β-hCG、Activin A、Inhibin A在输卵管妊娠早期诊断中的价值的研究
摘要
目的：异位妊娠是妇产科常见的急腹症,近二十年来发病率呈上升趋势,提高诊断技术可以减少异位妊娠的误诊率及漏诊率,为其保守治疗及保留输卵管的再生育功能创造有利条件。目前异位妊娠早期诊断主要依靠超声和血清人绒毛膜促性腺激素β亚单位(β-hCG)化验检查,但是在妊娠4～5周时,尚不能完全确定妊娠部位。本研究旨在检测血清激活素A (ACT A)、抑制素A(INH A)在输卵管妊娠早期诊断中的灵敏度和特异度,探讨血清激活素A (ACT A)、抑制素A(INH A)在输卵管妊娠早期诊断中的意义,以及其在子宫内膜组织中的表达和有无诊断价值。
方法：选取自2008年11月至2009年10月山西医科大学第二医院门诊及住院患者80例作为研究对象。对于全部符合纳入标准的病人,根据妊娠结局或组织学检查分为：A组：宫内妊娠组,B组：输卵管妊娠组。病人于治疗前抽取静脉血5ml,置于非抗凝试管中,静置1h,3000转／分,离心10分钟,吸取离心后的血清,置于-70℃的冰箱内保存待检。宫内妊娠组人流前及输卵管妊娠组术前行诊刮术取子宫内膜组织,常温下保存于福尔马林液待检；
血清采用固相夹心法酶联免疫吸附试验(ELISA)测定,所得数据应用SPSS11.5统计软件包进行统计学分析。正态分布资料用均数、标准差描述,两组均数间差别比较采用t检验(Sutdent'-test)o分别作血清ACT A、INH A受试者工作曲线(ROC),确定ACTA、INHA的诊断界值及其诊断输卵管妊娠的灵敏度、特异度。并应用四格表分析联合诊断早期输卵管妊娠的灵敏度、特异度。内膜组织采用免疫组化法测定,计算其在子宫内膜组织的表达率,P<0.05为差别有统计学意义。
结果：1.两组患者年龄、身高、体重、孕次、流产次数、停经天数、月经周期的比较差别均无统计学意义(P>0.05)；2.输卵管妊娠组ACT A、INH A、β-hCG水平分别为0.24±0.17ng/ml,26.4±4.33 pg/ml,6673.2±3636.4mIu/ml,宫内妊娠组的0.51±0.31ng/ml, 44.85±6.22pg/ml,10112.2±7600.7mIu/ml,应用两组比较的t检验,差别有统计学意义；3.用ROC曲线进行分析：ACT A的ROC曲线下面积为0.57,最佳截断值是0.35 ng/ml,灵敏度93%,特异度20%,阳性似然比见、阴性似然比为1.1、0.25;INH A曲线下面积为0.71,最佳截断值是28.6pg/ml,灵敏度90%,特异度32%,阳性似然比2.58,阴性似然比0.32；β-hCG曲线下面积为0.73,最佳截断值是3236.6 mIu/ml,灵敏度88%,特异度60%。4.ACTA、INH A在子宫内膜组织中的表达率,差别无统计学意义。
结论：1. ACT A和INH A对输卵管妊娠的早期诊断有一定价值。2. ACT A最佳截断值0.35ng/ml,灵敏度93%,特异度20%；INH A最佳截断值28.6 ng/ml,灵敏度90%,特异度32%。3. ACT A、INH A与β-hCG联合诊断价值不大。4.ACT A和INH A在宫内妊娠和输卵管妊娠的子宫内膜组织中都有表达,但是没有统计学意义,没有诊断价值。
objective:Ectopic pregnancy(EP) is a frequent surgical abdomen of obstetrics and gynecology, the incidence of which is rising in the recent twenty years. The developing of diagnostic techniques can reduce the rate of misdiagnosis and missed diagnosis, in order to create favorable conditions for better reserve fertility and conservative treatment of EP. The most common methods of early diagnosis of ectopic pregnancy are using ultrasound with serial measurements of human chorionic gonadotropin (β-hCG). However, these cannot find the embryo as early as gestational 4-5weeks,not only for EP, but also for intrauterine pregnnacy. .The objective of this study was to explore the possibility that an isolated measurement of Activin、Inhibin rather thanβ-hCG could be used as a single test for ectopic pregnancy, And the significant of compound of Activin、Inhibit、β-hCG in the diagnosis of ectopic pregnancy.
Methods:From November 2008 to October 2009, There were 80 cases that met the criteria altogether,serum samples were collected in the Second Hospital of Shanxi Medical University. The blood samples were centrifuged 3000r/min for 10 minutes and placed in-70℃refrigerator kept for inspection.Activin、Inhibin and P-hCG was determined by ELISA.The data was analyzed by SPSS 11.5 of windows statistical package.Data of Normal distribution were described with mean and Standard deviation.The comparison of the difference of Means of two groups was processed by student't-test and ROC curve which was drawn concerning serum Activin A、Inhibin A、β-hCG. The area below the cuvre was calculated. Youden index was used to determine the cut-off Point of Activin A、Inhibin A and their sensitivity, specificity. It meant significant if P<0.05. Endometrial tissue was determined by immunohistochemistry method, Calculated positive rate of endometrial tissues. It meant significant if P<0.05.
Results:1. There was no significant diffrence on age, height, weight, gravidity, Abortion times, menelipsis weeks, menstrual cycle between the two groups(P>0.05).
2.The value of ACT a、INH a、β-hCGwere 0.24±0.17ng/ml,26.4±4.33 pg/ml,6673.2±3636.4mlu/ml in the tubal pregnancy group.They were 0.51±0.31ng/ml,44.85±6.22 pg/ml, 10112.2±7600.7mIu/ml in the intrauterine pregnancy group.There were difference between the two groups(P<0.05).
3..Determined by ROC, The best cut off value of ACT A was 0.35 ng/ml with the sensitivity specificity was 93%,20%. The best cut off value of INH A was 28.6 ng/ml with the sensitivity specificity was 90%,32%;The best cut off value ofβ-hCG was 3236.6 mlu/ml with the sensitivity specificity was 88%,60%.
4. ACT A and INH A are expressed in the endometrial tissues of intrauterine pregnancy and tubal pregnancy, ACT A and INH A of the endometrial tissues has no value in the diagnosis of early tubal pregnancy.
Conclusions:1. ACT A and INH A has some value in the diagnosis of early ectopic pregnancy.2. The best cut off value of ACT A was 0.35 ng/ml with the sensitivity specificity was 93%,20%. The best cut off value of INH A was 28.6 ng/ml with the sensitivity specificity was 90%,32%; The best cut off value ofβ-hCG was 3236.6 mIu/ml with the sensitivity specificity was 88%,60%.3. The diagnostie of the combination ACT A、INH A andβ-hCG has no value.4. ACT A and INH A are expressed in the endometrial tissues of intrauterine pregnancy and ectopic pregnancy, ACT A and INH A of the endometrial tissues has no value in the diagnosis of early ectopic pregnancy.
方法：选取自2008年11月至2009年10月山西医科大学第二医院门诊及住院患者80例作为研究对象。对于全部符合纳入标准的病人,根据妊娠结局或组织学检查分为：A组：宫内妊娠组,B组：输卵管妊娠组。病人于治疗前抽取静脉血5ml,置于非抗凝试管中,静置1h,3000转／分,离心10分钟,吸取离心后的血清,置于-70℃的冰箱内保存待检。宫内妊娠组人流前及输卵管妊娠组术前行诊刮术取子宫内膜组织,常温下保存于福尔马林液待检；
血清采用固相夹心法酶联免疫吸附试验(ELISA)测定,所得数据应用SPSS11.5统计软件包进行统计学分析。正态分布资料用均数、标准差描述,两组均数间差别比较采用t检验(Sutdent'-test)o分别作血清ACT A、INH A受试者工作曲线(ROC),确定ACTA、INHA的诊断界值及其诊断输卵管妊娠的灵敏度、特异度。并应用四格表分析联合诊断早期输卵管妊娠的灵敏度、特异度。内膜组织采用免疫组化法测定,计算其在子宫内膜组织的表达率,P<0.05为差别有统计学意义。
结果：1.两组患者年龄、身高、体重、孕次、流产次数、停经天数、月经周期的比较差别均无统计学意义(P>0.05)；2.输卵管妊娠组ACT A、INH A、β-hCG水平分别为0.24±0.17ng/ml,26.4±4.33 pg/ml,6673.2±3636.4mIu/ml,宫内妊娠组的0.51±0.31ng/ml, 44.85±6.22pg/ml,10112.2±7600.7mIu/ml,应用两组比较的t检验,差别有统计学意义；3.用ROC曲线进行分析：ACT A的ROC曲线下面积为0.57,最佳截断值是0.35 ng/ml,灵敏度93%,特异度20%,阳性似然比见、阴性似然比为1.1、0.25;INH A曲线下面积为0.71,最佳截断值是28.6pg/ml,灵敏度90%,特异度32%,阳性似然比2.58,阴性似然比0.32；β-hCG曲线下面积为0.73,最佳截断值是3236.6 mIu/ml,灵敏度88%,特异度60%。4.ACTA、INH A在子宫内膜组织中的表达率,差别无统计学意义。
结论：1. ACT A和INH A对输卵管妊娠的早期诊断有一定价值。2. ACT A最佳截断值0.35ng/ml,灵敏度93%,特异度20%；INH A最佳截断值28.6 ng/ml,灵敏度90%,特异度32%。3. ACT A、INH A与β-hCG联合诊断价值不大。4.ACT A和INH A在宫内妊娠和输卵管妊娠的子宫内膜组织中都有表达,但是没有统计学意义,没有诊断价值。
objective:Ectopic pregnancy(EP) is a frequent surgical abdomen of obstetrics and gynecology, the incidence of which is rising in the recent twenty years. The developing of diagnostic techniques can reduce the rate of misdiagnosis and missed diagnosis, in order to create favorable conditions for better reserve fertility and conservative treatment of EP. The most common methods of early diagnosis of ectopic pregnancy are using ultrasound with serial measurements of human chorionic gonadotropin (β-hCG). However, these cannot find the embryo as early as gestational 4-5weeks,not only for EP, but also for intrauterine pregnnacy. .The objective of this study was to explore the possibility that an isolated measurement of Activin、Inhibin rather thanβ-hCG could be used as a single test for ectopic pregnancy, And the significant of compound of Activin、Inhibit、β-hCG in the diagnosis of ectopic pregnancy.
Methods:From November 2008 to October 2009, There were 80 cases that met the criteria altogether,serum samples were collected in the Second Hospital of Shanxi Medical University. The blood samples were centrifuged 3000r/min for 10 minutes and placed in-70℃refrigerator kept for inspection.Activin、Inhibin and P-hCG was determined by ELISA.The data was analyzed by SPSS 11.5 of windows statistical package.Data of Normal distribution were described with mean and Standard deviation.The comparison of the difference of Means of two groups was processed by student't-test and ROC curve which was drawn concerning serum Activin A、Inhibin A、β-hCG. The area below the cuvre was calculated. Youden index was used to determine the cut-off Point of Activin A、Inhibin A and their sensitivity, specificity. It meant significant if P<0.05. Endometrial tissue was determined by immunohistochemistry method, Calculated positive rate of endometrial tissues. It meant significant if P<0.05.
Results:1. There was no significant diffrence on age, height, weight, gravidity, Abortion times, menelipsis weeks, menstrual cycle between the two groups(P>0.05).
2.The value of ACT a、INH a、β-hCGwere 0.24±0.17ng/ml,26.4±4.33 pg/ml,6673.2±3636.4mlu/ml in the tubal pregnancy group.They were 0.51±0.31ng/ml,44.85±6.22 pg/ml, 10112.2±7600.7mIu/ml in the intrauterine pregnancy group.There were difference between the two groups(P<0.05).
3..Determined by ROC, The best cut off value of ACT A was 0.35 ng/ml with the sensitivity specificity was 93%,20%. The best cut off value of INH A was 28.6 ng/ml with the sensitivity specificity was 90%,32%;The best cut off value ofβ-hCG was 3236.6 mlu/ml with the sensitivity specificity was 88%,60%.
4. ACT A and INH A are expressed in the endometrial tissues of intrauterine pregnancy and tubal pregnancy, ACT A and INH A of the endometrial tissues has no value in the diagnosis of early tubal pregnancy.
Conclusions:1. ACT A and INH A has some value in the diagnosis of early ectopic pregnancy.2. The best cut off value of ACT A was 0.35 ng/ml with the sensitivity specificity was 93%,20%. The best cut off value of INH A was 28.6 ng/ml with the sensitivity specificity was 90%,32%; The best cut off value ofβ-hCG was 3236.6 mIu/ml with the sensitivity specificity was 88%,60%.3. The diagnostie of the combination ACT A、INH A andβ-hCG has no value.4. ACT A and INH A are expressed in the endometrial tissues of intrauterine pregnancy and ectopic pregnancy, ACT A and INH A of the endometrial tissues has no value in the diagnosis of early ectopic pregnancy.
引文
[1]乐杰主编,妇产科学,第七版：人民卫生出版社,2008,105—112.
[2]Anderson W J, Frankmd, Hogan M P H, et al. Sudden death, ectopitic pregnancy, mortality [1].Am Coll Obstet Gyne,2004,103 (6):1218-1223
[3]Kurt T,Barnhart,Paolo R,et al.Acute and chronic presentation of ectopic pregnancy may be two clinical entities.Fertility And Sterility,2003,80(6):1345-1451.
[4]Florio P, Severi FM, Bocchi C, et al.Single serum activin a testing to predict ectopic pregnancy[J]. J Clin Endocrinol Metab,2007,92(5):1748-1753.
[5]Segal S, Gor H, Correa N, et al.Inhibin A:marker for diagnosis of ectopic and early abnormal pregnancies[J]. Reprod Biomed Online,2008,17(6):789-794.
[6]Michel E, Riv IIN, Rick W M. Manual of clinical problems in obstertrics an gynecology [M]. Lipp incott Williams Ilkins Inc 2001:10-11.
[7]Cole LA. Human chorionic gonadotropin and associated molecules[J]. Expert Rev Mol Diagn,2009,9(1):51-73.
[8]Borrelli PT,Butler SA,Docherty SM, et al. Human chorionic gonadotropin isoforms in the diagnosis of ectopic Pregnancy.Clin Chem 2003, 49:2045-2049.
[9]Lozeau AM, Potter B. Diagnosis and management of ectopic pregnancy[J]. Am Fam Physician,2005,72(9):1707-1714.
[10]Ohnishi N,Miyata T,Ohnishi H,et al.Activin A is an autocrine activator of rat pancreatic stellate cells:otentialtherapeutic role of follistatin for pancreatic fibrosis [J].Gut,2003,52(10):1487-1493.
[11]Liu ZH,Shintani Y,Wakatsuki M,et al.Regulation of immunoreactive activin A secretion from cultured rat anterior pituitary cells[J].Endocrine J,1996,43(1):39.
[12]Emily PT, Tierney BS,Linda CG, et al. Role of activin A as a mediator of in vitro endomet rial stromal cell decidualization via the cyclic adenosine monophosphate pathway [J]. Fertil Steril,2004,81[Suppl 1]:899-903.
[13]Welt C,Sidis Y, Keutmann H, et al. Activins, inhibins, and follistatins:from endocrinology to signaling:a paradigm for the new millennium[J].Exp Biol Med (Maywood), 2002,227(9):724-752.
[14]Emma Kirkl,8, Aris T. Papageorghiou2, Ben Van Calster3, et al. The use of serum inhibin A and activin A levels in predicting the outcome of pregnancies of unknown location [J].Human Reproduction, Vol.24, No.10 pp.2451-2456,2009 Advanced Access publication on June 23,2009.
[15]Abe Y et al. [J]Clin Endocrinol Metab,1990;71:133-137.
[16]Jones RL,Salamonsen LA,Findlay JK.Activin A promotes human endometrial stromal cell decidualization in vitro[J].J Clin Endocrinol Metab,2002,87(8):4001-4004.
[1]Cole LA. Human chorionic gonadotropin and associated molecules[J]. Expert Rev Mol Diagn,2009,9(1):51-73.
[2]Agostini A, Blanc K, Ronda I, et al. Prognostic value of human chorionic gonadotropin changes after methotrexate injection for ectopic pregnancy [J].Fertil Stertil,2007, 88(2):504-506.
[3]Cabar FR, Pereira PP, Schultz R, et al. Predictive factors of trophoblastic invasion into the ampullary region of the tubal wall in ectopic pregnancy [J]. H Reprod,2006,21(9):2426-2431.
[4]Menon S, Colins J, Barnhart KT et al. Establishing a human chorionic gonadotropin cut off to guide methotexate treatment of ectopic pregnancy:a systematic review[J].Fertil Steril,2007,87(3):481-484.
[5]Elito Junior J,Montenegro NA,Soares Rda C, et al. Unruptured ectopic pregnancy:diagnosis and treatment. State of art.Rev Bras Ginecol Obstet,2008,30(3):149-159.
[6]Shippey SH, Bhoola SM, Royek AB, et al. Diagnosis and management of hepatic ectopic pregnancy [J].Obstet Gynecol,2007,109(2 pt2):544-546.
[7]Fu J, Henne MB, Blusmstein S, et al.Rupture of ectopic pregnancy with minimally detectable beta-human chorionic gonadotropin levels:a report of 2 cases.[J].J Reprod Med,2007,52(6): 541-542.
[8]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 [J]. Eur J Obstet Gynecol Reprod Biol,2006,125(2):226-232.
[9]Cabar FR, Fettback PB,Pereira PP, et al. Serum markers in the diagnosis of tubal pregnancy.CLINICS,2008;63(5):701-708.
[10]El Bishry G, Ganta S. The role of single serum progesterone measurement in conjunction with beta hCG in the management of suspected ectopic pregnancy[J]. J Obstet Gynaecol, 2008,28(4):413-417.
[11]Basu A, Maitra SK, Shrivastav TG.Development of dual-enzyme-based simultaneous immunoassay for measurement of progesterone and human chorionic gonadotropin. [J]. Anal Biochem.2007,366(2):175-181.
[12]Daponte A, Pournaras S, Zintzaras E, et al. The value of a single combined measurement of VEGF, glycodelin, progesterone, PAPP-A, HPL and LIF for differentiating between ectopic and abnormal intrauterine pregnancy[J]. Hum Reprod,2005,20(11):3163-3166.
[13]Fasouliotis SJ,Spandorfer SD,Witkin SS, et al. Maternal serum vascular endothelial growth factor levels in early ectopic and intrauterine pregnancies after in vitro fertilization treatment [J]. Fertil Steril,2004,82(2):309-313.
[14]Ugurlu EN, Ozaksit G, Karaer A, et al. The value of vascular endothelial growth factor, pregnancy-associated plasma protein-A, and progesterone for early differentiation of ectopic pregnancies, normal intrauterine pregnancies, and spontaneous miscarriages[J]. Fertil Steril,2008:8.
[15]Ugurlu EN, Ozaksit G, Karaer A, et al. The value of vascular endothelial growth factor, pregnancy-associated plasma protein-A, and progesterone for early differentiation of ectopic pregnancies, normal intrauterine pregnancies, and spontaneous miscarriages[J]. Fertil Steril,2009,91(5):1657-1661.
[16]Tierney EP,Giudice LC.Role of activin A as a mediator of in vitro endometral stromal cell decidualization via the cyclic adenosine monophosphate pathway [J].Fertil Steril,2004,81(Suppl 1):899-903.
[17]Refaat B, Amer S, Ola B, et al. The expression of activin-betaA-and-betaB-subunits, follistatin, and activin type Ⅱ receptors in fallopian tubes bearing an ectopic pregnancy[J]. J Clin Endocrinol Metab,2008,93(1):293-299.
[18]Florio P, Severi FM, Bocchi C, et al.Single serum activin a testing to predict ectopic pregnancy[J]. J Clin Endocrinol Metab,2007,92(5):1748-1753.
[19]Segal S, Gor H, Correa N, et al.Inhibin A:marker for diagnosis of ectopic and early abnormal pregnancies[J]. Reprod Biomed Online,2008,17(6):789-794.
[2]Anderson W J, Frankmd, Hogan M P H, et al. Sudden death, ectopitic pregnancy, mortality [1].Am Coll Obstet Gyne,2004,103 (6):1218-1223
[3]Kurt T,Barnhart,Paolo R,et al.Acute and chronic presentation of ectopic pregnancy may be two clinical entities.Fertility And Sterility,2003,80(6):1345-1451.
[4]Florio P, Severi FM, Bocchi C, et al.Single serum activin a testing to predict ectopic pregnancy[J]. J Clin Endocrinol Metab,2007,92(5):1748-1753.
[5]Segal S, Gor H, Correa N, et al.Inhibin A:marker for diagnosis of ectopic and early abnormal pregnancies[J]. Reprod Biomed Online,2008,17(6):789-794.
[6]Michel E, Riv IIN, Rick W M. Manual of clinical problems in obstertrics an gynecology [M]. Lipp incott Williams Ilkins Inc 2001:10-11.
[7]Cole LA. Human chorionic gonadotropin and associated molecules[J]. Expert Rev Mol Diagn,2009,9(1):51-73.
[8]Borrelli PT,Butler SA,Docherty SM, et al. Human chorionic gonadotropin isoforms in the diagnosis of ectopic Pregnancy.Clin Chem 2003, 49:2045-2049.
[9]Lozeau AM, Potter B. Diagnosis and management of ectopic pregnancy[J]. Am Fam Physician,2005,72(9):1707-1714.
[10]Ohnishi N,Miyata T,Ohnishi H,et al.Activin A is an autocrine activator of rat pancreatic stellate cells:otentialtherapeutic role of follistatin for pancreatic fibrosis [J].Gut,2003,52(10):1487-1493.
[11]Liu ZH,Shintani Y,Wakatsuki M,et al.Regulation of immunoreactive activin A secretion from cultured rat anterior pituitary cells[J].Endocrine J,1996,43(1):39.
[12]Emily PT, Tierney BS,Linda CG, et al. Role of activin A as a mediator of in vitro endomet rial stromal cell decidualization via the cyclic adenosine monophosphate pathway [J]. Fertil Steril,2004,81[Suppl 1]:899-903.
[13]Welt C,Sidis Y, Keutmann H, et al. Activins, inhibins, and follistatins:from endocrinology to signaling:a paradigm for the new millennium[J].Exp Biol Med (Maywood), 2002,227(9):724-752.
[14]Emma Kirkl,8, Aris T. Papageorghiou2, Ben Van Calster3, et al. The use of serum inhibin A and activin A levels in predicting the outcome of pregnancies of unknown location [J].Human Reproduction, Vol.24, No.10 pp.2451-2456,2009 Advanced Access publication on June 23,2009.
[15]Abe Y et al. [J]Clin Endocrinol Metab,1990;71:133-137.
[16]Jones RL,Salamonsen LA,Findlay JK.Activin A promotes human endometrial stromal cell decidualization in vitro[J].J Clin Endocrinol Metab,2002,87(8):4001-4004.
[1]Cole LA. Human chorionic gonadotropin and associated molecules[J]. Expert Rev Mol Diagn,2009,9(1):51-73.
[2]Agostini A, Blanc K, Ronda I, et al. Prognostic value of human chorionic gonadotropin changes after methotrexate injection for ectopic pregnancy [J].Fertil Stertil,2007, 88(2):504-506.
[3]Cabar FR, Pereira PP, Schultz R, et al. Predictive factors of trophoblastic invasion into the ampullary region of the tubal wall in ectopic pregnancy [J]. H Reprod,2006,21(9):2426-2431.
[4]Menon S, Colins J, Barnhart KT et al. Establishing a human chorionic gonadotropin cut off to guide methotexate treatment of ectopic pregnancy:a systematic review[J].Fertil Steril,2007,87(3):481-484.
[5]Elito Junior J,Montenegro NA,Soares Rda C, et al. Unruptured ectopic pregnancy:diagnosis and treatment. State of art.Rev Bras Ginecol Obstet,2008,30(3):149-159.
[6]Shippey SH, Bhoola SM, Royek AB, et al. Diagnosis and management of hepatic ectopic pregnancy [J].Obstet Gynecol,2007,109(2 pt2):544-546.
[7]Fu J, Henne MB, Blusmstein S, et al.Rupture of ectopic pregnancy with minimally detectable beta-human chorionic gonadotropin levels:a report of 2 cases.[J].J Reprod Med,2007,52(6): 541-542.
[8]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 [J]. Eur J Obstet Gynecol Reprod Biol,2006,125(2):226-232.
[9]Cabar FR, Fettback PB,Pereira PP, et al. Serum markers in the diagnosis of tubal pregnancy.CLINICS,2008;63(5):701-708.
[10]El Bishry G, Ganta S. The role of single serum progesterone measurement in conjunction with beta hCG in the management of suspected ectopic pregnancy[J]. J Obstet Gynaecol, 2008,28(4):413-417.
[11]Basu A, Maitra SK, Shrivastav TG.Development of dual-enzyme-based simultaneous immunoassay for measurement of progesterone and human chorionic gonadotropin. [J]. Anal Biochem.2007,366(2):175-181.
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