4 Discussion
The location of REP is rather complex but is generally situated around the posterior aspect of major blood vessels. From an anatomical and surgical perspective, it can be simplistically categorized into two types: pelvic REP and abdominal REP. The former refers to pregnancies located in the retroperitoneum below the iliac arteries and veins, comprising 34.6 % (9/26) of cases. The latter refers to pregnancies occurring within the retroperitoneum surrounding the iliac arteries, veins, abdominal aorta, and inferior vena cava, constituting 65.4 % (17/26) of cases.57 The previous literature review focused on retroperitoneal pregnancy in general, while this article represents the first study exclusively addressing the unique and high-risk subset of retroperitoneal "para-aortic" ectopic pregnancies (a notably large blood vessel). This study includes literature from both Chinese and English sources, encompassing a total of 55 cases, enhancing the generalizability of the derived data.
This review reveals the characteristics of RPEP: Extrauterine pregnancy adjacent to blood vessels is commonly found in locations such as the abdominal aorta, inferior vena cava, and iliac vessels. Ectopic pregnancy represents a potentially life-threatening diagnosis, in the case of rupture, and timely intervention allows for surgical excision.58 Nevertheless, based on the collected data from RPEP patients, while some experienced acute abdominal symptoms and rupture of the pregnancy sac, none of them compromised the integrity of the large blood vessels surrounding RPEP. This may be attributed to the thicker walls of these major blood vessels, resulting in an earlier diagnosis compared to the time when the pregnancy sac invades major blood vessels and causes rupture. Nevertheless, due to their proximity to major blood vessels within the abdominal cavity, surgical intervention in RPEP carries higher sever bleeding risks compared to other locations of ectopic pregnancy. The later the diagnosis, the higher the treatment risk associated with RPEP; therefore, it is imperative to widely disseminate the concept of RPEP and related diagnostic and treatment strategies, enhancing the diagnostic efficiency of medical personnel.
The mechanism of embryo migration to the retroperitoneal space is indeed intriguing. Several pathogenesis pathways have been proposed to explain this phenomenon: (1) Transvascular Transfer: During implantation, fertilized egg cells may detach and enter ruptured lymphatic capillaries, eventually migrating to the retroperitoneal space. (2) Implantation transfer: In this scenario, the embryo initially implants on the peritoneal surface following a ruptured or aborted tubal pregnancy. It then invades the retroperitoneal space through trophoblastic infiltration of the peritoneum. (3) Fistula transfer: After undergoing salpingectomy, the broken end of the fallopian tube may connect with the retroperitoneum. The embryo can then implant through the fistula or peritoneal defect. Among the 55 cases identified in the literature, a significant proportion of patients (50.9 %, 28/55) had a history of salpingectomy. This suggests that salpingectomy may be one of the risk factors for retroperitoneal ectopic pregnancies. (4) The fertilized ovum implant on superficial endometriosis tissue, followed by its movement towards vascularized retroperitoneal structures through trophoblastic invasion.59 It suggests that endometriosis tissue present within the fallopian tube provides a uterine-like environment where the fertilized ovum can successfully implant.60
As for RPEP, we believe that the likelihood of transvascular transfer is higher, and the reasons for this are as follows: Some reported cases have shown the presence of lymphatic vessels in the resected pregnancy tissue.21,42,47 Liang et al.5 utilized CT reconstruction techniques to observe typical signs of inflammatory responses along the left gonadal vessels, suggesting obstructed lymphatics caused by embryo migration. Vascular metastasis, often observed in diseases involving cell nourishment, typically terminates in lung tissues. Indeed, lymphatic metastasis, as observed in conditions like endometrial cancer and others, tends to spread to the lymph nodes around the aorta and portal vein in the liver.61 In terms of postoperative pathology, the presence of lymphoid tissue in 5 cases out of 53 (excluding the 2 conservative cases) is noteworthy.
Based on previous reports, we conducted the distinction between RPEP and common ectopic pregnancy as Table 4. It appears that patients with history of artificial abortion, embryo transfer, salpingectomy, and uterine cavity operation, accounted for 65.5 % (36/55) of the cases. If a patient has these risk factors, and a normal location cannot identify the pregnancy sac during initial examination, RPEP should be considered as a potential diagnosis. In 12.7 % (7/55) of cases, the absence of embryo detection through vaginal ultrasound and uterine curettage led to exploratory laparotomy to locate the ectopic pregnancy. However, due to the partial concealment of the gestational sac, some cases concluded the exploratory surgery without identifying the embryo's location, resulting in missed diagnoses and unnecessary medical interventions. As Table 4, transabdominal ultrasound (TAS) serves as the primary method for diagnosing RPEP. TAS offers the advantage of being both economical and convenient, allowing for a preliminary localization of the ectopic pregnancy sac. If needed, abdominal CT or MRI examinations can be pursued. In comparison, MRI provides higher resolution images of soft tissues and multi-directional imaging, facilitating the evaluation of the relationship between the placental implant site and surrounding tissues.62 Physicians should meticulously report the distance and boundary between the pregnancy sac and the surrounding vessels to guide the operative procedure.
Distinction between RPEP and Common ectopic pregnancy.
Conservative management, interventional therapy, and surgery are all viable treatment options for RPEP. Conservative treatment is considered appropriate for patients who do not exhibit any of the following criteria: significant pain, an adnexal mass of 35 mm or larger, a fetal heartbeat visible on an ultrasound scan, serum hCG level of 5000 IU/L or more.63 Conservative management of RPEP involves imaging-guided intracapsular injection of MTX or intramuscular injection of MTX. This approach is chosen when the pregnancy sac is closely adjacent to large vessels, making surgical intervention risky. Interventional therapy can also be considered in such cases. However, conservative management carries the risk of persistent ectopic pregnancy, and there is a possibility of trophoblast erosion into the celiac vessels, which can lead to bleeding and shock. Therefore, close monitoring and follow-up are necessary to assess the effectiveness of the treatment.31 Indeed, MTX can be utilized as an adjunctive treatment to consolidate the therapeutic effect in cases where there is still residue after surgical resection of RPEP. However, for the majority of RPEPs, surgical treatment remains the primary choice, and it includes both laparotomy and laparoscopy. Laparotomy is preferred when patients present with unstable vital signs, as it allows for quicker access and intervention during emergency situations. laparoscopy offers several advantages, such as a clear vision field and effective hemostasis, making it an increasingly mainstream approach for RPEP surgery.
Once RPEP is diagnosed, adequate preoperative preparations should be made, including the improvement of intraoperative hemostasis equipment. For example, if preoperative auxiliary examination indicates that the pregnancy sac has invaded deep blood vessels and there is a high risk of bleeding during surgery, a hemostatic balloon can be placed in the abdominal blood vessels to prevent massive intraoperative bleeding. The surgical excision of ectopic pregnancy adjacent to major blood vessels is similar to the lymph node clearance in gynecological malignancies. Therefore, it is advisable for the surgeon performing the RPEP procedure to be a gynecological oncology specialist or an expert familiar with retroperitoneal structures. Regular monitoring the patient's plasma β-hCG levels should occur once a week after the operation for RPEP. For patients who undergo conservative treatment, more frequent reexamination is necessary, with β-hCG levels checked every 2–3 days until the plasma β-hCG becomes negative twice.64 As illstrated in Table 3, The time for postoperative hCG to return to normal did not show a significant difference, whether the pregnancy sac was located around the abdominal aorta and inferior vena cava or near the iliac vessels. Persistent or rising levels of β-hCG after treatment indicate that the trophoblast is still active and that further intervention is required.31
