克罗米芬与GnRH拮抗剂在控制性超促排卵中抑制LH峰效果的比较

目的:探讨克罗米芬(CC)与GnRH拮抗剂(GnRH-A)在控制性超促排卵(COH)中对黄体生成素(LH)峰抑制效果的比较。方法:对应用CC后置方案和拮抗剂方案的181个周期的资料进行回顾性分析。其中应用CC抑制LH峰方案65例(CC组),应用GnRH-A(思则凯组)抑制LH峰方案116例。比较2种药物对LH峰的抑制作用、Gn用量、获卵数、可移植胚胎数、优质胚胎数、受精率等。结果:hCG注射日LH值与加用CC或思则凯日LH值的差值[LH(d-)]具有统计学差异(1.30±5.12 IU/L vs-1.37±7.15 IU/L,P=0.004);Gn用量、获卵数、可移植胚胎数、优质胚胎数、受精率等CC组和思则凯组比较差异无统计学意义(P0.05)。结论:CC与思则凯对早发LH峰均有一定抑制效果,但较CC相比其抑制早发LH峰效果可能更明显。     

Pregnancy outcome following frozen embryo transfer after artificial cycle or treatment by clomiphene citrate

The optimal method to prepare endometrium before frozen embryo transfer (FET) is not yet established. We retrospectively studied 4496 FET and detailed pregnancy and miscarriage rates in three groups of patients according to the endometrium preparation they have followed before their successive FET: clomifene citrate (CC, group 1), artificial cycle (AC, group 2) or switch between CC and AC (group 3). The overall pregnancy rates per transfer were 24.3, 20.8 and 17.3% while the miscarriage rates reached 23.2, 29.8 and 42.5%, respectively. Group 1 experienced the highest ongoing pregnancy rate (18.6%), the lowest being observed in group 3 (10.0%, p?相似文献   

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??Objective To investigate the safety and efficacy of application of regional sodium citrate anticoagulation in children with high risk of bleeding in the continuous blood purification??CBP??. Methods A total of 11 patients with severe hepatic dysfunction and severe bleeding due to different diseases were treated with regional sodium citrate anticoagulation during CBP from March 2015 to May 2016. The changes of ACT??serum calcium and arterial blood gas before and after treatment of CBP were monitored??and the clinical bleeding performance and the operation status of the filter were observed. Results??After the application??the ACT value after the filter during the treatment with regional citrate was significantly longer than the ACT value before the filter??before the filter??the ACT values before treatment and after treatment had no significant changes. During the treatment??the value of calcium ions after the filter was significantly lower than the value before the filter??and the value of 2 cases after the filter was once lower than 0.2 mmol/L??then was corrected by slowing down the citrate solution dripping. Before the filter??the values of calcium level in 8 cases had no significant changes before the treatment and during treatment. All cases completed CBP treatment successfully withould severe bleeding or aggrevation of bleeding. Conclusion The clinical effect of regional sodium citrate anticoagulation in pediatric critical ill patients with CBP is effective. It has the advantages of less influence on the systemic coagulation and higher safety. It is suitable for the children with hepatic dysfunction??severe bleeding or who are not suitable for heparin anticoagulation. It is an effective and feasible??safe anticoagulation method in critical ill children with CBP.     

Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: Clomethiazole-mediated amelioration

Mitochondria play a central role in both the physiological and pathophysiological regulation of cell survival/death. Increasing evidence places mitochondrial dysfunction at the center of many neuropathological conditions. The present study investigates the extent of mitochondrial dysfunction in cortical, hippocampal and cerebellar tissues in a rat model of hypoxia-ischemia (HI). We hypothesized that; mitochondrial dysfunction in situ may be prevented by treatment with clomethiazole (CMZ), a GABA(A) receptor agonist. Assessment of mitochondrial FAD-linked respiration at both 1- and 3-day post-HI revealed a marked decrease in activity from ipsilateral cortical and hippocampal regions (P<0.001). In addition, small changes were seen in contralateral cortical and hippocampal tissues as well as in the cerebellum at 3-days (P<0.05). Assessment of the mitochondrial electron transport chain (complexes I-V), and mitochondrial markers of integrity (citrate synthase) and oxidative stress (aconitase) confirmed mitochondrial impairment in ipsilateral regions following HI. Complexes I, II-III, V and citrate synthase were also impaired in contralateral regions and cerebellum 3-days post-HI. Treatment with CMZ (414 mg/kg/day via minipumps) provided marked protection to all aspects of neuronal tissue assessed. Circulating cytokine (interleukin [IL]-1alpha, IL-1beta, tumor necrosis factor [TNF]-alpha, granulocyte macrophage colony-stimulating factor [GM-CSF], IL-4 and IL-10) levels were also assessed in these animals 3-days post-HI. Plasma IL-1alpha, IL-1beta, TNF-alpha and GM-CSF levels were significantly increased post-HI. Treatment with CMZ ameliorated the increases in IL-1alpha, IL-1beta, TNF-alpha and GM-CSF levels while increasing plasma IL-4 and IL-10 levels. This study provides evidence of the extent of mitochondrial damage following an HI-insult. In addition, we have shown that protection afforded by CMZ extends to preservation of mitochondrial function and integrity via anti-inflammatory mediated pathways.     

The Selection of a Pharmaceutical Salt—The Effect of the Acidity of the Counterion on Its Solubility and Potential Biopharmaceutical Performance

A roadmap for the selection of a pharmaceutical salt form for a development candidate is presented. The free base of the candidate did not have sufficient chemical stability for development. The initially selected salt form turned out to be undevelopable because it was unstable during scale-up synthesis and storage. The rationale for the new solid form screening and the criteria for selection are discussed. Before the final selection, the pH solubility profiles of the 2 new salts, a benzoate and a besylate, were compared. Atypical solubility behavior was observed for the benzoate salt in hydrochloric acid with and without normal saline. A scheme is proposed illustrating how the pKas of the counterion and active pharmaceutical ingredient, the medium composition, and final pH affect the solubility and solution equilibria of the 2 selected salt forms. This scheme also includes the equilibria between solution and solid phases in different pH ranges. The pharmaceutical importance of this research is that it sheds light on how the acidity of the counterion can affect the solubility of the selected salt form in the gastric environment. With a well-designed formulation strategy, this property potentially can be translated to optimal biopharmaceutical performance of the drug product.     

枸橼酸西地那非对宫腔粘连术后冻融胚胎移植妊娠结局的影响

目的：观察枸橼酸西地那非（万艾可）对宫腔粘连（intrauterine adhesion,IUA）分离术后冻融胚胎移植（frozen embryo transfer,FET）患者妊娠结局的影响。方法：选择2017年1-12月在南京医科大学附属妇产医院行FET的不孕症患者,在进入FET周期前宫腔镜检查确诊IUA,行宫腔镜下IUA分离术,术后复查宫腔镜显示宫腔形态正常行FET,共310例。根据患者是否添加枸橼酸西地那非将患者分为2组,其中A组（对照组）实施激素替代周期FET,共190例;B组（治疗组）为激素替代周期并在患者月经干净后每日阴道给予枸橼酸西地那非50 mg,应用至移植前,共120例。首先比较2组患者的妊娠结局,其次将A组及B组患者进一步分为轻度IUA组和中重度IUA组,比较2组之间的差异。结果：B组临床妊娠率［50.83%（61/120）］高于A组［34.74%（66/190）］,差异有统计学意义（P＜0.05）;B组胚胎种植率［31.17%（72/231）］略高于A组［21.82%（79/362）］,但差异无统计学意义（P＞0.05）。与A组相比,B组轻度IUA患者的临床妊娠率与胚胎种植率差异无统计学意义（P＞0.05）;B组中重度IUA患者的临床妊娠率［44.78%（30/67）］及胚胎种植率［28.46%（37/130）］均高于A组,差异有统计学意义（P＜0.05）。2组间流产率和异位妊娠率比较差异均无统计学意义（P＞0.05）。结论：应用枸橼酸西地那非可提高IUA术后患者子宫内膜容受性,尤其对中重度IUA术后患者可显著提高其FET妊娠率。     

去氧孕烯炔雌醇片预处理联合氯米芬用于宫颈机能不全患者体外受精-胚胎移植的临床研究

目的 观察去氧孕烯炔雌醇片预处理联合氯米芬用于宫颈机能不全患者体外受精-胚胎移植的临床疗效,并分析其不良妊娠结局的影响因素。方法 将120例拟接受体外受精-胚胎移植的宫颈机能不全患者随机分为观察组和对照组,对照组给予氯米芬微刺激治疗,观察组给予去氧孕烯炔雌醇片预处理联合氯米芬微刺激治疗。比较两组患者的周期取消率、生化妊娠率及临床妊娠率、获卵数、正常受精卵数、早孕期流产率、血清胰岛素样生长因子1（IGF-1）、胰岛素样生长因子结合蛋白3（IGFBP-3）。结果 观察组患者的促性腺激素（GTH）用量、GTH刺激天数少于对照组,人绒毛膜促性腺素（HCG）注射日雌激素值小于对照组,周期取消率、早孕期流产率、晚期流产率、早产率低于对照组（P <0.05）,正常受精率、生化妊娠率、临床妊娠率、活产率、A型子宫内膜率高于对照组,获卵数、正常受精卵数多于对照组,扳机日子宫内膜厚度厚于对照组（P <0.05）。观察组患者刺激前后血清IGF-1、IGFBP-3水平的差值大于对照组（P <0.05）。一般Logistic回归分析结果显示,不孕年龄［O^R=0.882（95% CI：0.511,0.999）］、不同刺激方案［O^R=1.062（95% CI：1.001,2.112）］、GTH用量［O^R=0.712（95% CI：0.526,0.941）］、获卵数［O^R=1.122（95% CI：1.022,1.201）］、可利用胚胎数［O^R=2.012（95% CI：1.561,2.300）］是妊娠不良结局的危险因素（P <0.05）。结论 去氧孕烯炔雌醇片预处理联合氯米芬可显著改善患者的IGF-1、IGFBP-3水平及妊娠结局;且可利用胚胎数较多、GTH用量较少的患者,其妊娠结局较好、获卵数较多。     

In vitro effects of clomiphene citrate on sperm parameters and fertilisation rate in male NMRI mice

Clomiphene citrate (CC), as a medication in male infertility, improves the sperm parameters in oral consumption but various detrimental side effects have been reported including testicular tumours, gynaecomastia, skin allergic reactions and ocular symptoms. Therefore, this study was designed to evaluate the in vitro effects of CC on sperm parameters and fertilisation rate in IVF protocol. Sperm samples of NMRI adult mice were divided into six groups: group 1 received no treatment (control group), while groups of 2, 3, 4, 5 and 6 (experimental groups) were incubated with the doses of 0.001, 0.01, 0.1, 1 and 10 µg/ml of CC in culture medium respectively. Sperm parameters (viability, morphology and motility), DNA fragmentation levels and fertilisation rate in IVF were evaluated. The results demonstrated that the doses of 0.1 µg/ml (p = .000007 for viability and p = .00006 for fertilisation rate) and 1 µg/ml (p = .032 for viability and p = .005 for fertilisation rate) CC cause a significant improvements; also, the dose of 0.1 µg/ml CC found effective on sperm motility (p = .0003). In the field of IVF, the application of 0.1 and 1 µg/ml of CC in the culture medium may improve the sperm parameters in IVF protocol with no side effects.