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Dokkyo Journal of Medical Sciences 47（1）（2020）47（1）：15〜 25，2020The efficacy and complications of UAE for intractable uterine bleeding 15

Original

Efficacy and Complications of Emergent Transcatheter Arterial Embolization for the Management of Intractable Uterine Bleeding

Emi Motegi 1）, Kiyoshi Hasegawa 1）, Shoko Ochiai 1）, Mariko Watanabe 1）, Kazumi Tada 1）, Susumu Miyashita 1）, Satoshi Obayashi 1）, Kensuke Inamura 2）, Hiroaki Ikeda 2）, Yasukazu Shioyama 2）, Yasushi Kaji 2）, Ichio Fukasawa 1）

1 Department of Obstetrics and Gynecology, Dokkyo Medical University, Mibu, Tochigi, Japan 2 Department of Radiology, Dokkyo Medical University, Mibu, Tochigi, Japan

SUMMARY Objective：Transcatheter arterial embolization（TAE）, including uterine artery embolization（UAE）, is effective for the management of obstetric and gynecologic hemorrhage. Some adverse effects have been reported with TAE, such as , endometrial trauma, and subsequent infertility. Herein we report the efficacy and complications of emergent TAE for the management of severe intractable uterine bleeding at our institute. Methods：From 2010 to 2019, thirty-eight patients underwent emergent TAE for intractable uterine bleeding. We evaluated the efficacy and complications of TAE, including a change in , fertility, and outcomes in perinatal patients（group A；n＝23）, and in patients with gynecologic hemor- rhage（group B；n＝15）. Results：In group A, 7 cases of retained placenta, 4 cases of postpartum hemorrhage, 2 cases of placenta accrete, 2 cases of uterine artery pseudoaneurysm, 2 cases of , 1 case of cesarean scar pregnancy, and 5 cases of unexplained hemorrhage were included. The median age of the group A was 37. In group B, 4 cases of uterine artery pseudoaneurysm, 2 cases of uterine arteriovenous malformation, 3 cases of uterine fibroids, 1case of , and 5 cases of unexplained hemorrhage were included. The median age of the group B was 39. The first attempt at TAE successfully controlled hemorrhage in 33 of 38 patients（86.8％）without major complications, and the remaining 5 patients required an additional attempt at TAE to control hemorrhage. One patient（2.6％）had transient buttock pain and foot ischemia. Among the 33 patients who had adequate follow-up care, all patients resumed regular menstruation. The median time to resume regular menstruation after TAE was 3 months（range, 1-13 months）in group A（n ＝20）and 1 month（range, 1-6 months）in group B（n＝13）. Four of patients had 6 in total：3 full-term live births, 2 missed , and 1 artificial . Among the 13 patients who desired preg- nancy, 3（23％）conceived spontaneously. Conclusions：This retrospective study showed that emergent TAE may be effective and safe in treating intractable uterine bleeding with a high success rate. Ovarian and endometrial function were preserved based on the relatively early return of menstruation. Further prospective investigations with large number of patients are needed to confirm the preservation of ovarian function, fertility, and pregnancy outcome in reproductive-aged women. Received December 6, 2019；accepted January 29, 2020 Reprint requests to：Emi Motegi, MD Key Words：Transcatheter arterial emboliza- Department of Obstetrics and Gynecology, tion, uterine artery embolization, Dokkyo Medical University, 880 Kitakobayas- intractable uterine bleeding hi, Mibu, Tochigi 321-0293, Japan. 16 Emi Motegi DJMS

gynecologic procedures with emergent medical care. INTRODUCTION The obstetric maneuvers used to control hemorrhage Transcatheter arterial embolization（TAE）, includ- included uterine massage, uterine packing, administra- ing uterine artery embolization（UAE）, is effective for tion of uterine contraction agents, and appropriate the management of obstetric and gynecologic hemor- treatment for disseminated intravascular coagulation rhage. TAE is minimally invasive and fertility-pre- （DIC）in patients with postpartum hemorrhage（PPH） serving, so it is becoming an alternative to surgical for each clinical indication；however, all of the procedures. Indeed, the efficacy and safety of TAE for patients enrolled in this study were refractory to the treatment of postpartum hemorrhage（PPH）and these conservative treatments. In patients with gyne- symptomatic uterine fibroids have been well-estab- cologic hemorrhage, special gynecologic procedures lished 1,2）. except for emergency care were not performed before Some adverse effects have been reported with TAE TAE because all of the patients enrolled in the study in each clinical setting, including amenorrhea, trauma desired less invasive surgery than a to the , loss of ovarian reserve, and sub- and the subsequent loss of fertility. TAE, including sequent infertility, although it is still a matter of UAE, was performed after consultation with interven- debate 3,4）. tional radiologists when obstetrician-gynecologists Herein we report the efficacy and complications of determined that hemostasis was difficult to achieve emergent TAE for the management of severe intrac- using standard obstetric and gynecologic management table uterine bleeding at our institute. （other than invasive surgical intervention）, after dis- closing the safety, efficacy, and complication rate of MATERIALS AND METHODS TAE, and obtaining informed consent from each Patient characteristics patient. From January 2010 to April 2019, thirty-eight This retrospective study was approved by the insti- patients underwent emergent TAE, including UAE, tutional review board. for intractable uterine bleeding at Dokkyo Medical University Hospital. The patient population consisted Embolization methods of two groups：Group A（n＝23, Table 1）, patients Digital subtraction angiography（DSA）and subse- with obstetric hemorrhage, and Group B（n＝15, quent TAE were performed with local anesthesia by Table 2）, patients with gynecologic hemorrhage interventional radiologists. First, a 4.0-Fr introducer except for malignancy. The median age for group A sheath（Radifocus Introducer IIH；Terumo Co., was 37 years（range, 25-44 years）and the median Tokyo, Japan）was inserted into the right common age for group B was 39 years（range, 25-51 years）. femoral artery and a 4.2-Fr pig-tailed catheter（Hana- The etiology of hemorrhage in group A was as fol- ko Excellent EN Catheter［Hi-MAX］；Hanako Medi- lows：retained placenta, 7；postpartum hemorrhage cal Co., Saitama, Japan）was used to assess the inter- with disseminated intravascular coagulopathy, 4；pla- nal iliac arteries and its branches and/or other centa accreta, 2；uterine artery pseudoaneurysm, 2； potential bleeding sites, such as ovarian, inferior epi- cervical pregnancy, 2；cesarean scar pregnancy, 1； gastric, internal pudendal, and vaginal arteries. For and unexplained hemorrhage after normal vaginal selective catheterization of the uterine artery, a 2.0- delivery and cesarean section, 1 and 4, respectively Fr microcatheter（Michibiki PLUS；Hanaco Medical （Table 1）. The etiology of hemorrhage in group B Co.）was passed through the parent catheter with a was as follows：uterine artery pseudoaneurysm, 4； 0.016-inch micro-guidewire（Sakigake；Hanaco Medi- uterine arteriovenous malformation, 2；uterine cal Co.）. To embolize the internal iliac artery, glue fibroids, 3；adenomyosis, 1；and unexplained hemor- was infused through a 4.0-Fr catheter（Hi-MAX）, the rhage, 5（Table 2）. These patients were diagnosed by tip of which was placed in the anterior trunk and ultrasonography with color Doppler, MRI, and/or CT, gradually pulled back in the main trunk with continu- and initially treated using standard obstetric and ous infusion. 47（1）（2020） The efficacy and complications of UAE for intractable uterine bleeding 17 （months） and outcome 7 SA（6Ws） 9 SA（9Ws） 19 NVD（39Ws） Time to pregnancy ＋ ＋ ＋ ＋ ─ ＋ ＋ ＋ ─ ─ ─ ＋ ＋ ＋ ─ unknown unknown unknown unknown unknown unknown unknown Desire for pregnancy 3 2 1 3 2 4 5 3 2 3 2 3 1 2 ─ 1.5 unknown unknown Time to resumption of menstruation（months） 12（after breastfeeding） 12（after 7（during breastfeeding） 7（during 9（during breastfeeding） 9（during 9（during breastfeeding） 9（during 13（during breastfeeding） 13（during hys after TAE Treatment Complications buttock pain, foot ischemia, Embolic material GS GS GS NBCA GS NBCA GS NBCA MTX＋GS MTX＋GS NBCA NBCA NBCA NBCA GS NBCA NBCA NBCA NBCA NBCA GS GS GS NBCA NBCA, GS GS GS Table 1 Group A：Obstetrical hemorrhage vessels Embolic BUtA UOvA BUtA 1st BUtA 2nd UUtA BUtA UUtA BUtA BUtA UUtA UIIA 1st UUtA 2nd UUtA＋UOvA UIIA BUtA URLA UIIA UUtA UIIA UIIA BIIA BIIA BUtA UUtA BUtA BUtA BUtA BUtA UIIA BIIA diagnosis unexplained hemorrhage after NVD unexplained hemorrhage after CS unexplained hemorrhage after CS unexplained hemorrhage after CS unexplained hemorrhage after CS cesarean scar pregnancy uterine artery pseudoaneurysm cervical pregnancy cervical pregnancy uterine artery pseudoaneurysm placenta accreta placenta accreta PPH＋DIC（uterine cervical fibroid） PPH＋DIC（uterine PPH＋DIC（retroperitoneal hematoma） PPH＋DIC（retroperitoneal PPH＋DIC（） PPH＋DIC（placental PPH＋DIC（placental abruption） PPH＋DIC（placental retention of placenta retention of placenta retention of placenta retention of placenta retention of placenta retention of placenta retention of placenta 37 35 33 37 43 38 31 41 31 38 39 29 44 35 25 43 41 31 39 35 38 35 40 age 8 9 7 5 6 4 3 2 1 23 22 21 20 19 18 15 16 17 14 13 12 11 10 18 Emi Motegi DJMS mL

（months） and outcome Time to pregnancy 15 NVD（38Ws） 6 IA（9Ws） 6 NVD（40Ws）, PPH 6 NVD（40Ws）, 1,300 ─ ─ ＋ ─ ─ ＋ ─ ─ unknown unknown unknown unknown unknown Desire for pregnancy 1 1 1 1 3 1 1 1 6 5 1 1 1 ─ ─ Time to resumption of menstruation（months） hys hys after TAE Treatment GnRHa 2cycles GnRHa 4cycles Complications Table 2 Group B：Gynecological hemorrhage Embolic material NBCA GS GS NBCA NBCA, TAGM GS GS NBCA TAGM GS GS GS GS GS GS GS GS GS Embolic vessels BUtA BUtA 1st UUtA 2nd BUtA UUtA 1st BUtA UOvA 2nd BUtA UOvA UUtA BUtA BUtA BUtA UUtA BUtA 1st UUtA 2nd BUtA BUtA BUtA BUtA diagnosis uterine artery pseudoaneurysm uterine artery pseudoaneurysm uterine artery pseudoaneurysm AVM adenomyosis uterine artery pseudoaneurysm AVM uterine fibroids uterine fibroids uterine fibroids unexplained hemorrhage unexplained hemorrhage abnormalities） unexplained hemorrhage unexplained hemorrhage unexplained hemorrhage （suspicious of uterine vessel 40 25 34 41 51 27 39 49 50 45 26 18 35 44 28 age 1 2 3 6 4 5 7 8 9 10 11 12 13 14 15 PPH：postpartum hemorrhage, DIC：disseminated intravascular coagulation, BIIA：bilateral internal iliac artery, UIIA：unilateral internal iliac artery, BUtA：bilateral uter - ine artery, UUtA：unilateral uterine artery, UOvA：unilateral ovarian artery, URLA：unilateral artery of the round ligament from external iliac artery, GS：gelatin particles, sponge NBCA：n-butyl-2-cyanoacrylate, TAGM：Tris-acryl gelatin microspheres, MTX：methotrexate, hys：hysterectomy, AVM：uterine arteriovenous malformation, SA：Spontaneous abortion, IA：induced abortion, CS：cesarean section, NVD：normal vaginal delivery, GnRHa：Gonadotropin releasing hormone agonist, Ws：weeks 47（1）（2020） The efficacy and complications of UAE for intractable uterine bleeding 19

Gelatin sponge particles（［GS］ Gelpart or Seres- showed that embolization of multiple arteries, includ- cue；Nippon Kayaku Co., Tokyo, Japan）were com- ing the uterine arteries, was needed to control obstet- monly selected for absorbable and non-permanent ric hemorrhage compared to gynecologic hemorrhage. embolic materials for TAE；for some patients, tris- In group A, the following embolic materials were acryl gelatin microspheres（［TAGM］ EmbosphereV used：GS, 13 patients；and NBCA, 14 patients（there R；Nippon Kayaku, Co.）were also used. Moreover, was some overlap）. In group B, the following embolic non-absorbable and permanent embolic materials materials were used：GS, 13 patients；NBCA, 4 （N-butyl-2-cyanoacrylate［NBCA］ Histoacryl；B. patients；and TAGM, 2 patients. These findings Braun, Melsungen, Germany）mixed with iodized oil showed that NBCA was more frequently used as an （Lioiodol；Guerbet, Tokyo, Japan）at a 1：4 ratio（20 embolic material for controlling obstetric hemorrhage ％ glue）was used to achieve complete hemostasis compared to gynecologic hemorrhage. In group A, with or without GS. A 2.5-mL syringe containing methotrexate was used combined with GS for 2 2.5 mL of 20％ glue was connected to the microcathe- patients with cervical pregnancy. ter and the single-column injection technique was The first emergent TAE attempt successfully con- used. trolled intractable hemorrhage in 33 of 38 patients The embolic arteries and materials were selected （86.8％）without major complications. The remaining by interventional radiologists according to the findings 5 patients needed an additional TAE attempt to con- of DSA and hemorrhage points in each case. trol hemorrhage, as follows：cervical pregnancy, 1； After embolization of the uterine arteries was com- unexplained hemorrhage after cesarean section, 1； pleted, aortography was performed to search for other uterine artery pseudoaneurysm, 2；and unexplained bleeding arteries. The effect of TAE was evaluated hemorrhage（suspicious of uterine vessels abnormali- with respect to complete hemostasis, which was ty）, 1（Tables 1 & 2）. Hemostasis was confirmed in all defined as hemostasis achieved by TAE alone and 5 patients who underwent a 2 nd TAE attempt, there- requiring no additional hemostatic interventions. fore the success rate of controlling intractable uterine bleeding by TAE alone was 100％（38/38 patients）. Follow-up Hysterectomy after the first TAE attempt was sub- The patients were generally followed up at 2 weeks, sequently required as radical treatment in 3 patients 1 month, 3 months, 6 months, and thereafter at an for the following indications：adenomyosis；uterine internal of 3-6 month. Ultrasonography with color cervical fibroid；and placenta accreta（one each）. Doppler was routinely used if it was thought to be One patient（2.6％）had transient buttock pain and useful for each case, and pelvic MRI was scheduled foot ischemia, which promptly resolved without treat- 3-6 months after embolization as needed. ment. Changes in symptoms, complications associated with The median follow-up period after TAE was 26.5 TAE, time to resumption of menstruation, time to months（range, 4-114 months）. Among the 33 pregnancy after TAE, and pregnancy outcomes were patients in whom follow-up was adequate, all 33 obtained from the medical records, and were com- resumed normal menstruation. The median time to pared between Group A and B to evaluate the efficacy resume regular menstruation after TAE was 3 and complications of TAE. months（range, 1-13 months）in group A（n＝20）and 1 month（range, 1-6 months）in group B（n＝13）. The RESULTS patient in group A who had transient buttock pain In group A, the following arteries were embolized： and foot ischemia, also had hypomenorrhea, which uterine arteries, 17；internal iliac arteries, 9；ovarian gradually resolved. There was no apparent relation- artery, 2；and artery of the round ligament from the ship between the length of time for normal menstrua- external iliac artery（there was some overlap）, 1. In tion to resume and the vessels embolized or the group B, the following arteries were embolized：uter- embolic materials used. ine arteries, 15；and ovarian artery, 1. These findings Four patients had 6 pregnancies in total：3 full- 20 Emi Motegi DJMS term live births, 2 missed abortions, and 1 artificial complications 7）. abortion. Among 13 patients who desired pregnancy, For gynecologic hemorrhage, especially symptomat- 3（23％）conceived spontaneously. Among the 3 full- ic uterine fibroids, symptoms（menorrhagia, metror- term live births, there were no major obstetric com- rhagia, pelvic pain, and bulk symptoms）were signifi- plications except for a 1300 mL PPH（unknown etiolo- cantly decreased after TAE8）. The duration of gy）in 1 patient. menstruation was shortened, the fibroid volume was significantly reduced 8）, and the hospital stay was DISCUSSION shorter and recovery was faster compared with the The efficacy and safety of TAE, including UAE, for surgery group 3）. Notably, repeat TAE or hysterecto- the management of intractable uterine bleeding have my post-TAE was required for some patients due to been reported for obstetric hemorrhage due to PPH, inadequate symptom control. abnormal placentation, and cervical , Based on a randomized controlled trial（RCT）that and for gynecologic hemorrhage due to uterine compared TAE and hysterectomy in the treatment of fibroids, adenomyosis, or uterine vessels abnormali- severe symptomatic uterine fibroids, after 10 years of ties 1,2）. Obstetric hemorrhage remains a major cause follow-up, 69％ of all women underwent technically of maternal morbidity and mortality and TAE has successful TAE and a hysterectomy was avoided. been recommended as the first choice of treatment Moreover, the health-related quality of life and for PPH when uterine balloon tamponade fails to con- patient satisfaction rates did not differ between both trol hemorrhage. Intractable gynecologic hemorrhage groups 9）. In view of the short- and long-term clinical can lead to surgical interventions, including hysterec- and quality-of-life evidence that is available, it was tomy, and subsequent loss of fertility in reproductive- concluded that all women who are candidates for hys- aged women. terectomy due to symptomatic uterine fibroids should Therefore, the role of TAE has recently become the be offered TAE as a treatment option 9）. subject of debate for these conditions. Although there In the current study, TAE was also extremely are no fundamental objections regarding the effective- effective in controlling intractable hemorrhage. The ness of TAE for the management of intractable uter- first emergent TAE attempt successfully controlled ine hemorrhage, there are several unresolved issues hemorrhage in 33 of 38 patients（86.8％）, and in the involving the effects of TAE on ovarian function, fer- remaining 5 patients, complete hemostasis was tility, and pregnancy outcome. achieved with an additional TAE attempt, thus achieving a success rate with TAE of 100％（38/38 Efficacy patients）. Among the 4 patients with PPH and DIC, The success rate of TAE for obstetric hemorrhage the initial emergent TAE was effective without any due to intractable PPH has been reported to be 87％ complications. ～100％ 1）, and 90.7％（95％ confidence interval ［CI］； Ovarian artery embolization（OAE）with UAE has 85.7％ −94.0％）in a systematic review for this condi- been reported to control severe PPH 10）. In the current tion 5）. This success rate for TAE is equivalent or study, OAE was required to achieve complete hemo- superior to other surgical approaches［84.0％ for bal- stasis for 3 patients due to a cervical pregnancy, loon tamponade, 91.7％ for uterine compression unexplained hemorrhage after a normal vaginal deliv- sutures, and 84.6％ for iliac artery ligation of uterine ery, and a uterine artery pseudoaneurysm（Tables 1 devascularization］5）. The overall treatment failure & 2）. It is well-known that OAE through uterine-to- rate for PPH resulting from abnormal placentation, ovarian artery anastomosis is an aggressive emboliza- such as placenta increta or percreta, which appears to tion technique 11）. TAE of the utero-ovarian collateral be resistant to TAE and the main cause of hysterec- circulation is the most likely mechanism underlying a tomy after failed TAE, has been reported to be as decline in ovarian reserve and premature meno- high as 23％ 6）. Moreover, the success rate for TAE is pause 11）；however, in the current study 3 patients lower in patients with DIC, 37.5％ of whom develop who underwent OAE reported prompt resumption of 47（1）（2020） The efficacy and complications of UAE for intractable uterine bleeding 21 normal menstruation between 1 and 3 months. also rare, such as neuropathies involving the sciatic nerve, perineal nerve, and lower limbs 1）. Embolic materials There were no significant complications related to Several embolic materials have been used in TAE. TAE in the current study with the exception of one In the current study, GS and NBCA were used in 13 patient who had transient buttock pain and foot isch- and 14 patients in group A, respectively, while GS, emia. NBCA, and TAGM were used in 13, 4, and 2 patients It has been reported that skillful catheterization, in group B, respectively. This finding showed that proper and gentle injection of embolic materials, and NBCA was more frequently used as an embolic mate- choosing the appropriate vessels obviate complica- rial for controlling obstetric hemorrhage compared to tions 16）. Therefore, the incidence of complications fol- gynecologic hemorrhage. lowing TAE may be extremely low when TAE is per- NBCA is indicated for various conditions, including formed by a well-prepared team together with vascular diseases（aneurysms and malformations）, interventional radiology specialists. hemorrhage（trauma and inflammation）, tumors, and venous disease（varices）, regardless of the location of Changes in menstruation the target lesion. TAE with a NBCA-Lipiodol mixture It has been reported that all patients treated for has been reported to be highly effective in achieving PPH resumed normal menstruation 1）. There is a hemostasis in patients with PPH accompanied by DIC report that the most common untoward effect in and might be the first-line therapeutic strategy, espe- patients with PPH undergoing TAE with GS for cially for patients with desired fertility 12）. symptomatic uterine fibroids is transient amenor- More recently, TAGM has been used for emboliza- rhea；menorrhagia improved in 90％ of patients 12 tion instead of GS. The outcomes of TAE with TAGM months after treatment, although permanent amenor- are comparable to TAE with GS, suggesting that both rhea was reported in 2 of 33 patients［6％］ 2）. embolic agents are acceptable for the treatment of In the current study, among the patients who had uterine fibroids 13）. adequate follow-up evaluations, normal menstruation The success rate of achieving immediate complete was restored in all 33 patients. Relatively early hemostasis may be dependent, in part, on the choice resumption of menstruation after TAE was observed of embolic materials and embolic vessels. Our study in patients with obstetric（median, 3 months）and showed that embolization of multiple arteries（primari- gynecologic hemorrhage（median, 1 month）；only 1 ly the uterine arteries）is needed to control obstetric patient had transient hypomenorrhea. Based on these hemorrhage compared to gynecologic hemorrhage, results, it can be concluded that menstruation is not and NBCA is more frequently used for controlling adversely affected by TAE. obstetric hemorrhage compared to gynecologic hemor- rhage. Ovarian function McLucas et al. 17） reported that serum hormone lev- Safety els, such as follicle-stimulating hormone（FSH）, anti- TAE is thought to negatively impact endometrial Müllerian hormone（AMH）, and estradiol（E2）, are flow, ovarian blood flow, endocrine function, and not changed by TAE, suggesting that ovarian function follicular development. The complication rate of TAE is not adversely affected, and therefore women of is 6％～9％ and includes amenorrhea, permanent ovar- reproductive age with uterine fibroids may consider ian failure, fertility, transient fevers, groin hematomas, TAE as a treatment option. Based on a study with a contrast reactions, pseudoaneurysms, and iliac artery large sample size, it was confirmed that TAE did not perforation 1,14,15）. Ischemic complications, such as tran- affect ovarian reserve in women＜40 years of age, as sient buttock or foot ischemia, small bowel necrosis, evidenced by no significant change in AMH levels and uterine, vaginal, cervical, and bladder necrosis, after embolization 18）. are rarely reported 1）. Neurologic complications are There is a report, however, that the AMH level 22 Emi Motegi DJMS recovered in patients treated for uterine fibroids who regarding fertility in each patient was insufficient. were＜40 years of age, but not in patients ≧40 years Indeed, the follow-up period for some patients was of age 19）. The subtle difference in ovarian failure rates relatively short and the information was only obtained between TAE for PPH and TAE for fibroids may be from the medical records. explained by the younger age of patients undergoing Based on the aforementioned studies, the adverse the former procedure 20）. effects of TAE on fertility remain controversial and Therefore, additional prospective studies with a warrant further study. large number of patients are warranted to better elu- cidate the relationship between patient age and Pregnancy outcomes changes in ovarian function after TAE for obstetric or The pregnancy complication rates have been gynecologic hemorrhage. reported to be similar in patients with untreated uter- ine fibroids 22）；however, higher pregnancy loss rates Fertility following TAE have been reported in patients with The 2013 Royal College of Obstetricians and Gyne- uterine fibroids compared with patients who have cologists guidelines conclude that there is poor evi- undergone a myomectomy 22,26,27）. In a systematic dence regarding TAE and fertility, and therefore rec- review Karlsen et al. 26）reported a pregnancy rate of ommends that women of childbearing age who wish 50％（13/26）after TAE and 78％（31/40）after myo- to become pregnant in the near future should be mectomy（no statistical difference）and a pregnancy offered TAE only after an informed discussion 21）. loss rate of 60％（9/15）after TAE and 20％（6/15） Preservation of fertility has been reported in after myomectomy［ p＜0.05］. Karlsen et al. 26）conclud- patients with uterine fibroids 22）or intractable PPH 22）. ed that the pregnancy rate was lower and the preg- In a systematic review, Mohan et al. 22）reported that nancy loss rate was higher after TAE than myomec- pregnancy rates following TAE are comparable to tomy. Karlsen et al. 26）also found very low-quality age-adjusted rates in the general population. McLucus evidence regarding the assessed outcomes and the et al. 24）also reported in a review that pregnancy rates reported proportions are uncertain. Homer et al. 27） following TAE and myomectomy（48％ and 46％ for reported that the risk for pregnancy loss appeared to abdominal and laparoscopic myomectomy, respective- be increased after TAE compared with pregnancies ly）were comparable and concluded that TAE is a complicated by fibroids matched for age and fibroid valid alternative to myomectomy for women who location（odds ratio［OR］ 2.8, p＜0.0001）, and there wish to conceive. Moreover, Cheng et al. 23）reported was an increased risk for cesarean section（OR 2.1, p that of 23 patients who attempted pregnancy, 19（82.6 ＜0.0001）and PPH（OR 6.4, p＜0.0001）. In contrast, ％）conceived, giving birth to 12 full-term live infants. the risks for critical adverse obstetric complications, A possible adverse effect of TAE on fertility poten- fetal growth restriction（FGR）, preterm delivery, and tial in patients with uterine fibroids has been report- malpresentation were no more likely after TAE when ed 8）, especially in the patients＞40 years of age 25）. compared with women with untreated fibroids. Specifically, Torre et al. 8）reported that TAE might The increase in rate suggests that the have had a negative impact on fertility, which may endometrial cavity incurs irreversible damage as a not be related to ovarian function. Therefore, TAE consequence of embolization. TAE-induced endometri- should not be performed routinely in young women of al ischemia imparts a marked deleterious effect on reproductive age and extensive fibroids. TAE should potential implantation sites. A reduction in fibroid vol- only be considered after appropriate counselling with ume after TAE could result in distortion of the endo- the women who still wish to conceive. metrial cavity, which is almost certain to escalate the In the current study, among 13 patients who had risk for pregnancy loss in combination with relative desired fertility, 3（23％）had natural conceptions. The endometrial ischemia 27）. pregnancy rate was relatively low compared with pre- While subsequent pregnancies are clearly possible vious reports 23,24）, possibly because the information after TAE for PPH, there are reports of recurrent 47（1）（2020） The efficacy and complications of UAE for intractable uterine bleeding 23 severe PPH at subsequent deliveries［31.6％ -100 es in TAE treatment protocols, patient backgrounds, ％］20,28）. It has been reported that TAE after the first embolic materials used or embolic vessels targeted, delivery with PPH increased the rate of TAE after duration of follow-up, and skills of the interventional the second delivery［OR, 25.56；95％ CI, 9.86- radiologists in each study. Therefore, it is difficult to 66.23］29）. The increased risk for PPH is likely due to compare the results of each report regarding efficacy, myometrial compromise as a consequence of emboliza- safety, and short- and long-term complications. tion-induced ischemia, which might contribute to a Indeed, based on a review of fertility after TAE, reduced capacity for efficient contractility after deliv- Karlsen et al. 26）reported very low-quality evidence ery and consequently to uterine atony. regarding the assessed outcomes. There is a need for In the current study, 4 patients had 6 pregnancies well-designed prospective randomized studies to in total, including 3 full-term live births and 2 missed improve the evidence base. abortions. Of the 3 full-term live births, one had a There is no doubt that ovarian function, fertility, PPH, although the reason was not specifically identi- and pregnancy outcomes are for the most part unaf- fied. The pregnancy loss rate in the current study fected by TAE based on recent studies. In patients was 33％（2/6）, which is consistent with previous with symptomatic uterine fibroids and desired fertility, reports 26,27）. The incidence of PPH in subsequent TAE is becoming a valid alternative to myomectomy, deliveries after TAE was also the same as in a previ- although not a perfect alternative, but TAE should be ous report 29）. included as a treatment option for all patients. There are reports that pregnancy outcome is not CONCLUSION affected by TAE in PPH patients 23,30）. The adverse effects on pregnancy outcome are also In conclusion, based on our retrospective study, controversial. Therefore, to formally address the emergent TAE may be effective and safe in treating impact of embolization on pregnancy risk profiles, a intractable uterine bleeding with a high success rate prospective study that incorporates TAE and non- and without major complications. Ovarian or endome- treatment arms is needed. trial function may be sufficiently preserved based on There were some limitations in this study. First, the relatively early recovery of normal menstruation this was a retrospective study and the sample size after TAE. Nevertheless, there are inconsistent results was relatively small. Second, many causes of obstetric regarding the effects of TAE on ovarian function, fer- or gynecologic hemorrhage were included in this tility, and pregnancy outcomes based on previous study, and the efficacy and complications of TAE studies. Further prospective studies with a large num- were analyzed in all patients. Therefore, it is some- ber of patients are needed to confirm the preservation what difficult to precisely assess the effect of TAE on of ovarian function, fertility, and pregnancy outcomes menstruation, fertility, ovarian function, and pregnan- in reproductive-aged women. cy outcome because of the diverse patient back- grounds. Acknowledgement. We are immensely grateful to Nevertheless, the current study demonstrated the our esteemed colleagues and well-prepared team of high success rate of TAE for emergency treatment of department of Radiology who cooperated with IVR. various causes of intractable hemorrhage without any deaths or major complications. 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