計金雙，倪洋洋，賈文娟，盧湘怡，王潔爽，黃磊

輸卵管妊娠破裂的相關(guān)危險因素分析

計金雙1，倪洋洋1，賈文娟1，盧湘怡1，王潔爽1，黃磊2

1.江漢大學醫(yī)學院，湖北武漢 430056；2.武漢市中心醫(yī)院婦科，湖北武漢 430014

探討輸卵管妊娠破裂的相關(guān)危險因素?；仡櫺苑治鑫錆h市中心醫(yī)院2017—2021年婦科收治住院的輸卵管妊娠病例的臨床特征，將其分為輸卵管妊娠破裂組與未破裂組。采用2檢驗、檢驗、非參數(shù)檢驗進行兩組的差異比較，用受試者操作特征曲線（receiver operating characteristic curve，ROC曲線）分析相關(guān)變量找到最佳臨界值，通過多元二項邏輯回歸分析發(fā)現(xiàn)危險因素。共納入885例輸卵管妊娠，其中未破裂患者780例（88.1%），破裂患者105例（11.9%）。主要癥狀（腹痛、陰道出血）、輸卵管妊娠類型、B超包塊最大直徑和術(shù)前人絨毛膜促性腺激素（human chorionic gonadotropin，HCG）水平差異有統(tǒng)計學意義（<0.001）。多元二項邏輯回歸分析顯示，年齡、停經(jīng)天數(shù)與輸卵管妊娠破裂無關(guān)（>0.05）。B超包塊最大直徑>3.5cm（=3.966，95%：2.473～6.358，<0.001）和術(shù)前血清HCG>2600mIU/ml （4.756，95%：2.916～7.759，<0.001）是輸卵管妊娠破裂的重要危險因素。當輸卵管妊娠患者的B超包塊最大直徑>3.5cm及術(shù)前血清HCG>2600mIU/ml時可能有破裂的風險。

輸卵管妊娠；異位妊娠；破裂；危險因素；人絨毛膜促性腺激素

異位妊娠占妊娠的1%～2%[1-2]。其中，輸卵管妊娠占異位妊娠的90%以上[3]。異位妊娠破裂引起的出血是孕產(chǎn)婦早期死亡的主要原因[1,3]。2011—2013年美國因輸卵管妊娠破裂導致的死亡人數(shù)占所有妊娠相關(guān)死亡人數(shù)的2.7%[4]。在非洲，每100例異位妊娠中約有1例孕婦死于輸卵管妊娠破裂[5]。在既往的報道中，異位妊娠的破裂率為14.0%～20.2%[6-7]。然而，在另一項研究中，92例輸卵管妊娠中有91例輸卵管妊娠破裂[8]。近年來，隨著診斷方法的改進，異位妊娠相關(guān)的死亡率有所下降，但仍缺少準確判斷及預防輸卵管妊娠破裂的方法。本研究通過回顧性分析輸卵管妊娠患者的臨床特征，分析變量的差異，利用多元二項邏輯回歸分析輸卵管妊娠破裂的風險因素。

1 資料與方法

1.1 一般資料

回顧性分析武漢市中心醫(yī)院2017—2021年收治住院的輸卵管妊娠病例，根據(jù)輸卵管妊娠是否破裂將其分為輸卵管妊娠破裂組與未破裂組。向醫(yī)院信息科申請脫敏數(shù)據(jù)，缺失信息向醫(yī)院醫(yī)學資訊科申請補錄。輸卵管妊娠診斷：均經(jīng)腹腔鏡手術(shù)及病理診斷[3]。納入標準：確診為輸卵管間質(zhì)部妊娠；輸卵管峽部妊娠；輸卵管壺腹部妊娠；輸卵管傘部妊娠。排除標準：病例信息缺失。本研究經(jīng)武漢市中心醫(yī)院倫理委員會批準（倫理審批號：WHZXKYL2022-034）。

1.2 研究變量

患者的臨床特征：①臨床表現(xiàn)：停經(jīng)天數(shù)、主要癥狀（腹痛、陰道出血）；②B超與實驗室檢查資料：B超包塊最大直徑（cm）與內(nèi)膜厚度（cm），術(shù)前人絨毛膜促性腺激素（human chorionic gonadotropin，HCG）（mIU/ml）；③輸卵管妊娠部位、輸卵管妊娠類型；④既往史：人工流產(chǎn)史、異位妊娠史、剖宮產(chǎn)史。

1.3 統(tǒng)計學方法

2 結(jié)果

2.1 輸卵管妊娠患者的臨床特征比較

兩組患者的年齡、產(chǎn)次、停經(jīng)天數(shù)、B超檢查的內(nèi)膜厚度、輸卵管妊娠部位、異位妊娠史、剖宮產(chǎn)史、人工流產(chǎn)史差異無統(tǒng)計學意義（>0.05），見表1。

表1 兩組患者的臨床特征比較

2.2 輸卵管妊娠破裂患者的危險因素分析

血清HCG和B超包塊最大直徑預測輸卵管妊娠破裂的受試者操作特征曲線（receiver operating characteristic curve，ROC曲線）見圖1。血清HCG的曲線下面積（area under the curve，AUC）為0.731。血清HCG濃度對輸卵管妊娠破裂的最佳預測水平為2578.45mIU/ml，臨界值顯示敏感度72.0%，特異性66.0%，陽性預測值（positive predictive value，PPV）21.3%，陰性預測值（negative predictive value，NPV）94.8%。取2600mIU/ml為臨界值。B超包塊最大直徑的AUC為0.678。B超包塊最大直徑對輸卵管妊娠破裂的最佳預測為3.45cm，臨界值顯示敏感度62.0%，特異性為70.0%，PPV 22.0%，NPV 93.2%。取3.5cm為臨界值。

圖1 血清HCG和B超包塊最大直徑預測輸卵管妊娠破裂的ROC曲線

多元二項邏輯回歸顯示，術(shù)前血清HCG>2600mIU/ml （=4.756，95%：2.916～7.759，<0.001）和B超包塊最大直徑>3.5cm（=3.966，95%：2.473～6.358，<0.001）是輸卵管妊娠破裂的重要危險因素。既往有異位妊娠史（=0.363，95%：0.137～0.960，=0.041）、人工流產(chǎn)史（=0.591，95%：0.368～0.948，=0.029）是輸卵管妊娠破裂的保護性因素。年齡、停經(jīng)天數(shù)與輸卵管妊娠破裂無明顯相關(guān)（>0.05），見表2。

3 討論

本研究通過回顧性分析輸卵管妊娠患者的臨床特征，利用多元二項邏輯回歸分析，探討輸卵管妊娠破裂的風險因素。主要發(fā)現(xiàn)B超包塊最大直徑>3.5cm和術(shù)前HCG>2600mIU/ml的輸卵管妊娠患者可能有破裂的風險，既往異位妊娠史、人工流產(chǎn)史是輸卵管妊娠破裂的保護性因素。在輸卵管妊娠的治療中，臨床醫(yī)生應重點關(guān)注輸卵管妊娠破裂風險較高的患者。

較高的輸卵管妊娠破裂率可能是由于該類患者沒有明顯的體征，導致診斷延誤[6-7]。本研究中，輸卵管破裂的發(fā)生率為11.9%，比既往研究低，分析原因：一方面大部分患者有腹痛、陰道流血等癥狀，所以就診及時；另一方面，因研究期間疫情的原因?qū)е戮驮\患者人數(shù)減少。本研究中，73.3%的輸卵管妊娠破裂位于壺腹部，無間質(zhì)部與傘部妊娠的病例，與既往研究結(jié)果一致[9-10]。B超診斷輸卵管妊娠有較高的敏感度和特異性，尤其床旁超聲能快速診斷輸卵管妊娠破裂，為臨床治療節(jié)約時間[6,11-12]。

本研究表明，血清HCG>2600mIU/ml的輸卵管妊娠患者更容易發(fā)生破裂?？紤]隨著血清HCG水平的升高，滋養(yǎng)細胞活性程度高，侵蝕能力增強，滋養(yǎng)細胞破壞輸卵管管壁從而導致異位妊娠破裂的可能性更大[14]。有研究表明，血清HCG>1750mIU/ml發(fā)生輸卵管妊娠破裂的可能性較大[7]；另有研究認為HCG為1500～3000mIU/ml發(fā)生輸卵管妊娠破裂的可能性較大[15-16]。本研究發(fā)現(xiàn)異位妊娠史是輸卵管妊娠破裂的保護性因素，這與其他研究不同[17-18]。可歸因于本研究中既往有異位妊娠史的輸卵管妊娠破裂患者僅6例，存在偏倚。有研究報道，年齡>35歲會增加異位妊娠的風險，但本研究未得出相關(guān)結(jié)論[19]。

表2 輸卵管妊娠破裂患者的多元二項邏輯回歸分析

注：*表示輸卵管妊娠破裂組，以未破裂組為參照

[1] Centers for Disease Control and Prevention(CDC). Ectopic pregnancy–United States, 1990—1992[J]. MMWR Morb Mortal Wkly Rep, 1995, 44(3): 46–48.

[2] HSU J Y, CHEN L, GUMER A R, et al. Disparities in the management of ectopic pregnancy[J]. Am J Obstet Gynecol, 2017, 217(1): 1–49.

[3] AmericanCollegeofObstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology. Acog practice bulletin no. 193: Tubal ectopic pregnancy[J]. Obstet Gynecol, 2018, 131(3): e91–e103.

[4] CREANGA A A, SYVERSON C, SEED K, et al. Pregnancy-related mortality in the United States, 2011-2013[J]. Obstet Gynecol, 2017, 130(2): 366–373.

[5] LEKE R J, GOYAUX N, MATSUDA T, et al. Ectopic pregnancy in Africa: A population-based study[J]. Obstet Gynecol, 2004, 103(4): 692–697.

[6] URQUHART S, BARNES M, FLANNIGAN M. Comparing time to diagnosis and treatment of patients with ruptured ectopic pregnancy based on type of ultrasound performed: A retrospective inquiry[J]. J Emerg Med, 2022, 62(2): 200–206.

[7] FARAJI DARKHANEH R, ASGHARNIA M, FARAHMAND PORKAR N, et al. Predictive value of maternal serum β-HCG concentration in the ruptured tubal ectopic pregnancy[J]. Iran J Reprod Med, 2015, 13(2): 101–106.

[8] AWOLEKE J O, ADANIKIN A I, AWOLEKE A O. Ruptured tubal pregnancy: Predictors of delays in seeking and obtaining care in a Nigerian population[J]. Int J Womens Health, 2015, 7: 141–147.

[9] JOB-SPIRA N, FERNANDEZ H, BOUYER J, et al. Ruptured tubal ectopic pregnancy: Risk factors and reproductive outcome: Results of a population-based study in France[J]. Am J Obstet Gynecol, 1999, 180(4): 938–944.

[10] BOUYER J, COSTE J, FERNANDEZ H, et al. Sites of ectopic pregnancy: A 10 year population-based study of 1800 cases[J]. Hum Reprod, 2002, 17(12): 3224–3230.

[11] STONE B S, MURUGANANDAN K M, TONELLI M M, et al. Impact of point-of-care ultrasound on treatment time for ectopic pregnancy[J]. Am J Emerg Med, 2021, 49: 226–232.

[12] TIMOR-TRITSCH I E, YEH M N, PEISNER D B, et al. The use of transvaginal ultrasonography in the diagnosis of ectopic pregnancy[J]. Am J Obstet Gynecol, 1989, 161(1): 157–161.

[13] CACCIATORE B. Can the status of tubal pregnancy be predicted with transvaginal sonography? A prospective comparison of sonographic, surgical, and serum hcg findings[J]. Radiology, 1990, 177(2): 481–484.

[14] Practice Committeeof the American Society for Reproductive Medicine. Early diagnosis and management of ectopic pregnancy[J]. Fertil Steril, 2004, 82 Suppl 1: S146–S148.

[15] GOKSEDEF B P C, KEF S, AKCA A, et al. Risk factors for rupture in tubal ectopic pregnancy: Definition of the clinical findings[J]. Eur J Obstet Gynecol Reprod Biol, 2011, 154(1): 96–99.

[16] FUKAMI T, TSUJIOKA H, MATSUOKA S, et al. Rupture risk factors of fallopian tubal pregnancy[J]. Clin Exp Obstet Gynecol, 2016, 43(6): 800–802.

[17] SINDOS M, TOGIA A, SERGENTANIS T N, et al. Ruptured ectopic pregnancy: Risk factors for a life-threatening condition[J]. Arch Gynecol Obstet, 2009, 279(5): 621–623.

[18] LATCHAW G, TAKACS P, GAITAN L, et al. Risk factors associated with the rupture of tubal ectopic pregnancy[J]. Gynecol Obstet Invest, 2005, 60(3): 177–180.

[19] CORREA-DE-ARAUJO R, YOON S S S. Clinical outcomes in high-risk pregnancies due to advanced maternal age[J]. J Womens Health(Larchmt), 2021, 30(2): 160–167.

Analysis of risk factors associated with ruptured tubal pregnancy

JI Jinshuang, NI Yangyang, JIA Wenjuan, LU Xiangyi, WANG Jieshuang, HUANG Lei

1.Medical College, Jianghan University, Wuhan 430056, Hubei, China; 2.Department of Gynecology, the Central Hospital of Wuhan, Wuhan 430014, Hubei, China

The aim of study was to explore the risk factors associated with ruptured tubal pregnancy.We retrospectively studied the clinical characteristics of inpatients with tubal pregnancy in the Central Hospital of Wuhan during 2017-2021 and divided them into ruptured and unruptured groups. The clinical characteristics of two groups were compared by2test,test, and nonparametric test. Analysis of correlation variables with receiver operating characteristic (ROC) curve to find optimal prediction value. Multivariate binomial logistic regression to analyze the relevant variables to find risk factors.There were 855 patients with tubal pregnancy, of which 780 (88.1%) were unruptured and 105 (11.9%) were ruptured. The main symptom (abdominal pain, vaginal bleeding), the type of tubal pregnancy, the maximum diameter of cladding block by ultrasound and the preoperative human chorionic gonadotropin (HCG) in two groups were significantly different (<0.001). In multivariate binomial logistic regression analysis, the variables of age, menstrual days, history of induced abortion were not linked to the ruptured ectopic pregnancy significantly (>0.05). And the maximum diameter of cladding block by ultrasound (3.966, 95%: 2.473-6.358,<0.001) and the preoperative serum HCG value>2600mIU/ml (4.756, 95%: 2.916-7.759,<0.001) were the important risk factors to the ruptured tubal pregnancy.When the maximum diameter of the B-ultrasound mass in patients with tubal pregnancy was greater than 3.5 cm and the preoperative serum HCG was greater than 2600mIU/ml, there may be a risk of rupture.

Tubal pregnancy; Ectopic pregnancy; Rupture; Risk factor; Human chorionic gonadotropin

R711

A

10.3969/j.issn.1673-9701.2023.27.015

黃磊，電子信箱：1084488372@qq.com

（2022–12–20）

（2023–09–05）