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De Vos M.,Center for Reproductive Medicine | Smitz J.,Laboratory of Clinical Chemistry and Radioimmunology | Woodruff T.K.,Northwestern University
The Lancet | Year: 2014

Enhanced long-term survival rates of young women with cancer and advances in reproductive medicine and cryobiology have culminated in an increased interest in fertility preservation methods in girls and young women with cancer. Present data suggest that young patients with cancer should be referred for fertility preservation counselling quickly to help with their coping process. Although the clinical application of novel developments, including oocyte vitrification and oocyte maturation in vitro, has resulted in reasonable success rates in assisted reproduction programmes, experience with these techniques in the setting of fertility preservation is in its infancy. It is hoped that these and other approaches, some of which are still regarded as experimental (eg, ovarian tissue cryopreservation, pharmacological protection against gonadotoxic agents, in-vitro follicle growth, and follicle transplantation) will be optimised and become established within the next decade. Unravelling the complex mechanisms of activation and suppression of follicle growth will not only expand the care of thousands of women diagnosed with cancer, but also inform the care of millions of women confronted with reduced reproductive fitness because of ageing.

Roosens B.,Vrije Universiteit Brussel | Bala G.,Vrije Universiteit Brussel | Droogmans S.,Vrije Universiteit Brussel | Hostens J.,SkyScan N.V. | And 7 more authors.
Experimental Gerontology | Year: 2012

Background: Cardiovascular calcification is an independent predictor of morbidity and mortality and increases with age. Animal models are frequently used to investigate the underlying pathophysiology. Only scarce data regarding the effect of aging on calcifications in these animal models are available. The aim of this study is to investigate the occurrence of cardiovascular calcifications in normal, aging rats. Methods: A mixed inbred/outbred population of 44 male Lewis/Wistar rats was studied. Group 1 of three-month-old rats, group 2 twelve-month-old, group 3 twenty-four-month-old and group 4 thirty-month-old rats. Calibrated integrated backscatter (cIB) values and blood parameters (creatinine, parathyroid hormone (PTH)) were measured, followed by ex-vivo micro-CT and histology as reference methods. Results: Cardiovascular calcifications developed with age, as demonstrated by significantly increasing cIB values of the aortic valve and myocardium. This was confirmed by a significant increase in the calcified volume on ex-vivo micro-CT and in the histological calcium score. There was also a significantly higher level of creatinine and PTH with age. Conclusions: As in humans, cardiovascular calcifications progressively increase with age in the normal rat. Therefore the aging rat model could be used for studying calcifying cardiovascular disease. cIB might have a value in future studies for the early detection of subclinical calcifications in humans. © 2012 Elsevier Inc.

Roosens B.,Centrum Voor Hart en Vaatziekten | Roosens B.,Vrije Universiteit Brussel | Bala G.,Centrum Voor Hart en Vaatziekten | Bala G.,Vrije Universiteit Brussel | And 13 more authors.
Ultrasound in Medicine and Biology | Year: 2013

Chronic kidney disease (CKD) and secondary hyper-parathyroidism are associated with calcific aortic valve disease (CAVD). Innovative modalities for imaging CAVD are warranted. Our aim was to use echocardiographic calibrated integrated backscatter (cIB) to quantitatively determine the preventive effect of the calcimimetic R-568 on CAVD in a CKD rat model, and to compare the results with those of micro-computed tomography and histology. Thirty-six male Wistar rats were followed for 7wk. Rats were divided into four groups with respect to treatment: (1) adenine 0.5% to induce CKD+vehicle; (2) adenine+R-568 (30mg/kg/d); (3) control, normal diet+vehicle; (4) controls, normal diet+R-568. At week 7, cIB values of the aortic valve were significantly lower in R-568-treated group 2 than in vehicle-treated group 1. This was confirmed by the significantly lower calcified volume observed on micro-computed tomography and the calcified area observed on histology. There were no significant differences in fractional area change and aortic valve area between groups. In conclusion, echocardiographic cIB was able to quantitatively assess a reduction in CAVD by R-568 in a rat model of CKD. © 2013 World Federation for Ultrasound in Medicine & Biology.

Guzman L.,Center for Reproductive Medicine | Ortega-Hrepich C.,Center for Reproductive Medicine | Polyzos N.P.,Center for Reproductive Medicine | Anckaert E.,Laboratory of Clinical Chemistry and Radioimmunology | And 6 more authors.
Human Reproduction | Year: 2013

Study Questio: NWhich baseline patient characteristics can help assisted reproductive technology practitioners to identify patients who are suitable for in-vitro maturation (IVM) treatment? Summary Answer: In patients with polycystic ovary syndrome (PCOS) who undergo oocyte IVM in a non-hCG-triggered system, circulating anti-Müllerian hormone (AMH), antral follicle count (AFC) and total testosterone are independently related to the number of immature oocytes and hold promise as outcome predictors to guide the patient selection process for IVM.WHAT IS ALREADY KNOWNPatient selection criteria for IVM treatment have been described in normo-ovulatory patients, although patients with PCOS constitute the major target population for IVM. With this study, we assessed the independent predictive value of clinical and endocrine parameters that are related to oocyte yield in patients with PCOS undergoing IVM.STUDY Design: , SIZE, DURATIONCohort study involving 124 consecutive patients with PCOS undergoing IVM whose data were prospectively collected. Enrolment took place between January 2010 and January 2012. Only data relating to the first IVM cycle of each patient were included.PARTICIPANTS/MATERIALS, SETTING, METHODPatients with PCOS underwent oocyte retrieval for IVM after minimal gonadotrophin stimulation and no hCG trigger. Correlation coefficients were calculated to investigate which parameters are related to immature oocyte yield (patient's age, BMI, baseline hormonal profile and AMH, AFC). The independence of predictive parameters was tested using multivariate linear regression analysis. Finally, multivariate receiver operating characteristic (ROC) analyses for cumulus oocyte complexes (COC) yield were performed to assess the efficiency of the prediction model to select suitable candidates for IVM. Main Results and the Role of Chance: Using multivariate regression analysis, circulating baseline AMH, AFC and baseline total testosterone serum concentration were incorporated into a model to predict the number of COC retrieved in an IVM cycle, with unstandardized coefficients [95% confidence interval (CI)] of 0.03 (0.02-0.03) (P < 0.001), 0.012 (0.008-0.017) (P < 0.001) and 0.37 (0.18-0.57) (P < 0.001), respectively. Logistic regression analysis shows that a prediction model based on AMH and AFC, with unstandardized coefficients (95% CI) of 0.148 (0.03-0.25) (P < 0.001) and 0.034 (-0.003-0.07) (P = 0.025), respectively, is a useful patient selection tool to predict the probability to yield at least eight COCs for IVM in patients with PCOS. In this population, patients with at least eight COC available for IVM have a statistically higher number of embryos of good morphological quality (2.9 ± 2.3; 0.9 ± 0.9; P < 0.001) and cumulative ongoing pregnancy rate [30.4% (24 out of 79); 11% (5 out of 45); P = 0.01] when compared with patients with less than eight COC. ROC curve analysis showed that this prediction model has an area under the curve of 0.7864 (95% CI = 0.6997-0.8732) for the prediction of oocyte yield in IVM.LIMITATIONS, REASONS FOR CAUTIONThe proposed model has been constructed based on a genuine IVM system, i.e. no hCG trigger was given and none of the oocytes matured in vivo. However, other variables, such as needle type, aspiration technique and whether or not hCG-triggering is used, should be considered as confounding factors. The results of this study have to be confirmed using a second independent validation sample. Wider Implications of the Findings: The proposed model could be applied to patients with PCOS after confirmation through a further validation study. Study Funding/Competing Interest: (S)This study was supported by a research grant by the Institute for the Promotion of Innovation by Science and Technology in Flanders, Project number IWT 070719. © 2013 The Author.

Roosens B.,Centrum voor Hart en Vaatziekten CHVZ | Roosens B.,Vrije Universiteit Brussel | Bala G.,Centrum voor Hart en Vaatziekten CHVZ | Bala G.,Vrije Universiteit Brussel | And 14 more authors.
Cardiovascular Ultrasound | Year: 2013

Background: Calcification is an independent predictor of mortality in calcific aortic valve disease (CAVD). The aim of this study was to evaluate the use of non-invasive, non-ionizing echocardiographic calibrated integrated backscatter (cIB) for monitoring progression and subsequent regression of aortic valvular calcifications in a rat model of reversible renal failure with CAVD, compared to histology. Methods. 28 male Wistar rats were prospectively followed during 21 weeks. Group 1 (N=14) was fed with a 0.5% adenine diet for 9 weeks to induce renal failure and CAVD. Group 2 (N=14) received a standard diet. At week 9, six animals of each group were killed. The remaining animals of group 1 (N=8) and group 2 (N=8) were kept on a standard diet for an additional 12 weeks. cIB of the aortic valve was calculated at baseline, 9 and 21 weeks, followed by measurement of the calcified area (Ca Area) on histology. Results: At week 9, cIB values and Ca Area of the aortic valve were significantly increased in the adenine-fed rats compared to baseline and controls. After 12 weeks of adenine diet cessation, cIB values and Ca Area of group 1 decreased compared to week 9, while there was no longer a significant difference compared to age-matched controls of group 2. Conclusions: cIB is a non-invasive tool allowing quantitative monitoring of CAVD progression and regression in a rat model of reversible renal failure, as validated by comparison with histology. This technique might become useful for assessing CAVD during targeted therapy. © 2013 Roosens et al; licensee BioMed Central Ltd.

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