The Role of Uterine Artery Doppler in the Second and Third Trimesters for Prediction of Preeclampsia and Fetal Growth Restriction Developed as a Consequence of Placental-Mediated Diseases.

Placenta-mediated pregnancy disorders represent a disease that includes preeclampsia (PE) and the birth of small for gestational age (SGA) children, these conditions increase the risk of mortality and morbidity both maternal and fetal/neonatal, in the short and long-term. METHODS: The prospective study included 106 patients in whom ultrasound Doppler scans of uterine artery (UtA) were performed in the 2nd trimester between 20.0-23.6 weeks of gestation and the 3rd trimester between 28.0-32.6 weeks of gestation. RESULTS: In the second trimester, the average of the UtA-PI percentiles was statistically significant (p<0.05) in correlation with PE and SGA, as in the third trimester. Statistically significant (p<0.05) was also the correlation of UtA-PI >95 percentile with the development of PE and SGA. On the other hand, the present notch, in the two trimesters studied, analyzed as a single index, did not present a statistically significant association (p>0.05). CONCLUSIONS: The results of our study showed that UtA-PI Doppler is the best predictor of preeclampsia considering the association of intrauterine growth restriction, as most studies have found.

Intraplacental Villous Artery Doppler can Improve the Ability to Predict Placenta-Mediated Disease.

OBJECTIVE: Evaluation of Intraplacental Villous Artery Doppler (IPVA) as a predictive factor compared to umbilical artery (UA) Doppler in placenta-mediated disease (PMD). METHODS: This prospective study included a group of 106 pregnant women, of which 76 patients constituted the PMD group: preeclampsia (PE) and small for gestational age (SGA), and 30 pregnant women constituted the control group. IPVA and UA Doppler evaluation was performed in 2 pregnancy periods: 20.0-23.6 weeks, and 28.0-32.6 weeks of gestation. RESULTS: From the study of maternal characteristics and risk factors for the presented pathology, we found that no studied risk factor was statistically involved in the evolution toward PMD during pregnancy. In the control group, we noticed a decrease in IPVA PI and RI, along with an increase in gestational age, while in the PMD group, these indices increased. Both in the 2nd and the 3rd trimester, we had a significant statistical difference between the two groups (p<0.001). Regarding the degree of prediction of the changes that occurred at this level, we found a good statistical correlation. A higher degree of positive predictability is noted, for IPVA-PI, but also for UA-PI, but with better sensitivity (72.27%) for UA PI in the 2nd trimester. CONCLUSIONS: We can conclude that both Doppler measurements, IPVA and UA can be used to evaluate and detect pregnancy complications that belong to PMD, preeclampsia, and/or fetal growth restriction.

Prediction of Preterm Birth with Serial Measurements of Ultrasound Markers.

To compare the ability of cervical length (CL), anterior cervical angle (ACA), and cervical consistency index (CCI) to predict premature birth. METHODS: This prospective study involved 85 pregnant women who gave birth prematurely and a control group of 31 pregnant women who gave birth at term. The study was performed in the Obstetrics and Gynecology Clinic of the Municipal Clinical Hospital Filanthropia Craiova between January 1, 2019, and January 1, 2022. Cases were examined using transvaginal ultrasonography (TVU) in the second and third trimesters of pregnancy, and cervical length (CL), Anterior Cervical Angle (ACA), and Cervical Consistency Index (CCI) were measured. RESULTS: The mean value from the three measurements at all three parameters was statistically significant with preterm birth (p<0.05). Cervical length <25mm, was highly significant in the prediction of preterm labor with a sensitivity of 99%, specificity of 61%, positive predictive value (PPV) of 78%, negative predictive value (NPV) of 97 %, and a positive likelihood ratio (LR+) of 2.54 and negative likelihood ratio (LR-) of 0.02. CCI also remains, despite low specificity and PPV values, a potential predictive parameter in the prediction of preterm birth, with a sensitivity of 73%, NPV of 92% and a LR+of 1.32 and LR- of 0.6 also correlated with CL, CCI being more difficult to interpret as an independent predictive parameter. CONCLUSIONS: CL remains the standard parameter for predicting the preterm birth, but in combination with other parameters, the prediction rate can increase significantly.

Analysis of the relationship between placental histopathological aspects of preterm and term birth.

OBJECTIVES: This study aims to establish a correlation between placental histopathological and immunohistochemical (IHC) changes and preterm birth with fetal growth restriction (FGR, formerly called intrauterine growth restriction - IUGR). PATIENTS, MATERIALS, AND METHODS: This prospective study was performed on a group of 30 parturients, with singleton gestation, of which 15 patients gave birth at term, and the other 15 patients gave birth prematurely. After the statistical correlation of the clinical and demographic data with premature birth (PB) and term birth (TB), we performed histological and IHC research on the respective placentae. To observe normal and pathological microscopic placental structures, we used the Hematoxylin-Eosin (HE) and Periodic Acid Schiff-Hematoxylin (PAS-H) classical stainings, but also special immunostaining with anti-cluster of differentiation 34 (CD34) and anti-vascular endothelial growth factor (VEGF) antibodies. RESULTS: We found a statistically significant difference between the TB∕PB categories and the age of the patients, their antepartum weight, the weight of the newborns, and the placenta according to the sex of the newborn. Histological analysis revealed in the case of TB, small areas of perivillous amyloid deposition, with the significant extension of these areas both intravillous and perivillous in the case of PB. Massive intravillous calcifications, syncytial knots, and intravillous vascular thrombosis were also frequently present in PB. With PAS-H staining were highlighted the intra∕extravillous vascular basement membranes, but especially the massive fibrin deposits rich in glycosaminoglycans. By the IHC technique with the anti-CD34 antibody, we noticed the numerical vascular density, higher in the case of TB, but in the case of PB, there were large areas of placental infarction, with a lack of immunostaining in these areas. Through the anti-VEGF antibody, we observed the presence of signal proteins that determined and stimulated the formation of neoformation vessels in the areas affected by the lack of post-infarction placental vascularization. We observed a highly significant difference between placental vascular density between TB∕PB and newborn weight, sex, or placental weight. CONCLUSIONS: Any direct proportional link between the clinical maternal-fetal and histological elements yet studied must be considered. Thus, establishing an antepartum risk group can prevent a poor pregnancy outcome.

Maternal Lipid Profile as a Risk Factor for Gestational Diabetes Mellitus in Obese Women.

As dyslipidemia is frequently associated with gestational diabetes mellitus, the aim of this study was to establish a correlation between the evolution of the maternal lipid profile evaluated in the first and third pregnancy trimester for a series of parameters: triglycerides, cholesterol, high-density lipoprotein cholesterol (HDL-C), blood sugar fasting (BSF), triglyceride-glucose index (TyG index), TG/HDL-C ratio, leptin and the risk of gestational diabetes mellitus occurrence. The results were statistically interpreted, establishing the mean value of the obtained results and the standard deviation. From the studied parameters, only HDL-C and Tyg were statistically significant different in the  first trimester for the two study groups, while in the third trimester statistically significant differences were observed also for triglycerides, blood sugar fasting and the TG/HDL-C ratio.

Doppler Uterine Artery Ultrasound in the Second Trimester of Pregnancy to Predict Adverse Pregnancy Outcomes.

PURPOSE: To determine in uterine artery (UtA) the mean pulsatility index (PI), systolic/diastolic (S/D) ratio and the presence/absence of notch in the second trimester of pregnancy, with normal or abnormal pregnancy outcome. MATERIAL AND METHODS: We performed an analysis of 135 cases with high risk pregnancy in Obstetrics and Gynecology Department of The Municipal Hospital Filantropia, Craiova, between October 2016 and May 2020. The ultrasound evaluation in the second trimester was performed during the second trimester morphology scan, or after this, but up to 24 weeks of pregnancy. RESULTS: The study showed only in the case of early preeclampsia (PE) a statistical significance for mean PI-UtA percentiles in the second trimester. In the other studied categories of pregnancy outcome, even we did not have a statistical significance, we found a specificity of 75% and positive predictive value of 88.89% in late PE. The presence of notch in the second trimester was statistically significant (p value <0.05) in the case of premature birth (PB) and early PE. A positive predictive value of 77.50% we found only in case of late PE. CONCLUSIONS: Our results show that routine Doppler screening of the uterine arteries during the second trimester did not make an accurate prediction of fetal growth restriction, preeclampsia or preterm birth. However, we believe that the present study results prove that this screening may select a population with increased risk of adverse outcome, which would give them the opportunity to benefit from an early intervention.

Relationship between Serum Leptin Values and Abdominal Circumference Assessed in the First Trimester of Pregnancy in Obese Women.

Higher serum leptin values have been correlated with several complications of pregnancy, while the abdominal circumference (AC) is an anthropometric measurement usually used to diagnose abdominal obesity. For this study we compared serum leptin levels between two groups of pregnant women: those with abdominal obesity (AC>88cm) and those without abdominal obesity (AC<88cm), diagnosed at the beginning of pregnancy. Serum leptin levels were obtained through measurements performed between 11-14 and 28-32 weeks of gestation. Higher serum leptin levels were found in the group of pregnant women with abdominal obesity comparing to the group without abdominal obesity, but a positive correlation between abdominal circumference and the leptin values was found only at 11-14 weeks of pregnancy. Our study showed that a simple measurement of AC performed at the beginning of pregnancy may predict the average serum levels of leptin throughout the gestation period. A better understanding of the role of leptin during development is needed to make us able to know how maternal-placental-fetal leptin exchange influence the fetal development.

Can Ultrasound Analysis of the Yolk Sac be a Predictor of Pregnancy Outcome?

The Yolk sac is the first source of transfer between the mother and the embryo, with a nutritional and gas exchange function, vital for the development of the embryo, to which we can add primitive hematopoiesis, the production of stem cells and germ cells. Although normal-term pregnancies with abnormal aspects of the yolk sac have been described, the smaller or larger size of the yolk sac is associated with pregnancy loss. Our study aimed to determine whether the yolk sac size change, determined by measuring diameter (2D ultrasonography) or volume (3D ultrasonography), is independently associated with adverse pregnancy outcomes. The results of the study did not show a statistical significance between 2D and 3D measurements with adverse pregnancy outcomes, noting only an abrupt increase in the diameter and volume of the yolk sac preceding pregnancy loss. However, the evaluation of the yolk sac remains an important element in the ultrasound evaluation of pregnancy in the first trimester.

The Implications of the First Trimester 2d and Volumetric Ultrasound in Pregnancy Outcome.

BACKGROUND: The purpose is to investigate the role of the first trimester ultrasound markers: cown rump lengh (CRL), gestational sac volume (GSV), embryonic volume (EV) and yolk sac volume (YSV) as parameters for outcome. METHODS: Observational clinical study that was carried out in the Obstetrics and Gynecology Clinic. The study included a number of 81 unselected patients evaluated from the first trimester. Patients were evaluated in the first trimester by transvaginal ultrasound and followed up during pregnancy. Correlations between the GSV, EV, YSV and CRL was made for assessing outcome. RESULTS: Our study results show that patients with abnormal early ultrasound parameters had a higher incidence of pregnancy complications. CONCLUSIONS: An early pregnancy evaluation can be a helpful tool in predicting outcome.

The role of mediating factors involved in angiogenesis during implantation.

Angiogenesis is a critical component of normal implantation and placentation and underlines the importance of vascularization in early pregnancy. Differentiated expression of angiogenesis factors in different decision tissues during different stages of implantation, indicates their involvement in the regulation of vascular remodeling and angiogenesis. Disorders in vascular development may play a role in the pathogenesis of recurrent abortions. The success of implantation, placentation and subsequent pregnancy evolution requires coordination of vascular development and adaptations at both sides of the maternal-fetal interface. The human implantation process is a continuous process, which begins with the apposition and attachment of the blastocyst to the apical surface of the luminal endometrial epithelium and continues throughout the first trimester of pregnancy until the extravillous trophoblast invades and remodels maternal vascularization. Numerous regulatory molecules play functional roles in many processes, including preparation of the endometrial stroma (decidualization), epithelium for implantation, control of trophoblastic adhesion and invasion. These regulatory molecules include cytokines, chemokines, and proteases, many of which are expressed by different cell types, having slightly different functions as the implant progresses.

Evaluation of iNOS -2087A>G polymorphism in recurrent pregnancy loss.

BACKGROUND: Due to its role in angiogenesis, the inducible nitric oxide synthase (iNOS) gene promoter polymorphism may have a presumed role in recurrent spontaneous abortions (RSA). It is an intensely studied protein, a biological mediator, a modulator and an effector molecule by implication in numerous physiological processes: vasodilatation, angiogenesis, immunity, tissue remodeling, smooth muscle activity. AIM: Our study aims to investigate a possible association between iNOS -2087A>G (rs2297518) polymorphism and the occurrence of idiopathic recurrent pregnancy loss (RPL). PATIENTS, MATERIALS AND METHODS: In this study, as in the previously published one, 169 women, diagnosed with RPL, in the Clinics of Obstetrics and Gynecology, "Filantropia" Municipal Hospital, Craiova, Romania, were subjected to the analysis, from October 2009 to October 2016. As a control group, we used 145 women. Subjects from both groups were genotyped using specific probes for TaqMan polymerase chain reaction (PCR), allelic discrimination technique. RESULTS: We evaluated in this study a possible association between iNOS -2087A>G (rs2297518) polymorphism and the occurrence of idiopathic RPL. The chi-square test showed no significant association between the presence of this polymorphism and the increased risk to develop RPL. When we performed a comparative analysis of the frequency of genotypes and our statistical data, it was observed that this polymorphism, iNOS -2087A>G (rs2297518), has not been associated with an increased risk of developing RPL. Also, when one genotype was compared with another, we did not obtain any association that would have statistical significance, between the presence of this polymorphism and the increased risk for patients to develop RPL [in dominant - A allele carriers, iNOS 2087 AG+AA vs. GG: odds ratio (OR) 1.31, 95% confidence interval (CI) 0.83-2.07, p=0.24]. Analyzing the overall risk of developing RPL by iNOS 2087 single-nucleotide polymorphism (SNP) genotype frequencies, between controls and RPL patients (which were stratified by number of consecutive PLs), taking into account the number of consecutive pregnancies, the chi-square test showed no association between the presence of this polymorphism and the increased risk for developing RPL in all three subgroups we analyzed (in a dominant model - A allele carriers, iNOS 2087 AG+AA vs. GG: the first subgroup, OR 1.31, 95% CI 0.83-2.07, p=0.24; the second subgroup, OR 1.26, 95% CI 0.76-2.11, p=0.37; the three subgroup, OR 1.4, 95% CI 0.77-2.53, p=0.272). CONCLUSIONS: The iNOS -2087A>G (rs2297518) gene polymorphism does not influence RPL in the study area of Dolj County, Romania.

Determination of VEGFR-2 (KDR) -604A>G polymorphism in recurrent pregnancy loss.

BACKGROUND: Placental angiogenesis and vascular adaptation during pregnancy, along with diminished placental trophoblastic vascular endothelial growth factor immunoreactivity, play an important role in the early stages of human pregnancy, being possible causes of recurrent pregnancy loss (RPL). AIMS: Our focus was directed towards investigating a possible association between vascular endothelial growth factor receptor-2 (kinase insert domain receptor) VEGFR-2 (KDR) -604A>G (rs 2071559) gene polymorphism and RPL in the study area of Dolj County, Romania. PATIENTS, MATERIALS AND METHODS: In this study, 169 women, diagnosed with RPL, were included. They were hospitalized in the Clinics of Obstetrics and Gynecology, "Filantropia" Municipal Hospital, Craiova, during the following period: October 2009-October 2016. The control group consisted of 145 women. All subjects were genotyped by means of allelic discrimination TaqMan polymerase chain reaction assay with specific probes. RESULTS: No statistically significant difference was observed between the RPL patients and the control group, when one genotype was compared to another [in a dominant model, -604 AG+GG vs. AA: odds ratio (OR) 1.71, 95% confidence interval (CI) 0.99-2.96, p=0.051]. While studying the overall risk of RPL by the genotype frequencies of KDR polymorphism between controls and RPL patients, which were stratified according to the number of consecutive pregnancy losses (PLs), the chi-square test showed a significant association between the presence of this polymorphism and the increased risk observed in patients with four or more consecutive PLs, to develop RPL (in a dominant model - G allele carriers, KDR -604 AG+GG vs. AA: OR 1.91, 95% CI 1.03-3.52, p=0.037). These results prove that G allele carriers have an increased risk of RPL about 1.91-fold higher than those with the AA genotype do. Although our results bear limited statistical significance, the study nonetheless represents a step forward in the evaluation of recurrent abortion, which has not yet been explored sufficiently. CONCLUSIONS: VEGFR-2 (KDR) polymorphism does not influence RPL susceptibility in the study area of Dolj County, Romania. Therefore, further studies, which include a larger sample size, are required in order to clarify the role of KDR polymorphism in RPL.

Adenosarcoma of the uterine cervix: positive and differential diagnosis.

Adenosarcoma is considered as being a variety of mixed Müllerian tumor having a small grade of malignity. Present case refers to a perimenopause patient examined for a structure of bleeding endocervical polypoid. Diagnostic evaluation performed after biopsy revealed a cervical leiomyosarcoma followed by operation. The range of occurrence is interesting, having in mind positive and differential diagnosis problems that occurred.

The uterine carcinosarcoma - a case report.

The carcinosarcoma is a malignant mixed müllerian tumor with a highly malignant, biphasic tumor consisting of both epithelial and mesenchymal components. The presented case refers to a patient in climax with a vaginal bleeding. The Doppler echography highlights a polypoid mass, which prolapses in the cervical channel. The histopathological and immunohistochemical analysis of the surgically resected piece allowed the carcinosarcoma diagnosis. The uterine carcinosarcoma's incidence is rare, that is why this case is interesting taking in consideration the biphasic pattern of the tumor.

The Importance of the Correlation between the Ultrasonographic Evaluation of Endometrium and Histopathological Findings in Patients with Endometrial Hyperplasia and Carcinoma.

PURPOSE: The aim of this study was to estimate how ultrasonographic evaluation of endometrium and histopathological findings are correlated in a group of premenopausal and postmenopausal women. MATERIAL AND METHODS: I have studied 106 premenopausal and postmenopausal women who underwent endometrial biopsy based on results of transvaginal ultrasonography. RESULTS: Mean age of patients was 52.29±8.14 years. Postmenopausal status <10 years was common in 20 patients (18.86%), postmenopausal status >10 years was common in 21 patients (19.81%), and premenopausal status in 65 patients (61.32%). Transvaginal sonography reported EH in 97 cases (91.50%) and EH was confirmed by pathology in 88 cases (83.01%). CONCLUSION: Endometrial thickness was correlated with histopathological diagnosis much better in postmenopausal women.

Immunohistochemical reaction of the glandular epithelium in endometrial hyperplasia compared to endometrial carcinoma.

The histopathological and immunohistochemical diagnosis of endometrial biopsies is used for estimating the risk of progression in endometrial hyperplastic lesions in carcinoma and for guiding the clinical management. The objective of this study was to evaluate the immunohistochemical expression of the estrogen receptor (ER) and progesterone receptor (PR), p14, p53, phosphatase and tensin homolog (PTEN), Ki67, in patients with endometrial hyperplasia (EH) with/without atypia versus endometrioid endometrial carcinoma type 1. After the histopathological determining of the lesion type at endometrial level, the cases were studied using immunohistochemical methods, namely by the use of an antibody panel. The immunohistochemical staining of PR was nuclearly and cytoplasmatically positive in EH with/without atypia and cytoplasmatically negative in endometrioid carcinoma, and in ER, the immunohistochemical staining was cytoplasmatically negative in the forms of EH without atypia and positive in various stages of intensity in the rest of the cases. The immunohistochemical staining of p14 was moderately expressed in the endometrioid carcinoma and negative in EH without atypia at nuclear level, and at cytoplasm level, it generally had a positive expression. In our study, the nuclear and cytoplasmic study of immunoxpression p53, both in hyperplastic lesions and in the endometroid endometrial carcinoma, was negative, similar to the immunohistochemical expression of PTEN. At nuclear level, the immunohistochemical staining of Ki67 was positive in EH with atypia and in endometrioid endometrial carcinoma, while at cytoplasm level, it was positive only in endometrioid endometrial carcinoma. The nuclear and cytoplasmic study of this immunohistochemical marker panel shows a different reactivity in EH with÷without atypia and endometrioid endometrial carcinoma.

Postmenopausal osteoporosis - clinical, biological and histopathological aspects.

Osteoporosis is one of the most common disorders in postmenopausal women, affecting the quality of life and increasing the risk for fractures in minor traumas. Changes in the bone microarchitecture causes static changes in the body and affects motility. In this study, we analyzed two groups of women, one with physiological menopause and one with surgically induced menopause. The diagnosis of osteoporosis was suspected based on the clinical symptoms and confirmed by assessing bone mineral density by the dual-energy X-ray absorptiometry (DEXA). Comparing some clinical and biological aspects there was noted that a much higher percentage of women with surgically induced menopause exhibited increases in body mass index, changes in serum lipids, cholesterol, triglycerides, blood glucose, serum calcium, magnesemia and osteocalcin. In contrast, no significant differences were observed in the histopathological aspects of bone tissue examined from these two groups. In all patients, there was identified a significant reduction in the number of osteocytes and osteoblasts, the expansion of haversian channels, reducing the number of trabecular bone in the cancellous bone with wide areola cavities often full of adipose tissue, non-homogenous demineralization of both the compact bone and the cancellous bone, atrophy and even absence of the endosteal, and the presence of multiple microfractures. Our study showed that early surgically induced menopause more intensely alters the lipid, carbohydrate and mineral metabolism, thus favoring the onset of osteoporosis.

Corpuscular Haemolytic Anaemias - Lepore Haemoglobinopathy.

Haemoglobinopathies are hereditary conditions in which the fundamental lesion affects the synthesis rate or the structure of the globin in normal hemoglobin. The synthesis of the polypeptide chains in globin is genetically coded. Clinically, haemoglobinopathies manifest most commonly in the form of hemolytic anemia and, more rarely, cyanosis and polyglobulia. They differ from "acquired haemoglobinopathies", such as methemoglobinemia, in which hemoglobin is usually compromised due to the action of toxic substances. The clinical aspects are in close relationship to the nature and level of the structural anomaly of the Hb molecule. The heterozygous form of the Lepore syndrome is hematologically characterized by a similar pattern to minor ß-thalassemia and electrophoretically by abnormal Hb D fractions at a rate of 5-10% and a decreased percentage of HbA. In homozygous forms, Lepore Hb represents 10-20% on electrophoresis, the rest consisting of HbF; HbA and HbA2 are completely absent. From a clinical point of view, Hb Lepore heterozygotes are similar to those with minor ß - thalassemia.

The importance of immunohistochemical evaluation of the vascular changes from the decidua and placenta in recurrent pregnancy loss.

The angiogenesis is a complex process, incompletely understood, regulated by various stimulating and inhibiting angiogenic factors. In the present study, we proposed to evaluate the angiogenic changes that occur in the cases with recurrent pregnancy loss comparing with a control group represented by women with requested abortion. The evaluation of the changes in the vascular bed was made by immunohistochemical methods, evaluating the answer of the curettage products to the mouse anti-human CD31 and CD34 monoclonal antibodies immunolabeling. The endothelial cells reaction to the CD31 antibody was different, very intense in the normal or slightly congestive vessels. The endothelial cells from the strongly congestive vessels had a light and scratchy reaction. We found intense positive reactions in the control group for CD34 in the vessels from the villous axis and also in the vessels from the spongious decidua. In the study group, we found light positive reaction in the vessels from the decidua situated in the proximity of the necrotic areas; we found a light positive reaction also in the vessels and mesenchymal fibroblasts from some chorial villous axis.

The contribution and the importance of modern ultrasound techniques in the diagnosis of major structural abnormalities in the first trimester - case reports.

We describe a series of cases where modern ultrasound (US) techniques diagnosed major structural abnormalities of the fetus in the first trimester (FT), unapparent when using the basic protocol of US investigation. In some cases, major structural abnormalities can be revealed in the FT scan solely to specialized personnel. Perhaps early screening should be confined in specialized centers, because congenital abnormalities detailed diagnostic has a huge impact in counseling the couple and also in prenatal advice of future pregnancies.