scholarly journals Investigation of Cumulus Cell Factors Associated With Embryo Development and Pregnancy Outcome in Human IVF

2021 ◽  
Author(s):  
◽  
Jozsef Ekart
Keyword(s):  
Candidate Genes ◽  
Pregnancy Outcome ◽  
Live Birth ◽  
Young Women ◽  
Pregnancy Outcomes ◽  
Mrna Levels ◽  
Successful Pregnancy ◽  
Expression Levels ◽  
Healthy Women ◽  
Qpcr Method

<p>Recent evidence suggests that the expression of some candidate genes in cumulus cells (CC) have the potential to serve as markers of oocyte quality. The aims of this study were: 1) to validate a multiplex quantitative polymerase chain reaction (QPCR) method to measure four genes simultaneously in extracts from individual CC and; 2) to investigate the relationships in individual cumulus-oocyte-complexes (COC) amongst the expression levels of a range of candidate genes (N=8) from individual CC, the numbers of CC per COC and developmental indicators (good blastocyst development and live birth outcome) of the associated oocytes following in vitro fertilization (IVF) with intra-cytoplasmic sperm injection (ICSI). Sixty eight women were recruited for this study following approval from NZ Multi-Regional Ethics Committee and classified into four research groups: young and healthy women (<38 years, N=25), young women with polycystic ovarian syndrome (<38 years, N=11), young with diminished ovarian reserve (<38 years, N=12) and older and healthy women (≥40 years, N=20). Following exogenous rFSH-assisted ovarian stimulation, 608 COC were collected and subjected to ICSI. Oocyte and embryo quality, and pregnancy outcomes were recorded. Expression levels of the following candidate genes HAS2, FSHR, SLC2A4 (GLUT4), ALCAM, SFRP2, VCAN, NRP1 and PR in CC extracts from individual COC were measured by TaqMan QPCR and normalized against the house-keeping gene, RPL19. The numbers of CC from individual COC were calculated from RPL19 expression levels plotted against a standard curve of CC number. These results were then assessed against the outcomes of the associated oocytes following ICSI. HAS2, FSHR, ALCAM, VCAN, NRP1 and PR mRNA were detectable in most samples (98.5%) whereas those for SLC2A4 and SFRP2 were generally undetectable. The minimum number of CC required for QPCR was estimated to be ~70. The mean levels of FSHR mRNA were up-regulated in young women with PCOS compared to those in the other two groups of women <38y. Expression levels of HAS2 across all four groups of women were correlated to both biological (age, basal serum FSH and serum AMH) and treatment (amount of rFSH used for stimulation, follicle numbers and COC retrieved) variables. Investigations related to oocyte development in young and healthy women showed that 1) mean mRNA levels of VCAN, HAS2 and PR were higher (P=0.002, P<0.05, P<0.05, respectively) in CC associated with oocytes that resulted in good quality blastocysts and those of VCAN were higher (P<0.05) in CC associated with oocytes that resulted in a live birth, compared with those with developmental failure. However, the expression levels of all measurable candidate genes were highly variable for individual CC from COC from each woman. Indeed, 99.7% of individual COC were different in CC mRNA levels and cell composition. The application of a ranking method to score the relative CC mRNA levels of selected candidate genes from each COC recovered from individual women was evaluated. This approach demonstrated a predictive power of 80% efficiency for selecting good quality oocytes (at least one), whilst requiring the insemination of no more than three oocytes in any treatment cycle. Furthermore, this selection method resulted in a pregnancy and live birth rate of 60 and 52% respectively (N=25 women). This outcome is similar to that achieved when all metaphase II (MII) oocytes are inseminated. In conclusion, this study has validated a multiplex QPCR method to quantify the expression levels of four genes in CC of individual human COC simultaneously using as few as 70 cells. Moreover, that there is sufficient cDNA so that many more candidate genes can be measured in the same extract. From the knowledge of the mRNA levels of at least four genes, VCAN, FSHR, HAS2 and PR in CC, it is possible to improve upon existing biological indicators the potential to predict good blastocyst formation and a successful pregnancy outcome. It is concluded that the application of a multiplex QPCR approach to assess the expression levels of a limited number of marker genes in CC can be used to select the best oocytes for successful pregnancy outcomes.</p>

scholarly journals Investigation of Cumulus Cell Factors Associated With Embryo Development and Pregnancy Outcome in Human IVF

2021 ◽  
Author(s):  
◽  
Jozsef Ekart
Keyword(s):  
Candidate Genes ◽  
Pregnancy Outcome ◽  
Live Birth ◽  
Young Women ◽  
Pregnancy Outcomes ◽  
Mrna Levels ◽  
Successful Pregnancy ◽  
Expression Levels ◽  
Healthy Women ◽  
Qpcr Method

<p>Recent evidence suggests that the expression of some candidate genes in cumulus cells (CC) have the potential to serve as markers of oocyte quality. The aims of this study were: 1) to validate a multiplex quantitative polymerase chain reaction (QPCR) method to measure four genes simultaneously in extracts from individual CC and; 2) to investigate the relationships in individual cumulus-oocyte-complexes (COC) amongst the expression levels of a range of candidate genes (N=8) from individual CC, the numbers of CC per COC and developmental indicators (good blastocyst development and live birth outcome) of the associated oocytes following in vitro fertilization (IVF) with intra-cytoplasmic sperm injection (ICSI). Sixty eight women were recruited for this study following approval from NZ Multi-Regional Ethics Committee and classified into four research groups: young and healthy women (<38 years, N=25), young women with polycystic ovarian syndrome (<38 years, N=11), young with diminished ovarian reserve (<38 years, N=12) and older and healthy women (≥40 years, N=20). Following exogenous rFSH-assisted ovarian stimulation, 608 COC were collected and subjected to ICSI. Oocyte and embryo quality, and pregnancy outcomes were recorded. Expression levels of the following candidate genes HAS2, FSHR, SLC2A4 (GLUT4), ALCAM, SFRP2, VCAN, NRP1 and PR in CC extracts from individual COC were measured by TaqMan QPCR and normalized against the house-keeping gene, RPL19. The numbers of CC from individual COC were calculated from RPL19 expression levels plotted against a standard curve of CC number. These results were then assessed against the outcomes of the associated oocytes following ICSI. HAS2, FSHR, ALCAM, VCAN, NRP1 and PR mRNA were detectable in most samples (98.5%) whereas those for SLC2A4 and SFRP2 were generally undetectable. The minimum number of CC required for QPCR was estimated to be ~70. The mean levels of FSHR mRNA were up-regulated in young women with PCOS compared to those in the other two groups of women <38y. Expression levels of HAS2 across all four groups of women were correlated to both biological (age, basal serum FSH and serum AMH) and treatment (amount of rFSH used for stimulation, follicle numbers and COC retrieved) variables. Investigations related to oocyte development in young and healthy women showed that 1) mean mRNA levels of VCAN, HAS2 and PR were higher (P=0.002, P<0.05, P<0.05, respectively) in CC associated with oocytes that resulted in good quality blastocysts and those of VCAN were higher (P<0.05) in CC associated with oocytes that resulted in a live birth, compared with those with developmental failure. However, the expression levels of all measurable candidate genes were highly variable for individual CC from COC from each woman. Indeed, 99.7% of individual COC were different in CC mRNA levels and cell composition. The application of a ranking method to score the relative CC mRNA levels of selected candidate genes from each COC recovered from individual women was evaluated. This approach demonstrated a predictive power of 80% efficiency for selecting good quality oocytes (at least one), whilst requiring the insemination of no more than three oocytes in any treatment cycle. Furthermore, this selection method resulted in a pregnancy and live birth rate of 60 and 52% respectively (N=25 women). This outcome is similar to that achieved when all metaphase II (MII) oocytes are inseminated. In conclusion, this study has validated a multiplex QPCR method to quantify the expression levels of four genes in CC of individual human COC simultaneously using as few as 70 cells. Moreover, that there is sufficient cDNA so that many more candidate genes can be measured in the same extract. From the knowledge of the mRNA levels of at least four genes, VCAN, FSHR, HAS2 and PR in CC, it is possible to improve upon existing biological indicators the potential to predict good blastocyst formation and a successful pregnancy outcome. It is concluded that the application of a multiplex QPCR approach to assess the expression levels of a limited number of marker genes in CC can be used to select the best oocytes for successful pregnancy outcomes.</p>

The effect of Day 3 cell number on pregnancy outcomes in vitrified-thawed single blastocyst transfer cycles

2020 ◽  
Vol 35 (11) ◽  
pp. 2478-2487
Author(s):  
Jiayi Wu ◽  
Jie Zhang ◽  
Yanping Kuang ◽  
Qiuju Chen ◽  
Yun Wang
Keyword(s):  
Pregnancy Rate ◽  
Live Birth ◽  
Young Women ◽  
Pregnancy Outcomes ◽  
Cell Number ◽  
Blastocyst Transfer ◽  
Cell Group ◽  
Single Blastocyst Transfer ◽  
Significant Difference ◽  
Blastomere Number

Abstract STUDY QUESTION Does cell number on Day 3 have an impact on pregnancy outcomes in vitrified-thawed single blastocyst transfer cycles? SUMMARY ANSWER A low Day 3 cell number (≤5 cells) was independently associated with decreased live birth rate (LBR) during single blastocyst transfer cycles in young women. WHAT IS KNOWN ALREADY Day 3 cell number is an effective predictor of IVF success rates when transferring cleavage stage embryos. However, the association between Day 3 blastomere number and pregnancy outcomes after blastocyst transfer is still unknown. STUDY DESIGN, SIZE, DURATION A retrospective cohort study of 3543 patients who underwent frozen-thawed single blastocyst transfers from January 2013 to June 2018 at a tertiary-care academic medical center. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were grouped into six groups according to the Day 3 cell number: ≤4 cells, 5 cells, 6 cells, 7 cells, 8 cells and &gt;8 cells. The primary outcome measure was LBR. A logistic regression analysis was performed to explore the independent association between Day 3 blastomere number and LBR after adjustment for some potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE In women &lt;35 years old, the LBR varied significantly according to Day 3 cell number, with the rate of 31.2%, 34.4%, 41.9%, 45.1%, 48.1% and 48.2% for the ≤4-cell, 5-cell, 6-cell, 7-cell, 8-cell and &gt;8-cell groups, respectively (P &lt; 0.001). This significant difference was also observed in the high- and low-quality blastocyst subgroups of young women. However, for women ≥35 years old, the rate of live birth was similar between groups. Furthermore, after accounting for confounding factors, the LBR was significantly decreased in the ≤4-cell (adjusted odds ratio (aOR): 0.62, 95% CI: 0.48–0.80, P &lt; 0.001) and 5-cell (aOR: 0.73, 95% CI: 0.57–0.92, P = 0.009) groups as compared to the 8-cell group. Likewise, the blastocysts arising from ≤4-cell (aOR: 0.73, 95% CI: 0.57–0.93, P = 0.010) or 5-cell (aOR: 0.77, 95% CI: 0.61–0.97, P = 0.024) embryos were associated with lower clinical pregnancy rate than those from 8-cell embryos. No significant differences were observed in biochemical pregnancy rate and miscarriage rate. LIMITATIONS, REASONS FOR CAUTION A limitation of the current study was its retrospective design. Future prospective studies are needed to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS Our observations suggested that a low Day 3 cell number was related to decreased LBR after blastocyst transfer in young women, which provided vital information for clinicians in selecting blastocyst during IVF treatment. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Natural Science Foundation of China (NSFC) (31770989 to Y.W.; 81671520 to Q.C.) and the Shanghai Ninth People’s Hospital Foundation of China (JYLJ030 to Y.W.). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Expression of Ara-C Metabolizing Enzymes Mediates in Vitro Sensitivity to Ara-C in Primary AML Cells From Patients with Denovo AML,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3481-3481
Author(s):  
Ajay Abraham ◽  
Savitha Varatharajan ◽  
Ashok kumar Jayavelu ◽  
Shaji R Velayudhan ◽  
Rayaz Ahmed ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Candidate Genes ◽  
P Value ◽  
Mrna Levels ◽  
Wild Type ◽  
Mutation Status ◽  
Expression Levels ◽  
In Vitro Sensitivity ◽  
Mrna Expression Levels

Abstract Abstract 3481 Wide inter-individual variation in terms of treatment outcome and toxic side effects of treatment exist among patients with AML receiving chemotherapy with cytarabine (ara-C) and daunorubicin. The pre-requisite for the cytotoxic action of pro-drug Ara-C is the enzymatic conversion to its active tri-phosphorylated form ara-CTP. Many drug activating (Deoxycytidine kinase (dCK) and human Equilibrative Nucleoside Transporter 1 (hENT1) and deactivating (Cytidine deaminase (CDA), 5'nucleotidase (NT5C2) genes and ribonucleoside reductase (RRM1), which are involved in transport and biotransformation of cytarabine contribute to the variation in ara-C sensitivity in AML patients. FLT3-ITD and NPM1 mutations act as major poor and good prognostic markers respectively in cytogenetically normal AML. The effect of these mutations in ara-C metabolism remains to be elucidated. The present study aims to determine independent as well as the combined effect of ara-C metabolizing genes mRNA expression on in-vitro ara-C cytotoxicity and the role of FLT3-ITD and NPM mutations on mRNA expression of these genes. Diagnostic bone marrow sample (median blasts 65%; range 21 – 98%) from 98 adult patients with de novo AML (other than AML-M3) were included in this study. mRNA expression levels for each target gene relative to housekeeping gene GAPDH was analyzed using Taqman based gene expression assays. In vitro cytotoxicity was assessed using MTT cell viability assay and IC-50 was calculated. In vitro sensitivity or resistance was classified on the basis of the IC-50 values <6uM and >6uM ara-C respectively. FLT3 ITD and NPM mutation status at diagnosis were determined through PCR followed by Genescan analysis using genomic DNA samples. Type of NPM mutation was identified by sequencing. When ara-C IC-50 values were compared with the mRNA expression levels of these candidate genes, Ara-C sensitive samples (n= 30; IC-50 < 6uM) showed significantly higher mRNA expression of dCK and hENT1 compared to those with Ara-C resistance (n=51) IC50 >6uM (median 314 (61.56 – 1232) vs. 180 (31.87 – 749.2); p = 0.0004 and median 172.1 (44.12 – 657.6) vs. 96.19 (37.49 – 432.4), p= 0.0008 respectively. RRM1 and NT5C2 did not show any association with in vitro Ara-C cytotoxicity, while CDA showed a trend towards association with lower CDA expression in ara-C sensitive samples. Based on these findings we put forward Ara-C resistance index (RI). RI is calculated by the formula RI = ΔCT (dCK X ENT1)/ ΔCT CDA. (Smaller ΔCT value= higher mRNA expression). RI values were significantly higher in resistant (IC50 >6uM) compared to sensitive cells (median: 6.084; range 1.89–11.82) vs. 3.702 (1.89–9.80); p=<0.0001). This association should now be validated in an independent cohort. Effects of NPM and FLT3 mutation status on Ara-C metabolizing genes were then evaluated. No significant association was found between FLT3-ITD status and the mRNA expression of these candidate genes. Interestingly, dCK mRNA levels were significantly higher in samples with NPM mutation (n=39) compared to NPM wild type (n=59); median 272.3 (41.64–1232) vs. 188.6 (31.87–1030); p value= 0.01. When analysed separately, patients with NPM type A mutation (n=27) showed significantly higher dCK expression (median 347.4 (41.64–1232) vs. 188.6 (31.87–1030); p value= 0.003 compared to those with wild type NPM1. This first report showing an association between expression profiles of ara-C metabolizing genes and NPM mutation should form the basis for evaluating their clinical correlations. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Using Deep Learning in a Monocentric Study to Characterize Maternal Immune Environment for Predicting Pregnancy Outcomes in the Recurrent Reproductive Failure Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunyu Huang ◽  
Zheng Xiang ◽  
Yongnu Zhang ◽  
Dao Shen Tan ◽  
Chun Kit Yip ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Live Birth ◽  
Pregnancy Outcomes ◽  
Prediction Models ◽  
Reproductive Failure ◽  
Clinical Pregnancy ◽  
Clinical Samples ◽  
Ongoing Pregnancy ◽  
Biochemical Pregnancy ◽  
Immune Factors

Recurrent reproductive failure (RRF), such as recurrent pregnancy loss and repeated implantation failure, is characterized by complex etiologies and particularly associated with diverse maternal factors. It is currently believed that RRF is closely associated with the maternal environment, which is, in turn, affected by complex immune factors. Without the use of automated tools, it is often difficult to assess the interaction and synergistic effects of the various immune factors on the pregnancy outcome. As a result, the application of Artificial Intelligence (A.I.) has been explored in the field of assisted reproductive technology (ART). In this study, we reviewed studies on the use of A.I. to develop prediction models for pregnancy outcomes of patients who underwent ART treatment. A limited amount of models based on genetic markers or common indices have been established for prediction of pregnancy outcome of patients with RRF. In this study, we applied A.I. to analyze the medical information of patients with RRF, including immune indicators. The entire clinical samples set (561 samples) was divided into two sets: 90% of the set was used for training and 10% for testing. Different data panels were established to predict pregnancy outcomes at four different gestational nodes, including biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth, respectively. The prediction models of pregnancy outcomes were established using sparse coding, based on six data panels: basic patient characteristics, hormone levels, autoantibodies, peripheral immunology, endometrial immunology, and embryo parameters. The six data panels covered 64 variables. In terms of biochemical pregnancy prediction, the area under curve (AUC) using the endometrial immunology panel was the largest (AUC = 0.766, accuracy: 73.0%). The AUC using the autoantibodies panel was the largest in predicting clinical pregnancy (AUC = 0.688, accuracy: 78.4%), ongoing pregnancy (AUC = 0.802, accuracy: 75.0%), and live birth (AUC = 0.909, accuracy: 89.7%). Combining the data panels did not significantly enhance the effect on prediction of all the four pregnancy outcomes. These results give us a new insight on reproductive immunology and establish the basis for assisting clinicians to plan more precise and personalized diagnosis and treatment for patients with RRF.

scholarly journals Improving the Metrics and Data Reporting for Maternal Mortality:A Challenge to Public Health Surveillance and Effective Prevention

2019 ◽  
Vol 11 (2) ◽  
Author(s):  
James Studnicki ◽  
David Reardon ◽  
Donna Harrison ◽  
John Fisher ◽  
Ingrid Skop
Keyword(s):  
Maternal Mortality ◽  
Pregnancy Outcome ◽  
Live Birth ◽  
Pregnancy Outcomes ◽  
Maternal Mortality Ratio ◽  
Mortality Data ◽  
Evidence Based ◽  
Maternal Deaths ◽  
Effective Prevention ◽  
Mortality Ratio

AbstractBackgroundThe current measuring metric and reporting methods for assessing maternal mortality are seriously flawed. Evidence-based prevention strategies require consistently reported surveillance data and validated measurement metrics.Main BodyThe denominator of live births used in the maternal mortality ratio reinforces the mistaken notion that all maternal deaths are consequent to a live birth and, at the same time, inappropriately inflates the value of the ratio for subpopulations of women with the highest percentage of pregnancies ending in outcomes other than a live birth. Inadequate methods for identifying induced or spontaneous abortion complications assure that most maternal deaths associated with those pregnancy outcomes are unlikely to be attributed. Absent the ability to identify all maternal deaths, and without the ability to differentiate those deaths by specific pregnancy outcomes, existing variations in pregnancy outcome-specific maternal deaths are masked by the use of an aggregated (all outcome) numerator. Under these circumstances, clear and accurate data is not available to inform evidence-based preventive strategies. As the result, algorithms applied for analyzing maternal mortality data may return distorted results.ConclusionImprovement in the effectiveness of maternal mortality surveillance will require: mandatory certification of all fetal losses; linkage of death, birth and all fetal loss (induced and natural) certificates; modification of the structure of the overall maternal mortality ratio to enable pregnancy outcome-specific ratio calculations; development of the appropriate ICD codes which are specific to induced and spontaneous abortions; education for providers on identifying and reporting early pregnancy losses; and, flexible information systems and methods which integrate these capabilities and inform users. 

scholarly journals Successful Pregnancy Outcome in Unicornuate Uterus

2019 ◽  
Vol 7 (4) ◽  
pp. 307-308
Author(s):  
Feriha Fatima Khidri ◽  
Faiza Kamran Ali ◽  
Hafsa Shabir Ahmed
Keyword(s):  
Case Report ◽  
Caesarean Section ◽  
Pregnancy Outcome ◽  
Pregnancy Outcomes ◽  
Successful Pregnancy ◽  
Unicornuate Uterus ◽  
Obstetric History

Pregnancy with a unicornuate uterus is an infrequent obstetrical presentation. Unicornuate uterus leads to various complications, including infertility and poor pregnancy outcomes. It may be asymptomatic and remain undiagnosed till the woman is unable to conceive or present with a bad obstetric history. Here we present a case report of a patient with unicornuate uterus diagnosed during caesarean section along with delivery of alive baby.Key Words: Outcome, Pregnancy, Unicornuate uterusAddress

scholarly journals Association between endometrial indoleamine 2,3-dioxygenase expression level and pregnancy outcomes in women undergoing first in vitro fertilization treatment

2020 ◽  
Author(s):  
Su Liu ◽  
Hongxia Wei ◽  
Yuye Li ◽  
Ruochun Lian ◽  
Xiaohui Wang ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Live Birth ◽  
Pregnancy Outcomes ◽  
Luteal Phase ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Expression Level ◽  
Vitro Fertilization ◽  
Expression Levels

Abstract BackgroundIndoleamine 2,3-dioxygenase (IDO) has been reported to play a key role in placental development during normal pregnancy. However, the question of whether endometrial IDO expression affects in vitro fertilization (IVF) pregnancy outcomes remains unclear. The current study was undertaken to investigate whether there was any association between endometrial IDO expression and IVF treatment outcome.MethodsThis retrospective study was designed to compare pregnancy outcomes among women with different endometrial IDO expression levels under their first IVF treatment. A total of 140 women undergoing their IVF treatment were selected from January 2017 to December 2017. Endometrial samples were collected during mid-luteal phase before IVF cycle. The endometrial IDO expression levels were analyzed by immunohistochemistry, and compared between women who were pregnant or not. A logistic regression analysis was performed to determine the impact of endometrial IDO expression on live birth.ResultsNo significant differences in the endometrial IDO expression levels were found between women who had clinical pregnancy and those who failed (P>0.05). However, the endometrial IDO expression level was significantly higher among women who had live birth compared with those who had no live birth (P=0.031). Additionally, after adjusting for differences in maternal age, BMI and duration of gonadotropin stimulation, women with higher IDO expression level had an increased live birth rate (adjusted odds ratio [aOR] 2.863, 95% confidence interval [CI] 1.180-6.947). ConclusionsHigher endometrial IDO expression level during mid-luteal phase is associated with an increased live birth rate in women undergoing their first IVF treatment.

scholarly journals AB0338 PREGNANCY OUTCOMES IN ADOLESCENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1194.1-1194
Author(s):  
P. Alba ◽  
Y. Tissera ◽  
N. Cucchiaro ◽  
V. Savio ◽  
R. Serrano Morales ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Adolescent Pregnancy ◽  
Pregnancy Outcome ◽  
Young Women ◽  
Lupus Erythematosus ◽  
Pregnancy Outcomes ◽  
Fetal Outcome ◽  
Maternal Outcomes ◽  
Systemic Lupus ◽  
Fetal Outcomes

Background:Systemic lupus erythematosus (SLE) is a autoimmune disease that affects adolescents and young women of childbearing age. In spite of the improvement in fetal and maternal SLE pregnancy outcome in the last decades, they have increased risk of adverse outcomes including disease flare, abortions, preeclampsia (PE) and premature birth (PB). However, pregnancy outcomes among adolescents with SLE have not been well explored.Objectives:To evaluate maternal and fetal outcomes in pregnant adolescents with SLE.Methods:We retrospectively studied all pregnant SLE adolescent patients, who attended to 3 Maternity Hospitals in Argentina in the last 5 years. Demographic, clinical, and laboratory data were collected. The presence of Antiphospholipid Syndrome (APS) and the Antiphospholipid antibodies (AA), and maternal and fetal outcome were evaluated. Adolescent pregnancy was defined it is happened between 10 and 19 years old. Lupus activity was evaluated by SELENA SLEDAI at the conception and each trimester of pregnancy and puerperium.Results:32 pregnancies in 21 patients were included. Mean age was 18 years old, 66% was mestizo ethnicity and mean disease duration of 2 years. Renal involvement was found in 19, Mucocutaneous in 21, and hematological in 14 patients. 4 patients had positive Anti-SSA/Ro antibodies, 1 Anti-SSB/La, 2 Lupus anticoagulant, 6 Ig G ACL, 3 Ig M ACL, and 8 patients fulfilled APS criteria. Activity disease was 0 SELENA SLEDAI in 1 ° trimester, 4 in 2°,3° trimester and puerperium. Maternal and fetal outcomes are shown in Table 1. Cesarean section was performed in 58%(n=18) of the patients, 6 had abortions and 1 fetal death.Table 1.Maternal outcomesDisease Flares13(41%) 7 renal (PE)/Hellp6 (19%)Gestational Diabetes1 (3%)Maternal outcomesSpontaneous Membrane Rupture1 (3%)Mortality0Fetal outcomeLive birth24 (75%)Gestational age (weeks)32 (32-38)Weight (grs)2805 (2100-3340)IUGR5 (16%)PB8 (25%)Conclusion:Maternal and fetal complications were high in adolescent pregnancy with SLE, including disease activity, PE and PB. A tight control of patients should be performed before and after conception. These patients should be managed by a multidisciplinary team, thus allowing an improvement of maternal and fetal prognosis.References:[1]Ling N, Lawson E, von Scheven E. Adverse Pregnancy outcome in adolescents and young women with systemic lupus erythematosus: a national estimate. Pediatric Rheumatology 2018, 16:26.[2]FraserA, Brockert J, Ward R: Association of young maternal age with adverse reproductive outcomes. N Engl J Med 1995, 223:1113-1117. 26.Disclosure of Interests:None declared

scholarly journals Longer Duration and Proper Titration of Low Molecular Weight Heparin (LMWH), Are Independent Factors for Successful Pregnancy Outcome. Retrospective Analysis from a Single Center

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5065-5065
Author(s):  
Maria Stamou ◽  
Stergios Intzes ◽  
Eleftheria Lamprianidou ◽  
Menelaos Konstantinos Papoutselis ◽  
Zoe Bezirgiannidou ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Live Birth ◽  
Pregnancy Complications ◽  
Pregnancy Loss ◽  
Single Center ◽  
Successful Pregnancy ◽  
Live Births ◽  
Continuous Parameter ◽  
At Iii ◽  
Thrombophilia Screening

Abstract The role of thrombophilia and LMWH use in pregnancy loss (PL) and pregnancy complications (PC) is debated. In this retrospective study from a single center we analyzed the clinical outcome of pregnancies in relation to thrombophilic factors and the use of LMWH, aspirin and folic acid in 143 women followed up for a total of 173 pregnancies referred to our center from 2003 to 2016. Methods: Women were referred to our unit for: more than 2 unexplained PL (n=96, 78 experienced only early PL, 11 had only late PL, 7 had both early and late), one pregnancy loss(n=45) or one pregnancy complication (placenta abruption, intrauterine growth restriction, eclampsia, n=2). Mutations in Factor V-Leiden (FVL, G1691A), Prothrombin (PTG, G20210A) and MTHFR (C677T, A 1206C) were checked by DNA hybridization Kit. Plasma levels of antithrombin-III, protein-C, free Protein-S, APCR, FVIII, FXII, PT aPTT, fibrinogen, homocysteine and La-test were measured by photometry (DACO). Anticardiolopin and anti-β2GPI antibodies (IGG and IGM) were measured by ELISA in serum (APLA). End points were live birth and pregnancy complications. The prevalence of thrombophilia in our cohort was similar with previous studies and 34/143 (23,4%) women were negative for all thrombophilic factors. We observed mutations in FVL(11,6%), PTG (9,6%), MTHFR (homozygous or double heterozygous, 33,3%) and deficiencies of AT-III (3,3%), Prot-C (1,6%), Prot-S (8,8%), APS (8,7%). Combined severe trombophilic factors were found in 31 women (21,5%) (FVL+PTG 4/31, Natural Anticoagulants one out 3 Def + MTHFR 3/31, APS + MTHFR 2/31, FVL+MTHFR 16/31, PTG + MTHFR 6/31). We then separated our cohort into women with <2 complications or women with >2 complications. The second group had significantly higher incidence of FVL mutation (12,5 vs 8,3%, p=0.05) and deficiencies of AT-III and Free Prot-S ( 6,5 vs 0 %, p=0.01) compared to the first one. By contrast, women in the first group had higher incidence of La-test (12,5 vs 4,5%, p=0,03), APLA ( 12 vs 6,6%, p=0.03) and Prot.C deficiency (4,5 vs 0%, p=0.01). In univariate analysis both hereditary and acquired thrombophilic factors did not correlated with pregnancy outcome (live birth or pregnancy complications). Only age as a continuous parameter correlated negatively with live birth and positively with pregnancy complications (p=0.01 and p=0.025, respectively), whereas high BMI as a continuous parameter also negatively affected live births (p= 0.049). Logistic regression analysis reveals that the age of 35 is the cut off for unfortunate pregnancy outcome. Pregnancies were proceeded with (n=143, 81,7%) or without (n=32, 18,3%,) LMWH. The decision to use LMWH were based in a positive thrombophilia screening test (n=84) or to prior history >2 pregnancy complications with negative trombophilia testing (n=59). Concomitant use of ASA was prescribed in 78 pregnancies (dose less than 100 mg/day) and concomitant follic acid in 143 pregnancies. The percentage of live births were identical in women treated with LMWH (87,4%) or not (87,5%, p=0.9). In multivariate analysis, the only factor that was strongly correlated to live birth was the duration of LMWH treatment (odds ratio, OR =3,567, 95% CI (1.845, 6,894), p= 0,01) and the titration of the dose with anti-Xa (OR=5,138, 95% CI (1,717, 15,376), p = 0,01, fig.1a). By ROC analysis the duration of LMWH which correlated to live birth was ≥ 5.5 months(fig. 1b). The addition of ASA was insignificant for live birth (p=0.7), while the duration (>6months) of follic acid also appeared to add a benefit in combination with LMWH (p=0.01). Moreover, pregnancies proceeded without LMWH exhibited higher rates of pregnancy complications (18,75 vs 11,2%, p=0.08) and prematurity (14,3 vs 8,8%, p=0.05). In summary, our findings argue against hereditary thrombophilia screening in the cases of previous pregnancy loss or pregnancy complications. On the contrary, testing for APS even after the first event might be of value as this population often has laboratory evidence of APS and may benefit from proper anticoagulation. The use of LMWH and folic acid but not of ASA was related to less pregnancy complications or prematurity, whereas proper titration of LMWH by using anti-Xa and long duration of therapy were the only important factors for successful pregnancy outcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals Methylobacterium oryzae Influences Isoepoxydon Dehydrogenase Gene Expression and Patulin Production by Penicillium expansum

Water ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1427
Author(s):  
Tiago Barros Afonso ◽  
Lúcia Chaves Simões ◽  
Nelson Lima
Keyword(s):  
Gene Expression ◽  
Distribution Systems ◽  
Water Distribution ◽  
Penicillium Expansum ◽  
Transcriptional Level ◽  
Positive Trend ◽  
Mrna Levels ◽  
Expression Levels ◽  
Production Values ◽  
Methylobacterium Oryzae

Biofilms can be considered the main source of microorganisms in drinking water distribution systems (DWDS). The ecology of a biofilm is dependent on a variety of factors, including the presence of microbial metabolites excreted by its inhabitants. This study reports the effect of the Gram-negative bacteria Methylobacterium oryzae on the idh gene expression levels and patulin production of Penicillium expansum mature biofilms. For this purpose, a RT-qPCR method to quantify idh mRNA levels was applied. In addition, the idh expression levels were compared with the patulin production. The results obtained revealed that the effect of the bacterium on pre-established P. expansum biofilms is dependent on the time of interaction. More mature P. expansum biofilms appear to be more resistant to the inhibitory effect that M. oryzae causes towards idh gene expression and patulin production. A positive trend was observed between the idh expression and patulin production values. The results indicate that M. oryzae affects patulin production by acting at the transcriptional level of the idh gene.

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