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.

Fetal-maternal incompatibility in the Rh system. Rh isoimmunization associated with hereditary spherocytosis: case presentation and review of the literature.

Next to A and B antigens, agglutinogen D exhibits the highest immunogenicity. Following the transfusion of D-positive red blood cells (RBCs), almost 80% of D-negative recipients develop anti-D antibodies (Abs). Subsequently, anti-D immunization further promotes the synthesis of Abs towards other blood group antigens in or outside the Rh system. The D antigen is also involved in 95% of cases of hemolytic disease of the newborn. Transfusions, hemotherapy, grafts, and obstetric history (abortions, ectopic pregnancy, births) are all risk factors for Rh isoimmunization. In the case of ABO compatibility between mother and fetus, Rh-positive fetal RBCs that have reached the maternal bloodstream are not destroyed by group agglutinins, and Rh antigenic sites are not hidden by the maternal immune system. But a Rh-negative mother with a homozygous Rh-positive husband will certainly have a Rh-positive fetus. As it has an irreversible evolution, the Rh isoimmunization once installed cannot be influenced in the sense of decreasing the Ab titer, therefore, injectable globulin has no effect. A particular case was that of a newborn with Rh system incompatibility associated with hereditary spherocytosis The clinical balance at birth reflects the severe jaundice of the female newborn of 3140 g, gestational age 38∕39 weeks, extracted by lower-segment transverse Caesarean section, with a double loop nuchal cord, Apgar score 8. Because the jaundice was severe and atypical (face and upper chest), we considered the possibility of coexistence of hemolytic disease of the newborn by Rh blood group incompatibility associated with hereditary spherocytosis, as it turned out to be true and mentioned. Changes in genes encoding proteins in the structure of the RBC membrane have amplified hemolysis induced by maternal-fetal isoimmunization in the Rh system. Massive hemolysis accentuated by congenital spherocytosis, confirmed later, imposed blood transfusion and dynamic monitoring.

Impact of COVID-19 on fertility and assisted reproductive technology (ART): a systematic review.

The appearance of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major obstacle for the performing of current medical activities throughout the world. COVID-19 has affected humanity in many ways, thus causing a great medical, social, economic, and political instability. The aim of this study was to make an analysis of the scientific data obtained by so far to highlight the impact that COVID-19 has had on fertility and assisted reproductive technology (ART). Infection with SARS-CoV-2 alters the normal immune response by local and systemic damage to tissues and organs. After the virus enters the body, the first lesions are produced in the respiratory tract. Extrapulmonary lesions specific to COVID-19 include acute renal lesions/acute kidney damage, hepatocellular lesions, neurological diseases, myocardial dysfunction and arrhythmia, gastrointestinal diseases but also genital impairment. The possible impairment of the male reproductive system is because angiotensin-converting enzyme 2 (ACE2) receptors are in an increased number in the testes, seminiferous duct cells, spermatogonia, Leydig cells and Sertoli cells. Many published studies to date have pointed out that COVID-19 could also affect female fertility and disrupt the functions of the female reproductive system. The theory that this virus can also be transmitted sexually and can cause infertility or testicular damage is supported by the fact that the virus can be isolated in the semen of COVID-19 patients but only during the disease. Choosing the best method of treating infertility during the COVID-19 pandemic is multifactorial, but the risk of infection and compliance with specific ART hygiene protocols must always be considered. Currently, there is no scientific basis regarding the fact that the COVID-19 vaccination would influence fertility.

Clinical and morphopathological assay in vulvovaginal candidiasis.

Candida vulvovaginitis is characterized by the appearance of inflammatory changes in the vaginal and vulvar epithelium secondary to infection with Candida species. The purpose of this study was to analyze and compare the clinical, microbiological, and histopathological aspects of pregnant and non-pregnant patients, symptomatic or asymptomatic in the case of candida vaginitis and to correlate the microscopic aspects with the symptoms before applying the local treatment with Nystatin. The study presents a retrospective analysis of the management of vaginitis in 166 pregnant or non-pregnant patients during 2021-2022. We observed the structure of the Malpighian squamous epithelium without keratinization present on the vaginal mucosa and the structure of the subepithelial connective tissue, which shows increased numerical values of inflammatory and vascular cellularity in the case of candida vaginitis symptomatic compared to asymptomatic ones. We noticed also in the microscopic study that in cases of asymptomatic patients before treatment, the number of inflammatory cells and blood vessels situated immediately under the epithelium was significantly lower compared to their number in symptomatic patients before treatment. Analyzing the results obtained after the administration of the treatment proposed by us, we can say that local Nystatin treatment is beneficial and safe for pregnant and non-pregnant patients and is a good alternative for patients with recurrent vulvovaginal candidiasis.

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 procoagulant status. Hypercoagulability as a risk factor of primary and secondary infertility.

Thrombophilia is a disorder that makes patients susceptible to intravascular thrombosis that may increase the risk of developing a pregnancy on a known pathology. The female patient diagnosed with hypoplastic uterus and hereditary thrombophilia had a favorable evolution under properly administered anticoagulant treatment. The homozygous status for the C677T mutation may lead to an increase in plasma homocysteine levels, especially in pregnant women, being an associated risk factor for thrombosis. The risk of developing intravascular thrombosis requires primary prevention measures by adding D-dimers in the early diagnostic algorithm, being the most accurate marker of hypercoagulability and endogenous fibrinolysis. The corroboration of the hypercoagulability status with the results of genotyping, the frequencies of the minor/major alleles studied, single mononucleotide polymorphisms (SNPs) and the establishment of preventive therapy, aims to prevent intravascular thrombosis and thromboembolic phenomena.

Status thymicolymphaticus: real or fake?

Sudden infant death syndrome (SIDS) is the sudden, unexpected death of an infant less than one year of age that remains unexplained after a full investigation. SIDS is the most frequent cause of death of infants between two weeks and one year of age, explaining 35% to 55% of all deaths in this age group. We report a newborn male who died soon after birth. The newborn was cyanotic, bradycardic at first, and then asystolic; without any vesicular murmur, apneic, low amplitude thorax movements, even under conditions of positive pressure ventilation on the endotracheal tube. The microscopic aspect thymus highlighted a corticomedullary ratio quite high in favor of the cortical, rich in lymphocyte population, with the dilated subcapsular sinuses. In this report, we considered that cardiorespiratory failure, which was the immediate cause of death, could have been caused by the thymus hypertrophy. This hypertrophy can be a complication of an intrapartum preexistent condition, most probably of hepatic nature.

Correlation of clinical and biological evidence - a dominant therapeutic element of succeeding in ectopic pregnancy.

Tubal pathology, smoking, pelvic inflammatory disease, miscarriage, medical or surgical abortion, usage of intrauterine devices (IUDs) for women with salpingitis latent injuries, older than 40 years, are risk factors for ectopic pregnancy. The objective of this study concerns the correlation of the clinical and biological evidence for the early diagnosis of the ectopic pregnancy and, as soon as possible, for the estimation for eventual risk of complications that may appear. The transvaginal ultrasound test, minimal increases in serum beta-human chorionic gonadotropin (ß-hCG) dynamics and blood counts are investigations of choice in achieving our objective. Overcoming ß-hCG critical level (>1198 IU÷mL), the decrease of platelets and changes in platelet constants announce the imminent risk of ectopic pregnancy rupture and the need to take a quick decision on the course of treatment.

Apert syndrome - clinical case.

Apert syndrome - acrocephalosyndactyly - is a rare autosomal dominant disorder representing 1:65 000 cases of living newborns. Characteristic malformations of the Apert syndrome are early craniostenosis, microviscerocranium and II-V finger syndactyly of hand and toes with proximal phalanx of the bilateral thumb "in delta". It is difficult to determine prenatal diagnosis in the second quarter, when examining the morphology of fetal signs; the dysmorphism signs appeared in the third pregnancy quarter. We present here the case of a newborn with Apert syndrome that was born prematurely in our Clinic after a monitored pregnancy, where there was issued a suspicion of cranio-facial dysmorphism, malposition and malformation of the feet and hands in the third quarter of prenatal pregnancy. The diagnosis of Apert syndrome was placed on clinical signs, laboratory and genetic tests. The clinical outcome of the baby in the maternity was favorable, the therapeutic management being established by a multidisciplinary team. Immediate complications were due to the case of prematurity: respiratory distress syndrome and the characteristics of the syndrome: micrognathia and naso-facial dysmorphism, syndactyly, bilateral foot metatarsus adductus.

Utility of Cerebroplacental Ratio in IUGR Fetuses from Pregnancy with Preeclampsia in Prediction the Risk for Perinatal Complications.

PURPOSE: The aim of this study was to show that is the incidence of intrauterine growth restriction (IUGR) in women with preeclampsia (PE), assessment of cerebroplacental ratio (CPR) to establish the diagnostic value of CPR in fetuses with preeclampsia with/without IUGR. MATERIAL AND METHODS: We performed an analysis of 49 cases with gestational hypertension and PE and 16 cases with normal pregnancy for control lot, study in Obstetrics and Gynecology Clinic of the Municipal Hospital Filantropia, Craiova, between October 2013 and October 2015. It was performed clinical and laboratory evaluation and management of each case. CPR ratio was measured in the third trimester in all cases, being studied according to the normal and abnormal values obtained, following the evolution of the newborn. RESULTS: Mild PE cases were predominant with 21 cases (19.27%), severe PE accounted for 16 cases (14.68%) and gestational hypertension was found in 16 cases in our study. Distribution of IUGR cases presented interesting and contradictory data, because we met cases of IUGR in pregnancies without PE, at a rate of only 1.54%. The incidence of IUGR was significantly higher in cases with severe early-onset PE (10.20%). Cases of severe PE, but with late-onset, had IUGR in only 2.04% of cases. We found a significant statistical significance (p <0.005) on the incidence of IUGR in cases with severe early-onset PE. CPR identified adverse perinatal outcomes in 18.46% of cases with CPR <1.08. CONCLUSIONS: This study shows that early onset severe PE and concomitantly IUGR affects a significant proportion of pregnancies. CPR can be used to identify fetuses with an increased risk of intrauterine compromise.

Velamentous insertion of the umbilical cord vessels with vasa praevia--a case report.

Among the abnormal cord insertion pathology, velamentous cord insertion associated with rupture of vasa praevia is the most severe condition related to the outcome of the newborn. In velamentous cord insertion, the fetal vessels run freely through the fetal membranes without protection from Wharton's jelly, umbilical vessels diverging as they traverse the membranes. When the membranes are ruptured, complete tearing of fetal vessels through the torn membranes or partial rupture near the site of membrane rupture may occur. Velamentous insertion occurs in approximately 1% of singleton gestations, but is observed in as many as 15% of monochorionic twin gestations. The risk of perinatal death was doubled in pregnancies with velamentous cord insertion relative to normal cord insertion. This condition can be diagnosed by ultrasonography with a sensitivity of 67% and specificity of 100% in the second trimester. We report a case of a newborn who came from a velamentous cord insertion condition associated with rupture of vasa praevia after the spontaneously membranes rupture. After a difficult resuscitation and stabilization, the newborn survived with a good outcome after the follow-up.