识别促性腺激素释放激素激动剂对垂体-卵巢轴降调节抑制程度及意义

本文通过文献复习讨论促性腺激素释放激素激动剂(GnRH-a)联合促性腺激素(Gn)诱导排卵治疗方案对垂体卵巢轴的降调节作用及意义.广义的降调节作用包括:对血清促性腺激素:卵泡刺激素、黄体生成素(FSH、LH)水平、卵泡周期性发育和类固醇激素合成的影响.临床常见的垂体降调节程度包括过度抑制、部分抑制和未能达到抑制.过度抑制被认为是垂体卵巢轴完全静息状态所需要的,适用于性激素依赖性肿瘤或疾病的治疗.体外受精-胚胎移植(IVF-ET)治疗周期中仅需要达到部分垂体卵巢轴降调节,即保留进入周期募集的卵泡对促性腺激素的反应性和类固醇激素合成.未能达到抑制的垂体卵巢轴伴随着卵泡晚期早发LH峰的风险,与无降调节周期相似.GnRH-a对垂体卵巢轴的降调节作用不仅与其类型、半衰期和患者个体差异有关,并且呈现出剂量与使用时间的依赖性.大部分过度抑制效应的患者可以通过降低GnRH-a剂量逆转,恢复卵巢对外源促性腺激素的反应性.极少数妇女存在降调节的延迟反应,与LH受体变异和受体后缺陷有关.     

控制性卵巢刺激中卵巢慢反应的发生原因及处理方法

对促性腺功能正常的妇女采用促性腺激素释放激素激动剂(GnRH-a)长方案进行控制性卵巢刺激(COS)仍是目前的“主流”方案.然而,GnRH-a降调节作用可能导致部分妇女内源性黄体生成素(LH)抑制过深,仅使用卵泡刺激素(FSH)促排卵可能出现卵巢慢反应甚至低反应,导致不良临床结局.GnRH-a降调节垂体抑制过深是发生卵巢慢反应的主要原因.临床上及时补充LH能有效改善卵巢慢反应,减少周期取消率,提高体外受精-胚胎移植(IVF-ET)成功率.     

进一步认识垂体降调节

控制性超排卵(COH)过程中使用促性腺激素释放激素激动剂(GnRH-a)进行垂体降调节可以有效地预防早发黄体生成素(LH)峰,降低了周期取消率,同时还可以改善卵泡发育的同步化,但垂体降调节也可能由于垂体抑制过度而出现促性腺激素(Gn)使用量增加、卵巢反应不良增加。因此适度地降调节对COH的顺利进行提供了保障。用于垂体降调节的GnRH-a分长效和短效两种剂型,不同的剂量和剂型的垂体抑制程度不同,保留的垂体反应性也不同。而GnRH-a是否通过调节卵巢旁分泌和自分泌影响卵泡的同步化发育尚未有定论。本文就垂体降调节的优缺点及降调节程度的研究发展进行总结。     

促性腺激素释放激素激动剂降调节对促性腺激素阈值的影响

1983年Porter等[1]将促性腺激素释放激素激动剂(GnRH-a)引入可控制性诱导排卵方案获得成功,并提出GnRH-a降调节概念.由于GnRH-a较天然GnRH-a具有更高的受体亲和力和抵抗酶降解能力,在注射后短期内先出现垂体激发作用,产生一过性升高(flare up)效应,并促使血清促性腺激素(Gn)水平暂时性升高;随后表现为持续的垂体-卵巢轴抑制效应,即垂体-卵巢轴降调节作用(down regulation).表现为GnRH-a脉冲式分泌节奏消失,Gn合成与释放显著减少,血清卵泡刺激素(FSH)、黄体生成素(LH)水平降低不足以维持卵泡发育,雌、孕激素达到绝经期水平,这是一种可逆的、以LH、雌二醇(E-2)水平为主的垂体降调节作用.     

降调节对高龄低储备导致的低反应患者是否合适

高龄女性因卵巢储备下降,伴随对外源性促性腺激素(Gn)反应性下降,一直是辅助生殖助孕中的难点。常规垂体去敏感"降调节"作用优势在于有利于卵泡同步性及改善子宫内膜容受性,但在高龄患者中容易出现下丘脑轴的过度抑制,需增加促性腺激素(Gn)使用的时间和剂量,且结果常不理想。因此,对于高龄低储备导致的低反应患者是否使用降调节,以及如何掌控降调尺度,选择合适的促性腺激素释放激素激动剂(GnRH-a)降调方案、降调剂量和时间、以及Gn剂量和种类等需要综合把控,同时兼顾经济效益,这是临床医生面临的挑战。     

体外受精周期中避孕药的应用

卵巢高反应患者在IVF周期中降调节前使用避孕药是利用其对卵巢的双重抑制作用,减低卵巢敏感性,减少获卵数和卵巢过度刺激综合征(OHSS)发生率;卵巢低反应患者在拮抗剂周期前应用口服避孕药(oral contraceptive pill,OCP)意在增加卵巢敏感性,增加获卵数;正常反应者应用OCP,不改变IVF妊娠结局。一I、VF周期应用OCP的目的IVF周期应用OCP的主要目的是对性腺轴的负反馈 促性腺激素释放激素激动剂(GnRH-a)降调节,具有双重抑制作用;对性腺轴的负反馈 直接大量促性腺激素(Gn) GnRH拮抗剂(思则凯),增加卵巢对Gn的敏感性;降低GnRH-a应…     

卵巢高反应人群的降调节方案

促排卵是目前体外受精-胚胎移植（IVF-ET）过程中的重要步骤，以期获得足够的高质量卵子和提高妊娠率。20多年来应用促性腺激素释放激素激动剂（GnRH-a）的垂体降调节方案一直是IVF的常规促排卵方案。卵巢高反应是指卵巢对促性腺激素（Gn）刺激异常敏感，发生多卵泡发育，[第一段]     

控制性超排卵中黄体生成素的过度抑制和黄体生成素预处理

体外受精-胚胎移植(IVF-ET)降调方案中,使用促性腺激素释放激素激动剂(GnRH-a)降调后,部分患者可能出现卵巢过度抑制,对卵泡刺激素(FSH)的反应延迟.而GnRH-a主要抑制黄体生成素(LH),因此可能存在LH不足,对IVF中出现卵巢过度抑制的患者可考虑LH预治疗.     

降调节与卵巢反应性

一、垂体降调节垂体降调节是上世纪80年代体外受精可控制性卵巢刺激(COS)周期提出的治疗新概念,亦是对生殖内分泌有关下丘脑-垂体-卵巢轴调节的新认识,基于临床使用促性腺激素(Gn)进行COS导致多卵泡发育,雌激素水平突升,促性腺激素峰平抑因子(gonadotrophine surge attenuates     

促性腺激素释放激素激动剂降调节的个体化与促性腺激素启动日时机选择

促性腺激素释放激素激动剂(GnRH-a)已经广泛地应用于体外受精(IVF)垂体降调节中.GnRH-a分长效和短效两种剂型,长效剂型患者接受性和依从性高,但有卵巢过度抑制倾向,会造成促性腺激素(Gn)用量增加、使用时间延长,因而增加经济负担,而短效者可接受性和依从性较差.两者临床效果无显著差异.临床上常用的GnRH-a降调节方案有长、超长、短、超短等方案,各种方案的临床效果总体上并无显著差异但各有优缺点,通常卵巢功能减退的患者建议给予短方案,甚至超短方案,而卵巢储备功能正常患者常用长方案.超长方案对于合并子宫内膜异位症或多囊卵巢综合征患者等能提高临床妊娠率.降调标准存在争议,因此文献报道对于Gn的启动时间亦有不同,需要根据患者个体及不同的降调节方案而定.适当延迟启动时间可能改善卵母细胞的质量和内膜接受性,从而提高临床妊娠率,而且适当推迟Gn启动时间对于减少Gn的用量,降低患者的经济负担也是十分有益的.     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.