Multiple Mild Stimulations Reduce Membrane Distribution of CX3CR1 Promoted by Annexin al in Microglia to Attenuate Excessive Dendritic Spine Pruning and Cognitive Deficits Caused by a Transient Ischemic Attack in Mice

A transient ischemic attack(TIA)can cause reversible and delayed impairment of cognition,but the specific mechanisms arestill unclear.Annexin al(ANXA1)is a phospholipid-binding protein.Here,we confirmed that cognition and hippocampal synapses were impaired in TIA-treated mice,and this could be rescued by multiple mild stimulations(MMS).TIA promoted the interaction of ANXAl and CX3CR1,increased the membrane distribution of CX3CR1 in microglila,and thus enhanced the CX3CR1 and CX3CL1 interaction.These phenomena induced by TIA could be reversed by MMS.Meanwhile,the CX3CR1 membrane distribution and CX3CR1-CX3CL1 interaction were upregulated in primary cultured microglia overexpressing ANXAl,and the spine density was significantly reduced in co-cultured microglia overexpressing ANXAl and neurons.Moreover,ANXAl overexpression in microglia abolished the protection of MMS after TIA.Collectively,our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.

Comparison of the Effects and Safety of Mild Ovarian Stimulation and Conventional Ovarian Stimulation with A Long GnRH Agonist Protocol on IVF Outcomes

Objective To conduct a Meta-analysis of studies that compared the efficacies of mild ovarian stimulation and conventional long GnRH agonist protocol in patients under- going IVF or intracytoplasmic sperm injection （ICSI）. Methods Meta-analysis was performed. All studies were published by July 2012 with data related to outcomes following mild ovarian stimulation compared with the conventional protocol. Odds ratios （ORs） and weighted/standardized mean difference （WMD/SMD） from individual study were pooled in fixed and random effect models. Main outcome measure was the efficacy of mild ovarian stimulation. Results Six articles were included in this Meta-analysis. The number of oocytes retrieved was lower, the cycle cancellation rate was higher and the incidence of ovarian hyperstimulation syndrome （OHSS） was lower in the mild stimulation group than in conventional ovarian stimulation group. Clinical pregnancy rates were similar in both mild and conventional stimulation groups. Conclusions The level of evidence supporting the use of mild stimulation protocols in IVF is low, considering the fewer oocytes retrieved and the higher rates of cycle cancellation.

Study of Combined Use of Clomiphene Citrate and Gonadotropins on the Infertile Patients with PCOS

Objective To investigate the efficacy and safety of combined use of clomiphene citrate （CC） and gonadotropins （Gn） on the infertile patients with PCOS. Methods A total of 367 infertile patients with PCOS were included in this retrospective study. Patients received CC from menstrual cycle day 3 until the day of triggering and human menopausal gonadotrophins （hMG） from menstrual cycle day 5 until the ovulation day. Gn duration and doses, serum LH and estradiol levels, transferable embryos, incidence of OHSS, frozen-thawed embryo implantation and clinical pregnancy rates were compared among CC plus hMG, long and short protocols. Results Gn duration and doses, blood estrogen level transferable embryos and incidence of OHSS in the group of CC plus hMG were decreased significantly than those of long and short protocols. No differences were observed in the frozen-thawed embryo implantation and clinical pregnancy rates among three groups. Conclusion Mild stimulation of CC combined with hMG on infertile patients with high risk for OHSS is safe and efficient.

Clomiphene Citrate or Medroxyprogesterone Acetate with Human Menopausal Gonadotropin in Poor Responders during In vitro Fertilization/Intracytoplasmic Sperm Injection Treatments Combined with Embryo Cryopreservation?

Objective:This study aimed to compare the efficacy of clomiphene citrate(CC)with human menopausal gonadotropin(hMG)and that of medroxyprogesterone acetate(MPA)with hMG in poor responders defined according to the Bologna criteria.Methods:The data of patients with poor ovarian response(POR)according to the Bologna criteria from September 2016 to November 2017 were retrospectively reviewed.All participants received either CC+hMG or the progesterone-primed ovarian stimulation protocol(PPOS)protocol.Results:A total of 340 patients and 563 in vitro fertilization cycles were analyzed in this study.The incidence of spontaneous luteinizing hormone(LH)surge and the mean LH level on trigger day were significantly lower in the PPOS group than in the CC+HMG group(0.04%vs.3.49%and 4.26±3.59 vs.9.38±6.92 mIU/mL,respectively,P<0.05);however,the incidence of premature ovulation was similar between the two groups.The number of viable embryos harvested was not statistically different between the two groups(1.7±1.1 vs.1.5±0.8,P=0.06).The mean dose and duration of hMG were significantly higher in the PPOS group than in the CC+hMG group(908.7±556.6 vs.177.9±214.5 IU and 6.0±3.4 vs.1.2±1.5 days,respectively,P<0.05).However,the number of oocytes retrieved,number of metaphase II oocytes,and fertilization rate were comparable between the two groups.Conclusions:The CC with low-dose gonadotropin strategy was superior to the MPA with hMG protocol for POR.