- Email: [email protected]
Endoscopic Treatment of Ectopic Pregnancy in a Cesarean Scar
Original Article
Endoscopic Treatment of Ectopic Pregnancy in a Cesarean Scar Hua Li, MD, Hong-Yan Guo, MD*, Jing-Song Han, MD, Jian-Liu Wang, MD, Guang-Wu Xiong, MD, Jie Shen, MD, and Jia-Jia Zhang, MD From the Department of Obstetrics and Gynecology, Third Hospital (Drs. Li, Guo, Han, Xiong, Shen, and Zhang), and People’s Hospital, Peking University (Dr. Wang), Beijing, China.
ABSTRACT Study Objective: To describe our experience with endoscopic removal of cesarean scar pregnancy. Design: Retrospective study (Canadian Task Force classification II-3). Setting: Tertiary-care university hospital. Patients: Twenty-one patients with cesarean scar pregnancy. Interventions: All the patients underwent removal of pregnancy mass at hysteroscopy or combined with laparoscopy. Nine patients received a methotrexate injection before the operation, and 13 underwent uterine artery embolization before surgery. Measurements and Main Results: Clinical data, serum b-human chorionic gonadotropin concentration, findings of ultrasound or magnetic resonance imaging examinations, therapeutic options, operative time, operative blood loss, and duration of hospitalization time were recorded. The mean serum b-human chorionic gonadotropin concentration at diagnosis was 53 350.4 IU/ L. Seventeen patients underwent hysteroscopy, which failed in 2, and the other 4 patients underwent hysteroscopy combined with laparoscopy. Mean operative time was 51.4 minutes, and mean blood loss was estimated at 48.1 mL. A gestational mass can be removed at hysteroscopy, with rapid recovery and a high success rate. If a cesarean scar pregnancy mass grows toward the bladder and abdominal cavity, hysteroscopy combined with laparoscopy is more appropriate. Preoperative uterine artery embolization can decrease blood loss substantially during the operation. No patients underwent hysterectomy. Conclusions: Endoscopy seems to be the optimal surgical management in patients with a cesarean scar pregnancy and who desire to preserve the uterus and fertility. However, further study is warranted. Journal of Minimally Invasive Gynecology (2011) 18, 31–35 Ó 2010 AAGL. All rights reserved. Keywords:
Cesarean scar; Ectopic pregnancy; Endoscopy; Treatment
Pregnancy in a cesarean scar of the uterus is the rarest form of ectopic pregnancy. Cases have been reported more commonly over the last decade, with the incidence ranging from 1:1800 to 1:2216 [1]. One reason for the increasing number of cesarean scar pregnancies (CSPs) is that abdominal deliveries are being performed more frequently, especially in China because of the 1-child family-planning policy. The wide use of Doppler transvaginal ultrasound examination may be another explanation [2]. Pregnancy in a cesarean scar may be dangerous for the patient because it may lead to heavy or life-threatening hemorThe authors have no commercial, proprietary, or financial interest in the products or companies described in this article. Corresponding author: Hong-Yan Guo, MD, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China. E-mail: [email protected] Submitted May 1, 2010. Accepted for publication August 5, 2010. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ - see front matter Ó 2010 AAGL. All rights reserved. doi:10.1016/j.jmig.2010.08.002
rhage, uterine rupture, and even hysterectomy [3]. To avoid serious complications, early diagnosis and appropriate treatment are required. Ultrasonography can enable prompt diagnosis, which allows for the choice of fertility preservation. To date, no standard method has been demonstrated for CSP. Local or systemic methotrexate (MTX) therapy has been used successfully [4]. However, hospitalization was prolonged, and time was required for the high concentration of serum b-human chorionic gonadotropin (b-hCG) to decrease to normal, indicating that long-term follow-up is needed. It has been reported that in approximately 24% of patients, MTX therapy failed [4]. Therefore, additional treatments were required including curettage, local resection at laparotomy, and even hysterectomy because of excessive hemorrhage. Surgical removal of the gestational sac can result in a shorter hospital stay and rapid decrease in the b-hCG concentration. Recently, endoscopic management of CSP has emerged as an alternative form of conservative treatment that includes
32
hysteroscopy and laparoscopy, both of which are minimally invasive operative techniques. They are beginning to have an important role in surgical treatment of CSP. Unlike blind suction and curettage, the sac can be removed under direct hysteroscopic observation, which seems to be less dangerous and more effective. When laparoscopy is performed, it results in less injury and more rapid recovery than with laparotomy. To date, only a few reports have been published that describe the application of endoscopy, with success rates of 95% to 100% [5–7]. The objective of the present study was to share our experience with management of CSP via endoscopy in 21 patients. The reasons why treatment with hysteroscopy alone failed in 2 cases is also analyzed. Between August 2004 and March 2010, 21 patients with CSP treated at endoscopy were recruited from Peking University Third Hospital and People’s Hospital, both of which are tertiary medical centers for clinical service and research. The study was approved by the institutional review board. Data collected from medical records included patient age, time of cesarean surgery, weeks of gestation, clinical findings, results of ultrasound or magnetic resonance imaging (MRI) examinations, therapeutic options, operative time, blood loss, and findings at follow-up. In all patients, serum b-hCG concentration was determined before treatment. The diagnosis of CSP was confirmed at transvaginal ultrasonography. The criteria of ultrasound diagnosis were as follows [1,2]: no gestational sac observed in the uterine cavity or cervical canal; gestational mass located in the anterior wall of the uterine isthmus; gestational sac embedded and surrounded by myometrium and fibrous tissue of the cesarean section scar; product of conception separated from the endometrial cavity or fallopian tube; and color Doppler ultrasound demonstrated blood flow surrounding the sac to exclude it from transportation along the cervical canal. To clarify equivocal ultrasound results or to determine whether the gestational sac protruded to the urinary bladder and abdominal cavity, MRI was performed. From December 2006, we began to treat CSP using operative hysteroscopy or combined hysteroscopy and laparoscopy, including those patients who did not respond to MTX therapy. Before the surgery, if ultrasound demonstrated that the sac had markedly increased blood flow signals or the patient had heavy vaginal bleeding, uterine artery embolization (UAE) was performed. With the patient under lumbar anesthesia, the cervix was dilated gradually using a Hegar dilator up to No. 10, after a naproxen suppository was administrated via the rectum. An operative hysteroscope with a 9-mm external sheath and a 4-mm 30-degree lens was placed inside the uterus to visualize the canal and cavity. A fluid management system (FluidSafe; Stryker Corp., Kalamazoo, MI) was used, with 5% glucose as the distention medium. A gestational sac, usually surrounded by a blood clot, was found in the myometrium of the cesarean scar. An electric loop using a dipolar electrosurgical system was used to remove the
Journal of Minimally Invasive Gynecology, Vol 18, No 1, January/February 2011
mass under direct vision by slowly moving the hysteroscope outward. Electrical coagulation was used to stop bleeding at the implantation site until all products of conception were cleared. To prevent uterine hemorrhage, especially in deeply implanted CSPs, hysteroscopy was performed under ultrasound guidance. In cases of heavy uterine bleeding intraoperatively, a No. 14 Foley catheter was inserted through the cervical canal, and the balloon was filled with 15 to 30 ml of water to compress the wound surface for homeostasis after surgery. If preoperative MRI demonstrated that the gestational sac was embedded deeply in the muscular layer of the uterine lower segment, hysteroscopy was performed under laparoscopic guidance with the patient under general anesthesia. When a ruptured uterus was found, the peritoneum between the uterus and the bladder was opened. After the products of conception were removed, bipolar electrocoagulation was used to stop bleeding, and absorbable suture was used to close the uterine wound. Patients were discharged when the b-hCG concentration had decreased considerably. Patients were followed up every week until the serum b-hCG concentration decreased to normal, with assessment of clinical status, and ultrasound examination 2 weeks or 1 month after the operation. The Kolmogorov-Smirnov method was used to test whether the data were normally distributed. Differences in the characteristics of patients at diagnosis and operation were estimated using the independent-samples t test or nonparametric test. A p value ,.05 was considered statistically significant, and all statistical tests were 2-sided. All analyses were performed using commercially available software (SPSS version 12.0; SPSS, Inc., Chicago, IL). Results The mean (SD; 95% confidence interval [CI]) age of the 21 patients with CSP was 35.1 (2.8; 95% CI, 33.86–36.42) years. Two patients had a history of 2 previous cesarean deliveries, whereas the others had only 1. Parity ranged from 1 to 2. The interval from the last cesarean delivery to the diagnosis of CSP was 5.9 (4.1; 95% CI, 4.00–7.71) years. Gestational age at diagnosis was 50.7 (13.9; 95% CI, 44.39–57.04) days. Fetal cardiac activity was present in 9 patients (43%). Thirteen patients (61.9%) exhibited vaginal bleeding. Two patients (9.5%) reported abdominal pain, whereas the other 6 (28.6%) had no symptoms. The serum b-hCG concentration at diagnosis was 53 350.4 IU/ L, the log transformation of which was 4.4 IU/L (0.7; 95% CI, 4.09–4.73). Ultrasonography was performed in all patients as a diagnostic tool. In addition, 10 patients underwent MRI, which clearly showed the diminished myometrium wall between the gestational sac and the bladder (Fig. 1). Operative time was 51.4 (26.7; 95% CI, 39.32–63.63) minutes, and blood loss was estimated at 48.1 (19.7; 95% CI, 28.29–66.90) mL. Nine patients (42.9%) were initially treated with systemic MTX, administered 1 to 3 times. However, the serum b-hCG
Li et al.
Endoscopic Treatment of Cesarean Scar Pregnancy
33 Table 1
Characteristics of patients at diagnosis and therapy in MTX and endoscopy groupsa Therapy
Variable Age, yr Parity, No. (%) 1 2 Time from CS to diagnosis, yr Gestational age, d Gestational sac diameter, cm Serum b-hCG, IU/Lc Operative time, min Operative blood loss, mL Hospitalization, d
MTX 1 95% CI endoscopy Endoscopy of the (n 5 9) (n 5 12) difference 35.9 (3.1) 8 (88.9) 1 (11.1) 6.3 (4.4)
34.6 (2.5) 11 (91.7) 1 (8.3) 5.5 (4.0)
21.29 to 3.90
p Value .39 .69b
23.01 to 4.67
.93
47.0 (17.8) 53.5 (10.0) 219.27 to 6.27 3.6 (1.6) 2.9 (1.7) 20.80 to 2.31
.26 .68
4.4 (0.6) 4.4 (0.7) 20.59 to 0.67 .69 46.1 (15.3) 55.5 (32.9) 232.22 to 13.44 .01 56.7 (20.7) 41.7 (18.9) 220.57 to 19.57 .32 13.6 (8.3)
7.5 (3.4)
0.57 to11.54
.03
CI 5 confidence interval; CS 5 cesarean section; MTX 5 methotrexate. a Unless otherwise indicated, values are given as mean (SD). b Fisher exact test. c Log transformation. Fig. 1. Magnetic resonance image of a cesarean scar pregnancy. The gestational sac (arrow) in the cesarean scar penetrated nearly the entire myometrium of the anterior wall of the uterus, and protruded into the bladder.
concentration in these patients decreased slowly (less than 25% of the former value), and the gestational sac grew larger. Hysteroscopy was suggested as a method for removal of the CSP mass. The other 12 patients (57.1%) were primarily treated at endoscopy. Characteristics of the patients at diagnosis, and therapy during endoscopy are given in Table 1. There was no statistically significant difference in patient characteristics including age, parity, gestational age, or serum b-hCG concentration between groups who did or did not receive MTX therapy. Compared with patients primarily managed at endoscopy, operative time was slightly shorter in the MTX injection group; however, hospitalization was prolonged. No difference in intraoperative blood loss was observed (Table 1). Thirteen patients (61.9%) underwent UAE before endoscopy, to prevent heavy bleeding during surgery in 12, and to control massive hemorrhage in 1. In the latter patient, a misdiagnosis of intrauterine pregnancy was made, and an artificial abortion was performed at another hospital. The patient was subsequently transferred to our hospital because of heavy bleeding. Hysteroscopy was performed within 24 hours after UAE. Eight patients (38.1%) did not undergo preoperative embolization. The results demonstrated that preoperative UAE was associated with significantly decreased blood loss during surgery. However, no correlation was observed in duration of hospitalization and operative time between groups with or without UAE. No statistically significant difference in patient characteristics at diagnosis was found between these 2 groups (Table 2).
Of 21 patients, 17 underwent hysteroscopy, and the other 4 patients underwent hysteroscopy combined with laparoscopy. Of these 4 patients, 2 underwent preoperative UAE, after which hysteroscopy was performed to remove the ectopic tissue under laparoscopic guidance. The mean operative time was 59 minutes, and blood loss was 10 mL. The third patient underwent laparoscopic bilateral uterine artery ligation followed by hysteroscopic resection of the gestational Table 2
Characteristics of patients at diagnosis and therapy in UAE 1 endoscopy and endoscopy groupsa Therapy
Variable Age, yr Parity, No. (%) 1 2 Time from CS to diagnosis, yr Gestational age, d Gestational sac diameter, cm Serum b-hCG, IU/Lc Operative time, min Operative blood loss, mL Hospitalization, d
UAE 1 endoscopy Endoscopy 95% CI of (n 5 13) (n 5 8) difference 34.7 (2.9) 7 (87.5) 1 (12.5) 5.4 (4.1)
35.9 (2.7) 12 (92.3) 1 (7.7) 6.6 (4.1)
21.47 to 3.84
p Value .83 .63b
22.65 to 5.13
.56
51.5 (12.2) 49.4 (17.1) 215.52 to 11.20 .72 3.1 (1.9) 3.3 (1.3) 21.40 to 1.84 .40 4.4 (0.7) 4.5 (0.7) 20.57 to 0.72 .82 48.8 (31.4) 55.9 (17.7) 218.44 to 32.65 .16 22.3 (9.8) 90.0 (32.8) 53.24 to 98.46 .02 10.0 (7.6)
10.3 (4.9)
26.08 to 6.58
CI 5 confidence interval; UAE 5 uterine artery embolization. a Unless otherwise indicated, values are given as mean (SD). b Fisher exact test. c Log transformation.
.25
34
sac. Operative time was 71 minutes, and blood loss was 100 mL. The fourth patient underwent MRI, which revealed that the gestational sac was deeply implanted in almost the entire myometrium, with accumulation of blood in the pouch of Douglas. A ruptured CSP was suspected, and was later confirmed at laparoscopy, and a subserous hematoma was found in the scar. After embolization, the gestational sac was excised at hysteroscopy, and the uterine cleft was sutured at laparoscopy. Operative time was 80 minutes, and blood loss was 100 mL. The patient recovered quickly after the operation. Endoscopic management was successful in 90.5% of patients. Hysteroscopy alone failed in 2 patients. Both patients subsequently underwent laparotomy, with a good outcome. The serum b-hCG concentration in the first patient decreased from 25 442 IU/L to 3164 IU/L within 7 days postoperatively. However, the b-hCG concentration plateaued, and ultrasonography revealed a mass with peripheral blood flow located within the cesarean scar. The patient was readmitted and underwent a wedge resection of the mass in the lower segment of uterus at laparotomy. Pathologic analysis demonstrated retained chorionic villi in the myometrium specimen. The second patient had heavy bleeding during hysteroscopy, and laparotomy was performed immediately. Ligation of the bilateral internal iliac arteries followed by wedge resection of the gestational products was performed. All 21 study patients surgeries were successful. No patients underwent hysterectomy. Discussion This study retrospectively investigated the endoscopic management of 21 patients with CSP. The surgery only group was compared with the group given MTX therapy or ancillary embolization. Our results showed that CSP can be treated at endoscopy with a high success rate and rapid recovery. Treatment failed in only 2 patients. The mean operative time was 51.4 minutes, and mean blood loss was estimated at 48.1 mL. Operative time was shorter after MTX therapy administered before surgery. Operative blood loss was less after preoperative UAE, as expected. As is well known, CSP is life-threatening because of its early implantation in the myometrium, and is thought to be more aggressive than placenta previa or placenta accreta [1]. Its development is primarily due to a defect in the lower uterine segment caused by previous cesarean surgery. The mechanism seems to occur when the embryo invades the myometrium through a microtubule between the cesarean scar and the endometrial canal [8]. In the present study, the mean interval from the last cesarean section to the diagnosis was 5.9 years, similar to that in a previous report [9]. Little is known about the natural history of CSP. The common symptom of CSP is vaginal bleeding, as observed in the present study; however, some patients have no symptoms. Transvaginal ultrasonography is a useful tool for differentiation and early diagnosis, with a sensitivity of 85%
Journal of Minimally Invasive Gynecology, Vol 18, No 1, January/February 2011
[10]. Color Doppler ultrasound can help to identify the peritrophoblastic flow. It has been suggested that transvaginal ultrasound be performed early in pregnant women with previous cesarean delivery to locate the sac [2], enabling timely diagnosis of CSP. Three-dimensional ultrasonography can provide improved images and anatomic details, enabling more precise diagnosis [2]. In our experience, MRI is also useful to provide a better image of the myometrium between the sac and the bladder. It is usually performed when findings at ultrasonography are equivocal [11]. To date, there is no agreement on the best approach of treatment for CSP. According to the limited reports of this rare entity, therapy varies. Expectant treatment is not recommended because of high risk of massive hemorrhage and uterine rupture [5]. Early diagnosis of CSP enables conservative management and use of various techniques in combination for uterine preservation. Patients can achieve successful future full-term pregnancy after conservative treatment [12]. The conservative approach can be medical or surgical. Various types of CSP have been proposed by Vial et al [13]. Products of conception in the first type could progress toward the cervical canal or uterine cavity. It may end in a viable birth, but there is high risk of heavy bleeding. In the second type, the sac is deeply implanted in the scar and progresses toward the bladder and abdominal cavity. This type ruptures easily, and when that happens, the wound gushes blood. In the first type of CSP, operative hysteroscopy can be effectively used to remove the gestational mass, with a high success rate. Our experience has demonstrated that, using operative hysteroscopy, the gestational sac at the implantation site can be observed clearly and removed from the uterine wall under direct visualization. It is much safer and more effective than dilation and curettage. Hysteroscopy has advantages, with a high success rate of 95% to 100%, and a low complication rate [5–7]. Moreover, surgical removal can prevent the toxic effects of MTX on reproduction, especially in patients who plan to become pregnant in the near future. The recommended interval between MTX injection and pregnancy is at least 6 months. To our disappointment, in the present study, hysteroscopy alone failed in 2 patients. Further analysis showed that both had the second type of CSP. The gestational mass in each of these 2 cases was deeply implanted and protruded into the abdominal cavity. However, in 1 study patient with suspected CSP rupture, treatment with hysteroscopy combined with laparoscopy was successful. In our experience, operative hysteroscopy alone cannot be used in patients with CSP rupture, and we suggest that direct laparoscopy or hysteroscopy combined with laparoscopy might be a better choice. At laparoscopy, the residual lesions that protrude into the abdominal cavity can be totally removed with less volume of blood loss and less injury. At the same time, ligation of the bilateral uterine arteries can be performed to prevent massive blood loss. Even in acute situations, uterine-preserving surgery can be performed in patients desiring future pregnancy [14].
Li et al.
Endoscopic Treatment of Cesarean Scar Pregnancy
Preoperative UAE can be used to control bleeding, as well as ligation of uterine arteries during operation. The CSP mass can be excised, followed by repair of the scar at laparoscopy or laparotomy. Laparoscopy has more advantages including a smaller wound, rapid recovery, shorter hospital stay, and less adhesion formation. It has been reported to be successful in patients with CSP [5]. If laparoscopy proves difficult, laparotomy can be performed. Laparotomy with wedge resection of the pregnancy sac can reduce the risk of residue in situ or of recurrence [11,14]. In the present study, treatment with hysteroscopy failed in 2 patients, and the CSP mass was subsequently resected at laparotomy, with a good outcome. Before surgery, patients should be informed of the operative risks including heavy bleeding, uterine rupture, and the possibility of conversion to laparotomy. Administration of MTX is also used as medical treatment in patients with unruptured CSP. Injection of MTX into the gestational sac under ultrasound guidance can be more effective because the dosage of MTX can be higher if given locally compared with systematically [4,10,15]. However, MTX treatment requires time for b-hCG concentration and CSP products to regress, and long follow-up is needed. In the present study, it took 20 to 108 days for the b-hCG concentration to decline to normal, and 28 to 198 days for resolution of the CSP mass [4]. A persistent gestational mass can be troublesome to patients. In addition, it is best to wait for more than 6 months to become pregnant after MTX injection therapy. Moreover, the success rate with MTX alone has been reported to be 76.2% [4]. Failed cases require further surgical treatment. According to Wang et al [4], nearly 19% of patients underwent hysterectomy as rescue management because of excessive bleeding; however, fertility was lost. In the present study, patients in whom MTX therapy failed subsequently underwent endoscopy to remove the gestational mass, and the uterus was preserved in all of them. Compared with medical treatment, patients with CSP treated at hysteroscopy exhibit more rapid decrease in b-hCG concentration, and have shorter hospitalization and follow-up times [6]; our results were similar. For these reasons, endoscopic removal of CSP might be preferred in patients with a desire for future fertility. Mean operative time was slightly shorter in the group who underwent endoscopy combined with MTX therapy. This may be because MTX has the ability to stop chorionic villi activity. The longer hospitalization duration is due to the time required for MTX therapy. However, blood loss during the procedure was not less. Before surgery, UAE can be used to control bleeding by temporarily blocking uterine perfusion. It has the advantages of less hemorrhage and shorter hospital stay for CSP management, and provides a better outcome than with MTX therapy [16]. We confirmed that UAE followed by hysteroscopy resulted in less volume of operative blood loss. Therefore, in our experience, treatment with UAE before surgery may be considered in patients with CSP, in particular those with
35
a high serum b-hCG concentration or increased blood flow signals around the gestational sac. During the operation, if only hysteroscopy is performed to treat the first type of CSP, it is best done under ultrasound guidance. After surgery, insertion of a Foley catheter for tamponade can effectively decrease the volume of blood loss after hysteroscopy. In conclusion, our experience demonstrates that endoscopy can be an optimal surgical treatment in patients with CSP who desire to preserve the uterus and fertility. The gestational mass in the cesarean scar can be removed at endoscopy, with a high success rate and rapid recovery. If the CSP mass grows toward the bladder and abdominal cavity, hysteroscopy combined with laparoscopy is more appropriate. Injection of MTX before endoscopy can decrease operative time but prolong hospitalization, whereas preoperative UAE can substantially decrease intraoperative blood loss.
References 1. Seow KM, Huang LW, Lin YH, et al. Cesarean scar pregnancy: issues in management. Ultrasound Obstet Gynecol. 2004;23:247–253. 2. Pascual MA, Hereter L, Graupera B, et al. Three-dimensional power Doppler ultrasound diagnosis and conservative treatment of ectopic pregnancy in a cesarean section scar. Fertil Steril. 2007;88: 706.e5–706.e7. 3. Marcus S, Cheng E, Goff B. Extrauterine pregnancy resulting from early uterine rupture. Obstet Gynecol. 1999;94:804–805. 4. Wang JH, Xu KH, Lin J, et al. Methotrexate therapy for cesarean section scar pregnancy with and without suction curettage. Fertil Steril. 2009; 92:1208–1213. 5. Wang CJ, Chao AS, Yuen LT, et al. Endoscopic management of cesarean scar pregnancy. Fertil Steril. 2006;85:494.e1–494.e4. 6. Deans R, Abbott J. Hysteroscopic management of cesarean scar ectopic pregnancy [published online ahead of print April 1, 2009]. Fertil Steril. 2010;93:1735–1740. 7. Yang Q, Piao S, Wang G, et al. Hysteroscopic surgery of ectopic pregnancy in the cesarean section scar. J Minim Invasive Gynecol. 2009;16:432–436. 8. Fylstra DL. Ectopic pregnancy within a cesarean scar: a review. Obstet Gynecol Surv. 2002;57:537–543. 9. Jiao LZ, Zhao J, Wan XR, et al. Diagnosis and treatment of cesarean scar pregnancy. Chin Med Sci J. 2008;23:10–15. 10. Rotas MA, Haberman S, Levgur M. Cesarean scar ectopic pregnancies: etiology, diagnosis, and management. Obstet Gynecol. 2006;107:1373–1381. 11. Ash A, Smith A, Maxwell D. Caesarean scar pregnancy. BJOG. 2007; 114:253–263. 12. Korkontzelos I, Tsirkas P, Antoniou N, et al. Successful term pregnancy after treatment of a cesarean scar ectopic gestation by endoscopic technique and conservative therapy. Fertil Steril. 2008;90: 2010.e13–2010.e15. 13. Vial Y, Petignat P, Hohlfeld P. Pregnancy in a cesarean scar. Ultrasound Obstet Gynecol. 2000;16:592–593. 14. Halperin R, Schneider D, Mendlovic S, et al. Uterine-preserving emergency surgery for cesarean scar pregnancies: another medical solution to an iatrogenic problem. Fertil Steril. 2009;91:2623–2627. 15. de Vaate AJ, Bro¨lmann HA, van der Slikke JW, et al. Therapeutic options of caesarean scar pregnancy: case series and literature review. J Clin Ultrasound. 2010;38:75–84. 16. Zhuang Y, Huang L. Uterine artery embolization compared with methotrexate for the management of pregnancy implanted within a cesarean scar. Am J Obstet Gynecol. 2009;201:152.e1–152.e3.
Endoscopic Treatment of Ectopic Pregnancy in a Cesarean Scar Hua Li, MD, Hong-Yan Guo, MD*, Jing-Song Han, MD, Jian-Liu Wang, MD, Guang-Wu Xiong, MD, Jie Shen, MD, and Jia-Jia Zhang, MD From the Department of Obstetrics and Gynecology, Third Hospital (Drs. Li, Guo, Han, Xiong, Shen, and Zhang), and People’s Hospital, Peking University (Dr. Wang), Beijing, China.
ABSTRACT Study Objective: To describe our experience with endoscopic removal of cesarean scar pregnancy. Design: Retrospective study (Canadian Task Force classification II-3). Setting: Tertiary-care university hospital. Patients: Twenty-one patients with cesarean scar pregnancy. Interventions: All the patients underwent removal of pregnancy mass at hysteroscopy or combined with laparoscopy. Nine patients received a methotrexate injection before the operation, and 13 underwent uterine artery embolization before surgery. Measurements and Main Results: Clinical data, serum b-human chorionic gonadotropin concentration, findings of ultrasound or magnetic resonance imaging examinations, therapeutic options, operative time, operative blood loss, and duration of hospitalization time were recorded. The mean serum b-human chorionic gonadotropin concentration at diagnosis was 53 350.4 IU/ L. Seventeen patients underwent hysteroscopy, which failed in 2, and the other 4 patients underwent hysteroscopy combined with laparoscopy. Mean operative time was 51.4 minutes, and mean blood loss was estimated at 48.1 mL. A gestational mass can be removed at hysteroscopy, with rapid recovery and a high success rate. If a cesarean scar pregnancy mass grows toward the bladder and abdominal cavity, hysteroscopy combined with laparoscopy is more appropriate. Preoperative uterine artery embolization can decrease blood loss substantially during the operation. No patients underwent hysterectomy. Conclusions: Endoscopy seems to be the optimal surgical management in patients with a cesarean scar pregnancy and who desire to preserve the uterus and fertility. However, further study is warranted. Journal of Minimally Invasive Gynecology (2011) 18, 31–35 Ó 2010 AAGL. All rights reserved. Keywords:
Cesarean scar; Ectopic pregnancy; Endoscopy; Treatment
Pregnancy in a cesarean scar of the uterus is the rarest form of ectopic pregnancy. Cases have been reported more commonly over the last decade, with the incidence ranging from 1:1800 to 1:2216 [1]. One reason for the increasing number of cesarean scar pregnancies (CSPs) is that abdominal deliveries are being performed more frequently, especially in China because of the 1-child family-planning policy. The wide use of Doppler transvaginal ultrasound examination may be another explanation [2]. Pregnancy in a cesarean scar may be dangerous for the patient because it may lead to heavy or life-threatening hemorThe authors have no commercial, proprietary, or financial interest in the products or companies described in this article. Corresponding author: Hong-Yan Guo, MD, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing 100191, China. E-mail: [email protected] Submitted May 1, 2010. Accepted for publication August 5, 2010. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ - see front matter Ó 2010 AAGL. All rights reserved. doi:10.1016/j.jmig.2010.08.002
rhage, uterine rupture, and even hysterectomy [3]. To avoid serious complications, early diagnosis and appropriate treatment are required. Ultrasonography can enable prompt diagnosis, which allows for the choice of fertility preservation. To date, no standard method has been demonstrated for CSP. Local or systemic methotrexate (MTX) therapy has been used successfully [4]. However, hospitalization was prolonged, and time was required for the high concentration of serum b-human chorionic gonadotropin (b-hCG) to decrease to normal, indicating that long-term follow-up is needed. It has been reported that in approximately 24% of patients, MTX therapy failed [4]. Therefore, additional treatments were required including curettage, local resection at laparotomy, and even hysterectomy because of excessive hemorrhage. Surgical removal of the gestational sac can result in a shorter hospital stay and rapid decrease in the b-hCG concentration. Recently, endoscopic management of CSP has emerged as an alternative form of conservative treatment that includes
32
hysteroscopy and laparoscopy, both of which are minimally invasive operative techniques. They are beginning to have an important role in surgical treatment of CSP. Unlike blind suction and curettage, the sac can be removed under direct hysteroscopic observation, which seems to be less dangerous and more effective. When laparoscopy is performed, it results in less injury and more rapid recovery than with laparotomy. To date, only a few reports have been published that describe the application of endoscopy, with success rates of 95% to 100% [5–7]. The objective of the present study was to share our experience with management of CSP via endoscopy in 21 patients. The reasons why treatment with hysteroscopy alone failed in 2 cases is also analyzed. Between August 2004 and March 2010, 21 patients with CSP treated at endoscopy were recruited from Peking University Third Hospital and People’s Hospital, both of which are tertiary medical centers for clinical service and research. The study was approved by the institutional review board. Data collected from medical records included patient age, time of cesarean surgery, weeks of gestation, clinical findings, results of ultrasound or magnetic resonance imaging (MRI) examinations, therapeutic options, operative time, blood loss, and findings at follow-up. In all patients, serum b-hCG concentration was determined before treatment. The diagnosis of CSP was confirmed at transvaginal ultrasonography. The criteria of ultrasound diagnosis were as follows [1,2]: no gestational sac observed in the uterine cavity or cervical canal; gestational mass located in the anterior wall of the uterine isthmus; gestational sac embedded and surrounded by myometrium and fibrous tissue of the cesarean section scar; product of conception separated from the endometrial cavity or fallopian tube; and color Doppler ultrasound demonstrated blood flow surrounding the sac to exclude it from transportation along the cervical canal. To clarify equivocal ultrasound results or to determine whether the gestational sac protruded to the urinary bladder and abdominal cavity, MRI was performed. From December 2006, we began to treat CSP using operative hysteroscopy or combined hysteroscopy and laparoscopy, including those patients who did not respond to MTX therapy. Before the surgery, if ultrasound demonstrated that the sac had markedly increased blood flow signals or the patient had heavy vaginal bleeding, uterine artery embolization (UAE) was performed. With the patient under lumbar anesthesia, the cervix was dilated gradually using a Hegar dilator up to No. 10, after a naproxen suppository was administrated via the rectum. An operative hysteroscope with a 9-mm external sheath and a 4-mm 30-degree lens was placed inside the uterus to visualize the canal and cavity. A fluid management system (FluidSafe; Stryker Corp., Kalamazoo, MI) was used, with 5% glucose as the distention medium. A gestational sac, usually surrounded by a blood clot, was found in the myometrium of the cesarean scar. An electric loop using a dipolar electrosurgical system was used to remove the
Journal of Minimally Invasive Gynecology, Vol 18, No 1, January/February 2011
mass under direct vision by slowly moving the hysteroscope outward. Electrical coagulation was used to stop bleeding at the implantation site until all products of conception were cleared. To prevent uterine hemorrhage, especially in deeply implanted CSPs, hysteroscopy was performed under ultrasound guidance. In cases of heavy uterine bleeding intraoperatively, a No. 14 Foley catheter was inserted through the cervical canal, and the balloon was filled with 15 to 30 ml of water to compress the wound surface for homeostasis after surgery. If preoperative MRI demonstrated that the gestational sac was embedded deeply in the muscular layer of the uterine lower segment, hysteroscopy was performed under laparoscopic guidance with the patient under general anesthesia. When a ruptured uterus was found, the peritoneum between the uterus and the bladder was opened. After the products of conception were removed, bipolar electrocoagulation was used to stop bleeding, and absorbable suture was used to close the uterine wound. Patients were discharged when the b-hCG concentration had decreased considerably. Patients were followed up every week until the serum b-hCG concentration decreased to normal, with assessment of clinical status, and ultrasound examination 2 weeks or 1 month after the operation. The Kolmogorov-Smirnov method was used to test whether the data were normally distributed. Differences in the characteristics of patients at diagnosis and operation were estimated using the independent-samples t test or nonparametric test. A p value ,.05 was considered statistically significant, and all statistical tests were 2-sided. All analyses were performed using commercially available software (SPSS version 12.0; SPSS, Inc., Chicago, IL). Results The mean (SD; 95% confidence interval [CI]) age of the 21 patients with CSP was 35.1 (2.8; 95% CI, 33.86–36.42) years. Two patients had a history of 2 previous cesarean deliveries, whereas the others had only 1. Parity ranged from 1 to 2. The interval from the last cesarean delivery to the diagnosis of CSP was 5.9 (4.1; 95% CI, 4.00–7.71) years. Gestational age at diagnosis was 50.7 (13.9; 95% CI, 44.39–57.04) days. Fetal cardiac activity was present in 9 patients (43%). Thirteen patients (61.9%) exhibited vaginal bleeding. Two patients (9.5%) reported abdominal pain, whereas the other 6 (28.6%) had no symptoms. The serum b-hCG concentration at diagnosis was 53 350.4 IU/ L, the log transformation of which was 4.4 IU/L (0.7; 95% CI, 4.09–4.73). Ultrasonography was performed in all patients as a diagnostic tool. In addition, 10 patients underwent MRI, which clearly showed the diminished myometrium wall between the gestational sac and the bladder (Fig. 1). Operative time was 51.4 (26.7; 95% CI, 39.32–63.63) minutes, and blood loss was estimated at 48.1 (19.7; 95% CI, 28.29–66.90) mL. Nine patients (42.9%) were initially treated with systemic MTX, administered 1 to 3 times. However, the serum b-hCG
Li et al.
Endoscopic Treatment of Cesarean Scar Pregnancy
33 Table 1
Characteristics of patients at diagnosis and therapy in MTX and endoscopy groupsa Therapy
Variable Age, yr Parity, No. (%) 1 2 Time from CS to diagnosis, yr Gestational age, d Gestational sac diameter, cm Serum b-hCG, IU/Lc Operative time, min Operative blood loss, mL Hospitalization, d
MTX 1 95% CI endoscopy Endoscopy of the (n 5 9) (n 5 12) difference 35.9 (3.1) 8 (88.9) 1 (11.1) 6.3 (4.4)
34.6 (2.5) 11 (91.7) 1 (8.3) 5.5 (4.0)
21.29 to 3.90
p Value .39 .69b
23.01 to 4.67
.93
47.0 (17.8) 53.5 (10.0) 219.27 to 6.27 3.6 (1.6) 2.9 (1.7) 20.80 to 2.31
.26 .68
4.4 (0.6) 4.4 (0.7) 20.59 to 0.67 .69 46.1 (15.3) 55.5 (32.9) 232.22 to 13.44 .01 56.7 (20.7) 41.7 (18.9) 220.57 to 19.57 .32 13.6 (8.3)
7.5 (3.4)
0.57 to11.54
.03
CI 5 confidence interval; CS 5 cesarean section; MTX 5 methotrexate. a Unless otherwise indicated, values are given as mean (SD). b Fisher exact test. c Log transformation. Fig. 1. Magnetic resonance image of a cesarean scar pregnancy. The gestational sac (arrow) in the cesarean scar penetrated nearly the entire myometrium of the anterior wall of the uterus, and protruded into the bladder.
concentration in these patients decreased slowly (less than 25% of the former value), and the gestational sac grew larger. Hysteroscopy was suggested as a method for removal of the CSP mass. The other 12 patients (57.1%) were primarily treated at endoscopy. Characteristics of the patients at diagnosis, and therapy during endoscopy are given in Table 1. There was no statistically significant difference in patient characteristics including age, parity, gestational age, or serum b-hCG concentration between groups who did or did not receive MTX therapy. Compared with patients primarily managed at endoscopy, operative time was slightly shorter in the MTX injection group; however, hospitalization was prolonged. No difference in intraoperative blood loss was observed (Table 1). Thirteen patients (61.9%) underwent UAE before endoscopy, to prevent heavy bleeding during surgery in 12, and to control massive hemorrhage in 1. In the latter patient, a misdiagnosis of intrauterine pregnancy was made, and an artificial abortion was performed at another hospital. The patient was subsequently transferred to our hospital because of heavy bleeding. Hysteroscopy was performed within 24 hours after UAE. Eight patients (38.1%) did not undergo preoperative embolization. The results demonstrated that preoperative UAE was associated with significantly decreased blood loss during surgery. However, no correlation was observed in duration of hospitalization and operative time between groups with or without UAE. No statistically significant difference in patient characteristics at diagnosis was found between these 2 groups (Table 2).
Of 21 patients, 17 underwent hysteroscopy, and the other 4 patients underwent hysteroscopy combined with laparoscopy. Of these 4 patients, 2 underwent preoperative UAE, after which hysteroscopy was performed to remove the ectopic tissue under laparoscopic guidance. The mean operative time was 59 minutes, and blood loss was 10 mL. The third patient underwent laparoscopic bilateral uterine artery ligation followed by hysteroscopic resection of the gestational Table 2
Characteristics of patients at diagnosis and therapy in UAE 1 endoscopy and endoscopy groupsa Therapy
Variable Age, yr Parity, No. (%) 1 2 Time from CS to diagnosis, yr Gestational age, d Gestational sac diameter, cm Serum b-hCG, IU/Lc Operative time, min Operative blood loss, mL Hospitalization, d
UAE 1 endoscopy Endoscopy 95% CI of (n 5 13) (n 5 8) difference 34.7 (2.9) 7 (87.5) 1 (12.5) 5.4 (4.1)
35.9 (2.7) 12 (92.3) 1 (7.7) 6.6 (4.1)
21.47 to 3.84
p Value .83 .63b
22.65 to 5.13
.56
51.5 (12.2) 49.4 (17.1) 215.52 to 11.20 .72 3.1 (1.9) 3.3 (1.3) 21.40 to 1.84 .40 4.4 (0.7) 4.5 (0.7) 20.57 to 0.72 .82 48.8 (31.4) 55.9 (17.7) 218.44 to 32.65 .16 22.3 (9.8) 90.0 (32.8) 53.24 to 98.46 .02 10.0 (7.6)
10.3 (4.9)
26.08 to 6.58
CI 5 confidence interval; UAE 5 uterine artery embolization. a Unless otherwise indicated, values are given as mean (SD). b Fisher exact test. c Log transformation.
.25
34
sac. Operative time was 71 minutes, and blood loss was 100 mL. The fourth patient underwent MRI, which revealed that the gestational sac was deeply implanted in almost the entire myometrium, with accumulation of blood in the pouch of Douglas. A ruptured CSP was suspected, and was later confirmed at laparoscopy, and a subserous hematoma was found in the scar. After embolization, the gestational sac was excised at hysteroscopy, and the uterine cleft was sutured at laparoscopy. Operative time was 80 minutes, and blood loss was 100 mL. The patient recovered quickly after the operation. Endoscopic management was successful in 90.5% of patients. Hysteroscopy alone failed in 2 patients. Both patients subsequently underwent laparotomy, with a good outcome. The serum b-hCG concentration in the first patient decreased from 25 442 IU/L to 3164 IU/L within 7 days postoperatively. However, the b-hCG concentration plateaued, and ultrasonography revealed a mass with peripheral blood flow located within the cesarean scar. The patient was readmitted and underwent a wedge resection of the mass in the lower segment of uterus at laparotomy. Pathologic analysis demonstrated retained chorionic villi in the myometrium specimen. The second patient had heavy bleeding during hysteroscopy, and laparotomy was performed immediately. Ligation of the bilateral internal iliac arteries followed by wedge resection of the gestational products was performed. All 21 study patients surgeries were successful. No patients underwent hysterectomy. Discussion This study retrospectively investigated the endoscopic management of 21 patients with CSP. The surgery only group was compared with the group given MTX therapy or ancillary embolization. Our results showed that CSP can be treated at endoscopy with a high success rate and rapid recovery. Treatment failed in only 2 patients. The mean operative time was 51.4 minutes, and mean blood loss was estimated at 48.1 mL. Operative time was shorter after MTX therapy administered before surgery. Operative blood loss was less after preoperative UAE, as expected. As is well known, CSP is life-threatening because of its early implantation in the myometrium, and is thought to be more aggressive than placenta previa or placenta accreta [1]. Its development is primarily due to a defect in the lower uterine segment caused by previous cesarean surgery. The mechanism seems to occur when the embryo invades the myometrium through a microtubule between the cesarean scar and the endometrial canal [8]. In the present study, the mean interval from the last cesarean section to the diagnosis was 5.9 years, similar to that in a previous report [9]. Little is known about the natural history of CSP. The common symptom of CSP is vaginal bleeding, as observed in the present study; however, some patients have no symptoms. Transvaginal ultrasonography is a useful tool for differentiation and early diagnosis, with a sensitivity of 85%
Journal of Minimally Invasive Gynecology, Vol 18, No 1, January/February 2011
[10]. Color Doppler ultrasound can help to identify the peritrophoblastic flow. It has been suggested that transvaginal ultrasound be performed early in pregnant women with previous cesarean delivery to locate the sac [2], enabling timely diagnosis of CSP. Three-dimensional ultrasonography can provide improved images and anatomic details, enabling more precise diagnosis [2]. In our experience, MRI is also useful to provide a better image of the myometrium between the sac and the bladder. It is usually performed when findings at ultrasonography are equivocal [11]. To date, there is no agreement on the best approach of treatment for CSP. According to the limited reports of this rare entity, therapy varies. Expectant treatment is not recommended because of high risk of massive hemorrhage and uterine rupture [5]. Early diagnosis of CSP enables conservative management and use of various techniques in combination for uterine preservation. Patients can achieve successful future full-term pregnancy after conservative treatment [12]. The conservative approach can be medical or surgical. Various types of CSP have been proposed by Vial et al [13]. Products of conception in the first type could progress toward the cervical canal or uterine cavity. It may end in a viable birth, but there is high risk of heavy bleeding. In the second type, the sac is deeply implanted in the scar and progresses toward the bladder and abdominal cavity. This type ruptures easily, and when that happens, the wound gushes blood. In the first type of CSP, operative hysteroscopy can be effectively used to remove the gestational mass, with a high success rate. Our experience has demonstrated that, using operative hysteroscopy, the gestational sac at the implantation site can be observed clearly and removed from the uterine wall under direct visualization. It is much safer and more effective than dilation and curettage. Hysteroscopy has advantages, with a high success rate of 95% to 100%, and a low complication rate [5–7]. Moreover, surgical removal can prevent the toxic effects of MTX on reproduction, especially in patients who plan to become pregnant in the near future. The recommended interval between MTX injection and pregnancy is at least 6 months. To our disappointment, in the present study, hysteroscopy alone failed in 2 patients. Further analysis showed that both had the second type of CSP. The gestational mass in each of these 2 cases was deeply implanted and protruded into the abdominal cavity. However, in 1 study patient with suspected CSP rupture, treatment with hysteroscopy combined with laparoscopy was successful. In our experience, operative hysteroscopy alone cannot be used in patients with CSP rupture, and we suggest that direct laparoscopy or hysteroscopy combined with laparoscopy might be a better choice. At laparoscopy, the residual lesions that protrude into the abdominal cavity can be totally removed with less volume of blood loss and less injury. At the same time, ligation of the bilateral uterine arteries can be performed to prevent massive blood loss. Even in acute situations, uterine-preserving surgery can be performed in patients desiring future pregnancy [14].
Li et al.
Endoscopic Treatment of Cesarean Scar Pregnancy
Preoperative UAE can be used to control bleeding, as well as ligation of uterine arteries during operation. The CSP mass can be excised, followed by repair of the scar at laparoscopy or laparotomy. Laparoscopy has more advantages including a smaller wound, rapid recovery, shorter hospital stay, and less adhesion formation. It has been reported to be successful in patients with CSP [5]. If laparoscopy proves difficult, laparotomy can be performed. Laparotomy with wedge resection of the pregnancy sac can reduce the risk of residue in situ or of recurrence [11,14]. In the present study, treatment with hysteroscopy failed in 2 patients, and the CSP mass was subsequently resected at laparotomy, with a good outcome. Before surgery, patients should be informed of the operative risks including heavy bleeding, uterine rupture, and the possibility of conversion to laparotomy. Administration of MTX is also used as medical treatment in patients with unruptured CSP. Injection of MTX into the gestational sac under ultrasound guidance can be more effective because the dosage of MTX can be higher if given locally compared with systematically [4,10,15]. However, MTX treatment requires time for b-hCG concentration and CSP products to regress, and long follow-up is needed. In the present study, it took 20 to 108 days for the b-hCG concentration to decline to normal, and 28 to 198 days for resolution of the CSP mass [4]. A persistent gestational mass can be troublesome to patients. In addition, it is best to wait for more than 6 months to become pregnant after MTX injection therapy. Moreover, the success rate with MTX alone has been reported to be 76.2% [4]. Failed cases require further surgical treatment. According to Wang et al [4], nearly 19% of patients underwent hysterectomy as rescue management because of excessive bleeding; however, fertility was lost. In the present study, patients in whom MTX therapy failed subsequently underwent endoscopy to remove the gestational mass, and the uterus was preserved in all of them. Compared with medical treatment, patients with CSP treated at hysteroscopy exhibit more rapid decrease in b-hCG concentration, and have shorter hospitalization and follow-up times [6]; our results were similar. For these reasons, endoscopic removal of CSP might be preferred in patients with a desire for future fertility. Mean operative time was slightly shorter in the group who underwent endoscopy combined with MTX therapy. This may be because MTX has the ability to stop chorionic villi activity. The longer hospitalization duration is due to the time required for MTX therapy. However, blood loss during the procedure was not less. Before surgery, UAE can be used to control bleeding by temporarily blocking uterine perfusion. It has the advantages of less hemorrhage and shorter hospital stay for CSP management, and provides a better outcome than with MTX therapy [16]. We confirmed that UAE followed by hysteroscopy resulted in less volume of operative blood loss. Therefore, in our experience, treatment with UAE before surgery may be considered in patients with CSP, in particular those with
35
a high serum b-hCG concentration or increased blood flow signals around the gestational sac. During the operation, if only hysteroscopy is performed to treat the first type of CSP, it is best done under ultrasound guidance. After surgery, insertion of a Foley catheter for tamponade can effectively decrease the volume of blood loss after hysteroscopy. In conclusion, our experience demonstrates that endoscopy can be an optimal surgical treatment in patients with CSP who desire to preserve the uterus and fertility. The gestational mass in the cesarean scar can be removed at endoscopy, with a high success rate and rapid recovery. If the CSP mass grows toward the bladder and abdominal cavity, hysteroscopy combined with laparoscopy is more appropriate. Injection of MTX before endoscopy can decrease operative time but prolong hospitalization, whereas preoperative UAE can substantially decrease intraoperative blood loss.
References 1. Seow KM, Huang LW, Lin YH, et al. Cesarean scar pregnancy: issues in management. Ultrasound Obstet Gynecol. 2004;23:247–253. 2. Pascual MA, Hereter L, Graupera B, et al. Three-dimensional power Doppler ultrasound diagnosis and conservative treatment of ectopic pregnancy in a cesarean section scar. Fertil Steril. 2007;88: 706.e5–706.e7. 3. Marcus S, Cheng E, Goff B. Extrauterine pregnancy resulting from early uterine rupture. Obstet Gynecol. 1999;94:804–805. 4. Wang JH, Xu KH, Lin J, et al. Methotrexate therapy for cesarean section scar pregnancy with and without suction curettage. Fertil Steril. 2009; 92:1208–1213. 5. Wang CJ, Chao AS, Yuen LT, et al. Endoscopic management of cesarean scar pregnancy. Fertil Steril. 2006;85:494.e1–494.e4. 6. Deans R, Abbott J. Hysteroscopic management of cesarean scar ectopic pregnancy [published online ahead of print April 1, 2009]. Fertil Steril. 2010;93:1735–1740. 7. Yang Q, Piao S, Wang G, et al. Hysteroscopic surgery of ectopic pregnancy in the cesarean section scar. J Minim Invasive Gynecol. 2009;16:432–436. 8. Fylstra DL. Ectopic pregnancy within a cesarean scar: a review. Obstet Gynecol Surv. 2002;57:537–543. 9. Jiao LZ, Zhao J, Wan XR, et al. Diagnosis and treatment of cesarean scar pregnancy. Chin Med Sci J. 2008;23:10–15. 10. Rotas MA, Haberman S, Levgur M. Cesarean scar ectopic pregnancies: etiology, diagnosis, and management. Obstet Gynecol. 2006;107:1373–1381. 11. Ash A, Smith A, Maxwell D. Caesarean scar pregnancy. BJOG. 2007; 114:253–263. 12. Korkontzelos I, Tsirkas P, Antoniou N, et al. Successful term pregnancy after treatment of a cesarean scar ectopic gestation by endoscopic technique and conservative therapy. Fertil Steril. 2008;90: 2010.e13–2010.e15. 13. Vial Y, Petignat P, Hohlfeld P. Pregnancy in a cesarean scar. Ultrasound Obstet Gynecol. 2000;16:592–593. 14. Halperin R, Schneider D, Mendlovic S, et al. Uterine-preserving emergency surgery for cesarean scar pregnancies: another medical solution to an iatrogenic problem. Fertil Steril. 2009;91:2623–2627. 15. de Vaate AJ, Bro¨lmann HA, van der Slikke JW, et al. Therapeutic options of caesarean scar pregnancy: case series and literature review. J Clin Ultrasound. 2010;38:75–84. 16. Zhuang Y, Huang L. Uterine artery embolization compared with methotrexate for the management of pregnancy implanted within a cesarean scar. Am J Obstet Gynecol. 2009;201:152.e1–152.e3.