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Belva F.,Universitair Ziekenhuis Brussel Brussel | Bonduelle M.,Universitair Ziekenhuis Brussel Brussel | Roelants M.,Environment and Health Youth Health Care | Michielsen D.,Universitair Ziekenhuis Brussel | And 3 more authors.
Human Reproduction | Year: 2016

STUDY QUESTION: What is the semen quality of young adult men who were conceived 18-22 years ago by ICSI for male infertility? SUMMARY ANSWER: In this cohort of 54 young adult ICSI men, median sperm concentration, total sperm count and total motile sperm count were significantly lower than in spontaneously conceived peers. WHAT IS KNOWN ALREADY: The oldest ICSI offspring cohort worldwide has recently reached adulthood. Hence, their reproductive health can now be investigated. Since these children were conceived by ICSI because of severe male-factor infertility, there is reasonable concern that male offspring have inherited the deficient spermatogenesis from their fathers. Previously normal pubertal development and adequate Sertoli and Leydig cell function have been described in pubertal ICSI boys; however, no information on their sperm quality is currently available. STUDY DESIGN, SIZE, DURATION: This study was conducted at UZ Brussel between March 2013 and April 2016 and is part of a large follow-up project focussing on reproductive and metabolic health of young adults, between 18 and 22 years and conceived after ICSI with ejaculated sperm. Results of both a physical examination and semen analysis were compared between young ICSI men being part of a longitudinally followed cohort and spontaneously conceived controls who were recruited cross-sectionally. PARTICIPANTS/MATERIALS, SETTING, METHOD: Results of a single semen sample in 54 young adult ICSI men and 57 spontaneously conceived men are reported. All young adults were individually assessed, and the results of their physical examination were completed by questionnaires. Data were analysed by multiple linear and logistic regression, adjusted for covariates. In addition, semen parameters of the ICSI fathers dating back from their ICSI treatment application were analysed for correlations. MAIN RESULTS AND THE ROLE OF CHANCE: Young ICSI adults had a lower median sperm concentration (17.7 million/ml), lower median total sperm count (31.9 million) and lower median total motile sperm count (12.7 million) in comparison to spontaneously conceived peers (37.0 million/ml; 86.8 million; 38.6 million, respectively). The median percentage progressive and total motility, median percentage normal morphology and median semen volume were not significantly different between these groups. After adjustment for confounders (age, BMI, genital malformations, time from ejaculation to analysis, abstinence period), the statistically significant differences between ICSI men and spontaneously conceived peers remained: An almost doubled sperm concentration in spontaneously conceived peers in comparison to ICSI men (ratio 1.9, 95% CI 1.1-3.2) and a two-fold lower total sperm count (ratio 2.3, 95% CI 1.3-4.1) and total motile count (ratio 2.1, 95% CI 1.2-3.6) in ICSI men compared to controls were found. Furthermore, compared to men born after spontaneous conception, ICSI men were nearly three times more likely to have sperm concentrations below the WHO reference value of 15 million/ml (adjusted odds ratio (AOR) 2.7; 95% CI 1.1-6.7) and four times more likely to have total sperm counts below 39 million (AOR 4.3; 95% CI 1.7-11.3). In this small group of 54 father-son pairs, a weak negative correlation between total sperm count in fathers and their sons was found. LIMITATIONS, REASONS FOR CAUTION: The main limitation is the small study population. Also, the results of this study where ICSI was performed with ejaculated sperm and for male-factor infertility cannot be generalized to all ICSI offspring because the indications for ICSI have nowadays been extended and ICSI is also being performed with non-ejaculated sperm and reported differences may thus either decrease or increase. WIDER IMPLICATIONS OF THE FINDINGS: These first results in a small group of ICSI men indicate a lower semen quantity and quality in young adults born after ICSI for male infertility in their fathers. © The Author 2016.


Belva F.,Universitair Ziekenhuis Brussel Brussel | De Schepper J.,Universitair Ziekenhuis Brussel | Van Steirteghem A.,Universitair Ziekenhuis Brussel Brussel | Tournaye H.,Universitair Ziekenhuis Brussel Brussel | Bonduelle M.,Universitair Ziekenhuis Brussel Brussel
Human Reproduction | Year: 2017

STUDY QUESTION: Are reproductive hormone levels (FSH, LH, inhibin B and testosterone) in male offspring conceived by ICSI because of male infertility comparable with those from peers born after spontaneous conception? SUMMARY ANSWER: In this cohort of 54 young men conceived by ICSI because of male-factor infertility, mean and median reproductive hormone levels were found to be comparable with results from spontaneously conceived peers, but ICSI-conceived men were more likely to have low inhibin B (< 10th percentile) and high FSH (>90th percentile) levels. WHAT IS KNOWN ALREADY: Since the worldwide oldest ICSI offspring have recently reached young adulthood, their reproductive health can now be investigated. This typically involves semen analysis and a hormonal profiling including the measurement of FSH, LH, inhibin B and testosterone. Circulating levels of FSH and inhibin B are generally known as markers of the exocrine function of the testis, i.e. spermatogenesis, while LH and testosterone reflect its endocrine function. We have previously observed a normal pubertal development and comparable levels of inhibin B and testosterone among pubertal ICSI boys when compared to spontaneously conceived peers. However, at present, information on the gonadal function of ICSI offspring in adulthood is still lacking. STUDY DESIGN, SIZE, DURATION: This study, conducted between March 2013 and April 2016 at the UZ Brussel, is part of a larger follow-up project focusing on reproductive and metabolic health of young adults between 18 and 22 years and conceived after ICSI because of male infertility. The ICSI men are part of a longitudinally followed cohort while the spontaneously conceived controls were recruited cross-sectionally. PARTICIPANTS/MATERIALS, SETTING, METHODS: Results of a single fasting blood sample from 54 young adult ICSI men were compared to that of 57 spontaneously conceived peers. Reproductive hormone analysis involved FSH, LH, testosterone and inhibin B measurement. Furthermore, the association between their reproductive hormones and their sperm parameters was examined. Data were analyzed by multiple linear and logistic regression adjusted for covariates. MAIN RESULTS AND THE ROLE OF CHANCE: ICSI men had comparable mean levels of FSH, LH, testosterone and inhibin B in comparison to spontaneously conceived counterparts, even after adjustment for confounders, such as age, BMI and season. Young ICSI-conceived men were more likely to have inhibin B levels below the 10th percentile (< 125.2ng/l; Adjusted Odds Ratio (AOR) 4.0; 95% CI: 0.9-18.4; P = 0.07) compared with spontaneously conceived peers and were more likely to have FSH levels above the 90th percentile (>5.5 IU/L; AOR 3.3; 95% CI: 0.9-11.9; P = 0.06) compared with spontaneously conceived peers, but neither difference reached statistical significance. FSH, LH and inhibin B, but not testosterone, levels were significantly associated with sperm concentration and total sperm count. LIMITATIONS, REASONS FOR CAUTION: The main limitation is the small study population. Furthermore, the results of this study should be interpreted according to the background of the participants: all subjects in our study group were conceived by ICSI because of severe male infertility and hence the results cannot be generalized to all ICSI offspring because the indications for performing ICSI have since been widened. WIDER IMPLICATIONS OF THE FINDINGS: These first results in a small group of ICSI men show reassuring reproductive hormonal levels. However, larger studies are required to confirm our results. Since inhibin B and FSH are consistently correlated with semen characteristics, we would suggest that the reproductive status of young adults conceived by ICSI is explored with a hormonal assessment given its easier acceptance compared to semen sampling. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Scheerlinck T.,Universitair Ziekenhuis Brussel Brussel | Delport H.,AZ Nikolaas | Kiewitt T.,BioMet
Journal of Bone and Joint Surgery - Series A | Year: 2010

Background: The cement mantle within a hip resurfacing head is important for implant survival. Too much cement leads to thermal bone necrosis, whereas not enough cement might cause mechanical failure and particle-induced osteolysis. We evaluated the impact of different cementing techniques on the quality of the cement mantle in hip resurfacing. Methods: Sixty bovine condyles were prepared to fit a size-46 ReCap (Biomet) implant and divided into five groups of twelve specimens each. In two of the groups, a polymeric replica was filled halfway with low-viscosity cement; suction was employed in one of those groups and not used in the other. Medium-viscosity cement was used in the remaining three groups: it was spread out within the implant in one group, it was packed on the bone in another, and a combination of those techniques was used in the third. Half of the sixty specimens had six anchoring holes. The specimens underwent computed tomography and were analyzed with custom-made segmentation software. Results: The cementing technique and anchoring holes influenced the cement quantity within the implant and the thickness of the cement mantle; suction and bone density did not. Both filling techniques involving the use of low-viscosity cement resulted in excessive cement within the implant (filling index, 47.30% to 60.66%) and large cement defects at the base. The combined technique also resulted in large cement quantities (filling index, 46.62% to 54.12%) but fewer cement defects at the base. The filling technique involving the use of medium-viscosity cement decreased the cement quantity (filling index, 43.31% to 45.68%), but cement packing was the best technique (filling index, 29.20% to 31.05%), resulting in the thinnest, most homogeneous cement mantle. However, distal cement defects remained, and the prevalence of proximal cement-implant interfacial gaps was about 10%. Conclusions: The results of this experimental study cannot be extrapolated directly to the in vivo situation, and they apply only to implants with an inner geometry similar to that of the size-46 ReCap resurfacing head and to the cement brands that we used. None of the cementing techniques was "perfect." Both of the filling techniques involving use of low-viscosity cement and the combined technique resulted in excessive cement proximally. The filling technique involving use of medium-viscosity cement was promising, but the cement-packing technique offered the best opportunity to control the quality of the cement mantle. However, the presence of interfacial gaps raised new questions. We suggest that the use of anchoring holes in cancellous bone should be considered with caution in order to avoid overfilling with cement. Clinical Relevance: This study should help the clinician to choose an optimal cementing technique for hip resurfacing. Copyright © 2010 by The Journal of Bone and Joint Surgery, Incorporated.


Mohades S.G.,Universitair Ziekenhuis Brussel | Struys E.,Universitair Ziekenhuis Brussel | Van Schuerbeek P.,Universitair Ziekenhuis Brussel Brussel | Mondt K.,Flemish Ministry of Education and Training | And 3 more authors.
Brain Research | Year: 2012

The impact of bilingualism on the microstructure of the white matter pathways related to language processing is assessed in elementary school children by magnetic resonance diffusion tensor imaging (MR-DTI). Forty children, 8-11 years old, subdivided into 3 different groups (15 simultaneous bilinguals, 15 sequential bilinguals and 10 monolinguals), were scanned. The hypothesis was that the starting age and the manner of second language acquisition would affect the characteristics of language circuitry. In each subject the mean fractional anisotropy (FA) was obtained for four major white matter pathways: 1 - the left arcuate fasciculus/superior longitudinal fasciculus (lAF/lSLF) that connects Broca's area in the opercular and triangular regions of the left inferior frontal gyrus to the posterior language zone, 2 - the left inferior occipitofrontal fasciculus (lIFOF), connecting anterior regions in the frontal lobe with posterior regions in the temporal occipital lobes, 3 - the bundle arising from the anterior part of the corpus callosum projecting to the orbital lobe (AC-OL) and 4 - the fibers emerging from the anterior midbody (AMB) of the corpus callosum that associate with the premotor and supplementary motor cortices (AMB-PMC). The three groups did not show significant differences in mean FA over the lAF/lSLF or AMB-PMC tracts. In simultaneous bilingual subjects the lIFOF tracts had higher mean FA value compared to monolinguals and also sequential bilinguals, whereas the comparison for the AC-OL fibers yielded a significantly lower mean FA value in simultaneous bilingual subjects compared to monolinguals. In both cases the FA value for sequential bilinguals was intermediate to that of the other two groups. To our knowledge, this study provides the first evidence of bilingualism related adaptation of white matter microstructure in the human brain. © 2011 Elsevier B.V. All rights reserved.


Weil-Olivier C.,University Paris Diderot | van der Linden M.,RWTH Aachen | de Schutter I.,Universitair Ziekenhuis Brussel Brussel | Dagan R.,Ben - Gurion University of the Negev | Mantovani L.,University of Naples
BMC Infectious Diseases | Year: 2012

Background: The burden of invasive pneumococcal disease in young children decreased dramatically following introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). The epidemiology of S. pneumoniae now reflects infections caused by serotypes not included in PCV7. Recently introduced higher valency pneumococcal vaccines target the residual burden of invasive and non-invasive infections, including those caused by serotypes not included in PCV7. This review is based on presentations made at the European Society of Pediatric Infectious Diseases in June 2011.Discussion: Surveillance data show increased circulation of the non-PCV7 vaccine serotypes 1, 3, 6A, 6C, 7 F and 19A in countries with routine vaccination. Preliminary evidence suggests that broadened serotype coverage offered by higher valency vaccines may be having an effect on invasive disease caused by some of those serotypes, including 19A, 7 F and 6C. Aetiology of community acquired pneumonia remains a difficult clinical diagnosis. However, recent reports indicate that pneumococcal vaccination has reduced hospitalisations of children for vaccine serotype pneumonia. Variations in serotype circulation and occurrence of complicated and non-complicated pneumonia caused by non-PCV7 serotypes highlight the potential of higher valency vaccines to decrease the remaining burden. PCVs reduce nasopharyngeal carriage and acute otitis media (AOM) caused by vaccine serotypes. Recent investigations of the interaction between S. pneumoniae and non-typeable H. influenzae suggest that considerable reduction in severe, complicated AOM infections may be achieved by prevention of early pneumococcal carriage and AOM infections. Extension of the vaccine serotype spectrum beyond PCV7 may provide additional benefit in preventing the evolution of AOM. The direct and indirect costs associated with pneumococcal disease are high, thus herd protection and infections caused by non-vaccine serotypes both have strong effects on the cost effectiveness of pneumococcal vaccination. Recent evaluations highlight the public health significance of indirect benefits, prevention of pneumonia and AOM and coverage of non-PCV7 serotypes by higher valency vaccines.Summary: Routine vaccination has greatly reduced the burden of pneumococcal diseases in children. The pneumococcal serotypes present in the 7-valent vaccine have greatly diminished among disease isolates. The prevalence of some non-vaccine serotypes (e.g. 1, 7 F and 19A) has increased. Pneumococcal vaccines with broadened serotype coverage are likely to continue decreasing the burden of invasive disease, and community acquired pneumonia in children. Further reductions in pneumococcal carriage and increased prevention of early AOM infections may prevent the evolution of severe, complicated AOM. Evaluation of the public health benefits of pneumococcal conjugate vaccines should include consideration of non-invasive pneumococcal infections, indirect effects of vaccination and broadened serotype coverage. © 2012 Weil-Olivier et al.; licensee BioMed Central Ltd.


Rose M.A.,Goethe University Frankfurt | Christopoulou D.,Pfizer | Myint T.T.H.,Pfizer | De Schutter I.,Universitair Ziekenhuis Brussel Brussel
International Journal of Clinical Practice | Year: 2014

Background Characterisation of risk groups who may benefit from pneumococcal vaccination is essential for the generation of recommendations and policy. Methods We reviewed the literature to provide information on the incidence and risk of invasive pneumococcal disease (IPD) in at-risk children in Europe and North America. The PubMed database was searched using predefined search terms and inclusion/exclusion criteria for papers reporting European or North American data on the incidence or risk of IPD in children with underlying medical conditions. Results Eighteen references were identified, 11 from North America and 7 from Europe, with heterogeneous study methods, periods and populations. The highest incidence was seen in US children positive for human immunodeficiency virus infection, peaking at 4167 per 100,000 patient-years in 2000. Studies investigating changes in incidence over time reported decreases in the incidence of IPD between the late 1990s and early 2000s. The highest risk of IPD was observed in children with haematological cancers or immunosuppression. Overall, data on IPD in at-risk children were limited, lacking incidence data for a wide range of predisposing conditions. There was, however, a clear decrease in the incidence of IPD in at-risk children after the introduction of 7-valent pneumococcal conjugate vaccine into immunisation programmes, as previously demonstrated in the general population. Conclusion Despite the heterogeneity of the studies identified, the available data show a substantial incidence of IPD in at-risk children, particularly those who are immunocompromised. Further research is needed to determine the true risk of IPD in at-risk children, particularly in the post-PCV period, and to understand the benefits of vaccination and optimal vaccination schedules. Linked Comment: Stein. Int J Clin Pract 2014; 68: 2-3. © 2013 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.


Petrussa L.,Vrije Universiteit Brussel | Van de Velde H.,Vrije Universiteit Brussel | Van de Velde H.,Universitair Ziekenhuis Brussel Brussel | De Rycke M.,Vrije Universiteit Brussel | De Rycke M.,Universitair Ziekenhuis Brussel Brussel
Molecular Human Reproduction | Year: 2014

DNA methylation is a key epigenetic modification which is essential for normal embryonic development. Major epigenetic reprogramming takes place during gametogenesis and in the early embryo; the complex DNA methylation patterns are established and maintained by DNA methyltransferases (DNMTs). However, the influence of assisted reproductive technologies (ART) on DNA methylation reprogramming enzymes has predominantly been studied in mice and less so in human oocytes and embryos. The expression and localization patterns of the four known DNMTs were analysed in human oocytes and IVF/ICSI embryos by immunocytochemistry and compared between a reference group of good quality fresh embryos and groups of abnormally developing embryos or embryo groups after cryopreservation. In humans, DNMT1o rather than DNMT1s seems to be the key player for maintaining methylation in early embryos. DNMT3b, rather than DNMT3a and DNMT3L, appears to ensure global DNA remethylation in the blastocysts before implantation. DNMT3L, an important regulator of maternal imprint methylation in mouse, was not detected in human oocytes (GV, MI and MII stage). Our study confirms the existence of species differences for mammalian DNA methylation enzymes. In poor quality fresh embryos, the switch towards nuclear DNMT3b expression was delayed and nuclear DNMT1, DNMT1s and DNMT3b expression was less common. Compared with the reference embryos, a smaller number of cryopreserved embryos showed nuclear DNMT1, while a delayed switch to nuclear DNMT3b and an extended DNMT1s temporal expression pattern were also observed. The spatial and temporal expression patterns of DNMTs seem to be disturbed in abnormally developing embryos and in embryos that have been cryopreserved. Further research must be performed in order to understand whether the potentially disturbed embryonic DNMT expression after cryopreservation has any long-term developmental consequences. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Van Heel W.,Universitair Ziekenhuis Brussel Brussel | Hachimi-ldrissi S.,Universitair Ziekenhuis Brussel Brussel
International Journal of Emergency Medicine | Year: 2011

Misuse of organophosphate insecticides, even in case of domestic application, can be life threatening. We report the case of siblings admitted with respiratory distress, pinpoint pupils and slurred speech. The symptoms appear after spraying the skin by insecticides. Plasma pseudocholinesterase level appeared to be very low, consistent with acute intoxication with organophosphate insecticide. Management of organophosphate poisoning consists of airway management, administration of oxygen and fluid, as well as atropine in increasing doses and pralidoxime. Decontamination of the patient's skin and the removal of the patient's clothes are mandatory in order to avoid recontamination of the patient as well as the surrounding healthcare personnel. Plasma pseudocholinesterase analysis is a cheap and an easy indicator for organophosphate insecticides intoxications and could be used for diagnosis and treatment monitoring. © 2011 van Heel and Hachimi-Idrissi; licensee Springer.


Fostier K.,Universitair Ziekenhuis Brussel Brussel | De Becker A.,Universitair Ziekenhuis Brussel Brussel | Schots R.,Universitair Ziekenhuis Brussel Brussel
OncoTargets and Therapy | Year: 2012

Carfilzomib is a second-generation proteasome inhibitor with well-documented clinical activity as a single agent in patients with relapsed/refractory multiple myeloma. Carfilzomib can partially overcome resistance in bortezomib-refractory patients and has significant efficacy in bortezomib-naïve patients. Responses generally occur rapidly and are durable in the majority of cases. Carfilzomib can be safely administered in patients with renal failure and adverse cytogenetics do not seem to interfere with its activity. Moreover, Carfilzomib has the advantage of a favorable safety profile, especially a low incidence of peripheral neuropathy, which is often the dose-limiting factor in thalidomide and bortezomib-based regimens. The most frequently observed high-grade adverse event is cytopenia. However, long-term tolerability is good with no cumulative toxicity. The place of Carfilzomib in the treatment of the advanced and the newly diagnosed myeloma patient is currently under examination in several ongoing phase 3 clinical trials. © 2012 Fostier et al, publisher and licensee Dove Medical Press Ltd.


de Paepe C.,Vrije Universiteit Brussel | Krivega M.,Vrije Universiteit Brussel | Cauffman G.,Vrije Universiteit Brussel | Cauffman G.,Universitair Ziekenhuis Brussel Brussel | And 3 more authors.
Molecular Human Reproduction | Year: 2014

During human preimplantation development the totipotent zygote divides and undergoes a number of changes that lead to the first lineage differentiation in the blastocyst displaying trophectoderm (TE) and inner cell mass (ICM) onDay5. TheTEis a differentiated epithelium needed for implantation and the ICMforms the embryo proper and serves as a source for pluripotent embryonic stem cells (ESCs). The blastocyst implants around Day7. The second lineage differentiation occurs in theICMafter implantation resulting in specification of primitive endoderm and epiblast. Knowledge on human preimplantation development is limited due to ethical and legal restrictions on embryo research and scarcity of materials. Studies in the human are mainly descriptive and lack functional evidence. Most information on embryo development is obtained from animal models and ESC cultures and should be extrapolated with caution. This paper reviews totipotency and the molecular determinants and pathways involved in lineage segregation in the human embryo, as well as the role of embryonic genome activation, cell cycle features and epigenetic modifications. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

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