The Effect of a Newly Designed Needle on the Pain and Bleeding of Patients During Oocyte Retrieval of a Single Follicle.

BACKGROUND: The purpose of this study was to evaluate the effect of needle type on pain and bleeding during oocyte pick-up (OPU). METHODS: From May through November 2013, patients undergoing OPU from a single follicle without any analgesic treatment were including this study. Eligible patients (n=75) were randomized 1:1 to undergo the procedure with either a reduced needle (17 gauge body, 20 gauge tip; RN group) or a standard needle (19 gauge; SN group). Overall pain was assessed by patients using a visual analogue scale (VAS), and vaginal bleeding after the procedure was recorded. Fisher exact, t-test or Wilcoxon test were used, and p<0.05 was considered to be statistically significant. RESULTS: The percentage of mature oocytes was 86.5% in the RN group and 91.7% in the SN group. Pain during OPU was significantly lower in the RN group than in the SN group (mean VAS score±SD: 3.2±2.0 cm vs. 4.9±2.2 cm, p<0.01; mean±SD). The frequency of vaginal bleeding was also significantly lower in the SN group (26.3% vs. 48.6%; p<0.05). The frequency of bleeding in the RN group was also significantly lower than that in the SN group (26.3% vs. 48.6%; p<0.05). No significant differences were found between the two groups with regard to fertilization and pregnancy rates. CONCLUSION: The newly designed needle significantly reduced pain and vaginal bleeding associated with single-follicle OPU in patients receiving no analgesic treatment, in comparison with a standard needle. The RN had no adverse effect on the quality of retrieved oocytes.

Clomiphene citrate affects the receptivity of the uterine endometrium.

Purpose: To investigate whether clomiphene citrate (CC) affects uterine receptivity or not, we evaluated pregnancy rates (PR) during the hormone replacement cycle (HRC) according to the period between the last day of CC administration and the day of embryo transfer (ET). Methods: From March 2008 through March 2010, a total of 378 treatment cycles among 378 patients who received CC and had to avoid fresh ET due to a thin uterine endometrium were recruited. All patients underwent thawed ET using HRC. PRs were evaluated according to the period between the last CC treatment and the day of ET. Results: PR for the groups in which the period between the last CC treatment and the day of ET increased to more than 91 days were significantly higher than that for group in which the period was less than 90 days (p < 0.05). Conclusions: A lower PR was shown by the patients who underwent thawed ET in the HRC within 90 days after their last CC treatment, which shows that CC affects the receptivity of the uterine endometrium.

Effects of raloxifene on the production of cytokines in stimulated whole blood in ex vivo and in vitro studies.

PURPOSE: The aims of this study were to determine the effects of raloxifene therapy on production of cytokines and in vitro effects of raloxifene on production of cytokines by whole blood cultures. METHODS: We obtained samples of peripheral blood from 6 postmenopausal women with osteopenia at baseline and after 3 and 6 months of raloxifene therapy and 10 postmenopausal women who did not receive raloxifene therapy. Whole blood from raloxifene-treated women was stimulated with lipopolysaccharide (LPS) or phytohemeagglutinin (PHA). Whole blood from postmenopausal women who were not treated with raloxifene was preincubated with raloxifene at concentrations of 10(-10)-10(-7) M and then stimulated with LPS or PHA. Concentrations of IL-1ß, IL-4, IL-6, IL-12p40, IL-12p70, TNF-α and IFN-γ in the supernatant were measured by respective ELISAs. RESULTS: In ex vivo cultures, raloxifene therapy inhibited LPS-stimulated production of IL-1ß, IL-6, IL-12p40, IL-12p70 and TNF-α, but not PHA-stimulated production of IL-4 and IFN-γ. In in vitro cultures, raloxifene at a concentration (10(-9) M) inhibited LPS-stimulated production of IL-1ß, IL-6 and IL-12p40 and PHA-stimulated production of IFN-γ. CONCLUSIONS: Raloxifene therapy decreases the production of IL-1ß, IL-6, IL-12 and TNF-α but not that of IL-4 and IFN-γ, suggesting that modulation of cytokines could play a role in the mechanisms of the osteoprotective effect of raloxifene.

ER calcium discharge stimulates GDNF gene expression through MAPK-dependent and -independent pathways in rat C6 glioblastoma cells.

Glial cell line-derived neurotrophic factor (GDNF), a neurotrophic and differentiation factor, is expressed under several pathophysiological conditions but its regulatory signals have not yet been clarified. Here, we found that endoplasmic reticulum (ER) Ca(2+) discharge by thapsigargin induced GDNF mRNA as well as COX2 and GRP78 expression in rat C6 glioblastoma cells. GDNF mRNA was immediately induced and peaked at 2h by thapsigargin, and the alternative transcript consisting of exon 3 and exon 4 appeared to be most inducible. In spite of intracellular Ca(2+) perturbation, Ca(2+)-dependent PKC was not responsible for this induction. Instead, a PKCdelta-specific inhibitor, rottlerin, suppressed the thapsigargin-induced GDNF mRNA expression. On the other hand, thapsigargin transiently enhanced phosphorylation status of mitogen-activated protein kinase (MAPK) pathway, including extracellular signal-regulated kinase (Erk), p38 MAPK and c-JUN amino-terminal kinase1 (JNK1) simultaneously; whereas specific inhibitors against MEK1 and JNK only reduced the thapsigargin-induced GDNF mRNA expression. In addition, a pan-PKC inhibitor (Ro-31-8220) attenuated the thapsigargin-enhanced phosphorylation levels of Erk1/2 and JNK1, whereas rottlerin did not. Thus, the present study demonstrated that the thapsigargin-stimulated ER Ca(2+) discharge up-regulated GDNF gene expression through both MAPK-dependent and -independent pathways in C6 glioblastoma cells.