High dose gonadotropin stimulation increases endometrial thickness but this gonadotropin induced thickening does not have an effect on implantation.

INTRODUCTION Endometrial thickness <8mm is related with lower pregnancy rates. This raises the question if endometrial thickness can be increased by gonadotropin stimulation to increase estradiol (E2) concentration and if such an artificial thickening of the endometrium has an effect on implantation. A model to address this question is the comparison of endometrial thickness and outcome parameters in conventional gonadotropin stimulated IVF (cIVF) compared to unstimulated natural cycle IVF (NC-IVF). MATERIAL AND METHODS Retrospective study including 235 cIVF and 616 NC-IVF cycles without embryo selection and with fresh transfer on day 2 and 3 from 2015 to 2019. Endometrial and E2 measurements were included and analysed between day -4 and -2 (0 = day of aspiration). The effects of E2 on endometrial thickness, endometrial growth and the effect of endometrial thickness on implantation rates and live births were analysed. RESULTS Endometrial thickness was found to be higher in cIVF compared to NC-IVF (p < 0.001). On day -2, the day when ovulation was triggered, mean endometrial thickness was 9.75 ± 2.05mm and 8.12 ± 1.66mm, respectively. The increase in endometrial thickness slowed down with increasing E2 concentrations (time x estradiol concentration: -0.19, p = 0.010). Implantation rates were not significantly different in cIVF and NC-IVF cycles (clinical pregnancy rate: 19.1% vs. 15.4% p = 0.2; live birth rate: 12.8% vs. 11.7%, p = 0.8). CONCLUSIONS Endometrial growth dynamic is different and endometrium is thicker in cIVF compared to NC-IVF. Pregnancy and live birth rates are not different. Gonadotropin induced thickening of the endometrium does not appear to improve implantation

Optimal Timing of Ovulation Triggering to Achieve Highest Success Rates in Natural Cycles-An Analysis Based on Follicle Size and Oestradiol Concentration in Natural Cycle IVF.

Introduction Timing of ovulation triggering is essential in infertility treatments including treatments based on natural menstrual cycles. However, data on follicle size and oestradiol (E2) concentration are limited. Therefore, the model of natural cycle IVF (NC-IVF) was applied to provide more detailed information on these parameters to better schedule the optimal time for triggering ovulation. Materials and Methods A retrospective cross-sectional analysis of 606 monofollicular NC-IVF cycles was performed at a university-based IVF centre from 2016 to 2019. Follicle size and E2 and LH serum concentrations were evaluated on day -5 to 0 (day 0 = day of oocyte retrieval). Ovulation was triggered if follicle size was 14-22 mm. Patients with irregular cycles, endometriosis >II°, cycles with azoospermia or cryptozoospermia and cycles with inconsistent data were excluded. All parameters were analysed inter- and intraindividually, and associations of the parameters were evaluated. Associations were adjusted for age, cause of infertility and number of previous transfers. Results The mean age of women undergoing NC-IVF was 35.8 ± 4.0 years. Follicle size increased by 1.04 ± 0.03 mm, and E2 concentration by 167 ± 11.0 pmol/l per day.Based on a multivariate adjusted mixed model with follicle size, E2 and their interaction, the number of retrieved oocytes was associated with E2 concentration (aOR 1.91, 95% CI: 1.03-3.56; p = 0.040). Maturity of oocytes was associated not only with E2 concentration (aOR 2.01, 95% CI: 1.17-3.45; p = 0.011) but also with follicle size (aOR 1.27, 95% CI: 1.01-1.60; p = 0.039), as was the interaction of both parameters (aOR 0.96, 95% CI: 0.93-0.99; p = 0.017).LH surge was calculated to start in 25% of cases at an E2 level of 637 pmol/l, in 50% of cases at 911 pmol/l and in 75% of cases at an E2 level of 1,480 pmol/l.The live birth rate per follicle aspiration cycle was (non-significantly) higher in cycles with follicles sizes at the time of oocyte retrieval of 18-22 mm (7.7%-12.5%) versus in cycles with follicles sizes of 14-17 mm (1.6%-4.3%). Conclusion The study contributes to an optimization of infertility treatments involving natural cycles. The study gives guidance about the number of days required after follicle monitoring to schedule the optimal time for triggering ovulation

Oocyte maturity, oocyte fertilization and cleavage-stage embryo morphology are better in natural compared with high-dose gonadotrophin stimulated IVF cycles.

RESEARCH QUESTION Does high-dose gonadotrophin stimulation have an effect on oocyte and early-stage embryo development? DESIGN This was a retrospective study including 616 natural cycle IVF (NC-IVF) and 167 conventional IVF (cIVF) cycles. In total, 2110 oocytes were retrieved and analysed in fresh cycles. In NC-IVF, only human chorionic gonadotrophin was applied to trigger ovulation. In cIVF, antagonist protocols with daily 150-300 IU of human menopausal gonadotrophins were performed. The effect of gonadotrophins on oocyte and early-stage embryo development was analysed. Primary outcomes were the occurrence of mature (metaphase II) oocytes, zygotes and embryos with good morphology at the cleavage stage 2 days after oocyte retrieval. RESULTS The mature oocyte rate (number of mature oocytes/number of retrieved oocytes) was higher in NC-IVF than cIVF cycles (89% versus 82%, adjusted odds ratio [aOR] 1.79, P = 0.001), as was the zygote rate per oocyte retrieved (70% versus 58%, aOR 1.76, P = 0.001) and the zygote rate per mature oocyte (79% versus 71%, aOR 1.62, P = 0.001). The percentage of zygotes that developed into cleavage-stage embryos was no different. For the transferred embryos, the probability of having a good embryo morphology with four blastomeres and a fragmentation of <10% (score 0) in cleavage-stage embryos was found to be higher in NC-IVF (proportional aOR for four blastomeres 2.00, P < 0.001; aOR 1.87 for a fragmentation score of 0, P = 0.003). CONCLUSIONS Oocyte maturity, oocyte fertilization and morphology of the cleavage-stage embryo are affected by high-dose gonadotrophin stimulation in fresh IVF cycles

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Burst nucleation by hot injection for size controlled synthesis of ε-cobalt nanoparticles

BACKGROUND: Reproducible growth of narrow size distributed ε-Co nanoparticles with a specific size requires full understanding and identification of the role of essential synthesis parameters for the applied synthesis method. For the hot injection methodology, a significant discrepancy with respect to obtained sizes and applied reaction conditions is reported. Currently, a systematic investigation controlling key synthesis parameters as injection-temperature and time, metal to surfactant ratio and reaction holding time in terms of their impact on mean ([Formula: see text] (mean)) and median ([Formula: see text] (median)) particle diameter using dichlorobenzene (DCB), Co(2)(CO)(8) and oleic acid (OA) as the reactant matrix is lacking. METHODS: A series of solution-based ε-Co nanoparticles were synthesized using the hot injection method. Suspensions and obtained particles were analyzed by DLS, ICP-OES, (synchrotron)XRD and TEM. Rietveld refinements were used for structural analysis. Mean ([Formula: see text] (mean)) and median ([Formula: see text] (median)) particle diameters were calculated with basis in measurements of 250–500 particles for each synthesis. 95 % bias corrected confidence intervals using bootstrapping were calculated for syntheses with three or four replicas. RESULTS: ε-Co NPs in the size range ~4–10 nm with a narrow size distribution are obtained via the hot injection method, using OA as the sole surfactant. Typically the synthesis yield is ~75 %, and the particles form stable colloidal solutions when redispersed in hexane. Reproducibility of the adopted synthesis procedure on replicate syntheses was confirmed. We describe in detail the effects of essential synthesis parameters, such as injection-temperature and time, metal to surfactant ratio and reaction holding time in terms of their impact on mean ([Formula: see text] (mean)) and median ([Formula: see text] (median)) particle diameter. CONCLUSIONS: The described synthesis procedure towards ε-Co nanoparticles (NPs) is concluded to be robust when controlling key synthesis parameters, giving targeted particle diameters with a narrow size distribution. We have identified two major synthesis parameters which control particle size, i.e., the metal to surfactant molar ratio and the injection temperature of the hot OA–DCB solution into which the cobalt precursor is injected. By increasing the metal to surfactant molar ratio, the mean particle diameter of the ε-Co NPs has been found to increase. Furthermore, an increase in the injection temperature of the hot OA-DCB solution into which the cobalt precursor is injected, results in a decrease in the mean particle diameter of the ε-Co NPs, when the metal to surfactant molar ratio [Formula: see text] is fixed at ~12.9. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13065-016-0156-1) contains supplementary material, which is available to authorized users

Structural and magnetic aspects of La4(Co1-xNix)3O10+δ (0 ≤ x ≤ 1)

The Ruddlesden–Popper (RP3) type oxides, La4Co3O10+δ and La4Ni3O10+δ, form a complete solid solution. Powder X-ray and neutron diffraction data show that La4(Co1−xNix)3O10+δ is isostructural to the monoclinic La4Co3O10+δ structure (P21/a) described for all compositions without any further structural distortions as suggested in the literature. A slight elongation of the Co/Ni–O bonds facing the rock salt interlayer occurs for Ni-rich compositions. The magnetic properties of the solid solution series are mapped in the temperature range from 4 to 300 K, and the results are presented in a magnetic phase diagram. Three regimes with antiferromagnetic order (AF) exist at low temperatures, TN 0.80. The possibility to tune the oxidation state of the transition metal atoms is demonstrated for La4Co3O10+δ, and exemplified by weakening of a temperature-induced spin transition at around 480 K. This is an Accepted Manuscript of an article published by Taylor & Francis Group in Phase Transitions: A Multinational Journal, available online: http://www.tandfonline.co