Unsuccessful medical treatment of cesarean scar ectopic pregnancy with systemic methotrexate: a report of two cases

Pregnancy implanted in a cesarean section scar is one of the rarest forms of ectopic pregnancy. A total of 20 cases have been reported in English literature (1–20). Eight of these patients were treated primarily with surgical intervention, either by a hysterotomy or a hysterectomy (1–8). Medical treatment of this rare condition, which is considered to be less invasive and therefore more likely to preserve the reproductive function, has been described with variable success (9–18). Conservative management with continuation of pregnancy has been adopted in two patients but both ended up in cesarean hysterectomy due to massive bleeding from the placental site (19,20). We report here two cases of scar ectopic pregnancy, both of which failed to respond to medical treatment and required subsequent surgical interventions. We further review all reported cases of medically treated scar ectopic pregnancies, with the aim to identify the common factors of failure. A 29-year-old, gravida 5, para 1 woman, with a previous history of emergency lower segment cesarean section for nonreasuring cardiotocogram at term, was referred to our unit at 7 weeks of gestation for a suspected ectopic pregnancy. Her hemodynamic condition on admission was stable. Pelvic examination showed a normal-sized uterus, a normal-looking uterine cervix and a closed cervical os. Transvaginal ultrasound examination showed that both the uterine cavity and cervical canal were empty, but there was a single viable fetus with crown-rump length (CRL) of 1.2 cm in a gestational sac implanted in the anterior wall of the uterus at the level of uterine isthmus. Only 3.5 mm of myometrium could be visualized between the sac and the bladder wall (Fig. 1). A diagnosis of a cesarean scar ectopic pregnancy was made. A gestational sac with a viable fetus implanted in the anterior isthmus wall of the uterus, with only 3.5 mm of myometrium between the sac and the bladder wall in Case 1. A multiple-dose systemic methotrexate (MTX)–folinic acid regime [1 mg/kg MTX intramuscularly (i.m.) on days 1, 3, 5, and 7 with 0.1 mg/kg folinic acid i.m. on days 2, 4, 6, 8] was given (16). The pretreatment serum human chorionic gonadotropin (HCG) level was 120 000 IU/L. After a completed course of MTX, the HCG level remained static at 119 000 IU/L. Repeated sonography showed a viable fetus with a CRL of 2.1 cm. Because the serum HCG level remained static and the viable fetus grew in size, an emergency laparotomy was performed. The uterus, fallopian tubes and ovaries looked normal and no blood was found in the abdominal cavity. A mass was palpable under the uterovesical peritoneal reflection, and the peritoneum was opened at this point. A 4-cm bluish mass was exposed at the site of the previous cesarean uterine scar (Fig. 2). The gestational mass was locally excised and the uterine defect was closed. The operation was uncomplicated and the serum HCG level returned to normal on postoperative day 57. A 4-cm cesarean scar ectopic pregnancy protruding from the anterior isthmus wall of uterus after reflection of the bladder in Case 1. A 34-year-old, gravida 3, para 1 woman, with a previous lower segment cesarean delivery for fetal distress, was referred to us at 8 weeks of gestation for a suspected ectopic pregnancy. Her hemodynamic condition on admission was stable. Pelvic examination showed a normal-sized uterus, and a normal-looking cervix with a closed os. A transvaginal sonography demonstrated a 1.6-cm empty gestational sac implanted in the anterior isthmus wall of the uterus. Both the uterine cavity and the cervical canal were clearly visualized and were empty. Only 4.3 mm of myometrium could be visualized between the sac and the bladder wall (Fig. 3). A diagnosis of a cesarean scar ectopic pregnancy was made. An empty gestational sac implanted in the anterior isthmus wall of the uterus, with only 4.3 mm of myometrium between the sac and the bladder wall in Case 2. The patient was treated medically with the same regime as described in Case 1; however, 5 days later she suddenly developed profuse vaginal bleeding after the third dose of MTX. It was complicated with hypovolemic shock that required an emergency laparotomy. An initial attempt at excising the ectopic pregnancy and repairing the uterine defect was unsuccessful in controlling the bleeding, and a total abdominal hysterectomy was required to achieve hemostasis. The patient had 6 units of blood transfusion but the operation was otherwise uncomplicated. The serum HCG level dropped from 12 300 IU/L to 1600 IU/L after three doses of MTX, and subsequently to a normal level 20 days after hysterectomy. Histologic examination of the uterus revealed the infiltration of trophoblastic cells in the lower segment of the uterus and upper endocervical canal. Focal fibrosis was also noted at this site, which was compatible with the scar formation of a previous cesarean section. No chorionic villi were seen in the rest of the endometrium. Pregnancy implanted in a cesarean section scar is one of the rarest forms of ectopic pregnancy, although recently there has appeared to be an increase in reported incidences. The first case of a scar ectopic was reported in English medical literature in 1978 by Larsen and Solomon (1). Up to April 2002, a further 19 cases have been reported. The vast majority of these cases were reported after 1998 (14 of 20 cases). In our unit, we encountered the first case of a scar ectopic in 2001 (18). The two cases reported here were diagnosed within 1 year after the first case. The apparent increased reporting of scar ectopic pregnancies in medical literature could be due to various reasons. First, there might be a true increase in the incidence of scar ectopic, as a result of a high cesarean birth rate worldwide. A national cesarean section rate of 27% and 40% has been reported in Brazil and Chile, respectively (21,22). The cesarean section rate in Hong Kong has risen from 16% in 1987 to 27% in 1999 (23). This high cesarean section rate at least partly contributed to the higher incidence of scar ectopic. Second, a spurious increase could have been due to a better diagnostic accuracy of this condition. Accurate diagnosis of cesarean scar pregnancy relies on a high index of suspicion as well as the availability of high-resolution transvaginal sonography. Strict imaging criteria have to be used to establish the diagnosis: empty uterus, empty cervical canal, development of the sac in the anterior part of isthmic portion, and a diminished myometrial layer between the bladder and the sac (10). The natural history of scar ectopic is unknown. But the only two case reports in which the patients were managed conservatively resulted in massive bleeding requiring hysterectomy (19,20). Therefore, it appears appropriate that these abnormal pregnancies should be terminated once the correct diagnosis has made to avoid subsequent risk of rupture and life-threatening hemorrhage. Primary surgical intervention, in the form of excision of the ectopic and repair of the scar, is probably the most conservative form of definitive treatment. Six out of seven published cases with primary excision of the scar ectopic have recovered uneventfully (1–6). The last one ended up with a hysterectomy because of placenta accreta (7). Medical therapy, on the other hand, is noninvasive and avoids further damage to the uterus, and therefore may maximize the chance of preservation of uterus in patients who desire fertility. However, the efficacy and safety of this treatment modality is still unknown. There were 12 reported cases, including ours (index cases 1 and 2), of a scar ectopic treated by primary medical therapy. In all cases, there was no evidence of rupture of the ectopic before commencement of therapy. The clinical details of these 12 cases are summarized in Table I. MTX has been used in all cases, although the route and regimes were variable. Direct injection of MTX was reported in three cases. Another eight cases were treated by systemic MTX and the last one was treated using combination therapy. Overall, 9 out of 12 scar ectopic pregnancies were successfully treated using medical therapy alone, but the medical treatment in remaining three (25%) failed. Two cases were complicated by rupture of the ectopic pregnancy and one had an unsatisfactory response, all requiring surgical intervention. Due to the small number of cases, it was impossible to conclude whether systemic or direct MTX administration is safer or more effective. Nonetheless, there appeared to be a substantial risk of rupture of the ectopic during or after MTX therapy. Therefore, patients receiving primary medical treatment of a scar ectopic should be monitored closely, preferably as in patients. Medical treatment using systemic MTX therapy has been used extensively in the management of tubal and cervical ectopic pregnancies (24–26). It is now well recognized that a higher failure rate of medical treatment is associated with a gestational age of ≥ 9 weeks, a fetal pole > 10 mm, the presence of embryonic cardiac activity and a serum HCG concentration of ≥ 10 000 IU/L (27). However, no similar or consistent pattern could be observed in cases of scar ectopic (Table I). Due to the rarity of this condition, it is important that all medically treated scar ectopic pregnancies be reported along with detailed clinical information. It is particularly important to report those resulted in failures so that a common factor could be identified. Only then could we confidently tell who would benefit safely from medical therapy. P. M. Lam Department of Obstetrics and Gynecology Prince of Wales Hospital Shatin Hong Kong e-mail: [email protected]