A Retrospective Study on the Clinical Effect of Uterine Artery Embolization Combined with Cervical Double Balloon for Patients with Complete Placenta Previa Undergoing Pregnancy Termination in the Second Trimester

Background 31 Pregnancy termination in the second trimester is a complex and delicate situation for 32 patients with complete placenta previa (CPP), which has less been reported. The 33 objective of this research was to investigate and evaluate the clinical effect of uterine 34 artery embolization(UAE) combined with cervical double balloon(CDB) for patients 35 with CPP. 36 We conducted a retrospective study based on a large medical center. The medical 38 records of patients who were diagnosed with CPP and treated UAE combined with 39 CDB for termination in second trimester in our hospital from January 2017 and 40 March 2021 were retrospectively reviewed. The clinical outcomes were analyzed. The adjuvant therapy of UAE, CDB, and/curettage step by step is a preferred choice for patients with CPP who underwent pregnancy termination in the second trimester.

Pregnancy termination in the second trimester is a complex and delicate situation for 32 patients with complete placenta previa (CPP), which has less been reported. The 33 objective of this research was to investigate and evaluate the clinical effect of uterine 34 artery embolization(UAE) combined with cervical double balloon(CDB) for patients 35 with CPP. 36 Methods 37 We conducted a retrospective study based on a large medical center. The medical 38 records of patients who were diagnosed with CPP and treated UAE combined with 39 CDB for termination in the second trimester in our hospital from January 2017 and 40 March 2021 were retrospectively reviewed. The clinical outcomes were analyzed. 41

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A total of 11 patients with CPP were included in this study. Prenatal diagnosis of CPP 43 was realized by trans-vaginal ultrasound. The average age was 34.2 years old, and the 44 gestational week was 21.6 weeks. Of the selected patients, 3 cases (3/11) had previous 45 caesarean delivery, 5 cases were at older maternal age (≥35 years old), 10 cases 46 underwent emergency UAE for prenatal bleeding equal or up to 400 mL and 1 case 47 underwent prophylactic UAE for placenta percreta, and all cases underwent CDB to 48 promote cervical ripening. It was worth noting that 5 cases (5/11) of selected patients 49 underwent curettage to take out fetus and placenta. 50 The uterus preservation was achieved in all 11 patients. The complications associated 51 with conservative management included prenatal hemorrhaging (10/11), blood 52 transfusion (5/11), fever (2/11), and septicemia (1/11). The mean dilation of cervix 53 was from 0cm to 1.9cm, the length of cervix was from 3.5cm to 0.6cm and the Bishop 54 scores were from 1.5 to 7.3 after using CDB, the changes of cervical conditions were 55 statistically significant (p＜0.05). The levels of WBC and CRP were higher after 56 termination with medicine+UAE+CDB and/or curettage.

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The adjuvant therapy of UAE, CDB, and/curettage step by step is a preferred choice 59 for patients with CPP who underwent pregnancy termination in the second trimester. Complete placenta previa(CPP)hinders the normal delivery channel of cervix, causing 65 severe bleeding and other complications, and even death [1] . The etiology of CPP is 66 currently unclear. Placental migration, maternal age, pregnancy times, history of 67 caesarean section, uterine cavity operation, abortion, and assisted reproductive 68 technology are risks for CPP [1] . With the release of universal two-child policy, more 69 elder women with a history of caesarean section choose to have pregnancy again [2] , 70 and they are more prone to fetal death, malformation and CPP in the second trimester 71 of pregnancy. In clinical practice, the proportion of pregnancy termination in the 72 second trimester with CPP is also increasing. However, there are limited data on 73 pregnancy termination in the second trimester for patients with CPP in the literature. 74 Mifepristone combined with ethacridine lactate or misoprostol are medicine methods 75 for induction in the second trimester for pregnant women with CPP in China. 76 Therefore, it is very important to find a suitable induction method for patients with 77 CPP. To deal with prenatal bleeding during medicine induction, emergency or 78 prophylactic uterine artery embolization (UAE) can be used. However, after UAE, 79 with the recanalization of uterine blood vessels, a high risk of prenatal hemorrhage is   inguinal area, and then Lidocaine was given for local anesthesia before surgery. The surgeon punctured the right femoral artery according to Seldinger's method, inserted 123 the 5F catheter sheath and catheter into the left uterine artery for arterial subtraction, 124 perfused Gentamicin 80,000 units, and embolized with gelatin sponge. The right 125 uterine artery was cannulated, perfused and embolized as well. After the operation, 126 the catheter and sheath were pulled out before applying the local pressure bandage. 127 The right lower limb was immobilized for 6h, and perioperative antibiotics were 128 given to prevent infection.    191 Among the 11 patients with CPP who underwent conservative management, the 192 complications included prenatal hemorrhaging (10/11), blood transfusion (5/11), fever 193 (2/11), and septicemia (1/11). (see in Table 2) 194 The cervical conditions were ripened by CDB, the mean dilation of cervix was from 197 0cm to 1.9cm, the length of cervix was from 3.5 cm to 0.6 cm and the Bishop scores 198 were from 1.5 to 7.3 after CDB , and the changes were statistically significant (p＜ 199 0.05). (see in Table 3) 200 The blood routine including WBC, HBG, CRP were changed by termination using 205 medicine+UAE+CDB and/or curettage, the mean WBC was higher on discharge (15.0 206 ×10 9 /L) than on admission (9.3×10 9 /L), and the median CRP was higher on 207 discharge (54.3 mg/L) than on admission (1.13 mg/L) (p＜0.05). (see in Table 4) 208  and those methods of drugs are effective and safe [8,9] . How to deal with the prenatal 230 bleeding during induction for CPP patients with unfavorable cervix in the second 231 trimester is the focus of current clinical work. In our study, we found the average 232 prenatal bleeding volume reached 400mL quickly and blood transfusion was 233 needed urgently(RBC, 0-4u).

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UAE with minimal invasion has been widely used in the field of gynecology and 235 obstetrics to control hemorrhages, including caesarean scar pregnancy [10] , postpartum cause of secondary inflammation [10] .The prenatal bleeding during labor induction was 254 very rapid, which reached with 400 mL in a short time. In order to reduce 255 complications of UAE and ensure the safety of pregnant women, prophylactic UAE 256 can be adopted to treat high-risk bleeding for pregnant women with CPP combined 257 with placenta accreta spectrum under the guidance of ultrasound and/or magnetic 258 resonance imaging [12,13] . 259 CDB is a good alternative method for inducing women with unfavorable 260 cervix [14] ,which has been a commonly used induction for the term pregnancies [15] , 261 prolonged pregnancies [16] , vaginal birth after caesarean section [17] , high risk of uterine 262 hyperstimulation [18] , and oligohydramnios [19] . CDB used in labor has low risk of 263 hyperstimulation and brings high maternal satisfaction [20] . We are grateful to these patients who gave informed consent to publish the paper. In 317 addition, we also thank the obstetricians and nurses for the diagnosis and treatment of 318 these pregnant women. Availability of data and materials 334 Access to the qualitative data will be given upon request to the corresponding author 335 after taking any necessary precautions to safeguard participants' privacy and 336 confidentiality.

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Ethical approval and patient consent 338 The study protocol was approved by the Ethics Committee of Maternal and Child 339 Health Hospital of Hubei Province. All included women signed written informed 340 consent for therapeutic procedures and also for the publication of those reports.

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Consent for publication 342 Not applicable.

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Conflicts of interest 344 The author has no conflict of interest regarding the publication of this paper. 345