术前药物应用联合腹腔镜保守性手术治疗异位妊娠的临床价值
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摘要
背景与目的
异位妊娠(Ectopic Pregnancy, EP)是指受精卵因某些原因未成功着床于正常子宫内膜,而种植于子宫体腔以外的部位,是妇产科常见的急腹症之一,可继发不孕甚至危及生命。腹腔镜检查为其诊断的金标准。在治疗方面,随着近年生活方式的转变,未婚年轻女性中EP的发生率呈上升趋势,渴望保留生育能力的患者逐渐增多,保守治疗越来越受到重视,其分为药物保守治疗与手术保守治疗。目前,临床上常用的药物有：甲氨蝶呤(MTX)、米非司酮、5-氟尿嘧啶(5-Fu)、中药制剂等,目前国内主要采用MTX与米非司酮的联合应用,因其除了具有药物起效快、成功率高等优点外,还可降低输卵管破裂、腹腔出血的危险性。保守性手术是指手术只清除异位的妊娠产物但保留患侧输卵管,能最大限度保留患者生育功能；腹腔镜手术除了具有创伤小、术后恢复快、并发症少等诸多优点外,还较肉眼直视有着更清晰的视野,是目前治疗未破裂型异位妊娠患者的首选术式。手术保守治疗的临床疗效明显优于药物治疗,但有术后再次出血及因异位妊娠部位滋养叶细胞残留而发生持续性异位妊娠(PEP)的潜在风险。国内有文献报道,腹腔镜联合术中药物治疗异位妊娠对预防PEP具有明显优势。本研究拟采用联合方法治疗未破裂型异位妊娠,即术前肌注MTX及口服米非司酮联合腹腔镜保守性手术治疗,从而研究术前药物应用联合腹腔镜保守性手术在治疗异位妊娠中的价值。
资料和方法
1收集我院2008年1月～2011年4月入住我院的生育期女性要求保留生育功能且符合保守治疗的160例未破裂型异位妊娠患者临床资料。保守治疗条件：①一般情况好,生命体征平稳,无明显内出血征象；②无药物治疗禁忌证；③附件区包块直径≤4cm;④血β-HCG<2000U/L。所有患者为术前彩超提示并术后病理证实的输卵管壶腹部、峡部或伞端妊娠(输卵管间质部妊娠一般不选取保守性手术治疗)。同患者交代病情及结合患者是否术前用药的意愿,签署相关同意书,根据患者术前是否用药及所用药物的不同,分组如下：其中直接采用腹腔镜保守性手术40例患者为A组,术前未进行任何预处理；B组术前肌注MTX50mg/m2;C组术前口服米非司酮50mg,每日2次,连用3d；D组术前肌注MTX50mg/m2及口服米非司酮50mg,每日2次,连用3d。四组患者在年龄、身高、体重、停经天数、腹痛、阴道流血天数、婚姻、包块大小及入院时血β-HCG水平等方面均无差异(P>0.05)。术前用药组各组间于用药前后的包块大小及入院时血β-HCG水平无显著差异(P>0.05),具有可比性。对所有患者就诊时均进行血常规、肝肾功能及血β-HCG检验等,并进行超声检查及全身体格检查；记录手术时间、术中出血量及电话随诊了解患者治疗后血,β-HCG恢复情况、输卵管再通情况及妊娠情况。对药物治疗组患者定期复查肝肾功能了解药物副反应情况并及时给予对症治疗。
2统计学处理：临床数据应用SPSS17.0软件进行统计分析,计量资料组间比较采用单因素方差分析,多组样本均数的两两比较采用LSD-t检验,计数资料采用χ2检验,χ2检验连续性校正或四格表确切概率法检验,以P<0.05为差异有统计学意义。
结果
1四组患者手术时间及术中出血量情况
单纯行腹腔镜保守性手术治疗组患者的手术时间及术中出血量分别为(57.3±17.4)min和(46.0±21.2)ml,而术前药物应用治疗组患者的手术时间及术中出血量减少,其中术前联合应用MTX及米非司酮组手术时间及术中出血量明显减少,为(38.4±6.8)min和(20.1±6.9)ml。运用单因素方差分析及LSD-t检验进行组间比较,结果显示B、C、D三组手术时间及术中出血量较A组减少,其中D组明显减少,B、C两组之间比较未见明显异常。
2四组患者术后血β-HCG下降至正常时间情况
对所有患者于入院时检测血β-HCG水平,并于术后定期严密监测并随访血β-HCG水平,记录血HCG下降至正常水平所需时间。采用单因素方差分析进行比较,结果显示各组间血β-HCG下降至正常水平所需时间无明显差异(F=0.76,P=0.5253>0.5)。
3四组患者术后3-4个月输卵管造影情况
术后3-4个月,于月经干净后3-7天A、B、C、D组患者行输卵管造影术,其中部分患者失访,结果显示四组间对侧输卵管通畅率无明显差异,治疗侧输卵管造影结果显示：A组通畅率为57.9%(22/38),周围粘连率为18.4%(7/38),梗阻率为23.7%(9/38)；B组通畅率为65.7%(23/35),周围粘连率为22.9%(8/35),梗阻率为11.4%(4/35)；C组通畅率为62.2%(23/37),周围粘连率为24.3%(9/37),梗阻率为13.5%(5/37)；D组通畅率为82.9%(29/35),周围粘连率为11.4%(4/35),梗阻率为5.7%(2/35)。四组比较差异有统计学意义(P<0.05),可见输卵管通畅率D组明显高于其他治疗组,且梗阻率明显低于其他治疗组。
4四组患者术后2年内自然妊娠情况
对所有患者进行电话随访以了解治疗后妊娠与否、异位妊娠发生与否等,D组患者术后2年内宫内妊娠发生情况：72.5%(29/40)患者于术后6个月发生宫内妊娠,87.5%(35/40)患者于术后1年发生宫内妊娠,92.5%(37/40)患者于术后2年发生宫内妊娠。D组与A、B、C组术后6个月内、1年内、2年内宫内妊娠率、不孕率及异位妊娠再发率比较,差异有统计学意义(p＝0.000<0.05);D组术后宫内妊娠率明显高于A、B、C三组。并可见四组中随时间进展治疗后异位妊娠再发的潜在风险性逐渐增高。
5四组患者术后第1次宫内妊娠时间情况
对所有患者进行电话随访以了解治疗后第1次自然宫内妊娠时间并记录,D组第1次术后宫内妊娠时间平均为(10.6±3.1)m,A组第1次术后宫内妊娠时间平均为(15.1±5.6)m,B组第1次术后宫内妊娠时间平均为(13.1±4.2)m,C组第1次术后宫内妊娠时间平均为(13.7±3.5)m,D组患者术后第1次自然宫内妊娠时间与A组、B组、C组对照,经LSD-t检验,差异有统计学意义(P<0.05)。可见D组治疗后第1次宫内妊娠时间明显提前。
6并发症及药物副作用
药物治疗组患者肌注MTX及口服米非司酮期间,多数患者出现胃肠不适,其中一例在外院行MTX治疗后转入我院出现严重骨髓移植,白细胞低至0.5×109／L,考虑外院用药剂量稍大所致,在我院治疗者未发现严重并发症,部分患者出现血白细胞轻度下降,及时给予对症处理后恢复,每周检查肝肾功能未见异常；所有患者腹腔镜保守性手术均获成功,无中转开腹,无一例出现手术并发症,A组患者发生持续性异位妊娠2例,给予术后药物治疗后痊愈。
结论
术前药物应用联合腹腔镜保守性手术治疗有生育要求的未破裂型异位妊娠疗效好,其中术前联合用药在治疗的同时最大限度的保留了患侧输卵管功能,对患者生育力影响小,是一种疗效显著的治疗方案,有重大临床价值,值得作为术前常规用药应用于临床。
Background and Objective
Ectopic pregnancy (EP) refers to that the fertilized egg implants outside the uterine cavity, but does not implant in normal endometrium successfully for some reasons. As a common clinical obstetric and gynecological acute abdomen, it can lead to infertility or even threaten life. Laparoscopy is the golden standard in the diagnosis of ectopic pregnancy. Due to the change of life style in recent years, the incidence of ectopic pregnancy among unmarried young women is on the rise; in terms of treatment, more and more patients are eager to preserve fertility, which leads to the situation where conservative treatment is receiving increasing attention. Conservative treatment consists of medicine conservative treatment and conservative operation treatment. So far, the commonly-used drugs in clinic are methotrexate (MTX), mifepristone,5-fluorouracil (5-Fu), traditional Chinese medicine preparation, etc. The medicine treatment of ectopic pregnancy in China mainly adopts the combined application of methotrexate (MTX) and mifepristone, for it not only has the advantages such as fast drug effect and high success rate, but also reduces the risk of the fallopian tube rupture and intraperitoneal hemorrhage. Conservative operation refers to that the operation only remove the product of conception but preserve the ipsilateral fallopian tube, which can retain the patients'reproductive function to the maximum. With such advantages as little trauma, rapid recovery after operation and less complications, as well as a clearer view during operation, laparoscopic operation is the preferred surgical method in the treatment of unruptured ectopic pregnancy. The clinical curative effect of conservative operation is superior to that of medication; however, the former method has the potential risk of postoperative rebleeding and persistent ectopic pregnancy (PEP) caused by the residual of trophoblast cells. It has been reported in the literature in China that laparoscopic operation combined with drug treatment has obvious advantages in the prevention of persistent ectopic pregnancy (PEP). This study is to adopt a combined method-preoperative drug application (intramuscular injection of methotrexate and oral mifepristone) plus laparoscopic conservative surgery-to treat the unruptured ectopic pregnancy, and thus to observe the value of this combined method in the treatment of ectopic pregnancy.
Materials and Methods
1We collect the clinical data of160unruptured ectopic pregnancy cases (in which the patients demand to preserve the reproductive function and accord with conservative treatment conditions) treated in the First Affiliated Hospital of Zhengzhou University from Jan.2008to Apr.2011.The selected conditions are as followa, firstly, the good ordinary circumstances, stable vital signs and no obvious signs of internal hemorrhage; secondly, no drug treatment contraindications; thirdly, the adnexal masses diameter≤4cm; the last,the serum beta-human chorinic gonadotropin (β-HCG)<2000U/L.Based on the results of preoperative gynecological ultrasonography and the postoperative pathology, all of the patients are confirmed as ectopic pregnancy in the fimbrial end、the isthmic section or the ampullary section(normally the interstitial tubal pregnancy are not treated by laparoscopic conservative surgery).We handed over the condition toward the patients and signed the relevant agreement with the patients according to whether premedication. According to the preoperative medication, the groups were as follows:40cases among them who undergo the laparoscopic conservative surgery directly were taken as group A, in which the patients received no drug treatment before operation;group B (40cases), in which the patients were treated with intramuscular injection of methotrexate (50mg/m2)before operation; group C (40cases), in which the patients were treated with oral mifepristone(50mg each time,twice-daily for three days) before operation; group D (40cases), in which the patients were treated with intramuscular injection of methotrexate(50mg/m2)and oral mifepristone(50mg each time,twice-daily for three days) before operation. All of the patients in the four groups share the same data concerning their age, height, weight and marital status, days of menolipsis, symptoms of abdominal pain, days of virginal bleeding, size of abdominal mass, and blood β-HCG value (P＞0.05). The difference of the size of abdominal mass and blood P-HCG value about before and after treatment among the groups which adopted preoperative medication were not statistically significant (P＞0.05),which makes the research results comparable. All of the patients were given blood routine examination, hepatorenal function examination, serum beta-human chorinic gonadotropin (β-HCG) examination, ultrasound examination and general physical examination. The operation time and intraoperative bleeding volume were recorded, and the recovery condition of blood β-HCG value and the condition of the tubal recanalization and intrauterine pregnancy were inquired about by way of telephone. The patients in the drug treatment groups also received regular examination of the liver and kidney function, so that the circumstances of the adverse drug reaction could be known and timely symptomatic treatment could be offered.
2Statistical analysis:All clinical data are analyzed by the SPSS17.0statistical software; measurement data are analyzed by one-way variance; pairwise comparison between groups adopts LSD-t test; and categorical data are analyzed by chi-square test. Categorical datas are analysed by chi-square test, calibration of the chi-square test or four table's exact probabilities.And P＜0.05is considered statistically significantly.
Results
1The data of operation time and intraoperative bleeding volume of patients in four groups
The operation time and the intraoperative bleeding volume in group A are (57.3±17.4) min and (46.0±21.2) ml, while the operation time and the intraoperative bleeding volume in groups with preoperative drug application are lesser, among which the data of group D are significantly lesser, which are (38.4±6.8) min and (20.1±6.9) ml. By means of one-way variance and LSD-t test in pairwise comparison between groups, it shows that there are significant differences between the analysis results of group A and those of group B, C, D.
2The Duration of blood P-HCG value of patients in four groups decreasing to normal after surgery
All of the patients were given serum beta-human chorinic gonadotropin (β-HCG) examination on admission. We monitor and follow up blood β-HCG level after surgery, and we record the duration of the serum β-HCG decreasing to normal. By means of one-way variance for comparison between groups, the results show that there is no significant difference among the four groups (F=0.76,P=0.5253＞0.05).
3The salpingography results of patients in four groups after three or four months since operation
Three or four months after operation, patients of A, B, C and D groups underwent fallopian tube radiography on the third to the seventh day after menstrual period, lost to follow up some patients.The analysis results show that there is no significant difference among the four groups concerning the tubal patency rate of the untreated side, while the fallopian tube radiographic results of the treated side are quite different. In group A, tubal patency rate is57.9%(23/38), peritubal adhesion rate is18.4%(7/38), and obstruction rate is23.7%(9/38); in group B, tubal patency rate is65.7%(23/35), peritubal adhesion rate is22.9%(8/35), and obstruction rate is11.4%(4/35); in group C, tubal patency rate is62.2%(23/37), peritubal adhesion rate is24.3%(9/37), and obstruction rate is13.5%(5/37); in group D, tubal patency rate is82.9%(29/35), peritubal adhesion rate is11.4%(4/35), and obstruction rate is5.7%(2/35). The differences among the four groups are statistically significant (P＜0.05). Evidently, the tubal patency rate in group D is greater than that in group A, B and C; and the obstruction rate in group D is lesser that that in group A, B and C.
4The data of natural pregnancy of patients in four groups within2
years after operation
We follow up all the patients in the past two years to know whether there is intrauterine pregnancy or ectopic pregnancy and the occurrence time. The data of intrauterine pregnancy of the patients in group D within2years after operation:72.5%(29/40) patients were pregnant within six months,87.5%(35/40) patients were pregnant within one year, and92.5%(37/40) patients were pregnant within two years. There are significant differences between group D and group A, B and C concerning the intrauterine pregnancy rate, infertility rate and reoccurrence rate of ectopic pregnancy within six months, one year and two years after treatment (P=0.000<0.05). It also shows that the postoperative intrauterine pregnancy rate of group D is obviously higher than that of group A, B and C. And obviously, the potential risk of recurrence of ectopic pregnancy after treatment increases gradually over the course of time.
5The first intrauterine pregnancy time of patients in four groups after treatment
All the patients were followed up to inquire about the first intrauterine pregnancy time after operation. In group D, the time is (10.6±3.1) m; in group A, the time is (15.1±5.6) m; In group B, the time is (13.1±4.2) m; in group C, the time is (13.7±3.5) m. By way of LSD-t test in pairwise comparison between groups, the results show that there are significant differences between group D and group A, B and C. Evidently, the first intrauterine pregnancy time of group D is much earlier.
6Complications and adverse drug reactions
In the groups with preoperative drug application, the symptom of gastrointestinal discomfort appeared among the majority of patients, one who was treated by MTX was found severe bone marrow transplantation,the white blood cell count droped to0.5×109/L,maybe the reason was that the dose is slightly larger,those who were treated in our hospital were found no serious complications, the white blood cell count of some patients decreased slightly. The patients recovered after receiving symptomatic treatment. There was no liver and kidney dysfunction among the patients in the weekly examination. The laparoscopic conservative surgery of all the patients was successful, and there was no conversion to laparotomy or occurrence of surgical complications. Although there were two cases of persistent ectopic pregnancy (PEP) in group A, they recovered by receiving drug therapy after surgery.
Conclusions
Preoperative drug application combined with laparoscopic conservative surgery in the treatment of unruptured ectopic pregnancy who demand to preserve the reproductive function can achieve remarkable effect. Moreover, preoperative application of MTX and mifepristone can reserve the function of the diseased fallopian tube to the maximum and has momentous clinical value.
异位妊娠(Ectopic Pregnancy, EP)是指受精卵因某些原因未成功着床于正常子宫内膜,而种植于子宫体腔以外的部位,是妇产科常见的急腹症之一,可继发不孕甚至危及生命。腹腔镜检查为其诊断的金标准。在治疗方面,随着近年生活方式的转变,未婚年轻女性中EP的发生率呈上升趋势,渴望保留生育能力的患者逐渐增多,保守治疗越来越受到重视,其分为药物保守治疗与手术保守治疗。目前,临床上常用的药物有：甲氨蝶呤(MTX)、米非司酮、5-氟尿嘧啶(5-Fu)、中药制剂等,目前国内主要采用MTX与米非司酮的联合应用,因其除了具有药物起效快、成功率高等优点外,还可降低输卵管破裂、腹腔出血的危险性。保守性手术是指手术只清除异位的妊娠产物但保留患侧输卵管,能最大限度保留患者生育功能；腹腔镜手术除了具有创伤小、术后恢复快、并发症少等诸多优点外,还较肉眼直视有着更清晰的视野,是目前治疗未破裂型异位妊娠患者的首选术式。手术保守治疗的临床疗效明显优于药物治疗,但有术后再次出血及因异位妊娠部位滋养叶细胞残留而发生持续性异位妊娠(PEP)的潜在风险。国内有文献报道,腹腔镜联合术中药物治疗异位妊娠对预防PEP具有明显优势。本研究拟采用联合方法治疗未破裂型异位妊娠,即术前肌注MTX及口服米非司酮联合腹腔镜保守性手术治疗,从而研究术前药物应用联合腹腔镜保守性手术在治疗异位妊娠中的价值。
资料和方法
1收集我院2008年1月～2011年4月入住我院的生育期女性要求保留生育功能且符合保守治疗的160例未破裂型异位妊娠患者临床资料。保守治疗条件：①一般情况好,生命体征平稳,无明显内出血征象；②无药物治疗禁忌证；③附件区包块直径≤4cm;④血β-HCG<2000U/L。所有患者为术前彩超提示并术后病理证实的输卵管壶腹部、峡部或伞端妊娠(输卵管间质部妊娠一般不选取保守性手术治疗)。同患者交代病情及结合患者是否术前用药的意愿,签署相关同意书,根据患者术前是否用药及所用药物的不同,分组如下：其中直接采用腹腔镜保守性手术40例患者为A组,术前未进行任何预处理；B组术前肌注MTX50mg/m2;C组术前口服米非司酮50mg,每日2次,连用3d；D组术前肌注MTX50mg/m2及口服米非司酮50mg,每日2次,连用3d。四组患者在年龄、身高、体重、停经天数、腹痛、阴道流血天数、婚姻、包块大小及入院时血β-HCG水平等方面均无差异(P>0.05)。术前用药组各组间于用药前后的包块大小及入院时血β-HCG水平无显著差异(P>0.05),具有可比性。对所有患者就诊时均进行血常规、肝肾功能及血β-HCG检验等,并进行超声检查及全身体格检查；记录手术时间、术中出血量及电话随诊了解患者治疗后血,β-HCG恢复情况、输卵管再通情况及妊娠情况。对药物治疗组患者定期复查肝肾功能了解药物副反应情况并及时给予对症治疗。
2统计学处理：临床数据应用SPSS17.0软件进行统计分析,计量资料组间比较采用单因素方差分析,多组样本均数的两两比较采用LSD-t检验,计数资料采用χ2检验,χ2检验连续性校正或四格表确切概率法检验,以P<0.05为差异有统计学意义。
结果
1四组患者手术时间及术中出血量情况
单纯行腹腔镜保守性手术治疗组患者的手术时间及术中出血量分别为(57.3±17.4)min和(46.0±21.2)ml,而术前药物应用治疗组患者的手术时间及术中出血量减少,其中术前联合应用MTX及米非司酮组手术时间及术中出血量明显减少,为(38.4±6.8)min和(20.1±6.9)ml。运用单因素方差分析及LSD-t检验进行组间比较,结果显示B、C、D三组手术时间及术中出血量较A组减少,其中D组明显减少,B、C两组之间比较未见明显异常。
2四组患者术后血β-HCG下降至正常时间情况
对所有患者于入院时检测血β-HCG水平,并于术后定期严密监测并随访血β-HCG水平,记录血HCG下降至正常水平所需时间。采用单因素方差分析进行比较,结果显示各组间血β-HCG下降至正常水平所需时间无明显差异(F=0.76,P=0.5253>0.5)。
3四组患者术后3-4个月输卵管造影情况
术后3-4个月,于月经干净后3-7天A、B、C、D组患者行输卵管造影术,其中部分患者失访,结果显示四组间对侧输卵管通畅率无明显差异,治疗侧输卵管造影结果显示：A组通畅率为57.9%(22/38),周围粘连率为18.4%(7/38),梗阻率为23.7%(9/38)；B组通畅率为65.7%(23/35),周围粘连率为22.9%(8/35),梗阻率为11.4%(4/35)；C组通畅率为62.2%(23/37),周围粘连率为24.3%(9/37),梗阻率为13.5%(5/37)；D组通畅率为82.9%(29/35),周围粘连率为11.4%(4/35),梗阻率为5.7%(2/35)。四组比较差异有统计学意义(P<0.05),可见输卵管通畅率D组明显高于其他治疗组,且梗阻率明显低于其他治疗组。
4四组患者术后2年内自然妊娠情况
对所有患者进行电话随访以了解治疗后妊娠与否、异位妊娠发生与否等,D组患者术后2年内宫内妊娠发生情况：72.5%(29/40)患者于术后6个月发生宫内妊娠,87.5%(35/40)患者于术后1年发生宫内妊娠,92.5%(37/40)患者于术后2年发生宫内妊娠。D组与A、B、C组术后6个月内、1年内、2年内宫内妊娠率、不孕率及异位妊娠再发率比较,差异有统计学意义(p＝0.000<0.05);D组术后宫内妊娠率明显高于A、B、C三组。并可见四组中随时间进展治疗后异位妊娠再发的潜在风险性逐渐增高。
5四组患者术后第1次宫内妊娠时间情况
对所有患者进行电话随访以了解治疗后第1次自然宫内妊娠时间并记录,D组第1次术后宫内妊娠时间平均为(10.6±3.1)m,A组第1次术后宫内妊娠时间平均为(15.1±5.6)m,B组第1次术后宫内妊娠时间平均为(13.1±4.2)m,C组第1次术后宫内妊娠时间平均为(13.7±3.5)m,D组患者术后第1次自然宫内妊娠时间与A组、B组、C组对照,经LSD-t检验,差异有统计学意义(P<0.05)。可见D组治疗后第1次宫内妊娠时间明显提前。
6并发症及药物副作用
药物治疗组患者肌注MTX及口服米非司酮期间,多数患者出现胃肠不适,其中一例在外院行MTX治疗后转入我院出现严重骨髓移植,白细胞低至0.5×109／L,考虑外院用药剂量稍大所致,在我院治疗者未发现严重并发症,部分患者出现血白细胞轻度下降,及时给予对症处理后恢复,每周检查肝肾功能未见异常；所有患者腹腔镜保守性手术均获成功,无中转开腹,无一例出现手术并发症,A组患者发生持续性异位妊娠2例,给予术后药物治疗后痊愈。
结论
术前药物应用联合腹腔镜保守性手术治疗有生育要求的未破裂型异位妊娠疗效好,其中术前联合用药在治疗的同时最大限度的保留了患侧输卵管功能,对患者生育力影响小,是一种疗效显著的治疗方案,有重大临床价值,值得作为术前常规用药应用于临床。
Background and Objective
Ectopic pregnancy (EP) refers to that the fertilized egg implants outside the uterine cavity, but does not implant in normal endometrium successfully for some reasons. As a common clinical obstetric and gynecological acute abdomen, it can lead to infertility or even threaten life. Laparoscopy is the golden standard in the diagnosis of ectopic pregnancy. Due to the change of life style in recent years, the incidence of ectopic pregnancy among unmarried young women is on the rise; in terms of treatment, more and more patients are eager to preserve fertility, which leads to the situation where conservative treatment is receiving increasing attention. Conservative treatment consists of medicine conservative treatment and conservative operation treatment. So far, the commonly-used drugs in clinic are methotrexate (MTX), mifepristone,5-fluorouracil (5-Fu), traditional Chinese medicine preparation, etc. The medicine treatment of ectopic pregnancy in China mainly adopts the combined application of methotrexate (MTX) and mifepristone, for it not only has the advantages such as fast drug effect and high success rate, but also reduces the risk of the fallopian tube rupture and intraperitoneal hemorrhage. Conservative operation refers to that the operation only remove the product of conception but preserve the ipsilateral fallopian tube, which can retain the patients'reproductive function to the maximum. With such advantages as little trauma, rapid recovery after operation and less complications, as well as a clearer view during operation, laparoscopic operation is the preferred surgical method in the treatment of unruptured ectopic pregnancy. The clinical curative effect of conservative operation is superior to that of medication; however, the former method has the potential risk of postoperative rebleeding and persistent ectopic pregnancy (PEP) caused by the residual of trophoblast cells. It has been reported in the literature in China that laparoscopic operation combined with drug treatment has obvious advantages in the prevention of persistent ectopic pregnancy (PEP). This study is to adopt a combined method-preoperative drug application (intramuscular injection of methotrexate and oral mifepristone) plus laparoscopic conservative surgery-to treat the unruptured ectopic pregnancy, and thus to observe the value of this combined method in the treatment of ectopic pregnancy.
Materials and Methods
1We collect the clinical data of160unruptured ectopic pregnancy cases (in which the patients demand to preserve the reproductive function and accord with conservative treatment conditions) treated in the First Affiliated Hospital of Zhengzhou University from Jan.2008to Apr.2011.The selected conditions are as followa, firstly, the good ordinary circumstances, stable vital signs and no obvious signs of internal hemorrhage; secondly, no drug treatment contraindications; thirdly, the adnexal masses diameter≤4cm; the last,the serum beta-human chorinic gonadotropin (β-HCG)<2000U/L.Based on the results of preoperative gynecological ultrasonography and the postoperative pathology, all of the patients are confirmed as ectopic pregnancy in the fimbrial end、the isthmic section or the ampullary section(normally the interstitial tubal pregnancy are not treated by laparoscopic conservative surgery).We handed over the condition toward the patients and signed the relevant agreement with the patients according to whether premedication. According to the preoperative medication, the groups were as follows:40cases among them who undergo the laparoscopic conservative surgery directly were taken as group A, in which the patients received no drug treatment before operation;group B (40cases), in which the patients were treated with intramuscular injection of methotrexate (50mg/m2)before operation; group C (40cases), in which the patients were treated with oral mifepristone(50mg each time,twice-daily for three days) before operation; group D (40cases), in which the patients were treated with intramuscular injection of methotrexate(50mg/m2)and oral mifepristone(50mg each time,twice-daily for three days) before operation. All of the patients in the four groups share the same data concerning their age, height, weight and marital status, days of menolipsis, symptoms of abdominal pain, days of virginal bleeding, size of abdominal mass, and blood β-HCG value (P＞0.05). The difference of the size of abdominal mass and blood P-HCG value about before and after treatment among the groups which adopted preoperative medication were not statistically significant (P＞0.05),which makes the research results comparable. All of the patients were given blood routine examination, hepatorenal function examination, serum beta-human chorinic gonadotropin (β-HCG) examination, ultrasound examination and general physical examination. The operation time and intraoperative bleeding volume were recorded, and the recovery condition of blood β-HCG value and the condition of the tubal recanalization and intrauterine pregnancy were inquired about by way of telephone. The patients in the drug treatment groups also received regular examination of the liver and kidney function, so that the circumstances of the adverse drug reaction could be known and timely symptomatic treatment could be offered.
2Statistical analysis:All clinical data are analyzed by the SPSS17.0statistical software; measurement data are analyzed by one-way variance; pairwise comparison between groups adopts LSD-t test; and categorical data are analyzed by chi-square test. Categorical datas are analysed by chi-square test, calibration of the chi-square test or four table's exact probabilities.And P＜0.05is considered statistically significantly.
Results
1The data of operation time and intraoperative bleeding volume of patients in four groups
The operation time and the intraoperative bleeding volume in group A are (57.3±17.4) min and (46.0±21.2) ml, while the operation time and the intraoperative bleeding volume in groups with preoperative drug application are lesser, among which the data of group D are significantly lesser, which are (38.4±6.8) min and (20.1±6.9) ml. By means of one-way variance and LSD-t test in pairwise comparison between groups, it shows that there are significant differences between the analysis results of group A and those of group B, C, D.
2The Duration of blood P-HCG value of patients in four groups decreasing to normal after surgery
All of the patients were given serum beta-human chorinic gonadotropin (β-HCG) examination on admission. We monitor and follow up blood β-HCG level after surgery, and we record the duration of the serum β-HCG decreasing to normal. By means of one-way variance for comparison between groups, the results show that there is no significant difference among the four groups (F=0.76,P=0.5253＞0.05).
3The salpingography results of patients in four groups after three or four months since operation
Three or four months after operation, patients of A, B, C and D groups underwent fallopian tube radiography on the third to the seventh day after menstrual period, lost to follow up some patients.The analysis results show that there is no significant difference among the four groups concerning the tubal patency rate of the untreated side, while the fallopian tube radiographic results of the treated side are quite different. In group A, tubal patency rate is57.9%(23/38), peritubal adhesion rate is18.4%(7/38), and obstruction rate is23.7%(9/38); in group B, tubal patency rate is65.7%(23/35), peritubal adhesion rate is22.9%(8/35), and obstruction rate is11.4%(4/35); in group C, tubal patency rate is62.2%(23/37), peritubal adhesion rate is24.3%(9/37), and obstruction rate is13.5%(5/37); in group D, tubal patency rate is82.9%(29/35), peritubal adhesion rate is11.4%(4/35), and obstruction rate is5.7%(2/35). The differences among the four groups are statistically significant (P＜0.05). Evidently, the tubal patency rate in group D is greater than that in group A, B and C; and the obstruction rate in group D is lesser that that in group A, B and C.
4The data of natural pregnancy of patients in four groups within2
years after operation
We follow up all the patients in the past two years to know whether there is intrauterine pregnancy or ectopic pregnancy and the occurrence time. The data of intrauterine pregnancy of the patients in group D within2years after operation:72.5%(29/40) patients were pregnant within six months,87.5%(35/40) patients were pregnant within one year, and92.5%(37/40) patients were pregnant within two years. There are significant differences between group D and group A, B and C concerning the intrauterine pregnancy rate, infertility rate and reoccurrence rate of ectopic pregnancy within six months, one year and two years after treatment (P=0.000<0.05). It also shows that the postoperative intrauterine pregnancy rate of group D is obviously higher than that of group A, B and C. And obviously, the potential risk of recurrence of ectopic pregnancy after treatment increases gradually over the course of time.
5The first intrauterine pregnancy time of patients in four groups after treatment
All the patients were followed up to inquire about the first intrauterine pregnancy time after operation. In group D, the time is (10.6±3.1) m; in group A, the time is (15.1±5.6) m; In group B, the time is (13.1±4.2) m; in group C, the time is (13.7±3.5) m. By way of LSD-t test in pairwise comparison between groups, the results show that there are significant differences between group D and group A, B and C. Evidently, the first intrauterine pregnancy time of group D is much earlier.
6Complications and adverse drug reactions
In the groups with preoperative drug application, the symptom of gastrointestinal discomfort appeared among the majority of patients, one who was treated by MTX was found severe bone marrow transplantation,the white blood cell count droped to0.5×109/L,maybe the reason was that the dose is slightly larger,those who were treated in our hospital were found no serious complications, the white blood cell count of some patients decreased slightly. The patients recovered after receiving symptomatic treatment. There was no liver and kidney dysfunction among the patients in the weekly examination. The laparoscopic conservative surgery of all the patients was successful, and there was no conversion to laparotomy or occurrence of surgical complications. Although there were two cases of persistent ectopic pregnancy (PEP) in group A, they recovered by receiving drug therapy after surgery.
Conclusions
Preoperative drug application combined with laparoscopic conservative surgery in the treatment of unruptured ectopic pregnancy who demand to preserve the reproductive function can achieve remarkable effect. Moreover, preoperative application of MTX and mifepristone can reserve the function of the diseased fallopian tube to the maximum and has momentous clinical value.
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