Microbial colonisation of human follicular fluid and adverse in vitro fertilisation outcomes

This study, investigating 263 women undergoing trans-vaginal oocyte retrieval for in vitro fertilisation (IVF) found that microorganisms colonising follicular fluid contributed to adverse IVF (pre-implantation) and pregnancy (post-implantation) outcomes including poor quality embryos, failed pregnancy and early pregnancy loss (< 37 weeks gestation). Some microorganisms also showed in vitro growth patterns in liquid media that appeared to be enhanced by the hormonal stimulation protocol used for oocyte retrieval. Elaborated cytokines within follicular fluid were also associated with adverse IVF outcomes. This study is imperative because infertility affects 16% of the human population and the numbers of couples needing assistance continues to increase. Despite significant improvements in the technical aspects of assisted reproductive technologies (ART), the live birth rate has not increased proportionally. Overt genital tract infection has been associated with both infertility and adverse pregnancy outcomes (including miscarriage and preterm birth) as a direct result of the infection or the host response to it. Importantly, once inflammation had become established, medical treatment often failed to prevent these significant adverse outcomes. Current evaluations of fertility focus on the ovary as a site of steroid hormone production and ovulation. However, infertility as a result of subclinical colonisation of the ovary has not been reported. Furthermore, identification of the microorganisms present in follicular fluid and the local cytokine profile may provide clinicians with an early indication of the prognosis for IVF treatment in infertile couples, thus allowing antimicrobial treatment and/or counselling about possible IVF failure. During an IVF cycle, multiple oocytes undergo maturation in vivo in response to hormonal hyperstimulation. Oocytes for in vitro insemination are collected trans-vaginally. The follicular fluid that bathes the maturing oocyte in vivo, usually is discarded as part of the IVF procedure, but provides a unique opportunity to investigate microbial causes of adverse IVF outcomes. Some previous studies have identified follicular fluid markers that predict IVF pregnancy outcomes. However, there have not been any detailed microbiological studies of follicular fluid. For this current study, paired follicular fluid and vaginal secretion samples were collected from women undergoing IVF cycles to determine whether microorganisms in follicular fluid were associated with adverse IVF outcomes. Microorganisms in follicular fluid were regarded as either "colonisers" or "contaminants"; colonisers, if they were unique to the follicular fluid sample, and contaminants if the same microorganisms were detected in the vaginal and follicular fluid samples indicating that the follicular fluid was merely contaminated during the oocyte retrieval process. Quite unexpectedly, by these criteria, we found that follicular fluid from approximately 30% of all subjects was colonised with bacteria. Fertile and infertile women with colonised follicular fluid had decreased embryo transfer rates and decreased pregnancy rates compared to women with contaminated follicular fluids. The observation that follicular fluid was not always sterile, but contained a diverse range of microorganisms, is novel. Many of the microorganisms we detected in follicular fluid are known opportunistic pathogens that have been detected in upper genital tract infections and are associated with adverse pregnancy outcomes. Bacteria were able to survive for at least 28 weeks in vitro, in cultures of follicular fluid. Within 10 days of establishing these in vitro cultures, several species (Lactobacillus spp., Bifidobacterium spp., Propionibacterium spp., Streptococcus spp. and Salmonella entericus) had formed biofilms. Biofilms play a major role in microbial pathogenicity and persistence. The propensity of microbial species to form biofilms in follicular fluid suggests that successful treatment of these infections with antimicrobials may be difficult. Bifidobacterium spp. grew, in liquid media, only if concentrations of oestradiol and progesterone were similar to those achieved in vivo during an IVF cycle. In contrast, the growth of Streptococcus agalactiae and Escherichia coli was inhibited or abolished by the addition of these hormones to culture medium. These data suggest that the likelihood of microorganisms colonising follicular fluid and the species of bacteria involved is influenced by the stage of the menstrual cycle and, in the case of IVF, the nature and dose of steroid hormones administered for the maturation of multiple oocytes in vivo. Our findings indicate that the elevated levels of steroid hormones during an IVF cycle may influence the microbial growth within follicular fluid, suggesting that the treatment itself will impact on the microflora present in the female upper genital tract during pre-conception and early post-conception phases of the cycle. The effect of the host immune response on colonising bacteria and on the outcomes of IVF also was investigated. White blood cells reportedly compose between 5% and 15% of the cell population in follicular fluid. The follicular membrane is semi-permeable and cells are actively recruited as part of the normal menstrual cycle and in response to microorganisms. A previous study investigated follicular fluid cytokines from infertile women and fertile oocyte donors undergoing IVF, and concluded that there were no significant differences in the cytokine concentrations between the two groups. However, other studies have reported differences in the follicular fluid cytokine levels associated with infertile women with endometriosis or polycystic ovary syndrome. In this study, elevated levels of interleukin (IL)-1 á, IL-1 â and vascular endothelial growth factor (VEGF) in vaginal fluid were associated with successful fertilisation, which may be useful marker for successful fertilisation outcomes for women trying to conceive naturally or prior to oocyte retrieval for IVF. Elevated levels of IL-6, IL-12p40, granulocyte colony stimulating factor (GCSF) and interferon-gamma (IFN ã) in follicular fluid were associated with successful embryo transfer. Elevated levels of pro-inflammatory IL-18 and decreased levels of anti-inflammatory IL-10 were identified in follicular fluid from women with idiopathic infertility. Successful fertilisation and implantation is dependent on a controlled pro-inflammatory environment, involving active recruitment of pro-inflammatory mediators to the genital tract as part of the menstrual cycle and early pregnancy. However, ongoing pregnancy requires an enhanced anti-inflammatory environment to ensure that the maternal immune system does not reject the semi-allergenic foetus. The pro-inflammatory skew in the follicular fluid of women with idiopathic infertility, correlates with normal rates of fertilisation, embryo discard and embryo transfer, observed for this cohort, which were similar to the outcomes observed for fertile women. However, their pregnancy rate was reduced compared to fertile women. An altered local immune response in follicular fluid may provide a means of explaining infertility in this cohort, previously defined as 'idiopathic'. This study has found that microorganisms colonising follicular fluid may have contributed to adverse IVF and pregnancy outcomes. Follicular fluid bathes the cumulus oocyte complex during the in vivo maturation process, and microorganisms in the fluid, their metabolic products or the local immune response to these microorganisms may result in damage to the oocytes, degradation of the cumulus or contamination of the IVF culture system. Previous studies that have discounted bacterial contamination of follicular fluid as a cause of adverse IVF outcomes failed to distinguish between bacteria that were introduced into the follicular fluid at the time of trans-vaginal oocyte retrieval and those that colonised the follicular fluid. Those bacteria that had colonised the fluid may have had time to form biofilms and to elicit a local immune response. Failure to draw this distinction has previously prevented consideration of bacterial colonisation of follicular fluid as a cause of adverse IVF outcomes. Several observations arising from this study are of significance to IVF programs. Follicular fluid is not always sterile and colonisation of follicular fluid is a cause of adverse IVF and pregnancy outcomes. Hormonal stimulation associated with IVF may influence whether follicular fluid is colonised and enhance the growth of specific species of bacteria within follicular fluid. Bacteria in follicular fluid may form biofilms and literature has reported that this may influence their susceptibility to antibiotics. Monitoring the levels of selected cytokines within vaginal secretions may inform fertilisation outcomes. This study has identified novel factors contributing to adverse IVF outcomes and that are most likely to affect also natural conception outcomes. Early intervention, possibly using antimicrobial or immunological therapies may reduce the need for ART and improve reproductive health outcomes for all women.

What's happening down under : young adolescent education in Australia

The middle years are an important period of learning, in which knowledge of fundamental disciplines are developed, yet this is also a time when students are at the greatest risk of disengagement from learning. Student motivation and engagement in these years is critical, and can be influenced by tailoring approaches to teaching with learning activities and learning environments that specifically consider the needs of middle years’ students.

The story of the sixties...a pile-up on the freeway of advanced art

When does 1960s art begin and end? Certainly, aside from a few affinities, the decade’s artistic output does not exactly correspond to its popular conception as the ‘Swinging Sixties’. While it was rare that psychedelic art was truly challenging, the decade saw a number of perceptions change regarding the aims, boundaries and possibilities of experiencing art. Thus, this era has come to represent a watershed or crisis in modernist art. While in the Australian context many of these nascent trends were properly realised in the 1970s – with the full force and impact of post-object art – other challenges were first articulated in the 1950s. So, like any other demarcation of a decade, its limits and boundaries are porous.

Understanding the use of technology in organisations : a structurational approach

Information Technology and its relationship to organisational performance has long been the interest of researchers. While there is concurrence that IT does contribute to performance, and we are efficiently expanding our knowledge on what factors cause better leveraging of IT resources in organisations, we have done little to understand how these factors interact with technology that results in improved performance. Using a structurational lens that recognises the recursive interaction between technology and people in the presence of social practices, and the norms that inform their ongoing practices, we propose an ethnographic approach to understanding the interaction between technology and resources, aiming to provide richer insight on the nature of the environment that promotes better use of IT resources. Such insights could provide the IT users with at least an initial conception of the IT usage platform that they could promote in their organisations to leverage the most from their IT resources.

‘Personal Response’ and English Teaching

A case study relating to secondary education, examining the teacher student relationship as it operates within the English classroom is the topic of this paper. It describes how a certain conception of 'personal response' to literature provided a means for the teacher/counsellor to form the ethical capacities of children. 'Personal response' is usually associated with the moment in which the child is freed to be most natural. But for all the emphasis upon the irreducibly individual nature of the 'genuinely felt response', this pedagogic exercise finds its place within a series of strategies designed both to cherish and correct the child, to nurture and to scrutinise, to guide and to reconstruct.

Corporate profit and impression management in developing markets

In this study, we examine how organisations in Fiji communicate or legitimise their profit. We base the need for understanding this phenomenon on the following premise. Organisations are part of a wider society, and in competition for scarce resources. Organisations obtain the rights to consume resources upon conception, but must continually legitimise their rights of existence and the need to access the resources. Legitimacy is the ability to continue to justify one’s authority to exist in a society. Organisations rights to resources are contractual, and have a moral obligation to act in a responsible manner and justify their outcomes, actions, and activities to external stakeholders. Such justifications would be an attempt at legitimizing their existence by some form of impression management. Impression management refers to the process by which individuals attempt to influence the impression of others (Melo et al. 2009). In corporate reporting, impression management occurs when management selects, display, and presents that information in a manner that distorts readers’ perceptions of corporate achievements (Neu 1991; Patten 2002), and is managed best through disclosures (O’Donovan 2002). In developing economies, there is significant Government protection that creates near-monopoly sectors and industries. The rendered protection permits organisations to provide essential services to the community at reasonable costs. Organisations in these sectors and industries have an ominous need to legitimise their position and actions. The bond between the organisations and the society is much stronger, making organisations devote more effort in communicating their activities. Protection permits organisations to make reasonable profits to sustain their operations. Society may not accept abnormal profits from operational efficiencies. Profit is fundamental to the society’s perception of an organisation, amplifying the need for the firm to justify a level of profit. Abnormal profit for organisations construes bad news, and organisations would make relevant disclosures to manage stakeholder impressions on profit (Patten 2002). Organisations can manage impressions by disclosing information in a particular way. That is, organisations would want to put the impression that the abnormal profit is justified and the society will obtain its benefits in future. Such form of impression management requires unambiguous disclosure of information. The readability of corporate disclosures is an important indicator of organisational abnormal profit-related legitimacy efforts in developing economies.

Identity and genetic origins : an ethical exploration of the late discovery of adoptive and donor-insemination offspring status

This thesis is an ethical and empirical exploration of the late discovery of genetic origins in two contexts, adoption and sperm donor-assisted conception. This exploration has two interlinked strands of concern. The first is the identification of ‘late discovery’ as a significant issue of concern, deserving of recognition and acknowledgment. The second concerns the ethical implications of late discovery experiences for the welfare of the child. The apparently simple act of recognition of a phenomenon is a precondition to any analysis and critique of it. This is especially important when the phenomenon arises out of social practices that arouse significant debate in ethical and legal contexts. As the new reproductive technologies and some adoption practices remain highly contested, an ethical exploration of this long neglected experience has the potential to offer new insights and perspectives in a range of contexts. It provides an opportunity to revisit developmental debate on the relative merit or otherwise of biological versus social influences, from the perspective of those who have lived this dichotomy in practise. Their experiences are the human face of the effects arising from decisions taken by others to intentionally separate their biological and social worlds, an action which has then been compounded by family and institutional secrecy from birth. This has been accompanied by a failure to ensure that normative standards and values are upheld for them. Following discovery, these factors can be exacerbated by a lack of recognition and acknowledgement of their concerns by family, friends, community and institutions. Late discovery experiences offer valuable insights to inform discussions on the ethical meanings of child welfare, best interests, parental responsibility, duty of care and child identity rights in this and other contexts. They can strengthen understandings of what factors are necessary for a child to be able to live a reasonably happy or worthwhile life.

Theorizing Police Response to Domestic Violence in Singapore: Police Subculture Revisited

This article focuses on the well documented, yet potentially contested concept of rank-and-file policesubculture to conceptualize policeresponse to situations of domesticviolence in Singapore. It argues that the utility of the concept to explaining police behavior is often undermined by an all-powerful, homogenous, and deterministic conception of it that fails to take into account the value of agency in police decision-making and the range of differentiated policeresponse in situations of domesticviolence. Through reviewing the literature on policeresponse to domesticviolence, this study called for the need to rework the concept of policesubculture by treating it as having a relationship with, and response to, the structural conditions of policing, while retaining a conception of the active role played by street-level officers in instituting a situational practice. Using Pierre Bourdieu's relational concepts of ‘habitus’ and ‘field,’ designating the cultural dispositions of policesubculture and structural conditions of policing respectively, the study attempted to reconceptualize the problem of policing domesticviolence with reference to the Singaporean context.

Methodological challenges when estimating the effects of season and seasonal exposures on birth outcomes

Background Many previous studies have found seasonal patterns in birth outcomes, but with little agreement about which season poses the highest risk. Some of the heterogeneity between studies may be explained by a previously unknown bias. The bias occurs in retrospective cohorts which include all births occurring within a fixed start and end date, which means shorter pregnancies are missed at the start of the study, and longer pregnancies are missed at the end. Our objective was to show the potential size of this bias and how to avoid it. Methods To demonstrate the bias we simulated a retrospective birth cohort with no seasonal pattern in gestation and used a range of cohort end dates. As a real example, we used a cohort of 114,063 singleton births in Brisbane between 1 July 2005 and 30 June 2009 and examined the bias when estimating changes in gestation length associated with season (using month of conception) and a seasonal exposure (temperature). We used survival analyses with temperature as a time-dependent variable. Results We found strong artificial seasonal patterns in gestation length by month of conception, which depended on the end date of the study. The bias was avoided when the day and month of the start date was just before the day and month of the end date (regardless of year), so that the longer gestations at the start of the study were balanced by the shorter gestations at the end. After removing the fixed cohort bias there was a noticeable change in the effect of temperature on gestation length. The adjusted hazard ratios were flatter at the extremes of temperature but steeper between 15 and 25°C. Conclusions Studies using retrospective birth cohorts should account for the fixed cohort bias by removing selected births to get unbiased estimates of seasonal health effects.

Design overview of USDL

Enabling web-based service networks and ecosystems requires a way of describing services by a "commercial envelope" as discussed in Chapter 1. A uniform conception of services across all walks of life (including technical services) is required capturing business, operational and technical aspects. Therefore, our proposed Unified Service Description Language (USDL) particularly draws from and generalizes the best-of-breed approaches presented in Part I. The following chapter presents the design rationale of USDL where the different aspects are put in a framework of descriptions requirements. This is followed by the subsequent chapters of this part that provide details on specific aspects such as pricing or legal issues.

The geostationary orbit : a critical legal geography of space’s most valuable real estate

This chapter attends to the legal and political geographies of one of Earth's most important, valuable, and pressured spaces: the geostationary orbit. Since the first, NASA, satellite entered it in 1964, this small, defined band of Outer Space, 35,786km from the Earth's surface, and only 30km wide, has become a highly charged legal and geopolitical environment, yet it remains a space which is curiously unheard of outside of specialist circles. For the thousands of satellites which now underpin the Earth's communication, media, and data industries and flows, the geostationary orbit is the prime position in Space. The geostationary orbit only has the physical capacity to hold approximately 1500 satellites; in 1997 there were approximately 1000. It is no overstatement to assert that media, communication, and data industries would not be what they are today if it was not for the geostationary orbit. This chapter provides a critical legal geography of the geostationary orbit, charting the topography of the debates and struggles to define and manage this highly-important space. Drawing on key legal documents such as the Outer Space Treaty and the Moon Treaty, the chapter addresses fundamental questions about the legal geography of the orbit, questions which are of growing importance as the orbit’s available satellite spaces diminish and the orbit comes under increasing pressure. Who owns the geostationary orbit? Who, and whose rules, govern what may or may not (literally) take place within it? Who decides which satellites can occupy the orbit? Is the geostationary orbit the sovereign property of the equatorial states it supertends, as these states argued in the 1970s? Or is it a part of the res communis, or common property of humanity, which currently legally characterises Outer Space? As challenges to the existing legal spatiality of the orbit from launch states, companies, and potential launch states, it is particularly critical that the current spatiality of the orbit is understood and considered. One of the busiest areas of Outer Space’s spatiality is international territorial law. Mentions of Space law tend to evoke incredulity and ‘little green men’ jokes, but as Space becomes busier and busier, international Space law is growing in complexity and importance. The chapter draws on two key fields of research: cultural geography, and critical legal geography. The chapter is framed by the cultural geographical concept of ‘spatiality’, a term which signals the multiple and dynamic nature of geographical space. As spatial theorists such as Henri Lefebvre assert, a space is never simply physical; rather, any space is always a jostling composite of material, imagined, and practiced geographies (Lefebvre 1991). The ways in which a culture perceives, represents, and legislates that space are as constitutive of its identity--its spatiality--as the physical topography of the ground itself. The second field in which this chapter is situated—critical legal geography—derives from cultural geography’s focus on the cultural construction of spatiality. In his Law, Space and the Geographies of Power (1994), Nicholas Blomley asserts that analyses of territorial law largely neglect the spatial dimension of their investigations; rather than seeing the law as a force that produces specific kinds of spaces, they tend to position space as a neutral, universally-legible entity which is neatly governed by the equally neutral 'external variable' of territorial law (28). 'In the hegemonic conception of the law,' Pue similarly argues, 'the entire world is transmuted into one vast isotropic surface' (1990: 568) on which law simply acts. But as the emerging field of critical legal geography demonstrates, law is not a neutral organiser of space, but is instead a powerful cultural technology of spatial production. Or as Delaney states, legal debates are “episodes in the social production of space” (2001, p. 494). International territorial law, in other words, makes space, and does not simply govern it. Drawing on these tenets of the field of critical legal geography, as well as on Lefebvrian concept of multipartite spatiality, this chapter does two things. First, it extends the field of critical legal geography into Space, a domain with which the field has yet to substantially engage. Second, it demonstrates that the legal spatiality of the geostationary orbit is both complex and contested, and argues that it is crucial that we understand this dynamic legal space on which the Earth’s communications systems rely.

Pregnancy losses in young Australian women : findings from the Australian Longitudinal Study on Women's Health

INTRODUCTION: Little research has examined recognized pregnancy losses in a general population. Data from an Australian cohort study provide an opportunity to quantify this aspect of fecundity at a population level. METHOD: Participants in the Australian Longitudinal Study on Women's Health who were aged 28-33 years in 2006 (n = 9,145) completed up to 4 mailed surveys over 10 years. Participants were categorized according to the recognized outcome of their pregnancies, including live birth, miscarriage/stillbirth, termination/ectopic, or no pregnancy. RESULTS: At age 18-23, more women reported terminations (7%) than miscarriages (4%). By 28-33 years, the cumulative frequency of miscarriage (15%) was as common as termination (16%). For women aged 28-33 years who had ever been pregnant (n = 5,343), pregnancy outcomes were as follows: birth only (50%); loss only (18%); and birth and loss (32%), of which half (16%) were birth and miscarriage. A comparison between first miscarriage and first birth (no miscarriage) showed that most first miscarriages occurred in women aged 18-23 years who also reported a first birth at the same survey (15%). Half (51%) of all first births and first miscarriages in women aged 18-19 ended in miscarriage. Early childbearers (<28 years) often had miscarriages around the same time period as their first live birth, suggesting proactive family formation. Delayed childbearers (32-33 years) had more first births than first miscarriages. CONCLUSION: Recognized pregnancy losses are an important measure of fecundity in the general population because they indicate successful conception and maintenance of pregnancy to varying reproductive endpoints.

Triclosan and benzophenone-3 in Australian pooled infant urine

The period of developmental vulnerability begins at conception and extends through gestation, parturition, infanthood and adolescence. The World Health Organisation (WHO) acknowledges that children experience quantitatively and qualitatively different exposures to chemicals than adults, and that children may be more or less sensitive to a chemical than adults [1, 2]. For instance, because of mouthing behaviours, children have higher exposure to chemicals through non-dietary ingestion than adults [3, 4], and the possibility exists for different metabolism and/or toxicity between different groups due to the immaturity of defense mechanisms that are fully developed in adults [1]. Traditional toxicological studies are inappropriate for assessing the results of exposure at very low levels during critical periods of development. Biomonitoring data can be used to identify where policies should be directed in order to reduce exposure.

Framing Movements for Gesture Interface Design

Gesture interfaces are an attractive avenue for human-computer interaction, given the range of expression that people are able to engage when gesturing. Consequently, there is a long running stream of research into gesture as a means of interaction in the field of human-computer interaction. However, most of this research has focussed on the technical challenges of detecting and responding to people’s movements, or on exploring the interaction possibilities opened up by technical developments. There has been relatively little research on how to actually design gesture interfaces, or on the kinds of understandings of gesture that might be most useful to gesture interface designers. Running parallel to research in gesture interfaces, there is a body of research into human gesture, which would seem a useful source to draw knowledge that could inform gesture interface design. However, there is a gap between the ways that ‘gesture’ is conceived of in gesture interface research compared to gesture research. In this dissertation, I explore this gap and reflect on the appropriateness of existing research into human gesturing for the needs of gesture interface design. Through a participatory design process, I designed, prototyped and evaluated a gesture interface for the work of the dental examination. Against this grounding experience, I undertook an analysis of the work of the dental examination with particular focus on the roles that gestures play in the work to compare and discuss existing gesture research. I take the work of the gesture researcher McNeill as a point of focus, because he is widely cited within gesture interface research literature. I show that although McNeill’s research into human gesture can be applied to some important aspects of the gestures of dentistry, there remain range of gestures that McNeill’s work does not deal with directly, yet which play an important role in the work and could usefully be responded to with gesture interface technologies. I discuss some other strands of gesture research, which are less widely cited within gesture interface research, but offer a broader conception of gesture that would be useful for gesture interface design. Ultimately, I argue that the gap in conceptions of gesture between gesture interface research and gesture research is an outcome of the different interests that each community brings to bear on the research. What gesture interface research requires is attention to the problems of designing gesture interfaces for authentic context of use and assessment of existing theory in light of this.

Affecting interference

This collaborative project by Daniel Mafe and Andrew Brown, one of a number in they have been involved in together, conjoins painting and digital sound into a single, large scale, immersive exhibition/installation. The work as a whole acts as an interstitial point between contrasting approaches to abstraction: the visual and aural, the digital and analogue are pushed into an alliance and each works to alter perceptions of the other. For example, the paintings no longer mutely sit on the wall to be stared into. The sound seemingly emanating from each work shifts the viewer’s typical visual perception and engages their aural sensibilities. This seems to make one more aware of the objects as objects – the surface of each piece is brought into scrutiny – and immerses the viewer more viscerally within the exhibition. Similarly, the sonic experience is focused and concentrated spatially by each painted piece even as the exhibition is dispersed throughout the space. The sounds and images are similar in each local but not identical, even though they may seem to be the same from casual interaction, closer attention will quickly show this is not the case. In preparing this exhibition each artist has had to shift their mode of making to accommodate the other’s contribution. This was mainly done by a process of emptying whereby each was called upon to do less to the works they were making and to iterate the works toward a shared conception, blurring notions of individual imagination while maintaining material authorship. Empting was necessary to enable sufficient porosity where each medium allowed the other entry to its previously gated domain. The paintings are simple and subtle to allow the odd sonic textures a chance to work on the viewer’s engagement with them. The sound remains both abstract, using noise-like textures, and at a low volume to allow the audience’s attention to wander back and forth between aspects of the works.