Long Ying, Zhu Huili, Hu Yuanyuan, Shen Licong, Fu Jing, Huang Wei
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
Cochrane Database Syst Rev. 2020 Jul 1;7(7):CD011174. doi: 10.1002/14651858.CD011174.pub2.
Non-tubal ectopic pregnancy is the implantation of an embryo at a site lying outside the uterine cavity or fallopian tubes. Sites include a caesarean scar, the cornua uteri, the ovary, the cervix, and the abdomen. There has been an increasing trend in the occurrence of these rare conditions, especially caesarean scar pregnancy (CSP).
To evaluate the clinical effectiveness and safety of surgery, medical treatment, and expectant management of non-tubal ectopic pregnancy in terms of fertility outcomes and complications.
We searched the Cochrane Gynaecology and Fertility (CGF) Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) search portal and nine other databases to 12 December 2019. We handsearched reference lists of articles retrieved and contacted experts in the field to obtain additional data.
We included randomized controlled trials (RCTs) published in all languages that examined the effects and safety of surgery, medical treatment, and expectant management of non-tubal ectopic pregnancy.
We used Cochrane standard methodological procedures. Primary outcomes were treatment success and complications.
We included five RCTs with 303 women, all reporting Caesarean scar pregnancy. Two compared uterine arterial embolization (UAE) or uterine arterial chemoembolization (UACE) plus methotrexate (MTX) versus systemic MTX and subsequent dilation and suction curettage; one compared UACE plus MTX versus ultrasonography-guided local MTX injection; and two compared suction curettage under hysteroscopy versus suction curettage under ultrasonography after UAE/UACE. The quality of evidence ranged from moderate to very low. The main limitations were imprecision (small sample sizes and very wide confidence intervals (CI) for most analyses), multiple comparisons with a small number of trials, and insufficient data available to assess heterogeneity. UAE/UACE versus systemic MTX prior to suction curettage Two studies reported this comparison. One compared UAE with systemic MTX and one compared UACE plus MTX versus systemic MTX, in both cases followed by a suction curettage. We are uncertain whether UAE/UACE improved success rates after initial treatment (UAE: risk ratio (RR) 1.00, 95% CI 0.90 to 1.12; 1 RCT, 72 women; low-quality evidence; UACE: RR 0.87, 95% CI 0.54 to 1.38; 1 RCT, 28 women; low-quality evidence). We are uncertain whether UAE/UACE reduced rates of complications (UAE: RR 0.47, 95% CI 0.13 to 1.75; 1 RCT, 72 women; low-quality evidence; UACE: RR 0.62, 95% CI 0.26 to 1.48; 1 RCT, 28 women; low-quality evidence). We are uncertain whether UAE/UACE reduced adverse effects (UAE: RR 1.58, 95% CI 0.41 to 6.11; 1 RCT, 72 women; low-quality evidence; UACE: RR 1.16, 95% CI 0.32 to 4.24; 1 RCT, 28 women; low-quality evidence), and it was not obvious that the types of events had similar values to participants (e.g. fever versus vomiting). Blood loss was lower in UAE/UACE groups than systemic MTX groups (UAE: mean difference (MD) -378.70 mL, 95% CI -401.43 to -355.97; 1 RCT, 72 women; moderate-quality evidence; UACE: MD -879.00 mL, 95% CI -1135.23 to -622.77; 1 RCT, 28 women; moderate-quality evidence). Data were not available on time to normalize β-human chorionic gonadotropin (β-hCG). UACE plus MTX versus ultrasonography-guided local MTX injection We are uncertain whether UACE improved success rates after initial treatment (RR 0.95, 95% CI 0.56 to 1.60; 1 RCT, 45 women; very low-quality evidence). Adverse effects: the study reported the same number of failed treatments in each arm (RR 0.88, 95% CI 0.40 to 1.92; 1 RCT, 45 women). We are uncertain whether UACE shortened the time to normalize β-hCG (MD 1.50 days, 95% CI -3.16 to 6.16; 1 RCT, 45 women; very low-quality evidence). Data were not available for complications. Suction curettage under hysteroscopy versus under ultrasonography after UAE/UACE. Two studies reported this comparison. One compared suction curettage under hysteroscopy versus under ultrasonography after UAE, and one compared these interventions after UACE. We are uncertain whether suction curettage under hysteroscopy improved success rates after initial treatment (UAE: RR 0.91, 95% CI 0.81 to 1.03; 1 RCT, 66 women; very low-quality evidence; UACE: RR 1.02, 95% CI 0.96 to 1.09; 1 RCT, 92 women; low-quality evidence). We are uncertain whether suction curettage under hysteroscopy reduced rates of complications (UAE: RR 4.00, 95% CI 0.47 to 33.91; 1 RCT, 66 women; very low-quality evidence; UACE: RR 0.18, 95% CI 0.01 to 3.72; 1 RCT, 92 women; low-quality evidence). We are uncertain whether suction curettage under hysteroscopy reduced adverse effects (UAE: RR 3.09, 95% CI 0.12 to 78.70; 1 RCT, 66 women; very low-quality evidence; UACE: not estimable; 1 RCT, 92 women; very low-quality evidence). We are uncertain whether suction curettage under hysteroscopy shortened the time to normalize β-hCG (UAE: MD 4.03 days, 95% CI -1.79 to 9.85; 1 RCT, 66 women; very low-quality evidence; UACE: MD 0.84 days, 95% CI -1.90 to 3.58; 1 RCT, 92 women; low-quality evidence). Non-tubal ectopic pregnancy other than CSP No studies reported on non-tubal ectopic pregnancies in locations other than on a caesarean scar.
AUTHORS' CONCLUSIONS: For Caesarean scar pregnancies (CSP) it is uncertain whether there is a difference in success rates, complications, or adverse events between UAE/UACE and administration of systemic MTX before suction curettage (low-quality evidence). Blood loss was lower if suction curettage is conducted after UAE/UACE than after administration of systemic MTX (moderate-quality evidence). It is uncertain whether there is a difference in treatment success rates, complications, adverse effects or time to normalize β-hCG between suction curettage under hysteroscopy and under ultrasonography (very low-quality evidence). There are no studies of non-tubal ectopic pregnancy other than CSP and RCTs for these types of pregnancy are unlikely.
非输卵管异位妊娠是指胚胎着床于子宫腔或输卵管以外的部位。这些部位包括剖宫产瘢痕、子宫角、卵巢、宫颈和腹腔。这些罕见情况的发生率呈上升趋势，尤其是剖宫产瘢痕妊娠（CSP）。
从生育结局和并发症方面评估非输卵管异位妊娠的手术、药物治疗及期待治疗的临床有效性和安全性。
我们检索了Cochrane妇科与生育（CGF）小组专门的对照试验注册库、Cochrane系统评价数据库、医学期刊数据库（MEDLINE）、荷兰医学文摘数据库（Embase）、临床试验注册库（ClinicalTrials.gov）、世界卫生组织（WHO）检索门户以及其他九个数据库，检索截止至2019年12月12日。我们手工检索了所获文章的参考文献列表，并联系了该领域的专家以获取更多数据。
我们纳入了所有语言发表的随机对照试验（RCT），这些试验研究了非输卵管异位妊娠的手术、药物治疗及期待治疗的效果和安全性。
我们采用Cochrane标准方法程序。主要结局为治疗成功率和并发症。
我们纳入了5项RCT，共303名女性，均报告为剖宫产瘢痕妊娠。两项试验比较了子宫动脉栓塞术（UAE）或子宫动脉化疗栓塞术（UACE）联合甲氨蝶呤（MTX）与全身应用MTX及后续的扩张刮宫术；一项试验比较了UACE联合MTX与超声引导下局部MTX注射；两项试验比较了UAE/UACE后宫腔镜下刮宫术与超声引导下刮宫术。证据质量从中等至极低。主要局限性包括不精确性（大多数分析样本量小且置信区间（CI）非常宽）、少量试验的多次比较以及评估异质性的数据不足。UAE/UACE与刮宫术前全身应用MTX的比较 两项研究报告了这一比较。一项比较了UAE与全身应用MTX，另一项比较了UACE联合MTX与全身应用MTX，两种情况均随后进行刮宫术。我们不确定UAE/UACE在初始治疗后是否提高了成功率（UAE：风险比（RR）1.00，95%CI 0.90至1.12；1项RCT，72名女性；低质量证据；UACE：RR 0.87，95%CI 0.54至1.38；1项RCT，28名女性；低质量证据）。我们不确定UAE/UACE是否降低了并发症发生率（UAE：RR 0.47，95%CI 0.13至1.75；1项RCT，72名女性；低质量证据；UACE：RR 0.62，95%CI 0.26至1.48；1项RCT，28名女性；低质量证据）。我们不确定UAE/UACE是否减少了不良反应（UAE：RR 1.58，95%CI 0.41至6.11；1项RCT，72名女性；低质量证据；UACE：RR 1.16，95%CI 0.32至4.24；1项RCT，28名女性；低质量证据），而且不同事件类型对参与者的影响价值并不明显（例如发热与呕吐）。UAE/UACE组的失血量低于全身应用MTX组（UAE：平均差（MD）-378.70 mL，95%CI -401.43至-355.97；1项RCT，72名女性；中等质量证据；UACE：MD -879.00 mL，95%CI -1135.23至-622.77；1项RCT，28名女性；中等质量证据）。关于β-人绒毛膜促性腺激素（β-hCG）恢复正常的时间没有可用数据。UACE联合MTX与超声引导下局部MTX注射的比较 我们不确定UACE在初始治疗后是否提高了成功率（RR 0.95，95%CI 0.56至1.60；1项RCT，45名女性；极低质量证据）。不良反应：该研究报告每组治疗失败的数量相同（RR 0.88，95%CI 0.40至1.92；1项RCT，45名女性）。我们不确定UACE是否缩短了β-hCG恢复正常的时间（MD 1.50天，95%CI -3.16至6.16；1项RCT，45名女性；极低质量证据）。关于并发症没有可用数据。UAE/UACE后宫腔镜下刮宫术与超声引导下刮宫术的比较 两项研究报告了这一比较。一项比较了UAE后宫腔镜下刮宫术与超声引导下刮宫术，另一项比较了UACE后这两种干预措施。我们不确定宫腔镜下刮宫术在初始治疗后是否提高了成功率（UAE：RR 0.91，95%CI 0.81至1.03；1项RCT，66名女性；极低质量证据；UACE：RR 1.02，95%CI 0.96至1.09；1项RCT，92名女性；低质量证据）。我们不确定宫腔镜下刮宫术是否降低了并发症发生率（UAE：RR 4.00，95%CI 0.47至33.91；1项RCT，66名女性；极低质量证据；UACE：RR 0.18，95%CI 0.01至3.72；1项RCT，92名女性；低质量证据）。我们不确定宫腔镜下刮宫术是否减少了不良反应（UAE：RR 3.09，95%CI 0.12至78.70；1项RCT，66名女性；极低质量证据；UACE：无法估计；1项RCT，92名女性；极低质量证据）。我们不确定宫腔镜下刮宫术是否缩短了β-hCG恢复正常的时间（UAE：MD 4.03天，95%CI -1.79至9.85；1项RCT，66名女性；极低质量证据；UACE：MD 0.84天，95%CI -1.90至3.58；1项RCT，92名女性；低质量证据）。除CSP外的非输卵管异位妊娠 没有研究报告剖宫产瘢痕以外部位的非输卵管异位妊娠情况。
对于剖宫产瘢痕妊娠（CSP），不确定UAE/UACE与刮宫术前全身应用MTX在成功率、并发症或不良事件方面是否存在差异（低质量证据）。UAE/UACE后进行刮宫术的失血量低于全身应用MTX后（中等质量证据）。不确定宫腔镜下刮宫术与超声引导下刮宫术在治疗成功率、并发症、不良反应或β-hCG恢复正常时间方面是否存在差异（极低质量证据）。除CSP外没有关于非输卵管异位妊娠的研究，且针对此类妊娠的RCT不太可能开展。
