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Clayton South, Australia

Rombauts L.,Monash IVF | Rombauts L.,Monash University | Motteram C.,Monash IVF | Berkowitz E.,Monash Health | And 2 more authors.
Human Reproduction | Year: 2014

STUDY QUESTION Is endometrial thickness measured prior to embryo transfer associated with placenta praevia? SUMMARY ANSWER Following IVF, the risk of placenta praevia is increased 4-fold in women with an endometrial thickness of >12 mm compared with women with an endometrial thickness of <9 mm. WHAT IS KNOWN ALREADY Placenta praevia is a serious complication of pregnancy with adverse maternal and neonatal outcomes. Placenta praevia is 2- to 6-fold more likely to occur following IVF treatment but it remains unknown what factors contribute to that increased risk. STUDY DESIGN, SIZE, DURATION Retrospective cohort study involving 4007 women who had 4537 singleton assisted reproduction technology (ART) births occurring between January 2006 and June 2012 with no loss to follow-up. The primary outcome measure was the diagnosis of placenta praevia, made by the treating obstetrician on a transvaginal ultrasound in the third trimester. PARTICIPANTS/MATERIALS, SETTING, METHODS Women who had singleton births following single embryo transfer performed at Monash IVF in Melbourne, Australia were included. Of the 4537 cycles leading to a singleton ART birth, 2951 were stimulated cycles with fresh embryo transfers; 355 were hormone replacement therapy frozen embryo transfers and 1231 were natural cycles with frozen embryo transfers. The dataset was analysed using binary logistic general estimating equations to calculate odds ratios for placenta praevia adjusted (aOR) for known confounders. MAIN RESULTS AND THE ROLE OF CHANCE The study groups did not differ significantly in age, BMI and aetiologies of infertility prior to IVF treatment. When compared with stimulated cycles, placenta praevia was less common in women undergoing natural cycles with frozen embryo transfers (OR 0.44, 95% confidence interval (CI) 0.27-0.70, P < 0.01) but hormone replacement therapy frozen embryo transfer cycles were not associated with a lower risk (OR 0.89, 95% CI 0.48-1.63). After adjusting for confounders, smoking (aOR 2.58, 95% CI 1.07-6.24, P = 0.04, endometriosis (aOR 2.01, 95% CI 1.21-3.33, P < 0.01) and endometrial thickness remained statistically significant as independent risk factors for placenta praevia. Compared with women with an endometrial thickness of <9 mm, women with an endometrial thickness of 9-12 mm had an aOR of 2.02 (95% CI 1.12-3.65, P = 0.02) and women with an endometrial thickness >12 mm had an aOR of 3.74 (95% CI 1.90-7.34, P < 0.01). These differences remained statistically significant after performing a sensitivity analysis limited to women with no previous births. LIMITATIONS, REASONS FOR CAUTION The study is retrospective in nature, not all confounders may have been accounted for and details on previous intrauterine surgery, a known risk factor, were not available. In addition, ultrasound assessments were carried out by several highly trained operators measuring the endometrial thickness, the main independent variable, in a two-dimensional plane and some inter-observer variability may therefore be present. WIDER IMPLICATIONS OF THE FINDINGS The findings of a higher risk of placenta praevia in patients with endometriosis and in those that smoke are in agreement with the current literature on natural conception. There have so far been no reports of an association between endometrial thickness and placenta praevia after ART. This novel finding warrants further study to elucidate the underlying cause of the association and to assess how to minimize harm to IVF patients and their offspring. The fact that the observed increased risk is not linked to the type of embryo transfer (fresh/frozen) but to the type of endometrial preparation, suggests that the risk of placenta praevia in ART can be reduced by considering an elective frozen embryo transfer in a natural cycle, especially given the growing evidence that this strategy also provides a number of other maternal and neonatal benefits. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Kaparakis-Liaskos M.,MIMR PHI Institute of Medical Research
Cytokine | Year: 2015

The host has developed an array of systems that enables protection against infection and response to injury, ultimately resulting in the generation of a pro-inflammatory response. The most rapid immune response is mediated via the innate immune system, which is comprised of germ line encoded pathogen recognition receptors (PRRs). This PRR mediated system functions by specifically recognizing conserved structures of microbial molecules or products, known as microbial-associated molecular patterns (MAMPs), ultimately enabling transduction of signaling cascades, gene transcription and the development of a pro-inflammatory innate immune response. The intracellular PRRs nucleotide-binding oligomerization domain protein 1 (NOD1) and NOD2 will be the focus of this review. A brief overview of NOD1 and NOD2 and recent advances in the field regarding the intracellular location and mechanisms of NOD1 signaling will be discussed. These new findings have broadened our understanding of the mechanisms whereby NOD1 signaling results in the induction of the cellular degradation pathway of autophagy and the development of pro-inflammatory responses that activate the adaptive immune system. © 2015 Elsevier Ltd.

Krishnan S.M.,Monash University | Sobey C.G.,Monash University | Latz E.,University of Bonn | Latz E.,University of Massachusetts Medical School | And 3 more authors.
British Journal of Pharmacology | Year: 2014

Chronic inflammation in the kidneys and vascular wall is a major contributor to hypertension. However, the stimuli and cellular mechanisms responsible for such inflammatory responses remain poorly defined. Inflammasomes are crucial initiators of sterile inflammation in other diseases such as rheumatoid arthritis and gout. These pattern recognition receptors detect host-derived danger-associated molecular patterns (DAMPs), such as microcrystals and reactive oxygen species, and respond by inducing activation of caspase-1. Caspase-1 then processes the cytokines pro-IL-1β and pro-IL-18 into their active forms thus triggering inflammation. While IL-1β and IL-18 are known to be elevated in hypertensive patients, no studies have examined whether this occurs downstream of inflammasome activation or whether inhibition of inflammasome and/or IL-1β/IL-18 signalling prevents hypertension. In this review, we will discuss some known actions of IL-1β and IL-18 on leukocyte and vessel wall function that could potentially underlie a prohypertensive role for these cytokines. We will describe the major classes of inflammasome-activating DAMPs and present evidence that at least some of these are elevated in the setting of hypertension. Finally, we will provide information on drugs that are currently used to inhibit inflammasome/IL-1β/IL-18 signalling and how these might ultimately be used as therapeutic agents for the clinical management of hypertension. © 2014 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Gargett C.E.,Monash University | Schwab K.E.,MIMR PHI Institute of Medical Research | Brosens J.J.,University of Warwick | Puttemans P.,Leuven Institute for Fertility and Embryology | And 2 more authors.
Molecular Human Reproduction | Year: 2014

The pathogenesis of early-onset endometriosis has recently been revisited, sparked by the discovery of endometrial stem/progenitor cells and their possible role in endometriosis, and because maternal pregnancy hormone withdrawal following delivery induces uterine bleeding in the neonate. The neonatal uterus has a large cervix to corpus ratio which is functionally blocked with mucous, supporting the concept of retrograde shedding of neonatal endometrium. Only 5% show overt bleeding. Furthermore, the presence of endometriosis in premenarcheal girls and even in severe stage in adolescents supports the theory that earlyonset endometriosis may originate from retrograde uterine bleeding soon after birth. Endometrial stem/progenitor cells have been identified in menstrual blood suggesting they may also be shed during neonatal uterine bleeding. Thus, we hypothesised that stem/progenitor cells present in shedding endometrium may have a role in the pathogenesis of early-onset endometriosis through retrograde neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed endometrial stem/progenitor cells are postulated to survive in the pelvic cavity in the absence of circulating oestrogens supported by niche cells also shed during neonatal uterine bleeding. According to this hypothesis, during thelarche, under the influence of rising oestrogen levels, endometrial stem/progenitor cells proliferate and establish ectopic endometrial lesions characteristic of endometriosis. This New Research Horizon review builds on recent discussions on the pathogenesis of early-onset endometriosis and raises new avenues for research into this costly condition. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Hooper S.B.,MIMR PHI Institute of Medical Research | Hooper S.B.,Monash University | Polglase G.R.,MIMR PHI Institute of Medical Research | Polglase G.R.,Monash University | And 3 more authors.
Paediatric Respiratory Reviews | Year: 2015

The newborn's transition from fetal to neonatal life includes aeration of the lungs, establishment of pulmonary gas exchange and changing the fetal circulation into the adult phenotype. This review summarizes the latest research findings, which show that lung aeration, airway liquid clearance and cardiovascular changes are directly interconnected at birth. The mechanisms of airway liquid clearance at birth are reviewed and the particular importance of the transpulmonary pressure gradient during lung aeration is discussed. Further, we summarize research findings which prove that lung aeration triggers the increase in pulmonary blood flow (PBF) at birth, and how the increase in PBF secures the preload for left ventricular output. Consequently, we review animal experiments which suggest that delaying umbilical cord clamping until breathing commences facilitates hemodynamic stability during transition. These data are reviewed with respect to the clinical applicability: As lung aeration is the key to successful transition to newborn life, providing adequate respiratory support at birth must be the primary objective of neonatal staff attending to the newborn infant. Clinical studies are needed to demonstrate whether the obvious benefits of delaying cord clamping until breathing commences hold true in human babies. © 2015 Elsevier Ltd.

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