Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 208e210

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Research Letter

Cesarean scar pregnancy: What can we offer? Beng Kwang Ng*, Pei Shan Lim, Shuhaila Ahmad, Nirmala Chandralega Kampan, Abdul Kadir Abdul Karim, Mohd Hashim Omar Department of Obstetrics and Gynaecology, UKM Medical Centre, Kuala Lumpur, Malaysia

a r t i c l e i n f o Article history: Accepted 25 November 2014

Cesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy where implantation of the gestational sac occurs at the previous scar with the surrounding myometrium [1]. The incidence reported by Seow et al [2] was extremely low (approximately 1 in 2000), which is consistent with the prevalence of 1:1800 reported by Jurkovic et al [3]. The precise mechanism is still not clear and poorly understood. Implantation of the conceptus into the myometrium through a microscopic tract or scar defect had been suggested [4]. Catastrophic and life-threatening complications such as uterine rupture and massive hemorrhage could occur in case of misdiagnosis. Therefore, prompt and early diagnosis is essential to facilitate early intervention. This is a case of CSP successfully treated with local injection of methotrexate (MTX) and hypertonic dextrose solution. Subsequent vaginal bleeding after the termination of CSP was effectively controlled by tranexamic acid followed by gonadotropin releasing hormone analog (GnRHa). This approach resulted in avoidance of surgical intervention. A 30-year-old gravida 3 para 2 woman in the 9th week of amenorrhea who had two previous cesarean sections (CSs), was referred for an incidental finding of CSP during her first antenatal visit. She was asymptomatic, and the result of her physical examination was unremarkable. An ultrasound scan noted a gestational sac embedded at the previous CS scar. The pregnancy was considered viable with a crown rump length of 25.8 mm. The uterine cavity was empty with no free fluid seen in the pouch of Douglas (Figs. 1e3). Her serum beta human chorionic globulin

* Corresponding author: Department of Obstetrics and Gynaecology, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Cheras, 56000 Kuala Lumpur, Malaysia. E-mail addresses: [email protected], [email protected] (B.K. Ng).

(hCG) was elevated, at 60,670 mIU/mL. In view of the fact that the patient was asymptomatic and hemodynamically stable, she was treated medically. A direct injection of MTX into the gestational sac was performed under transvaginal scan guidance. A repeat ultrasound scan 3 days later showed persistent fetal heart activity; however, she remained asymptomatic. Therefore, another intragestational sac injection was given using 10 mL hypertonic dextrose 50%, which successfully led to the cessation of fetal heart activity 3 days later. She had persistent vaginal spotting with no abdominal pain. Serial beta-hCG showed a decreasing trend to a level of < 1.2 mIU/mL 4 months later although the gestational sac remained visible. Soon after the beta-hCG level had normalized, the amount of vaginal bleeding increased. She sought medical help from a private gynecologist, who gave her an intramuscular depo medroxyprogesterone acetate (150 mg). However, the vaginal bleeding worsened to the point where she required blood transfusion. She was readmitted to our center for further management. Fortunately, despite heavy vaginal bleeding, there was no abdominal pain and she remained hemodynamically stable. The couple was counseled for laparoscopic resection of the gestational sac but they were very reluctant. The sac was noted to be round and remained at the same size (3.4 cm  2.8 cm). Therefore, intravenous tranexamic acid was administered, which effectively reduced the vaginal bleeding followed by a trial of GnRHa (Lucrin PDS depot 3.75 mg; Abbvie, Zuellig Pharma, Takeda, Japan). She was successfully managed with a dose of three monthly injections of GnRHa after which she became amenorrheic. The couple was advised on the potential risk of scar rupture in future pregnancy. She was given combined oral contraceptive pills, and she has remained well with regular menstrual cycles. The ectopic gestational sac was completely absorbed 1 year after the therapy. With the increasing rate of CSs worldwide, the rate of CSP was likewise expected to increase although it is rare. The incidence of CSP was < 0.05% [2]. For women with ectopic pregnancy with at least one previous CS, its rate was 6.1% [2]. Conflicting results were reported with regard to the association between risks of CSP and number of previous CSs. Multiple CS was thought to be associated with an increased risk of CSP [3]. However, Rotas et al [5] could not demonstrate its correlation with the number of CSs (52% after 1 CS, 36% after 2 CSs, and 12% after  3 CSs).

http://dx.doi.org/10.1016/j.tjog.2014.11.022 1028-4559/Copyright © 2015, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.

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Fig. 3. Transvaginal ultrasound image showing a gestational sac implanted anteriorly into the cesarean section scar. The bladder wall is seen just adjacent to the gestational sac. Fig. 1. Enlarged image of fetal echo with demonstration of fetal heart activity.

Vial et al [6] proposed two different types of ectopic CSP: endogenic and exogenic. The endogenic type occurs when the gestational sac is implanted on the cesarean scar, and may later progress into intrauterine pregnancy, which subsequently results to giving birth to a live fetus. The exogenic type arises from a deeply implanted gestational sac into the defect of a scar and may later grow toward the bladder or abdominal cavity [6]. The former type may result in a more favorable outcome (i.e., viable fetus with the risk of morbidly adherent placenta), but the latter would probably progress to uterine rupture and severe hemorrhage [7,8]. The mean gestational age at diagnosis was generally about 6.9e7.5 weeks [2,5], and the average duration between CS to current pregnancy was reported to be between 6 months and 12 years [2]. In reported cases where presenting symptoms could be assessed, although the majority were diagnosed early (< 9 weeks), most cases had either vaginal bleeding or abdominal pain [9e14]. Asymptomatic cases were mainly diagnosed at  8 weeks' gestation [15e17]. Our patient was asymptomatic and she was 9 weeks

Fig. 2. A midline sagittal transabdominal scan image showing a gestational sac with fetal echo seen implanted at previous cesarean scar. The uterine cavity is empty. The myometrium anterior to the gestational sac is thinned out.

pregnant when the diagnosis of CSP was made, and her last CS occurred 1 year ago. Ultrasound scan, especially high-frequency transvaginal sonography, aids in the early diagnosis of CSP, thereby allowing a more conservative approach [2,6] with higher success rates in medical treatment. The ultrasonographic criteria for diagnosing a CSP include an empty uterine cavity with no gestational sac in the cervical canal, and pregnancy located anterior to the uterine isthmus with a defective myometrial layer was found between the gestational sac and the urinary bladder [2,4]. The trophoblastic flow surrounding the gestational mass was reported to be prominent [9]. Various options of managementdincluding systemic or local administration of MTX, uterine artery embolization (UAE), dilatation and curettage (D&C), local resection of the gestational mass via laparoscopy or laparotomy, as well as hysterectomydhad been reported with different success rates. The surgical approach with evacuation techniques alone (i.e., D&C) was not recommended for CSP owing to the high risk of massive hemorrhage, except for selected cases [1]. Rotas et al [5] performed a systematic review on CSP. They reported that only 23% of patients who were managed primarily by D&C were uncomplicated, and the remaining 76% of patients required systemic MTX, laparotomy excision of the ectopic mass, or hysterectomy [5]. Resection of the CSP had been performed via the vaginal approach [13], laparoscopy [14,18], or laparotomy [7] with good outcomes. He et al [13] reported on a successful transvaginal approach to remove CSP and repair the uterine defect in six patients. None of the patients required conversion to laparotomy [13]. This approach requires surgeons to be familiar with vaginal surgery as it is a narrow surgical field and difficulties might be encountered. Similarly, the laparoscopic approach requires skillful laparoscopists who are capable of suturing laparoscopically and able to handle difficult situations. MTX had been used effectively in tubal and cervical pregnancies particularly in gestational age < 9 weeks, fetal pole < 10 mm, absence of fetal heart activity, and serum HCG < 10,000 mIU/mL [19]. A local injection of MTX directly into the gestational sac of a CSP had the advantage of minimizing side effects produced by systemic MTX administration. It yields an excellent result either alone [9], in combination with potassium chloride into the fetal thorax [4], or in combination with UAE and potassium chloride [15].

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Other proposed combinations include priming with mifepristone [11] and misoprostol [12]. Although surgical intervention might be avoided, medical therapy carries the risk of failure and slow regression of hCG level, and requires prolonged follow-up. This patient was diagnosed at 9 weeks' gestation with a viable CSP and serum hCG of > 60,000 mIU/mL. Fetal heart activity persisted after 3 days of local MTX, and her CSP was successfully terminated with additional intragestational sac hypertonic dextrose 50%. Her HCG level only declined to a normal range 4 months after the treatment, whereas complete absorption of the ectopic mass took 1 year. Persistent bleeding after medical treatment requiring further intervention is not an uncommon problem even though hCG may be undetectable. Additional interventions described include multiple intragestational injection, D&C, UAE, Foley balloon tamponade, wedge resection, and hysterectomy [5]. There was no consensus regarding the best approach for this issue. Pang et al [17] described the use of tranexamic acid followed by repeated UAEs in a patient who developed heavy vaginal bleeding 102 days after medical treatment. UAE was performed owing to the presence of uterine arteriovenous fistula feeding a venous aneurysm. Four doses of GnRHa were given to reduce uterine vascularity [17]. This patient had increased vaginal bleeding soon after hCG normalized and her condition worsened after receiving intramuscular depo medroxyprogesterone acetate. Her bleeding was successfully reduced by tranexamic acid. She became amenorrheic after receiving GnRHa without requiring invasive intervention. The use of combined oral contraceptive pills subsequently did not lead to excessive vaginal bleeding although the ectopic mass remained at the CS scar. There were two possible explanations for the increment in vaginal bleeding. (1) One factor could be the resumption of menstruation following normalization of hCG. The presence of persistent gestational sac in the cesarean scar leads to heavy menstruation. (2) Another explanation is the development of arteriovenous malformation (AVM) as described by Lin et al [20] and Kochhar et al [21]. However, we did not investigate further to distinguish the cause of heavy vaginal bleeding. The aim of using GnRHa in this case was to create a pseudomenopausal amenorrheic state while waiting for the spontaneous absorption of the CSP mass. The reduction of uterine vascularity following GnRHa leading to the regression of AVM had been described by Nonaka et al [22], whereas Pang et al [17] described the regression of post-CSP venous aneurysm by GnRHa in conjunction with embolization. If AVM had been present in this case, regression of AVM by GnRHa could be another reason for the resolution of symptoms. In conclusion, early and accurate diagnosis of CSP is achieved with the advancement of ultrasound scan, thus enhancing the success of medical treatment in CSP. GnRHa is a potential effective adjuvant therapy for CSP with persistent vaginal bleeding after medical treatment where invasive intervention might be avoided.

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Cesarean scar pregnancy: What can we offer?

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