Retroperitoneal ectopic pregnancy: successful expectant management in condition of early pregnancy failure

Background Retroperitoneal ectopic pregnancy (REP) refers to abnormal implantation of the fertilized egg in the retroperitoneal cavity. REP can be divided into pelvic and abdominal positions. Extremely rare, the incidence of REP is less than 1% of ectopic pregnancy (EP). Herein, we report the first case of paraaortic-located REP in association with successful expectant management, thus raising awareness among healthcare providers, particularly in low-resource settings. Case presentation A reproductive-age woman presented at our tertiary referral hospital because of amenorrhea and a positive pregnancy test. Based on serial serum β-hCG levels and imaging modalities including transabdominal ultrasound, transvaginal sonography, and magnetic resonance imaging (MRI), a REP of 7–9 weeks of gestational age adherent to abdominal paraaortic region was detected. Since the pregnancy was spontaneously arrested without clinical symptoms, expectant management was first indicated following careful evaluation. After a 1-month follow-up, the ectopic mass naturally degenerated without complications and her β-hCG concentration returned to a negative value. Therefore, the patient recovered completely and avoided unnecessary surgery as well as toxicity of medical treatment when using systemic methotrexate. Conclusions In addition to transvaginal and transabdominal ultrasound, MRI is necessary for the diagnosis of nonviable REP. Alongside the great vessels in the abdominal cavity should be taken into consideration in all suspected cases relating to this rare entity. Expectant management may be carefully indicated in conditions of nonviable REP and unruptured REP, where applicable.


Introduction
Retroperitoneal ectopic pregnancy (REP) refers to the implantation of a fertilized egg in the retroperitoneal cavity.REP can be divided into pelvic and abdominal positions [1].The location is related to many different structures such as the kidneys, pancreas, abdominal paraaortic region, iliac artery, and obturator fossa [2].Along with the development of assisted reproductive technology in the past decades, the number of ectopic pregnancies has increased, including at uncommon sites [3][4][5].Among them, REP is exceedingly rare, accounting for less than 1% in ectopic pregnancies.Before 2021, 25 cases were reported in the literature following the report of Wen et al. [6].Until today, a total of 36 cases have been found in the PubMed database [7,8].This uncommon site increases the maternal mortality rate higher than other sites in the first trimester.The mortality rate is 5.1 per 1000 cases [6].However, the development mechanism of REP remains unclear [9].Risk factors include reduced or impaired tubal transport activity, increased tubal receptivity for blastocyst implantation, tubal damage due to surgery or infection, peritoneal defects, and in vitro fertilization (IVF) [1].
Regarding clinical characteristics, symptoms can range from asymptomatic to severe manifestation associated with a ruptured EP which leads to immediate hypovolemic shock and death [1,10].Similar to almost all ectopic pregnancies, the common symptoms of REP include amenorrhea, abdominal pain, and vaginal bleeding [7].Early diagnosis is usually difficult because of extremely specific location of the REP mass [11].An accurate diagnosis is often made following the exclusion of other common sites.Transabdominal sonography (TAS) and transvaginal sonography (TVS) are first-line tools for assessment of REP [12].However, some early ectopic pregnancies require additional imaging modalities such as MRI and computed tomography (CT) scans due to missed diagnosis on ultrasound [1,13,14].
Treatment includes surgical intervention, medical treatment with methotrexate, and expectant management [6].In some cases, after failed medical treatment, a surgical method is indicated with the cooperation of an experienced multidisciplinary team [3].Recently, Lorenzo et al. have mentioned a case of REP requiring of surgery after a failure of methotrexate treatment [15].Moreover, laparotomy must be the preferred method of treatment in ruptured REP cases with severe hemorrhage [10].
Herein, we hereby describe an uncommon case of REP at our tertiary referral hospital and review the literature (Table 1).To our knowledge, this is the first REP case of paraaortic location with successful expectant management in the literature, with neither medical treatment nor surgical removal.Through this report, we aimed to increase physician awareness regarding REP in abdominal ectopic pregnancies and suggest an option management in condition of early failure of pregnancy.

Presentation case
A 38-year-old female patient (G5P2) was transferred to our hospital owing to suspicion of abdominal ectopic pregnancy.Her obstetric anamnesis included one vaginal birth, one cesarean delivery, one ectopic pregnancy with salpingectomy, and one preterm birth at 22 weeks GA.She had also undergone an appendectomy in the past year.
On admission, the patient was stable.A general physical examination result was unremarkable.On gynecological examination, the uterus and bilateral ovaries were normal in size.The patient was asymptomatic and denied the use of urgent contraceptive pills.She complained of a retarded menstrual cycle of two weeks and her urine human chorionic gonadotropin (HCG) test was positive.Laboratory tests revealed the positive pregnancy tests.The quantitative serum beta-human chorionic gonadotropin (β-hCG) titer test was 51,586 m-international units per milliliter (mIU/mL).
Abdominal ultrasound showed no intrauterine gestational sac, with an endometrial thickness of 6 mm, and both adnexal structures were normal.Several fibroid nodules approximate 8-11 mm in diameter were detected within the intramural layer.After observing the lateral sides of the uterus and pelvis, the abdominal cavity was carefully scanned.An abnormal heterogeneous mass was found in the retroperitoneal cavity adjacent to the abdominal aorta, corresponding to a gestational sac at 7-9 weeks with a visible embryo, but absence of fetal cardiac activity (Fig. 1).Subsequently, MRI was performed to confirm the definite diagnosis and assist a deep investigation of the abdominal cavity (Fig. 2).
Upon monitoring, the β-hCG concentration gradually decreased every 48 h (Fig. 3).After consultation, the expectant management was indicated.The patient was sent to home after 2-week hospitalization.The serum β-hCG level was monitored every week after discharge until negative value.Ultrasonography was repeated weekly along with β-hCG during the first 2 weeks after discharge.Then, ultrasound was followed-up monthly until the mass dramatically reduced in size without blood supply after six months.During outpatient follow-up, the patient was strictly monitored without any relevant complications.
Despite the lack of criteria for laparoscopic imaging and pathologic examination, the retroperitoneal mass reduced in size and the β-hCG level returned to the normal range after 1 month, and she continued to be stable after 3 months.This regression supported the confirmative diagnosis.The patient was thankful to the team for successful management without surgical or medical intervention.

Discussion
In the present case, the patient had a retroperitoneal ectopic pregnancy with natural conception.This may be a rare occurrence since almost all cases have been reported relative to IVF treatment [16][17][18].Retroperitoneal implantation of a fertilized ovum may be primary or secondary to a ruptured EP originating at another site.However, an original tendency of embryonic location alongside the great blood vessels and invasion into the lymph node tissue has been found in some cases [9,18].
Accordingly, since the EP was hidden in the retroperitoneum, thus initial detection was relatively difficult.Therefore, it is necessary to rule out the possibility of EP and determine its location, especially alongside the large vessels [7].Previously, Salma et al. reported a case of REP requiring 2 times of exploratory laparotomy since the diagnosis was neglected on the initial ultrasound and the first assessment of laparotomy [19].Then, Park et al. also mentioned the similar case which its diagnosis was delayed on TAS and the first laparotomy until the presence of complication or elevated serum β-hCG levels after surgery [10].In this case, since the presence of elevated serum β-hCG and no intrauterine pregnancy was observed on ultrasound, thus the team decided to perform the MRI scan to elucidate the ambiguous diagnosis.Although MRI is not the first tool in the assessment of REP in low-resource settings owing to its high cost, particularly, in the repeated indication of monitoring, it is often required following a suspected ultrasound to evaluate the surrounding vasculature [6,18].
Generally, REP is a life-threatening condition because the gestational sac is located next to the fragile structures.Therefore, the trophoblastic tissue directly invades the neighboring organs.Consequently, it is very difficult to completely assess and remove REP mass because it is covered by the peritoneum.Hence, the placental invasion commonly results in adverse outcomes such as massive hemorrhage [10].Owing to the limitations of the current data and insufficiently practical guidelines, the management of REP remains a challenge for physicians [1].
In the present case, the early pregnancy failure occurred spontaneously before hospitalization.The etiology of early fetal death may be caused by implantation in area unfavorable for fetal development.Therefore, the gestational sac size was naturally limited.In our patient, the β-hCG concentration gradually decreased.Furthermore, the clinical manifestations were absent with stable hemodynamic parameters.These advantages have contributed to the success of expectant management.The limitation of the non-surgical intervention was noted that our team could not assess the REP tissue for histopathological examination and exclude other malignant pathologies.However, since no sign of proliferative vascularity was detected on ultrasound, the mass size was gradually decreased, and the serum β-hCG levels returned to negative value.All these progressions supported for the benign pathology of ectopic pregnancy.
Similar to almost all ectopic pregnancies, treatment should be individualized and based on gestational age, gestational sac size, relative organs, clinical characteristics, β-hCG level, presence of fetal cardiac activity, and desire of the patient (Table 1).Although surgical intervention including laparoscopy and laparotomy is a rapidly effective therapy, it is highly related to severe complications and increased risk of vascular injury.Thus, a multidisciplinary team that includes a gynecologist, vascular surgeon, radiologist, and anesthetist is necessary in all cases [16,17].By summarizing of REP cases in the literature, Xu et al. concluded that multidisciplinary requirements substantially reduce surgical complications, thus increasing the survival rate of patients [7].A methotrexate regimen can be used under suitable conditions to kill the trophoblast cells in the conservative management or reduce intraoperative hemorrhage [20].A systemic administration of MTX in nonruptured REP before surgical method may be significant [21].However, its side effects should be monitored and an adequate protocol is currently lacking [1].

Conclusions
In summary, an importance of considering the possibility of REP should be emphasized in suspected cases of abdominal ectopic pregnancy with unknown location.In addition, expectant management can be considered in the case of nonviable pregnancy without complications, and multidisciplinary team could be immediately assessed.

Fig. 1 Fig. 2
Fig. 1 Transabdominal ultrasound in a reproductive-age woman (G5P2) revealed the following: a visible embryo 15 mm in length corresponding to 7 weeks and 6 days of gestational age without fetal heart activity (A).The mass is absent with a Doppler signal (B).The gestational sac measured 56 × 60 × 44 mm in dimension and was located in the right upper quadrant of the abdominal cavity (C).The kidneys and surrounding organs are normal (D)

Table 1
Retroperitoneal ectopic pregnancy in the last 5 years