Direct Visualization of a Cesarean Scar Ectopic Pregnancy After Medical Management

Introduction

Cesarean scar ectopic pregnancies (CSEP) are rare and can have life-threatening complications. These cases are becoming increasingly common due to higher cesarean delivery rates. The true incidence is unknown and is estimated to range from 1 in 1800 to 1 in 2226 of overall pregnancies [1,2]. CSEP may have variable initial clinical presentations and can be difficult to diagnose promptly. Complications of CSEP include adherent placenta/placenta accreta spectrum, uterine rupture, severe hemorrhages, and preterm birth [1,2].

Medical, surgical, and minimally invasive therapies alone or in combination have been described in the literature, but the optimal treatment modality is unknown and varies depending on patient characteristics, treatment location, and other factors [2]. Minimally invasive techniques, such as intra-gestational sac injection of methotrexate or KCl, have been reported to be more effective than stand-alone systemic methotrexate, but are less effective than surgical treatments [3]. More specifically, a recently reported success rate of 74.5% without additional intervention for intra-sac injection of either KCl or methotrexate alone was still inferior to surgical intervention, with a 90% efficacy of surgical excision [3]. However, surgical treatment carries the traditional risks of surgery, including recovery time and potential surgical complications, and is less feasible in lower-resource facilities. Further review of combinations of medical and minimally invasive treatments is needed to determine if the treatment efficacy can be increased closer to levels for surgical intervention.

This report presents a case of a 44-year-old patient diagnosed with CSEP treated by multi-dose systemic methotrexate-leucovorin and ultrasound-guided intra-gestational sac injection of potassium chloride (KCl). The beta human gonadotropin (hCG) level was monitored until it reached undetectable levels. However, based on sonographic evaluation, the patient had persistence of residual tissue within the cesarean scar defect. Ultimately, 8 months after treatment for CSEP, the patient had a scheduled hysteroscopic resection of residual tissue with concomitant laparoscopic sterilization. We report a novel hysteroscopic finding after medical treatment of a CSEP with intra-gestational sac injection of KCl.

Case Report

A 44-year-old gravida 5 para 3 patient with a history of 3 at-term cesarean births presented to our institution with heavy vaginal bleeding, abdominal pain, and nausea that started 11 days after medical termination of pregnancy with mifepristone and misoprostol self-administered and given by an outside clinic. All previous cesarean sections were performed without complications but for unknown indications. The patient previously had a surgical termination of pregnancy via suction dilatation and curettage at an unknown early gestation and 1 spontaneous miscarriage. The patient reported a 13-year smoking history of half a pack per day.

On presentation to the hospital, the patient’s pulse rate (65 beats/min), blood pressure (112/66 mmHg), pulmonary effort (18 breaths/min, SpO2=100% on room air), oral temperature (36.9°C), and skin condition (capillary refill <2 seconds) were unremarkable during the initial examination. There was no abdominal distention or tenderness. Physical examination was only remarkable for heavy vaginal bleeding. Her hCG level at presentation was 55 480 mIU.

An ultrasound of the abdomen and pelvis was performed on the same day by a maternal fetal medicine specialist and revealed a live CSEP with crown-rump-length (CRL) of 1.19 cm, which correlates to 7 weeks gestational age (Figure 1). The ultrasound showed a gestational sac with yolk sac and live embryo in the anterior myometrium of the lower uterine segment at the level of the presumed prior cesarean scar site. The gestational sac extended to the uterine serosa and no appreciable residual myometrium was seen. Doppler interrogation showed circular vascularity around the gestational sac and along the anterior uterine serosa at the serosal/bladder interface. The entire sac including the outer trophoblastic tissue measured 4.1×2.8×2.1 cm.

Several treatment options exist for CSEP. Surgical, medical, and minimally invasive therapies and various combinations of such treatments have been described in the literature [3]. At our institution, patients diagnosed with CSEP are routinely offered medical management via multi-dose systemic methotrexateleucovorin in conjunction with ultrasound-guided intra-gestational sac injection of potassium chloride. The patient received a total of 3 doses of systemic methotrexate (1 mg/kg) on hospital days 1, 3, and 5, alternating with 3 doses of leucovorin (0.1 mg/kg) on hospital days 2, 4, and 6. Two mL of potassium chloride was injected using a 20-gauge spinal needle inserted through the external cervical os into the gestational sac under continuous ultrasound guidance with cessation of fetal cardiac activity at completion of the procedure. The heavy vaginal bleeding ceased the day after the first dose of systemic methotrexate was given. The patient was discharged 3 days after the potassium chloride injection and hCG levels had decreased more than 15% from the previous measurement. The patient was stable, ambulatory, tolerating a regular diet, and had normal bowel function. She was followed weekly then monthly until hCG levels reached an undetectable level after 4 months. She began having intermittent vaginal spotting during the last month prior to complete resolution of hCG levels. One month after the resolution of hCG levels, she resumed her normal menstrual cycle.

Serial follow-up ultrasound performed 164 days after the intragestational sac KCl procedure revealed the CSEP had disinte-grated and the gestational sac had collapsed. A smaller amorphous tissue mass measuring 13.7 mm was seen (Figure 2). After resolution of her hCG levels, the patient presented requesting permanent sterilization. During surgical planning, she revealed recent depressive symptoms and anxiety affecting her quality of life due to residual CSEP tissue seen on ultrasound, believing she continued to carry her undesired pregnancy. She therefore desired a definitive resection of the residual CSEP tissue.

A laparoscopic bilateral salpingectomy and operative hysteroscopy was performed without any complications. Intraoperative findings during the laparoscopic approach revealed the bladder seen adherent to the anterior aspect of the uterus with a thin appearing anterior uterine wall consistent with a history of cesarean deliveries. Pelvic structures otherwise appeared normal. Hysteroscopic approach findings exhibited abundant tissue consistent with necrotic and distorted products of conception within a cesarean scar (Figure 3). The tissue was completely resected by hysteroscopy and sent to pathology.

The patient did well postoperatively and was discharged on the same day. Pathology examination of the hysteroscopic resection of the CSEP residual tissue showed products of conception revealed as predominantly degenerated/necrotic chorionic villi and decidua admixed with scant viable benign endometrial tissue, endocervical glandular epithelium, exocervical squamous, and blood clots.

Discussion

Although the pathogenesis of CSEP is not completely understood, the mechanism has been proposed to include a blasto-cyst implanting within a microscopic dehiscence tract in the scar from a previous cesarean delivery. Because of the fibrous nature of the scar tissue, these inherently deficient implantation sites are at risk for dehiscence, placenta accreta spectrum, and hemorrhage as the pregnancy progresses [2,3].

There is no established standard treatment of care for management of cesarean scar ectopic pregnancies. Management may be conservative, medical, minimally invasive, or a combination of such treatments, depending on clinical circumstances. Management decisions may also be informed by clinical classification systems based on patient risk factors for adverse outcomes, including anterior myometrium thickness at the scar and diameter of the gestational sac [2]. Treatment modalities include, but are not limited to, hysteroscopy, laparoscopy, laparotomy, sharp curettage, uterine aspiration, uterine artery embolization (UAE), needle-guided sac aspiration, use of balloon catheters, and methotrexate (both systemically administered or local guided injection) [3]. The medical literature on different management options consists predominantly of case series, as the choice of treatment modality is heavily dependent on hospital resources, practitioner comfort and technique, and patient circumstances [4]. Local or intra-gestational sac injection of methotrexate is currently preferred to stand-alone systemic methotrexate [3]. Although more limited in use, intrasac injection of KCl rather than methotrexate has been used for treatment of CSEP, with similar efficacy [3]. In some settings, particularly lower-resourced facilities, KCl may be preferable due to the greater cost and access controls associated with methotrexate due to its chemotherapeutic properties.

Systemic methotrexate with direct intra-gestational potassium chloride injection has been described as a uterine-preserving treatment of cesarean scar ectopic pregnancies only in a small number of cases, mainly for the management of heterotopic CSEP with a co-existing intra-uterine pregnancy [5]. This approach is less resource intensive than more common surgical interventions and has the potential to be particularly valuable in resource-constrained treatment centers. Further review is needed to determine if this relatively inexpensive treatment combination can increase efficacy closer to surgical intervention while only increasing total treatment time by approximately 1 week when compared to intra-gestational sac injection alone. Accordingly, we report the direct intra-abdominal and intra-uterine visualization after medical treatment of a cesarean scar ectopic pregnancy with this minimally invasive approach, which has not been previously described in the literature.

The gestational mass takes weeks to months to resolve after a patient has been treated medically with direct intra-gestational injection, with 1 study reporting a mean timeline of 88 days (ranging from 26 to 177 days) [2]. In our patient, the CSEP tissue was still present 240 days later. Our case provides pathologic evidence of a remaining necrotic gestational mass even after resolution of hCG levels. Therefore, the time needed for CSEP tissue to completely resolve remains unknown and cannot be based on hCG levels.

While this extended post-therapy timeline was understood by our patient, she continued to have anxiety, which affected dayto-day life, with the incomplete resolution of the CSEP. In the event of persistent tissue retention, hysteroscopic resection offers a safe and effective approach to remove the remaining tissue. In our patient, we successfully resected the residual tissue and discharged the patient the same day. Our experience and continued advances in minimally invasive technology and techniques that make hysteroscopic resection procedures less painful and invasive suggests the potential to perform the procedure in-office [6]. In-office hysteroscopic procedures have a number of benefits, including increasing accessibility of this treatment option to patients in rural areas or who are uncomfortable in a hospital setting, decreased recovery time by foregoing general anesthesia, and decreased cost [6].

Conclusions

Direct visualization of the intra-abdominal cavity and intra-uterine cavity showed that a combined medical management with systemic methotrexate and local potassium chloride injection is an effective treatment modality for live cesarean scar ectopic pregnancies, with minimal anatomical harm. Resolution of hCG after treatment of CSEP does not always correspond with tissue expulsion or resolution. The pregnancy tissue may persist for many months. In case of persistent tissue retention, hysteroscopic resection offers a safe and effective approach for patients concerned about the persistence of residual tissue.