Chaim Sheba Medical Center Tel Hashomer

Tel Aviv, Israel

Chaim Sheba Medical Center Tel Hashomer

Tel Aviv, Israel
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Kivilevitch Z.,Ultrasound Unit | Achiron R.,Chaim Sheba Medical Center Tel Hashomer | Zalel Y.,Chaim Sheba Medical Center Tel Hashomer
American Journal of Obstetrics and Gynecology | Year: 2010

Objective: The objective of the study was to evaluate the magnitude of normal fetal brain asymmetry. Study Design: This was a prospective study. Normal fetuses between 19-28 weeks of gestation were studied. The cerebral atria, occipital cortex, and hemispheres in both sides were measured. The difference between each side was evaluated and was correlated with sex, head biometry, and estimated weight. Results: Four hundred six fetuses were studied. Mean atrial width was larger in the males and on the left side (5.2% and 6.5%, respectively). Mean cortical width was 2.6% larger in males but 5.5% thinner on the left side. Mean hemisphere width was larger in males and on the left side (2.3% and 1.5%, respectively). The atria and the cortex presented an inverse relationship regarding fetal growth parameters. Conclusion: Brain asymmetry represents normal fetal brain developmental phenomena. It is sex dependent and lateralized in most cases to the left. Lateralization was more accentuated in males. © 2010 Mosby, Inc. All rights reserved.


PubMed | University of London, Chaim Sheba Medical Center Tel Hashomer and Arcispedale Santa Maria Nuova Asmn Instituto Of Ricovero E Cura A Carattere Scientifico Irccs
Type: Review | Journal: Reproductive biology and endocrinology : RB&E | Year: 2016

In the literature, there is growing evidence that subfertile patients who conceived after infertility treatments have an increased risk of pregnancy and perinatal complications and this is particularly true for patients who conceived through use of high technology infertility treatments. Moreover, high technology infertility treatments include many concomitant clinical and biological risk factors. This review aims to summarize in a systematic fashion the current evidence regarding the relative effect of the different procedures for high technology infertility treatments on the risk of adverse pregnancy and perinatal outcome. A literature search up to August 2016 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar and an evidence-based hierarchy was used to determine which articles to include and analyze. Data on prepregnancy maternal factors, low technology interventions, specific procedures for male factor, ovarian tissue/ovary and uterus transplantation, and chromosomal abnormalities and malformations of the offspring were excluded. The available evidences were analyzed assessing the level and the quality of evidence according to the Oxford Centre for Evidence-Based Medicine guidelines and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. Current review highlights that every single procedure of high technology infertility treatments can play a crucial role in increasing the risk of pregnancy and perinatal complications. Due to the suboptimal level and quality of the current evidence, further well-designed studies are needed.


Reinisch W.,Universitatsklinik For Innere Medizin Iii | Angelberger S.,Universitatsklinik For Innere Medizin Iii | Petritsch W.,Medical University of Graz | Shonova O.,Nemocnice Ceske Budejovice | And 11 more authors.
Gut | Year: 2010

Objective: The aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn's disease (CD) with moderate or severe endoscopic recurrence. Methods: This was a 1 year, double-blind, double-dummy, randomised study which took place in 21 gastroenterology centres in Austria, the Czech Republic, Germany and Israel. The study participants were 78 adults with CD who had undergone resection with ileocolonic anastomosis in the preceding 6-24 months without subsequent clinical recurrence and with a Crohn's disease activity index (CDAI) score <200, but with moderate or severe endoscopic recurrence. The study drugs were azathioprine 2.0-2.5 mg/kg/day or mesalazine 4 g/day over 1 year. The primary end point was therapeutic failure during 1 year, defined as a CDAI score ≥200 and an increase of ≥60 points from baseline, or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction. Results: Treatment failure occurred in 22.0% (9/41) of azathioprine-treated patients and 10.8% (4/37) of mesalazine-treated patients, a difference of 11.1% (95% CI -5.0% to 27.3%, p=0.19). Clinical recurrence was significantly less frequent with azathioprine versus mesalazine (0/41 (0%) vs 4/37 (10.8%), p=0.031), whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprine-treated patients (9/41 (22.0%) vs 0%, p=0.002). The proportion of patients showing ≥1 point reduction in Rutgeerts score between baseline and month 12 was 63.3% (19/30) and 34.4% (11/32) in the azathioprine and mesalazine groups, respectively (p=0.023). Conclusions: In this population of patients with postoperative CD at high risk of clinical recurrence, superiority for azathioprine versus mesalazine could not be demonstrated for therapeutic failure. Clinical trial registration number NCT00946946.


Kocabas N.A.,Free University of Colombia | Kocabas N.A.,Free University of Brussels | Faghel C.,Free University of Colombia | Barreto M.,Free University of Colombia | And 8 more authors.
International Clinical Psychopharmacology | Year: 2010

Catechol-O-methyltransferase (COMT) has been suggested to be involved in the pathogenesis and pharmacological treatment of affective disorders. The nonsynonymous single nucleotide polymorphism (SNP) in exon 4 (Val108/158Met; rs4680) influences the COMT enzyme activity. Inconsistent results were found between Val158Met polymorphism (rs4680) and treatment response phenotypes in genetic association studies. However, the haplotype combinations of alleles at the Val108/158Met SNP with the other synonymous SNPs in the COMT gene region have shown association between enzyme activity/amount and COMT-dependent phenotypes. We carried out this study to define the functional impact of COMT genotypes/haplotypes on susceptibility and on treatment response phenotypes of major depressive disorder (MDD). Three hundred and ninety-six patients with MDD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [(DSM)-IV] and 295 healthy controls were recruited for this study and genotyped for the seven COMT SNPs (rs2075507, rs737865, rs6269, rs4633, rs4818, rs4680, and rs165599). This is the first study with all these SNPs to investigate for MDD and treatment response phenotypes. Our results show that none of the seven SNPs, including the rs4680, was significantly associated with MDD after permutation correction in single SNP analyses. Although several haplotype combinations showed significance, the combinations of G-T-G-G haplotype for rs6269, rs4633, rs4818 and rs4680 were only present in the MDD group (G-T 4.5%, corrected sim P=0.0001; G-T-G 3.87%, corrected sim P=0.001; G-T-G-G 3.3% corrected sim P=0.0025). In the treatment response phenotypes, the GG genotype of the rs2075507 SNP (located in the promoter region of MB-COMT) was less common in resistant patients in a single SNP analysis with low corrected sim P=0.052 and power=0.086. However, in the haplotype analysis, the haplotypes of exonic SNPs, rs4633, rs4818, and rs4680, were related to the treatment response phenotypes investigated, especially the phenotype of the response to antidepressant treatment. The C-C-A haplotype of these SNPs was overrepresented (almost four-and eight-fold) in the responders compared with the nonresponders and controls, respectively, after Bonferroni correction (corrected sim P=0.048, 0.0001, respectively). Both nonsynonymous and synonymous SNPs within haplotypes may be more relevant than the single SNP in conferring MDD susceptibility and treatment response phenotypes. Despite the limited power of our analysis, this finding suggests that the polymorphic COMT gene that influences catecholaminergic neurotransmission may play a role in the individual response to antidepressants. © Lippincott Williams & Wilkins.


Gilam A.,Tel Aviv University | Edry L.,Tel Aviv University | Mamluk-Morag E.,Tel Aviv University | Mamluk-Morag E.,Institute of Human Genetics | And 10 more authors.
Breast Cancer Research and Treatment | Year: 2013

Several lines of evidence indicate that sequence alterations within microRNA (miRNA)-binding sites can modify the binding to its target gene resulting in altered expression patterns. We hypothesized that a single nucleotide polymorphism (SNP) located in the miR-515-5p binding site of igf-1r gene may alter IGF-1R regulation, with consequent effects on breast cancer risk in BRCA1 mutation carriers. Computational prediction revealed that the rs28674628 SNP in the igf-1r 3′ UTR is located within a predicted binding site for miR-515-5p. The effect of this SNP on breast cancer risk was evaluated by genotyping 115 Jewish Ashkenazi carriers of the 185delAG mutation in the BRCA1 gene using the Sequenom platform followed by Kaplan-Meier analysis. Additional data set of 378 Jewish BRCA1 carriers was analyzed to validate our results. MiRNA transfection, Western blot analysis, luciferase reporter assay, real time PCR, and immunohistochemistry were performed to assess direct regulation of igf-1r by miR-515-5p. We show direct regulation of IGF-1R by miR-515-5p. We identified that disrupting miR-515-5p and igf-1r 3′ UTR binding by SNP may cause elevated IGF-1R protein levels. Interestingly, miR-515-5p is downregulated in tumor tissue compared to its non-neoplastic surrounding tissue while IGF-1R levels are elevated. This igf-1r SNP was found to be significantly associated with age at diagnosis of breast cancer in Jewish Ashkenazi BRCA1 mutation carriers. These findings support the hypothesis that a SNP located in igf-1r gene may alter miRNA regulation of IGF-1R, with a putative effect on BRCA1 penetrance and breast cancer risk. © 2013 Springer Science+Business Media New York.


Haas J.,Chaim Sheba Medical Center Tel Hashomer | Haas J.,Tel Aviv University | Zilberberg E.,Chaim Sheba Medical Center Tel Hashomer | Zilberberg E.,Tel Aviv University | And 7 more authors.
Journal of Ovarian Research | Year: 2014

Background: Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation- 40 and 34 hours prior to OPU, respectively (double trigger) was suggested as the treatment of genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger improves the number of oocytes retrieved in patients with low (<50%) number of oocytes retrieved per number of preovulatory follicles. Methods. In this proof of concept cohort historical study, we compared the stimulation characteristics of 8 IVF cycles, which include the double trigger to the patients' previous IVF attempt, triggered with hCG-only. Results: Patients who received the double trigger (study group) had a significantly higher number of oocytes retrieved, number of 2PN, number of embryos transferred and significantly higher proportions of the number of oocytes retrieved to the number of follicles >10 mm and >14 mm in diameter on day of hCG administration, with a tendency toward a higher number of TQE, as compared to their previous cycles (hCG-only trigger). Three ongoing clinical pregnancies were recorded in the study group and none in the hCG-only trigger group. Conclusions: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (double trigger), is suggested as a valuable new tool in the armamentarium for treating patients with low/poor oocytes yield despite an apparently normal follicular development and E2 levels and in the presence of optimal hCG levels on the day of OPU. © 2014 Haas et al.; licensee BioMed Central Ltd.


PubMed | Chaim Sheba Medical Center Tel Hashomer
Type: Comparative Study | Journal: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology | Year: 2015

With the recent trend toward single embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. All consecutive patients undergoing natural cycle Day-3 FET cycles between May 2012 and March 2015 in our IVF unit were evaluated. While following spontaneous ovulation, all patients received progesterone luteal support. Since June 2014, patients underwent the same aforementioned natural cycle FET cycles, with two additional injections, one of recombinant hCG (250mcg) and the other of GnRH-agonist (triptorelin 0.1mg), on the day of transfer and 4d later, respectively. While the patients clinical characteristics, the prevalence of embryos that survived the thawing process and the number of embryos transferred were comparable between the earlier as compared with the later period, implantation rate, positive -hCG, clinical, and ongoing pregnancy rates were significantly higher during the later period. We, therefore, suggest that when natural cycle FET is offered, the addition of two injections of recombinant hCG and GnRH-agonist, on the day of transfer and 4d later, respectively, might increase clinical pregancy rates. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.


PubMed | Chaim Sheba Medical Center Tel Hashomer
Type: Journal Article | Journal: American journal of reproductive immunology (New York, N.Y. : 1989) | Year: 2015

Ovarian hyperstimulation syndrome (OHSS) is similar to vascular leak syndrome (VLS), which may be attributable to the massive increase in systemic inflammatory cytokines. The hyperstimulated human ovaries were demonstrated to contain interleukin (IL)-2, which, in turn, was suggested to activate the systemic inflammatory response characteristic of OHSS. As the source of follicular fluid IL-2 is still unclear, in the present study, we sought to validate the presence of IL-2 and IL-2 mRNA expression in human luteinized granulosa cells.IL-2 nuclear expression was detected using real-time PCR and immunofluorescence staining of human luteinized granulosa cell from 6 patients undergoing in vitro fertilization treatment. Calretinin immunofluorescence staining was used as a marker of granulosa cells.IL-2-positive immunofluorescence staining was detected within nuclei of granulosa cells, together with positive stain for calretinin, confirming the presence of granulosa cell. Moreover, IL-2 gene expression was demonstrated in luteinized granulosa cells by real-time PCR.In the present study, we provided firm evidence for the IL-2 production by human luteinized granulosa cells, as demonstrated by the presence of IL-2 and IL-2 mRNA expression in luteinized granulosa cells. Further studies are justified in an attempt to clarify the regulation and the cause-and-effect relationship between IL-2 production by the hyperstimulated ovaries and OHSS.


PubMed | Chaim Sheba Medical Center Tel Hashomer
Type: Journal Article | Journal: Journal of assisted reproduction and genetics | Year: 2016

Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. In the present study, we aim to evaluate the outcome of natural cycle FET with modified luteal support.All consecutive patients undergoing natural or artificial hormone replacement (AHR) day-2/3 FET cycles between May 2012 and June 2015 in our IVF unit were evaluated. While AHR FET cycles were consistent, those undergoing natural cycle FET received progesterone luteal support, and from June 2014, patients received two additional injections, one of recombinant hCG and the other of GnRH-agonist, on day of transfer and 4days later, respectively (modified luteal support).Patients clinical characteristics and laboratory/embryological variables were comparable between those undergoing natural vs. AHR cycles, during the earlier as compared to the later period. Moreover, while implantation, clinical, and ongoing pregnancy rates were significantly higher during the later period in patients undergoing the natural cycle FET with the modified luteal support (31, 51, and 46%, respectively), as compared to natural (17, 26, and 20%, respectively), or AHR FET in the late study period (15, 22, and 17%, respectively), the natural cycle FET without the additional two injections yielded the same results, as the AHR cycles.We therefore suggest that in ovulatory patients undergoing FET, natural cycle FET with the modified luteal support should be the preparation protocol of choice. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.


PubMed | Chaim Sheba Medical Center Tel Hashomer
Type: Clinical Trial | Journal: Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology | Year: 2015

Human chorionic gonadotropin (hCG) is usually used at the end of controlled ovarian hyperstimulation (COH), as a surrogate LH surge, to induce final oocyte maturation and resumption of meiosis. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation - 40 and 34h prior to OPU, respectively (double trigger) was suggested to improve IVF outcome in patient with genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger might improve the proportions of metaphase-II (MII) oocytes in patients with low proportion of mature oocytes (<66%) per number oocytes retrieved.We compared the stimulation characteristics of 12 IVF cycles, which include the cycle with the double trigger to the same patients previous IVF attempt, triggered with hCG-only.Patients who received the double trigger (study group) had a significantly higher number of mature oocytes - MII (6.5 versus 3.6 p<0.008), number of embryos transferred (2.4 versus 1.1 p<0.03), a significantly higher proportions of MII oocytes per number of oocytes retrieved (69.7% versus 47.1% p<0.03) and a higher number of top quality embryos (3.1 versus 1 p<0.02), as compared to their previous control cycles (hCG-only trigger). Six pregnancies were recorded in the study group and none in the control group.Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34h prior to OPU, respectively (double trigger) improves IVF outcome in patients with high proportion of immature oocytes.

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