Comparison of effect of CTG + STan with CTG alone on emergency Cesarean section rate: STan Australian Randomized controlled Trial (START).

OBJECTIVE: To investigate whether use of ST analysis of the fetal electrocardiogram (STan) as an adjunct to continuous cardiotocography (CTG) reduces the rate of emergency Cesarean section (EmCS) compared with CTG alone. METHODS: This was a randomized controlled trial of patients with a singleton fetus in cephalic presentation at ≥ 36 weeks' gestation, requiring continuous electronic fetal monitoring during labor at a tertiary maternity hospital in Adelaide, Australia, between January 2018 and July 2021. Participants were randomized to undergo CTG + STan or CTG alone. The calculated sample size was 1818 participants. The primary outcome was EmCS. Secondary outcomes included metabolic acidosis, a composite adverse perinatal outcome, and other maternal and neonatal morbidity and safety outcomes. RESULTS: The present study enrolled 970 women, of whom 967 were included in the primary analysis. EmCS occurred in 107/482 (22.2%) deliveries in the CTG + STan arm and in 107/485 (22.1%) in the CTG arm (adjusted relative risk, 1.02 (95% CI, 0.81-1.27); P = 0.89). There was no difference in the rate of adverse maternal or neonatal outcomes between arms. CONCLUSIONS: The addition of STan as an adjunct to continuous CTG did not reduce the EmCS rate. The smaller-than-anticipated sample size meant that this study was underpowered to detect absolute differences of ≤ 5% and, therefore, this negative finding could be due to a Type-2 error. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Comparing the effect of STan (cardiotocographic electronic fetal monitoring (CTG) plus analysis of the ST segment of the fetal electrocardiogram) with CTG alone on emergency caesarean section rates: study protocol for the STan Australian Randomised controlled Trial (START).

BACKGROUND: Cardiotocography is almost ubiquitous in its use in intrapartum care. Although it has been demonstrated that there is some benefit from continuous intrapartum fetal monitoring using cardiotocography, there is also an increased risk of caesarean section which is accompanied by short-term and long-term risks to the mother and child. There is considerable potential to reduce unnecessary operative delivery with up to a 60% false positive diagnosis of fetal distress using cardiotocography alone. ST analysis of the fetal electrocardiogram is a promising adjunct to cardiotocography alone, and permits detection of metabolic acidosis of the fetus, potentially reducing false positive diagnosis of fetal distress. METHODS: This study will be a single-centre, parallel-group, randomised controlled trial, conducted over 3 years. The primary hypothesis will be that the proportion of women with an emergency caesarean section on ST analysis will not equal that for women on cardiotocography monitoring alone. Participants will be recruited at the Women's and Children's Hospital, a high-risk specialty facility with approximately 5000 deliveries per annum. A total of 1818 women will be randomised to the treatment or conventional arm with an allocation ratio of 1:1, stratified by parity. The primary outcome is emergency caesarean section (yes/no). Statistical analysis will follow standard methods for randomised trials and will be performed on an intention-to-treat basis. Secondary maternal and neonatal outcomes will also be analysed. Additional study outcomes include psychosocial outcomes, patient preferences and cost-effectiveness. DISCUSSION: Approximately 20% of Australian babies are delivered by emergency caesarean section. This will be the first Australian trial to examine ST analysis of the fetal electrocardiogram as an adjunct to cardiotocography as a potential method for reducing this proportion. The trial will be among the first to comprehensively examine ST analysis, taking into account the impact on psychosocial well-being as well as cost-effectiveness. This research will provide Australian evidence for clinical practice and guideline development as well as for policy-makers and consumers to make informed, evidence-based choices about care in labour. TRIAL REGISTRATION: ANZCTR, ACTRN1261800006268 . Registered on 19 January 2018.

Postterm pregnancy.

Postterm pregnancy is a pregnancy that extends to 42 weeks of gestation or beyond. Fetal, neonatal and maternal complications associated with this condition have always been underestimated. It is not well understood why some women become postterm although in obesity, hormonal and genetic factors have been implicated. The management of postterm pregnancy constitutes a challenge to clinicians; knowing who to induce, who will respond to induction and who will require a caesarean section (CS). The current definition and management of postterm pregnancy have been challenged in several studies as the emerging evidence demonstrates that the incidence of complications associated with postterm pregnancy also increase prior to 42 weeks of gestation. For example the incidence of stillbirth increases from 39 weeks onwards with a sharp rise after 40 weeks of gestation. Induction of labour before 42 weeks of gestation has the potential to prevent these complications; however, both patients and clinicians alike are concerned about risks associated with induction of labour such as failure of induction and increases in CS rates. There is a strong body of evidence however that demonstrates that induction of labour at term and prior to 42 weeks of gestation (particularly between 40 & 42 weeks) is associated with a reduction in perinatal complications without an associated increase in CS rates. It seems therefore that a policy of induction of labour at 41 weeks in postterm women could be beneficial with potential improvement in perinatal outcome and a reduction in maternal complications.

New undergraduate curricula in the UK and Australia.

There are many challenges facing undergraduate education in the smaller specialities such as obstetrics and gynaecology (O&G). These are similar throughout the world, although the emphasis may vary according to geography and the approach of those involved in medical education in general. The number of medical students has increased because of the greater number of doctors required, the gender balance and also because it provides revenue for the universities. This means that strategies must be developed to include more teaching units in both primary and secondary care as well as those at a distance from the main teaching provider. Australia and the UK both have this problem but, obviously, the distances involved in Australia are much greater. One of the drivers for the change in undergraduate medical education in the UK was factual overload and the need to teach basic competencies to the students. National curricula that take this into account are being developed and that in the UK has been taken up by a majority of the medical schools. The opportunities offered by O&G to provide basic skills and competencies difficult to find elsewhere in the curriculum are unparalleled. These include issues such as communication in situations where great sensitivity is required and also the impact of cultural beliefs and ethnicity on clinical practice. However, factual knowledge of medical science is also essential and ways of achieving a balance are discussed.

Estrogen receptor polymorphisms and the risk of endometrial cancer.

OBJECTIVE: There is evidence that estrogens and some of their metabolites are involved in endometrial cancer pathogenesis. As estrogens mediate their effects via the estrogen receptors, ESR1 and ESR2, the objective of this investigation was to determine whether six single nucleotide polymorphisms (SNPs) in these two genes were over-represented in a population of endometrial cancer patients compared with a healthy matched control population, thereby associating differences in these genes with endometrial cancer. DESIGN: The study is a case-control investigation large enough to detect a two-fold increased risk, assuming a dominant genetic model, with P = 0.05 and 80% power. SETTING: The study and control populations were all from the Hunter-New England region of New South Wales, Australia collected between the years 1992 and 2005. POPULATION: The study consisted of 191 endometrial cancer patients and 291 healthy controls matched for gender and age. METHODS: Two SNPs in ESR1 and four SNPs in ESR2 were genotyped using PCR-based restriction fragment length polymorphism analysis and real-time PCR. Odds ratios were calculated using unconditional logistic regression and SIMHAP was used for haplotype analysis, adjusting for potential endometrial cancer risk factors. Kaplan-Meier survival analysis, Cox regression and t tests were used to examine the patient's age of diagnosis of endometrial cancer and genotype. MAIN OUTCOME MEASURES: Over-representation of ESR1 and ESR2 polymorphisms in the endometrial cancer population compared with the control population indicates an involvement in the development and/or progression of disease. RESULTS: Two ESR1 (rs2234693 and rs9340799) and two ESR2 (rs1255998 and rs944050) polymorphisms were associated with an increased risk of endometrial cancer. Following adjustment for risk factors, the association with the ESR1 and ESR2 polymorphisms (rs2234693, rs1255998 and rs944050) remained highly significant. Haplotype analysis revealed that carriers of the ESR1 haplotype (variant alleles; rs2234693 and rs9340799) and the ESR2 haplotype (variant allele; rs1255998 and wild-type alleles; rs944050, rs4986938 and rs1256049) were at an increased risk (OR 1.862, P = 0.013 and OR 1.918, P = 0.046 respectively). This risk was even greater in women carrying both risk haplotypes (OR 5.041, P = 0.007). CONCLUSIONS: Our data suggest that the ESR1 (rs2234693 and rs9340799) and the ESR2 (rs1255998 and rs944050) polymorphisms may be associated with an increased risk of developing endometrial cancer.

Placental cord drainage after spontaneous vaginal delivery as part of the management of the third stage of labour.

BACKGROUND: Cord drainage in the third stage of labour involves unclamping the previously clamped and separated umbilical cord and allowing the blood from the placenta to drain freely into an appropriate receptacle. Currently there are no systematic reviews of the effects of placental cord drainage on the management of the third stage of labour. OBJECTIVES: The objective of this review was to assess the specific effects of placental cord drainage on the third stage of labour, with or without the prophylactic use of oxytocics. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials register (July 2005), CINAHL (1982 to December 2004) and the National Research Register (December 2004). SELECTION CRITERIA: Randomised trials involving placental cord drainage as a variable within the package of interventions as part of the management of the third stage of labour. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the quality of trials and extracted data. MAIN RESULTS: Two studies met our inclusion criteria in terms of quality and relevance. Cord drainage could impact the third stage of labour as the results show a statistically significant reduction in the length of third stage of labour (one trial, n = 147, weighted mean difference (minutes) -5.46, 95% confidence interval (CI) -8.02 to -2.90). In the incidence of retained placenta at 30 minutes after birth (one trial, n = 477, relative risk 0.28, 95% CI 0.10 to 0.73) a significant difference was found, but this should be interpreted with caution due to potential intervention bias. AUTHORS' CONCLUSIONS: It is difficult to draw conclusions from such a small number of studies, especially where the review outcomes were presented in a variety of formats. However, there does appear to be some potential benefit from the use of placental cord drainage in terms of reducing the length of the third stage of labour. More research is required to investigate the impact of cord drainage on the management of the third stage of labour.

The "tamponade test" in the management of massive postpartum hemorrhage.

OBJECTIVE: Massive postpartum hemorrhage is a major cause of pregnancy-related death in the United States. To date there is no diagnostic test to identify those women with intractable hemorrhage who will need surgery. Delay in making this decision can be catastrophic. The successful use of the inflated stomach balloon of a Sengstaken-Blakemore tube as a therapy for obstetric hemorrhage has been reported previously. Using the insertion of the Sengstaken-Blakemore tube as a diagnostic test has not been reported. An inflated Sengstaken-Blakemore balloon catheter creates tamponade and identifies those who will or will not need surgery. This is the basis for the "tamponade test." We evaluated the tamponade test in the management of women with massive postpartum hemorrhage. METHODS: In this prospective study, 16 cases of intractable postpartum hemorrhage were managed by the tamponade test. All 16 women had persistent bleeding despite the maximal and optimal application of conservative measures. Their condition deteriorated, such that surgical intervention was considered mandatory. It was at this predefined end point that the tamponade test was applied. RESULTS: Fourteen (87.5%) had a positive tamponade test result and therefore did not require surgery. Two (12.5%) had a negative test result and underwent laparotomy. CONCLUSION: This diagnostic test rapidly identifies those patients with postpartum hemorrhage who will require a laparotomy. Even when results are positive, life-threatening hemorrhage is arrested and time is also allowed to correct any consumptive coagulopathy.

Ultrasound, hysteroscopy and endometrial biopsy in the investigation of endometrial cancer.

Over the course of the last two decades hysteroscopy with endometrial biopsy has begun to replace dilation and curettage as the method of choice for the diagnosis of endometrial carcinoma. In the majority of women this can be performed as an outpatient procedure with no loss in diagnostic accuracy. Transvaginal ultrasound measurement of endometrial thickness provides a highly sensitive and less invasive alternative means of assessing the endometrium but has a low positive predictive value for cancer, especially in women taking hormone replacement therapy. The cut-off value used to define normality needs to take into account patient age and ethnic origin. Ultrasound screening may not be suitable for women taking tamoxifen and those with recurrent or late-onset abnormal uterine bleeding.

Immunoscintigraphy of ovarian carcinoma using a monoclonal antibody (111In-NCRC48) defining a polymorphic epithelial mucin (PEM) epitope.

An anti-polymorphic epithelial mucin (PEM) monoclonal antibody NCRC48 (IgG3) has been tested for its capacity to localize in tumours according to accepted guidelines for human administration. Following radiolabelling with 111In, 1 mg antibody was administered to 19 patients with a clinical suspicion of ovarian malignancy. Initial imaging and biodistribution studies confirm the safety of this conjugate although six out of 11 patients tested developed an antibody response to the monoclonal antibody. Immunoscintigraphy with this antibody was compared with magnetic resonance imaging and ultrasound in relation to the final tumour histology, the final accuracies being 79, 79 and 64% respectively. Positive localization of antibody was confirmed in malignant tissue with little evidence of uptake in benign tissue.

C595--a monoclonal antibody against the protein core of human urinary epithelial mucin commonly expressed in breast carcinomas.

Urinary mucins which express determinants for the anti-breast carcinoma monoclonal antibody, NCRC-11 (IgM), closely resemble the mammary mucins found in milk fat globules and carcinomas. An IgG3 monoclonal antibody, C595, was prepared against urinary mucins isolated on a NCRC-11 antibody affinity column, and this 'second generation' antibody was shown to have a very similar pattern of reactivity to the original NCRC-11 antibody. By immunohistology, the profile of reactivity of both antibodies with tumour and normal tissue specimens was virtually identical. Both antibodies reacted with epithelial mucins isolated from breast tumours or normal urine using an NCRC-11 antibody affinity column, although the antibodies were unreactive with other antigen preparations. Heterologous immunoradiometric assays ('sandwich' tests) confirmed that NCRC-11 and C595 epitopes were co-expressed on the same molecule. C595 antibodies inhibited the binding of radiolabelled NCRC-11 antibodies to antigen, suggesting that the two epitopes were in close topographical proximity. The protein core of the mammary mucins has recently been shown to consist predominantly of a repeated 20 amino acid sequence (Gendler et al., 1988). Peptides with this complete sequence and small fragments were synthesised, and the C595 antibody was found to recognise an epitope within this repeat. The ability to identify and synthesise monoclonal antibody-defined determinants, as well as those in the adjacent or overlapping sequences within the protein core of epithelial mucins, is viewed as a strategy for facilitating the production of antibodies of new and novel specificity to complement the panels of existing anti-breast cancer reagents.