new ones must be implemented in order to reduce the burden of gynaecological cancers.