[Effects of estradiol on the day of human chorionic gonadotropin administration on adverse perinatal outcomes].

Objective: To investigate the association between estradiol on the day of human chorionic gonadotropin (HCG) administration and birth outcomes among singleton live births following fresh embryo transfers. Methods: Based on the clinical reproduction medicine management system of the First Affiliated Hospital of Nanjing Medical University, this retrospective cohort study collected data of fresh embryo transfer cycles during January 2013 and December 2016, including pregnant women's age, body mass index (BMI), type and cause of infertility, assisted reproductive therapy indicators (fertilization mode, ovulation stimulation protocol, estradiol levels on HCG administration day), adverse birth outcomes[small for gestational age (SGA), premature and low birth weight (LBW)], etc.. A total of 2 060 women with singleton pregnancy (2 061 fresh embryo transfer cycles) were enrolled. Multivariate logistic regression was used to analyze the association between estradiol on HCG administration day and singletons' adverse birth outcomes. Results: The age and BMI of the 2 060 pregnant women were (29.63±3.92) years old and (22.29±2.86) kg/m2. Incidences of SGA, premature and LBW were 9.8% (201/2 061), 6.9% (143/2 061) and 3.5% (73/2 061), respectively. After adjusting for confounders, the risk of LBW in 4 000-4 499 pg/ml group was significantly elevated when compared to estradiol<1 500 pg/ml group [OR (95%CI): 4.42 (1.13-17.24)]. A protective effect of premature was observed in estradiol≥4 500 pg/ml group [OR (95%CI): 0.50 (0.25-0.97)]. Conclusion: The high level of estradiol on HCG administration day might be a risk factor for LBW, but a protective factor for premature.

[Cumulative live birth rates per oocytes retrieved cycle: evaluation of clinical outcomes of IVF/ICSI].

Objective: Using of cumulative live birth rate (CLBR) per oocytes retrieved cycle, to assess the clinical outcomes of in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) , and to explore impact factors on CLBR following utilization of all fresh and frozen embryos in one complete IVF/ICSI cycle using gonadotropin-releasing hormone (GnRH) agonist, GnRH-antagonist and clomiphene mild stimulation protocols. Methods: Of the patients who underwent IVF/ICSI from January 1st, 2014 to December 31st, 2015 in the First Affiliated Hospital, Nanjing Medical University, a total of 6 142 oocytes retrieved cycles were included. The clinical and laboratory parameters of different ovarian stimulation protocols, and the effects of the age, number of oocytes retrieved and number of embryos available on the CLBR of each oocytes retrieved cycle were analyzed. Results: The CLBR was 69.0% (2 004/2 906) in the GnRH-agonist protocol versus 67.4% (644/955) in the GnRH-antagonist protocol (P>0.05); the CLBR of clomiphene mild stimulation protocol was 53.2% (1 215/2 281) , significantly lower than those of the other two protocols (all P<0.05). The CLBR significantly decreased with age increased. When divided into four groups according to the patients' age, we found that CLBR were not statistically significant using three different protocols in the 20-25 years old group (all P>0.05). There was a strong association between the number of oocytes retrieved and embryos available on CLBR. CLBR rose significantly with an increasing number of oocytes up to 6, then the rising trend slowed down. Patients were categorized into four groups according to the number of oocytes retrieved, CLBR was significantly higher using GnRH-antagonist protocol (50.0%) than mild stimulation protocol (37.0%) in low ovarian responder (0-4 oocytes) group (P<0.05) . The CLBR were no significant difference among three protocols in normal (10-15 oocytes) and high responders (≥15 oocytes) group (all P>0.05) . The incidence rate of ovarian hyperstimulation syndrome in GnRH-agonist protocols (5.2%, 152/2 906) were significantly higher than those of GnRH-antagonist (4.4%, 42/955) and clomiphene mild stimulation protocols (1.5%, 34/2 281; all P<0.05) . Conclusions: CLBR is an important index to assess the clinical outcomes of IVF/ICSI. Age, number of oocytes retrieved and embryos available could affect CLBR obviously. According to the different age and ovarian response of patients, we should design ovarian stimulation protocols based on target oocytes number in order to get higher CLBR and reduce complications.

Endogenous nitric oxide induces activation of apoptosis signal-regulating kinase 1 via S-nitrosylation in rat hippocampus during cerebral ischemia-reperfusion.

Apoptosis signal-regulating kinase 1 (ASK1) is a general mediator of cell death in response to a variety of stimuli, including reactive oxygen species, tumor necrosis factor α, lipopolysaccharide, endoplasmic reticulum stress, calcium influx and ischemia. Here we reported ASK1 was activated by nitric oxide (NO) through S-nitrosylation during cerebral ischemia-reperfusion. The reagents that abrogate neuronal nitric oxide synthase (nNOS) activity such as nNOS inhibitor 7NI and N-methyl-D-aspartate receptor antagonist MK801 prevented ASK1 activation via decreasing ASK1 S-nitrosylation. In HEK293 cells, over-expressed ASK1 could be S-nitrosylated by both exogenous and endogenous NO and Cys869 was identified as the site of ASK1 S-nitrosylation. S-nitrosylation increased the level of ASK1 phosphorylation at Thr845, which represents ASK1 activation. Our results further confirmed that S-nitrosylation led to the increment of ASK1 dimerization. S-nitrosylation of ASK1 also activated the downstream JNK signaling and JNK-mediated nucleic pathway. The exogenous NO (SNP and GSNO) reversed the effect of endogenous NO by suppressing S-nitrosylation of ASK1 and exerted neuroprotection during ischemia-reperfusion. These results suggest that inhibiting ASK1 S-nitrosylation may be a novel approach for stroke therapy.