Diagnostic Strategies for Postmenopausal Bleeding

Postmenopausal bleeding (PMB) is a common clinical problem. Patients with PMB have 10%-15% chance of having endometrial carcinoma and therefore the diagnostic workup is aimed at excluding malignancy. Patient characteristics can alter the probability of having endometrial carcinoma in patients with PMB; in certain groups of patients the incidence has been reported to be as high as 29%. Transvaginal sonography (TVS) is used as a first step in the diagnostic workup, but different authors have come to different conclusions assessing the accuracy of TVS for excluding endometrial carcinoma. Diagnostic procedures obtaining material for histological assessment (e.g., dilatation and curettage, hysteroscopy, and endometrial biopsy) can be more accurate but are also more invasive. The best diagnostic strategy for diagnosing endometrial carcinoma in patients with PMB still remains controversial. Future research should be focussed on achieving a higher accuracy of different diagnostic strategies

Timing of elective pre-labour caesarean section: a decision analysis

__Background:__ Since caesarean sections (CSs) before 39+0 weeks gestation are associated with higher rates of neonatal respiratory morbidity, it is recommended to delay elective CSs until 39+0 weeks. However, this bears the risk of earlier spontaneous labour resulting in unplanned CSs, which has workforce and resource implications, specifically in smaller obstetric units. __Aim:__ To assess, in a policy of elective CSs from 39+0 weeks onward, the number of unplanned CSs to prevent one neonate with respiratory complications, as compared to early elective CS. __Materials and Methods:__ We performed a decision analysis comparing early term elective CS at 37+0–6 or 38+0–6 weeks to elective prelabour CS, without strict medical indication, at 39+0–6 weeks, with earlier unplanned CS, in women with uncomplicated singleton pregnancies. We used literature data to calculate the number of unplanned CSs necessary to prevent one neonate with respiratory morbidity. __Results:__ Planning all elective CSs at 39+0–6 weeks required 10.9 unplanned CSs to prevent one neonate with respiratory morbidity, compared to planning all elective CSs at 38+0–6 weeks. Compared to planning all elective CSs at 37+0–6 weeks we needed to perform 3.3 unplanned CSs to prevent one neonate with respiratory morbidity. __Conclusion:__ In a policy of planning all elective pre-labour CSs from 39+0 weeks of gestation onward, between three and 11 unplanned CSs have to be performed to prevent one neonate with respiratory morbidity. Therefore, in our opinion, fear of early term labour and workforce disutility is no argument for scheduling elective CSs <39+0 weeks

Mechanical methods for induction of labour

Background Mechanical methods were the first methods developed to ripen the cervix and induce labour.During recent decades they have been substituted by pharmacological methods. Potential advantages of mechanical methods, compared with pharmacological methods may include reduction in side effects that could improve neonatal outcomes. This is an update of a review first published in 2001, last updated in 2012. Objectives To determine the effectiveness and safety of mechanical methods for third trimester (> 24 weeks' gestation) induction of labour in comparison with prostaglandin E2 (PGE2) (vaginal and intracervical), low-dose misoprostol (oral and vaginal), amniotomy or oxytocin. Search methods For this update, we searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies (9 January 2018). We updated the search in March 2019 and added the search results to the awaiting classification section of the review. Selection criteria Clinicaltrials comparingmechanicalmethodsusedforthirdtrimester cervicalripeningorlabourinductionwithpharmacologicalmethods. Mechanical methods include: (1) the introduction of a catheter through the cervix into the extra-amniotic space with balloon insufflation; (2) introduction of laminaria tents, or their synthetic equivalent (Dilapan), into the cervical canal; (3) use of a catheter to inject fluid into the extra-amniotic space (EASI). This review includes the following comparisons: (1) specific mechanical methods (balloon catheter, laminaria tents or EASI) compared with prostaglandins (different types, different routes) or with oxytocin; (2) single balloon compared to a double balloon; (3) addition of prostaglandins or oxytocin to mechanical methods compared with prostaglandins or oxytocin alone. Data collection and analysis Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data and assessed the quality of the evidence using the GRADE approach. Main results This review update includes a total of 113 trials (22,373 women) contributing data to 21 comparisons. Risk of bias of trials varied. Overall, the evidence was graded from very-low to moderate quality. All evidence was downgraded f

A Structured Assessment to Decrease the Amount of Inconclusive Endometrial Biopsies in Women with Postmenopausal Bleeding

Objective. To determine whether structured assessment of outpatient endometrial biopsies decreases the number of inconclusive samples. Design. Retrospective cohort study. Setting. Single hospital pathology laboratory. Population. Endometrial biopsy samples of 66 women with postmenopausal bleeding, collected during the usual diagnostic work-up an

Regional differences in severe postpartum hemorrhage: A nationwide comparative study of 1.6 million deliveries

Background: The incidence of severe postpartum hemorrhage (PPH) is increasing. Regional variation may be attributed to variation in provision of care, and as such contribute to this increasing incidence. We assessed reasons for regional variation in severe PPH in the Netherlands. Methods: We used the Netherlands Perinatal Registry and the Dutch Maternal Mortality Committee to study severe PPH incidences (defined as blood loss ≥ 1000 mL) across both regions and neighborhoods of cities among all deliveries between 2000 and 2008. We first calculated crude incidences. We then used logistic multilevel regression analyses, with hospital or midwife practice as second level to explore further reasons for the regional variation. Results: We analyzed 1599867 deliveries in which the incidence of severe PPH was 4.5%. Crude incidences of severe PPH varied with factor three between regions while between neighborhoods variation was even larger. We could not explain regional variation by maternal characteristics (age, parity, ethnicity, socioeconomic status), pregnancy characteristics (singleton, gestational age, birth weight, pre-eclampsia, perinatal death), medical interventions (induction of labor, mode of delivery, perineal laceration, placental removal) and health care setting. Conclusions: In a nationwide study in The Netherlands, we observed wide practice variation in PPH. This variation could not be explained by maternal characteristics, pregnancy characteristics, medical interventions or health care setting. Regional variation is either unavoidable or subsequent to regional variation of a yet unregistered variable

Does ovarian hyperstimulation in intrauterine insemination for cervical factor subfertility improve pregnancy rates?

Background: Intrauterine insemination (IUI) can be performed with or without controlled ovarian hyperstimulation (COH). Studies in which the additional benefit of COH on IUI for cervical factor subfertility is assessed are lacking. We assessed whether COH in IUI improved pregnancy rates in cervical factor subfertility. Methods: We performed a historical cohort study among couples with cervical factor subfertility, treated with IUI. A cervical factor was diagnosed by a well-timed, non-progressive post-coital test with normal semen parameters. We compared ongoing pregnancy rate per cycle in groups treated with IUI with or without COH. We tabulated ongoing pregnancy rates per cycle number and compared the effectiveness of COH by stratified univariable analysis. Results: We included 181 couples who underwent 330 cycles without COH and 417 cycles with COH. Ongoing pregnancy rates in IUI cycles without and with COH were 9.7% and 12.7%, respectively (odds ratio 1.4; 95% confidence interval 0.85-2.2). The pregnancy rates in IUI without COH in cycles 1, 2, 3 and 4 were 14%, 11%, 6% and 15%, respectively. For IUI with COH, these rates were 17%, 15%, 14% and 16%, respectively. Conclusions: Although our data indicate that COH improves the pregnancy rate over IUI without COH, IUI without COH generates acceptable pregnancy rates in couples with cervical factor subfertility. Since IUI without COH bears no increased risk for multiple pregnancy, this treatment should be seriously considered in couples with cervical factor subfertility

Adverse drug reactions to tocolytic treatment for preterm labour: Prospective cohort study

Objective To evaluate the incidence of serious maternal complications after the use of various tocolytic drugs for the treatment of preterm labour in routine clinical situations. Design Prospective cohort study. Setting 28 hospitals in the Netherlands and Belgium. Participants 1920 consecutive women treated with tocolytics for threatened preterm labour. Main outcome measures Maternal adverse events (those suspected of being causally related to treatment were considered adverse drug reactions) leading to cessation of treatment. Results An independent panel evaluated the recorded adverse events, without knowledge of the type of tocolytic used. Of the 1920 women treated with tocolytics, 1327 received a single course of treatment (69.1%), 282 sequential courses (14.7%), and 311 combined courses (16.2%). Adverse drug reactions were categorised as serious or mild in 14 cases each. The overall incidence of serious adverse drug reaction was 0.7%. Compared with atosiban, the relative risk of an adverse drug reaction for single treatment with a (3 adrenoceptor agonist was 22.0 (95% confidence interval 3.6 to 138.0) and for single treatment with a calcium antagonist was 12 (1.9 to 69). Multiple drugtocolysis led to five serious adverse drug reactions (1.6%). Multiple gestation, preterm rupture of membranes, and comorbidity were not independent risk factors for adverse drug reactions. Conclusions The use of (3 adrenoceptor agonists or multiple tocolytics for preventing preterm birth is associated with a high incidence of serious adverse drug reactions. Indometacin and atosiban were the only drugs not associated with serious a

Early nasogastric tube feeding in optimising treatment for hyperemesis gravidarum: The MOTHER randomised controlled trial (Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding)

Background: Hyperemesis gravidarum (HG), or intractable vomiting during pregnancy, is the single most frequent cause of hospital admission in early pregnancy. HG has a major impact on maternal quality of life and has repeatedly been associated with poor pregnancy outcome such as low birth weight. Currently, women with HG are admitted to hospital for intravenous fluid replacement, without receiving specific nutritional attention. Nasogastric tube feeding is sometimes used as last resort treatment. At present no randomised trials on dietary or rehydration interventions have been performed. Small observational studies indicate that enteral tube feeding may have the ability to effectively treat dehydration and malnutrition and alleviate nausea and vomiting symptoms. We aim to evaluate the effectiveness of early enteral tube feeding in addition to standard care on nausea and vomiting symptoms and pregnancy outcomes in HG patients. Methods/Design: The MOTHER trial is a multicentre open label randomised controlled trial ( www.studies-obsgyn.nl/mother ). Women ≥ 18 years hospitalised for HG between 5 + 0 and 19 + 6 weeks gestation are eligible for participation. After informed consent participants are randomly allocated to standard care with intravenous rehydration or early enteral tube feeding in addition to standard care. All women keep a weekly diary to record symptoms and dietary intake until 20 weeks gestation. The primary outcome will be neonatal birth weight. Secondary outcomes will be the 24-h Pregnancy Unique Quantification of Emesis and nausea score (PUQE-24), maternal weight gain, dietary intake, duration of hospital stay, number of readmissions, quality of life and side-effects. Also gestational age at birth, placental weight, umbilical cord plasma lipid concentration and neonatal morbidity will be evaluated. Analysis will be according to the intention to treat principle. Discussion: With this trial we aim to clarify whether early enteral tube feeding is more effective in treating HG than intravenous rehydration alone and improves pregnancy outcome. Trial registration: Trial registration number: NTR4197. Date of registration: October 2nd 2013

Nifedipine versus atosiban in the treatment of threatened preterm labour (Assessment of Perinatal Outcome after Specific Tocolysis in Early Labour: APOSTEL III-Trial)

Background: Preterm birth is the most common cause of neonatal morbidity and mortality. Postponing delivery for 48 hours with tocolytics to allow for maternal steroid administration and antenatal transportation to a centre wit

Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: A multicenter randomized placebo controlled trial

Background: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. Methods/design: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. Discussion: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. Trial registration: Clinical trial registration number of the Dutch Trial Register: NTR 5675. EudraCT-registration number: 2015-003220-31