Risk factors and early diagnosis of persistent ectopic pregnancy in fallopian tubal pregnancy patients: propensity score matching analysis

doi:10.3877/cma.j.issn.1673-5250.2020.02.009

Objective

To explore risk factors and early diagnosis method of persistent ectopic pregnancy (PEP) in fallopian tubal pregnancy (FTP) patients based on propensity score matching (PSM) analysis.

Methods

From January 2011 to December 2018, a total of 17 patients with FTP who underwent laparoscopic conservative operations therapy (COT) in the West China Second University Hospital of Sichuan University and developed to PEP after operation were selected as research subjects and included into PEP group. At the same time, 148 patients who received laparoscopic COT in our hospital during the same period and recovered well after operation were randomly selected as control group. Clinical data of patients in two groups were collected by retrospective analysis. Mann-Whitney U test was used to compare the duration of serum β-human chorionic gonadotropin (hCG) decreased to <20 mIU/mL and <10 mIU/mL after operation, and the decrease ratio of serum β-hCG within 24-48 h after operation compared with that before operation in two matched groups. The incidence rates of pelvic adhesion, tubal interstitial and ampulla pregnancy were compared by chi-square test. The receiver operator characteristic (ROC) curve of decrease ratio of serum β-hCG within 24-48 h after operation compared with that before operation for diagnosis of PEP in FTP patients after COT was drawn and the area under ROC curve (ROC-AUC) was calculated. According to the maximum principle of Youden index, the optimal cut-off value of decrease ratio of serum β-hCG within 24-48 h after operation compared with that before operation for diagnosis of PEP in FTP patients after COT was determined. This study met the requirements of World Medical Association Declaration of Helsinki revised in 2013.

Results

①After PSM, 65 patients in control group were matched successfully. There were no significant differences between two groups matched by PSM in terms of age, gravidity, body mass index (BMI) and menopause duration (P>0.05). ②After PSM, the incidence rates of pelvic adhesion and tubal interstitial pregnancy in PEP group were 88.2% (15/17) and 29.4% (5/17), respectively, which were significantly higher than those 61.5% (40/65) and 3.1% (2/65) in control group, and both the differences were statistically significant (χ²=4.349, P=0.037; χ²=8.834, P=0.003). ③After PSM, the duration of serum β-hCG decreased to <20 mIU/mL and <10 mIU/mL after operation in PEP group was 45.0 d (32.7-61.2 d) and 59.5 d (41.0-68.7 d), respectively, which were significantly longer than those 15.0 d (10.0-19.0 d) and 17.5 d (10.7-27.2 d) in control group, and both the differences were statistically significant (Z=4.703, 4.418; P<0.001). ④After PSM, the decrease ratio of serum β-hCG within 24-48 h after operation compared with that before operation in PEP group was 47.0% (-8.0%-70.1%), which was significantly lower than that 69.0% (61.2%-79.2%) in control group, and the difference was statistically significant (Z=3.506, P<0.001). The ROC-AUC of decrease ratio of serum β-hCG within 24-48 h after operation compared with that before operation for diagnosis of PEP in FTP patients after COT was 0.777 (95%CI: 0.626-0.929, P<0.001). According to the maximum principle of Youden index, the optimal cut-off value of decrease ratio of serum β-hCG within 24-48 h after operation compared with that before operation for diagnosis of PEP in FTP patients after COT was 52.9%, and the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, missed diagnosis rate and misdiagnosis rate were 64.7%, 95.4%, 78.6%, 91.2%, 89.0%, 35.3% and 4.6%, respectively.

Conclusions

Tubal interstitial pregnancy and pelvic adhesion may be high risk factors of PEP in FTP patients after COT. The decrease ratio of serum β-hCG within 24-48 h after operation compared with that before operation may be one of the indicators for early diagnosis of PEP in FTP patients after COT.

Key words: Pregnancy, tubal, Persistent ectopic pregnancy, Propensity score matching, Chorionic gonadotropin, beta subunit, human, Early diagnose, Female

表1 PSM前、后，2组患者一般临床资料比较

组别	PSM前					PSM后
组别	例数	年龄(岁，±s)	孕次[次，M(P₂₅～P₇₅)]	BMI(kg/m²，±s)	停经时间(d，±s)	例数	年龄(岁，±s)	孕次[次，M(P₂₅～P₇₅)]	BMI(kg/m²，±s)	停经时间(d，±s)
PEP组	17	29.2±5.6	3.0(2.0～4.0)	20.4±2.3	46.5±7.3	17	29.2±5.6	3.0(2.0～4.0)	20.4±2.3	46.5±7.3
对照组	148	30.2±5.3	2.0(1.0～3.0)	21.1±2.6	50.2±10.6	65	29.2±4.7	3.0(2.0～4.0)	20.7±2.7	46.3±7.9
检验值	?	t＝0.688	Z＝1.571	t＝0.928	t＝1.392	?	t＝0.003	Z＝0.404	t＝－0.374	t＝0.099
P值	?	0.493	0.116	0.355	0.166	?	0.997	0.687	0.709	0.921

表1 PSM前、后，2组患者一般临床资料比较

组别	PSM前					PSM后
组别	例数	年龄(岁，±s)	孕次[次，M(P₂₅～P₇₅)]	BMI(kg/m²，±s)	停经时间(d，±s)	例数	年龄(岁，±s)	孕次[次，M(P₂₅～P₇₅)]	BMI(kg/m²，±s)	停经时间(d，±s)
PEP组	17	29.2±5.6	3.0(2.0～4.0)	20.4±2.3	46.5±7.3	17	29.2±5.6	3.0(2.0～4.0)	20.4±2.3	46.5±7.3
对照组	148	30.2±5.3	2.0(1.0～3.0)	21.1±2.6	50.2±10.6	65	29.2±4.7	3.0(2.0～4.0)	20.7±2.7	46.3±7.9
检验值	?	t＝0.688	Z＝1.571	t＝0.928	t＝1.392	?	t＝0.003	Z＝0.404	t＝－0.374	t＝0.099
P值	?	0.493	0.116	0.355	0.166	?	0.997	0.687	0.709	0.921

表2 PSM后，2组患者术前相关临床资料比较

组别	例数	超声检查EP包块直径[cm，M(P₂₅～P₇₅)]	术前血清β-hCG水平[mIU/mL，M(P₂₅～P₇₅)]	既往EP史[例数(%)]	输卵管手术史[例数(%)]	其他盆腔手术史[例数(%)]	孕囊[例数(%)]	卵黄囊[例数(%)]	胎心搏动[例数(%)]
PEP组	17	3.0(2.1～3.9)	3 426.7(1 971.3～19 941.6)	3(17.6)	3(17.6)	6(35.3)	3(17.6)	3(17.6)	2(11.8)
对照组	65	3.1(2.2～3.8)	3 032.0(1 362.0～6 396.3)	25(38.5)	19(29.2)	17(26.2)	9(13.8)	8(12.3)	1(1.5)
检验值	?	Z＝0.452	Z＝1.355	χ²＝2.596	χ²＝0.426	χ²＝0.197	χ²<0.001	χ²＝0.031	—
P值	?	0.651	0.175	0.107	0.514	0.657	0.993	0.861	0.107

表2 PSM后，2组患者术前相关临床资料比较

组别	例数	超声检查EP包块直径[cm，M(P₂₅～P₇₅)]	术前血清β-hCG水平[mIU/mL，M(P₂₅～P₇₅)]	既往EP史[例数(%)]	输卵管手术史[例数(%)]	其他盆腔手术史[例数(%)]	孕囊[例数(%)]	卵黄囊[例数(%)]	胎心搏动[例数(%)]
PEP组	17	3.0(2.1～3.9)	3 426.7(1 971.3～19 941.6)	3(17.6)	3(17.6)	6(35.3)	3(17.6)	3(17.6)	2(11.8)
对照组	65	3.1(2.2～3.8)	3 032.0(1 362.0～6 396.3)	25(38.5)	19(29.2)	17(26.2)	9(13.8)	8(12.3)	1(1.5)
检验值	?	Z＝0.452	Z＝1.355	χ²＝2.596	χ²＝0.426	χ²＝0.197	χ²<0.001	χ²＝0.031	—
P值	?	0.651	0.175	0.107	0.514	0.657	0.993	0.861	0.107

表3 PSM后，2组患者术中情况比较

组别	例数	盆腔黏连[例数(%)]	左、右侧FTP[例数(%)]		FTP部位[例数(%)]			手术持续时间[min， M(P₂₅～P₇₅)]	术中失血量[mL，M(P₂₅～P₇₅)]
组别	例数	盆腔黏连[例数(%)]	左侧	右侧	间质部	壶腹部	伞部	手术持续时间[min， M(P₂₅～P₇₅)]	术中失血量[mL，M(P₂₅～P₇₅)]
PEP组	17	15(88.2)	3(17.6)	14(82.4)	5(29.4)	11(64.7)	1(5.9)	60.0(37.5～65.0)	150.0(32.5～400.0)
对照组	65	40(61.5)	27(41.5)	38(58.5)	2(3.1)	61(93.8)	2(3.1)	50.0(40.0～72.5)	150.0(60.0～245.0)
检验值	?	χ²＝4.349	χ²＝3.315		χ²＝8.834	χ²＝8.138	—	Z＝0.304	Z＝0.366
P值	?	0.037	0.069		0.003	0.004	0.507	0.761	0.714

表3 PSM后，2组患者术中情况比较

组别	例数	盆腔黏连[例数(%)]	左、右侧FTP[例数(%)]		FTP部位[例数(%)]			手术持续时间[min， M(P₂₅～P₇₅)]	术中失血量[mL，M(P₂₅～P₇₅)]
组别	例数	盆腔黏连[例数(%)]	左侧	右侧	间质部	壶腹部	伞部	手术持续时间[min， M(P₂₅～P₇₅)]	术中失血量[mL，M(P₂₅～P₇₅)]
PEP组	17	15(88.2)	3(17.6)	14(82.4)	5(29.4)	11(64.7)	1(5.9)	60.0(37.5～65.0)	150.0(32.5～400.0)
对照组	65	40(61.5)	27(41.5)	38(58.5)	2(3.1)	61(93.8)	2(3.1)	50.0(40.0～72.5)	150.0(60.0～245.0)
检验值	?	χ²＝4.349	χ²＝3.315		χ²＝8.834	χ²＝8.138	—	Z＝0.304	Z＝0.366
P值	?	0.037	0.069		0.003	0.004	0.507	0.761	0.714

表4 PSM后，2组患者术后血清β-hCG水平下降至<20 mIU/mL与<10 mIU/mL的时间，以及术后24～48 h血清β-hCG水平较术前下降率比较[M(P₂₅～P₇₅)]

组别	术后血清β-hCG水平下降至<20 mIU/mL的时间(d)		术后血清β-hCG水平下降至<10 mIU/mL的时间(d)		术后24～48 h血清β-hCG水平较术前下降率(%)
组别	例数^a	时间	例数^a	时间	例数	下降率
PEP组	14	45.0(32.7～61.2)	12	59.5(41.0～68.7)	17	47.0(－8.0～70.1)
对照组	34	15.0(10.0～19.0)	32	17.5(10.7～27.2)	65	69.0(61.2～79.2)
Z值	?	4.703	?	4.418	?	3.506
P值	?	<0.001	?	<0.001	?	<0.001

表4 PSM后，2组患者术后血清β-hCG水平下降至<20 mIU/mL与<10 mIU/mL的时间，以及术后24～48 h血清β-hCG水平较术前下降率比较[M(P₂₅～P₇₅)]

组别	术后血清β-hCG水平下降至<20 mIU/mL的时间(d)		术后血清β-hCG水平下降至<10 mIU/mL的时间(d)		术后24～48 h血清β-hCG水平较术前下降率(%)
组别	例数^a	时间	例数^a	时间	例数	下降率
PEP组	14	45.0(32.7～61.2)	12	59.5(41.0～68.7)	17	47.0(－8.0～70.1)
对照组	34	15.0(10.0～19.0)	32	17.5(10.7～27.2)	65	69.0(61.2～79.2)
Z值	?	4.703	?	4.418	?	3.506
P值	?	<0.001	?	<0.001	?	<0.001

图1 术后24～48 h血清β-hCG水平较术前下降率诊断FTP患者接受COT后发生PEP的ROC曲线

[1]	Ting WH, Lin HH, Hsiao SM. Factors predicting persistent ectopic pregnancy after laparoscopic salpingostomy or salpingotomy for tubal pregnancy: a retrospective cohort study [J]. J Minim Invasive Gynecol, 2019, 26(6): 1036-1043. DOI: 10.1016/j.jmig.2018.10.004.
[2]	Seifer DB, Diamond MP, DeCherney AH. Persistent ectopic pregnancy [J]. Obstet Gynecol Clin North Am, 1991, 18(1): 153-159.
[3]	Spandorfer SD, Sawin SW, Benjamin I, et al. Postoperative day 1 serum human chorionic gonadotropin level as a predictor of persistent ectopic pregnancy after conservative surgical management [J]. Fertil Steril, 1997, 68(3): 430-434. DOI: 10.1016/s0015-0282(97)00253-7.
[5]	Hsu MI, Tang CH, Hsu PY, et al. Primary and repeated surgeries for ectopic pregnancies and distribution by patient age, surgeon age, and hospital levels: an 11-year nationwide population-based descriptive study in Taiwan [J]. J Minim Invasive Gynecol, 2012, 19(5): 598-605. DOI: 10.1016/j.jmig.2012.05.008.
[4]	中国优生科学协会肿瘤生殖学分会. 输卵管妊娠诊治的中国专家共识[J]. 中国实用妇科与产科杂志，2019, 35(7): 780-787. DOI: 10.19538/j.fk2019070116.
[6]	王永吉. 倾向指数第一讲倾向指数的基本概念和研究步骤[J]. 中华流行病学杂志，2010, 31(3): 347-348. DOI: 10.3760/cma.j.issn.0254-6450.2010.03.026.
[7]	黄福强. 倾向评分配比在SPSS软件上的实现[J]. 南方医科大学学报，2015, 35(11): 1597-1601. DOI: 10.3969/j.issn.1673-4254.2015.11.15.
[8]	官静. 持续性异位妊娠高危因素探讨[J]. 华夏医学，2008, 21(1): 135-137. DOI: 10.3969/j.issn.1008-2409.2008.01.072.
[9]	Zhang Y, Chen J, Lu W, et al. Clinical characteristics of persistent ectopic pregnancy after salpingostomy and influence on ongoing pregnancy [J]. J Obstet Gynaecol Res, 2017, 43(3): 564-570. DOI: 10.1111/jog.13251.
[10]	Poppe WA, Vandenbussche N. Postoperative day 3 serum human chorionic gonadotropin decline as a predictor of persistent ectopic pregnancy after linear salpingotomy [J]. Eur J Obstet Gynecol Reprod Biol, 2001, 99(2): 249-252. DOI: 10.1016/s0301-2115(01)00397-9.
[11]	Kayatas S, Demirci O, Kumru P, et al. Predictive factors for failure of salpingostomy in ectopic pregnancy [J]. J Obstet Gynaecol Res, 2014, 40(2): 453-458. DOI: 10.1111/jog.12187.
[12]	Seifer DB, Gutmann JN, Doyle MB, et al. Persistent ectopic pregnancy following laparoscopic linear salpingostomy [J]. Obstet Gynecol, 1990, 76(6): 1121-1125.
[13]	Billieux MH, Petignat P, Anguenot JL, et al. Early and late half-life of human chorionic gonadotropin as a predictor of persistent trophoblast after laparoscopic conservative surgery for tubal pregnancy [J]. Acta Obstet Gynecol Scand, 2003, 82(6): 550-555. DOI: 10.1034/j.1600-0412.2003.00154.x.
[14]	王玉东. 2016年英国皇家妇产科医师学会及早期妊娠学会《异位妊娠的诊断和管理》指南解读[J]. 中国实用妇科与产科杂志，2017, 33(9): 916-919. DOI: 10.19538/j.fk2017090111.
[15]	Mol F, van Mello NM, Strandell A, et al. Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomised controlled trial [J]. Lancet, 2014, 383(9927): 1483-1489. DOI: 10.1016/S0140-6736(14)60123-9.
[16]	Lagana AS, Vitale SG, De Dominici R, et al. Fertility outcome after laparoscopic salpingostomy or salpingectomy for tubal ectopic pregnancy A 12-years retrospective cohort study [J]. Ann Ital Chir, 2016, 87: 461-465.
[17]	Cheng X, Tian X, Yan Z, et al. Comparison of the fertility outcome of salpingotomy and salpingectomy in women with tubal pregnancy: a systematic review and Meta-analysis [J]. PLoS One, 2016, 11(3): e152343. DOI: 10.1371/journal.pone.0152343.
[18]	Abe T, Akira S, Negishi Y, et al. Relevance of declines in serum human chorionic gonadotropin levels to the management of persistent ectopic pregnancy [J]. J Obstet Gynaecol Res, 2009, 35(5): 961-966. DOI: 10.1371/journal.pone.0152343.
[19]	Morse AN, Si W, Qin S, et al. Optimal use of peri-operative human chorionic gonadotrophin concentrations to identify persistent ectopic pregnancy after laparoscopic salpingostomy: a retrospective cohort study[J]. Reprod Biomed Online, 2018, 36(3): 361-368. DOI: 10.1016/j.rbmo.2017.12.006.
[20]	Akira S, Negishi Y, Abe T, et al. Prophylactic intratubal injection of methotrexate after linear salpingostomy for prevention of persistent ectopic pregnancy[J]. J Obstet Gynaecol Res, 2008, 34(5): 885-889. DOI: 10.1111/j.1447-0756.2008.00746.x.
[21]	Graczykowski JW, Mishell J. Methotrexate prophylaxis for persistent ectopic pregnancy after conservative treatment by salpingostomy [J]. Obstet Gynecol, 1997, 89(1): 118-122. DOI: 10.1016/s0029-7844(96)00370-5.
[22]	崔潇华，张红霞，赵新然，等. 宫外孕协定方预防输卵管妊娠腹腔镜保守性手术后持续性异位妊娠的临床价值 [J]. 河北中医，2012, 34(1): 29-30. DOI: 10.3969/j.issn.1002-2619.2012.01.012.

[1]	Shuqin Zhang, Lian Chen. Diagnosis and treatment of postpartum intrauterine retained products of conception[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(05): 493-497.
[2]	Jiechun Shi, Ziyu Fan, Yan Xing. Early warning efficiency of different screening methods on cervical adenocarcinoma in situ[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(05): 575-581.
[3]	Dan Tang, Xiaoxi Yao, Bowen Yang, Shaolong Xue, Mengyao Li, Liuxing Wei, Mingrong Xi. The impact of doublecortin-like kinase 1 on the clinical characteristics of endometrioid adenocarcinoma patients[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(05): 582-590.
[4]	Yi Wei, Yuxi Zhou, Ye Yang, Xiufeng Ling, Chun Zhao. Current research status on roles of microRNA on endometrial receptivity[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(03): 266-270.
[5]	Lin Lin, Simeng Tian, Yonghua Yu, Feifei Xu, Mingli Huang. Current research status on treatment of intrauterine adhesion by stem cells and their exosomes[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(03): 271-275.
[6]	Xin Li, Yi Wei, Juan Zhang, Juanjuan Zhang, Xiufeng Ling, Chun Zhao, Mianqiu Zhang. Influencing factors on clinical pregnancy outcomes of frozen-thaw embryo transfer cycle in women of advanced age[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(03): 276-283.
[7]	Weicong Gao, Li Li, Zhonghua Zhang, Xianghui Zhu, Suqiao Liu. Impact of impaired glucose regulation on recurrence within 2 years after modified radical surgery in patients with cervical cancer[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(02): 231-237.
[8]	Yuping Li, Hui Ma, Hang Yu. Clinical efficacy of laparoscopic uterine artery ligation combined with myomectomy for the treatment of uterine fibroids[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(02): 238-244.
[9]	Lin Yang, Rutie Yin. Current research status on etiology and treatment of patients with white lesions of vulva[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(02): 157-165.
[10]	Li Wang, Yueying Wang, Fen Zhou, Yukun Guo, Lina Wei. Current research status in effect of gonadotropin-releasing hormone antagonist on endometrial receptivity[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(06): 629-635.
[11]	Likun Wei, Xuhong Zhang, Ying Luo, Fengxia Xue, Yingmei Wang, Xueru Song, Lina Tian, Yanfang Zhang, Yanxia Wang, Wenyan Tian. Malignant transformation of ovarian endometrioma and pelvic abscesses: a case report and literature review[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(06): 696-702.
[12]	Yuan Wu, Biqing Zhu, Dan He, Hairong Wang, Qian Li. Construction of a prognostic nomogram model and risk stratification system for cervical cancer patients with intensity modulated radiation therapy and after-loading therapy[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(06): 734-744.
[13]	Juan Gu, Qingqing Sun, Fangfang Hu, Yijuan Cao, Yujuan Qi. Clinical application of endometrial receptivity array to improve pregnancy outcomes in women with repeated embryo implantation failure[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 582-587.
[14]	Shaohua Qu, Yedong Hu, Xiuhao Zhao, Wenna Li, Pengcheng Xiang, Zitian Xiao, Qiming Ma, Junyi Han. Effects of medical versus surgical therapy on ineffective esophageal motility in patients with gastroesophageal reflux diseases[J]. Chinese Archives of General Surgery(Electronic Edition), 2024, 18(01): 23-28.
[15]	Yafang Wang, Suran Rong, Xiangxin Shi, Xiao'ou Yang, Jinjin1 Xu, Jingxiang Wang. The effect of cutting balloon on the long-term prognosis of mild-to-moderate coronary artery calcification lesions in the elderly[J]. Chinese Journal of Geriatrics Research(Electronic Edition), 2024, 11(03): 19-23.

Viewed

Full text

Abstract

Please choose a citation manager

Content to export