Publications (110) View all
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Article: Emerging concepts about prenatal genesis, aberrant metabolism and treatment paradigms in polycystic ovary syndrome
Selma F Witchel, Sergio E Recabarren, Frank González, Evanthia Diamanti-Kandarakis, Kai I Cheang, Antoni J Duleba, Richard S Legro, Roy Homburg, Renato Pasquali, Rogerio A Lobo, Christos C Zouboulis, Fahrettin Kelestimur, Franca Fruzzetti, Walter Futterweit, Robert J Norman, David H AbbottEndocrine 06/2013; · 1.42 Impact Factor -
Article: The longer-term health outcomes for children born as a result of IVF treatment: Part I-General health outcomes.
Roger Hart, Robert J Norman[show abstract] [hide abstract]
ABSTRACT: BACKGROUND Several million children have been born from in vitro fertilization (IVF) treatment, but limited data exist regarding their health and development beyond the first year of life. It has been alleged that IVF may lead to long-term adverse consequences, in addition to the documented worse perinatal outcome and increased risk of congenital abnormalities in children born resulting from IVF treatment.METHODSA search strategy restricted to studies relating to the medical condition of children of at least 1 year of age born as a result of IVF treatment was performed to include case series, data linkage and prospective studies published 1 January 2000-1 April 2012.RESULTSLimited long-term follow-up data suggest that there is potentially an increase in the incidence of raised blood pressure, elevated fasting glucose, increase in total body fat composition, advancement of bone age and potentially subclinical thyroid disorder in the IVF offspring. Whether these potential associations are related to the IVF treatment per se, the adverse obstetric outcomes associated with IVF treatment or are related to the genetic origin of the children is yet to be determined.CONCLUSIONS This review provides evidence to suggest that the short-term health outcome for children born from IVF treatment is positive. However, it is expected that the cardiovascular and metabolic risk factors found in childhood and tracking into adulthood could be worse in later life, and may be responsible for chronic cardiometabolic disease. These observations need to be addressed by further studies.Human Reproduction Update 02/2013; · 9.23 Impact Factor -
Article: The longer-term health outcomes for children born as a result of IVF treatment. Part II: mental health and development outcomes.
Roger Hart, Robert J Norman[show abstract] [hide abstract]
ABSTRACT: BACKGROUND Limited data exist with regard to longer-term mental health and psychological functioning of children born from IVF treatment. With the known adverse perinatal outcome for children born from IVF treatment, it would be expected that there is a negative impact upon their mental development.METHODSA search strategy restricted to studies relating to the medical condition of children of at least 1 year of age, born from IVF treatment was performed to include case series, data linkage and prospective studies published from 1 January 2000 to 1 April 2012.RESULTSLimited long-term follow-up data suggest that there is an increase in the incidence of cerebral palsy and neurodevelopmental delay related to the confounders of prematurity and low birthweight. Previous reports of associations with autism and attention-deficit disorder are believed to be related to maternal and obstetric factors. There exists a potential increase in the prevalence of early adulthood clinical depression and binge drinking in the offspring of IVF, with the reassuring data of no changes with respect to cognitive development, school performance, social functioning and behaviour. Whether these potential associations are related to the IVF treatment, the adverse obstetric outcomes associated with IVF treatment, the genetic or subsequent environmental influences on the children is yet to be determined.CONCLUSIONS In general, the longer-term mental and emotional health outcome for children born from IVF treatment is reassuring, and is very similar to that of naturally conceived children; however, further studies are required to explore any association with depression, and its causality in more detail.Human Reproduction Update 02/2013; · 9.23 Impact Factor -
Article: Small glutamine-rich tetratricopeptide repeat-containing protein alpha is present in human ovaries but may not be differentially expressed in relation to polycystic ovary syndrome.
Miriam S Butler, Xing Yang, Carmela Ricciardelli, Xiaoyan Liang, Robert J Norman, Wayne D Tilley, Theresa E Hickey[show abstract] [hide abstract]
ABSTRACT: OBJECTIVE: To evaluate the expression and function of small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA), an androgen receptor (AR) molecular chaperone, in human ovarian tissues. DESIGN: Examine the effect of SGTA on AR subcellular localization in granulosa tumor cells (KGN) and SGTA expression in ovarian tissues. SETTING: University-based research laboratory. PATIENT(S): Archived tissues from premenopausal women and granulosa cells from infertile women receiving assisted reproduction. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): AR subcellular localization and SGTA protein or mRNA levels. RESULT(S): SGTA and AR proteins were expressed in the cytoplasm of KGN cells and exposure to androgen stimulated AR nuclear localization. SGTA protein knockdown increased AR nuclear localization at low (0-0.1 nmol/L) but not high (1-10 nmol/L) concentrations of androgen hormone. In ovarian tissues, SGTA was localized to the cytoplasm of granulosa cells at all stages of folliculogenesis and in thecal cells of antral follicles. SGTA protein levels were similar when comparing primordial and primary follicles within core biopsies (n = 40) from women with and without polycystic ovary syndrome (PCOS). Likewise, SGTA mRNA levels were not significantly different in granulosa cells from preovulatory follicles after hyperstimulation of women with and without PCOS. CONCLUSION(S): SGTA is present in human ovaries and has the potential to modulate AR signalling, but it may not be differentially expressed in PCOS.Fertility and sterility 02/2013; · 3.97 Impact Factor -
Article: Metformin versus clomiphene citrate for infertility in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis.
Marie L Misso, Michael F Costello, Marie Garrubba, Jennifer Wong, Roger Hart, Luk Rombauts, Angela M Melder, Robert J Norman, Helena J Teede[show abstract] [hide abstract]
ABSTRACT: BACKGROUND Recent studies suggest that metformin may be more effective in women with polycystic ovary syndrome (PCOS) who are non-obese. The objective here is to determine and compare the effectiveness of metformin and clomiphene citrate for improving fertility outcomes in women with PCOS and a BMI < 32 kg/m(2) (BMI 32 kg/m(2) was used to allow for international differences in BMI values which determine access to infertility therapy through the public health system).METHODS Databases were searched for English language articles until July 2011. Inclusion criteria: women of any age, ethnicity and weight with PCOS diagnosed by all current criteria, who are infertile; at least 1000 mg of any type of metformin at any frequency, including slow release and standard release, compared with any type, dose and frequency of clomiphene citrate. Outcomes: rates of ovulation, live birth, pregnancy, multiple pregnancies, miscarriage, adverse events, quality of life and cost effectiveness. Data were extracted and risk of bias assessed. A random effects model was used for meta-analyses of data, using risk ratios (relative risk).RESULTSThe search returned 4981 articles, 580 articles addressed metformin or clomiphene citrate and four randomized controlled trials (RCTs) comparing metformin with clomiphene citrate were included. Upon meta-analysis of the four RCTs, we were unable to detect a statistically significant difference between the two interventions for any outcome in women with PCOS and a BMI < 32 kg/m(2), owing to significant heterogeneity across the RCTs.CONCLUSIONS Owing to conflicting findings and heterogeneity across the included RCTs, there is insufficient evidence to establish a difference between metformin and clomiphene citrate in terms of ovulation, pregnancy, live birth, miscarriage and multiple pregnancy rates in women with PCOS and a BMI < 32 kg/m(2). However, a lack of superiority of one treatment is not evidence for equivalence, and further methodologically rigorous trials are required to determine whether there is a difference in effectiveness between metformin and placebo (or no treatment) or between metformin and clomiphene citrate for ovulation induction in women with PCOS who are non-obese. Until then, caution should be exercised when prescribing metformin as first line pharmacological therapy in this group of women.Human Reproduction Update 09/2012; · 9.23 Impact Factor