ＣＤ４５单抗介导的淋巴瘤荷瘤裸鼠三步法预定位放免显像

摘 要： 【目的】 评价生物素化ＣＤ４５单抗介导的９９ｍＴｃ－生物素在人Ｒａｊｉ细胞移植瘤裸鼠模型中三步法预定位放免显像的价值。【方法】 ＣＤ４５单抗及ＤＴＰＡ－生物素的９９ｍＴｃ标记采用直接标记法。取人Ｒａｊｉ细胞移植瘤裸鼠１８只,随机分为２组,每组９只。实验组为三步法预定位放免显像组,静注生物素化ＣＤ４５单抗１００ μｇ,４８ ｈ后静注亲和素２００ μｇ,再过４８ ｈ静注９９ｍＴｃ－生物素７．４ ＭＢｑ（２０ μｇ）;对照组为９９ｍＴｃ－ＣＤ４５单抗放免显像组,静注９９ｍＴｃ－ＣＤ４５单抗１００ μｇ。上述两组裸鼠分别于注药后３、６、１２ ｈ分别进行ＳＰＥＣＴ显像,每个时间点各取３只裸鼠断颈处死后,取脏器组织及肿瘤,称重后在γ计数仪中测量放射性计数,经放射性衰变校正后计算各脏器的％ＩＤ／ｇ及肿瘤／非肿瘤（Ｔ／ＮＴ）比值。【结果】平均每分子ＣＤ４５单抗约结合１２分子生物素,ＣＤ４５单抗及ＤＴＰＡ－生物素的９９ｍＴｃ标记率分别＞７０％和＞８０％。三步法给药后荷瘤裸鼠ＳＰＥＣＴ显像及生物分布示：整个显像期间血池内放射性均较低,肝脾见较多放射性浓聚;注射标记物后３－６ｈ,肿瘤显影清晰,并持续到１２ ｈ;注药后３、６和１２ ｈ肿瘤的％ＩＤ／ｇ分别为１．７３ ± ０．２２、１．２４ ± ０．０３和０．９４ ± ０．０７;肿瘤／血液比值分别为３．５、４．９和７．８;肿瘤／肌肉比值分别为８．２、８．９和１０．４。而静注９９ｍＴｃ－ＣＤ４５单抗后则可见肝脾及肾脏明显放射性聚集,１２ｈ血池内见较多放射性分布,肿瘤部位见有少量放射性集聚,１２ ｈ肿瘤的％ＩＤ／ｇ为０．８９ ± ０．１３,肿瘤／血液及肿瘤／肌肉的比值分别为１．６和２．５。【结论】与９９ｍＴｃ－ＣＤ４５单抗相比较,９９ｍＴｃ－生物素三步法预定位放免显像明显改善肿瘤Ｔ／ＮＴ比值,标记物注射后３ ｈ即可使肿瘤显影。     

99mTc—DTPA—甲硝唑正常动物体内分布研究

目的：探讨＾９９ｍＴｃ－ＤＴＰＡ－甲硝唑在正常动物的体内分布。方法：经小鼠和家兔耳缘静脉注射＾９９ｍＴｃ－ＤＰＴＡ－甲硝唑（３．７ＭＢｑ）后５ｍｉｎ２４ｈ,连续采集血液和其它脏器标本,测其放射性。结果：＾９９ｍＴｃ－ＤＴＰＡ－甲硝唑正常小鼠生物分布除肝脏、肾脏外,其余器官无明显分布。家兔血液清除研究在血中清除快,在血中呈双指数下降Ｔ１／２α为０．４５ｈ,Ｔ１／２β为３．１８ｈ。结论：＾９９ｍＴｃ－     

运动态^99mTc—MIBI心肌断层显像诊断冠心病的临床价值

目的探讨运动态９９ｍＴｃ－ＭＩＢＩ心肌断层显像对冠心病诊断价值。方法对患者进行次极量踏车运动高峰时静注９９ｍＴｃ－ＭＩＢＩ并于不同时间断层显像,比较不同时间的缺血／正常放射性比值和１ｈ、３ｈ放射性清除率之间的差异。结果２２例冠心病患者中,运动后１５ｍｉｎ与１ｈ对心肌缺血的诊断基本一致,而３ｈ与１ｈ对心肌缺血的诊断差异较大（Ｐ＜０．０１）。结论运动态９９ｍＴｃ－ＭＩＢＩ心肌断层显像对冠心病诊断有一定价值。     

~(99m)Tc-NOET与~(201)T1心肌显像在冠心病诊断中的对比研究

目的： 比较９９ｍＴｃＮＯＥＴ（ＮＯＥＴ：Ｎ乙氧基Ｎ乙基氨荒酸钠）和２０１Ｔ１ 心肌显像在冠心病（ＣＨＤ） 诊断中作用。方法：ＣＨＤ组：２３ 例,其中冠脉造影１４ 例;对照组：８ 例,其中冠脉造影２ 例。所有对象均进行９９ｍＴｃＮＯＥＴ及２０１Ｔ１ 运动—再分布ＳＰＥＣＴ显像。结果：①运动及再分布显像的心肌节段的放射性摄取一致性分别为２６９／２７９（９６．４％ , Ｋ ＝ ０．８９ ±０．０６） 和２６０／２７９（９３．２％ ,Ｋ＝０．７９±０．１８） ,一致性极好。②在本研究中,９９ｍＴｃＮＯＥＴ心肌显像诊断ＣＨＤ的敏感性和特异性分别为９１．３％ 、８７．５％ ,而２０１Ｔ１ 分别为８６．９％ 、８７．５ ％ 。９９ｍＴｃＮＯＥＴ和２０１Ｔ１ 显像诊断冠脉病变的敏感性和特异性分别为７１．４％ 、８５．０％ 和７５．０％ 、８５．０％ ,两者比较均无显著性差异。③再分布心肌节段一致性达８０％ 。结论：９９ｍＴｃＮＯＥＴ心肌显像在冠心病上的作用与２０１Ｔ１ 相似;两种显像剂在正常心肌内动力学基本相似,但灌注异常的心肌节段有一定差异,机理不详,可能是两者生物行为不同所致。     

^99mTc—octreotide的动物体内分布,药物动力学和临床初步应用研究

为研究＾９９ｍＴｃ－０ｃｔｒｅｏｔｉｄｅ作为肿瘤生长抑素受体显像剂的可能性，在无菌、无热原及安全实验的基础上，经动物体内分布、正常人药物动力学一系列实验后，进行临床受体显像。结果：动物体内分布实验显示血、心放射性呈“双峰”现象，＾９９ｍＴｃ－ｏｃｔｒｅｏｔｉｄｅ经泌尿系统排泄，正常人药物动力学拟合方程符合二室开放模型，ｔ１／２α＝２１分钟，ｔ１／２β＝１７０分钟；４例临床受体显像结果图像清晰，病灶放射性浓聚明显。上述结果提示，＾９９ｍＴｃ－ｏｃｔｒｅｏｔｉｄｅ是一种良好的肿瘤生长抑素受体显像剂。     

Tc-99m标记抗AFP抗体在人肝癌裸鼠模型中的定位显像研究

目的：揭示锝（Ｔｃ）－９９ｍ标记的单克隆抗体在肿瘤定位中的作用。方法：通过ＳＭＭＣ－７７２１－ＣＳ细胞株诱导原发性肝癌实体瘤裸鼠模型，将Ｔｃ－９９ｍ标记抗ＡＦＰ单克隆抗体（ＡｎｔｉＡＦＰ－ＭｃＡｂ）和正常鼠免疫球蛋白（ＮＭＩｇＧ）通过尾静脉注射荷瘤裸鼠，分别在１５ｍｉｎ、１２ｈ、２４ｈ作单光子发射计算机断层显像（ＳＰＥＣＴ）。结果：在注射标记抗体２４ｈ能得到清晰的肿瘤显像，对照组无肿瘤显像，其中靶与非靶放射性比率（Ｔ／ＮＴ）与对照组比较，ｔ＝３．１０４，Ｐ＜０．０５，有显著差异；肿瘤定位指数（ＬＩ－组织与血液放射性比率）单抗组为２．６８±０．０５，对照组为１．２３±０．０１，肿瘤组织摄取率为２８．６８％±４．００％。结论：Ｔｃ－９９ｍ标记抗ＡＦＰ抗体具有良好的定位效果     

血小板活化因子拮抗剂BN52021对大鼠肾电解质转运的影响

目的确定血小板活化因子拮抗剂ＢＮ５２０２１对正常和肾病大鼠尿电解质排泄的影响。方法制备大鼠阿霉素肾病模型，观察ＮＢ５２０２１使用后大鼠尿电解质的排泄情况。结果用ＢＮ５２０２１后１周，大鼠尿Ｎａ＋排泄量从对照组的２．４８７６±０．１８６２ｍｍｏｌ／２４ｈ增加到处理组的３．９８０６±１．０８９６ｍｍｏｌ／２４ｈ，Ｃｌ－１排泄量从１．５１４９±０．２０８７ｍｍｏｌ／２４ｈ增加到２．２４００±０．６４４９ｍｍｏｌ／２４ｈ，而Ｋ＋的排泄则从１．２４７９±０．０５４７ｍｍｏｌ／２４ｈ减少到０．４５０７±０．２１１８ｍｍｏｌ／２４ｈ（Ｐ均＜０．０１）；且ＢＮ５２０２１处理的大鼠，肾髓质的Ｎａ＋－Ｋ＋－ＡＴＰ酶活性为１．８±１．７μｍｏｌＰ·ｍｇ－１蛋白·ｈ－１，较对照组的４．６±１．１μｍｏｌＰ·ｍｇ－１蛋白·ｈ－１（Ｐ＜０．０１），明显受到抑制。结论ＢＮ５２０２１抑制大鼠肾脏Ｎａ＋、Ｃｌ－１的重吸收及Ｋ＋的分泌，这一作用与大鼠肾髓质的Ｎａ＋、Ｋ＋－ＡＴＰ酶活性的抑制有关。     

99mTc标记卵巢癌单抗片段F(ab'''')2 放射免疫显像的实验研究

目的：为了改进放射免疫显像（ＲＩＩ），进行９９ｍＴｃ标记卵巢癌单克隆抗体ＣＯＣ１８３Ｂ２Ｆ（ａｂ’）２ＲＩＩ的研究。方法：采用无花果酶制备单抗ＣＯＣ１８３Ｂ２片段Ｆ（ａｂ’）２，改进ＳｎＣｌ２法进行９９ｍＴｃ标记片段Ｆ（ａｂ’）２及正常鼠ＩｇＧ（ＮＭＩｇＧ）；９９ｍＴｃＣＯＣ１８３Ｂ２或９９ｍＴｃＮＭＩｇＧ标记物分别经腹腔注入荷人卵巢癌裸鼠体内，１８ｈ进行ＲＩ。显像后测定并计算肿瘤与非肿瘤组织放射性活度比值（Ｔ／ＮＴ）。结果：（１）无花果酶可制备ＣＯＣ１８３Ｂ２单抗片段Ｆ（ａｂ’）２；（２）改进ＳｎＣｌ２法进行９９ｍＴｃ标记Ｆ（ａｂ’）２，标记率达９０％以上；（３）１８ｈ后ＲＩ，可见９９ｍＴｃＣＯＣ１８３Ｂ２组荷瘤裸鼠较９９ｍＴｃＮＭＩｇＧ对照组移植瘤图像清晰，且Ｔ／ＮＴ值明显高。结论：应用片段Ｆ（ａｂ’）２可改善ＲＩＩ。     

肺,心放射性比值及左室腔,主肌放射性比值评价左心室功能

为了评价＾９９ｍ＾Ｔｃ－ＭＩＢＩ心肌显像时，肺、心放射性比值（ＬＨＲ）及左室腔、心肌放射性比值（Ｃ／Ｍ）与左心室功能的关系。比较２种方法的临床应用价值。正常对照组４２例，心肌梗死组３６例，３ｄ内完成静息相＾９９ｍＴｃ－ＭＩＢＩ心肌支显 门控心血池显像。在＾９９ｍＴｃ－ＭＩＢＩ心肌以显像正前位和与其相邻的图像上分别计算ＬＨＲ，取其平均值；在心肌断层短轴图像中，选取左室中间１帧，计算Ｃ／Ｍ，分别与门控     

^99mTc标记抗癌胚抗原单抗C50片段Fab‘及其生物分布研究

目的：研究克服＾９９ｍＴｃ示记抗癌胚抗原（ｃａｒｃｉｎｏｅｍｂｒｙｏｎｉｃ ａｎｔｉｇｅｎ,ＣＥＡ）单抗体内生物半衰期长、血液廓清速度慢、晚时相放射性信号弱等缺点的方法,用直接标记法进行了＾９９ｍＴｃ标记抗ＣＥＡ抗体Ｃ５０片断Ｆａｂ’的研究。方法：经胃蛋白酶切得的Ｃ５０片段Ｆ（ａｂ’）２用适量的２－巯基乙醇还原,Ｓｅｐｈａｄｅｘ Ｇ５０柱分离获得纯度大于９０％的Ｆａｂ’片断。取０．６～１．０ｍｇ纯化的片段Ｆａｂ’（体积〈１．０ｍｌ）,加入０．４～０．８ｍｇ葡庚糖酸钠及新鲜配制的ＳｎＣｌ２溶液５～１０μｇ,然后加入新鲜淋洗的Ｎａ＾９９ｍＴｃＯ４淋洗液,反应１０～１５ｍｉｎ。用高压液相色谱监测放化纯度和抗体纯度。荷ＣＬ－１８７（结肠癌）裸鼠静脉注射＾９９ｍＴｃ－Ｆａｂ’,观察标记抗体片段在不同时相的体内分布。结果：     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas： report of 9 cases

Objective：To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas（SPTP）. Methods：Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin（HE） staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results：Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin（9/9 cases）, AAT（9/9 cases）, NSE（9/9 cases）, ACT（7/9 cases）, CK20（2/9 cases）, CgA（1/9 cases）, S-100（3/gcases）, PR（4/gcases）, Syn（3/9 cases） and CD56（5/9cases）, negative in CEA and ER. Conclusion：SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.