Mechanisms of SARS-CoV-2 Placental Transmission.

The widespread occurrence of SARS-CoV-2 infections and the diverse range of symptoms have placed significant strain on healthcare systems worldwide. Pregnancy has also been affected by COVID-19, with an increased risk of complications and unfavorable outcomes for expectant mothers. Multiple studies indicate that SARS-CoV-2 can infiltrate the placenta, breach its protective barrier, and infect the fetus. Although the precise mechanisms of intrauterine transmission remain unclear, factors such as perinatal infection, macrophages, sexual intercourse, and the virus' interaction with host angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP-1) proteins appear to play a role in this process. The integrity of the placental barrier fluctuates throughout pregnancy and appears to influence the likelihood of fetal transmission. The expression of placental cell receptors, like ACE2, changes during pregnancy and in response to placental damage. However, due to the consistent presence of others, such as NRP-1, SARS-CoV-2 may potentially enter the fetus at different stages of pregnancy. NRP-1 is also found in macrophages, implicating maternal macrophages and Hofbauer cells as potential routes for viral transmission. Our current understanding of SARS-CoV-2's vertical transmission pathways remains limited. Some researchers question the ACE2-associated transmission model due to the relatively low expression of ACE2 in the placenta. Existing studies investigating perinatal transmission and the impact of sexual intercourse have either involved small sample sizes or lacked statistical significance. This review aims to explore the current state of knowledge regarding the potential mechanisms of COVID-19 vertical transmission, identifying areas where further research is needed to fill the gaps in our understanding.

Blood type ABO and the cytokine profile of follicular fluid in women undergoing IVF/ET.

OBJECTIVES: ABO blood type was hypothesised to be related to a number of infertility processes. There is still an open debate on ABO blood group's incompatibility and infertility. It was associated with ovarian reserve in women with subfertility. There is still not enough information on the influence of blood type and the immunology of follicular fluid (FF). MATERIAL AND METHODS: 78 patients were selected, who underwent in vitro fertilization (IVF) between April 2021 and January 2022. FF samples from each individual patient were taken on the day of ovarian puncture and stored at -80°C until immunological assessment. Concentration of chosen interleukins - IL-1α, IL-2, IL-4, IL-5, IL-6, IL-8 IL-10, IL-15, IL-1ß, IL-18, IFN, LIF, TNFα, GCSF and PIBF-1 were measured using commercially available ELISA kits. RESULTS: All assessed cytokines were present in the FF of exanimated patients. The concentration was compared to the blood type ABO of all women undergoing in vitro fertilization. No statistical relevance was found between blood type ABO and the concentration of GCSF, PIBF1, LIF, IL-15, IL-5, IL-8, IL-1 alfa, IL-1 beta, INF gamma, IL-2HS, IL-4HS, IL-6HS, IL-10HS in the FF obtained during ovarian puncture (p > 0,05). There was no statistically significant correlation between blood type ABO and the quality of embryo, and the positive pregnancy test in patients undergoing IVF/ET. CONCLUSIONS: The blood type ABO does not influence the wide cytokine profile of FF obtained during ovarian puncture in women with infertility of different origin, as well as embryo quality and pregnancy rate.

Ductus venosus opens in high-risk pregnancies without signs of increased central venous pressure.

OBJECTIVES: It has been belived that changes in diastolic blood velocities in the fetal ductus venosus were due to increased central venous pressure secondary to increased fetal heart strain during hypoxia or heart failure. There have been recent reports of changes in ductus venosus blood velocity without signs of increased fetal heart strain. The aim of this evaluation was to compare blood velocity in the right hepatic vein as a marker of increased central venous pressure in relationship to changes in ductus venosus blood velocity. MATERIAL AND METHODS: Fifty pregnancies suspected of fetal growth resitriction were evaluated by Doppler ultrasound. Blood velocity was recorded in the right hepatic vein, ducus venosus and in the umbilical vein. Placental blood flow was also recorded in the uterine and umbilical arteries as well as the fetal middle cerebral artery. RESULTS: Increased umbilical artery pulsatility index was recorded in 19 fetuses and 20 has signes of brain sparing according to recordings in the middle cerebral artery. Abnormal blood velocity in the ductus venosus was recorded in 5 fetuses, none of these fetuses had an abnormal pulsatility in the right hepatic vein. CONCLUSIONS: Opening of the ductus venosus is not only related to fetal cardiac strain. This might indicate that the ductus venosus does not primarily open due to increased central venous pressure in moderate fetal hypoxia. Increased fetal cardiac strain might be a late event in the process of chronic fetal hypoxia.

Assessment of RANTES, MIP4A, MMP7, MMP9, MMP14, TIMP 1, TIMP 2 and TIMP 3 concentration in the follicular fluid of patients undergoing in vitro fertilization/embryo transfer procedure.

Introduction: Matrix metalloproteinases (MMP) degrade extracellular matrix. Some studies show that MMP9 concentration in follicular fluid (FF) may play a role in oocyte maturation and in vitro fertilization (IVF) success. The immunology of follicular fluid is still not fully understood. Aim: Assessment of RANTES, MIP4A, MMP7, MMP9, MMP14, TIMP 1, TIMP 2 and TIMP 3 concentration in the follicular fluid of patients undergoing in vitro fertilization/embryo transfer procedure. Material and methods: This case-control study included 20 randomly selected patients with a positive pregnancy (PPG) test and 20 patients with a negative pregnancy (NPG) test after IVF/ET. In FF obtained during oocyte retrieval, the concentrations of MIP4A, MMP7, MMP14, TIMP 1, TIMP 2, TIMP 3, RANTES, IL-12p40, and IL-17A were measured. Their effect on the characteristics of follicles, embryos, and the efficiency of IVF and ET were analysed. Results: There was no statistically significant relationship between a positive pregnancy test and the results of the immunoassay performed. The number of COC-1 correlates significantly and positively with RANTES (r = 0.34; p = 0.038) and IP-10 (r = 0.329; p = 0.038). MII correlates significantly and positively with RANTES (r = 0.341, p = 0.031). The number of top-quality embryos correlates significantly and positively with IL-17A (r = 0.451, p = 0.004) and TIMP 1 (r = 0.44, p = 0.005). Conclusions: The concentration of IL-17A and TIMP 1 may predict IVF/ET success. Further studies are required on the influence of the follicular fluid immunological environment on oocyte maturation and quality and, subsequently, embryo development.

Influence of gestational diabetes in twin pregnancy on the condition of newborns and early neonatal complications.

OBJECTIVES: Diabetes mellitus is the most common metabolic complication in pregnancy and increasing worldwide. In Europe, it occurs in 3-5% of pregnant women. The rate of twin pregnancy has been increased similarly to gestational diabetes mellitus (GDM). Twin pregnancy is associated with a higher complication rate compared to singleton pregnancy. The growing prevalence of GDM and twin pregnancy has given rise to their increasing concurrent presentation. MATERIAL AND METHODS: The retrospective analysis included 212 twin-pregnant patients. The analysis excluded cases of miscarriage and early fetal death in the first trimester of pregnancy. The influence of GDM on the condition of newborns and mothers after delivery was analyzed. For statistical analysis R 3.6.2 software was used. RESULTS: No statistically significant relationship between GDM and Non-GDM group and periparturient complications was found. Birth weight was significantly higher in the GDM G2 group. Apgar Score was the lowest in the GDM G1 group. In the group of larger newborns of the GDMG1 group respiratory distress syndrome (RDS) , a higher incidence of second-degree intracranial bleeding and grade II of preterm retinopathy were observed. There was no statistically significant relationship between GDM G1, GDM G2 and other neonatal complications. CONCLUSIONS: In summary, our results indicate that GDM in twin pregnancy does not increase the risk of cesarean section but increases some neonatal complications. In conclusion women with twin pregnancies complicated by GDM require specialist care during pregnancy and childbirth should take place in a third-level reference center.

The Impact of Surgical Techniques in Patients with Rectal Cancer on Spine Mobility and Abdominal Muscle Strength-A Prospective Study.

The aim of this non-randomized study was to evaluate the impact of spine joint mobility and chest mobility on inhalation and exhalation, and to assess the abdominal muscle strength in patients undergoing surgery for colorectal cancer with one of the following methods: anterior resection, laparoscopic anterior resection or abdominoperineal resection. In patients who were successively admitted to the Department of Surgical Oncology at the Oncology Center in Bydgoszcz, the impact of spine joint mobility, muscle strength and chest mobility on inhalation and exhalation wasassessed three times, i.e., at their admission and three and six months after surgery. The analysis included 72 patients (18 undergoing abdominoperineal resection, the APR group; 23 undergoing laparoscopic anterior resection, the LAR group; and 31 undergoing anterior resection, the AR group). The study groups did not differ in terms of age, weight, height, BMIor hospitalization time (p > 0.05). Three months after surgery, reductions in spine joint mobility regarding flexion, extension and lateral flexion, as well asreductions in the strength of the rectus abdominis and oblique muscles, were noted in all study groups (p < 0.05). In comparison between the groups, the lowest values suggesting the greatest reduction in the range of mobility were recorded in the APR group. Surgical treatment and postoperative management in colorectal cancer patients caused a reduction in spine mobility, abdominal muscle strength and chest mobility. The patients who experienced those changes most rapidly and intensively werethose undergoing abdominoperineal resection.

Concentrations of matrix metallopeptidase 9, interleukin 4, and interleukin 8 in follicular fluid, and the results of in vitro fertilization.

OBJECTIVE: Cytokines and enzymes in follicular fluid (FF) may have a crucial role in fertility. This study aimed to analyse the results of in vitro fertilization/embryo transfer (IVF/ET) and compare them with matrix metalloproteinase 9 (MMP-9) and cytokine concentrations in FF. METHODS: This case-control study included 20 randomly selected patients with a positive pregnancy (PPG) test and 20 with a negative pregnancy (NPG) test after IVF/ET. In FF obtained during oocyte retrieval, the concentrations of soluble forms of MMP-9, interleukin 1 (IL-1) alpha, IL-1 beta, interferon gamma, IL-2, IL-4, IL-6, IL-8, and IL-10 were measured. Their effect on the characteristics of follicles, embryos, and the efficiency of IVF and ET were analysed. RESULTS: High-sensitivity IL-4 concentrations were significantly higher in patients with a PPG test than in those with an NPG test (3.15 ± 3.23 vs 1.91 ± 0.35 pg/mL). The number of top-quality embryos achieved was significantly higher in patients with a PPG test than in those with an NPG test (2.6 ± 1.39 vs 1.75 ± 1.21), and they were negatively correlated with IL-8 concentrations in FF. CONCLUSION: Further research on the role of IL-4 and IL-8 in FF is required to establish any clinical benefit of determining their concentrations in FF of infertile women.

Progesterone-induced blocking factor 1 and cytokine profile of follicular fluid of infertile women qualified to in vitro fertilization: The influence on fetus development and pregnancy outcome.

Introduction: Progesterone is essential for both the initiation and the maintenance of pregnancy. The immunological effects of progesterone are mediated by the progesterone-induced blocking factor (PIBF), which is an immunomodulatory factor with anti-abortive properties. The aim of the research was to establish the cytokine profile and PIBF1 concentration in follicular fluid (FF) of patients undergoing in vitro fertilization (IVF).Methods: Seventy-eight patients who qualified for IVF underwent a detailed medical interview, including the course of fertility treatment and physical, gynecological, and cytological examinations. The concentration of PIBF1, IL-18, IL-2, IL-4, IL-6, IL-10, interferon-γ (IFN-γ), IL-1α, IL-1ß, IL-5, IL-8, and IL-15 in FF during ovarian puncture was measured using commercially available ELISA kits.Results: IL-1 beta concentration was lower in the FF of patients with successful IVF. IL-8 concentration in FF correlated with the number of cumulus-oocyte complexes (COC-1), metaphase II (MII), and top-quality embryos. PIBF1 concentration had a positive correlation with the number of MII and top-quality embryos. IL-2 and IL-6 concentrations were positively correlated with the number of COC-1 and MII. An important parameter in assessing the chances of successful IVF is the number of top-quality embryos achieved.Conclusion: Higher PIBF1 concentration in FF may indicate a greater possibility of successful IVF due to the higher number of top-quality embryos. IL-1 beta concentration was found to be lower in the FF of patients with successful IVF. Therefore, PIBF1 and IL-1 beta in FF could be candidates for a marker of successful IVF.

First-Trimester Fetal Hepatic Artery Examination for Adverse Outcome Prediction.

OBJECTIVE: To assess whether there are differences in first-trimester fetal hepatic artery flows depending on pregnancy outcomes. METHODS: The prospective study conducted in 2012-2020 included 1841 fetuses from singleton pregnancies assessed during the routine first-trimester ultrasound examination (between 11- and 14-weeks' gestation). Also, each fetus was examined to determine their hepatic artery flows by measuring the artery's pulsatility index (HA-PI) and peak systolic velocity (HA-PSV). RESULTS: The fetuses that were classified as belonging to the adverse pregnancy outcome group (those with karyotype abnormalities and congenital heart defects) were characterized by a significantly lower HA-PI and higher HA-PSV compared to normal outcome fetuses. CONCLUSION: Hepatic artery flow assessment proved to be a very useful tool in predicting adverse pregnancy outcomes, in particular karyotype abnormalities and congenital heart defects.

The Prognostic Role of CDK9 in Bladder Cancer.

Introduction: Most patients with urothelial carcinoma are diagnosed with non-invasive tumors, but the prognosis worsens with the progression of the disease. Overexpression of cyclin-dependent kinase 9 has been recently linked to increased cancer proliferation, faster progression, and worse prognosis. However, some cancers seem to contradict this rule. In this work, we explored the prognostic role of CDK9 expression in urothelial carcinoma. Materials and Methods: We performed immunohistochemical analysis on 72 bladder cancer samples. To assess a larger group of patients, the Cancer Genome Atlas (TCGA) database containing 406 cases and transcriptomics information through the Human Pathology Atlas were analyzed. Results: CDK9 is overexpressed in urothelial cancer tissues when compared to normal urothelial tissues (p < 0.05). High CDK9 expression was observed in low-stage, low-grade, and non-muscle-invasive tumors (p < 0.05). The patients with high CDK9 expression had a significantly higher 5-year overall survival rate than those with low CDK9 expression (77.54% vs. 53.6% in the TMA group and 57.75% vs. 35.44% in the TCGA group, respectively) (p < 0.05). The results were consistent in both cohorts. Multivariate Cox regression analysis indicated that low CDK9 status was an independent predictor for poor prognosis in the TCGA cohort (HR 1.60, CL95% 1.1−2.33, p = 0.014). Conclusions: High CDK9 expression predicts a favorable prognosis in urothelial carcinoma and is associated with clinicopathological features characteristic for early-stage disease. The decrease in CDK9 expression can be associated with the build-up of genetic instability and may indicate a key role for CDK9 in the early stages of urothelial carcinoma.

The role of individual blood flow parameters through ductus venosus in the first and second trimesters of pregnancy in predicting the condition of the fetus and newborn.

OBJECTIVES: To predict fetal and neonatal outcome during pregnancy based on detailed analysis of ductus venosus blood flow velocities in first and second-trimester fetuses. MATERIAL AND METHODS: A retrospective analysis was made in 680 patients with single pregnancies in years 2015 and 2016. The following ductus venosus blood flow velocities in first and second-trimester were analyzed: S-wave velocity, D-wave velocity, a-wave velocity, Tmax velocity, PIV. Results were divided into sub-groups with reduced value, normal value and increased value and compared with fetal and neonatal condition. RESULTS: The relationship between the increased PIV value in the first trimester of pregnancy and an increased risk of chromosomal aberrations was observed, whereas the increased DV PI value in the second trimester of pregnancy with reduced A -wave were associated with a higher incidence of FGR. No correlation between the remaining DV blood flow velocities in the first and second trimester of pregnancy and the more frequent occurrence of fetal and neonatal complications has been confirmed. CONCLUSIONS: The increased DV PIV is a good prognostic tool for the detection of chromosomal aberrations in first trimester of pregnancy. In the second trimester, the increased DV PIV and the reduced A- wave velocity correlate with the fetal growth restriction. Ductus venosus seems to be an indirect indicator of intrauterine hypoxia with moderate prognostic value for adverse obstetric outcomes.

Abnormal sperm morphology is associated with sensitization to inhaled allergens.

BACKGROUND: Allergy is associated with the loss of tolerance of environmental antigens, combined with a pathological immune response. There were no studies up to date that would show whether the quality of semen decreases in people with allergic diseases. MATERIAL AND METHODS: The research included men who reported to the Gynecological Outpatient Clinic due to reproductive difficulties, defined as the lack of pregnancy after one year of regular intercourse. Semen quality was assessed according to the World Health Organization (WHO) standard. All patients underwent skin prick tests with the most important inhalation allergens (such as hazel, silver birch, mugwort, rye, dog, cat, Dermatophagoides farinae, Dermatophagoides pteronyssinus, alder, Alternaria alternata, Cladosporium herbarum, and grass mix). The data was statistically analyzed. RESULTS: Results of 52 patients aged 25-52 years (34.62 ± 4.96) were analyzed. The mean BMI (Body mass index) was 28.25 (+ -3.77). It was found that 38 men (73%) had increased body weight, and 14 men (26.9%) were obese (BMI > = 30). 13 patients were smokers (25%), and 24 patients (46%) had skin tests positive for at least one inhaled allergen. Sperm tail defects were statistically more significant in patients allergic to birch, rye, cat, alder, and grass. In patients allergic to Alternaria alternata, head defects were statistically more significant (p < .05). No association was found between allergy to house dust mites, mugwort, hazel, and dogs and the deterioration of semen. CONCLUSION: Allergy due to inhalation allergens had an influence on the quality of male semen. Further research is necessary to establish the immunological bases of this phenomenon.

Function of Follicular Cytokines: Roles Played during Maturation, Development and Implantation of Embryo.

A balance within the immune system is necessary for the proper development of ovarian follicles. Numerous cytokines were detected in follicular fluid, the role of which in reproductive physiology seems crucial. They influence the development and maturation of the follicle, ovulation, and corpus luteum formation, as well as embryo implantation and maintenance of pregnancy. The analysis of follicular fluid requires its collection by puncturing of the ovary, which is usually executed in connection with various gynaecological procedures. When interpreting such test results, clinical indications for a given procedure and the method of patient preparation should be taken into account. This review revealed the results of currently available studies on the concentration of pro-inflammatory cytokines in follicular fluid in various forms of infertility. Additionally, it presented cytokines, whose concentration has a significant impact on the size of ovarian follicles, their number, the effectiveness of in vitro fertilisation, development of the embryo, and chances of correct implantation. Despite the many recent publications, the knowledge of follicular fluid immunology in the context of reproductive pathology is superficial and further research is required to extensively understand the roles of individual cytokines in reproductive pathology. In the future, this knowledge may enable patients' individual qualifications to individual methods of infertility treatment, as well as the possible adjustment of the treatment regimen to the patient's immune profile.

The NLRP3 Inflammasome Role in the Pathogenesis of Pregnancy Induced Hypertension and Preeclampsia.

Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of these diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate the crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1ß, IL-18, and gasdermin D. Production of these proinflammatory chemokines is the beginning of a local and general inflammation, which results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. The NLRP3 inflammasome is a critical complex in the mediation of the inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Herein, the presented article delineates molecular mechanisms of these processes, indicating directions of future advance.

Screening for trisomy 21 based on maternal age, nuchal translucency measurement, first trimester biochemistry and quantitative and qualitative assessment of the flow in the DV - the assessment of efficacy.

OBJECTIVES: The aim of the study was to compare effects of addition of two methods of ductus venosus (DV) flow assessment: qualitative - the assessment of shape of the A-wave (positive or negative), and quantitative - based on the pulsatility index for veins (DVPI) to the basic screening for trisomy 21 at 11 to 13 + 6 weeks of pregnancy. MATERIAL AND METHODS: The ultrasound examination was performed in 8230 fetuses in singleton pregnancies at 11- -13 + 6 wks, as a part of a routine screening for chromosomal defects. In DV A-wave was assessed and DVPI was calculated. After the scan blood sample was taken for first trimester biochemistry (BC). Risk for chromosomal defects was calculated and high-risk patients were offered an invasive test for karyotyping. RESULTS: Basic screening with following combination of markers: MA, NT and BC provided lowest detection rate (DR) 87.50% for FPR = 6.94%. After adding qualitative DV A-wave assessment DR increased to 88.75% for FPR = 5.65%. The best DR = 93.75% for FPR = 5.55% was achieved when quantitative DVPI was added. The application of the Receiver Operating Curves curve confirmed validity of the addition of DV flow assessment to the screening model. The highest diagnostic power of the test was achieved when DVPI was added, with the ROC AUC of 0.974. CONCLUSIONS: The assessment of DV flow performed at 11-13 + 6 weeks increases DR for trisomy 21 and reduces FPR. The screening model based on the quantitative DV flow analysis (DVPI) gives better results compared to the qualitative flow assessment.

Analysis of the origin of birth defects in pregnant women from the Kujawy-Pomerania Region.

OBJECTIVES: The aim of the study was to analyze the origin of birth defects in pregnant women from the Kujawy-Pomerania Region, and to identify factors affecting the formation of developmental disorders in the Province. MATERIAL AND METHODS: The correlation between maternal age and fetal defects was investigated. We also attempted to determine whether environmental or family factors play a role in the formation of fetal abnormalities. RESULTS: The analysis confirmed a correlation between the incidence of chromosomal aberrations and maternal age. CONCLUSIONS: Higher rates of neural tube defects were observed in fetuses born to mothers who did not take folic acid. The influence of other factors on developmental anomalies was not confirmed.

Nasal bone in screening for T21 at 11-13 + 6 weeks of gestation - a multicenter study.

OBJECTIVES: Trisomy 21 is one of the most common chromosomal defects diagnosed prenatally. Screening for Down syndrome is based on maternal age, measurement of crown-rump length, nuchal translucency and fetal heart rate, together with free ß-hCG and PAPP-A at 11 to 13 + 6 weeks. Introduction of additional ultrasound marker of trisomy 21 (evaluation of the nasal bone) may result in increased DR and decreased invasive diagnostic testing rates (FPR). MATERIAL AND METHODS: Ultrasound scan with NB evaluation was performed in 5814 fetuses during routine screening for chromosomal defects at 11 to 13 + 6 weeks of gestation. DR and FPR coefficients were calculated for 4 levels of risk as cut-off points for screening model 1, based on MA, NT, and first trimester biochemistry, as well as for screening model 2, based on MA, NT, first trimester biochemistry and NB. RESULTS: There were 5708 normal cases, 71 cases of trisomy 21 and 35 cases of other chromosomal defects. NB was absent in 46 (64.8%) cases and present in 25 (35.3%) cases of trisomy 21, comparing to present NB in 5463 (95.7%) and absent in 245 (4.3%) of normal cases. CONCLUSIONS: First-semester screening with additional NB assessment significantly increases the detection rate for trisomy 21 and decreases the rate of false-positive results. Adding NB evaluation at the risk level of 1:50 causes only a small increase in detection rate. Invasive procedures should be performed in that group regardless NB assessment.