Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells.

Estrogen receptor alpha (ERα) is a ligand-dependent master transcriptional regulator and key driver of breast cancer pathology. Small molecule hormones and competitive antagonists favor unique ERα conformational ensembles that elicit ligand-specific transcriptional programs in breast cancer and other hormone-responsive tissues. By affecting disparate ligand binding domain structural features, unconventional ligand scaffolds can redirect ERα genomic binding patterns to engage novel therapeutic transcriptional programs. To improve our understanding of these ERα structure-transcriptional relationships, we develop a series of chemically unconventional antagonists based on the antiestrogens elacestrant and lasofoxifene. High-resolution x-ray co-crystal structures show that these molecules affect both classical and unique structural motifs within the ERα ligand binding pocket. They show moderately reduced antagonistic potencies on ERα genomic activities but are effective anti-proliferative agents in luminal breast cancer cells. Interestingly, they favor a 4-hydroxytamoxifen-like accumulation of ERα in breast cancer cells but lack uterotrophic activities in an endometrial cell line. Importantly, RNA sequencing shows that the lead molecules engage transcriptional pathways similar to the selective estrogen receptor degrader fulvestrant. This advance shows that fulvestrant-like genomic activities can be achieved without affecting ERα accumulation in breast cancer cells.

Incarcerated aboriginal women's experiences of accessing healthcare and the limitations of the 'equal treatment' principle.

BACKGROUND: Colonization continues in Australia, sustained through institutional and systemic racism. Targeted discrimination and intergenerational trauma have undermined the health and wellbeing of Australia's Aboriginal and Torres Strait Islander population, leading to significantly poorer health status, social impoverishment and inequity resulting in the over-representation of Aboriginal people in Australian prisons. Despite adoption of the 'equal treatment' principle, on entering prison in Australia entitlements to the national universal healthcare system are revoked and Aboriginal people lose access to health services modelled on Aboriginal concepts of culturally safe healthcare available in the community. Incarcerated Aboriginal women experience poorer health outcomes than incarcerated non-Indigenous women and Aboriginal men, yet little is known about their experiences of accessing healthcare. We report the findings of the largest qualitative study with incarcerated Aboriginal women in New South Wales (NSW) Australia in over 15 years. METHODS: We employed a decolonizing research methodology, 'community collaborative participatory action research', involving consultation with Aboriginal communities prior to the study and establishment of a Project Advisory Group (PAG) of community expert Aboriginal women to guide the project. Forty-three semi-structured interviews were conducted in 2013 with Aboriginal women in urban and regional prisons in NSW. We applied a grounded theory approach for the data analysis with guidance from the PAG. RESULTS: Whilst Aboriginal women reported positive and negative experiences of prison healthcare, the custodial system created numerous barriers to accessing healthcare. Aboriginal women experienced institutional racism and discrimination in the form of not being listened to, stereotyping, and inequitable healthcare compared with non-Indigenous women in prison and the community. CONCLUSIONS: 'Equal treatment' is an inappropriate strategy for providing equitable healthcare, which is required because incarcerated Aboriginal women experience significantly poorer health. Taking a decolonizing approach, we unpack and demonstrate the systems level changes needed to make health and justice agencies culturally relevant and safe. This requires further acknowledgment of the oppressive transgenerational effects of ongoing colonial policy, a true embracing of diversity of worldviews, and critically the integration of Aboriginal concepts of health at all organizational levels to uphold Aboriginal women's rights to culturally safe healthcare in prison and the community.

The high prevalence and impact of rheumatic heart disease in pregnancy in First Nations populations in a high-income setting: a prospective cohort study.

OBJECTIVE: To describe the epidemiology of rheumatic heart disease (RHD) in pregnancy in Australia and New Zealand (A&NZ). DESIGN: Prospective population-based study. SETTING: Hospital-based maternity units throughout A&NZ. POPULATION: Pregnant women with RHD with a birth outcome of ≥20 weeks of gestation between January 2013 and December 2014. METHODS: We identified eligible women using the Australasian Maternity Outcomes Surveillance System (AMOSS). De-identified antenatal, perinatal and postnatal data were collected and analysed. MAIN OUTCOME MEASURES: Prevalence of RHD in pregnancy. Perinatal morbidity and mortality. RESULTS: There were 311 pregnancies associated with women with RHD (4.3/10 000 women giving birth, 95% CI 3.9-4.8). In Australia, 78% were Aboriginal or Torres Strait Islander (60.4/10 000, 95% CI 50.7-70.0), while in New Zealand 90% were Maori or Pasifika (27.2/10 000, 95% CI 22.0-32.3). One woman (0.3%) died and one in ten was admitted to coronary or intensive care units postpartum. There were 314 births with seven stillbirths (22.3/1000 births) and two neonatal deaths (6.5/1000 births). Sixty-six (21%) live-born babies were preterm and one in three was admitted to neonatal intensive care or special care units. CONCLUSION: Rheumatic heart disease in pregnancy persists in disadvantaged First Nations populations in A&NZ. It is associated with significant cardiac and perinatal morbidity. Preconception planning and counselling and RHD screening in at-risk pregnant women are essential for good maternal and baby outcomes. TWEETABLE ABSTRACT: Rheumatic heart disease in pregnancy persists in First Nations people in Australia and New Zealand and is associated with major cardiac and perinatal morbidity.

Cumulative live birth rates following a 'freeze-all' strategy: a population-based study.

STUDY QUESTION: What is the cumulative live birth rate following a 'freeze-all' strategy compared with a 'fresh-transfer' strategy? SUMMARY ANSWER: The 'freeze-all' strategy resulted in a similar cumulative live birth rate as the 'fresh-transfer' strategy among high responders (>15 oocytes retrieved) but did not benefit normal (10-15 oocytes) and suboptimal responders (<10 oocytes). WHAT IS KNOWN ALREADY: Frozen-thawed embryo transfer is associated with a decreased risk of adverse obstetric and perinatal outcomes compared with fresh embryo transfer. It is unclear whether the 'freeze-all' strategy should be offered to all women undergoing ART treatment. STUDY DESIGN SIZE DURATION: A population-based retrospective cohort study using data collected by the Victorian Assisted Reproductive Treatment Authority. This study included 14 331 women undergoing their first stimulated ART cycle with at least one oocyte fertilised between 1 July 2009 and 30 June 2014 in Victoria, Australia. Demographic characteristics, type of ART procedures and resulting pregnancy and birth outcomes were recorded for the stimulated cycle and associated thaw cycles until 30 June 2016, or until a live birth was achieved, or until all embryos from the stimulated cycle had been used. PARTICIPANTS/MATERIALS SETTING METHODS: Women were grouped by whether they had undergone the 'freeze-all' strategy (n = 1028) where all embryos were cryopreserved for future transfer, or the 'fresh-transfer' strategy (n = 13 303) where selected embryo(s) were transferred in the stimulated cycle, and remaining embryo(s) were cryopreserved for future use. A discrete-time survival model was used to evaluate the cumulative live birth rate following 'freeze-all' and 'fresh-transfer' strategy. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1028 women undergoing 'freeze-all' strategy and 13 303 women undergoing 'fresh-transfer' strategy had 1788 and 22 334 embryo transfer cycles resulting in 452 and 5126 live births, respectively. Most women (61.3%) in the 'freeze-all' group had more than 15 oocytes retrieved in the stimulated cycle compared with 18.1% of women in the 'fresh-transfer' group (P < 0.001). For high responders (>15 oocytes), the cumulative live birth rate in the 'freeze-all' group was similar to the 'fresh-transfer' group (56.8% vs. 56.2%, adjusted hazard ratio (AHR) 0.90, 95% CI 0.77-1.04). However, the likelihood of a live birth was lower in the 'freeze-all' group compared with the 'fresh-transfer' group among normal responders (10-15 oocytes) (33.2% vs. 46.3%, AHR 0.62, 95% CI 0.46-0.83) and suboptimal responders (<10 oocytes) (14.6% vs. 28.0%, AHR 0.67, 95% CI 0.14-1.01). During the minimum follow-up time of 2 years, 34.1%, 24.4% and 8.4% of suboptimal, normal and high responders, respectively, in the 'freeze-all' group did not return for any embryo transfer after the stimulated cycle, whereas all women in the 'fresh-transfer' group had at least one embryo transferred in the stimulated cycle. LIMITATIONS REASONS FOR CAUTION: A limitation of this population-based study is the lack of information available on clinic-specific protocols for the 'freeze-all' strategy and the potential impact of these on outcomes. Data were not available on whether the 'freeze-all' strategy was used to prevent ovarian hyperstimulation syndrome (OHSS). WIDER IMPLICATIONS OF THE FINDINGS: This study presents population-based evidence on clinical efficacy associated with a 'freeze-all' and 'fresh-transfer' strategy. The 'freeze-all' strategy may benefit some subgroups of patients, including women who are high responders and those who are at risk of OHSS, but should not be offered universally. Clinicians should consider the potential impact of electively deferring embryo transfer on treatment discontinuation in choosing the optimal embryo transfer strategy for couples undergoing ART treatment. STUDY FUNDING/COMPETING INTERESTS: No specific funding was received to undertake this study. There is no conflict of interest, except that M.B. is a shareholder in Genea Ltd.

ICSI does not increase the cumulative live birth rate in non-male factor infertility.

STUDY QUESTION: What is the cumulative live birth rate following ICSI cycles compared with IVF cycles for couples with non-male factor infertility? SUMMARY ANSWER: ICSI resulted in a similar cumulative live birth rate compared with IVF for couples with non-male factor infertility. WHAT IS KNOWN ALREADY: The ICSI procedure was developed for couples with male factor infertility. There has been an increased use of ICSI regardless of the cause of infertility. Cycle-based statistics show that there is no difference in pregnancy rates between ICSI and IVF in couples with non-male factor infertility. However, evidence indicates that ICSI is associated with an increased risk of adverse perinatal outcomes. STUDY DESIGN, SIZE, DURATION: A population-based cohort of 14 693 women, who had their first ever stimulated cycle with fertilization performed for at least one oocyte by either IVF or ICSI between July 2009 and June 2014 in Victoria, Australia was evaluated retrospectively. The pregnancy and birth outcomes following IVF or ICSI were recorded for the first oocyte retrieval (fresh stimulated cycle and associated thaw cycles) until 30 June 2016, or until a live birth was achieved, or until all embryos from the first oocyte retrieval had been used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Demographic, treatment characteristics and resulting outcome data were obtained from the Victorian Assisted Reproductive Treatment Authority. Data items in the VARTA dataset were collected from all fertility clinics in Victoria. Women were grouped by whether they had undergone IVF or ICSI. The primary outcome was the cumulative live birth rate, which was defined as live deliveries (at least one live birth) per woman after the first oocyte retrieval. A discrete-time survival model was used to evaluate the cumulative live birth rate following IVF and ICSI. The adjustment was made for year of treatment in which fertilization occurred, the woman's and male partner's age at first stimulated cycle, parity and the number of oocytes retrieved in the first stimulated cycle. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4993 women undergoing IVF and 8470 women undergoing ICSI had 7980 and 13 092 embryo transfers, resulting in 1848 and 3046 live deliveries, respectively. About one-fifth of the women (19.0% of the IVF group versus 17.9% of the ICSI group) had three or more cycles during the study period. For couples who achieved a live delivery, the median time from oocyte retrieval to live delivery was 8.9 months in both IVF (range: 4.2-66.5) and ICSI group (range: 4.5-71.3) (P = 0.474). Fertilization rate per oocyte retrieval was higher in the IVF than in the ICSI group (59.8 versus 56.2%, P < 0.001). The overall cumulative live birth rate was 37.0% for IVF and 36.0% for ICSI. The overall likelihood of a live birth for women undergoing ICSI was not significantly different to that for women undergoing IVF (adjusted hazard ratio (AHR): 0.99, 95% CI: 0.92-1.06). For couples with a known cause of infertility, non-male factor infertility (female factor only or unexplained infertility) was reported for 64.0% in the IVF group and 36.8% in the ICSI group (P < 0.001). Among couples with non-male factor infertility, ICSI resulted in a similar cumulative live birth rate compared with IVF (AHR: 0.96, 95% CI: 0.85-1.10). LIMITATIONS, REASONS FOR CAUTION: Data were not available on clinic-specific protocols and processes for IVF and ICSI and the potential impact of these technique aspects on clinical outcomes. The reported causes of infertility were based on the treating clinician's classification which may vary between clinicians. WIDER IMPLICATIONS OF THE FINDINGS: This population-based study found ICSI resulted in a lower fertilization rate per oocyte retrieved and a similar cumulative live birth rate compared to conventional IVF. These data suggest that ICSI offers no advantage over conventional IVF in terms of live birth rate for couples with non-male factor infertility. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was received to undertake this study. There is no conflict of interest, except that M.B. is a shareholder in Genea Ltd. TRIAL REGISTRATION NUMBER: N/A.

Risk of ectopic pregnancy lowest with transfer of single frozen blastocyst.

STUDY QUESTION: What type of transferred embryo is associated with a lower rate of ectopic pregnancy? SUMMARY ANSWER: The lowest risk of ectopic pregnancy was associated with the transfer of blastocyst, frozen and single embryo compared with cleavage stage, fresh and multiple embryos. WHAT IS KNOWN ALREADY: Ectopic pregnancy is a recognized complication following assisted reproductive technology (ART) treatment. It has been estimated that the rate of ectopic pregnancy is doubled in pregnancies following ART treatment compared with spontaneous pregnancies. However, it was not clear whether the excess rate of ectopic pregnancy following ART treatment is related to the underlying demographic factors of women undergoing ART treatment, the number of embryos transferred or the developmental stage of the embryo. STUDY DESIGN, SIZE, DURATION: A population-based cohort study of pregnancies following autologous treatment cycles between January 2009 and December 2011 were obtained from the Australian and New Zealand Assisted Reproduction Technology Database (ANZARD). The ANZARD collects ART treatment information and clinical outcomes annually from all fertility centres in Australia and New Zealand. PARTICIPANTS/MATERIALS, SETTING, METHODS: Between 2009 and 2011, a total of 44 102 pregnancies were included in the analysis. The rate of ectopic pregnancy was compared by demographic and ART treatment factors. Generalized linear regression of Poisson distribution was used to estimate the likelihood of ectopic pregnancy. Odds ratios, adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated. MAIN RESULTS AND THE ROLE OF CHANCE: The overall rate of ectopic pregnancy was 1.4% for women following ART treatment in Australia and New Zealand. Pregnancies following single embryo transfers had 1.2% ectopic pregnancies, significantly lower than double embryo transfers (1.8%) (P < 0.01). The highest ectopic pregnancy rate was 1.9% for pregnancies from transfers of fresh cleavage embryo, followed by transfers of frozen cleavage embryo (1.7%), transfers of fresh blastocyst (1.3%), and transfers of frozen blastocyst (0.8%). Compared with fresh blastocyst transfer, the likelihood of ectopic pregnancy was 30% higher for fresh cleavage stage embryo transfers (AOR 1.30, 95% CI 1.07-1.59) and was consistent across subfertility groups. Transfer of frozen blastocyst was associated with a significantly decreased risk of ectopic pregnancy (AOR 0.70, 95% CI 0.54-0.91) compared with transfer of fresh blastocyst. LIMITATIONS, REASON FOR CAUTION: A limitation of this population-based study is the lack of information available on clinical- specific protocols and processes for embryo transfer (i.e. embryo quality, cryopreservation protocol, transfer techniques, etc.) and the potential impact on outcomes. WIDER IMPLICATIONS OF THE FINDINGS: The lowest risk of ectopic pregnancy was associated with the transfer of a single frozen blastocyst. This finding adds to the increasing evidence of better perinatal outcomes following frozen embryo transfers. The approach of freezing all embryos in the initiated fresh cycle and transfer of a single frozen blastocyst in the subsequent thaw cycle may improve the overall pregnancy and birth outcomes following ART treatment, in part by reducing the ectopic pregnancy rate. STUDY FUNDING/COMPETING INTERESTS: There is no funding for this study. Authors declared no competing interest related to this study.

Clinical outcomes following cryopreservation of blastocysts by vitrification or slow freezing: a population-based cohort study.

STUDY QUESTION: What are the clinical efficacy and perinatal outcomes following transfer of vitrified blastocysts compared with transfer of fresh or of slow frozen blastocysts? SUMMARY ANSWER: Compared with slow frozen blastocysts, vitrified blastocysts resulted in significantly higher clinical pregnancy and live delivery rates with similar perinatal outcomes at population level. WHAT IS KNOWN ALREADY: Although vitrification has been reported to be associated with significantly increased post-thaw survival rates compared with slow freezing, there has been a lack of general consensus over which method of cryopreservation (vitrification versus slow freezing) is most appropriate for blastocysts. STUDY DESIGN, SIZE, DURATION: A population-based cohort of autologous fresh and initiated thaw cycles (a cycle where embryos were thawed with intention to transfer) performed between January 2009 and December 2011 in Australia and New Zealand was evaluated retrospectively. A total of 46 890 fresh blastocyst transfer cycles, 12 852 initiated slow frozen blastocyst thaw cycles and 20 887 initiated vitrified blastocyst warming cycles were included in the data analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pairwise comparisons were made between the vitrified blastocyst group and slow frozen or fresh blastocyst group. A Chi-square test was used for categorical variables and t-test was used for continuous variables. Cox regression was used to examine the pregnancy outcomes (clinical pregnancy rate, miscarriage rate and live delivery rate) and perinatal outcomes (preterm delivery, low birthweight births, small for gestational age (SGA) births, large for gestational age (LGA) births and perinatal mortality) following transfer of fresh, slow frozen and vitrified blastocysts. MAIN RESULTS AND THE ROLE OF CHANCE: The 46 890 fresh blastocyst transfers, 11 644 slow frozen blastocyst transfers and 19 978 vitrified blastocyst transfers resulted in 16 845, 2766 and 6537 clinical pregnancies, which led to 13 049, 2065 and 4955 live deliveries, respectively. Compared with slow frozen blastocyst transfer cycles, vitrified blastocyst transfer cycles resulted in a significantly higher clinical pregnancy rate (adjusted relative risk (ARR): 1.47, 95% confidence intervals (CI): 1.39-1.55) and live delivery rate (ARR: 1.41, 95% CI: 1.34-1.49). Compared with singletons born after transfer of fresh blastocysts, singletons born after transfer of vitrified blastocysts were at 14% less risk of being born preterm (ARR: 0.86, 95% CI: 0.77-0.96), 33% less risk of being low birthweight (ARR: 0.67, 95% CI: 0.58-0.78) and 40% less risk of being SGA (ARR: 0.60, 95% CI: 0.53-0.68). LIMITATIONS, REASONS FOR CAUTION: A limitation of this population-based study is the lack of information available on clinic-specific cryopreservation protocols and processes for slow freezing-thaw and vitrification-warm of blastocysts and the potential impact on outcomes. WIDER IMPLICATIONS OF THE FINDINGS: This study presents population-based evidence on clinical efficacy and perinatal outcomes associated with transfer of fresh, slow frozen and vitrified blastocysts. Vitrified blastocyst transfer resulted in significantly higher clinical pregnancy and live delivery rates with similar perinatal outcomes compared with slow frozen blastocyst transfer. Comparably better perinatal outcomes were reported for singletons born after transfer of vitrified blastocysts than singletons born after transfer of fresh blastocysts. Elective vitrification could be considered as an alternative embryo transfer strategy to achieve better perinatal outcomes following Assisted Reproduction Technology (ART) treatment. STUDY FUNDING/COMPETING INTERESTS: No specific funding was obtained. The authors have no conflicts of interest to declare.

Barriers to dental care for children with autism spectrum disorder.

AIMS: This study examined the problems encountered by children with autism spectrum disorder (ASD), when accessing dental care. STUDY DESIGN: This was a cross-sectional, case-control questionnaire study. METHODS: A piloted questionnaire was developed to identify the main barriers to dental care experienced by patients with ASD in Hull and East Riding. The study group was comprised of parents/carers of children with ASD, and the control group was comprised of parents/carers of age matched healthy, neurotypical children. STATISTICS: Results were analysed using Chi-square and Fisher's exact tests where appropriate. Significance was deemed at p < 0.05. Ordinal data was presented using medians and 25th and 75th centiles and compared using Mann-Whitney U test. METHODS: A piloted questionnaire was developed to identify the main barriers to dental care experienced by patients with ASD in Hull and East Riding. The study group was comprised of parents/carers of children with ASD, and the control group was comprised of parents/carers of age matched healthy, neurotypical children. RESULTS: 112 subjects completed the questionnaire. There was no significant difference in accessing dental care between study and control groups (p = 0.051), although access was perceived as more difficult in the ASD group (p < 0.001). There was a significantly greater perceived difficulty in travelling to the dental surgery in the ASD group. Predicted negative behaviours were more frequent in the ASD group. All suggested interventions were predicted to be helpful in a significantly greater proportion of the ASD group. CONCLUSION: Difficulties exist for children with ASD in accessing dental care in the Hull and East Riding area.

Hospital utilization, costs and mortality rates during the first 5 years of life: a population study of ART and non-ART singletons.

STUDY QUESTION: Do singletons conceived following assisted reproduction technologies (ARTs) have significantly different hospital utilization, and therefore costs, compared with non-ART children during the first 5 years of life? SUMMARY ANSWER: ART singletons have longer hospital birth-admissions and a small increased risk of re-admission during the first 5 years of life resulting in higher costs of hospital care. WHAT IS KNOWN ALREADY: ART singletons are at greater risk of adverse perinatal outcomes compared with non-ART singletons. Long-term physical and mental health outcomes of ART singletons are generally reassuring. There is a scarcity of information on health service utilization and the health economic impact of ART conceived children. STUDY DESIGN, SIZE, DURATION: A population cohort study using linked birth, hospital and death records. Perinatal outcomes, hospital utilization and costs, and mortality rates were compared for non-ART and ART singletons to 5 years. Adjustments were made for maternal age, parity, sex, birth year, socioeconomic status and funding source. Australian Diagnosis Related Groups cost-weights were used to derive costs. All costs are reported in 2009/2010 Australian dollars. PARTICIPANTS/MATERIALS, SETTING, METHODS: All babies born in Western Australia between 1994 and 2003 were included; 224 425 non-ART singletons and 2199 ART conceived singletons. Hospital admission and death records in Western Australia linked to 2008 were used. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, ART singletons had a significantly longer length of stay during the birth-admission (mean difference 1.8 days, P < 0.001) and a 20% increased risk of being admitted during the first 5 years of life. The average adjusted difference in hospital admission costs up to 5 years of age was $2490, with most of the additional cost occurring during the birth-admission ($1473). The independent residual cost associated with ART conception was $342 during the birth-admission and an additional $548 up to 5 years of age, indicating that being conceived as an ART child predicts not only higher birth-admission costs but excess costs to at least 5 years of age. LIMITATIONS, REASONS FOR CAUTION: This study could not investigate the impact of different ART practices and techniques on perinatal outcomes or hospital utilization, nor could it adjust for parental characteristics such as cause of infertility and treatment-seeking behaviour. This study related to ART treatment undertaken before 2003. WIDER IMPLICATIONS OF THE FINDINGS: Clinicians and patients should be aware of the risk of poorer perinatal outcomes and increased hospitalization of ART singletons compared with non-ART singletons. These differences are significant enough to affect health-care resource consumption, but are substantially and significantly less than those associated with ART multiple birth infants. Understanding the short- and long-term health services and economic impact of ART is important for setting the research agenda in ART, for informing economic evaluations of infertility and treatment strategies, and for providing an important input to clinical and administrative decision making. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used to undertake this study and the authors report no conflicts of interest. A number of the authors receive Research Grants to their institutions from the Australian Government. G.M.C. receives grant support to her institution from the Australian Government, Australian Research Council (ARC) Linkage Grant No LP1002165; ARC Linkage Grant Partner Organisations are IVFAustralia, Melbourne IVF and Queensland Fertility Group. V.P.H. is employed as an Economics Research Associate on the same grant. TRIAL REGISTRATIONS NUMBER: NA.

Higher prevalence of gestational diabetes mellitus following assisted reproduction technology treatment.

STUDY QUESTION: Do mothers following assisted reproduction technology (ART) treatment have increased likelihood of gestational diabetes mellitus (GDM) compared with non-ART mothers after controlling for maternal factors and plurality? SUMMARY ANSWER: ART mothers had 28% increased likelihood of GDM compared with non-ART mothers. WHAT IS KNOWN ALREADY: Advanced maternal age and multiple pregnancies are independently associated with increased likelihood of GDM. Given the average age of mothers having ART treatment is higher than non-ART mothers and the higher multiple pregnancy rate following ART treatment, ART treatment might be expected to be associated with increased risk of GDM. STUDY DESIGN, SIZE, DURATION: A population retrospective cohort study of 400 392 mothers who gave birth in Australia between 2007 and 2009, using the Australian National Perinatal Data Collection from five states (Australian Capital Territory, Queensland, Tasmania, Victoria and Western Australia) where a code for ART treatment is available. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included 13 732 ART mothers and 386 660 non-ART mothers. The prevalence of GDM was compared between ART and non-ART mothers. Logistic regressions were used to assess the association between ART treatment and GDM. Odds ratio (OR), adjusted OR (AOR) and 95% confidence interval (CI) were calculated. MAIN RESULTS AND THE ROLE OF CHANCE: A larger proportion of ART mothers were aged ≥40 years compared with non-ART counterpart (11.7 versus 3.4%, P < 0.01). The prevalence of GDM was 7.6% for ART mothers and 5.0% for non-ART mothers (P < 0.01). Mothers who had twins had higher prevalence of GDM than those who gave births to singletons (8.8 versus 7.5%, P = 0.06 for ART mothers; and 7.3 versus 5.0%, P < 0.01 for non-ART mothers). Overall, ART mothers had a 28% increased likelihood of GDM compared with non-ART mothers (AOR 1.28, 95% CI 1.20-1.37). Of mothers who had singletons, ART mothers had higher odds of GDM than non-ART mothers (AOR 1.26, 95% CI 1.18-1.36). There was no significant difference in the likelihood of GDM among mothers who had twins between ART and non-ART (AOR 1.18, 95% CI 0.94-1.48). For mothers aged <40 years, the younger the maternal age, the higher the odds of GDM for ART singleton mothers compared with non-ART singleton mothers. LIMITATIONS, REASONS FOR CAUTION: It was not possible to investigate which ART procedure is associated with increased risk of GDM and how the risk could have been minimized. The information on BMI and smoking during pregnancy was not stated for a large proportion of mothers. These limitations may have reduced the validity of the study. WIDER IMPLICATIONS OF THE FINDINGS: In agreement with other studies, our data suggest that the underlying cause of subfertility and some particular ART procedures might have played an important role in the increased likelihood of GDM. Together with the public education on not delaying motherhood, minimizing multiple pregnancies by applying single embryo transfer may diminish the excess risk of GDM related to ART treatment.

International Committee for Monitoring Assisted Reproductive Technologies (ICMART) world report: assisted reproductive technology 2004.

STUDY QUESTION: Have changes in assisted reproductive technology (ART) practice and outcomes occurred globally between 2003 and 2004? SUMMARY ANSWER: Globally, ART practice has changed with an increasing prevalence of the use of ICSI rather than conventional IVF. In 2004, a small but increasing number of countries are incorporating single embryo transfer. There remain unacceptably high rates of three or more embryo transfers in select countries resulting in multiple births and adverse perinatal outcomes. WHAT IS KNOWN ALREADY: World data on the availability, effectiveness and safety of ART have been published since 1989. The number of embryos transferred is a major determinant of the iatrogenic increase in multiple pregnancies and is highly correlated with the likelihood of multiple birth and excess perinatal morbidity and mortality. STUDY DESIGN, SIZE, DURATION: Cross-sectional survey of countries and regions undertaking surveillance of ART procedures started in 2004 and their corresponding outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of total, 2184 clinics from 52 reporting countries and regions. Number of ART clinics, types of cycles and procedures, pregnancy, delivery and multiple birth rates and perinatal outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 954 743 initiated cycles resulted in an estimated 237 809 babies born. This was a 2.3% increase in the number of reported cycles from 2003. The availability of ART varied by country and ranged from 14 to 3844 treatment cycles per million population. Over one-third (37.2%) of ART clinics performed <100 cycles per year with only 19.9% performing ≥ 500 cycles per year. Of all cycles, 60.6% were ICSI. Frozen embryo transfers (FETs) represented 31% of the initiated cycles. The overall delivery rate per fresh aspiration for IVF and ICSI was 20.2% compared with 16.6% per FET. The average number of embryos transferred was 2.35. Single (16.3%) and double embryo transfers accounted for 73.2% of cycles. The overall proportion of deliveries with twins and triplets from IVF and ICSI was 25.1 and 1.8%, respectively, but varied widely by country and region. The proportion of premature deliveries per fresh aspiration for IVF and ICSI was 33.7% compared with 26.3% per FET. The perinatal death rate was 25.8 per 1000 births for fresh aspiration for IVF and ICSI compared with 14.2 per 1000 births per FET. LIMITATIONS, REASONS FOR CAUTION: Data are incomplete with seven countries not providing data to the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) in 2004 that had in 2003. The validity of data reflects current data collection practice. In 2004, 79.3% of the clinics in participating countries reported to their national or regional registries and to ICMART. In addition, the number of ART cycles per million population is a measure which is affected by a country's government policy, regulation, funding and the number of service providers. WIDER IMPLICATIONS OF THE FINDINGS: ART practice, effectiveness and outcomes vary markedly internationally. Notably, the increasing proportion of cycles that are FET, the change in practice to single embryo transfer and the cessation of the transfer of three or more embryos in some countries has resulted in improved perinatal outcomes with minimal impact on pregnancy rates. STUDY FUNDING/COMPETING INTEREST(S): ICMART receives financial support from ASRM, ESHRE, FSA, Japan Society for Reproductive Medicine, REDLARA, MEFS and SART.

The effect on human sex ratio at birth by assisted reproductive technology (ART) procedures--an assessment of babies born following single embryo transfers, Australia and New Zealand, 2002-2006.

OBJECTIVE: To assess the effect on the human sex ratio at birth by assisted reproductive technology (ART) procedures. DESIGN: Retrospective population-based study. SETTING: Fertility clinics in Australia and New Zealand. POPULATION: The study included 13,368 babies by 13,165 women who had a single embryo transfer (SET) between 2002 and 2006. METHODS: Logistic regression was used to model the effect on the sex ratio at birth of ART characteristics [in vitro fertilisation (IVF) or intracytoplasmic sperm insemination (ICSI) SET, cleavage-stage or blastocyst SET, and fresh or thawed SET] and biological characteristics (woman's and partner's age and cause of infertility). MAIN OUTCOME MEASURES: Proportion of male births. RESULTS: The crude sex ratio at birth was 51.3%. Individual ART procedures had a significant effect on the sex ratio at birth. More males were born following IVF SET (53.0%) than ICSI SET (50.0%), and following blastocyst SET (54.1%) than cleavage-stage SET (49.9%). For a specific ART regimen, IVF blastocyst SET produced more males (56.1%) and ICSI cleavage-stage SET produced fewer males (48.7%). CONCLUSIONS: The change in the sex ratio at birth of SET babies is associated with the ART regimen. The mechanism of these effects remains unclear. Fertility clinics and patients should be aware of the bias in the sex ratio at birth when using ART procedures.

A comparative analysis of assisted reproductive technology cycles in Australia and New Zealand 2004-2007.

BACKGROUND: There are different funding arrangements for fertility treatments between New Zealand (NZ) and Australia. In NZ, there are two options for patients accessing treatment: either meeting specified criteria for age, no smoking and BMI for publicly funding or funding their own treatment. This differs from Australia, which has no explicit eligibility criteria restricting access to fertility treatment. An analysis of assisted reproductive technology (ART) in Australia and NZ was undertaken to consider the impact of these different funding approaches. METHODS: Data were extracted from the Australian and New Zealand Assisted Reproduction Database between 2004 and 2007. A total of 116 111 autologous fresh cycles were included. RESULTS: In Australia, more cycles were in women aged 40 years or older compared with those in NZ (23.5 versus 16.0%, P < 0.01). Single embryo transfer was more common in NZ than that in Australia, in women < 35 years of age (75.1 versus 59.6%, P < 0.01). In women <35 years, the crude rates of clinical pregnancy (37.5 versus 31.2%, P < 0.01) and live delivery (31.6 versus 26%, P < 0.01) following fresh ART cycles were significantly higher in NZ than that in Australia. These differences in outcomes persisted in older age groups. CONCLUSIONS: The purpose of the criteria used in NZ to access public funding for fertility treatments is to optimize pregnancy outcomes. This approach has resulted in a healthier population of women undergoing treatment and may explain the improved pregnancy outcomes seen in NZ couples who undergo fertility treatments.

Age-specific success rate for women undertaking their first assisted reproduction technology treatment using their own oocytes in Australia, 2002-2005.

BACKGROUND: Woman's age is an independent factor determining the success of assisted reproductive technology treatment. This study presents the age-specific success rate of first autologous fresh treatment in Australia during 2002-2005. METHODS: This is a retrospective population-based study of 36,412 initiated first autologous fresh cycles conducted in Australian clinics during 2002-2005. Pregnancy and live delivery rates per initiated cycle were determined for each age. RESULTS: The overall live delivery rate per initiated cycle was 20.4% with the highest success rate in women aged between 22 and 36 years. Male factor only infertility had a higher live delivery rate (22.0%) than female factor only infertility (19.2%). Advancing woman's age was associated with a decline in success rate. For women > or = 30 years, each additional 1 year in age was associated with an 11% (99% CI: 10-12%) reduction in the chance of achieving pregnancy and a 13% (99% CI: 12-14%) reduction in the chance of a live delivery. If women aged 35 years or older would have had their first autologous fresh treatment 1 year earlier, 15% extra live deliveries would be expected. CONCLUSIONS: This study suggested that women aged 35 years or older should be encouraged to seek early fertility assessment and treatment where clinically indicated.

Body change strategies in children: relationship to age and gender.

The "Body Image and Body Change Inventory Questionnaire" was administered to 958 students, aged 8.00-13.99 years, to determine the types of strategies used by children to accomplish changes in body size/shape. Each individual strategy score was compared for each gender and with respect to age. The girls' score for food restrictive practices was significantly higher than for other body change strategies. For the boys, the score for the use of food and exercise strategies to increase muscle size was significantly higher than all other practices except exercise strategies to increase body size. Both boys and girls reported the lowest scores for food and exercise strategies to increase body weight. The variance explained by age was small and not considered biologically significant. While the findings do not demonstrate a relationship between desire to change body size/shape and age, weight concerns should not be overlooked, as both genders seem concerned with keeping their body weight low. The different practices used by each gender demonstrate that different body image ideals hold for boys and girls.

Media influence on the body image of children and adolescents.

To study the media messages portrayed to children, 925 students, from 9 to up to 14 years of age, completed "The Sociocultural Influences Questionnaire." The media section is the focus of this paper, and the responses from three questions were selected to examine the media's influence to be slimmer, increase weight, or increase muscle size. While the girls and boys exhibited different levels of agreement with each media influence, both genders disagreed that media messages were implying they should gain weight. This is in agreement with the belief that the media perpetuates the ideal of thinness and there is a negative stigma associated with being overweight.

Comparison of selected reasons for hospitalization of children among children's/tertiary hospitals, Australia, 1996-97 and 1997-98.

OBJECTIVES: To describe the major characteristics of admissions to children's/tertiary hospitals (compared to other hospitals) and to compare characteristics of local and non-local admissions to specialist children's hospitals. METHODS: A cross-sectional analysis of a routinely collected data set of hospitalizations in Australia in 1996-97 and 1997-98. RESULTS: Hospital-specific proportions of asthma and bronchitis, tonsillectomy and/or adenoidectomy and gastroenteritis varied considerably. Multivariate analysis comparing the characteristics of admitted patients by locality showed that non-local admissions of patients with asthma and bronchitis and gastroenteritis to selected children's hospitals were significantly more likely to be Indigenous children and/or children who had been transferred from another hospital. Non-local admissions of tonsillectomy and/or adenoidectomy patients to selected hospitals were significantly more likely to be public patients. CONCLUSIONS: Differences in the characteristics of admitted patients to children's hospitals by locality raise issues about equality of access and availability of appropriate services for these children and their families.

Anxiety related to dental general anaesthesia: changes in anxiety in children and their parents.

AIM: To examine the anxiety levels of children referred for dental general anaesthesia and their parents at various key points of the referral and anaesthetic procedure. METHODS: Structured interviews and anxiety measures were conducted with 50 children attending the Department of Paediatric Dentistry, Leeds Dental Institute, and progressing to general anaesthetic (GA) and their parents. Interviews were conducted with parents and children prior to initial assessment, following assessment and prior to a GA. Anxiety was measured at each interview, using the Visual Analogue Scale for parents and the Venham's Picture test for children. A fourth telephone interview was conducted with parents one week after the GA when the degree of upset caused to parents and children by the procedure was evaluated. RESULTS: Anxiety of children remained constant at each interview. Parent and child anxiety were not related. There was a rise in parent anxiety following initial assessment in those families attending in response to a routine referral and progressing to GA (p<0.05). There was a further rise in parent anxiety in these families immediately prior to the GA itself (p<0.001). Parent upset was strongly related to their anxiety at each of the three interviews prior to the GA (p<0.01, 0.05 and 0.001 respectively) and to the distress of their child (p<0.02). Child distress was strongly related to anxiety at each of the three interviews prior to the GA. CONCLUSION: The anxiety levels of children did not appear to change throughout the whole GA assessment and treatment process. Parent anxiety rose significantly following assessment and again just prior to the GA. Factors contributing to parent upset post treatment were child upset and pre treatment parent anxiety levels. Children who were most anxious prior to GA found the procedure most distressing.

Prevalence of sexually transmitted diseases and human immunodeficiency virus among women attending prenatal services in Apia, Samoa.

There is no routine prenatal screening for sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV) in pregnancy in Samoa. Testing for chlamydial infection is not available. To gather information on pregnant women, a prevalence survey was conducted in Apia, Samoa, utilizing two prenatal hospital clinics. Pregnant (n=427) women were tested for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis using polymerase chain reaction (PCR), and for syphilis (n=441) by rapid plasmid reagin (RPR) and HIV (n=441) by enzyme-linked immunosorbent assay (ELISA). Results were: chlamydia 30.9% (132); trichomoniasis 20.8%; gonorrhoea 3.3%; syphilis 0.5%; and HIV 0%. Overall 42.7% had at least 1 STD. Young women aged <25 years were three times more likely to have a STD than older women (odds ratio=3.0, 95% confidence intervals 2.0, 4.5). The lack of inexpensive, reliable field diagnostics remain a barrier to sustainable STD control programmes for pregnant women living in developing countries.

Effectiveness of postmigration screening in controlling tuberculosis among refugees: a historical cohort study, 1984-1998.

OBJECTIVES: This study assessed the effectiveness of postmigration screening for the control of tuberculosis (TB) among refugee migrants. METHODS: We conducted a historical cohort study among 24 610 predominantly Southeast Asian refugees who had arrived in Sydney, Australia, between 1984 and 1994. All had been screened for TB before arrival and had radiologic follow-up for 18 months after arrival. Incident cases of TB were identified by record linkage analysis with confirmatory review of case notes. RESULTS: The crude annual incidence rate over 10-year follow-up was 74.9 per 100 000 person-years. Only 29.6% of the cases were diagnosed as a result of routine follow-up procedures. CONCLUSIONS: Enhanced passive case finding is likely to be more effective than active case finding for the control of TB among refugees.