血清F-β-HCG，PROG，CK，β-HCG测定在异位妊娠早期诊断中价值的研究
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摘要
背景目的 目前，异位妊娠早期诊断主要依靠超声和系列的血清人绒毛膜促性腺激素β亚单位(β-HCG)化验检查，但是在孕4-5周时，对于诊断宫内妊娠或异位妊娠来说，即使高分辨率的阴道超声检查，想在影像学上得到明确的孕囊图像均太早，且宫腔内的假孕囊和蜕膜征易误诊。在异位妊娠时，β-HCG变异范围(标准差)较大，使异位妊娠和宫内妊娠之间的β-HCG水平有较大范围的重叠，仅单次测定血清β-HCG作为一个诊断指标对于异位妊娠的早期诊断价值不大。本研究旨在检测人绒毛膜促性腺激素游离β亚单位(F-β-HCG)、孕酮(PROG)、肌酸激酶(CK)、β-HCG在异位妊娠早期诊断中的灵敏度和特异度，探讨F-β-HCG、PROG、CK、β-HCG在异位妊娠早期诊断中的意义。
方法 研究对象：自2005年1月至2005年10月山东省立医院门诊收治的符合纳入标准的患者80例作为研究对象，纳入标准：①平素月经周期规律，末次月经日期明确，停经30～60天；②年龄为20～40岁；③尿妊娠试验阳性；④B超未能确定妊娠位置；⑤不规则阴道出血排除宫颈息肉和／或宫颈糜烂；⑥肝肾功能正常；⑦生命体征正常；⑧患者知情同意。
对于符合纳入标准的患者，治疗前均抽取静脉血，离心，吸取离心后的血清2ml，其中1ml立即进行β-HCG、PROG、CK测定；1ml置于-20℃的冰箱内保存待检F-β-HCG，同时记录患者的姓名、年龄、孕产史、孕龄、联系方式等并追踪观察。根据最后的妊娠结局或组织学检查将研究对象分为两组：A组为宫内妊娠组：B组为异位妊娠组。
血清β-HCG，PROG采用电化学发光法测定，血清CK采用连续监测酶法
Background/aims
The most common methods of Early diagnosis of ectopic pregnancy(EP) are using ultrasound with serial measurements of P-human chorionic gonadotropin (HCG). Using ultrasound can not find the embryo as early as pregnancy 4-5 weeks, not only for EP, but also for intrauterine pregnancy. Furthermore the false embryo often leads to misdiagnosis. And many researches have shown that in the early phase of pregnancy the difference of β-HCG is not obvious between EP and intrauterine pregnancy. So β-HCG is not enough in the diagnosis of early EP. The objective of this study was to explore the possibility that an isolated measurement of F-β-HCG, CK, PROG rather than β-HCG could be used as a single test for ectopic pregnancy, and the significant of compound of F-β-HCG, PROG, β-HCG in the diagnosis of ectopic pregnancy.
Methods
From January 2005 to October 2005, serum samples were collected at the outpatient departments of Shandong Shengli Hospital. The selective criteria were as follows: ①Regular menstrual cycle; clear last menstrual period (LMP):30d-60d; ②20-40 years old;③with a positive pregnancy test;④with inconclusive ultrasonogr-aphic findings;⑤the pregnant woman who has cervical polyp or cervical erosion was excluded;⑥The function of liver, kidney is normal;⑦willingness;⑧hemodynamic stability.There were 80 cases that meet the above criteria altogether. The blood
方法 研究对象：自2005年1月至2005年10月山东省立医院门诊收治的符合纳入标准的患者80例作为研究对象，纳入标准：①平素月经周期规律，末次月经日期明确，停经30～60天；②年龄为20～40岁；③尿妊娠试验阳性；④B超未能确定妊娠位置；⑤不规则阴道出血排除宫颈息肉和／或宫颈糜烂；⑥肝肾功能正常；⑦生命体征正常；⑧患者知情同意。
对于符合纳入标准的患者，治疗前均抽取静脉血，离心，吸取离心后的血清2ml，其中1ml立即进行β-HCG、PROG、CK测定；1ml置于-20℃的冰箱内保存待检F-β-HCG，同时记录患者的姓名、年龄、孕产史、孕龄、联系方式等并追踪观察。根据最后的妊娠结局或组织学检查将研究对象分为两组：A组为宫内妊娠组：B组为异位妊娠组。
血清β-HCG，PROG采用电化学发光法测定，血清CK采用连续监测酶法
Background/aims
The most common methods of Early diagnosis of ectopic pregnancy(EP) are using ultrasound with serial measurements of P-human chorionic gonadotropin (HCG). Using ultrasound can not find the embryo as early as pregnancy 4-5 weeks, not only for EP, but also for intrauterine pregnancy. Furthermore the false embryo often leads to misdiagnosis. And many researches have shown that in the early phase of pregnancy the difference of β-HCG is not obvious between EP and intrauterine pregnancy. So β-HCG is not enough in the diagnosis of early EP. The objective of this study was to explore the possibility that an isolated measurement of F-β-HCG, CK, PROG rather than β-HCG could be used as a single test for ectopic pregnancy, and the significant of compound of F-β-HCG, PROG, β-HCG in the diagnosis of ectopic pregnancy.
Methods
From January 2005 to October 2005, serum samples were collected at the outpatient departments of Shandong Shengli Hospital. The selective criteria were as follows: ①Regular menstrual cycle; clear last menstrual period (LMP):30d-60d; ②20-40 years old;③with a positive pregnancy test;④with inconclusive ultrasonogr-aphic findings;⑤the pregnant woman who has cervical polyp or cervical erosion was excluded;⑥The function of liver, kidney is normal;⑦willingness;⑧hemodynamic stability.There were 80 cases that meet the above criteria altogether. The blood
引文
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2. Lee JK, Oh MJ, Shin JS, et al.Clinical Effectiveness of Urinary Human Chorionic Gonadotropin Related protein (HCGRP) Quantification for Diagnosis of Ectopic pregnancy. J Korean Med Sci, 2005, 20(3):461-467.
3. Cracia CR, Barnhart KT. Diagnosing ectopic pregnancy:decision analysis compared six strategies. Obstet Gynecol, 2001, 97(3): 464-470.
4. Liao SX, Huang FF, Yang YL, et al.Screening for chromosomal abnormalities using nuchal translucency measurement with materal serum biochemistry markers in first trimester[J]. Beijing Da Xue Xue Bao, 2005, 37(1):39-41.
5．王小平，向阳，张德永等．化学发光法测定绒毛膜促性腺激素游离β亚单位对滋养细胞疾病的诊断价值[J]．中国实用妇科与产科杂志，2001，17(11)：660-662．
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7. Della-Giustina D, Denny M. Ectopic pregnancy. Emerg Med Clin North Am, 2003, 21(8):565-584.
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9. Tenore JL. Ectopic pregnancy. Am Fam physician 2000, 61 (4): 1080-1088.
10. Buckley RG, King KJ, Disney JD, et al. History and physical examination to estimate the risk of ectopic pregnancy: validation of a clinical prediction model. Ann Emerg Med, 1999, 34(5):589-594.
11. Mol BW, Van der Veen F, Bossuyt PM. Implementation of probabilistic decision rules improves the predictive values of algorithms in the diagnostic management of ectopic pregnancy. Hum Reprod, 1999,14:2855-2862.
12. Sagiv R, Golan A, Arbel-Alon S. Three conservative approaches to treatment of interstitial pregnancy. J Am Assoc Gynecol Laparosc, 2001, 8(1):154-158.
13．乐杰主编，妇产科学，第五版：人民卫生出版社，2000，108-109．
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16. Cole LA. Immunoassay of human chorionic gonadotropin, its free subunits, and metabolites.Clinical Chemistry, 1997, 43(12):2233-2243.
17．许建营，陈淑霞，朱红鹏主编．异位妊娠(第一版)．中国医药科技出版社出版，2002：35-41．
18. Heather Murray, Hanadi Baakdah, Trevor Bardell, et al. Diagnosis and treatment of ectopic pregnancy. CMAJ, 2005, 173(8):905-912.
19. Dart RG, Mitterando J, Dart LM. Rate of change of serial beta-human chorionic gonadotropin values as a predictor of ectopic pregnancy in patients with indeterminate transvaginal ultrasound findings. Ann Emerg Med, 1999, 34:703-710.
20. Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, Hummel AC, Guo W. Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined. Obstet Gynecol, 2004, 104:50-55.
21. Heather Murray, Hanadi Baakdah, Trevor Bardell, et al. Diagnosis and treatment of ectopic pregnancy. CMAJ, 2005, 173(8):905-912.
22. Borrelli PT, Butler SA, Docherty SM, Staite EM, Borrelli AL, Iles RK. Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy. Clin Chem 2003, 49:2045-2049.
23．樊世荣．绒毛膜促性腺激素和孕酮检测在异位妊娠诊治中的价值．中国实用妇科与产科杂志，2000，16(4)：200-201．
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28. Katsikis I, Rousso D, Farmakiotis D, et al. Receiver operator characteristics and diagnostic value of progesterone and CA-125 in the prediction of ectopic and abortive intrauterine gestations. Eur J Obstet Gynecol Reprod Biol, 2006, 125(2):226-232.
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1. Luciano AA, Roy G, Solima E. Ectopic pregnancy:from surgical emergency to medical management. Ann N Y Acad Sci, 2001,943:235-254.
2. Jae-Kwan Lee, Min-Jeong Oh, Joong-Sik Shin, et al. Clinical Effectiveness of Urinary Human Chorionic Gonadotropin Related protein (hCGRP) Quantification for Diagnosis of Ectopic pregnancy. J Korean Med Sci, 2005, 20:461-467.
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7．君桂然，杨玉风，杨素娟，et al．ELISA法测定绒毛膜促性腺激素游离β亚单位对异位妊娠的诊断价值．中华综合临床医学杂志，2003，5(12)：40-41．
8. Borrelli PT, Butler SA, Dosherty SM, et al. Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy. Clin Chem, 2003, 49(2):2045-2049.
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10. Buckley RG, King KJ, Disney JD, et al. Serum progesterone testing to predict ectopic pregnancy in symptomatic first-trimester patients. Ann Emerg Med, 2000, 36(2):95-100.
11. Dart R, Ramanujam R, Dart L, et al. progesterone as a predictor of ectopic pregnancy when the ultrasound is indeterminate. Am J Emerg Med, 2002, 20(7): 575-579.
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13. Robert G.. Serum progesterone to predict ectopic pregnancy in symptomatic first trimester patients. J Accid Emerg Med, 2000, 17(6) 562-565.
14. Develioglu OH, Askalli C, Uncu G, et al. Evaluation of semm creatine kinase in ectopic pregnancy with reference to tubal status and histopathology. BJOG, 2002, 109(2): 121-128.
15. Katsikis I, Rousso D, Farmakiotis D, et al. Receiver operator characteristics and diagnostic value of progesterone and CA-125 in the prediction of ectopic and abortive intrauterine gestations. Eur J Obstet Gynecol Reprod Biol, 2006, 125(2): 226-232.
16. Lavie O, Beller U, Neuman M, et al. Maternal serum creatine kinase: a possible predictor of tubal pregnancy[J]. Am J Obstet Gynecol, 1993, 169(5)1149-1150.
17. Chardra L, Jain A. Maternal serum creatine kinase as a biochemical marker of tubal pregnancy [J]. Int J Gynecol Obstet, 1995, 49: 21
18. Birkhahn RH, Gaeta TJ, Leo pJ, et al. The utility of maternal creatinc kinase in the evaluation of ectopic pregnancy. Am J Emerg Med, 2000, 18(6): 695-697.
19. Develioglu OH, Askalli C, Uncu G, et al. Evaluation of serum creatine kinase in ectopic pregnancy with reference to tubal status and histopathology. BJOG, 2002, 109(2): 121-128.
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2. Lee JK, Oh MJ, Shin JS, et al.Clinical Effectiveness of Urinary Human Chorionic Gonadotropin Related protein (HCGRP) Quantification for Diagnosis of Ectopic pregnancy. J Korean Med Sci, 2005, 20(3):461-467.
3. Cracia CR, Barnhart KT. Diagnosing ectopic pregnancy:decision analysis compared six strategies. Obstet Gynecol, 2001, 97(3): 464-470.
4. Liao SX, Huang FF, Yang YL, et al.Screening for chromosomal abnormalities using nuchal translucency measurement with materal serum biochemistry markers in first trimester[J]. Beijing Da Xue Xue Bao, 2005, 37(1):39-41.
5．王小平，向阳，张德永等．化学发光法测定绒毛膜促性腺激素游离β亚单位对滋养细胞疾病的诊断价值[J]．中国实用妇科与产科杂志，2001，17(11)：660-662．
6. Elson J, Tailor A, Banerjee S, Salim R, Hillaby K, Jurkovic D. Expectant management of tubal ectopic pregnancy: prediction of successful outcome using decision tree analysis. Ultrasound Obstet Gynecol, 2004, 23(6):552-556.
7. Della-Giustina D, Denny M. Ectopic pregnancy. Emerg Med Clin North Am, 2003, 21(8):565-584.
8. Cynthia M Farquhar.Ectopic pregnancy. Lancet, 2005, 366: 583-591.
9. Tenore JL. Ectopic pregnancy. Am Fam physician 2000, 61 (4): 1080-1088.
10. Buckley RG, King KJ, Disney JD, et al. History and physical examination to estimate the risk of ectopic pregnancy: validation of a clinical prediction model. Ann Emerg Med, 1999, 34(5):589-594.
11. Mol BW, Van der Veen F, Bossuyt PM. Implementation of probabilistic decision rules improves the predictive values of algorithms in the diagnostic management of ectopic pregnancy. Hum Reprod, 1999,14:2855-2862.
12. Sagiv R, Golan A, Arbel-Alon S. Three conservative approaches to treatment of interstitial pregnancy. J Am Assoc Gynecol Laparosc, 2001, 8(1):154-158.
13．乐杰主编，妇产科学，第五版：人民卫生出版社，2000，108-109．
14. Stenman UH, Alfthan H, Hotakainen K. Human chorionic gonadotropin in cancer.Clinical Biochemistry, 2004, 37(7):549-561.
15. Birken S, Berger P, Bidart JM, et al. Preparation and characterization of new WHO reference reagents for human chorionic gonadotropin and metabolites. Clin Chem, 2003, 49:144-54.
16. Cole LA. Immunoassay of human chorionic gonadotropin, its free subunits, and metabolites.Clinical Chemistry, 1997, 43(12):2233-2243.
17．许建营，陈淑霞，朱红鹏主编．异位妊娠(第一版)．中国医药科技出版社出版，2002：35-41．
18. Heather Murray, Hanadi Baakdah, Trevor Bardell, et al. Diagnosis and treatment of ectopic pregnancy. CMAJ, 2005, 173(8):905-912.
19. Dart RG, Mitterando J, Dart LM. Rate of change of serial beta-human chorionic gonadotropin values as a predictor of ectopic pregnancy in patients with indeterminate transvaginal ultrasound findings. Ann Emerg Med, 1999, 34:703-710.
20. Barnhart KT, Sammel MD, Rinaudo PF, Zhou L, Hummel AC, Guo W. Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined. Obstet Gynecol, 2004, 104:50-55.
21. Heather Murray, Hanadi Baakdah, Trevor Bardell, et al. Diagnosis and treatment of ectopic pregnancy. CMAJ, 2005, 173(8):905-912.
22. Borrelli PT, Butler SA, Docherty SM, Staite EM, Borrelli AL, Iles RK. Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy. Clin Chem 2003, 49:2045-2049.
23．樊世荣．绒毛膜促性腺激素和孕酮检测在异位妊娠诊治中的价值．中国实用妇科与产科杂志，2000，16(4)：200-201．
24．君桂然，杨玉凤，杨素娟，et al．ELISA法测定绒毛膜促性腺激素游离β亚单位对异位妊娠的诊断价值．中华综合临床医学杂志，2003，5(12)：40-41．
25. Buckley RG, King KJ, Disney JD, et al. Serum progesterone testing to predict ectopic pregnancy in symptomatic first-trimester patients. Ann Emerg Med, 2000, 36(2):95-100.
26. Dart R, Ramanujam P, Dart L. Progesterone as a predictor of ectopic pregnancy when the ultrasound is indeterminate. Am J Emerg Med, 2002, 20(7):575-579.
27. Robert G. Serum progesterone to predict ectopic pregnancy in symptomatic first trimester patients. J Accid Emerg Med, 2000, 17 (6) 562-565.
28. Katsikis I, Rousso D, Farmakiotis D, et al. Receiver operator characteristics and diagnostic value of progesterone and CA-125 in the prediction of ectopic and abortive intrauterine gestations. Eur J Obstet Gynecol Reprod Biol, 2006, 125(2):226-232.
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