|Year : 2018 | Volume
| Issue : 2 | Page : 88-94
Comparison of Five Treatment Strategies for Cesarean Scar Pregnancy
Feng-Yi Xiao, Xiao-Hong Xue, Xin Lu
Department of Gynaecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200032, China
|Date of Submission||05-Mar-2018|
|Date of Web Publication||4-Oct-2018|
No. 419 Fangxie Road, Huangpu District, Shanghai 200032
No. 419 Fangxie Road, Huangpu District, Shanghai 200032
Source of Support: None, Conflict of Interest: None
Objective: To explore appropriate treatment strategy for cesarean scar pregnancy (CSP) in the first and second trimester.
Methods: Clinical characteristics and treatment strategies in 182 patients with CSP were retrospectively analyzed. Treatment strategies were as follows: Group A (n = 102), uterine artery chemoembolization (UACE) followed by dilation and curettage (D&C); Group B (n = 63), D&C; Group C (n = 6), hysteroscopy; Group D (n = 6), laparotomy; and Group E (n = 5), laparoscopy. The basic clinical findings were collected and analyzed, along with the curative effects.
Results: The preoperative serum beta-human chorionic gonadotropin (β-HCG) level was in the order of Group D, A>B, C>E (P = 0.001); the size of gestational sac (GS) was in the order of Group D, E>A, C>B (P = 0.000); and the thickness of the anterior myometrium was in the order of Group B>A, C>D, E (P = 0.000). Three cases in the second trimester were all in Group D; two cases were treated with UACE before laparotomy with moderate blood loss (100 and 200 mL, respectively) and the third case was initially treated with D&C and had severe hemorrhage.
Conclusions: The diameter of GS, thickness of the anterior myometrium, and preoperative β-HCG level are important factors for the choice of treatment. UACE combined with D&C is a useful measure for most Type 2 CSP cases in the first trimester. For Type 2 CSP cases in the second trimester, UACE before laparotomy could be a reasonable choice.
Keywords: Cesarean Scar Pregnancy; Hysteroscopy; Laparoscopy; Laparotomy; Uterine Artery Chemoembolization
|How to cite this article:|
Xiao FY, Xue XH, Lu X. Comparison of Five Treatment Strategies for Cesarean Scar Pregnancy. Reprod Dev Med 2018;2:88-94
| Introduction|| |
Cesarean scar pregnancy (CSP) is a comparatively uncommon category of ectopic pregnancy, accounting for about 1% of all ectopic pregnancies. Two types of CSP have been described: one is characterized by implantation of the gestational sac (GS) on the scar with progression toward either the cervico-isthmic space or the uterine cavity and may develop into a viable birth; another is a deep GS implantation into a postcesarean section defect with progression toward rupture and hemorrhage during the first trimester of pregnancy. The following criteria of ultrasound findings have been outlined for the diagnosis of CSP: (1) an empty uterus with a clear view of the endometrial layer; (2) an empty cervical canal; (3) a discontinuity in the anterior wall of the uterus, demonstrated on a sagittal view of the uterus when the direction of the ultrasound beam runs through the amniotic sac; and (4) the GS located in the anterior part of the isthmus of the uterus, with a diminished myometrial layer between the bladder and the sac., If not diagnosed and treated appropriately, CSP may cause hemorrhage and uterine rupture and may require hysterectomy. Even with timely intervention, the possibility of intraoperative and postoperative hemorrhage still exists.
Many treatment strategies have been reported, most of which aim to preserve the uterus. Expectant therapy is generally not recommended because of the risk of uterine rupture. Termination of pregnancy in the early stage with medication or surgery reduces the risk of invasion of the bladder and surrounding organs. Most of the literature suggests that patients with serum beta-human chorionic gonadotropin (β-HCG) levels <5,000 IU/L can be treated with medication. Methotrexate (MTX) can be injected intramuscularly or directly into the GS or a combination of both. Operative modalities include dilation and curettage (D&C), hysteroscopic GS removal, laparoscopic removal of CSP, and open surgery for CSP dissection or hysterectomy. [10,11] However, to the best of our knowledge, the clinical manifestations and their significance for the choice of treatment in Type 2 CSP using several different strategies in a single center have not been reported, especially those in the second trimester. To explore the indications for various treatment strategies for CSP in the first and second trimester, the clinical records of 182 patients were retrospectively analyzed.
| Methods|| |
Clinical information of 182 CSP patients who received treatment in our hospital between January 2011 and April 2014 was retrospectively analyzed. The patients' mean age was 34.0 ± 4.9 years; median gravidity was 3 (range 1–8); median parity was 1 (range 1–2); median cesarean section was 1 (range 1–2); and mean gestational age was 51.1 ± 14.6 (28–120) days, with three patients in the second trimester of pregnancy; time interval from the last cesarean section was 6.1 ± 4.2 (0.5–20) years; preoperative serum β-HCG was 52,703.2 ± 52,837.0 (17.9–200,000) mIU/mL. Inclusion criteria were women with Type 2 CSP in the first or second trimester. Exclusion criteria were patients who had received curettage or mifepristone or MTX treatment before admission. All patients signed informed consent forms before treatment. This study was approved by the ethics committee of our hospital.
The patients were divided into five treatment groups: Group A (n = 102), uterine artery chemoembolization (UACE) followed by D&C; Group B (n = 63), D&C; Group C (n = 6), hysteroscopic removal of CSP; Group D (n = 6), laparotomy; and Group E (n = 5), laparoscopic dissection of CSP and repair of the uterus. Clinical history, laboratory and sonographic examination results, and curative effects of the five methods were collected and analyzed. Differences in age, gravidity, number of previous cesarean section, and time interval from last cesarean section were not statistically different among the five groups (P > 0.05). Gestational age was advanced in Group D and not significantly different among the other four groups [Table 1] and [Figure 1].
|Figure 1: Comparison between groups on gestational age. The values show the means ± standard deviation. *,†indicate that the value for the difference between the two groups compared is P < 0.05 and P < 0.001, respectively. Only differences with statistical significance are indicated. UACE: Uterine artery chemoembolization; D&C: Dilation and curettage.|
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Uterine artery chemoembolization followed by dilation and curettage
Type 2 CSP with gestational age ≤90 days and abundant blood supply to the GS.
After puncturing of the right femoral artery, a 5-F Roberts uterine artery catheter was correctly placed in the bilateral uterine artery with the guidance of a 0.889-mm guidewire. After the intubation and angiography, a 100–150 mg dose of MTX and 80,000 units of gentamicin were infused bilaterally before the embolization procedure with gelatin sponge particles (diameter of 0.7–1.0 mm). When the blood flow of bilateral uterine artery was slower, the arteries were embolized with fresh gelatin sponge particles (diameter of 2–3 mm) until the blood flow stopped. With the head of the catheter back in the iliac artery, extubation was exerted after satisfactory embolization was confirmed by angiography. The puncture point was locally bandaged by a hemostatic instrument for artery with pressure for 8 h. Within 48 h after UACE, D&C was performed on all patients under the guidance of ultrasound.
Dilation and curettage
Type 2 CSP with gestational age ≤65 days and little blood supply to the GS.
GS removal with D&C under the guidance of ultrasound was performed. Some patients received preoperative oral mifepristone for cervical preparation or mifepristone combined with misoprostol to induce abortion. After most of the GS had been discharged, a D&C was performed for the remaining pregnancy tissue in the scar. In some occasions, a Foley catheter balloon was placed into the isthmic portion of the cervix to reduce continuous bleeding with a total volume of <80 mL.
Hysteroscopic removal of cesarean scar pregnancy
Type 2 CSP with gestational age ≤90 days.
A hysteroscopic examination would first be performed to locate the GS, and then, the GS would be removed with hysteroscopic electrode resection and/or suction curettage.
Laparotomy for dissection of cesarean scar pregnancy and repair of the uterus
Type 2 CSP with the thickness of the anterior myometrium ≤2 mm and profuse blood supply to the GS or CSP in the second trimester.
Under general anesthesia, six units of diluted pituitrin was injected into the myometrium. An incision was made through the serosa, myometrium, and endometrium of the protruding area with a unipolar electric knife, the CSP was removed using grasping forceps, and the uterine cavity and lower uterine segment underwent curettage. Fifty mg/m2 of MTX was injected into the myometrium of the lower uterine segment, and the cesarean scar tissue was trimmed at the incision margin and sutured continuously.
Type 2 CSP with the thickness of the anterior myometrium ≤2 mm and profuse blood supply to the GS.
The general procedure was similar to that for open surgery, with the main difference being use of minimally invasive techniques and instruments.
SPSS 17.0 software (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Continuous variables were compared between two groups using the t-test or Mann–Whitney test and between multiple groups using ANOVA or Kruskal–Wallis test; P < 0.05 was considered statistically significant. Quantitative variables were expressed as mean ± standard deviation.
| Results|| |
The serum β-HCG level before treatment was elevated in all patients in the order of Group D, A>B, C>E (P = 0.001) [Table 2] and [Figure 2].
|Table 2: Laboratory examination and sonographic features of the 5 groups|
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|Figure 2: Comparison on preoperative β-HCG level and sonographic features among the five groups. The values show the means ± standard deviation. *,†,‡Indicate that the value for the difference between the two groups compared is P < 0.05, P < 0.01, and P < 0.001, respectively. Only differences with statistical significance are indicated. β-HCG: Beta-human chorionic gonadotropin; UACE: Uterine artery chemoembolization; D&C: Dilation and curettage; GS: Gestational sac.|
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Transvaginal sonography confirmed the diagnosis of CSP in all patients. The diameter of GS was 22.6 ± 13.5 (3–88) mm, and the size of GS was in the order of Group D, E>A, C>B (P = 0.000) [Table 2] and [Figure 2]. Three patients in Group D were in the second trimester when diagnosed, and one had a fetal biparietal diameter of 37 mm, with placenta accreta. The thickness of the anterior myometrium was 2.5 ± 2.2 (0–14) mm, with a thickness order of Group B>A, C>D, E (P = 0.000) [Table 2] and [Figure 2]. Two of the three second-trimester pregnancies were detected with placenta accreta, and one underwent hysterectomy.
Patients in Group D and Group E had the largest GS size and the minimum thickness of the anterior myometrium (P < 0.05). Patients in Group A had higher preoperative β-HCG level, larger GS size, and thinner thickness of the anterior myometrium than those in Group B (P = 0.000).
The operative time was in the order of Group D, E>C>A>B (P = 0.000). The intraoperative blood loss was in the order of Group D, E>C>A, B (P = 0.000) [Table 3] and [Figure 3]. Two laparotomy cases without UACE had much greater average intraoperative blood loss (1850 and 3500 mL) than the other four with UACE (50–600 mL). The laparoscopy and laparotomy groups seemed to have the greatest amount of intraoperative blood loss since one case in the laparoscopy group and two in the laparotomy group were initially treated with direct D&C, and laparoscopy or laparotomy was emergently performed as a rescue measure for hemorrhage.
|Figure 3: Comparison of the treatment outcomes among the five groups. The values show the means ± standard deviation. *,†,‡Indicate that the value for the difference between the two groups compared is P < 0.05, P < 0.01, and P < 0.001, respectively. Only differences with statistical significance are indicated. β-HCG: Beta-human chorionic gonadotropin; UACE: Uterine artery chemoembolization; D&C: Dilation and curettage.|
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The time of hospitalization was in the order of Group D, C, E, A>B (P = 0.000). The laparotomy group required the longest hospitalization, followed by hysteroscopy, laparoscopy, and UACE + D&C groups. No significant differences were detected between groups in the percentage by which β-HCG decreased in 3 days after treatment (P = 0.684) and the time of β-HCG normalization (P = 0.369), which indicates that the treatment selected for each group was equally effective in clearing trophoblastic tissue. The time of menstruation recovery was not significantly different between groups (P = 0.219) [Table 3] and [Figure 3].
Five patients had 25.3 ± 26.9% (4.5%–70.1%) elevation of serum β-HCG after UACE, and 31 had 41.3 ± 25.6% (0.3%–91.3%) decrease. Patients with intraoperative blood loss of >200 mL had greater diameter of GS (48.4 ± 20.6 mm) and less thickness of the anterior myometrium (0.8 ± 1.4 mm) compared with those with a blood loss of <200 mL [P < 0.05, [Table 4]]. Three cases in the second trimester were all in Group D. Two were sonographically diagnosed with placenta accreta and treated with UACE before laparotomy, with moderate blood loss (100 and 200 mL, respectively); the third case was treated with D&C initially, followed by severe hemorrhage, and was transferred for emergent laparotomy.
|Table 4: Laboratory examination and sonographic features of patients with different volumes of bleeding|
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| Discussion|| |
The incidence of CSP has been increasing in recent years. Many reports have described different treatment strategies for CSP with various success rates and complications. Most were case reports or comparisons of two different treatment strategies,,,, but none compared the effectiveness of a wide range of treatment strategies, especially for cases in the second trimester.
A study by Lan et al. on 79 patients concluded that a diagnosis of CSP should receive UACE as the primary treatment. In our data, compared with the D&C group, those who underwent UACE combined with D&C had significantly larger GS and decreased thickness of the anterior myometrium, while the intraoperative blood loss and postoperative decline of β-HCG were not significantly different between the two groups. This indicates that our criteria for the choice of UACE before D&C in some patients were appropriate. Wang and Tseng stated that D&C is suitable only for CSP patients with gestational age below 7 weeks in whom there is no indication of deep sac implantation. However, our data showed that UACE helped expand the indication for D&C.
HCG is produced primarily by differentiated syncytiotrophoblasts and represents an embryonic signal that is essential for the maintenance of pregnancy. We also found that after UACE, some patients did not have an obvious decline of β-HCG, and a few even rise. It is reported that the half-life of serum β-HCG is approximately 24 h. Therefore, on 24 h after removal of GS, the concentration of β-HCG should decline to half of the preoperative level and reduce by half in every subsequent 24 h. A persistent high level of β-HCG after UACE may reflect that failure to remove the trophoblastic tissue, and the destruction of trophoblastic cells by MTX may even cause β-HCG to be secreted into the circulation.
Laparoscopic operation has some advantages in dealing with CSP. The defect in the scar could be repaired, which may reduce the risk of uterine rupture and CSP in the future. However, this procedure requires the operator to be well equipped with laparoscopic skills.
The laparotomy group had the greatest GS diameter and the minimum thickness of the anterior myometrium. Compared with laparoscopy, laparotomy causes greater trauma with longer postoperative recovery time and hospital stay, but hemostatic procedure such as suturing is relatively simpler and more convenient, especially for more complicated cases as those in the second trimester. Therefore, laparotomy should be chosen over laparoscopy when the situation is more emergent and complicated. Moreover, the choice also depends on the laparoscopic skill of a surgeon. Two laparotomy cases without UACE had much greater average intraoperative blood loss than the other four with UACE, which suggests that for patients with greater risk of heavy bleeding, UACE should be considered as a pretreatment for laparotomy to reduce the risk of hemorrhage.
Timor-Tritsch and Monteagudo deemed that in the case of CSP, local MTX and hysteroscopy directed procedures had the lowest complication rates. The electrocoagulation function of hysteroscopy can effectively reduce the blood loss during surgery, and the hemostatic effect of UACE may not be as important in patients who are going to be treated with hysteroscopy as in those with D&C.
When heavy bleeding occurs during surgery, effective methods need to be adopted. Utilization of chemoembolization, Foley catheter balloon, bilateral uterine artery ligation, or transitions to laparoscopy or laparotomy have all been reported to be effective measures.,,,, In our hospital, the remedies for extensive hemorrhage include direct transition to laparotomy or laparoscopy, emergent UACE to block the blood supply of the uterine arteries, intrauterine packing with gauze, Foley catheter compression, or a combination of several methods, which all proved effective to reduce bleeding under different circumstances. The reason that laparoscopy and laparotomy groups had the greatest amount of blood loss was partially because they were adopted as remedy measures after hemorrhage in D&C, and the total blood loss was counted together.
In this study, we retrospectively analyzed Type 2 CSP cases from our clinical practice. However, our study has certain limitations. First, multiple operators were involved, thus raising the issue of bias. Second, the number of cases in the second trimester was relatively small and may have compromised our results. The number of cases in the hysteroscopy, laparoscopy, and laparotomy was comparatively smaller. However, these were the actual number of treatment given during the time span of our study, which also indicates that UACE and D&C would suffice for the treatment of most of the Type 2 CSP patients in the first trimester. Future prospective studies with a larger sample of second-trimester CSP cases may provide better guidance for appropriate treatment of CSP.
In conclusion, the sonographic findings of diameter of GS, thickness of the anterior myometrium, and preoperative serum β-HCG level are important factors for the treatment choice-making. Large GS size and deep infiltration of GS are indicative of the risk of intraoperative hemorrhage. UACE combined with D&C is a useful measure for most Type 2 CSP cases in the first trimester. For Type 2 CSP cases in the second trimester, UACE before laparotomy should be a reasonable choice.
We would like to thank all the gynecologists in our hospital for their valued input into the care of the patients discussed in this article.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]