Current applications of indocyanine green (ICG) in abdominal, gynecologic and urologic surgery: a meta-review and quality analysis with use of the AMSTAR 2 instrument.

BACKGROUND: Indocyanine green (ICG) is an injectable fluorochrome that has recently gained popularity as a means of assisting intraoperative visualization during laparoscopic and robotic surgery. Many systematic reviews and meta-analyses have been published. We conducted a meta-review to synthesize the findings of these studies. METHODS: PubMed and Embase were searched to identify systematic reviews and meta-analyses coping with the uses of ICG in abdominal operations, including Metabolic Bariatric Surgery, Cholecystectomy, Colorectal, Esophageal, Gastric, Hepato-Pancreato-Biliary, Obstetrics and Gynecology (OG), Pediatric Surgery, Surgical Oncology, Urology, (abdominal) Vascular Surgery, Adrenal and Splenic Surgery, and Interdisciplinary tasks, until September 2023. We submitted the retrieved meta-analyses to qualitative analysis based on the AMSTAR 2 instrument. RESULTS: We identified 116 studies, 41 systematic reviews (SRs) and 75 meta-analyses (MAs), spanning 2013-2023. The most thoroughly investigated (sub)specialties were Colorectal (6 SRs, 25 MAs), OG (9 SRs, 15 MAs), and HPB (4 SRs, 12 MAs). Interestingly, there was high heterogeneity regarding the administered ICG doses, routes, and timing. The use of ICG offered a clear benefit regarding anastomotic leak prevention, particularly after colorectal and esophageal surgery. There was no clear benefit regarding sentinel node detection after OG. According to the AMSTAR 2 tool, most meta-analyses ranked as "critically low" (34.7%) or "low" (58.7%) quality. There were only five meta-analyses (6.7%) that qualified as "moderate" quality, whereas there were no "high" quality reviews. CONCLUSIONS: Regardless of the abundance of pertinent literature and reviews, surgeons should be cautious when interpreting their results on ICG use in abdominal surgery. Future reviews should focus on ensuring methodological vigor; establishing clear protocols of ICG dose, route of administration, and timing; and improving reporting quality. Other sources of data (e.g., registries) and novel methods of data analysis (e.g., machine learning) might also contribute to an enhanced role of ICG as a decision-making tool in surgery.

Proteomics in the study of female fertility: an update.

INTRODUCTION: Female fertility has been a field of interest for the scientific community throughout the years. The contribution of proteomics in the study of female fertility as well as female infertility and in vitro fertilization (IVF) has been significant. Proteomics is a recently developed field, extensively applied to the identification and quantification of proteins, which could be used as potential biomarkers in a diagnostic, prognostic, or predictive manner in a variety of medical conditions. AREAS COVERED: The present review focuses on proteomic studies of the oocyte and endometrial environment as well as on conditions related to infertility, such as polycystic ovarian syndrome, endometriosis, obesity, and unexplained infertility. Moreover, this review presents studies that have been done in an effort to search for fertility biomarkers in individuals following the IVF procedure. EXPERT OPINION: The comprehension of the molecular pathways behind female fertility and infertility could contribute to the diagnosis, prognosis, and prediction of infertility. Moreover, the identification of proteomic biomarkers for IVF cycles could predict the possible outcome of an IVF cycle, prevent an unsuccessful IVF, and monitor the IVF cycle in a personalized manner, leading to increased success rates. [Figure: see text].

Prenatal Exposure to Bisphenol A: Is There an Association between Bisphenol A in Second Trimester Amniotic Fluid and Fetal Growth?

Background and Objectives: Fetal growth abnormalities increase the risk of negative perinatal and long-term outcomes. Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical to which humans may be exposed in a number of ways, such as from the environment, via various consumer products, and through the individual's diet. Since the compound possesses estrogen-mimicking properties and exerts epigenetic and genotoxic effects, it has been associated with harmful effects impacting the entire spectrum of human life, including, vitally, the intrauterine period. We investigated the role of maternal exposure to BPA in abnormal fetal growth velocity, both impaired and excessive. Materials and Methods: Amniotic fluid samples were collected from 35 women who underwent amniocentesis early in the second trimester due to medical reasons. Pregnancies were followed until delivery, and birth weights were recorded. The amniotic fluid samples were subsequently divided into three groups based on fetal birth weight, as follows: AGA (appropriate for gestational age), SGA (small for gestational age), and LGA (large for gestational age). Amniotic fluid BPA levels were determined by gas chromatography coupled with mass spectrometry. Results: BPA was detected in 80% (28/35) of our amniotic fluid samples. Median concentration was 281.495 pg/mL and ranged from 108.82 pg/mL to 1605.36 pg/mL. No significant association was observed between the study groups regarding BPA concentration. A significant positive correlation between amniotic fluid BPA concentration and birth weight centile (r = 0.351, p-value = 0.039) was identified. BPA levels were also inversely associated with gestational age in pregnancies at term (between 37 and 41 weeks) (r = -0.365, p-value = 0.031). Conclusions: Our findings suggest that maternal exposure to BPA during the early second trimester of pregnancy can potentially contribute to increased birthweight percentiles and to decreased gestational age in pregnancies at term.

Meta-analysis of GnRH-antagonists versus GnRH-agonists in poor responder protocols.

PURPOSE: Considering the insufficient evidence supporting an ideal protocol for poor responder management in IVF/ICSI cycles, the aim of the current meta-analysis was to compare GnRH-antagonist versus GnRH-agonist protocols in poor responders, evaluating effectiveness and safety. METHODS: Meta-analysis was conducted using Medcalc 16.8 version software. Standardized mean differences (SMD), odds ratios (OR), and the respective 95% confidence intervals (CI) were determined appropriately. The Cochran Q statistic and the I2 test were used to assess studies' heterogeneity. RESULTS: GnRH-agonists were shown to correlate with fewer cancelled IVF/ICSI cycles (p = 0.044, OR = 1.268 > 1, 95% CI 1.007, 1.598), a larger number of embryos transferred (p = 0.008, SMD = - 0.230, 95% CI - 0.400, - 0.0599), and more clinical pregnancies (p = 0.018, OR = 0.748 < 1, 95% CI 0.588, 0.952). However, GnRH-antagonists resulted in a significantly shorter duration of ovarian stimulation (p = 0.007, SMD = - 0.426. 95% CI - 0.736, - 0.115). The number of oocytes and mature oocytes retrieved in both protocols did not differ statistically (p = 0.216, SMD = - 0.130, 95% CI - 0.337, 0.0763 and p = 0.807, SMD = - 0.0203, 95% CI - 0.183, 0.142, respectively). Moreover, a high heterogeneity among studies was observed regarding duration of ovarian stimulation (I2 = 90.6%), number of oocytes (I2 = 82.83%)/mature oocytes retrieved (I2 = 70.39%), and embryos transferred (I2 = 72.83%). CONCLUSIONS: Based on the present meta-analysis, agonist protocols could be suggested as a first choice approach, in terms of effectiveness. Due to the high studies' heterogeneity, results should be considered with caution. Accordingly, larger cohort studies and meta-analyses like the present one will enhance the robustness of the emerging results to identify the ideal protocol for poor responders.

The influence of delayed cord clamping and cord milking on inflammatory cytokines in umbilical vein and neonatal circulation.

INTRODUCTION: The purpose of the present study was to compare the levels of tumor necrosis factor α (TNF-α), and interleukins (IL) 1, 6, 8 and 10 in the umbilical cord and neonatal circulation among neonates with early and late cord clamping. MATERIAL AND METHODS: A consecutive series of 76 cases of uncomplicated pregnancy and an uneventful parturition was evaluated. In 40 cases, delayed cord clamping was used and in the remaining 36, early cord clamping was practiced. Blood samples were collected from the umbilical vein immediately after cord clamping and at 24 h from the median cubital or basilic vein of the neonate. RESULTS: Significant differences were noted in the hematocrit and hemoglobin levels at 24 h that favored delayed clamping. None of the evaluated markers of inflammation differ between the two groups. Spearman's rho revealed a significant correlation between umbilical cord TNF-α and TNF-α neonatal values at 24 h (r = 0.551, p = 0.022) in the early clamped group. Significant correlations were also noted between umbilical cord TNF-α and TNF-α neonatal values at 24 h (r = 0.728, p = 0.001), umbilical cord IL-10 and neonatal IL-10 at 24 h (r = 0.487, p = 0.047) and umbilical cord IL-1b and neonatal IL-1b at 24 h (r = 0.516, p = 0.034). CONCLUSIONS: Delayed cord clamping or cord milking does not alter the levels of inflammatory cytokines in cord blood and neonatal serum. Future studies should evaluate the impact of delayed cord clamping in selected high-risk pregnancies.

Administration of low-molecular-weight heparin in patients with two or more unsuccessful IVF/ICSI cycles: a multicenter cohort study.

To compare the effects of the administration of low-molecular-weight heparin (LMWH) in subfertile patients with two or more unsuccessful IVF/ICSI cycles. In this six-center two-arm retrospective cohort study, the study population (230 women) underwent a GnRH-antagonist protocol and was classified into two groups, according to the couse of LMWH or not. Groups were compared regarding the clinical and IVF/ICSI cycle characteristics and reproductive outcomes, whereas clinical pregnancy and miscarriage constituted the primary endpoints. Logistic regression analysis was performed to determine the potential predictors of clinical pregnancy, miscarriage and live birth rates using the Enter method. Baseline characteristics were comparable in the two groups. There was no statistically significant difference between the two study groups with regard neither to clinical pregnancy and miscarriage rates (33/133 vs. 20/97, p = .456 and 15/133 vs. 9/97, p = .624, respectively), nor to the secondary outcomes preset for this study (all p values >.05). Logistic regression revealed that age of the woman and ICSI and dose of gonadotrophins used were predictors of clinical pregnancy and live birth, respectively. In conclusion, there is no evidence to support the standard addition of LMWH in patients with two or more unsuccessful IVF/ICSI cycles.

Does the type of GnRH analogue used, affect live birth rates in women with endometriosis undergoing IVF/ICSI treatment, according to the rAFS stage?

Since the introduction of gonadotropin-releasing hormone (GnRH) antagonists, an extensive amount of literature investigating the role of the downregulation protocols on pregnancy outcomes has been published. However, these studies were mainly performed in the general infertile population where patients with endometriosis were often excluded or underrepresented. This study is a large retrospective cohort study including 386 endometriosis patients undergoing IVF/ICSI, who had been previously classified according to the rAFS system. Patients were stimulated either a long GnRH agonist or GnRH antagonist protocol. Depending on endometriosis stage, patients were divided into two groups: endometriosis stage I-II and endometriosis stage III-IV. Each group was subdivided, based on the type GnRH analog used. When comparing the GnRH agonist and antagonist groups, patients with endometriosis stage I-II, had a tendency toward higher ß-hCG positive, clinical pregnancy, and live birth rates (42.8% vs. 26.7%; p = .07) in favor of GnRH agonist use. In endometriosis stage III-IV, no differences were observed between agonist and antagonist cycle in any of the pregnancy outcomes. Multivariate regression analysis did not reveal any significant predictor of live birth after adjusting for relevant confounders. Based on our findings, the chance to have a liveborn in endometriosis population seems not to be affected by the type of GnRH analog used, at least in advanced stages. Findings from stage I-II endometriosis cases merit consideration and further evaluation in a larger sample size is warranted.

Predictive value of repeated measurements of luteal progesterone and estradiol levels in patients with intrauterine insemination and controlled ovarian stimulation.

OBJECTIVE: The objective of this study is to assess if the difference of repeated measurements of estradiol and progesterone during luteal phase predict the outcome of intrauterine insemination. DESIGN: Prospective study. SETTING: Reproductive clinic. PATIENTS: 126 patients with infertility. INTERVENTION(S): Patients underwent controlled ovarian stimulation with recombinant FSH (50-150 IU/d). The day of IUI patients were given p.o natural micronized progesterone in a dose of 100 mg/tds. RESULTS: The area under the receiver characteristic operating curve (ROC curve) in predicting clinical pregnancy for % change of estradiol level on days 6 and 10 was 0.892 with 95% CI: 0.82-0.94. A cutoff value of change > -29.5% had a sensitivity of 85.7 with a specificity of 90.2. The corresponding ROC curve for % change of progesterone level was 0.839 with 95% CI: 0.76-0.90. A cutoff value of change > -33% had a sensitivity of 85 with a specificity of 75. CONCLUSIONS: The % change of estradiol and progesterone between days 6 and 10 has a predictive ability of pregnancy after IUI with COS of 89.2% and 83.4%, respectively. The addition of % of progesterone to % change of estradiol does not improve the predictive ability of % estradiol and should not be used.

Human Chorionic Gonadotropin: The Pregnancy Hormone and More.

To thoroughly review the uses of human chorionic gonadotropin (hCG) related to the process of reproduction and also assess new, non-traditional theories. Review of the international literature and research studies. hCG and its receptor, LH/CGR, are expressed in numerous sites of the reproductive tract, both in gonadal and extra-goanadal tissues, promoting oocyte maturation, fertilization, implantation and early embryo development. Moreover, hCG seems to have a potential role as an anti-rejection agent in solid organ transplantation. Future research needs to focus extensively on the functions of hCG and its receptor LH/CGR, in an effort to reveal known, as well as unknown clinical potentials.

Single nucleotide polymorphisms in the Anti-Müllerian hormone (AMH Ile(49)Ser) and Anti-Müllerian hormone type II receptor (AMHRII -482 A>G) as genetic markers in assisted reproduction technology.

PURPOSE: The aim of the study was to evaluate whether the presence Antimullerian hormone (AMH) and Antimullerian hormone type II receptor (AMHRII) single nucleotide polymorphisms (SNPs) Ile(49)Ser and -482A>G respectively are related to the assisted reproduction outcome. METHODS: A prospective cross-sectional observational study was conducted in order to assess the distribution of AMH and AMHRII SNPs in two cohorts, one of healthy women (N = 100) and the control group and the IVF/ICSI group (N = 151) consisted of women undergoing IVF/ICSI treatment for infertility. Furthermore, a prospective longitudinal observational study was performed on the latter group to assess possible associations of these SNPs with patients' characteristics and controlled ovarian stimulation (COS) and pregnancy outcome. RESULTS: Among non-carriers of the AMH (Ile(49)Ser) polymorphism, basal FSH levels were lower in those with more than two of previous IVF attempts and fertilization rate was statistically higher in those with peak serum E2 levels below 1500 pg/ml, whereas among non-carriers of the AMHRII (-482 A>G) polymorphism, number of follicles was higher in those with more than two previous IVF attempts and total dose of gonadotropins was lower in those with peak serum E2 levels above 1500 pg/ml. CONCLUSIONS: There was evidence that in specific subgroups of women undergoing IVF/ICSI, AMH and AMHRII SNPs may be related to patients' characteristics and controlled ovarian stimulation and pregnancy outcome and thus may provide a means for the prediction of ovarian response in specific subgroups of women entering an IVF/ICSI program.

Laparoscopic Surgery During Pregnancy: A Meta-Review and Quality Analysis Using the Assessment of Multiple Systematic Reviews (AMSTAR) 2 Instrument.

Accumulation of experience with minimally invasive surgery over the last three decades has rendered laparoscopic surgery the mainstay of management for surgical pathology during pregnancy. In the present meta-review, we compiled the available evidence on the safety of laparoscopic and robotic-assisted surgeries during pregnancy, based on relevant systematic reviews (SR) and meta-analyses (MA). A systematic review was performed for articles published until February 2024 in English using PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online) and Google Scholar based on predefined selection and exclusion criteria. We implemented the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included SRs and MAs examining women of childbearing age (population) who had undergone laparoscopic surgery or robotic-assisted laparoscopic surgery during pregnancy (intervention). The presence of comparison to open surgery was desirable but not mandatory (comparator). The included studies should necessarily report on fetal loss (outcome), and optionally on other metrics of fetal, maternal, or operative performance. We considered SRs/MAs analyzing randomized trials, observational studies, case reports, and case series (study design). The methodological quality of SRs/MAs not exclusively including case reports and case series was assessed with the Assessment of Multiple Systematic Reviews (AMSTAR) 2 instrument. A total of 1229 articles were screened, of which 78 were potentially eligible. Of these, 33 articles met our inclusion criteria, 18 containing SRs only and 15 SRs with MA. The examined disciplines were laparoscopic appendectomy (10 studies, 30.3%), laparoscopic cerclage for cervical insufficiency (eight studies, 24.2%), adnexal-ovarian laparoscopic surgery (five studies, 15.2%), laparoscopic cholecystectomy and biliary tree exploration (three studies, 9.1%), laparoscopic myomectomy (two studies, 6.1%), and one study each for laparoscopic surgery regarding pancreatic indications, adrenal indications, and bariatric complications (3.0%). The odds ratio/relative risk for fetal loss rate ranged from 0-1.9, with variable statistical significance depending on the discipline. Twenty-three out of the 33 studies were submitted to quality evaluation with the AMSTAR 2 instrument, with three being of "low quality" (13.0%) and the remaining 20 of "critically low quality" (87.0%). In conclusion, the widespread acceptance of laparoscopic surgery for treating surgical pathology during pregnancy is substantiated by heterogeneous and low-quality evidence. Literature mainly revolves around laparoscopic appendectomy, whereas other disciplines that may commonly arise during pregnancy, such as cholecystectomy and the acute abdomen following bariatric surgery, are underrepresented in the literature. Factors such as anatomical alterations that may affect surgical access, surgeon's expertise, and the biological course of the underlying pathology should be taken into consideration when selecting the appropriate mode of operating during pregnancy.

Infant, Neonatal, and Post-neonatal Mortality in Greece: A Nationwide Time-Trend Analysis.

INTRODUCTION: Infant mortality is a crucial perinatal measure and is also regarded as an important public health indicator. This study aimed to comprehensively present time trends in infant, neonatal, and post-neonatal mortality in Greece. METHODS: The annual infant mortality rate (IMR), the neonatal mortality rate (NMR), and the post-neonatal mortality rate (PNMR) were calculated based on official national data obtained from the Hellenic Statistical Authority, spanning 67 years from 1956 to 2022. The time trends of the mortality rates were evaluated using joinpoint regression analysis, and the annual percent changes (APC) and the overall average annual percent change (AAPC) were calculated with a 95% confidence interval (95% CI). RESULTS: The IMR exhibited accelerating declines over more than 50 years, with an APC of -1.9 (-2.8 to -1.0) from 1956 to 1968, -5.4 (-5.6 to -5.2) from 1968 to 1999, and -7.3 (-8.9 to -5.7) between 1999 and 2008. In 2008, IMR reached its all-time low of 2.7 per 1,000 live births, down 16.6-fold from its peak at 44.1 per 1,000 live births in 1957. This improving trend was reversed following the onset of the economic crisis in the country, leading to a 57% increase in IMR from 2008 to 2016, with an upward trend APC of 3.4 (1.2 to 5.5). In the recent period 2016-2022, there was an improvement with an APC of -3.7 (-6.2 to -1.1), resulting in an IMR of 3.1 per 1,000 live births in 2022. The decrease in IMR was estimated to have prevented 209,109 infant deaths in the country from 1958 to 2022. From 1956 to 2022, the IMR decreased with an AAPC of -3.9 (-4.3 to -3.4), while the PNMR saw a decline with an AAPC of -4.5 (-5.1 to -3.9) and the NMR with an AAPC of -3.2 (-3.7 to -2.6). CONCLUSION: Greece achieved an impressive decrease in infant mortality rates, but this progress was halted and completely reversed during the economic crisis. Although there have been some recent improvements after the country's economic recovery, the rates have yet to reach pre-crisis levels.

Correlation of Serum Prolactin Levels With Metabolic and Cardiovascular Risk in Greek Women With Polycystic Ovarian Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among females. PCOS is associated with various metabolic and cardiovascular complications, including insulin resistance, dyslipidemia, and an increased risk of type 2 diabetes mellitus and cardiovascular disease. The role of serum prolactin (PRL) in the development of these complications in PCOS is not well understood. AIM: This study aims to investigate the correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS. METHODS: The study utilized secondary outcomes from a prospectively collected patient database at the Third Department of Obstetrics and Gynecology, Medical School of the University of Athens. Data were collected from patients who visited the Gynecological Endocrinology - Pediatric and Adolescence Endocrinology Outpatient Clinic between January 2007 and December 2015. Measurements of various parameters, including PRL levels, BMI, waist circumference, hormone levels, lipid profiles, and insulin sensitivity, were obtained. Statistical analyses, including Mann-Whitney tests, chi-square tests, Spearman correlations, and multiple linear regression analyses, were conducted using SPSS software (IBM Corp., Armonk, NY, USA). RESULTS: The study included 247 women with PCOS, with a mean age of 24.7 years. Participants were divided into two groups based on the median PRL level. Women with higher PRL levels (>14.9) had lower BMI and waist circumference, higher levels of certain hormones and insulin sensitivity, and lower levels of fasting insulin, total cholesterol, and total lipids. Factors associated with lower PRL levels included being overweight/obese and smoking more than 10 cigarettes per day. Higher age, BMI, waist circumference, and certain hormone levels were associated with lower PRL levels. CONCLUSION: The findings suggest a correlation between serum PRL levels and metabolic and cardiovascular risk factors in Greek women with PCOS. Further research is needed to elucidate the role of PRL in the pathophysiology of PCOS and to explore its potential as a diagnostic and therapeutic target.

The Contribution of Multiple Pregnancies in Stillbirths in Greece: A Time-Trend Analysis.

Introduction Multiple pregnancy is an established risk factor for fetal death. This study aimed to examine the impact of multifetal pregnancies on stillbirth rates (SBRs) in the Greek population. Methods Data on live births and stillbirths by multiplicity were derived from the Hellenic Statistical Authority, covering a 65-year period from 1957 to 2021. The SBR for multiple and single gestations, and the population attributable risk (%) (PAR (%)) stillbirth attributable to multifetal gestations were calculated, and temporal trends were assessed using joinpoint regression analysis, with annual percentage changes (APC) and 95% confidence interval (95% CI). Results In the period 1957-2021, multiple pregnancies accounted for 9.4% of total stillbirths in Greece and the overall relative risk of fetal death among multifetal gestations was 3.34, in comparison with singletons. The SBR in multiple births remained unchanged from 1957 to 1976 and showed downward trends from 1976 to 2021 (APC = -3.0, 95% CI: -3.4 to -2.7, p < 0.001). PAR (%), after two decades of stability, showed an increasing trend over the period 1975-2011 (APC = 3.4, 95% CI: 2.8 to 4.0, p < 0.001), which was reversed in the more recent decade 2011-2021 (APC = -6.1, 95% CI: -9.6 to -2.5, p = 0.001), with PAR (%) decreasing from a historical high of 19.3% in 2012 to 8.6% in 2021. Conclusion The high incidence of multiple births has a considerable impact on stillbirth rates in the Greek population. The recent downward trends of SBR and PAR (%) of multiple gestations are encouraging, however more measures and targeted interventions are needed to improve perinatal outcomes in multifetal gestation.

The Effectiveness of Metabolic Bariatric Surgery in Preventing Gynecologic Cancer - from Pathophysiology to Clinical Outcomes.

Obesity and cancer represent two pandemics of current civilization, the progression of which has followed parallel trajectories. To time, thirteen types of malignancies have been recognized as obesity-related cancers, including breast (in postmenopausal women), endometrial, and ovarian cancer. Pathophysiologic mechanisms that connect the two entities include insulin resistance, adipokine imbalance, increased peripheral aromatization and estrogen levels, tissue hypoxia, and disrupted immunity in the cellular milieu. Beyond the connection of obesity to carcinogenesis at a molecular and cellular level, clinicians should always be cognizant of the fact that obesity might have secondary impacts on the diagnosis and treatment of gynecologic cancer, including limited access to effective screening programs, resistance to chemotherapy and targeted therapies, persisting lymphedema, etc. Metabolic bariatric surgery represents an attractive intervention not only for decreasing the risk of carcinogenesis in high-risk women living with obesity but most importantly as a measure to improve disease-specific and overall survival in patients with diagnosed obesity-related gynecologic malignancies. The present narrative review summarizes current evidence on the underlying pathophysiologic mechanisms, the clinical data, and the potential applications of metabolic bariatric surgery in all types of gynecologic cancer, including breast, endometrial, ovarian, cervical, vulvar, and vaginal.

Measurement of Calprotectin and PTH in the Amniotic Fluid of Early Second Trimester Pregnancies and Their Impact on Fetuses with Growth Disorders: Are Their Levels Related to Oxidative Stress?

Background: During the early stages of human fetal development, the fetal skeleton system is chiefly made up of cartilage, which is gradually replaced by bone. Fetal bone development is mainly regulated by the parathyroid hormone parathormone (PTH) and PTH-related protein, with specific calprotectin playing a substantial role in cell adhesion and chemotaxis while exhibiting antimicrobial activity during the inflammatory osteogenesis process. The aim of our study was to measure the levels of PTH and calprotectin in early second trimester amniotic fluid and to carry out a comparison between the levels observed among normal full-term pregnancies (control group) and those of the groups of embryos exhibiting impaired or enhanced growth. Methods: For the present prospective study, we collected amniotic fluid samples from pregnancies that underwent amniocentesis at 15 to 22 weeks of gestational age during the period 2021-2023. Subsequently, we followed up on all pregnancies closely until delivery. Having recorded fetal birthweights, we then divided the neonates into three groups: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Results: In total, 64 pregnancies, including 14 SGA, 10 LGA, and 40 AGA fetuses, were included in our study. Both substances were detected in early second trimester amniotic fluid in both groups. Concentrations of calprotectin differed significantly among the three groups (p = 0.033). AGA fetuses had a lower mean value of 4.195 (2.415-6.425) IU/mL, whereas LGA fetuses had a higher mean value of 6.055 (4.887-13.950) IU/mL, while SGA fetuses had a mean value of 5.475 (3.400-9.177) IU/mL. Further analysis revealed that only LGA fetuses had significantly higher calprotectin concentrations compared to AGA fetuses (p = 0.018). PTH concentration was similar between the groups, with LGA fetuses having a mean value of 13.18 (9.51-15.52) IU/mL, while SGA fetuses had a mean value of 14.18 (9.02-16.00) IU/mL, and AGA fetuses had similar concentrations of 13.35 (9.05-15.81) IU/mL. The differences in PTH concentration among the three groups were not statistically significant (p = 0.513). Conclusions: Calprotectin values in the amniotic fluid in the early second trimester were higher in LGA fetuses compared to those in the SGA and AGA categories. LGA fetuses can possibly be in a state of low-grade chronic inflammation due to excessive fat deposition, causing oxidative stress in LGA fetuses and, eventually, the release of calprotectin. Moreover, PTH concentrations in the amniotic fluid of early second trimester pregnancies were not found to be statistically correlated with fetal growth abnormalities in either LGA or SGA fetuses. However, the early time of collection and the small number of patients in our study should be taken into account.

Second Trimester Amniotic Fluid Angiotensinogen Levels Linked to Increased Fetal Birth Weight and Shorter Gestational Age in Term Pregnancies.

BACKGROUND: Despite the considerable progress made in recent years in fetal assessment, the etiology of fetal growth disturbances is not as yet well understood. In an effort to enhance our knowledge in this area, we investigated the associations of the amniotic fluid angiotensinogen of the renin-angiotensin system with fetal growth abnormalities. METHODS: We collected amniotic fluid samples from 70 pregnant women who underwent amniocentesis during their early second trimester. Birth weight was documented upon delivery, after which the embryos corresponding to the respective amniotic fluid samples were categorized into three groups as follows: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Amniotic fluid angiotensinogen levels were determined by using ELISA kits. RESULTS: Mean angiotensinogen values were 3885 ng/mL (range: 1625-5375 ng/mL), 4885 ng/mL (range: 1580-8460 ng/mL), and 4670 ng/mL (range: 1995-7250 ng/mL) in the SGA, LGA, and AGA fetuses, respectively. The concentrations in the three groups were not statistically significantly different. Although there were wide discrepancies between the mean values of the subgroups, the large confidence intervals in the three groups negatively affected the statistical analysis. However, multiple regression analysis revealed a statistically significant negative correlation between the angiotensinogen levels and gestational age and a statistically significant positive correlation between the birth weight and angiotensinogen levels. DISCUSSION: Our findings suggest that fetal growth abnormalities did not correlate with differences in the amniotic fluid levels of angiotensinogen in early second trimester pregnancies. However, increased angiotensinogen levels were found to be consistent with a smaller gestational age at birth and increased BMI of neonates.

Evaluation of IOTA-ADNEX Model and Simple Rules for Identifying Adnexal Masses by Operators with Varying Levels of Expertise: A Single-Center Diagnostic Accuracy Study.

Objectives The discrimination of ovarian lesions presents a significant problem in everyday clinical practice with ultrasonography appearing to be the most effective diagnostic technique. The aim of our study was to externally evaluate the performance of different diagnostic models when applied by examiners with various levels of experience. Methods This was a diagnostic accuracy study including women who were admitted for adnexal masses, between July 2018 and April 2021, to a Greek tertiary oncology center. Preoperatively sonographic data were evaluated by an expert gynecologist, a 6 th and a 1 st year gynecology resident, who applied the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR) and Assessment of Different NEoplasias in the adneXa (ADNEX) model to discriminate between benign and malignant ovarian tumors. The explant pathology report was used as the reference diagnosis. Kappa statistics were used for the investigation of the level of agreement between the examined systems and the raters. Results We included 66 women, 39 with benign and 27 with malignant ovarian tumors. ADNEX (with and without "CA-125") had high sensitivity (96-100%) when applied by all raters but a rather low specificity (36%) when applied by the 1st year resident. SR could not be applied in 6% to 17% of the cases. It had slightly lower sensitivity, higher specificity, and higher overall accuracy, especially when applied by the 1st year resident (61% vs. 92%), compared to ADNEX. Conclusion Both ADNEX and SR can be utilized for screening in non-oncology centers since they offer high sensitivity even when used by less experienced examiners. In the hands of inexperienced examiners, SR appears to be the best model for assessing ovarian lesions.