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.

Microorganisms within human follicular fluid : effects on IVF

Our previous study reported microorganisms in human follicular fluid. The objective of this study was to test human follicular fluid for the presence of microorganisms and to correlate these findings with the in vitro fertilization (IVF) outcomes. In this study, 263 paired follicular fluids and vaginal swabs were collected from women undergoing IVF cycles, with various causes for infertility, and were cultured to detect microorganisms. The cause of infertility and the IVF outcomes for each woman were correlated with the microorganisms detected within follicular fluid collected at the time of trans-vaginal oocyte retrieval. Microorganisms isolated from follicular fluids were classified as: (1) ‘colonizers’ if microorganisms were detected within the follicular fluid, but not within the vaginal swab (at the time of oocyte retrieval); or (2) ‘contaminants’ if microorganisms detected in the vagina at the time of oocyte retrieval were also detected within the follicular fluid. The presence of Lactobacillus spp. in ovarian follicular fluids was associated with embryo maturation and transfer. This study revealed microorganisms in follicular fluid itself and that the presence of particular microorganisms has an adverse affect on IVF outcomes as seen by an overall decrease in embryo transfer rates and pregnancy rates in both fertile and infertile women, and live birth rates in women with idiopathic infertility. Follicular fluid microorganisms are a potential cause of adverse pregnancy outcomes in IVF in both infertile women and in fertile women with infertile male partners.

Microbial colonisation of follicular fluid : alterations in cytokine expression and adverse assisted reproductive technology outcomes

Previous studies have measured cytokine expression within follicular fluid collected at the time of trans-vaginal oocyte retrieval and compared the profiles with the aetiology of infertility and/or successful or unsuccessful assisted reproductive technology (ART) outcomes. Seventy-one paired follicular fluid and vaginal swab specimens collected from ART patients were cultured to detect microorganisms and then were tested for the presence of cytokines by multiplex fluorescence bead assays. Specimen selection was based on two criteria: whether the follicular fluid specimen was colonised (with microorganisms prior to oocyte retrieval) or contaminated by lower genital tract microflora at the time of oocyte retrieval and; the aetiology of infertility...

GPX - Gardens Point XML Information Retrieval at INEX 2004

Traditional information retrieval (IR) systems respond to user queries with ranked lists of relevant documents. The separation of content and structure in XML documents allows individual XML elements to be selected in isolation. Thus, users expect XML-IR systems to return highly relevant results that are more precise than entire documents. In this paper we describe the implementation of a search engine for XML document collections. The system is keyword based and is built upon an XML inverted file system. We describe the approach that was adopted to meet the requirements of Content Only (CO) and Vague Content and Structure (VCAS) queries in INEX 2004.

Peer to peer English/Chinese cross-language information retrieval

Peer to peer systems have been widely used in the internet. However, most of the peer to peer information systems are still missing some of the important features, for example cross-language IR (Information Retrieval) and collection selection / fusion features. Cross-language IR is the state-of-art research area in IR research community. It has not been used in any real world IR systems yet. Cross-language IR has the ability to issue a query in one language and receive documents in other languages. In typical peer to peer environment, users are from multiple countries. Their collections are definitely in multiple languages. Cross-language IR can help users to find documents more easily. E.g. many Chinese researchers will search research papers in both Chinese and English. With Cross-language IR, they can do one query in Chinese and get documents in two languages. The Out Of Vocabulary (OOV) problem is one of the key research areas in crosslanguage information retrieval. In recent years, web mining was shown to be one of the effective approaches to solving this problem. However, how to extract Multiword Lexical Units (MLUs) from the web content and how to select the correct translations from the extracted candidate MLUs are still two difficult problems in web mining based automated translation approaches. Discovering resource descriptions and merging results obtained from remote search engines are two key issues in distributed information retrieval studies. In uncooperative environments, query-based sampling and normalized-score based merging strategies are well-known approaches to solve such problems. However, such approaches only consider the content of the remote database but do not consider the retrieval performance of the remote search engine. This thesis presents research on building a peer to peer IR system with crosslanguage IR and advance collection profiling technique for fusion features. Particularly, this thesis first presents a new Chinese term measurement and new Chinese MLU extraction process that works well on small corpora. An approach to selection of MLUs in a more accurate manner is also presented. After that, this thesis proposes a collection profiling strategy which can discover not only collection content but also retrieval performance of the remote search engine. Based on collection profiling, a web-based query classification method and two collection fusion approaches are developed and presented in this thesis. Our experiments show that the proposed strategies are effective in merging results in uncooperative peer to peer environments. Here, an uncooperative environment is defined as each peer in the system is autonomous. Peer like to share documents but they do not share collection statistics. This environment is a typical peer to peer IR environment. Finally, all those approaches are grouped together to build up a secure peer to peer multilingual IR system that cooperates through X.509 and email system.

Semantic and context-based retrieval of digital cultural objects [Published in Chinese]

Cultural objects are increasingly generated and stored in digital form, yet effective methods for their indexing and retrieval still remain an important area of research. The main problem arises from the disconnection between the content-based indexing approach used by computer scientists and the description-based approach used by information scientists. There is also a lack of representational schemes that allow the alignment of the semantics and context with keywords and low-level features that can be automatically extracted from the content of these cultural objects. This paper presents an integrated approach to address these problems, taking advantage of both computer science and information science approaches. We firstly discuss the requirements from a number of perspectives: users, content providers, content managers and technical systems. We then present an overview of our system architecture and describe various techniques which underlie the major components of the system. These include: automatic object category detection; user-driven tagging; metadata transform and augmentation, and an expression language for digital cultural objects. In addition, we discuss our experience on testing and evaluating some existing collections, analyse the difficulties encountered and propose ways to address these problems.

Improvement to Chinese information retrieval by incorporating word segmentation and query expansion

The increasing diversity of the Internet has created a vast number of multilingual resources on the Web. A huge number of these documents are written in various languages other than English. Consequently, the demand for searching in non-English languages is growing exponentially. It is desirable that a search engine can search for information over collections of documents in other languages. This research investigates the techniques for developing high-quality Chinese information retrieval systems. A distinctive feature of Chinese text is that a Chinese document is a sequence of Chinese characters with no space or boundary between Chinese words. This feature makes Chinese information retrieval more difficult since a retrieved document which contains the query term as a sequence of Chinese characters may not be really relevant to the query since the query term (as a sequence Chinese characters) may not be a valid Chinese word in that documents. On the other hand, a document that is actually relevant may not be retrieved because it does not contain the query sequence but contains other relevant words. In this research, we propose two approaches to deal with the problems. In the first approach, we propose a hybrid Chinese information retrieval model by incorporating word-based techniques with the traditional character-based techniques. The aim of this approach is to investigate the influence of Chinese segmentation on the performance of Chinese information retrieval. Two ranking methods are proposed to rank retrieved documents based on the relevancy to the query calculated by combining character-based ranking and word-based ranking. Our experimental results show that Chinese segmentation can improve the performance of Chinese information retrieval, but the improvement is not significant if it incorporates only Chinese segmentation with the traditional character-based approach. In the second approach, we propose a novel query expansion method which applies text mining techniques in order to find the most relevant words to extend the query. Unlike most existing query expansion methods, which generally select the highly frequent indexing terms from the retrieved documents to expand the query. In our approach, we utilize text mining techniques to find patterns from the retrieved documents that highly correlate with the query term and then use the relevant words in the patterns to expand the original query. This research project develops and implements a Chinese information retrieval system for evaluating the proposed approaches. There are two stages in the experiments. The first stage is to investigate if high accuracy segmentation can make an improvement to Chinese information retrieval. In the second stage, a text mining based query expansion approach is implemented and a further experiment has been done to compare its performance with the standard Rocchio approach with the proposed text mining based query expansion method. The NTCIR5 Chinese collections are used in the experiments. The experiment results show that by incorporating the text mining based query expansion with the hybrid model, significant improvement has been achieved in both precision and recall assessments.