The clinical significance of electronic fetal heart rate monitoring in twins.

OBJECTIVES: Fully effective intrapartum cardiotocographic (CTG) fetal heart monitoring is still missing. Visual analysis is far from credibility. Additional, computerized analysis techniques were proposed however they did not substantially decrease possible risks of fetal asphyxia. In twin pregnancies the problem is even more complicated. Our goal is to find the most valuable parameters in intrapartum CTG surveillance in twins, based on actual FIGO criteria. MATERIAL AND METHODS: Study included 58 women in labor who had been admitted to Delivery Department of tertiary care hospital with twin pregnancy in a period of one year. The features of the CTG (e.g., baseline, oscillation, decelerations, brady- or tachycardia) were grouped to create three variables that were closest to the FIGO CTG scale. All three groups were compared according to neonatal status (Apgar score at 5 min ≥ 7 or < 7; pH value in umbilical artery ≥ 7.20, < 7.20 or < 7.10 and BE (base excess) > or ≤ -12). Fetal status and its acid - base equilibrium was compared either with long term variability (LTV), short term variability (STV), or percentage of the signal loss. RESULTS: Out of 58 twin pregnancies, a total of 116 babies were born. One baby was born dead. From this group, 11 deliveries were natural births and 47 deliveries were C-sections. None of the analyzed features (pH, BE, Apgar, CTG features except tracing length, CTG FIGO categories) were statistically different between groups of singleton and twin pregnancies, except percentage of C-sections. No differences were found either for STV or LTV and fetal status.org CTG categories. CONCLUSIONS: Prior to cardiotocographic tracing of twins during labor, ultrasound examination should be mandatory. Considerable loss of signal in CTG tracing in twins should provoke ultrasonographic confirmation of the fetal status.

Outcome dependent twin growth curves based on birth weight percentiles for Polish population.

OBJECTIVE: The objective of this study is to determine a healthy fetal growth pattern of twins from a Polish population based on an outcome-dependent growth curve. METHODS: The fetal growth data of live-born twin pregnancies between 25th and 40th week gestation in the period of 1 January 2005 to 31 March 2018 from the database of a tertiary care women's hospital in Western Poland was used to calculate birth weight percentiles. The growth curves of singletons from the same database were used as comparison. Because this study aimed for an outcome-dependent approach for the calculation of fetal growth curves, all babies born that may have high risk of unfavorable outcome were excluded. After application of all exclusion criteria, 1317 records referring to 2634 children were included in our analysis. Growth curves of singletons from the same database were used as reference for this study. RESULTS: A linear relationship between 10th, 50th, and 90th percentiles and gestational age were found for twins but not for singletons suggesting the different mechanisms of intrauterine growth between singleton and twin pregnancies. Week-to-week weight gain equal to or higher than 150 g in twins also predict a favorable outcome in absence of other pathologies. CONCLUSION: The calculated outcome-dependent fetal growth curves for twins in this study may help in the accurate diagnosis of small or large twin fetuses for their gestational age in this Western Poland population.

Effect of Protoberberine-Rich Fraction of Chelidonium majus L. on Endometriosis Regression.

Endometriosis is a gynecological disease defined by the presence of endometrial tissue outside the uterus. To date, the effective treatment of this disease is still based on invasive surgery or laparoscopy. Chelidonium majus L. (Papaveraceae) belongs to medicinal, latex-bearing plants. Extracts from the plant are a rich source of pharmacologically active agents. Protoberberine compounds derived from C. majus possess anticancer and antiproliferative activities. In the present study of a rat model of endometriosis, we investigated the influence of the plant protoberberine-rich fraction (BBR) obtained from the medicinal plant C. majus on the development of endometriosis. To understand of BBR therapeutic potential for endometriosis, metabolomics has been applied to study. BBR was prepared from an ethanolic extract of dry plants C. majus. Rats (n = 16) with confirmed endometriosis were treated with BBR administered orally (1 g/kg) for 14 days. Blood serum samples were collected from all of the animals and metabolites were studied using the NMR method. The metabolomic pattern was compared before and after the protoberberine treatment. The performed analysis showed significant changes in the concentrations of metabolites that are involved in energy homeostasis, including glucose, glutamine, and lactate. Histopathological studies showed no recurrence of endometriosis loci after treatment with BBR. The results of the study found that BBR treatment prevents the recurrence of endometriosis in rats. Moreover, metabolomics profiling can be applied to better understand the mechanisms of action of these protoberberine secondary plant metabolites. Our findings provide new insights into the pharmaceutical activity of natural protoberberine plant compounds.

Outcome dependent growth curves for singleton pregnancies based on birth weight of babies for Polish population.

OBJECTIVES: To create outcome dependent fetal growth curves and birth weight standards that can be analyzed for use in clinic specifically for Western European populations. MATERIAL AND METHODS: We conducted a retrospective study on fetal growth and birth weight trends from live birth singleton pregnancies between 2005 and 2018 at one of the largest tertiary gynecologic-obstetric hospitals in Poland. The inclusion criteria were at least 22 weeks of gestation at birth regardless of delivery mode (vaginal or C-section), no congenital anomalies diagnosed before and after delivery and an Apgar score of at least 7 in the first minute. The final sample had a total of 39,413 cases (18,562 girls and 20,851 boys). We presented 7 (for all fetuses in the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles) and 6 (for boys and girls each at 10th, 50th and 90th percentiles) fetal growth curves between 25 and 40 weeks of gestation. Birth weight trends were obtained and analyzed from all babies in the 5th, 10th, 25th, 50th, 75th and 95th percentiles born between 22 to 42 weeks of gestation with also separate trends for boys and girls. RESULTS: The largest differences in fetal growth curves were observed in the 10th and 50th percentiles between 22 and 34 weeks of gestation. A decreasing fetal weight gain pattern was observed between 27 and 30 weeks and after 38 weeks of gestation, the decrease was more drastic in female. A significant increase from 2009 to 2017 was observed in the weight of 50th percentile babies born at or after 35 weeks. We found significant discrepancies between our results and the most used European fetal growth curves particularly in the 10th and 90th percentile weights at 30 weeks. CONCLUSIONS: Separate scales for boys and girls were implied and given the overall difference form commonly used references. We believe there is significant value in using these unique patterns found in fetal growth curves and birth weights of ethnically homogenous population (such as Poland) at everyday clinical practice for more opportunities of safe obstetric care and higher chances of delivering a healthy child.

The impact of surgical treatment of obesity on the female fertility.

As obesity is considered to be a pandemic of the twenty-first century, the bariatric surgery becomes more common through the global population. The adverse effects of obesity on fertility can be reversed through the bariatric surgery procedures. In this review, we presented the effects of bariatric surgery on hypothalamic-pituitary-ovarian axis and fertility, ovarian reserve, and contraception efficacy.

Significance of intratissue estrogen concentration coupled with estrogen receptors levels in colorectal cancer prognosis.

Dysregulation of estrogen related pathways is implicated colorectal cancer (CRC) development. However, significance of intratissue concentration of estrone (E1) and 17ß-estradiol (E2) in relation to estrogen receptor (ESR) expression level was not addressed so far. Herein, we measured E1 and E2 intratissue concentration using liquid chromatography electrospray ionization tandem mass spectrometry (ESI LC/MS) and mRNA levels of ESR1 and ESR2 using RT-qPCR in cancerous and histopathologically unchanged tissue from 75 and 110 CRC patients, respectively. The obtained results were associated with clinicopathological factors, expression of estrogen dependent genes (CTNNB1, CCND1) and prognostic significance. We found no statistically significant differences in E1 or E2 concentration between cancerous tissue and histopathologically unchanged counterparts. Moreover, mRNA levels of ESR1 and ESR2 were significantly decreased in cancerous tissue compared with histopathologically unchanged (p=0.00001). Log rank analysis revealed no benefit of low E1 to E2 ratio, high E1, E2 concentration or ESR1, ESR2 mRNA level for patients' overall (OS) and disease free survival (DFS). Interestingly, we have observed that patients with low ESR1 mRNA level coupled with low E1 intratissue concentration had a significant decrease in DFS compared with group of patients with high ESR1 mRNA level and high E1 concentration (HR=0.16, 95% CI 0.02-1.05; p=0.06). Furthermore, patients with low E1 concentration and low ESR1 transcript had significantly higher CTNNB1 and CCND1 mRNA level compare with subgroup with high level of both grouping factors. Our study indicates a potential value of estrogen intratissue concentration and its receptor expression level for CRC patients' prognosis.

Effect of DNA methylation profile on OATP3A1 and OATP4A1 transcript levels in colorectal cancer.

Epidemiological studies indicate that 17ß-estradiol (E2) prevents colorectal cancer (CRC). Organic anion transporting polypeptides (OATPs) are involved in the cellular uptake of various endogenous and exogenous substrates, including hormone conjugates. Because transfer of estrone sulfate (E1-S) can contribute to intra-tissue conversion of estrone to the biologically active form -E2, it is evident that the expression patterns of OATPs may be relevant to the analysis of CRC incidence and therapy. We therefore evaluated DNA methylation and transcript levels of two members of the OATP family, OATP3A1 and OATP4A1, that may be involved in E1-S transport in colorectal cancer patients. We detected a significant reduction in OATP3A1 and a significant increase in OATP4A1 mRNA levels in cancerous tissue, compared with histopathologically unchanged tissue (n=103). Moreover, we observed DNA hypermethylation in the OATP3A1 promoter region in a small subset of CRC patients and in HCT116 and Caco-2 colorectal cancer cell lines. We also observed increased OATP3A1 transcript following treatment with 5-aza-2-deoxycytidine and sodium butyrate. The OATP4A1 promoter region was hypomethylated in analyzed tissues and CRC cell lines and was not affected by these treatments. Our results suggest a potential mechanism for OATP3A1 downregulation that involves DNA methylation during colorectal carcinogenesis.

Clinical significance of DNA methylation mRNA levels of TET family members in colorectal cancer.

PURPOSE: Ten eleven translocation (TET) enzyme activity is essential for active DNA demethylation in biological processes, and their altered expression has been observed in various malignancies. Therefore, we investigated DNA methylation and mRNA levels of all TETs in colorectal cancer (CRC) patients. METHODS: TET mRNA levels were evaluated using quantitative RT-PCR in primary cancerous and histopathologically unchanged colorectal tissues from patients who underwent radical surgical colon resection (n = 113). DNA methylation levels of the TET CpG island were assessed using bisulfite DNA sequencing and high-resolution melting analysis. RESULTS: We found reduced transcript levels of TET1, TET2 and TET3 in cancerous tissue compared with their histopathologically unchanged counterparts (p = 0.000011; p = 0.000001; p = 0.00031, respectively). Importantly, multivariate Cox regression analysis revealed favorable overall survival (OS) and disease-free survival (DFS) outcomes for patients with high TET2 mRNA levels in histopathologically unchanged tissue (HR(OS) = 0.091, 95 % CI 0.011-0.77, p = 0.028; HR(DFS) = 0.21, 95 % CI 0.04-1.06, p = 0.059). Moreover, we found no DNA methylation in the TET2 and TET3 promoter regions in cancerous and histopathologically unchanged tissue. In contrast, we reported TET1 DNA hypermethylation in a small fraction of patients (n = 12/113). CONCLUSION: To best of our knowledge, our study is the first to investigate TET mRNA levels in a cohort of CRC patients and correlate them with patients' prognosis. Present study provides the evidence that TET2 mRNA expression may be an independent prognostic factor for disease recurrence and outcome. Additionally, our findings initially indicate the importance of DNA methylation in regulating TET1 expression.