Interventional radiology in ectopic pregnancy management

Roxana Elena Bohiltea1,2, Bogdan Dorobat3, Bianca-Margareta Mihai2, Tiberiu-Augustin Georgescu4,5, Nicolae Bacalbasa1, Irina Balescu6, Ionita Ducu7, Corina Grigoriu1,7 1Department of Obstetrics and Gynecology, “Carol Davila” University of Medicine and Pharmacy Bucharest, Romania 2Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, Bucharest, Romania 3Department of Interventional Radiology, University Emergency Hospital Bucharest, Bucharest, Romania 4Department of Pathology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania 5“Alessandrescu-Rusescu” National Institute for Mother and Child Health, Bucharest, Romania 6Department of Visceral Surgery, Ponderas Academic Hospital, Bucharest, Romania 7Department of Obstetrics and Gynecology, Emergency University Hospital, Bucharest, Romania


INTRODUCTION
Ectopic pregnancies represent extrauterine pregnancies, the vast majority are located in the fallopian tube; other locations implied are the cervix, the uterine horn, the hysterotomy or cesarean scar, ovary or the abdominal cavity (1). Regarding the incidence of ectopic pregnancy, there has been reported a range between 6 and 16% of patients who present to an emergency department with first trimester vaginal bleeding and/or pelvic pain (2). Ectopic pregnancies represent life-threatening pathologies. Due to modern methods of early diagnosis of pregnancy using transvaginal ultrasound, the maternal mortality rate has encountered a decreasing trend from 1.15 per 100,000 live births between 1980 and 1984 to 0.50 deaths per 100,000 between 2003 and 2007 (3). In contrast, cesarean scar pregnancies have an increasing tendency as the number of cesarean deliveries performed every year grows worldwide, the incidence raging from 1/2226 to 1/1899 of pregnancies (4,5). The diagnosis of ectopic pregnancies is realized in women with amenorrhea and an atypical increasing of β-hCG serum values trends and using transvaginal ultrasound evaluation, which reveals an empty uterine cavity. The clinical picture of ectopic pregnancy includes women who present to the emergency room most frequently for vaginal bleeding or pelvic pain and sometimes lipothymia, signs of hypovolemic shock such as tachycardia, hypotension (6).
Actual treatment of ectopic pregnancies consists in medical or radical treatment (surgical), the latter being the last treatment line in some cases and influencing primarily the woman's fertility or reproductive capacity. Interventional radiology, in well-selected cases with elevated β-hCG serum levels used as a complementary minimally invasive treatment, represents a useful tool in managing cases of ectopic pregnancies, either tubal (7), cervical (8) or cesarean scar pregnancy, having multiple advantages such as preserving the patient's fertility, reducing the surgical stress of the patient, reducing the bleeding in the management of cervical and cesarean scar pregnancies or even being cost-effective in relation to hysterectomy or salpingectomy.

CONVENTIONAL TREATMENT
There are two medical attitudes regarding the tubal pregnancy treatment: medical and surgical. The medical treatment involves Methotrexate (MTX) administration to patients who have a serum β-hCG value ≤ 5,000 mIU/ml, are hemodynamically stable, the tubal pregnancy does not present fetal cardiac activity and consent to medical treatment (9). Contraindications for MTX administrations make the patient a candidate for surgery (the patient is hemodynamically instable, presents an intrauterine pregnancy, there are signs and symptoms of tubal pregnancy rupture or associated pathologies that are contraindications for MTX administration) as well as the patient's desire for a surgery involving a simultaneous surgical procedure (10).
Concerning cervical pregnancies, the treatment varies from systemic MTX, dilatation and curettage, MTX or potassium chloride injection in the gestational sac, uterine artery embolization to hysterectomy. Being a rare pathology, there are not clear criteria for choosing the medical or surgical treatment as shown in the case of tubal pregnancy (11).
Cesarean scar pregnancy, pathology with a rising incidence nowadays, presents its own particularities in terms of treatment. The Society for Maternal-Fetal Medicine recommends surgery treatment respectively resection or medical treatment consisting of MTX administration in association with surgical treatment (12,13). Expectant management, curettage or MTX administration as single method of treatment are not recommended due to the elevated risk of maternal morbidity and mortality (perforation, hemorrhage, development of arteriovenous malformation etc.) (14,15). The different situations of this pathology require different approaches molded on each case. Other proposed treatments include laparoscopic management (16) robotically assisted or not (17), uterine arteries ligation (18) or transvaginal hysterotomy (19). There are protocols proposing the use of ultrasound guidance in vacuum aspiration due to the diminished amount of blood loss (20) whereas others propose curettage after a multidose regimen of MTX (21).

THE ROLE OF INTERVENTIONAL RADIOLOGY
Interventional radiology is widely used as an alternative, respectively it represents a conservative management in the gynecological sphere: uterine artery embolization (UAE) for uterine leiomyomas (22), uterine adenomyosis (23), arteriovenous malformations (24) and pelvic congestion syndrome (25). In the last years, interventional radiology has been indispensable in the management of obstetric hemorrhage: postpartum hemorrhage, abnormal placentation, abortion, as well as the therapeutic management of cervical ectopic pregnancy (CP) (26), cesarean scar pregnancy (CSP) (27) and fallopian tube ectopic pregnancy (TP) (28). We have a vast experience in in the collaboration with Interventional Radiology Department of Bucharest University Emergency Hospital regarding CP (Figures 1 and  2), CSP (Figures 3-6) and TP (Figures 7 and 8) treatment. More than this, we have submitted our cases to Cesarean Scar Pregnancy Register and we published recently a proposed minimal invasive 100% success rate therapeutical protocol for first trimester diagnosed CSP (29). Interventional radiology image of a cervical pregnancy before UAE UAE can be used as single method of treatment or in association with other procedures. In the vast majority of cases uterine artery embolization is used as a complementary method in the management of ectopic pregnancies to increase efficiency of the entire treatment, minimize blood loss and reduce the requirement of last line treatment-irreversible surgery, either salpingectomy or hysterectomy (26).

METHODS
In this paper we searched the literature using PubMed and we used the terms 'interventional radiology' and 'ectopic pregnancy' to identify the conservative treatment methods for tubal, cervical and cesarean scar pregnancy. The search included articles from 2010 until November 2021. We screened the abstracts in order to select relevant studies. We included case series, retrospective studies, prospective cohort studies, randomized control study and case reports.

RESULTS
The initial search returned a total of 56 articles. We screening the articles, removed the duplicates and selected the relevant articles to our paper. Therefore, 9 articles related to the use of interventional radiology in the treatment of ectopic pregnancies were included in our review. Our review includes a total of 415 patients treated with UAE: 155 patients with CSP, 62 with CP and 198 with TP (Figures 3 and 4). The treatment success rate was between 76.9% (30) and 100% (27,(31)(32)(33)(34). The main results are presented in Table 1.

UAE in association with MTX
256 patients were treated with MTX and UAE (30,(35)(36)(37) with success rates between 76.9% and 98.76%. This therapeutic management was successful in 238 patients. There were 18 patients that required additional therapies: 4 patients needed another UAE (29, 36), 6 patients needed subsequent MTX treatment (36) and 8 patients underwent surgery due to failure of treatment (36).

UAE in association with MTX and suction and curettage
4 patients (1 case of CSP and 3 cases of CP) were treated successfully using MTX administration, followed by UAE, suction and curettage (27,33). The patient with CSP was administered iv MTX with a slight decrease in the β-hCG, followed by UAE and a curettage was performed under simultaneous laparoscopic vision. The intra-operative blood loss was estimated at 50mL (27). The 3 cases of CP received a single dose of MTX: 1 patient was administered MTX intramuscular, the second patient was administered intra-arterial MTX prior to the finalization of the UAE and the third patient was given a parametrial shot of MTX simultaneously to the UAE. The curettage was performed in the first 72 hours after UAE to have a maximum benefit of the UAE (33).

UAE followed by suction and curettage
From our total of 415 patients, 133 were treated using UAE followed by curettage (31,33,34), among which Wu et al. (33) included 25 patients treated with UAE followed by hysteroscopic curettage. The success rates between 98% and 100%. One patient with CSP needed repeated suction and curettage (31); Ou et al. (31) compared the success rate of suction and curettage in cases of CSP in two groups: the first in which suction and curettage was used as single treatment and the second in which UAE was performed prior to suction and curettage. There were 4 cases of CSP in the first group in which the treatment failed: 2 patients received subsequently systematic MTX and 2 patients repeated the curettage. In the second group one patient needed a reintervention and a second curettage was performed.

UAE used as single treatment
A study by Niola et al. (32) published in 2014 included 41 cases of postpartum hemorrhage and 22 patients diagnosed with CP. The patients with CP were treated using UAE with a success rate of 100%, after which the patients were monitored using clinical and ultrasound examination at 1 month, 6 months and at 12 months 10 patients were pregnant and there were no issues during pregnancy, with an ulterior uneventful delivery.    (36). 11 patients of the 415 patients included in our paper (2.65%) needed a second approach: 6 patients needed MTX administration (36), 4 patients repeated the UAE (29,36) and 1 patient required a repeated suction and curettage (31).
Uterine artery embolization, used as single or combined treatment, was successful in 396 patients from the 415 selected for our study, result a 95.42% success rate, so we can conclude that 95.42% of women receiving this treatment had their fertility saved and did not undergo surgery, resulting in the best possible outcome.
In Romania, there are medical centers which present an interventional radiology department that make possible to form multidisciplinary teams (gynecologist, interventional radiologist, anesthesiologist) with the aim to minimally invasive treat pa-tients with ectopic pregnancies with significant results in reducing radical treatment among women of fertile age who desire to preserve their fertility or refuse surgery or have associated pathologies that might put their life at risk during surgery.

CONCLUSIONS
Uterine artery embolization has proven its utility in managing cases of ectopic pregnancies as single line treatment or combined with methotrexate administered either local, intramuscular, or intra arterial during uterine/ovarian artery embolization, associated with suction and/or curettage or with hysteroscopic curettage, thus avoiding a major surgical intervention that compromises the female fertility (hysterectomy or salpingectomy) with additional possible surgical complications, reducing the costs of medical healthcare and the surgical stress to which the patient is subjected.

Conflict of interest: none declared
Financial support: none declared