Ian S Fraser

University of Sydney, Sydney, New South Wales, Australia

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Publications (236)803.98 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess endometrial gene as well as protein expression of neuroendocrine and supposedly endometriosis-associated product PGP9.5 and pain symptoms in women with endometriosis and controls undergoing laparoscopy, using molecular biological and immuno-histochemical approaches in the same patients.
    Archives of Gynecology and Obstetrics 07/2014; · 1.33 Impact Factor
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    ABSTRACT: Globally, the prevalence of, and support for, female genital mutilation/cutting (FGM/C) is declining. However, the entrenched sense of social obligation that propagates the continuation of this practice and the lack of open communication between men and women on this sensitive issue are two important barriers to abandonment. There is limited evidence on the role of men and their experiences in FGM/C. Marriageability of girls is considered to be one of the main driving forces for the continuation of this practice. In some countries, more men than women are advocating to end FGM/C. Moreover, men, as partners to women with FGM/C, also report physical and psychosexual problems. The abandonment process involves expanding a range of successful programs, addressing the human rights priorities of communities and providing power over their own development processes. Anecdotal evidence exists that FGM/C is practised amongst African migrant populations in Australia. The Australian Government supports a taskforce to improve community awareness and education, workforce training and evidence building. Internationally, an African Coordinating Centre for abandonment of FGM/C has been established in Kenya with a major global support group to share research, promote solidarity, advocacy and implement a coordinated and integrated response to abandon FGM/C.
    Australian and New Zealand Journal of Obstetrics and Gynaecology 05/2014; · 1.30 Impact Factor
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    ABSTRACT: Objective To highlight the advantages of formal classification of causes of abnormal uterine bleeding from a clinical and scientific perspective.DesignReview and recommendations for local implementation.SettingResearch in the field of menstrual disorders had not been funded adequately with respect to the impact of symptoms on individuals, healthcare systems and society. This was confounded by a diverse terminology, which lead to confusion between clinical and scientific groups, ultimately harming the underlying evidence base. To address this, a formal classification system (PALM-COEIN) for the causes of abnormal uterine bleeding has been published for worldwide use by FIGO (International Federation of Gynecology and Obstetrics).Population & Main OutcomeThis commentary explains problems created by the prior absence of such a system, the potential advantages stemming from its use, and practical suggestions for local implementation.Results & Conclusions The PALM-COEIN classification is applicable globally and, as momentum gathers, will ameliorate recurrence of historic problems, and harmonise reporting of clinical and scientific research to facilitate future progress in women's health.This article is protected by copyright. All rights reserved.
    Acta Obstetricia Et Gynecologica Scandinavica 04/2014; · 1.85 Impact Factor
  • Cecilia H.M. Ng, Ian S. Fraser, Marina Berbic
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    ABSTRACT: Many women in the reproductive years have chronic medical conditions that are affected by pregnancy or in which the fetus is placed at increased risk. In most of these women, ongoing medical management of their conditions is greatly improved, even compared with a decade or two ago. However, their condition may still be seriously exacerbated by the physiological changes of pregnancy, and close monitoring of a carefully planned pregnancy is optimal. This requires effective and safe contraceptive use until pregnancy is desired and the medical condition is stabilised. Many contraceptives will also have adverse effects on some medical conditions, and there is now a considerable awareness of the complexities of some of these interactions. For this reason the World Health Organization has developed an excellent, simple and pragmatic programme of guidelines on a four point scale (the WHO “Medical Eligibility Criteria”: WHO-MEC), summarising risk of specific contraceptive methods in women with specified chronic medical conditions. The general approach to contraceptive management of many of these conditions is addressed in this article.
    Best Practice & Research Clinical Obstetrics & Gynaecology. 01/2014;
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    ABSTRACT: To investigate the immune environment of endometrial polyps (EPs). Prospective case-control study. Teaching hospital and university research laboratory. Reproductive-age women undergoing hysteroscopy dilation and curettage for benign indications. Samples were collected from women with (n = 23) and without (n = 40) EPs. Endometrial samples were immunohistochemically stained with antibodies against mast cells (MCs) and regulatory T cells (Tregs). Tryptase+, chymase+, and c-Kit+ MCs and Foxp3+ Tregs were quantified in EPs and polyp-adjacent, polyp-distant, and control endometrium. Densities of all MC types were highly significantly increased in EPs compared with adjacent, distant, and control endometrium. Chymase+ and c-Kit+ MCs were increased in density in adjacent compared with control endometrium. c-Kit+ MCs were also increased in distant compared with control endometrium. Foxp3+ Treg density was increased in EPs compared with distant and control endometrium and decreased in distant compared with control endometrium. This study provides novel insights into localized disturbances in the cellular immune environment within EPs consistent with EPs being inflammatory lesions associated with MC overactivity. Tregs are likely to be recruited to EPs in an attempt to suppress the inflammatory process due to the greatly increased presence of MCs. These immunologic disturbances are likely to be involved in the causation of abnormal bleeding and infertility in premenopausal women with EPs, and their role in the pathophysiology requires further research.
    Fertility and sterility 08/2013; · 3.97 Impact Factor
  • Marina Berbic, Ian S Fraser
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    ABSTRACT: Normal menstruation is an inflammatory process, where the endometrial concentrations and functions of several leukocyte types can change greatly through the menstrual cycle, especially during the premenstrual and menstrual phases. These leukocytes probably have a range of functions related to mucosal protection, decidualization, embryo implantation, and the process of menstrual tissue breakdown, repair and remodeling. Some of these leukocyte changes are apparently linked to changes in the pattern of circulating leukocytes. Many immune cells have been identified in the endometrium, and those with most relevance to the processes of menstruation include uterine natural killer cells, macrophages, mast cells, neutrophils, dendritic cells and Tregs. A range of disturbances in endometrial immune cell numbers, distributions and functions, and in a range of different inflammatory and other mediators, have been identified in women with heavy menstrual bleeding or endometriosis. Sufficient evidence exists to implicate these immune changes in some of the functional disturbances and symptoms identified in these women. This field is greatly under-researched, and ripe for the wider application of modern molecular and cellular techniques in human and animal model studies.
    Women s Health 07/2013; 9(4):387-95.
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    ABSTRACT: Recent studies suggest that changes in certain uterine immune cell populations in endometrium of women with endometriosis are likely to precede changes at ectopic sites. This preliminary study is a first look into the function of uterine-draining lymph nodes (LNs) during the menstrual cycle and in the presence of endometriosis. Paraffin-embedded obturator LNs were obtained from women with (n = 7, mean age 44.3) and without (n = 9, mean age 38.4) endometriosis, who had undergone hysterectomy for cervical or ovarian cancer and in whom LN involvement was not detected. Immunohistochemical staining for endometrial stromal cells and a range of immune cell populations was performed. The CD10+ endometrial stromal cells were detected in uterine-draining LNs throughout the menstrual cycle with numbers peaking during menstruation. The inflammatory process of menstruation was also associated with increased numbers of CD3+, CD4+, Foxp3+, DC-Sign+, CD68+, CD20+, CD79+, and plasma cells. In endometriosis, CD10+ endometrial stromal cells were further increased in numbers, but CD3+, CD4+, DC-Lamp+, FoxP3+, and plasma cells were reduced. This study indicates that efficient immunological responses may be required to contain shed endometrial fragments within the draining uterine LNs thus preventing their further dissemination with establishment of ectopic lesions at distant sites.
    Reproductive sciences (Thousand Oaks, Calif.) 05/2013; · 2.31 Impact Factor
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    ABSTRACT: Despite the importance of neuropilins (NRPs) in a number of processes that are altered in endometriosis, such as angiogenesis and neuronal guidance, these molecules have not been previously studied in the disease. Similarly, potent lymphangiogenic factors, vascular endothelial growth factor C (VEGF-C) and VEGF-D, have not been comprehensively investigated in endometriosis. The objective of this study was to examine their expression in women with and without endometriosis. NRPs and VEGFs were quantified in 79 histologically normal uterine tissue samples (37 control and 42 endometriosis, all menstrual cycle phases) using immunohistochemistry and automated cellular imaging analysis. NRP-1 was significantly reduced in women with endometriosis (P = .004). The normal significant menstrual cyclical variations in endometrial NRP-1, NRP-2, and VEGF-C were absent in endometriosis, and VEGF-D was dysregulated. Dysregulated expression of growth factors and receptors, such as NRPs and VEGFs, likely contribute to altered angiogenesis, lymphangiogenesis, neurogenesis and immune function in endometriosis and may reflect altered hormone signals.
    Reproductive sciences (Thousand Oaks, Calif.) 04/2013; · 2.31 Impact Factor
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    ABSTRACT: This study demonstrates a robust and thorough trial design leading to accurate and objective data collection. We recommend that future studies investigating heavy menstrual bleeding (HMB) should follow, and improve upon, this rigorous approach to menstrual trial data collection, not only to validate clinical results but also to improve the techniques used to acquire these results. We propose that the state-of-the-art methodology described here be used as the basis for new guidelines for the implementation of clinical trials in the area of HMB.
    Reproductive sciences (Thousand Oaks, Calif.) 02/2013; · 2.31 Impact Factor
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    ABSTRACT: Endometriosis is a common, benign gynecological disease affecting 10 - 15% of reproductively aged women. It is characterized by the presence of endometrial-like tissue at sites outside the uterus. The most widely accepted theory of endometriosis pathogenesis proposes that shed menstrual endometrium can reach the peritoneum, implant and grow as endometriotic lesions. Angiogenesis, lymphangiogenesis and neurogenesis are implicated in successful ectopic establishment and the generation of endometriosis-associated symptoms. This review considers these processes as they occur in the eutopic endometrium and ectopic endometriotic lesions of women with endometriosis. Their regulation is inter-connected and complex. Dysregulation in endometriosis occurs on a background of accumulating evidence that endometriosis is an endometrial disease with underlying genetic influences and cross talk with endometriotic lesions. Understanding the roles of angiogenesis, lymphangiogenesis and neurogenesis in endometriosis pathophysiology is essential for the development of novel therapeutic approaches.
    Frontiers in bioscience (Elite edition) 01/2013; E5:1033-56.
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    ABSTRACT: Historically, the terminology used for abnormal uterine bleeding has been inconsistent and confusing. The Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) has recently approved new definitions and a standardized classification system for menstrual disorders and other contributors to the problem of abnormal uterine bleeding. This article describes the need for these changes and aims to encourage their use in routine clinical practice, medical education and scientific research, with the hope that they will lead to improved reproductive healthcare for women.
    Obstetrics Gynaecology & Reproductive Medicine 01/2013; 23(11):331–336.
  • M Hickey, I S Fraser
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    ABSTRACT: Erratic, "unscheduled", vaginal bleeding continues to be the greatest disadvantage associated with widespread use of long-acting, progestogen-only methods of contraception. As a consequence, it is also the main reason for premature discontinuation of use of these methods in most cultures. From other perspectives, these methods have high acceptability, very high contraceptive efficacy and a range of valuable, added, non-contraceptive health benefits. There has been widespread awareness of the variability of these vaginal bleeding patterns associated with long-acting methods for several decades and much research has been invested into studying their patterns and implications. Considerable research has also been directed towards trying to understand the underlying mechanisms responsible for the unpredictable bleeding. Much has been clarified about the multiple mechanisms contributing to the appearance of superficial, thin-walled fragile vessels within the endometrium of many of those women with troublesome bleeding, but there is still little understanding of why some women develop these vessels and others have no fragile vessels (and may therefore develop amenorrhea). We now have several medical approaches to reliably stopping a prolonged episode of troublesome bleeding, but no good therapy to produce long-lasting relief from recurrence of erratic bleeding in predisposed women. Future understanding of the variability in individual endometrial responses in different women may be a key to solving this frustrating symptom.
    Reviews in Endocrine and Metabolic Disorders 12/2012; · 4.58 Impact Factor
  • Ian S Fraser
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    ABSTRACT: BACKGROUND: It has been recognized for well over half a century that hormonal preparations designed as contraceptives are also capable of offering health benefits through the treatment and prevention of benign gynecological disease and even some systemic conditions. Increasing attention is now being paid to the extent and detail of such added health benefits, and it is becoming clear that the long-acting, low-dose, hormonal contraceptive delivery systems may offer particular advantages in this regard. METHODS: Conventional databases were thoroughly searched, especially for publications from 2006 to 2012, which addressed non-contraceptive-related indications for therapy and prevention. RESULTS: A considerable literature now exists to demonstrate the multiple and substantial noncontraceptive health benefits of long-acting progestogen-releasing systems, especially the levonorgestrel-releasing intrauterine system. These benefits mainly relate to disturbances of menstruation and related symptoms, such as heavy menstrual bleeding (due to many causes); iron deficiency; pelvic pain, especially around endometriosis; and endometrial hyperplasia. The long-acting estrogen-progestogen systems may carry similar added health benefits to those of the combined oral contraceptives, but data are still lacking. CONCLUSION: Added health benefits are now becoming an important part of the contraceptive choice equation, and the long-acting delivery systems are recognized as suitable primary therapies for a range of gynecological disorders.
    Contraception 10/2012; · 3.09 Impact Factor
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    ABSTRACT: BACKGROUND: The study was conducted to characterize the changes in bleeding pattern over time in women receiving the levonorgestrel-releasing intrauterine system (LNG-IUS) for heavy menstrual bleeding (HMB). The reduction in menstrual blood loss volume has been well documented elsewhere. STUDY DESIGN: Post hoc pooled analysis of the impact of the LNG-IUS on bleeding patterns in four comparator studies of medical and surgical treatment options for HMB. We enrolled women aged ≥18 years with HMB without organic pathology. The change in the number of bleeding and spotting (B/S) days and bleeding patterns was assessed over the duration of the studies pooled. RESULTS: One hundred and sixty-three women received the LNG-IUS in randomized trials. Relative to pretreatment baseline, there was a transient increase in the mean number of bleeding days in the first month of treatment, which returned to baseline by the second month and declined thereafter. Although the number of spotting days also increased during the first month of treatment, these declined with continued use but remained elevated relative to baseline during the first year of treatment. CONCLUSION: In women with HMB, the LNG-IUS is associated with an initial increase in number of B/S days that improve over time.
    Contraception 10/2012; · 3.09 Impact Factor
  • Kirsten I Black, Ian S Fraser
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    ABSTRACT: Benign gynecological conditions impact on women's lives in a myriad of ways. Many of these conditions exert their burden on women's health because they remain undiagnosed, unacknowledged, or unreported for many years. Some of these conditions cause debilitating primary symptoms, especially of heavy menstrual bleeding, the lethargy of iron deficiency, and of persistent pelvic pain, with substantial impact on quality of life and ability to function on a day-to-day basis. The distressing quality of life impact of pelvic floor prolapse or of local vulval lesions should not be overlooked. Many also have secondary health consequences with adverse effects on fertility and reproductive outcome.
    International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 08/2012; 119 Suppl 1:S72-5. · 1.41 Impact Factor
  • Tevfik Yoldemir, Ian S Fraser
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    ABSTRACT: To determine whether older women with a poor response to follicular stimulation achieve pregnancy results that are comparable to those of younger poor responders. Two hundred five women undergoing in vitro fertilization treatment at the Fertility Unit in the Royal Prince Alfred Hospital in Sydney, Australia were selected for retrospective cohort analysis. The outcomes in women > 38 years of age with < 5 oocytes retrieved were compared with those in women ≤ 38 years who also had < 5 oocytes retrieved. Clinical and ongoing pregnancy rates were compared. Implantation rates (21.01 ± 0.38 % vs. 12.82 ± 0.27%, P = 0.11) and clinical pregnancy rates (25.71 ± 0.44% vs. 20.21 ± 0.40%, P = 0.41) were similar in the two groups following cleavage stage embryo transfer. The same was true for blastocyst stage embryo transfer (implantation rates 16.67 ± 0.33% vs. 13.89 ± 0.33%, P = 0.80, and clinical pregnancy rates 23.81 ± 0.44% vs. 16.67 ± 0.38%, P = 0.59). Ongoing pregnancies beyond the 12th week of gestation were also comparable between cleavage stage (24.28 ± 0.43% vs. 16.84 ± 0.34%, P = 0.24) and blastocyst stage embryo transfers (23.81 ± 0.44% vs. 11.11 ± 0.32%, P = 0.32). If older poor responders reach the stage of embryo transfer, they can achieve pregnancy rates similar to those of younger poor responders when matched numbers of embryos are transferred.
    Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC 05/2012; 34(5):459-64.
  • Ian S Fraser
    Journal of Family Planning and Reproductive Health Care 04/2012; 38(2):136. · 2.10 Impact Factor
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    ABSTRACT: In November 2010, the International Federation of Gynecology and Obstetrics formally accepted a new classification system for causes of abnormal uterine bleeding in the reproductive years. The system, based on the acronym PALM-COEIN (polyps, adenomyosis, leiomyoma, malignancy and hyperplasia-coagulopathy, ovulatory disorders, endometrial causes, iatrogenic, not classified) was developed in response to concerns about the design and interpretation of basic science and clinical investigation that relates to the problem of abnormal uterine bleeding. A system of nomenclature for the description of normal uterine bleeding and the various symptoms that comprise abnormal bleeding has also been included. This article describes the rationale, the structured methods that involved stakeholders worldwide, and the suggested use of the International Federation of Gynecology and Obstetrics system for research, education, and clinical care. Investigators in the field are encouraged to use the system in the design of their abnormal uterine bleeding-related research because it is an approach that should improve our understanding and management of this often perplexing clinical condition.
    American journal of obstetrics and gynecology 02/2012; 207(4):259-65. · 3.28 Impact Factor
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    ABSTRACT: The study was conducted to assess the efficacy of estradiol valerate/dienogest (E(2)V/DNG) administered using an estrogen step-down and progestogen step-up approach in a 28-day regimen in the treatment of heavy menstrual bleeding (HMB) using clinical end points allowing E(2)V/DNG to be compared with other available medical therapies. This was a pooled analysis of data from two identically designed randomized, placebo-controlled, multiple center studies conducted in Europe, Australia and North America that assessed the effectiveness of E(2)V/DNG in reducing menstrual blood loss (MBL) in women with HMB. Women aged ≥ 18 years with objectively confirmed HMB were randomized to E(2)V/DNG (n=220) or placebo (n=135) for seven treatment cycles. Outcomes analyzed included absolute reduction in MBL from baseline, proportion of women successfully treated (defined as MBL below 80 mL and ≥ 50% reduction in MBL), proportion with MBL below 80 mL and proportion with ≥ 50% reduction in MBL from baseline. At study end, 63.6% and 11.9% of patients were successfully treated with E(2)V/DNG and placebo, respectively, with 68.2% and 15.6% of women with MBL below 80 mL, and 70.0% and 17.0% with MBL reduction ≥ 50% (all p<.001). E(2)V/DNG is highly effective for the treatment of HMB and is associated with a high rate of treatment success.
    Contraception 01/2012; 86(2):96-101. · 3.09 Impact Factor
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    ABSTRACT: Mifepristone alone or in combination with ethinyl estradiol (EE) can effectively stop an episode of uterine bleeding in women using the etonogestrel-releasing contraceptive implant, Implanon® but could impair contraceptive efficacy. To examine the effects of administration of mifepristone alone or with EE on ovarian function and cervical mucus consistency in women using Implanon. Women using Implanon were randomized to mifepristone 25 mg twice daily on day 1 plus placebo 1 daily for 4 days or plus EE 20 mcg daily for days 2-5. Measurements of serum estradiol (E(2)), progesterone (P(4)), luteinizing hormone (LH), follicle-stimulating hormone (FSH), cervical mucus examination and maximal follicle size (by vaginal ultrasound) were carried out at various times. Following mifepristone intake, there was a dramatic increase in E(2) levels ranging from 543 to 1183 pmol/L (p=.000), which was not correlated with maximal follicle size or preceded by LH or FSH increase. The increase in E(2) triggered an LH increase resulting in development of a luteinized follicle in four women with no evidence of ovulation. One of these women had estradiol and progesterone levels suggestive of ovulation, but no corpus luteum was seen. Almost all women had very low mucus scores, which did not correlate with E(2) levels. Despite a transient increase in E(2) levels after mifepristone, there was no evidence of subsequent ovulation irrespective of whether they also received EE. The mechanism by which mifepristone in the presence of etonogestrel results in a rapid increase in E(2) levels remains unclear and could not be related to any significant changes in FSH, LH, ovarian follicle dynamics or subsequent possible ovulation. Pregnancy is very unlikely to occur if mifepristone and EE are given during use of Implanon to stop an episode of bleeding.
    Contraception 12/2011; 84(6):600-8. · 3.09 Impact Factor

Publication Stats

3k Citations
803.98 Total Impact Points

Institutions

  • 1977–2014
    • University of Sydney
      • Discipline in Obstetrics and Gynaecology
      Sydney, New South Wales, Australia
  • 2012
    • University of Melbourne
      • Department of Obstetrics and Gynaecology
      Melbourne, Victoria, Australia
  • 2011–2012
    • Oregon Health and Science University
      • Department of Obstetrics & Gynecology
      Portland, OR, United States
    • University of California, Los Angeles
      • Department of Obstetrics and Gynecology
      Los Angeles, CA, United States
    • Alpert Medical School - Brown University
      • Department of Obstetrics and Gynecology
      Providence, Rhode Island, United States
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
    • Shandong University
      Chi-nan-shih, Shandong Sheng, China
  • 1983–2012
    • Royal Prince Alfred Hospital
      • Fertility Unit
      Camperdown, New South Wales, Australia
  • 2009–2011
    • Family Planning NSW
      Sydney, New South Wales, Australia
    • University of Jinan (Jinan, China)
      Chi-nan-shih, Shandong Sheng, China
  • 2008–2010
    • Prince Henry's Institute
      Melbourne, Victoria, Australia
  • 2007–2008
    • Monash University (Australia)
      • Department of Obstetrics and Gynaecology
      Melbourne, Victoria, Australia
  • 2005–2008
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      Newcastle-on-Tyne, England, United Kingdom
    • Royal Perth Hospital
      Perth City, Western Australia, Australia
  • 2002–2008
    • University of Western Australia
      • School of Women's and Infants' Health
      Perth, Western Australia, Australia
  • 2004
    • Chulalongkorn University
      • Department of Obstetrics and Gynecology
      Bangkok, Bangkok, Thailand
  • 2000–2001
    • Imperial College London
      • Clinical Institute of Obstetrics and Gynaecology (CIOG)
      Londinium, England, United Kingdom