A double-blind, randomized, placebo-controlled trial of melatonin as an adjuvant agent for induction of labor: The MILO trial.

INTRODUCTION: Melatonin has been suggested to have a biological role in the onset and progress of labor. We tested the hypothesis that the addition of melatonin during an induction of labor will reduce the need for a cesarean birth. MATERIAL AND METHODS: This trial underwent protocol amendments that are detailed in the main text of the article. This trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12616000311459). At a multi-center health service including secondary and tertiary obstetric hospitals, we performed a randomized, double-blind, placebo-controlled trial in women with a singleton cephalic pregnancy, free of significant maternal or perinatal complications who were undergoing induction of labor (with or without cervical ripening). Women were randomized to 10 mg melatonin vs placebo, with cervical ripening as required, and then 6-h during their induction of labor to a maximum of four doses or until birth. The primary outcome was cesarean birth. Secondary outcomes included labor, maternal, and neonatal outcomes. Data were analyzed using intention to treat. Sub-group analyses based on mode of ripening and parity were also performed. RESULTS: Between 2019 and 2021 we randomized 189 women (103 to melatonin and 86 to placebo). The study was prematurely terminated due to logistical complications resulting from the COVID-19 pandemic. Cesarean rates were 28/103 (27.2%) in the melatonin group versus 20/84 (23.3%) in the placebo group (RR 1.17 95% CI 0.71-1.92). There were no significant differences in rate of cesarean birth between the melatonin and placebo groups for failure to progress (13.4% and 9.3%, respectively, RR 1.46; 95% CI 0.64-3.32) or suspected fetal distress (10.7% and 10.5%, respectively, RR 1.02; 95% CI 0.44-2.34). The melatonin group had significantly lower rates of spontaneous vaginal birth within 24 h (35.0% vs. 50.0%; RR 0.70 95% CI 0.50-0.98). The rates of secondary outcomes such as total length of labor, rate of postpartum hemorrhage, and instrumental birth were comparable. Babies born in the melatonin group were more likely to need admission to the special care nursery, namely for hypoglycemic monitoring (18.5% vs. 8.1% RR 2.26; 95% CI 1.00-5.10). CONCLUSIONS: In women undergoing induction of labor, melatonin does not reduce the cesarean section rate. Melatonin use intrapartum may also be associated with neonatal hypoglycemia.

Prognostic accuracy of ultrasound measures of fetal head descent to predict outcome of operative vaginal birth: a comparative systematic review and meta-analysis.

OBJECTIVE: This study aimed to compare the prognostic accuracy of intrapartum transperineal ultrasound measures of fetal descent before operative vaginal birth in predicting complicated or failed procedures. DATA SOURCES: We performed a predefined systematic search in Medline, Embase, CINAHL, and Scopus from inception to June 10, 2022. STUDY ELIGIBILITY CRITERIA: We included studies assessing the following intrapartum transperineal ultrasound measures before operative vaginal birth to predict procedure outcome: angle of progression, head direction, head-perineum distance, head-symphysis distance, midline angle, and/or progression distance. METHODS: Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Bivariate meta-analysis was used to pool sensitivities and specificities into summary receiver operating characteristic curves for each intrapartum transperineal ultrasound measure. Subgroup analyses were performed for measures taken at rest vs with pushing and prediction of failed vs complicated operative vaginal birth. RESULTS: Overall, 16 studies involving 2848 women undergoing attempted operative vaginal birth were included. The prognostic accuracy of intrapartum transperineal ultrasound measures taken at rest to predict failed or complicated operative vaginal birth was high for angle of progression (area under the receiver operating characteristic curve, 0.891; 9 studies) and progression distance (area under the receiver operating characteristic curve, 0.901; 3 studies), moderate for head direction (area under the receiver operating characteristic curve, 0.791; 6 studies) and head-perineum distance (area under the receiver operating characteristic curve, 0.747; 8 studies), and fair for midline angle (area under the receiver operating characteristic curve, 0.642; 4 studies). There was no study with sufficient data to assess head-symphysis distance. Subgroup analysis showed that measures taken with pushing tended to have a higher area under the receiver operating characteristic curve for angle of progression (0.927; 4 studies), progression distance (0.930; 2 studies), and midline angle (0.903; 3 studies), with a similar area under the receiver operating characteristic curve for head direction (0.802; 4 studies). The prediction of failed vs complicated operative vaginal birth tended to be less accurate for angle of progression (0.837 [4 studies] vs 0.907 [6 studies]) and head direction (0.745 [3 studies] vs 0.810 [5 studies]), predominantly because of lower specificity, and was more accurate for head-perineum distance (0.812 [6 studies] vs 0.687 [2 studies]). CONCLUSION: Angle of progression, progression distance, and midline angle measured with pushing demonstrated the highest prognostic accuracy in predicting complicated or failed operative vaginal birth. Overall, the measurements seem to perform better with pushing than at rest.

Indications and surgical route for hysterectomy for benign disorders: a retrospective analysis in a large Australian tertiary hospital network.

PURPOSE: Hysterectomy is a common but expensive and morbid procedure. Alternative treatments for heavy menstrual bleeding (HMB) are effective in up to 80% of cases, but there is substantial variation in surgical approach and pre-operative management of HMB. This study aims to assess the approach to hysterectomies for benign indications including alternative treatments and route of operation. METHODS: We retrospectively collected patient and surgical data on all hysterectomies for benign indications from 1/4/2018 to 31/6/2020 at our tertiary-led hospital network. RESULTS: Hysterectomies were performed in 582 women at a median age of 49(44-56) with a median BMI of 27.9(24.5-33.3)kg/m2 and 251(43%) were referred from private rooms. Hysterectomies for HMB were performed laparoscopically (TLH)(156, 51.7%) more often than abdominally (TAH)(133, 44%) or vaginally (4.3, 13%), with wide variation between sites. Approach was predicted by a history of previous abdomino-pelvic surgery and uterine size but not by other patient factors (BMI, parity or comorbidities). Referral source, on the other hand, was a significant predictor of route of hysterectomy. In women with HMB without uterine abnormalities, 45% tried a levonorgestrel intrauterine device and 25% tried endometrial ablation before proceeding to surgery. The use of alternative therapies pre-operatively did not vary between sites or referral sources. CONCLUSIONS: The variations in route of hysterectomy that are unexplained by patient factors suggest room for improvement and raises the question whether some of the patients undergoing a TAH may have been candidates for less invasive surgery. Uptake of alternative management strategies for HMB could also be improved.

Innate Immune Molecule NLRC5 Protects Mice From Helicobacter-induced Formation of Gastric Lymphoid Tissue.

BACKGROUND & AIMS: Helicobacter pylori induces strong inflammatory responses that are directed at clearing the infection, but if not controlled, these responses can be harmful to the host. We investigated the immune-regulatory effects of the innate immune molecule, nucleotide-binding oligomerization domain-like receptors (NLR) family CARD domain-containing 5 (NLRC5), in patients and mice with Helicobacter infection. METHODS: We obtained gastric biopsies from 30 patients in Australia. We performed studies with mice that lack NLRC5 in the myeloid linage (Nlrc5møKO) and mice without Nlrc5 gene disruption (controls). Some mice were gavaged with H pylori SS1 or Helicobacter felis; 3 months later, stomachs, spleens, and sera were collected, along with macrophages derived from bone marrow. Human and mouse gastric tissues and mouse macrophages were analyzed by histology, immunohistochemistry, immunoblots, and quantitative polymerase chain reaction. THP-1 cells (human macrophages, controls) and NLRC5-/- THP-1 cells (generated by CRISPR-Cas9 gene editing) were incubated with Helicobacter and gene expression and production of cytokines were analyzed. RESULTS: Levels of NLRC5 messenger RNA were significantly increased in gastric tissues from patients with H pylori infection, compared with patients without infection (P < .01), and correlated with gastritis severity (P < .05). H pylori bacteria induced significantly higher levels of chemokine and cytokine production by NLRC5-/- THP-1 macrophages than by control THP-1 cells (P < .05). After 3 months of infection with H felis, Nlrc5mø-KO mice developed gastric hyperplasia (P < .0001), splenomegaly (P < .0001), and increased serum antibody titers (P < .01), whereas control mice did not. Nlrc5mø-KO mice with chronic H felis infection had increased numbers of gastric B-cell follicles expressing CD19 (P < .0001); these follicles had features of mucosa-associated lymphoid tissue lymphoma. We identified B-cell-activating factor as a protein that promoted B-cell hyperproliferation in Nlrc5mø-KO mice. CONCLUSIONS: NLRC5 is a negative regulator of gastric inflammation and mucosal lymphoid formation in response to Helicobacter infection. Aberrant NLRC5 signaling in macrophages can promote B-cell lymphomagenesis during chronic Helicobacter infection.

Interval between IVF stimulation cycle and frozen embryo transfer: Is there a benefit to a delay between cycles?

BACKGROUND: There is currently limited evidence available regarding ideal timing for frozen embryo transfer (FET). Demonstrating that delaying FETs has few clinical benefits would allow patients to proceed with FET at their earliest convenience. AIMS: To examine whether the time interval between stimulation cycle and subsequent FET affects pregnancy and live birth rates. MATERIALS AND METHODS: This retrospective cohort study, based in a multi-site private in vitro fertilisation (IVF) clinic categorised women into two groups: those having FET cycles administered within 25-35 days or 50-70 days of IVF stimulation cycle and embryo freeze. Outcomes measured were clinical pregnancy and live birth rates. RESULTS: When comparing the patients who have had a 25-35 days gap between embryo freeze and FET, to the matched patients who had a 50-70 days gap, the statistically significant results showed an adjusted odds ratio for live birth of 1.31 (1.02-1.67). The adjusted odds ratio for clinical pregnancy in matched case : control analysis was not statistically significant at 1.22 (0.97-1.53). CONCLUSION: A gap of 25-35 days between embryo freeze and FET was associated with improved live birth rates compared to a gap of 50-70 days.

Microplastics in surface coastal waters around Plymouth, UK, and the contribution of boating and shipping activities.

Microplastics determined in surface water trawls from coastal waters around Plymouth, southwest England, ranged from 0.26 to 0.68 n m-3, with a decrease evident from the lower estuaries of the Tamar and Plym to areas in Plymouth Sound more remote from urbanisation. Microplastics were dominated by fibres of rayon and polypropylene and fragments of polyester and epoxy resins, with fragment concentration demonstrating a significant and positive linear relationship with concentration of floating and suspended matter retrieved by the trawls. Observations are attributed to the suspension of land-based (e.g., treated municipal waste) sources of textile fibres, and the flotation of land-based and in situ emissions of paints and resins from boating and shipping activities. The implied decoupling of microplastic transport based on shape and origin merits further investigation while the more general determination of floating and suspended matter concentration in microplastic studies is recommended.

Refugee child health: a systematic review of health conditions in children aged 0-6 years living in high-income countries.

This study describes the extent, quality and cultural appropriateness of current research on the health conditions of refugee children aged 0-6 years settled in high-income countries. A systematic review was conducted, including original articles published on the health conditions experienced by refugee children. A total of 71 papers were included. The studies varied considerably in their research design, population characteristics and health conditions. Studies included information on 37 different health conditions, with the majority non-communicable diseases, in particular growth, malnutrition and bone density. Although the studies identified a wide range of health issues, a coordinated effort to prioritise research on particular health topics was lacking, and health conditions studied do not align with the global burden of disease for this population. Additionally, despite being rated medium-high quality, most studies did not describe measures taken to ensure cultural competency and community involvement in their research. We suggest a coordinated research effort for this cohort, with greater emphasis on community engagement to improve the evidence-base of the health needs of refugee children after settlement.

The impact of adenomyosis on IVF outcomes: a prospective cohort study.

STUDY QUESTION: Does the presence of adenomyosis in women treated with IVF alter IVF outcomes? SUMMARY ANSWER: Adenomyosis does not significantly alter IVF outcomes when adjusted for confounding factors including maternal age and smoking status. WHAT IS KNOWN ALREADY: Studies evaluating adenomyosis and its impact on infertility, particularly when focusing on IVF, remain controversial. Many studies report that adenomyosis has a detrimental effect on IVF outcomes, however age is strongly related with both the prevalence of adenomyosis and worse reproductive outcomes. STUDY DESIGN SIZE DURATION: A prospective cohort study of women undergoing 4002 IVF cycles who had undergone a screening ultrasound assessing features of adenomyosis from 1 January 2016 to 31 March 2018 at a multi-site private fertility clinic. Of these women, 1228 fulfilled the inclusion criteria and commenced an IVF cycle, with a subset of 715 women undergoing an embryo transfer (ET). Women were defined as having adenomyosis if there was sonographic evidence of adenomyosis on ultrasound as per the Morphological Uterus Sonographic Assessment criteria, and were then compared to women without. PARTICIPANTS/MATERIALS SETTING METHODS: All women at a private multi-site IVF clinic who underwent a standardised ultrasound to identify features of adenomyosis and also commenced an IVF cycle were assessed for their outcomes. These included clinical pregnancy (defined as the presence of a gestational sac on ultrasound at 7 weeks' gestation), clinical pregnancy loss, number of cancelled cycles, number of useful embryos for transfer or freezing and live birth rates. As a secondary aim, initiated stimulation cycles and those that had an ET were analysed separately to determine when an effect of adenomyosis on IVF might occur: during stimulation or transfer. MAIN RESULTS AND THE ROLE OF CHANCE: When adjusting for confounders, women with and without sonographic features of adenomyosis had no significant differences in most of their IVF outcomes including live birth rates. LIMITATIONS REASONS FOR CAUTION: Adenomyosis had a detrimental impact on IVF outcomes prior to adjusting for confounding factors. No allowance was made for the possibility that confounding factors may merely reduce the effect size of adenomyosis on IVF outcomes. Second, despite a power calculation, the study was underpowered as not all fresh cycles led to an ET. WIDER IMPLICATIONS OF THE FINDINGS: This is one of the largest studies to evaluate adenomyosis and IVF outcomes, while also importantly adjusting for confounding factors. The results suggest that adenomyosis does not have the detrimental impact on IVF that has previously been suggested, possibly reducing the importance of screening for and treating this entity. STUDY FUNDING/COMPETING INTERESTS: The study received no external funding. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: ACTRN12617000796381.