Digital insertion of Foley catheter 16F versus 22F versus 28F in unripe cervix labor induction: A randomized trial.

AIM: To explore digital insertion in dorsal recumbent position of 16F, 22F, or 28F catheter bores on insertion failure, duration, and pain in unripe cervix labor induction. METHODS: A randomized trial was performed in a University hospital in Malaysia. Term women scheduled for labor induction, Bishop score ≤ 5, singleton, cephalic presentation, intact membrane, and reassuring pre-induction fetal heart rate tracing were recruited. Women with known gross fetal anomaly, allergy to latex and inability to consent or language difficulty were excluded. Participants were randomized to 16F, 22F, or 28F Foley catheter. Primary outcome was insertion failure and main secondary outcomes were insertion duration and pain (assessed by a Visual Numerical Rating Scale [VNRS] 0-10, higher score more pain). Analysis is done by analysis of variance (ANOVA), Kruskal-Wallis, and chi square test across the three arms and by t test and Mann-Whitney U test for pair wise comparisons. RESULTS: One hundred twenty-seven participants' data were analyzed. The insertion failure 7/43(16%) versus 4/42(10%) versus 5/42(12%), p = 0.64, insertion duration median [IQR] 2.8 [1.8-4.8] versus 2.8 [1.7-3.7] versus 2.8 [1.7-4.3] min, p = 0.68 and insertion pain VNRS mean {SD} 4.2 {2.5} versus 3.4 {2.3} versus 3.6 {2.2}, p = 0.26, insertion to delivery interval 26.0 {9.7} versus 25.6 {9.1} versus 22.8 {7.4} h, p = 0.45, and spontaneous vaginal delivery 20/43 (45%) versus 23/42(55%) versus 25/42(60%), p = 0.48 for 16F versus 22F versus 28F arms, respectively. Pairwise comparisons were not different. CONCLUSION: Foley catheter 16F versus 22F versus 28F resulted in similar digital insertion performance in the dorsal recumbent position for unripe cervix labor induction. CLINICAL TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN21224268.

Metformin in gestational diabetes mellitus: A double-blind placebo-controlled randomized trial.

OBJECTIVE: To evaluate the impact of preemptive metformin on the level of glycosylated hemoglobin (HbA1c) at 36 weeks of pregnancy in women with gestational diabetes mellitus controlled by diet change (GDMA1). METHODS: A randomized, double-blind, placebo-controlled trial was performed in a university hospital. Women with GDMA1 were recruited at 16-30 weeks of pregnancy and randomized to oral metformin 500 mg twice daily or identical placebo tablets to delivery. Level of HbA1c was taken at recruitment and at 36 weeks of pregnancy. The primary outcome was the change in level of HbA1c at recruitment and 36 weeks of pregnancy. RESULTS: Data from 106 participants were analyzed. The level of HbA1c during pregnancy increased significantly with a mean increase of 0.20% ± 0.31% (P < 0.001; metformin) versus 0.27% ± 0.31% (P < 0.001; placebo). An increment of 0.07% across trial arms was not significant (P = 0.310). Mean birth weight was significantly lower in the metformin group (2.81 ± 0.41 kg vs 2.98 ± 0.37 kg; P = 0.030). Rates of macrosomia (≥3.5 kg; 0/53 [0%] vs 4/53 [8%]; P = 0.123) and low birth weight (<2.5 kg; 11/53 [21%] vs 5/53 [9%]; P = 0.102) were not significantly different. CONCLUSION: Preemptive metformin did not prevent the level of HbA1c at 36 weeks of pregnancy from rising nor significantly reduce the increase of HbA1c. Mean birth weight was significantly lower in the metformin arm with a non-significant trend to low birth weight, which is concerning. ISRCTN: ISRCTN10845466.

Impact of IL1B gene polymorphisms and interleukin 1B levels on susceptibility to spontaneous preterm birth.

OBJECTIVE: Genetic factors influence susceptibility to preterm birth (PTB) and the immune pathway of PTB that involves the production of cytokines such as interleukins has been implicated in PTB disease. The aim of this study is to investigate the association of interleukin 1ß (IL1B) gene polymorphisms and IL1B levels with spontaneous PTB. STUDY DESIGN: Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the Sequenom MassARRAY platform. Maternal plasma was used to measure IL1B levels. RESULTS: There was no significant association between the allelic and genotype distribution of IL1B single nucleotide polymorphism (SNP) (rs1143634, rs1143627, rs16944) and the risk of PTB among Malaysian Malay women (rs1143634, P=0.722; rs1143627, P=0.543; rs16944, P=0.615). However, IL1B levels were significantly different between women who delivered preterm compared with those who delivered at term (P=0.030); high mean levels were observed among Malay women who delivered at preterm (mean=32.52) compared with term (mean=21.68). IL1B SNPs were not associated with IL1B plasma levels. CONCLUSION: This study indicates a significant association between IL1B levels and reduced risk of PTB among the Malaysian Malay women. This study shows the impact of IL1B levels on susceptibility to PTB disease; however, the high levels of IL1B observed among women in the preterm group are not associated with IL1B SNPs investigated in this study; IL1B high levels may be because of other factors not explored in this study and therefore warrant further investigation.

Role of Genistein in Preeclampsia: A Case-Control Study.

OBJECTIVE: To examine the association between genistein intake (estimated from a food frequency questionnaire [FFQ) and incidence of preeclampsia. STUDY DESIGN: The study was conducted at University Malaya Medical Center, Kuala Lumpur, and involved 32 women with preeclampsia and 32 healthy pregnant women (matched by parity and gestational age). A validated FFQ was used to collect information regarding dietary intake of genistein during their pregnancy. The association between preeclampsia and the level of genistein intake was evaluated by categorizing the participants into 3 groups according to tertiles of estimated genistein intake. RESULTS: The odds ratio estimates showed a four-fold increase in the risk of developing preeclampsia for tertile 1 (lowest intake) as compared with tertile 3 (highest intake) (crude OR, 4.38; 95% CI 1.21-15.81). CONCLUSION: Lower levels of genistein intake were associated with an increased risk of developing preeclampsia. These findings suggest a possible beneficial role of genistein in the prevention of preeclampsia.

Association of VEGFA gene polymorphisms and VEGFA plasma levels with spontaneous preterm birth.

BACKGROUND: Angiogenic pathway regulating genes such as vascular endothelial growth factor A (VEGFA) have been implicated in preterm birth (PTB) complications. Research shows that the VEGFA/VEGF receptor system plays an important role in the regulation of circulating progesterone level. Attenuation of VEGFA signaling at mid pregnancy results in onset of labor and parturition because of a reduction in circulating progesterone levels. The aim of this study was to investigate the association of VEGFA gene polymorphisms (rs2010963, rs3025039, rs699947, and rs10434) with spontaneous PTB and VEGFA plasma levels in preterm and term women. STUDY DESIGN: Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the SequenomMassARRAY platform. Maternal plasma was used to measure VEGFA levels. RESULTS: Results showed a significant association between rs2010963 variants and PTB at both allelic and genotypic levels. The frequencies of CG and GG genotypes were significantly higher in the preterm group (96%) than in the term group (87%) (P=0.012). The odds of the G allele occurring among the preterm group was 1.8 times higher than those in the term group (odds ratio 1.8, 95% confidence interval 1.2-2.6, P=0.003). After adjustment for Bonferroni correction, the association between rs2010963 variants and PTB remained significant (P=0.004). The rs69947 was associated with PTB at a nominal significance level (P=0.030). There was no significant association between rs3025039, rs10434, and PTB in this population. VEGFA gene polymorphisms were not associated with VEGFA plasma levels. This study indicated for the first time that the VEGFA rs2010963 polymorphisms may play a potential role in preterm complications.

Influence of endometriosis on assisted reproductive technology outcomes: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association of endometriosis on assisted reproductive technology (ART) outcomes and to review if surgical treatment of endometriosis before ART affects the outcomes. DATA SOURCES: We searched studies published between 1980 and 2014 on endometriosis and ART outcome. We searched MEDLINE, PubMed, ClinicalTrials.gov, and Cochrane databases and performed a manual search. METHODS OF STUDY SELECTION: A total of 1,346 articles were identified, and 36 studies were eligible to be included for data synthesis. We included published cohort studies and randomized controlled trials. TABULATION, INTEGRATION, AND RESULTS: Compared with women without endometriosis, women with endometriosis undertaking in vitro fertilization and intracytoplasmic sperm injection have a similar live birth rate per woman (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.84-1.06, 13 studies, 12,682 patients, I=35%), a lower clinical pregnancy rate per woman (OR 0.78, 95% CI 0.65-0.94), 24 studies, 20,757 patients, I=66%), a lower mean number of oocyte retrieved per cycle (mean difference -1.98, 95% CI -2.87 to -1.09, 17 studies, 17,593 cycles, I=97%), and a similar miscarriage rate per woman (OR 1.26, 95% CI (0.92-1.70, nine studies, 1,259 patients, I=0%). Women with more severe disease (American Society for Reproductive Medicine III-IV) have a lower live birth rate, clinical pregnancy rate, and mean number of oocytes retrieved when compared with women with no endometriosis. CONCLUSION: Women with and without endometriosis have comparable ART outcomes in terms of live births, whereas those with severe endometriosis have inferior outcomes. There is insufficient evidence to recommend surgery routinely before undergoing ART.

The immunohistochemistry signature of mismatch repair (MMR) proteins in a multiethnic Asian cohort with endometrial carcinoma.

Endometrial cancer is the most common gynecologic cancer in developed countries and is rising in incidence globally. Although the 5-year survival rates are >80%, factors beyond conventional pathologic features that predict clinical outcomes are still being elucidated. The aims of this study were to define the prevalence and associations of deficient mismatch repair (dMMR) protein expression (MLH1, MSH2, MSH6, PMS2) by immunohistochemistry in a multiethnic Southeast Asian cohort with endometrioid endometrial cancer. A total of 77 patients with adequate formalin-fixed paraffin-embedded specimens were identified. The sections were stained in 2 centers for 4 MMR proteins and examined by 2 independent specialist histopathologists. The mean age for the cohort was 58.6 yr, with 19.4% (15/77) of patients' cancers showing loss of 2 MMR proteins. All 13 cancers with absent MLH1 showed PMS2 loss (13/15), whereas absent MSH2 correlated with MHS6 loss (2/15). There were no significant differences for dMMR cases in age, body mass index, histopathologic characteristics, and clinical outcomes. In dMMR cases, an overrepresentation of patients of Indian ethnic origin was observed compared with Chinese and Malays. These findings suggest that dMMR protein expression in a Southeast Asian endometrial cancer cohort does not correlate with disease outcomes.

Human papillomavirus vaccination in the resourced and resource-constrained world.

Human papillomavirus has been established as the causal agent for cervical cancer. The identification of a clear cause presents an unparalleled opportunity for cancer control. As such, the development of prophylactic human papillomavirus vaccines has been rightly hailed as one of the significant scientific triumphs of the past 20 years. This story of scientific triumph over disease, however, is not yet complete. The fruit of scientific labour must be delivered to the people in order to fulfil the underlying intent of the research (i.e. to prevent cancer and save lives). The success of a vaccination programme, however, does not depend on the biological efficacy of the vaccine alone. Various other local factors, such as poverty, gender inequality, cultural traditions, or religious beliefs, can significantly constrain the success of any vaccination programme. In this chapter, we provide an overview of how the human papillomavirus vaccine works and its global uptake, as well as, how variations in local contexts can affect the successful implementation of a vaccination programme. Other factors besides vaccine costs also need serious attention. With better understanding of such factors, policy makers and medical health professionals will be better equipped to make informed decisions to maximise the potential benefits of the human papillomavirus vaccines for the most number of people in individual countries.

Contemporary approaches to hyperemesis during pregnancy.

PURPOSE OF REVIEW: Nausea and vomiting of pregnancy (NVP) affects 90% of pregnant women and its impact is often underappreciated. Hyperemesis gravidarum, the most severe end of the spectrum, affects 0.5-2% of pregnancies. The pathogenesis of this condition remains obscure and its management has largely been empirical. This review aims to provide an update on advances in pregnancy hyperemesis focusing on papers published within the past 2 years. RECENT FINDINGS: The cause of hyperemesis is continuing to be elaborated. Recent data attest to the effectiveness of the oral doxylamine-pyridoxine in NVP. Follow-up data of children exposed in early pregnancy to doxylamine-pyridoxine for NVP are reassuring. Evidence is increasing for ginger as an effective herbal remedy for NVP. Metoclopramide is effective in NVP and hyperemesis gravidarum, with a good balance of efficacy and tolerability. A recent large-scale study on first trimester exposure to metoclopramide is reassuring of its safety. Evidence is emerging for the treatment of acid reflux to ameliorate NVP. The role of corticosteroids for hyperemesis gravidarum remains controversial. Transpyloric feeding may be warranted for persistent weight loss, despite optimal antiemetic therapy. SUMMARY: Women with significant NVP should be identified so that they can be safely and effectively treated.

Effect of high levels of human chorionic gonadotropin and estradiol on the severity of hyperemesis gravidarum.

BACKGROUND: Serum human chorionic gonadotropin (hCG) and estradiol levels are higher in women with hyperemesis gravidarum (HG) than in unaffected pregnant controls. We postulated that higher levels of these hormones may be associated with clinically more severe HG. The aim of this study was to evaluate the effect of maternal hCG and estradiol levels on the severity of HG. METHODS: A prospective study was performed on 167 first trimester women hospitalized for HG. Venous blood was taken for hCG and estradiol levels. Scattergrams were plotted for hCG or estradiol levels vs. gestational age. A curve of best fit was drawn. Women were categorized into two groups according to their position above or below the curve. Prolonged hospital stay (> or =4 days) was used as a marker for HG severity. Multivariable logistic regression analysis was used to control for differences in characteristics, laboratory results on admission, and treatment received. RESULTS: After adjustment, high hCG level adjusted odds ratio (AOR) (2.2, 95% CI 1.0-4.9, p=0.04) and hyponatremia AOR (2.8, 95% CI 1.2-6.6, p=0.02) were independently associated with prolonged hospital stay. With bivariate analysis, high estradiol level was not associated with prolonged stay. CONCLUSIONS: High hCG but not estradiol is associated with more severe HG.

Gamma-glutamyltransferase level in pregnancy is an independent risk factor for gestational diabetes mellitus.

AIM: To evaluate the relationship between gamma-glutamyltransferase (GGT) level in pregnant women at oral glucose tolerance test (OGTT) and the diagnosis of gestational diabetes (GDM). METHODS: Blood was taken for analyzing GGT level from women at high risk of GDM at the time of their scheduled OGTT. GDM was diagnosed according to World Health Organization 1999 criteria. RESULTS: GGT level correlated positively with the 2-hour glucose level (Spearman's rho = 0.112: P < 0.05). GGT values that were stratified into quartiles demonstrated a significant trend with diagnosis of GDM (chi(2) for trend; P = 0.03). Multivariable logistic regression analysis taking into account maternal age, gestational age at OGTT, body mass index and a positive 50-g glucose challenge test (GCT) indicated that high GGT was an independent risk factor for GDM (adjusted odds ratio [AOR] 2.1 95% CI 1.2-3.8: P = 0.01). In the subset of women identified by a positive GCT, on multivariable logistic regression analysis, only high GGT was an independent risk factor for GDM (AOR 2.3 95% CI 1.3-4.2: P = 0.007). CONCLUSION: Raised GGT level is an independent risk factor for GDM in high risk pregnant women undergoing OGTT.

Thrombophilic mutations in pre-eclampsia and pregnancy-induced hypertension.

AIM: The aim of the present study was to determine the existence or prevalence of thrombophilic markers such as Factor V Leiden, prothrombin G20210A, protein S, protein C, activated protein C and anti-thrombin in pre-eclampsia and pregnancy-induced hypertensive patients. METHODS: Blood samples were collected from a total number of 124 women at the maternity unit, University of Malaya Medical Center. These included 49 patients with pre-eclampsia, 63 patients with pregnancy-induced hypertension and 12 normal pregnant women. DNA was extracted from the blood samples. Factor V Leiden (Taq I) and prothrombin G20210A (Hind III) genotyping was done on polymerase chain reaction-restriction fragment length polymorphism. Anti-thrombin activity and the concentrations of protein C, protein S and activated protein C were measured using the IL Coagulation System (Hemosil). RESULTS: Of the 124 subjects, one pre-eclampsia patient was homozygous for Factor V Leiden mutation but prothrombin G20210A mutation was not present in any of the subjects. The subject with Factor V Leiden mutation also had a low activated protein C resistance and a low protein S concentration. CONCLUSIONS: Factor V Leiden mutation is present in the Asian population and may very well serve as one of the genetic factors responsible for pre-eclampsia and other adverse pregnancy outcomes.

Pregnancy outcome in hyperemesis gravidarum and the effect of laboratory clinical indicators of hyperemesis severity.

OBJECTIVE: To determine pregnancy outcome in hyperemesis gravidarum and the effect of metabolic, biochemical, hematological and clinical indicators of disease severity on outcome. STUDY DESIGN: A retrospective study based on 166 women hospitalized for confirmed hyperemesis gravidarum from January 2004 to January 2005. For each woman, three controls matched for age, parity and ethnicity were obtained from our 2004 birth register. The effects of laboratory indicators of hyperemesis severity were separately analyzed within the hyperemesis gravidarum study group. Outcome measures include stillbirths, Apgar score, mode of delivery, low birthweight, preterm delivery, labor induction, pregnancy induced hypertension and gestational diabetes. Analysis was by t-test, Fisher's exact test and multivariable logistic regression analysis. RESULTS: Women with hyperemesis had similar pregnancy outcome compared to controls. In the analysis of laboratory indicators of hyperemesis severity and pregnancy outcomes, hypokalemia (adjusted odds ratio [AOR] 2.7: 95% confidence interval [CI] 1.0-6.8) was associated with emergency operative delivery, high creatinine (odds ratio 4.4: 95% CI 1.3-15) with labor induction and raised gamma glutamyltransferase (AOR 7.5: 95% CI 1.2-46) with the development of gestational diabetes. CONCLUSIONS: Hyperemesis gravidarum per se was not associated adverse pregnancy outcome. Hypokalemia, high creatinine and raised gamma glutamyltransferase in women with hyperemesis gravidarum were associated with adverse pregnancy outcome.