Longitudinal 8-Epi-Prostaglandin F2-Alpha and Angiogenic Profile Mediator Evaluation during Pregnancy in Women with Suspected or Confirmed Pre-eclampsia.

Background: In this exploratory study, we aimed to evaluate the dynamics of angiogenic [soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), soluble Endoglin (sEng), and sFlt-1/PlGF, PlGF/sFlt-1, and sEng/PlGF ratios] and oxidative stress [8-epi-prostaglandin F2 alpha (8-epi-PGF2α) and 8-epi-PGF2α/PlGF ratio] mediator levels in women with suspected or confirmed pre-eclampsia (PE) at least two times during pregnancy. We also wanted to identify the possible correlations between 8-epi-PGF2α and angiogenic mediator levels at the time of inclusion of pregnant women. Methods: We included 40 pregnant women with suspected or confirmed PE, with a mean age of 29 years (range between 18 and 41 years) and gestational age between 18 and 28 weeks at inclusion in this study. The Enzyme-Linked Immunosorbent Assay (ELISA) method to measure the levels of serum angiogenic and oxidative stress mediators was used. Results: The evaluation of baseline sFlt-1/PlGF ratios using a cut-off of 38 suggested that 25 pregnant women had a sFlt-1/PlGF ratio of >38 (sFlt-1/PlGF ratio of >38 group) and 15 had a sFlt-1/PlGF ratio of ≤38 (sFlt-1/PlGF ratio of ≤38 group). The increases in sFlt-1/PlGF ratio in the sFlt-1/PlGF ratio of >38 group were caused by both an increase in sFlt-1 (2.04-fold) and a decrease in PlGF levels (2.55-fold). The 8-epi-PGF2α median levels were higher in the sFlt-1/PlGF ratio of >38 group (1.62-fold). During follow-up after pregnancy, we observed that the mean values of sFlt-1 and sEng and the median values of 8-epi-PGF2α and sFlt-1/PlGF, sEng/PlGF, and 8-epi-PGF2α/PlGF ratios increased directly proportional to gestational age for each measurement time until delivery in both groups. For five women who had a sFlt-1/PlGF ratio ≤38 at inclusion, sFlt-1/PlGF ratio was observed to increase to >38 later in pregnancy. We observed that, in the sFlt-1/PlGF ratio >38 group, baseline 8-epi-PGF2α levels better correlated with angiogenic mediator levels. Conclusions: Our study shows that 33.33% of pregnant women evaluated for suspected or confirmed PE with a sFlt-1/PlGF ratio of ≤38 displayed a rise in sFlt-1/PlGF ratio in subsequent weeks. In addition, together with angiogenic mediators, 8-epi-PGF2 α can be utilized as an independent predictor factor to help clinicians identify or predict which pregnant women will develop PE.

Cytogenetic Analysis of Sporadic First-Trimester Miscarriage Specimens Using Karyotyping and QF-PCR: A Retrospective Romanian Cohort Study.

It is well known that first-trimester miscarriages are associated with chromosome abnormalities, with numerical chromosome abnormalities being the ones most commonly detected. Conventional karyotyping is still considered the gold standard in the analysis of products of conception, despite the extended use of molecular genetic techniques. However, conventional karyotyping is a laborious and time-consuming method, with a limited resolution of 5-10 Mb and hampered by maternal cell contamination and culture failure. The aim of our study was to assess the type and frequency of chromosomal abnormalities detected by conventional karyotyping in specimens of sporadic first-trimester miscarriages in a Romanian cohort, using QF-PCR to exclude maternal cell contamination. Long-term cultures were established and standard protocols were applied for cell harvesting, slide preparation, and GTG banding. All samples with 46,XX karyotype were tested for maternal cell contamination by QF-PCR, comparing multiple microsatellite markers in maternal blood with cell culture and tissue samples. Out of the initial 311 specimens collected from patients with sporadic first-trimester miscarriages, a total of 230 samples were successfully analyzed after the exclusion of 81 specimens based on unsuitable sampling, culture failure, or QF-PCR-proven maternal cell contamination. Chromosome abnormalities were detected in 135 cases (58.7%), with the most common type being single autosomal trisomy (71/135-52.6%), followed by monosomy (monosomy X being the only one detected, 24/135-17.8%), and polyploidy (23/135-17.0%). The subgroup analysis based on maternal age showed a statistically significant higher rate of single trisomy for women aged 35 years or older (40.3%) compared to the young maternal age group (26.1%) (p = 0.029). In conclusion, the combination of conventional karyotyping and QF-PCR can lead to an increased chromosome abnormality detection rate in first-trimester miscarriages. Our study provides reliable information for the genetic counseling of patients with first-trimester miscarriages, and further large-scale studies using different genetic techniques are required.

Early Onset Intrauterine Growth Restriction-Data from a Tertiary Care Center in a Middle-Income Country.

Background and Objectives: In this study, we aimed to describe the clinical and ultrasound (US) features and the outcome in a group of patients suspected of or diagnosed with early onset intrauterine growth restriction (IUGR) requiring iatrogenic delivery before 32 weeks, having no structural or genetic fetal anomalies, managed in our unit. A secondary aim was to report the incidence of the condition in the population cared for in our hospital, data on immediate postnatal follow-up in these cases and to highlight the differences required in prenatal and postnatal care. Materials and Methods: We used as single criteria for defining the suspicion of early IUGR the sonographic estimation of fetal weight < p10 using the Hadlock 4 technique at any scan performed before 32 weeks' gestation (WG). We used a cohort of patients having a normal evolution in pregnancy and uneventful vaginal births as controls. Data on pregnancy ultrasound, characteristics and neonatal outcomes were collected and analyzed. We hypothesized that the gestational age (GA) at delivery is related to the severity of the condition. Therefore, we performed a subanalysis in two subgroups, which were divided based on the GA at iatrogenic delivery (between 27+0 WG and 29+6 WG and 30+0−32+0 WG, respectively). Results: The prospective cohort study included 36 pregnancies. We had three cases of intrauterine fetal death (8.3%). The incidence was 1.98% in our population. We confirmed that severe cases (very early diagnosed and delivered) were associated with a higher number of prenatal visits and higher uterine arteries (UtA) pulsatility index (PI) centile in the third trimester­TT (compared with the early diagnosed and delivered). In the very early suspected IUGR subgroup, the newborns required significantly more NICU days and total hospitalization days. Conclusions: Patients with isolated very early and early IUGR­defined as ultrasound (US) estimation of fetal weight < p10 using the Hadlock 4 technique requiring iatrogenic delivery before 32 weeks' gestation­require closer care prenatally and postnatally. These patients represent an economical burden for the health system, needing significantly longer hospitalization intervals, GA at birth and UtA PI centiles being related to it.

The potential value of diagnostic and predictive serum biomarkers for preeclampsia.

BACKGROUND: Preeclampsia (PE), one of the classes of hypertensive pregnancy disorders, is one of the three causes of maternal morbidity and mortality worldwide. The angiogenic and anti-angiogenic factors are useful markers in predicting and diagnosing PE. AIM: This study aims to detect and measure the serum level of some biomarkers [hypoxia-inducible factor-1 subunit alpha (HIF-1A), vascular endothelial growth factor (VEGF), interferon-gamma-inducible protein of 10 kDa (IP-10), matrix metalloproteinase-13 (MMP-13)] in patients with PE and their correlation with the severity of the disease, to find a good predictor for PE. PATIENTS, MATERIALS AND METHODS: This prospective study aims to monitor 48 pregnant women who address obstetric consultation and who present risk factors for PE, and a control group with characteristics similar to the study group. Patients were divided into three groups: Group I (n=15) including normal pregnant (NP) women with blood pressure <140∕90 mmHg, without proteinuria, Group II (n=18) including patients with mild PE (MildPE), Group III (n=15) including patients with severe PE (SeverePE). The analysis of serum biomarkers was based on a quantitative sandwich enzyme-linked immunosorbent assay (ELISA), according to the manufacturer's instructions. RESULTS: In our study, we found that all biomarkers investigated have higher concentrations in the serum of patients with SeverePE and MildPE than those in the control subjects (Group I, NP), the concentrations were increasing along with the disease activity. The means concentrations of HIF-1A, VEGF, IP-10, MMP-13, better correlated with indices in SeverePE group than in MildPE group. We found that VEGF was the biomarker that best correlates with indices that assess the severity of PE. The best separation of patients with SeverePE from those with MildPE can be done with the help of MMP-13 (82% accuracy), followed by VEGF (80.40% accuracy) and the least good detection being done by dosing IP-10. CONCLUSIONS: We can say that, due to high specificity diagnostic accuracy, determination of serum concentrations of MMP-13 and VEGF, could be useful in the diagnosis and distinguishing of patients with SeverePE and may prove useful in the monitoring of the disease course.

The importance of perinatal autopsy. Review of the literature and series of cases.

Perinatal autopsy remains the gold-standard procedure used to establish the fetal, neonatal or infant abnormalities. Progressively, perinatal pathology has become a specialized field with important roles of audit for fetal prenatal diagnostic tools, in parents counseling regarding future pregnancies, in scientific research, for epidemiology of congenital abnormalities and teaching. The differences between prenatal ultrasound and autopsy reports represent a strong argument for the autopsy examination following termination of pregnancy. The reasons for such discrepancies are related to the ultrasonographic or pathological examination conditions, the type of the anomalies, the expertise and availability of the operators. Several facts led to an undesirable increase of refusals from parents to consent to a conventional invasive autopsy: the centralization of pathology services, the poor counseling provided by non-experts in fetal medicine and the clinicians' over-appreciation of the importance of the ultrasound diagnostic investigation. Although non-invasive alternatives have been tested with promising results, conventional autopsy remains the gold standard technique for the prenatal diagnosis audit. We report and analyze several cases of prenatally diagnosed malformed fetuses with different particularities that underline the necessity of perinatal autopsy. We discuss the antenatal findings and management and post-mortem autopsies in the respective pregnancies.

The study of p53 and p16 immunoexpression in serous borderline and malignant ovarian tumors.

The study assessed p53 and p16 immunoexpression in 20 cases of ovarian serous carcinomas and four cases of serous borderline tumors, the results being statistically analyzed in relation to clinicopathological data of the cases. The p53 immunoreaction was observed in 85% of cases, the medium percentage of positivity being 15% for borderline tumors, 45% for low-grade carcinomas and 60% for high-grade carcinomas. The p16 immunoreaction was observed in 75% of cases, the medium percentage of positivity being 30% for borderline tumors, 25% for low-grade carcinomas and 62% for high-grade carcinomas. The p53 and p16 reaction was also identified at the tubal epithelium in cases of invasive carcinomas. Statistical analysis indicated significant differences in p53 expression depending on tumor type and for p53 and p16 expression compared to the degree of tumor differentiation. The study indicated a diffuse immunostain for p53 and p16 in high-grade serous ovarian carcinomas. The presence of "p53 signature" and areas with variable tumor differentiation and reactivity, in the case of high-grade carcinomas, supporting the existence of multiple mechanisms of their occurrence and progression.

Clinical, histopathological and therapeutic considerations in non-neoplastic abnormal uterine bleeding in menopause transition.

With the decline of ovarian hormonal function, from the fifth decade of life, women enter the menopause transition, during which bleeding becomes irregular in duration and time of occurrence. Secondary to ovarian dysfunction, developmental and maturation endometrial anomalies occur, which are clinically translated by abnormal uterine bleeding, which in many cases at this age can be caused by organic lesions (fibroma, polyps, endometritis, endometrial hyperplasia, adenomyosis, etc.). The retrospective study included a total of 256 patients with abnormal uterine bleeding in menopause transition. Statistics showed that the incidence of these types of bleeding increases with age (64.5%) and parity (30.5%), with symptoms consisting mostly in different clinical forms of abnormal uterine bleeding (62.1%), and leiomyomas prevailing at histopathological examination (49.6%). Progesterone replacement therapy was the first therapeutic choice for correcting these types of bleeding. Progesterone therapy is useful not only for therapeutic purposes to amend the bleeding, but also as a precaution against the development of endometrial carcinoma. Progestogens cancel the proliferative and mitogenic effect of estrogens, even when administered in sequential regimen 10-12 days per month.

Clinical and cytopathological aspects in phyllodes tumors of the breast.

The frequency of mesenchymal breast tumors is very low, being represented mostly by tumors with biphasic proliferation (phyllodes tumors) and less by other types of non-epithelial tumors. From clinical point of view, phyllodes tumors (PT) can mimic a breast carcinoma. Therefore, the preoperative diagnosis by cytological examination on material obtained by fine needle aspiration (FNA) is very important for adequate treatment of these tumors. In current study, we assessed clinical aspects of 79 phyllodes tumors regarding patient's age and localization of the tumors. In 17 out of 79 cases, it has been performed FNA within the tumors with further cytological examination on the smears obtained. The median age of the patients was 46.07-year-old, being progressively higher with grade of the tumors with significant values between benign and borderline tumors (p=0.04954) and between benign and malignant ones (p=0.02890). The distinguish on the smears of stromal fragments and naked stromal nuclei with variable grade of atypia regarding the tumoral type, in detriment of epithelial elements have been conclusive for fibroepithelial lesion as cytopathological diagnosis. The preoperative differentiation between a breast phyllodes tumor and a breast carcinoma is extremely important for avoiding of a useless radical surgery for the patient. If the fine needle aspiration was correctly performed, the accuracy of the cytodiagnosis has been 82% in current study.