CLINICAL STUDY
Transcatheter Arterial Embolization for Secondary Postpartum Hemorrhage: Outcome in 52 Patients at a Single Tertiary Referral Center Hye sun Park, MD, Ji Hoon Shin, MD, Hyun-Ki Yoon, MD, Jin Hyoung Kim, MD, Dong-Il Gwon, MD, Gi-Young Ko, MD, and Kyu-Bo Sung, MD
ABSTRACT Purpose: To assess the safety and efficacy of transcatheter arterial embolization (TAE) for the management of secondary postpartum hemorrhage (PPH) and to determine the factors associated with the clinical outcomes. Materials and Methods: A retrospective analysis of 52 patients (mean age, 31.6 y; range, 25–40 y) undergoing TAE for secondary PPH was performed. Clinical data, including maternal characteristics, delivery details, embolization details, and transfusion requirements, were obtained. Univariate analyses were performed to determine the factors related to clinical outcomes. Results: The major cause of bleeding was retained placental tissue (44.2%; 23 of 52). Actively bleeding foci were observed in 25 (48.1%) patients. Technical and clinical successes were achieved in 100% and 90.4% (47 of 52) of patients, respectively. Gelatin sponge particles with (n ¼ 10) or without (n ¼ 38) permanent embolic materials, such as microcoils or N-butyl cyanoacrylate, were most commonly used (92.3%; 48 of 52), whereas permanent embolic materials alone were used in 7.7% (4 of 52) of patients. In five patients, embolization failed, and these patients were managed by hysterectomy (n ¼ 3), repeat TAE (n ¼ 1), or conservative management (n ¼ 1). Bleeding control was eventually achieved in all five patients. No maternal risk factors were related to clinical results. The median and mean follow-up periods were 3 months and 12.6 months (range, 1–62 mo). Regular menstruation resumed in all 44 patients with available follow-up, and 5 of the patients became pregnant. Conclusions: TAE for secondary PPH is safe and effective and showed technical and clinical success in 100% and 90.4% of patients, respectively. Approximately half of these patients showed a positive bleeding focus, and the use of permanent embolic materials was also common.
ABBREVIATIONS BCA = N-butyl cyanoacrylate, PPH = postpartum hemorrhage, TAE = transcatheter arterial embolization
Although mortality rates related to postpartum hemorrhage (PPH) have decreased in recent years, PPH remains the leading cause of pregnancy-related death worldwide. PPH occurs in approximately 6% of all deliveries and is an important cause of pregnancyrelated morbidity (1). Secondary PPH is defined as any
From the Department of Radiology and Research Institute of Radiology, University of Ulsan, College of Medicine, Asan Medical Center, 86, Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, Korea. Received November 30, 2013; final revision received May 9, 2014; accepted May 12, 2014. Address correspondence to J.H.S.; E-mail: [email protected] None of the authors have identified a conflict of interest. & SIR, 2014 J Vasc Interv Radiol 2014; 25:1751–1757 http://dx.doi.org/10.1016/j.jvir.2014.05.009
bleeding from the genital tract 24 hours to 6 weeks after the end of the third stage of labor. Secondary PPH commonly occurs 8–14 days postpartum, with a reported incidence rate of 0.5%–1.3% (2,3). Although secondary PPH tends to be associated with maternal morbidity rather than mortality, persistent PPH can be lifethreatening and requires surgical or endovascular management (3). With decreasing maternal mortality rates, there is increasing interest in the management of secondary PPH. Transcatheter embolization of the uterine arteries may be an attractive alternative treatment for intractable bleeding instead of hysterectomy. Compared with primary PPH, reports of transcatheter arterial embolization (TAE) of secondary PPH have been limited, with most studies enrolling o 25 patients (4–6). In some reports, the outcomes of primary and secondary PPH were not evaluated separately, and there
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were limitations in the identification of clinical outcomes of TAE in secondary PPH alone (6,7). The purpose of the present study was to determine the safety and clinical efficacy of TAE for intractable secondary PPH and to evaluate the factors associated with the clinical success of TAE in a large, single-center cohort.
MATERIALS AND METHODS Patient Selection The outcomes of all patients who underwent TAE for secondary PPH at our institution between January 2000 and December 2012 were retrospectively analyzed. The study population comprised 52 consecutive women who underwent TAE for treatment of intractable secondary PPH, which was defined as continuous vaginal bleeding despite medical management, including the administration of intravenous fluid, transfusion, or uterotonic agents. All patients had been admitted to the obstetrics department at our institution via the delivery room or the emergency department. All patients provided written informed consent, and the study protocol was approved by the institutional review board.
Analytic Items and Definitions A review of the obstetric charts was performed by two radiologists in consensus to collect data regarding maternal characteristics, cause of bleeding, mode of delivery, bleeding onset after delivery, risk factors for PPH (eg, placental anomaly, pregnancy-induced
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hypertension, coagulopathy), amount and product type of blood transfusion, details regarding the TAE procedure, complications related to TAE, and clinical outcome. The causes of bleeding were categorized into eight groups: retained placental tissue, placental anomaly such as placenta accreta/increta or placenta previa, uterine arteriovenous malformation, rupture or injury of the uterine artery, uterine subinvolution/atony, trauma, coagulopathy (ie, underlying coagulation disorder or disseminated intravascular coagulation), and unknown. Retained placental tissue was confirmed pathologically by curettage. The etiology was considered unknown when no specific cause of bleeding could be identified. Obstetric maneuvers used to control hemorrhage were documented and included uterine massage, uterine packing, administration of uterotonic agents, and surgical intervention (eg, inspection for and repair of lower genital tract tears, manual exploration of the uterine cavity, uterine suturing, and uterine artery ligation or hysterectomy). We also consulted the medical charts of women who regularly visited the outpatient obstetric clinic after their discharge to obtain information regarding their menstruation and pregnancies. Complications were categorized as major or minor according to the guidelines of the Society of Interventional Radiology (SIR) Standards of Practice Committee (8). Major complications were defined as complications requiring major therapy, complications necessitating an unplanned increase in the level of care or prolonged hospitalization (4 48 h), and complications resulting in permanent adverse sequelae or death. Minor
Table 1 . Characteristics of Patients, PPH, and Embolization Details with Transcatheter Arterial Embolization Characteristics
Total (n ¼ 52)
Success (n ¼ 47)
Failure (n ¼ 5)
P Value
Maternal characteristics Nullipara Previous cesarean delivery Type of delivery Vaginal delivery Cesarean delivery
44 8
39 8
5 0
1.000 1.000
34
30
4
.648
18 13.5 ⫾ 9.7
17 13.2 ⫾ 9.5
3.4 ⫾ 1.6 4.7 ⫾ 5.1
3.3 ⫾ 1.6 4.5 ⫾ 5.2
1 16 ⫾ 12.3
.756
3.8 ⫾ 2.0 6.2 ⫾ 4.8
.275 .452
Bleeding onset after delivery (d) Hospital stay (d) Transfusion* Causes of secondary PPH
.150
Retained placental tissue Placental anomaly
23 3
21 1
2 2
Placental accreta/increta
2
0
2
Placenta previa Uterine AVM
1 6
1 5
0 1
Rupture or injury of a uterine artery
9
9
0
Uterine subinvolution/atony Trauma (cervical laceration)
5 1
5 1
0 0
Coagulopathy (maternal ITP)
2
2
0
Unknown
3
3
0
AVM ¼ arteriovenous malformation; ITP ¼ idiopathic thrombocytopenic purpura; PPH ¼ postpartum hemorrhage. Packed red blood cells.
n
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complications were defined as complications requiring no or only nominal therapy, including overnight admission for observation.
Patient Obstetric Characteristics Table 1 summarizes obstetric characteristics of patients. TAE was performed in 52 patients (mean age, 31.6 y; range, 25–40 y) in the angiography suite to treat secondary PPH. Of these patients, 35 (67.3%) were primiparous, and 17 (32.7%) were multiparous. Among 35 primiparas, 26 had vaginal deliveries (26 of 35; 74.3%), and 9 had cesarean sections (9 of 35; 25.7%). Among 17 multiparas, 8 had vaginal deliveries (8 of 17; 47.1%), and 9 had cesarean sections (9 of 17; 52.9%). The most frequent cause of PPH was retained placental tissue (n ¼ 23; 44.2%), followed by a rupture or
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injury of the uterine artery (n ¼ 9), uterine arteriovenous malformation (n ¼ 6), uterine subinvolution/atony (n ¼ 5), placental anomaly (n ¼ 3), unknown (n ¼ 3), coagulopathy (n ¼ 2), and trauma (n ¼ 1). Uterine arteriovenous malformation was confirmed by angiographic observation of bilateral hypertrophy of the uterine arteries that fed a tortuous, hypertrophic arterial mass with large accessory feeding vessels and early drainage into enlarged hypertrophic veins. The mean time of bleeding onset after delivery was 13.3 days (median, 10 d; range, 1–39 d). The mean length of hospital stay was 3.4 days ⫾ 1.6 (range, 2–9 d). All patients were hemodynamically stable at the time of admission and initially medically managed (eg, administered intravenous fluids) before more invasive management such as TAE or surgery was considered. Trans-
Figure 1. A 33-year-old woman with massive PPH from an unknown cause 6 days after cesarean section. (a, b) Left internal iliac arteriograms show a prominent left uterine artery with a late opacified pseudoaneurysm (arrows). (c) Radiograph shows NBCA cast filling the pseudoaneurysm (short arrow) and the left uterine artery (arrowheads) after successful embolization. Extravasated NBCA (long arrow) is secondary to pseudoaneurysm rupture during the embolization. (d) Left internal iliac arteriogram shows no further bleeding focus after embolization.
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fusion was performed for patients who experienced blood loss that might threaten hemodynamic stability.
Angiography and Embolization Technique Digital subtraction angiography and TAE were performed by one of four interventional radiologists with 5–25 years of clinical experience. A 5-F vascular sheath was inserted into the right or left common femoral artery. Arteriograms of the bilateral internal iliac arteries were performed to identify the uterine artery or other potential bleeding sites. A Cobra Glidecath (Radifocus; Terumo, Tokyo, Japan) was introduced over a 0.035inch guide wire to obtain access to the internal iliac artery and its branches. A microcatheter (Renegade; Boston Scientific, Cork, Ireland, or MICROFERRET; Cook, Inc, Bloomington, Indiana) was required for superselection of the transverse or ascending segments of the uterine arteries. Aortograms were obtained to identify the ovarian artery in patients with continued or recurrent bleeding after embolization of both uterine arteries and anterior division of the internal iliac arteries. Selective arterial embolization was performed when a bleeding focus was identified by angiography. Uterine artery embolization was performed if no signs of active bleeding were observed by angiography, such as extravasation of contrast media or pseudoaneurysm, and only hypertrophied uterine arteries were observed. Embolization of the anterior divisions of both internal iliac arteries was considered when the uterine artery could not be easily accessed (eg, in patients who had undergone hysterectomy) or when vaginal bleeding continued despite embolization of both uterine arteries. Absorbable gelatin sponge particles (Spongostan; Johnson & Johnson, Gauteng, South Africa) were the embolic material of choice. Gelatin sponge particles were injected into the arteries as a slurry mixed with diluted contrast medium until stasis or occlusion was evident by angiography. Microcoils (Hilal or Tornado; Cook, Inc) and N-butyl cyanoacrylate (NBCA) (Histoacryl; B. Braun AG, Melsungen, Germany) were also used as primary embolic agents or as additional embolic materials at the discretion of the operator. Iliac angiograms were obtained after embolization to confirm the disappearance of the bleeding focus or to identify other arteries causing additional bleeding.
Definitions and Statistical Methods Technical success was defined as cessation of bleeding, as observed on angiography performed after embolization and on speculum inspection, which was performed immediately after TAE. Clinical success was defined as the cessation of bleeding after TAE with no further management, such as repeat TAE or additional surgery, during the patient’s hospital stay. Outcomes were compared between successful and failed TAE for secondary PPH. Univariate analyses
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were performed to determine the factors associated with clinical success. Univariate analysis of the categorical data was assessed using Fisher exact test, and univariate analysis of the continuous data was assessed using the Mann-Whitney test. All statistical analyses were performed using SPSS software (version 17.0 for Windows; SPSS, Chicago, Illinois).
RESULTS Angiography demonstrated the foci of bleeding in 25 patients (48%), including extravasations (n ¼ 13) and pseudoaneurysms (n ¼ 12) (Fig 1a–d). Of the 12 patients with pseudoaneurysm, 10 had cesarean sections, and 2 had uncomplicated vaginal deliveries. Embolization of 101 arteries was performed in 52 patients (Table 2). In 25 patients (48.1%) with actively bleeding foci, selective embolization was performed for arteries showing active bleeding, and additional embolization of the uterine arteries was performed if they were hypertrophied (Table 2). In all 27 patients without definite bleeding foci, selective embolization of both uterine arteries was performed, and an additional left ovarian artery embolization was performed in 1 patient because of hypertrophy of the left ovarian artery (Fig 2a–d). Gelatin sponge particles were used as single embolic agents in 38 patients (73.1%) or in combination with microcoils (n ¼ 7) or NBCA (n ¼ 3) in 10 patients (19.2%). Microcoils (n ¼ 1) and NBCA (n ¼ 3) were used as single embolic agents in four patients (7.7%). Permanent embolic materials were used at the discretion of operators when gelatin sponge particles were insufficient to fill the pseudoaneurysm completely or to stop extravasation. Detailed TAE results are shown in Figure 3. TAE was technically successful in all 52 study patients (100%). Table 2 . Arteries Embolized during Transcatheter Arterial Embolization No. Patients Patients with active bleeding (n ¼ 25) Bilateral UAs
8
Left UA
8
Right UA Bilateral UAs þ anterior branches of bilateral IIAs
2 2
Bilateral UAs þ anterior branch of left IIA
1
Left UA þ anterior branch of right IIA Anterior branches of bilateral IIAs
1 1
Bilateral UAs þ right ovarian artery
1
Left UA þ left ovarian artery Patients without definite bleeding foci (n ¼ 27) Bilateral UAs Bilateral UAs þ left ovarian artery IIA ¼ internal iliac artery; UA ¼ uterine artery.
1 26 1
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Figure 2. A 25-year-old woman with massive PPH from retained placental tissue 16 days after vaginal delivery. (a) Aortogram shows prominent uterine vascularity from the tortuous uterine arteries. (b) Delayed image of aortogram shows persistent amorphous opacification (arrows). Although embolization of the bilateral uterine arteries was performed with gelatin sponge particles (not shown), there was continued bleeding. (c, d) Aortograms with the catheter at the renal artery level show prominent left ovarian artery (arrows, c) and increased vascularity of the uterus (arrowheads, d). Embolization of the left ovarian artery was subsequently performed using gelatin sponge particles (not shown).
Figure 3. In-hospital results of TAE performed for secondary PPH.
Clinical success was achieved with initial TAE in 47 patients (90.4%; 47 of 52). The remaining five patients showed rebleeding after embolization, and two patients (20%; 2 of 5) showed active bleeding foci on angiography. Bleeding was eventually controlled in all of these patients; three underwent hysterectomy, one underwent repeat TAE, and one received conservative management. The clinical characteristics of these patients did not differ from the other 47 patients with clinical success (Table 3). There was no statistically significant difference in the technical success rate of TAE between patients with and without a bleeding focus, as observed by angiography (P ¼ 1). Procedurerelated complications were not observed in any of these patients.
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Table 3 . Characteristics of Five Patients without Clinical Success of Transcatheter Arterial Embolization
Age Type of delivery Bleeding onset (d)
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
32 Vaginal
27 Vaginal
30 Cesarean section
29 Vaginal
26 Vaginal
3
7
30
12
28
Cause Transfusion*
Placental anomaly 0
Retained placenta 9
Uterine AVM 2
Angiographic findings
Retained placenta Placental anomaly 10 10
No active bleeding
No active bleeding
No active bleeding
Extravasation
Pseudoaneurysm
Embolized artery Material
Both UA GSP
Both UA GSP
Both UA GSP
Both IIA þ UA Coil þ GSP
Right IIA þ left UA GSP
Additional management
Surgery
Conservative management
Surgery
TAE
Surgery
AVM ¼ arteriovenous malformation; GSP = gelatin sponge particle; IIA ¼ internal iliac artery; TAE ¼ transcatheter arterial embolization; UA ¼ uterine artery. n Packed red blood cells.
Eight patients were lost to follow-up after discharge. For the 44 patients with available follow-up, the median and mean follow-up periods were 3 months and 12.6 months (range, 1–62 mo), respectively. Regular menstruation resumed in all patients with follow-up, and five of the patients became pregnant. No patient experienced morbidity, and no patient died. Univariate analysis showed that the clinical success of TAE for secondary PPH was not related to any of the analyzed factors, including maternal obstetric characteristics, type of delivery, bleeding onset after delivery, length of hospital stay, cause of bleeding, and amount and product type of blood transfusion (P ¼ 1.00, P ¼ .65, P ¼ .76, P ¼ .275, P ¼ .15, and P ¼ .45).
DISCUSSION Secondary PPH, which is defined as PPH occurring between 24 hours and 6 weeks after labor, has received little attention compared with primary PPH owing to its relatively low incidence and association with maternal morbidity rather than mortality. In addition, because bleeding occurs most frequently between day 8 and day 14 of the puerperium, patients often have already been discharged from the hospital, and potential hemorrhage is often missed by clinicians (1–3). However, persistent PPH can be life-threatening, and it requires surgical or endovascular management (1–3). Consistent with the current literature, the most common cause of secondary PPH in the present study was retained placental tissue (1–3). Uterine atony, which is the most common cause of primary PPH, was the etiology of secondary PPH in five cases (9.6%). Although pseudoaneurysm of the uterine artery has been reported to be a rare cause of delayed PPH (4,5,7,9), it was noted on 23% of the initial angiograms (12 of 52). In this study, a cesarean section had been performed on most of the patients with a pseudoaneurysm observed on angiography, although some of these patients had a history of uncomplicated vaginal delivery. This reported rate was similar to rates obtained in
previous studies regarding the association of uterine artery pseudoaneurysms with a traumatic event or delivery (4,5,7,9). This finding introduces the possibility that pseudoaneurysms may be caused by surgery in some patients, although the minor trauma of an uncomplicated, spontaneous vaginal delivery may be sufficient to induce pseudoaneurysm formation (4,5,7,9). The administration of ergometrine with or without oxytocin is the initial primary conservative treatment of secondary PPH. When a bleeding source is suspected in the lower genital tract, careful inspection is necessary to rule out the possibility of a laceration or to identify retained placental fragments, which can be removed by suction evacuation and curettage. Surgical ligation of the uterine arteries or internal iliac arteries may be performed to preserve fertility (10,11). However, vascular ligation often fails to stop the bleeding owing to potential collateral circulation (10,11). TAE is a recognized method for the control of PPH (11). Many studies have documented the safety and clinical effectiveness of TAE for secondary PPH and have reported clinical success rates of TAE 4 90% for secondary PPH (2,4–7). The present study evaluated a much larger sample size and, consistent with previous studies, demonstrated a high clinical success rate (90.9%). There were no procedure-related complications. All of patients with available follow-up resumed menstruation, and five patients became pregnant during the follow-up period. Several research groups have reviewed the effects of embolization on the resumption of menses and future fertility (11–13). Some reports showed that there was an increased risk of placental disorders and fetal growth restriction (9), whereas other reports suggested favorable outcomes for the preservation of fertility (11,14,15). Although gelatin sponge particles were the most commonly used embolic materials, permanent embolic materials, such as microcoils and NBCA, were also used either alone or in combination with gelatin sponge particles in 14 patients (26.9%) and showed successful bleeding control. One patient who failed the initial TAE
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using gelatin sponge particles received additional TAE using a microcoil and was successfully treated. Several studies have also reported the use of permanent embolic materials, such as coils and NBCA, in patients with secondary PPH when clinical success with TAE could not be achieved using gelatin sponge particles alone (2) or if patients had underlying coagulopathy (16,17). Resumption of menstruation in all patients with available follow-up data suggests that the use of permanent embolic materials is safe in TAE. In the present study, there were no risk factors among the maternal risk factors assessed for the clinical success of TAE for secondary PPH. In addition, no reports have yet suggested any risk factors for poor outcomes of TAE for secondary PPH, although disseminated intravascular coagulation and massive transfusion are known to be associated with poor outcomes of TAE performed for primary PPH (18). As observed in the present study, patients with secondary PPH appear to be hemodynamically stable and receive fewer transfusions than patients with primary PPH (18). The present study has several limitations, including retrospective design based on a review of medical records. In addition, because there are no established clinical guidelines for embolization, management was determined by consensus agreement among referring obstetricians and interventional radiologists on a caseby-case basis. Given that our institution is a tertiary care center, there was also a selection bias because patients transferred from other institutions were included. Longterm follow-up data assessing fertility and ovarian function were not available for all study patients. In conclusion, TAE for secondary PPH is safe and effective and showed technical and clinical success in 100% and 90.4% of patients, respectively. Approximately half of these patients showed a positive bleeding focus, and the use of permanent embolic materials was also common.
REFERENCES 1. Carroli G, Cuesta C, Abalos E, Gulmezoglu AM. Epidemiology of postpartum haemorrhage: a systematic review. Best Pract Res Clin Obstet Gynaecol 2008; 22:999–1012.
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2. Pelage J-P, Soyer P, Repiquet D, et al. Secondary postpartum hemorrhage: treatment with selective arterial embolization. Radiology 1999; 212:385–389. 3. Hoveyda F, MacKenzie IZ. Secondary postpartum haemorrhage: incidence, morbidity and current management. BJOG 2001; 108:927–930. 4. Sharma AM, Burbridge BE. Case report: uterine artery pseudoaneurysm in the setting of delayed postpartum hemorrhage: successful treatment with emergency arterial embolization. Case Rep Radiol 2011; 2011:373482. 5. Kim GM, Yoon CJ, Seong NG, et al. Postpartum haemorrhage from ruptured pseudoaneurysm: efficacy of transcatheter arterial embolisation using N-butyl-2-cyanoacrylate. Eur Radiol 2013; 23:2344–2349. 6. Lee HJ, Jeon GS, Kim MD, et al. Usefulness of pelvic artery embolization in cesarean section compared with vaginal delivery in 176 patients. J Vasc Interv Radiol 2013; 24:103–109. 7. Dohan A, Soyer P, Subhani A, et al. Postpartum hemorrhage resulting from pelvic pseudoaneurysm: a retrospective analysis of 588 consecutive cases treated by arterial embolization. Cardiovasc Intervent Radiol 2013; 36:1247–1255. 8. Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol 2003; 14: S199–S202. 9. McGonegle SJ, Dziedzic TS, Thomas J, Hertzberg BS. Pseudoaneurysm of the uterine artery after an uncomplicated spontaneous vaginal delivery. J Ultrasound Med 2006; 25:1593–1597. 10. Gizzo S, Saccardi C, Patrelli TS, et al. Fertility rate and subsequent pregnancy outcomes after conservative surgical techniques in postpartum hemorrhage: 15 years of literature. Fertil Steril 2013; 99: 2097–2107. 11. Healey S, Buzaglo K, Seti L, Valenti D, Tulandi T. Ovarian function after uterine artery embolization and hysterectomy. J Am Assoc Gynecol Laparosc 2004; 11:348–352. 12. Spies JB, Roth AR, Gonsalves SM, Murphy-Skrzyniarz KM. Ovarian function after uterine artery embolization for leiomyomata: assessment with use of serum follicle stimulating hormone assay. J Vasc Interv Radiol 2001; 12:437–442. 13. Ahmad A, Qadan L, Hassan N, Najarian K. Uterine artery embolization treatment of uterine fibroids: effect on ovarian function in younger women. J Vasc Interv Radiol 2002; 13:1017–1020. 14. Stancato-Pasik A, Mitty HA, Richard HM 3rd, Eshkar N. Obstetric embolotherapy: effect on menses and pregnancy. Radiology 1997; 204: 791–793. 15. Yamashita Y, Harada M, Yamamoto H, et al. Transcatheter arterial embolization of obstetric and gynaecological bleeding: efficacy and clinical outcome. Br J Radiol 1994; 67:530–534. 16. Kanematsu M, Watanabe H, Kondo H, et al. Postpartum hemorrhage in coagulopathic patients: preliminary experience with uterine arterial embolization with N-butyl cyanoacrylate. J Vasc Interv Radiol 2011; 22: 1773–1776. 17. Yonemitsu T, Kawai N, Sato M, et al. Comparison of hemostatic durability between N-butyl cyanoacrylate and gelatin sponge particles in transcatheter arterial embolization for acute arterial hemorrhage in a coagulopathic condition in a swine model. Cardiovasc Intervent Radiol 2010; 33:1192–1197. 18. Lee HY, Shin JH, Kim J, et al. Primary postpartum hemorrhage: outcome of pelvic arterial embolization in 251 patients at a single institution. Radiology 2012; 264:903–909.
Transcatheter Arterial Embolization for Secondary Postpartum Hemorrhage: Outcome in 52 Patients at a Single Tertiary Referral Center Hye sun Park, MD, Ji Hoon Shin, MD, Hyun-Ki Yoon, MD, Jin Hyoung Kim, MD, Dong-Il Gwon, MD, Gi-Young Ko, MD, and Kyu-Bo Sung, MD
ABSTRACT Purpose: To assess the safety and efficacy of transcatheter arterial embolization (TAE) for the management of secondary postpartum hemorrhage (PPH) and to determine the factors associated with the clinical outcomes. Materials and Methods: A retrospective analysis of 52 patients (mean age, 31.6 y; range, 25–40 y) undergoing TAE for secondary PPH was performed. Clinical data, including maternal characteristics, delivery details, embolization details, and transfusion requirements, were obtained. Univariate analyses were performed to determine the factors related to clinical outcomes. Results: The major cause of bleeding was retained placental tissue (44.2%; 23 of 52). Actively bleeding foci were observed in 25 (48.1%) patients. Technical and clinical successes were achieved in 100% and 90.4% (47 of 52) of patients, respectively. Gelatin sponge particles with (n ¼ 10) or without (n ¼ 38) permanent embolic materials, such as microcoils or N-butyl cyanoacrylate, were most commonly used (92.3%; 48 of 52), whereas permanent embolic materials alone were used in 7.7% (4 of 52) of patients. In five patients, embolization failed, and these patients were managed by hysterectomy (n ¼ 3), repeat TAE (n ¼ 1), or conservative management (n ¼ 1). Bleeding control was eventually achieved in all five patients. No maternal risk factors were related to clinical results. The median and mean follow-up periods were 3 months and 12.6 months (range, 1–62 mo). Regular menstruation resumed in all 44 patients with available follow-up, and 5 of the patients became pregnant. Conclusions: TAE for secondary PPH is safe and effective and showed technical and clinical success in 100% and 90.4% of patients, respectively. Approximately half of these patients showed a positive bleeding focus, and the use of permanent embolic materials was also common.
ABBREVIATIONS BCA = N-butyl cyanoacrylate, PPH = postpartum hemorrhage, TAE = transcatheter arterial embolization
Although mortality rates related to postpartum hemorrhage (PPH) have decreased in recent years, PPH remains the leading cause of pregnancy-related death worldwide. PPH occurs in approximately 6% of all deliveries and is an important cause of pregnancyrelated morbidity (1). Secondary PPH is defined as any
From the Department of Radiology and Research Institute of Radiology, University of Ulsan, College of Medicine, Asan Medical Center, 86, Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, Korea. Received November 30, 2013; final revision received May 9, 2014; accepted May 12, 2014. Address correspondence to J.H.S.; E-mail: [email protected] None of the authors have identified a conflict of interest. & SIR, 2014 J Vasc Interv Radiol 2014; 25:1751–1757 http://dx.doi.org/10.1016/j.jvir.2014.05.009
bleeding from the genital tract 24 hours to 6 weeks after the end of the third stage of labor. Secondary PPH commonly occurs 8–14 days postpartum, with a reported incidence rate of 0.5%–1.3% (2,3). Although secondary PPH tends to be associated with maternal morbidity rather than mortality, persistent PPH can be lifethreatening and requires surgical or endovascular management (3). With decreasing maternal mortality rates, there is increasing interest in the management of secondary PPH. Transcatheter embolization of the uterine arteries may be an attractive alternative treatment for intractable bleeding instead of hysterectomy. Compared with primary PPH, reports of transcatheter arterial embolization (TAE) of secondary PPH have been limited, with most studies enrolling o 25 patients (4–6). In some reports, the outcomes of primary and secondary PPH were not evaluated separately, and there
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were limitations in the identification of clinical outcomes of TAE in secondary PPH alone (6,7). The purpose of the present study was to determine the safety and clinical efficacy of TAE for intractable secondary PPH and to evaluate the factors associated with the clinical success of TAE in a large, single-center cohort.
MATERIALS AND METHODS Patient Selection The outcomes of all patients who underwent TAE for secondary PPH at our institution between January 2000 and December 2012 were retrospectively analyzed. The study population comprised 52 consecutive women who underwent TAE for treatment of intractable secondary PPH, which was defined as continuous vaginal bleeding despite medical management, including the administration of intravenous fluid, transfusion, or uterotonic agents. All patients had been admitted to the obstetrics department at our institution via the delivery room or the emergency department. All patients provided written informed consent, and the study protocol was approved by the institutional review board.
Analytic Items and Definitions A review of the obstetric charts was performed by two radiologists in consensus to collect data regarding maternal characteristics, cause of bleeding, mode of delivery, bleeding onset after delivery, risk factors for PPH (eg, placental anomaly, pregnancy-induced
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hypertension, coagulopathy), amount and product type of blood transfusion, details regarding the TAE procedure, complications related to TAE, and clinical outcome. The causes of bleeding were categorized into eight groups: retained placental tissue, placental anomaly such as placenta accreta/increta or placenta previa, uterine arteriovenous malformation, rupture or injury of the uterine artery, uterine subinvolution/atony, trauma, coagulopathy (ie, underlying coagulation disorder or disseminated intravascular coagulation), and unknown. Retained placental tissue was confirmed pathologically by curettage. The etiology was considered unknown when no specific cause of bleeding could be identified. Obstetric maneuvers used to control hemorrhage were documented and included uterine massage, uterine packing, administration of uterotonic agents, and surgical intervention (eg, inspection for and repair of lower genital tract tears, manual exploration of the uterine cavity, uterine suturing, and uterine artery ligation or hysterectomy). We also consulted the medical charts of women who regularly visited the outpatient obstetric clinic after their discharge to obtain information regarding their menstruation and pregnancies. Complications were categorized as major or minor according to the guidelines of the Society of Interventional Radiology (SIR) Standards of Practice Committee (8). Major complications were defined as complications requiring major therapy, complications necessitating an unplanned increase in the level of care or prolonged hospitalization (4 48 h), and complications resulting in permanent adverse sequelae or death. Minor
Table 1 . Characteristics of Patients, PPH, and Embolization Details with Transcatheter Arterial Embolization Characteristics
Total (n ¼ 52)
Success (n ¼ 47)
Failure (n ¼ 5)
P Value
Maternal characteristics Nullipara Previous cesarean delivery Type of delivery Vaginal delivery Cesarean delivery
44 8
39 8
5 0
1.000 1.000
34
30
4
.648
18 13.5 ⫾ 9.7
17 13.2 ⫾ 9.5
3.4 ⫾ 1.6 4.7 ⫾ 5.1
3.3 ⫾ 1.6 4.5 ⫾ 5.2
1 16 ⫾ 12.3
.756
3.8 ⫾ 2.0 6.2 ⫾ 4.8
.275 .452
Bleeding onset after delivery (d) Hospital stay (d) Transfusion* Causes of secondary PPH
.150
Retained placental tissue Placental anomaly
23 3
21 1
2 2
Placental accreta/increta
2
0
2
Placenta previa Uterine AVM
1 6
1 5
0 1
Rupture or injury of a uterine artery
9
9
0
Uterine subinvolution/atony Trauma (cervical laceration)
5 1
5 1
0 0
Coagulopathy (maternal ITP)
2
2
0
Unknown
3
3
0
AVM ¼ arteriovenous malformation; ITP ¼ idiopathic thrombocytopenic purpura; PPH ¼ postpartum hemorrhage. Packed red blood cells.
n
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complications were defined as complications requiring no or only nominal therapy, including overnight admission for observation.
Patient Obstetric Characteristics Table 1 summarizes obstetric characteristics of patients. TAE was performed in 52 patients (mean age, 31.6 y; range, 25–40 y) in the angiography suite to treat secondary PPH. Of these patients, 35 (67.3%) were primiparous, and 17 (32.7%) were multiparous. Among 35 primiparas, 26 had vaginal deliveries (26 of 35; 74.3%), and 9 had cesarean sections (9 of 35; 25.7%). Among 17 multiparas, 8 had vaginal deliveries (8 of 17; 47.1%), and 9 had cesarean sections (9 of 17; 52.9%). The most frequent cause of PPH was retained placental tissue (n ¼ 23; 44.2%), followed by a rupture or
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injury of the uterine artery (n ¼ 9), uterine arteriovenous malformation (n ¼ 6), uterine subinvolution/atony (n ¼ 5), placental anomaly (n ¼ 3), unknown (n ¼ 3), coagulopathy (n ¼ 2), and trauma (n ¼ 1). Uterine arteriovenous malformation was confirmed by angiographic observation of bilateral hypertrophy of the uterine arteries that fed a tortuous, hypertrophic arterial mass with large accessory feeding vessels and early drainage into enlarged hypertrophic veins. The mean time of bleeding onset after delivery was 13.3 days (median, 10 d; range, 1–39 d). The mean length of hospital stay was 3.4 days ⫾ 1.6 (range, 2–9 d). All patients were hemodynamically stable at the time of admission and initially medically managed (eg, administered intravenous fluids) before more invasive management such as TAE or surgery was considered. Trans-
Figure 1. A 33-year-old woman with massive PPH from an unknown cause 6 days after cesarean section. (a, b) Left internal iliac arteriograms show a prominent left uterine artery with a late opacified pseudoaneurysm (arrows). (c) Radiograph shows NBCA cast filling the pseudoaneurysm (short arrow) and the left uterine artery (arrowheads) after successful embolization. Extravasated NBCA (long arrow) is secondary to pseudoaneurysm rupture during the embolization. (d) Left internal iliac arteriogram shows no further bleeding focus after embolization.
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fusion was performed for patients who experienced blood loss that might threaten hemodynamic stability.
Angiography and Embolization Technique Digital subtraction angiography and TAE were performed by one of four interventional radiologists with 5–25 years of clinical experience. A 5-F vascular sheath was inserted into the right or left common femoral artery. Arteriograms of the bilateral internal iliac arteries were performed to identify the uterine artery or other potential bleeding sites. A Cobra Glidecath (Radifocus; Terumo, Tokyo, Japan) was introduced over a 0.035inch guide wire to obtain access to the internal iliac artery and its branches. A microcatheter (Renegade; Boston Scientific, Cork, Ireland, or MICROFERRET; Cook, Inc, Bloomington, Indiana) was required for superselection of the transverse or ascending segments of the uterine arteries. Aortograms were obtained to identify the ovarian artery in patients with continued or recurrent bleeding after embolization of both uterine arteries and anterior division of the internal iliac arteries. Selective arterial embolization was performed when a bleeding focus was identified by angiography. Uterine artery embolization was performed if no signs of active bleeding were observed by angiography, such as extravasation of contrast media or pseudoaneurysm, and only hypertrophied uterine arteries were observed. Embolization of the anterior divisions of both internal iliac arteries was considered when the uterine artery could not be easily accessed (eg, in patients who had undergone hysterectomy) or when vaginal bleeding continued despite embolization of both uterine arteries. Absorbable gelatin sponge particles (Spongostan; Johnson & Johnson, Gauteng, South Africa) were the embolic material of choice. Gelatin sponge particles were injected into the arteries as a slurry mixed with diluted contrast medium until stasis or occlusion was evident by angiography. Microcoils (Hilal or Tornado; Cook, Inc) and N-butyl cyanoacrylate (NBCA) (Histoacryl; B. Braun AG, Melsungen, Germany) were also used as primary embolic agents or as additional embolic materials at the discretion of the operator. Iliac angiograms were obtained after embolization to confirm the disappearance of the bleeding focus or to identify other arteries causing additional bleeding.
Definitions and Statistical Methods Technical success was defined as cessation of bleeding, as observed on angiography performed after embolization and on speculum inspection, which was performed immediately after TAE. Clinical success was defined as the cessation of bleeding after TAE with no further management, such as repeat TAE or additional surgery, during the patient’s hospital stay. Outcomes were compared between successful and failed TAE for secondary PPH. Univariate analyses
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were performed to determine the factors associated with clinical success. Univariate analysis of the categorical data was assessed using Fisher exact test, and univariate analysis of the continuous data was assessed using the Mann-Whitney test. All statistical analyses were performed using SPSS software (version 17.0 for Windows; SPSS, Chicago, Illinois).
RESULTS Angiography demonstrated the foci of bleeding in 25 patients (48%), including extravasations (n ¼ 13) and pseudoaneurysms (n ¼ 12) (Fig 1a–d). Of the 12 patients with pseudoaneurysm, 10 had cesarean sections, and 2 had uncomplicated vaginal deliveries. Embolization of 101 arteries was performed in 52 patients (Table 2). In 25 patients (48.1%) with actively bleeding foci, selective embolization was performed for arteries showing active bleeding, and additional embolization of the uterine arteries was performed if they were hypertrophied (Table 2). In all 27 patients without definite bleeding foci, selective embolization of both uterine arteries was performed, and an additional left ovarian artery embolization was performed in 1 patient because of hypertrophy of the left ovarian artery (Fig 2a–d). Gelatin sponge particles were used as single embolic agents in 38 patients (73.1%) or in combination with microcoils (n ¼ 7) or NBCA (n ¼ 3) in 10 patients (19.2%). Microcoils (n ¼ 1) and NBCA (n ¼ 3) were used as single embolic agents in four patients (7.7%). Permanent embolic materials were used at the discretion of operators when gelatin sponge particles were insufficient to fill the pseudoaneurysm completely or to stop extravasation. Detailed TAE results are shown in Figure 3. TAE was technically successful in all 52 study patients (100%). Table 2 . Arteries Embolized during Transcatheter Arterial Embolization No. Patients Patients with active bleeding (n ¼ 25) Bilateral UAs
8
Left UA
8
Right UA Bilateral UAs þ anterior branches of bilateral IIAs
2 2
Bilateral UAs þ anterior branch of left IIA
1
Left UA þ anterior branch of right IIA Anterior branches of bilateral IIAs
1 1
Bilateral UAs þ right ovarian artery
1
Left UA þ left ovarian artery Patients without definite bleeding foci (n ¼ 27) Bilateral UAs Bilateral UAs þ left ovarian artery IIA ¼ internal iliac artery; UA ¼ uterine artery.
1 26 1
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Figure 2. A 25-year-old woman with massive PPH from retained placental tissue 16 days after vaginal delivery. (a) Aortogram shows prominent uterine vascularity from the tortuous uterine arteries. (b) Delayed image of aortogram shows persistent amorphous opacification (arrows). Although embolization of the bilateral uterine arteries was performed with gelatin sponge particles (not shown), there was continued bleeding. (c, d) Aortograms with the catheter at the renal artery level show prominent left ovarian artery (arrows, c) and increased vascularity of the uterus (arrowheads, d). Embolization of the left ovarian artery was subsequently performed using gelatin sponge particles (not shown).
Figure 3. In-hospital results of TAE performed for secondary PPH.
Clinical success was achieved with initial TAE in 47 patients (90.4%; 47 of 52). The remaining five patients showed rebleeding after embolization, and two patients (20%; 2 of 5) showed active bleeding foci on angiography. Bleeding was eventually controlled in all of these patients; three underwent hysterectomy, one underwent repeat TAE, and one received conservative management. The clinical characteristics of these patients did not differ from the other 47 patients with clinical success (Table 3). There was no statistically significant difference in the technical success rate of TAE between patients with and without a bleeding focus, as observed by angiography (P ¼ 1). Procedurerelated complications were not observed in any of these patients.
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Table 3 . Characteristics of Five Patients without Clinical Success of Transcatheter Arterial Embolization
Age Type of delivery Bleeding onset (d)
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
32 Vaginal
27 Vaginal
30 Cesarean section
29 Vaginal
26 Vaginal
3
7
30
12
28
Cause Transfusion*
Placental anomaly 0
Retained placenta 9
Uterine AVM 2
Angiographic findings
Retained placenta Placental anomaly 10 10
No active bleeding
No active bleeding
No active bleeding
Extravasation
Pseudoaneurysm
Embolized artery Material
Both UA GSP
Both UA GSP
Both UA GSP
Both IIA þ UA Coil þ GSP
Right IIA þ left UA GSP
Additional management
Surgery
Conservative management
Surgery
TAE
Surgery
AVM ¼ arteriovenous malformation; GSP = gelatin sponge particle; IIA ¼ internal iliac artery; TAE ¼ transcatheter arterial embolization; UA ¼ uterine artery. n Packed red blood cells.
Eight patients were lost to follow-up after discharge. For the 44 patients with available follow-up, the median and mean follow-up periods were 3 months and 12.6 months (range, 1–62 mo), respectively. Regular menstruation resumed in all patients with follow-up, and five of the patients became pregnant. No patient experienced morbidity, and no patient died. Univariate analysis showed that the clinical success of TAE for secondary PPH was not related to any of the analyzed factors, including maternal obstetric characteristics, type of delivery, bleeding onset after delivery, length of hospital stay, cause of bleeding, and amount and product type of blood transfusion (P ¼ 1.00, P ¼ .65, P ¼ .76, P ¼ .275, P ¼ .15, and P ¼ .45).
DISCUSSION Secondary PPH, which is defined as PPH occurring between 24 hours and 6 weeks after labor, has received little attention compared with primary PPH owing to its relatively low incidence and association with maternal morbidity rather than mortality. In addition, because bleeding occurs most frequently between day 8 and day 14 of the puerperium, patients often have already been discharged from the hospital, and potential hemorrhage is often missed by clinicians (1–3). However, persistent PPH can be life-threatening, and it requires surgical or endovascular management (1–3). Consistent with the current literature, the most common cause of secondary PPH in the present study was retained placental tissue (1–3). Uterine atony, which is the most common cause of primary PPH, was the etiology of secondary PPH in five cases (9.6%). Although pseudoaneurysm of the uterine artery has been reported to be a rare cause of delayed PPH (4,5,7,9), it was noted on 23% of the initial angiograms (12 of 52). In this study, a cesarean section had been performed on most of the patients with a pseudoaneurysm observed on angiography, although some of these patients had a history of uncomplicated vaginal delivery. This reported rate was similar to rates obtained in
previous studies regarding the association of uterine artery pseudoaneurysms with a traumatic event or delivery (4,5,7,9). This finding introduces the possibility that pseudoaneurysms may be caused by surgery in some patients, although the minor trauma of an uncomplicated, spontaneous vaginal delivery may be sufficient to induce pseudoaneurysm formation (4,5,7,9). The administration of ergometrine with or without oxytocin is the initial primary conservative treatment of secondary PPH. When a bleeding source is suspected in the lower genital tract, careful inspection is necessary to rule out the possibility of a laceration or to identify retained placental fragments, which can be removed by suction evacuation and curettage. Surgical ligation of the uterine arteries or internal iliac arteries may be performed to preserve fertility (10,11). However, vascular ligation often fails to stop the bleeding owing to potential collateral circulation (10,11). TAE is a recognized method for the control of PPH (11). Many studies have documented the safety and clinical effectiveness of TAE for secondary PPH and have reported clinical success rates of TAE 4 90% for secondary PPH (2,4–7). The present study evaluated a much larger sample size and, consistent with previous studies, demonstrated a high clinical success rate (90.9%). There were no procedure-related complications. All of patients with available follow-up resumed menstruation, and five patients became pregnant during the follow-up period. Several research groups have reviewed the effects of embolization on the resumption of menses and future fertility (11–13). Some reports showed that there was an increased risk of placental disorders and fetal growth restriction (9), whereas other reports suggested favorable outcomes for the preservation of fertility (11,14,15). Although gelatin sponge particles were the most commonly used embolic materials, permanent embolic materials, such as microcoils and NBCA, were also used either alone or in combination with gelatin sponge particles in 14 patients (26.9%) and showed successful bleeding control. One patient who failed the initial TAE
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using gelatin sponge particles received additional TAE using a microcoil and was successfully treated. Several studies have also reported the use of permanent embolic materials, such as coils and NBCA, in patients with secondary PPH when clinical success with TAE could not be achieved using gelatin sponge particles alone (2) or if patients had underlying coagulopathy (16,17). Resumption of menstruation in all patients with available follow-up data suggests that the use of permanent embolic materials is safe in TAE. In the present study, there were no risk factors among the maternal risk factors assessed for the clinical success of TAE for secondary PPH. In addition, no reports have yet suggested any risk factors for poor outcomes of TAE for secondary PPH, although disseminated intravascular coagulation and massive transfusion are known to be associated with poor outcomes of TAE performed for primary PPH (18). As observed in the present study, patients with secondary PPH appear to be hemodynamically stable and receive fewer transfusions than patients with primary PPH (18). The present study has several limitations, including retrospective design based on a review of medical records. In addition, because there are no established clinical guidelines for embolization, management was determined by consensus agreement among referring obstetricians and interventional radiologists on a caseby-case basis. Given that our institution is a tertiary care center, there was also a selection bias because patients transferred from other institutions were included. Longterm follow-up data assessing fertility and ovarian function were not available for all study patients. In conclusion, TAE for secondary PPH is safe and effective and showed technical and clinical success in 100% and 90.4% of patients, respectively. Approximately half of these patients showed a positive bleeding focus, and the use of permanent embolic materials was also common.
REFERENCES 1. Carroli G, Cuesta C, Abalos E, Gulmezoglu AM. Epidemiology of postpartum haemorrhage: a systematic review. Best Pract Res Clin Obstet Gynaecol 2008; 22:999–1012.
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2. Pelage J-P, Soyer P, Repiquet D, et al. Secondary postpartum hemorrhage: treatment with selective arterial embolization. Radiology 1999; 212:385–389. 3. Hoveyda F, MacKenzie IZ. Secondary postpartum haemorrhage: incidence, morbidity and current management. BJOG 2001; 108:927–930. 4. Sharma AM, Burbridge BE. Case report: uterine artery pseudoaneurysm in the setting of delayed postpartum hemorrhage: successful treatment with emergency arterial embolization. Case Rep Radiol 2011; 2011:373482. 5. Kim GM, Yoon CJ, Seong NG, et al. Postpartum haemorrhage from ruptured pseudoaneurysm: efficacy of transcatheter arterial embolisation using N-butyl-2-cyanoacrylate. Eur Radiol 2013; 23:2344–2349. 6. Lee HJ, Jeon GS, Kim MD, et al. Usefulness of pelvic artery embolization in cesarean section compared with vaginal delivery in 176 patients. J Vasc Interv Radiol 2013; 24:103–109. 7. Dohan A, Soyer P, Subhani A, et al. Postpartum hemorrhage resulting from pelvic pseudoaneurysm: a retrospective analysis of 588 consecutive cases treated by arterial embolization. Cardiovasc Intervent Radiol 2013; 36:1247–1255. 8. Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol 2003; 14: S199–S202. 9. McGonegle SJ, Dziedzic TS, Thomas J, Hertzberg BS. Pseudoaneurysm of the uterine artery after an uncomplicated spontaneous vaginal delivery. J Ultrasound Med 2006; 25:1593–1597. 10. Gizzo S, Saccardi C, Patrelli TS, et al. Fertility rate and subsequent pregnancy outcomes after conservative surgical techniques in postpartum hemorrhage: 15 years of literature. Fertil Steril 2013; 99: 2097–2107. 11. Healey S, Buzaglo K, Seti L, Valenti D, Tulandi T. Ovarian function after uterine artery embolization and hysterectomy. J Am Assoc Gynecol Laparosc 2004; 11:348–352. 12. Spies JB, Roth AR, Gonsalves SM, Murphy-Skrzyniarz KM. Ovarian function after uterine artery embolization for leiomyomata: assessment with use of serum follicle stimulating hormone assay. J Vasc Interv Radiol 2001; 12:437–442. 13. Ahmad A, Qadan L, Hassan N, Najarian K. Uterine artery embolization treatment of uterine fibroids: effect on ovarian function in younger women. J Vasc Interv Radiol 2002; 13:1017–1020. 14. Stancato-Pasik A, Mitty HA, Richard HM 3rd, Eshkar N. Obstetric embolotherapy: effect on menses and pregnancy. Radiology 1997; 204: 791–793. 15. Yamashita Y, Harada M, Yamamoto H, et al. Transcatheter arterial embolization of obstetric and gynaecological bleeding: efficacy and clinical outcome. Br J Radiol 1994; 67:530–534. 16. Kanematsu M, Watanabe H, Kondo H, et al. Postpartum hemorrhage in coagulopathic patients: preliminary experience with uterine arterial embolization with N-butyl cyanoacrylate. J Vasc Interv Radiol 2011; 22: 1773–1776. 17. Yonemitsu T, Kawai N, Sato M, et al. Comparison of hemostatic durability between N-butyl cyanoacrylate and gelatin sponge particles in transcatheter arterial embolization for acute arterial hemorrhage in a coagulopathic condition in a swine model. Cardiovasc Intervent Radiol 2010; 33:1192–1197. 18. Lee HY, Shin JH, Kim J, et al. Primary postpartum hemorrhage: outcome of pelvic arterial embolization in 251 patients at a single institution. Radiology 2012; 264:903–909.
