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REVIEW ARTICLE
Heterotopic Cesarean Scar Pregnancy Diagnosis, Treatment, and Prognosis Zhenbo OuYang, MD, Qian Yin, MD, Yujing Xu, MD, Yunyan Ma, MD, Qiushi Zhang, PhD, Yanhong Yu, PhD
Received December 4, 2013, from the Department of Gynecology, Guangdong No. 2 Provincial People’s Hospital, Guangzhou, China (Z.O., Y.M., Q.Z.); Department of Obstetrics and Gynecology, Nanfang Hospital of Southern Medical University, Guangzhou, China (Q.Y., Y.Y.); and Department of Obstetrics and Gynecology, Weifang People’s Hospital, Weifang, China (Y.X.). Revision requested December 18, 2013. Revised manuscript accepted for publication December 31, 2013. This work was supported by the Medical Science and Technology Research Fund of Guangdong (grant B2013063). Address correspondence to Zhenbo OuYang, MD, Department of Gynecology, Guangdong No. 2 Provincial People’s Hospital, 1 Shiliugang Rd, 510317 Guangzhou, China. E-mail: [email protected] Abbreviations
KCl, potassium chloride; MTX, methotrexate doi:10.7863/ultra.33.9.1533
Heterotopic cesarean scar pregnancy is a rare, life-threatening form of ectopic pregnancy. To provide information regarding the clinical manifestations, diagnosis, management, and prognosis of this condition, we reviewed all cases reported in the English literature. All literature on heterotopic cesarean scar pregnancy was retrieved by searching the PubMed database and tracking references of the relevant literature. Full texts were reviewed, and clinical manifestations, diagnostic methods, and the relationship between the treatment and prognosis were summarized. A total of 14 patients with heterotopic cesarean scar pregnancies were identified, including 6 spontaneous pregnancies and 8 following in vitro fertilization–embryo transfer. Gestational ages at diagnosis ranged from 5 weeks to 8 weeks 4 days. Only 5 cases presented with vaginal bleeding, and the others were asymptomatic. All 14 cases were diagnosed by transvaginal sonography. One patient with no future fertility requirements underwent pregnancy termination by methotrexate. Of the remaining 13 patients who desired to preserve their intrauterine gestations, 10 were treated by sonographically guided selective embryo reduction in situ (by embryo aspiration, drug injection, or both); 2 underwent laparoscopic and hysteroscopic excision of the ectopic pregnancy masses; and 1 was treated by expectant management. All operations were successful and maintained a living intrauterine gestation. Twelve cases resulted in live births by cesarean delivery (3 at term and 9 preterm). One patient underwent pregnancy termination at 12 weeks because of a fetal malformation confirmed by sonography. The possibility of heterotopic cesarean scar pregnancy after cesarean delivery should be considered, especially when pregnancy follows assisted reproductive technology. Transvaginal sonography is an important tool for diagnosis and management. Despite the many options, the best treatment for this condition remains unclear. Selective embryo reduction in situ with sonographic guidance is the main treatment modality and can result in a successful intrauterine gestation, albeit at high risk. Key Words—cesarean scar pregnancy; gynecologic ultrasound; heterotopic pregnancy; selective embryo reduction; transvaginal sonography
H
eterotopic cesarean scar pregnancy is one of the rarest forms of ectopic pregnancy, in which one pregnancy is located in the scar of a previous cesarean delivery, and the other is in the uterine cavity, potentially causing life-threatening complications.1–3 Because most patients need to preserve the viable intrauterine gestation, the treatment of heterotopic cesarean scar pregnancy is difficult and challenging.4,5 Because of its low incidence, only individual cases have been reported, and a standard treatment protocol has not been established.3,6,7 In the past decade, with the increased rate of cesarean delivery and widespread application of assisted reproductive technology, the incidence of heterotopic cesarean scar pregnancy has gradually increased.1,2 Therefore, to provide better guidance for treatment of heterotopic cesarean scar pregnancy, we summarized the clinical manifestations, diagnosis, treatment, and prognosis by a retrospective analysis of all reported cases.
©2014 by the American Institute of Ultrasound in Medicine | J Ultrasound Med 2014; 33:1533–1537 | 0278-4297 | www.aium.org
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OuYang et al—Heterotopic Cesarean Scar Pregnancy
Materials and Methods A PubMed search of English literature published up to August 2013 using the terms “heterotopic pregnancy” and “cesarean scar pregnancy” yielded 22 articles reporting heterotopic cesarean scar pregnancy. By reading the abstracts, we selected 13 articles and excluded 9 unrelated articles, all of which were case reports. An additional case was obtained by reference tracking. The full text of each of the 14 reports was reviewed carefully,1–14 and the clinical and diagnostic information was analyzed (Table 1).
Results A total of 14 patients with heterotopic cesarean scar pregnancies were identified, including 6 spontaneous pregnancies and 8 following in vitro fertilization–embryo transfer. Gestational ages at diagnosis ranged from 5 weeks to 8 weeks 4 days. Only 5 cases presented with vaginal bleeding, and the remaining 9 cases were asymptomatic. All 14 cases were diagnosed by routine first-trimester sonography. Twelve cases were twin pregnancies with 1 gestational sac implanted in the cesarean scar,1,2,5–14 and 2 cases were triplet pregnancies, 1 in which 2 gestational sacs were implanted in the cesarean scar3 and another in which 1 gestational sac was implanted in the scar and 2 were intrauterine.4 All cases were diagnosed by transvaginal sonography, and 1 patient, who was pregnant with an intrauterine device in situ, underwent transvaginal sonography combined with transabdominal sonography and pelvic magnetic resonance imaging. In each case, fetal cardiac activity was observed in all gestational sacs (in the uterine cavity or cesarean scar) at the initial visit. The patient with an intrauterine device had no future fertility requirements, and the pregnancy was terminated by methotrexate (MTX) injection.13 Of the remaining 13 patients who desired to preserve their intrauterine gestations, 10 were treated by selective embryo reduction in situ with sonographic guidance, including 6 cases of potassium chloride (KCl) injection, 2 cases of embryo aspiration, 1 case of embryo aspiration and KCl injection, and 1 case of MTX injection combined with KCl. One patient was treated by expectant management because the cardiac activity in the cesarean scar pregnancy disappeared on the fifth day of admission, and 2 patients were treated by laparoscopic and hysteroscopic excision of the ectopic pregnancy masses at the cesarean scar sites. All 13 embryo reduction operations were successful and maintained an ongoing living intrauterine gestation. One patient underwent pregnancy termination at 12 weeks 1534
because of trisomy 13, which was confirmed by sonography and chorionic villus sampling.6 The remaining 12 intrauterine pregnancies were generally uneventful, although 2 patients had a small amount of vaginal bleeding with or without uterine contractions.3,12 Another patient had placenta previa and placenta accreta.14 Eventually, the 12 pregnancies ended with live births by cesarean delivery, including 1 case of Miller syndrome, a rare genetic condition inherited as an autosomal recessive trait. Three of the 12 births were accomplished by elective cesarean delivery at term, and the other 9 were accomplished by emergency cesarean delivery because of vaginal bleeding, premature rupture of membranes, placental abruption, or preterm labor. During the emergency cesarean deliveries, 4 patients had massive bleeding and needed blood transfusions with or without bilateral internal iliac artery ligation,2,3,12,14 and 1 of the 4 also underwent subtotal hysterectomy.14 With the exception of the 2 patients who were treated by laparoscopy and hysteroscopy,5,11 a mass still could be detected at the previous cesarean scar site in the other 10 patients and could be observed on sonography in 9 of the 10. In 1 case, the mass was expelled automatically at 26 weeks 6 days, and in 2 cases, the mass disappeared by the third trimester and was thought to be completely selfabsorbed. All of the masses were removed during cesarean delivery in the remaining 6 patients, and pathologic examinations conducted in 2 of the 6 patients found placental and deciduous tissues. Three of the 6 patients had massive bleeding during surgery and needed emergency interventions.
Discussion Since cesarean scar pregnancy was reported by Larsen and Solomon15 in 1978, there has been increasing awareness of the condition and its treatment.1 There are already many successful treatment modalities, such as systemic or local injection of MTX, uterine artery embolization, and hysteroscopy or laparoscopy.9,10 Unlike those with cesarean scar pregnancies, most patients with heterotopic cesarean scar pregnancies want to preserve their viable intrauterine gestations or at least their fertility. This factor makes treatment much more difficult and challenging.5,8 In addition, because of the rarity of this condition, treatment experience is limited, and there is no standard method.3,6 Until recently, the incidence of heterotopic pregnancy in the general population was 1 per 30,000 deliveries.1 However, with improvements in assisted reproductive technology, the incidence of heterotopic cesarean scar pregnancy has increased and may occur in 1% of such con-
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J Ultrasound Med 2014; 33:1533–1537
IVF-ET
IVF-ET
IVF-ET
Spontaneous
IVF-ET
IVF-ET
Spontaneous
Spontaneous
Spontaneous
IVF-ET
Spontaneous
Spontaneous
IVF-ET
Wang et al2
Litwicka et al3
Hsieh et al4
Demirel et al5
Gupta et al6
Bai et al7
Uysal and Uysal8
Yazicioglu et al9
Jurkovic et al10
Wang et al11
Taşkin et al12
Dueñas-Garcia and Young13
Ugurlucan et al14 6
5
8+4
7
7
6+2
8
7+6
6+1
6+5
5
6
5
6
GA, wk+d
No
Vaginal bleeding Vaginal bleeding No
No
Vaginal bleeding
Vaginal bleeding No
Vaginal bleeding No
No
No
No
No
Presenting Symptoms
Hysteroscopic excision KCl injection
KCl injection
KCl injection
Expectant management KCl injection
Embryo aspiration Laparoscopic excision Embryo aspiration
KCl and MTX injection
KCl injection
KCl injection
TVS, TAS, and MRI TVS KCl injection and embryo aspiration
TVS
TVS
TVS
TVS
TVS
TVS
TVS
TVS
TVS
TVS
TVS
TVS
Diagnostic Method Treatment
Persistent
Persistent
Scar Mass
Placenta previa and placenta accreta
Vaginal bleeding
No
No
No
No
No
No
Persistent
No
Detached spontaneously at 26+6 wk Persistent
Persistent
Persistent
Vaginal Persistent bleeding and uterine contractions No Disappeared at 14 wk No No
No
No
Pregnancy Symptoms
No
Live birth by CD at 38 wk
Live birth by CD at 34 wk due to preterm labor Pregnancy termination by MTX
No
Yes
Complications and Interventions
No
No
Bilateral internal iliac artery ligation and blood transfusion due to massive bleeding Birth defect and blood transfusion due to blood loss
No
Bilateral internal iliac artery ligation and subtotal hysterectomy due to massive bleeding
Blood transfusion due to massing bleeding
No
No
No
No (disap- No peared) Yes No
No
No
Yes
Yes
Yes
Mass Excision
Live birth by CD at 31 wk Yes due to vaginal hemorrhage Live birth by CD at 39 wk No
Pregnancy termination at 12 wk due to fetal malformation Live birth by CD at 36+4 wk due to preterm labor Live birth by CD at 35 wk due to preterm labor Live birth by CD at 30+3 wk due to PROM
Live birth by CD at 32 wk due to preterm labor Live birth by CD at 38 wk
Live birth by CD at 36 wk due to placental abruption
Live birth by CD at 36 wk due to PROM Live birth by CD at 35 wk due to preterm labor
Pregnancy Outcome
CD indicates cesarean delivery; IVF-ET, in vitro fertilization–embryo transfer; MRI, magnetic resonance imaging; PROM, premature rupture of membranes; TAS, transabdominal sonography; and TVS, transvaginal sonography.
IVF-ET
Mode of Conception
Salomon et al1
Reference
Table 1. All Reported Heterotopic Cesarean Scar Pregnancy Cases
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ceptions.1,2 Of the 14 cases of heterotopic cesarean scar pregnancy reported up to August 2013, 8 occurred after in vitro fertilization–embryo transfer. Consequently, it is necessary to establish methods for diagnosis and treatment of this condition.2,11 Patients with heterotopic cesarean scar pregnancies do not have specific manifestations. Vaginal bleeding is the most common symptom, but most cases are diagnosed by routine first-trimester sonography without any symptoms.12,13 Transvaginal sonography, especially transvaginal color Doppler sonography, makes early diagnosis possible, even in asymptomatic cases, and thus is the most important method for diagnosis of this condition. The main sonographic criterion of heterotopic cesarean scar pregnancy is visualization of gestational sacs in the uterine cavity and anterior part of uterine isthmus, which leads to discontinuity of the anterior uterine wall. A sonographic diagnostic standard for cesarean scar pregnancy has been established, and the diagnostic sensitivity can be up to 85% for an experienced ultrasound physician.12 A combination of transabdominal and transvaginal sonography or even magnetic resonance imaging may be helpful when diagnosis is difficult.13 The treatment for heterotopic cesarean scar pregnancy is basically the same as that for cesarean scar pregnancy when the patient has no future fertility requirements and no need to retain the intrauterine pregnancy. Many methods can be used, such as systemic or local injection of MTX and dilation and curettage after uterine artery embolization. For those who want to preserve their intrauterine gestations, the treatment is quite different. Based on the treatment experience for cesarean scar pregnancy and other types of heterotopic pregnancies, the treatment for heterotopic cesarean scar pregnancy can be divided into 2 main categories: selective embryo reduction in situ and surgical removal of ectopic gestational tissue.11 The former mainly refers to sonographically guided embryo aspiration or drug injection in situ, and the latter involves resection of the scar pregnancy tissue through an abdominal laparoscopic and hysteroscopic approach.7,14 In the 13 cases discussed here in which there was a desire to preserve the intrauterine gestations, 10 were treated by selective embryo reduction in situ with sonographic guidance. Embryo reduction in situ can be further divided into 3 types: embryo aspiration, drug injection, and embryo aspiration combined with drug injection. Given the potential teratogenicity of MTX on the intrauterine gestation, hypertonic glucose and, more commonly, KCl are the main drugs used for treatment of heterotopic cesarean scar pregnancy.1,3 Embryo aspiration is suitable
1536
mainly during the initial weeks of gestation, so early diagnosis is vital. Although a cesarean scar pregnancy is terminated after drug injection, because the blood supply of the scar tissue is relatively poor, absorption of the gestational sac is extremely slow. Residual pregnancy tissue can cause not only abnormal vaginal bleeding but also massive bleeding during cesarean delivery.4,5 Therefore, for later gestations, local injection of a drug combined with aspiration is a more reasonable approach. Furthermore, an expectant method with supportive management might be a choice if the fetal cardiac activity of the cesarean scar pregnancy disappears spontaneously. Theoretically, the mechanism and prognosis of expectant management are similar to those of drug injection in situ.7 In view of the successful experience with laparoscopic and hysteroscopic excisions of ectopic masses in the treatment of cesarean scar pregnancy, some practitioners have applied these methods successfully to the treatment of heterotopic cesarean scar pregnancy.5,11 Because the pregnancy tissue at the scar is excised directly during the operation, symptoms such as vaginal bleeding will not appear during pregnancy.5 More importantly, endoscopic excision of a cesarean scar pregnancy can provide a strong lower uterine segment, which leads to fewer complications in the third trimester and at cesarean delivery. However, the difficulties of manipulations and massive blood loss are concerns during endoscopic surgery. More importantly, adverse effects of anesthesia, distention media, carbon dioxide, and electrical devices on the preserved intrauterine pregnancy are unknown and need further evaluation.7,11 Experience to date suggests that, compared to endoscopic surgery, embryo reduction in situ with sonographic guidance is much easier and has the advantages of a smaller lesion and higher success rate. In summary, although heterotopic cesarean scar pregnancy is very rare, its incidence will increase in parallel with the increased rate of cesarean delivery and more widespread application of assisted reproductive technology. Obviously, early diagnosis is warranted to reduce complications and improve treatment success. Therefore, the possibility of heterotopic cesarean scar pregnancy should be considered in any pregnancy occurring after cesarean delivery, especially those following assisted reproductive technology. Transvaginal sonography is an important tool for both diagnosis and treatment of heterotopic cesarean scar pregnancy. Despite the various treatment options for this condition, the best treatment is still unclear. Selective embryo reduction in situ with sonographic guidance is the most popular treatment at present. Fortunately, most intrauterine pregnancies can be preserved after treatment.
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Nevertheless, there are many complications during pregnancy and the perioperative period when the intrauterine gestation is continued, which require that thorough informed consent be obtained from the patient and that the pregnancy be treated as high risk.
References 1.
2.
3.
4.
5.
6. 7.
8.
9.
10.
11.
12. 13.
14. Ugurlucan FG, Bastu E, Dogan M, Kalelioglu I, Alanya S, Has R. Management of cesarean heterotopic pregnancy with transvaginal ultrasound-guided potassium chloride injection and gestational sac aspiration, and review of the literature. J Minim Invasive Gynecol 2012; 19:671–673. 15. Larsen JV, Solomon MH. Pregnancy in a uterine scar sacculus—an unusual cause of postabortal haemorrhage: a case report. S Afr Med J1978; 53:142–143.
Salomon LJ, Fernandez H, Chauveaud A, Doumerc S, Frydman R. Successful management of a heterotopic Caesarean scar pregnancy: potassium chloride injection with preservation of the intrauterine gestation—case report. Hum Reprod 2003; 18:189–191. Wang CN, Chen CK, Wang HS, Chiueh HY, Soong YK. Successful management of heterotopic cesarean scar pregnancy combined with intrauterine pregnancy after in vitro fertilization–embryo transfer. Fertil Steril 2007; 88:706.e13–706.e16. Litwicka K, Greco E, Prefumo F, et al. Successful management of a triplet heterotopic caesarean scar pregnancy after in vitro fertilization–embryo transfer. Fertil Steril 2011; 95:291.e1–291.e3. Hsieh BC, Hwang JL, Pan HS, Huang SC, Chen CY, Chen PH. Heterotopic Caesarean scar pregnancy combined with intrauterine pregnancy successfully treated with embryo aspiration for selective embryo reduction: case report. Hum Reprod 2004; 19:285–287. Demirel LC, Bodur H, Selam B, Lembet A, Ergin T. Laparoscopic management of heterotopic cesarean scar pregnancy with preservation of intrauterine gestation and delivery at term: case report. Fertil Steril 2009; 91:1293.e5–1293.e7. Gupta R, Vaikousi E, Whitlow B. Heterotopic caesarean section scar pregnancy. J Obstet Gynaecol 2010; 30:626–627. Bai XX, Gao HJ, Yang XF, Dong MY, Zhu YM. Expectant management of heterotopic cesarean scar pregnancy. Chin Med J (Engl) 2012; 125:1341–1344. Uysal F, Uysal A. Spontaneous heterotopic cesarean scar pregnancy: conservative management by transvaginal sonographic guidance and successful pregnancy outcome. J Ultrasound Med 2013; 32:547–548. Yazicioglu HF, Turgut S, Madazli R, Aygün M, Cebi Z, Sönmez S. An unusual case of heterotopic twin pregnancy managed successfully with selective feticide. Ultrasound Obstet Gynecol 2004; 23:626–627. Jurkovic D, Hillaby K, Woelfer B, Lawrence A, Salim R, Elson CJ. Firsttrimester diagnosis and management of pregnancies implanted into the lower uterine segment Cesarean section scar. Ultrasound Obstet Gynecol 2003; 21:220–227. Wang CJ, Tsai F, Chen C, Chao A. Hysteroscopic management of heterotopic cesarean scar pregnancy. Fertil Steril 2010; 94:1529.e15– 1529.e18. Taşkin S, Taşkin EA, Ciftçi TT. Heterotopic cesarean scar pregnancy: how should it be managed? Obstet Gynecol Surv 2009; 64:690–695. Dueñas-Garcia OF, Young C. Heterotopic cesarean scar pregnancy associated with a levonorgestrel-releasing intrauterine device. Int J Gynaecol Obstet 2011; 114:153–154.
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REVIEW ARTICLE
Heterotopic Cesarean Scar Pregnancy Diagnosis, Treatment, and Prognosis Zhenbo OuYang, MD, Qian Yin, MD, Yujing Xu, MD, Yunyan Ma, MD, Qiushi Zhang, PhD, Yanhong Yu, PhD
Received December 4, 2013, from the Department of Gynecology, Guangdong No. 2 Provincial People’s Hospital, Guangzhou, China (Z.O., Y.M., Q.Z.); Department of Obstetrics and Gynecology, Nanfang Hospital of Southern Medical University, Guangzhou, China (Q.Y., Y.Y.); and Department of Obstetrics and Gynecology, Weifang People’s Hospital, Weifang, China (Y.X.). Revision requested December 18, 2013. Revised manuscript accepted for publication December 31, 2013. This work was supported by the Medical Science and Technology Research Fund of Guangdong (grant B2013063). Address correspondence to Zhenbo OuYang, MD, Department of Gynecology, Guangdong No. 2 Provincial People’s Hospital, 1 Shiliugang Rd, 510317 Guangzhou, China. E-mail: [email protected] Abbreviations
KCl, potassium chloride; MTX, methotrexate doi:10.7863/ultra.33.9.1533
Heterotopic cesarean scar pregnancy is a rare, life-threatening form of ectopic pregnancy. To provide information regarding the clinical manifestations, diagnosis, management, and prognosis of this condition, we reviewed all cases reported in the English literature. All literature on heterotopic cesarean scar pregnancy was retrieved by searching the PubMed database and tracking references of the relevant literature. Full texts were reviewed, and clinical manifestations, diagnostic methods, and the relationship between the treatment and prognosis were summarized. A total of 14 patients with heterotopic cesarean scar pregnancies were identified, including 6 spontaneous pregnancies and 8 following in vitro fertilization–embryo transfer. Gestational ages at diagnosis ranged from 5 weeks to 8 weeks 4 days. Only 5 cases presented with vaginal bleeding, and the others were asymptomatic. All 14 cases were diagnosed by transvaginal sonography. One patient with no future fertility requirements underwent pregnancy termination by methotrexate. Of the remaining 13 patients who desired to preserve their intrauterine gestations, 10 were treated by sonographically guided selective embryo reduction in situ (by embryo aspiration, drug injection, or both); 2 underwent laparoscopic and hysteroscopic excision of the ectopic pregnancy masses; and 1 was treated by expectant management. All operations were successful and maintained a living intrauterine gestation. Twelve cases resulted in live births by cesarean delivery (3 at term and 9 preterm). One patient underwent pregnancy termination at 12 weeks because of a fetal malformation confirmed by sonography. The possibility of heterotopic cesarean scar pregnancy after cesarean delivery should be considered, especially when pregnancy follows assisted reproductive technology. Transvaginal sonography is an important tool for diagnosis and management. Despite the many options, the best treatment for this condition remains unclear. Selective embryo reduction in situ with sonographic guidance is the main treatment modality and can result in a successful intrauterine gestation, albeit at high risk. Key Words—cesarean scar pregnancy; gynecologic ultrasound; heterotopic pregnancy; selective embryo reduction; transvaginal sonography
H
eterotopic cesarean scar pregnancy is one of the rarest forms of ectopic pregnancy, in which one pregnancy is located in the scar of a previous cesarean delivery, and the other is in the uterine cavity, potentially causing life-threatening complications.1–3 Because most patients need to preserve the viable intrauterine gestation, the treatment of heterotopic cesarean scar pregnancy is difficult and challenging.4,5 Because of its low incidence, only individual cases have been reported, and a standard treatment protocol has not been established.3,6,7 In the past decade, with the increased rate of cesarean delivery and widespread application of assisted reproductive technology, the incidence of heterotopic cesarean scar pregnancy has gradually increased.1,2 Therefore, to provide better guidance for treatment of heterotopic cesarean scar pregnancy, we summarized the clinical manifestations, diagnosis, treatment, and prognosis by a retrospective analysis of all reported cases.
©2014 by the American Institute of Ultrasound in Medicine | J Ultrasound Med 2014; 33:1533–1537 | 0278-4297 | www.aium.org
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OuYang et al—Heterotopic Cesarean Scar Pregnancy
Materials and Methods A PubMed search of English literature published up to August 2013 using the terms “heterotopic pregnancy” and “cesarean scar pregnancy” yielded 22 articles reporting heterotopic cesarean scar pregnancy. By reading the abstracts, we selected 13 articles and excluded 9 unrelated articles, all of which were case reports. An additional case was obtained by reference tracking. The full text of each of the 14 reports was reviewed carefully,1–14 and the clinical and diagnostic information was analyzed (Table 1).
Results A total of 14 patients with heterotopic cesarean scar pregnancies were identified, including 6 spontaneous pregnancies and 8 following in vitro fertilization–embryo transfer. Gestational ages at diagnosis ranged from 5 weeks to 8 weeks 4 days. Only 5 cases presented with vaginal bleeding, and the remaining 9 cases were asymptomatic. All 14 cases were diagnosed by routine first-trimester sonography. Twelve cases were twin pregnancies with 1 gestational sac implanted in the cesarean scar,1,2,5–14 and 2 cases were triplet pregnancies, 1 in which 2 gestational sacs were implanted in the cesarean scar3 and another in which 1 gestational sac was implanted in the scar and 2 were intrauterine.4 All cases were diagnosed by transvaginal sonography, and 1 patient, who was pregnant with an intrauterine device in situ, underwent transvaginal sonography combined with transabdominal sonography and pelvic magnetic resonance imaging. In each case, fetal cardiac activity was observed in all gestational sacs (in the uterine cavity or cesarean scar) at the initial visit. The patient with an intrauterine device had no future fertility requirements, and the pregnancy was terminated by methotrexate (MTX) injection.13 Of the remaining 13 patients who desired to preserve their intrauterine gestations, 10 were treated by selective embryo reduction in situ with sonographic guidance, including 6 cases of potassium chloride (KCl) injection, 2 cases of embryo aspiration, 1 case of embryo aspiration and KCl injection, and 1 case of MTX injection combined with KCl. One patient was treated by expectant management because the cardiac activity in the cesarean scar pregnancy disappeared on the fifth day of admission, and 2 patients were treated by laparoscopic and hysteroscopic excision of the ectopic pregnancy masses at the cesarean scar sites. All 13 embryo reduction operations were successful and maintained an ongoing living intrauterine gestation. One patient underwent pregnancy termination at 12 weeks 1534
because of trisomy 13, which was confirmed by sonography and chorionic villus sampling.6 The remaining 12 intrauterine pregnancies were generally uneventful, although 2 patients had a small amount of vaginal bleeding with or without uterine contractions.3,12 Another patient had placenta previa and placenta accreta.14 Eventually, the 12 pregnancies ended with live births by cesarean delivery, including 1 case of Miller syndrome, a rare genetic condition inherited as an autosomal recessive trait. Three of the 12 births were accomplished by elective cesarean delivery at term, and the other 9 were accomplished by emergency cesarean delivery because of vaginal bleeding, premature rupture of membranes, placental abruption, or preterm labor. During the emergency cesarean deliveries, 4 patients had massive bleeding and needed blood transfusions with or without bilateral internal iliac artery ligation,2,3,12,14 and 1 of the 4 also underwent subtotal hysterectomy.14 With the exception of the 2 patients who were treated by laparoscopy and hysteroscopy,5,11 a mass still could be detected at the previous cesarean scar site in the other 10 patients and could be observed on sonography in 9 of the 10. In 1 case, the mass was expelled automatically at 26 weeks 6 days, and in 2 cases, the mass disappeared by the third trimester and was thought to be completely selfabsorbed. All of the masses were removed during cesarean delivery in the remaining 6 patients, and pathologic examinations conducted in 2 of the 6 patients found placental and deciduous tissues. Three of the 6 patients had massive bleeding during surgery and needed emergency interventions.
Discussion Since cesarean scar pregnancy was reported by Larsen and Solomon15 in 1978, there has been increasing awareness of the condition and its treatment.1 There are already many successful treatment modalities, such as systemic or local injection of MTX, uterine artery embolization, and hysteroscopy or laparoscopy.9,10 Unlike those with cesarean scar pregnancies, most patients with heterotopic cesarean scar pregnancies want to preserve their viable intrauterine gestations or at least their fertility. This factor makes treatment much more difficult and challenging.5,8 In addition, because of the rarity of this condition, treatment experience is limited, and there is no standard method.3,6 Until recently, the incidence of heterotopic pregnancy in the general population was 1 per 30,000 deliveries.1 However, with improvements in assisted reproductive technology, the incidence of heterotopic cesarean scar pregnancy has increased and may occur in 1% of such con-
J Ultrasound Med 2014; 33:1533–1537
J Ultrasound Med 2014; 33:1533–1537
IVF-ET
IVF-ET
IVF-ET
Spontaneous
IVF-ET
IVF-ET
Spontaneous
Spontaneous
Spontaneous
IVF-ET
Spontaneous
Spontaneous
IVF-ET
Wang et al2
Litwicka et al3
Hsieh et al4
Demirel et al5
Gupta et al6
Bai et al7
Uysal and Uysal8
Yazicioglu et al9
Jurkovic et al10
Wang et al11
Taşkin et al12
Dueñas-Garcia and Young13
Ugurlucan et al14 6
5
8+4
7
7
6+2
8
7+6
6+1
6+5
5
6
5
6
GA, wk+d
No
Vaginal bleeding Vaginal bleeding No
No
Vaginal bleeding
Vaginal bleeding No
Vaginal bleeding No
No
No
No
No
Presenting Symptoms
Hysteroscopic excision KCl injection
KCl injection
KCl injection
Expectant management KCl injection
Embryo aspiration Laparoscopic excision Embryo aspiration
KCl and MTX injection
KCl injection
KCl injection
TVS, TAS, and MRI TVS KCl injection and embryo aspiration
TVS
TVS
TVS
TVS
TVS
TVS
TVS
TVS
TVS
TVS
TVS
TVS
Diagnostic Method Treatment
Persistent
Persistent
Scar Mass
Placenta previa and placenta accreta
Vaginal bleeding
No
No
No
No
No
No
Persistent
No
Detached spontaneously at 26+6 wk Persistent
Persistent
Persistent
Vaginal Persistent bleeding and uterine contractions No Disappeared at 14 wk No No
No
No
Pregnancy Symptoms
No
Live birth by CD at 38 wk
Live birth by CD at 34 wk due to preterm labor Pregnancy termination by MTX
No
Yes
Complications and Interventions
No
No
Bilateral internal iliac artery ligation and blood transfusion due to massive bleeding Birth defect and blood transfusion due to blood loss
No
Bilateral internal iliac artery ligation and subtotal hysterectomy due to massive bleeding
Blood transfusion due to massing bleeding
No
No
No
No (disap- No peared) Yes No
No
No
Yes
Yes
Yes
Mass Excision
Live birth by CD at 31 wk Yes due to vaginal hemorrhage Live birth by CD at 39 wk No
Pregnancy termination at 12 wk due to fetal malformation Live birth by CD at 36+4 wk due to preterm labor Live birth by CD at 35 wk due to preterm labor Live birth by CD at 30+3 wk due to PROM
Live birth by CD at 32 wk due to preterm labor Live birth by CD at 38 wk
Live birth by CD at 36 wk due to placental abruption
Live birth by CD at 36 wk due to PROM Live birth by CD at 35 wk due to preterm labor
Pregnancy Outcome
CD indicates cesarean delivery; IVF-ET, in vitro fertilization–embryo transfer; MRI, magnetic resonance imaging; PROM, premature rupture of membranes; TAS, transabdominal sonography; and TVS, transvaginal sonography.
IVF-ET
Mode of Conception
Salomon et al1
Reference
Table 1. All Reported Heterotopic Cesarean Scar Pregnancy Cases
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ceptions.1,2 Of the 14 cases of heterotopic cesarean scar pregnancy reported up to August 2013, 8 occurred after in vitro fertilization–embryo transfer. Consequently, it is necessary to establish methods for diagnosis and treatment of this condition.2,11 Patients with heterotopic cesarean scar pregnancies do not have specific manifestations. Vaginal bleeding is the most common symptom, but most cases are diagnosed by routine first-trimester sonography without any symptoms.12,13 Transvaginal sonography, especially transvaginal color Doppler sonography, makes early diagnosis possible, even in asymptomatic cases, and thus is the most important method for diagnosis of this condition. The main sonographic criterion of heterotopic cesarean scar pregnancy is visualization of gestational sacs in the uterine cavity and anterior part of uterine isthmus, which leads to discontinuity of the anterior uterine wall. A sonographic diagnostic standard for cesarean scar pregnancy has been established, and the diagnostic sensitivity can be up to 85% for an experienced ultrasound physician.12 A combination of transabdominal and transvaginal sonography or even magnetic resonance imaging may be helpful when diagnosis is difficult.13 The treatment for heterotopic cesarean scar pregnancy is basically the same as that for cesarean scar pregnancy when the patient has no future fertility requirements and no need to retain the intrauterine pregnancy. Many methods can be used, such as systemic or local injection of MTX and dilation and curettage after uterine artery embolization. For those who want to preserve their intrauterine gestations, the treatment is quite different. Based on the treatment experience for cesarean scar pregnancy and other types of heterotopic pregnancies, the treatment for heterotopic cesarean scar pregnancy can be divided into 2 main categories: selective embryo reduction in situ and surgical removal of ectopic gestational tissue.11 The former mainly refers to sonographically guided embryo aspiration or drug injection in situ, and the latter involves resection of the scar pregnancy tissue through an abdominal laparoscopic and hysteroscopic approach.7,14 In the 13 cases discussed here in which there was a desire to preserve the intrauterine gestations, 10 were treated by selective embryo reduction in situ with sonographic guidance. Embryo reduction in situ can be further divided into 3 types: embryo aspiration, drug injection, and embryo aspiration combined with drug injection. Given the potential teratogenicity of MTX on the intrauterine gestation, hypertonic glucose and, more commonly, KCl are the main drugs used for treatment of heterotopic cesarean scar pregnancy.1,3 Embryo aspiration is suitable
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mainly during the initial weeks of gestation, so early diagnosis is vital. Although a cesarean scar pregnancy is terminated after drug injection, because the blood supply of the scar tissue is relatively poor, absorption of the gestational sac is extremely slow. Residual pregnancy tissue can cause not only abnormal vaginal bleeding but also massive bleeding during cesarean delivery.4,5 Therefore, for later gestations, local injection of a drug combined with aspiration is a more reasonable approach. Furthermore, an expectant method with supportive management might be a choice if the fetal cardiac activity of the cesarean scar pregnancy disappears spontaneously. Theoretically, the mechanism and prognosis of expectant management are similar to those of drug injection in situ.7 In view of the successful experience with laparoscopic and hysteroscopic excisions of ectopic masses in the treatment of cesarean scar pregnancy, some practitioners have applied these methods successfully to the treatment of heterotopic cesarean scar pregnancy.5,11 Because the pregnancy tissue at the scar is excised directly during the operation, symptoms such as vaginal bleeding will not appear during pregnancy.5 More importantly, endoscopic excision of a cesarean scar pregnancy can provide a strong lower uterine segment, which leads to fewer complications in the third trimester and at cesarean delivery. However, the difficulties of manipulations and massive blood loss are concerns during endoscopic surgery. More importantly, adverse effects of anesthesia, distention media, carbon dioxide, and electrical devices on the preserved intrauterine pregnancy are unknown and need further evaluation.7,11 Experience to date suggests that, compared to endoscopic surgery, embryo reduction in situ with sonographic guidance is much easier and has the advantages of a smaller lesion and higher success rate. In summary, although heterotopic cesarean scar pregnancy is very rare, its incidence will increase in parallel with the increased rate of cesarean delivery and more widespread application of assisted reproductive technology. Obviously, early diagnosis is warranted to reduce complications and improve treatment success. Therefore, the possibility of heterotopic cesarean scar pregnancy should be considered in any pregnancy occurring after cesarean delivery, especially those following assisted reproductive technology. Transvaginal sonography is an important tool for both diagnosis and treatment of heterotopic cesarean scar pregnancy. Despite the various treatment options for this condition, the best treatment is still unclear. Selective embryo reduction in situ with sonographic guidance is the most popular treatment at present. Fortunately, most intrauterine pregnancies can be preserved after treatment.
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Nevertheless, there are many complications during pregnancy and the perioperative period when the intrauterine gestation is continued, which require that thorough informed consent be obtained from the patient and that the pregnancy be treated as high risk.
References 1.
2.
3.
4.
5.
6. 7.
8.
9.
10.
11.
12. 13.
14. Ugurlucan FG, Bastu E, Dogan M, Kalelioglu I, Alanya S, Has R. Management of cesarean heterotopic pregnancy with transvaginal ultrasound-guided potassium chloride injection and gestational sac aspiration, and review of the literature. J Minim Invasive Gynecol 2012; 19:671–673. 15. Larsen JV, Solomon MH. Pregnancy in a uterine scar sacculus—an unusual cause of postabortal haemorrhage: a case report. S Afr Med J1978; 53:142–143.
Salomon LJ, Fernandez H, Chauveaud A, Doumerc S, Frydman R. Successful management of a heterotopic Caesarean scar pregnancy: potassium chloride injection with preservation of the intrauterine gestation—case report. Hum Reprod 2003; 18:189–191. Wang CN, Chen CK, Wang HS, Chiueh HY, Soong YK. Successful management of heterotopic cesarean scar pregnancy combined with intrauterine pregnancy after in vitro fertilization–embryo transfer. Fertil Steril 2007; 88:706.e13–706.e16. Litwicka K, Greco E, Prefumo F, et al. Successful management of a triplet heterotopic caesarean scar pregnancy after in vitro fertilization–embryo transfer. Fertil Steril 2011; 95:291.e1–291.e3. Hsieh BC, Hwang JL, Pan HS, Huang SC, Chen CY, Chen PH. Heterotopic Caesarean scar pregnancy combined with intrauterine pregnancy successfully treated with embryo aspiration for selective embryo reduction: case report. Hum Reprod 2004; 19:285–287. Demirel LC, Bodur H, Selam B, Lembet A, Ergin T. Laparoscopic management of heterotopic cesarean scar pregnancy with preservation of intrauterine gestation and delivery at term: case report. Fertil Steril 2009; 91:1293.e5–1293.e7. Gupta R, Vaikousi E, Whitlow B. Heterotopic caesarean section scar pregnancy. J Obstet Gynaecol 2010; 30:626–627. Bai XX, Gao HJ, Yang XF, Dong MY, Zhu YM. Expectant management of heterotopic cesarean scar pregnancy. Chin Med J (Engl) 2012; 125:1341–1344. Uysal F, Uysal A. Spontaneous heterotopic cesarean scar pregnancy: conservative management by transvaginal sonographic guidance and successful pregnancy outcome. J Ultrasound Med 2013; 32:547–548. Yazicioglu HF, Turgut S, Madazli R, Aygün M, Cebi Z, Sönmez S. An unusual case of heterotopic twin pregnancy managed successfully with selective feticide. Ultrasound Obstet Gynecol 2004; 23:626–627. Jurkovic D, Hillaby K, Woelfer B, Lawrence A, Salim R, Elson CJ. Firsttrimester diagnosis and management of pregnancies implanted into the lower uterine segment Cesarean section scar. Ultrasound Obstet Gynecol 2003; 21:220–227. Wang CJ, Tsai F, Chen C, Chao A. Hysteroscopic management of heterotopic cesarean scar pregnancy. Fertil Steril 2010; 94:1529.e15– 1529.e18. Taşkin S, Taşkin EA, Ciftçi TT. Heterotopic cesarean scar pregnancy: how should it be managed? Obstet Gynecol Surv 2009; 64:690–695. Dueñas-Garcia OF, Young C. Heterotopic cesarean scar pregnancy associated with a levonorgestrel-releasing intrauterine device. Int J Gynaecol Obstet 2011; 114:153–154.
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