Objective: This study aims to investigate the etiological and bleeding risk
factors of cesarean scar pregnancy (CSP) and attempts to determine the clinical
value of uterine artery embolization (UAE) combined with curettage,
methotrexate (MTX) chemotherapy combined with curettage, and uterine curettage
alone in terminating CSP. Materials and methods: A total of 154 patients with CSP and 155 patients with
cicatricial uterus termination of pregnancy in the same period who were
hospitalized in the Department of Obstetrics and Gynecology, Second Affiliated
Hospital of Nanchang University from January 2013 to March 2020 were enrolled in
this study. The clinical characteristics of the two groups were statistically
analyzed, and CSP patients were divided into the UAE + uterine curettage group (n
= 49), MTX + uterine curettage group (n = 33) and uterine curettage alone group
(n = 72) according to different treatment methods. The scar thickness,
intraoperative blood loss, time to resumption of menstruation and other
indicators were compared and analyzed among the three groups. Results: The proportion of CSP patients with cesarean section time
Cesarean scar pregnancy (CSP), defined as embryo implantation in the previous lower uterine segment anterior wall cesarean scar, is a serious long-term potential complication of cesarean section and is categorized as a special type of ectopic pregnancy [1]. If not managed properly, it can cause fatal massive hemorrhage or uterine rupture, therefore, once the diagnosis is confirmed, timely termination of pregnancy is recommended. However, no uniform treatment plan yet exists. Hence, this study retrospectively analyzed the clinical data of CSP patients who underwent uterine artery embolization (UAE) + uterine curettage, methotrexate (MTX) chemotherapy + uterine curettage and simple uterine curettage alone to terminate their pregnancies during a span of 7 years in the Second Affiliated Hospital of Nanchang University, to investigate the influencing factors regarding the incidence of CSP, bleeding risk factors and the feasibility and effectiveness in clinical application of the three treatment modalities
From January 2013 to March 2020, 154 patients with CSP and 155 pregnant patients with scarred uterus termination of pregnancy in the same period at the Second Affiliated Hospital of Nanchang University were enrolled in the study. The pregnant patients with scarred uterus terminated pregnancy were their own personal requirements and get husband’s understanding. Subjects were aged 22–47 years, and the number of previous pregnancies was 2–13, number of cesarean sections was 1–3. Of the 154 patients with CSP, 73 had no obvious symptoms while 81 had vaginal bleeding, of which 3 had spontaneous massive vaginal bleeding and the others had persistent slight bleeding. Twenty-five of the 81 patients with CSP vaginal bleeding had lower abdominal pain and discomfort. Of the 155 pregnant patients with scarred uterus, 12 had a little vaginal bleeding with lower abdominal distension discomfort.
(1) Diagnosis: Excluding 3 cases of bleeding were diagnosed by trans-abdominal gynecological color Doppler ultrasound, 151 patients with CSP were diagnosed by vaginal ultrasonography. Pelvic MRI was performed in 96 patients without emergency treatment or with vascular filling and rich blood flow around the gestational sac as indicated by color Doppler ultrasound.
(2) Classification: The latest Expert Consensus on the
Diagnosis and Treatment of Uterine Scar Pregnancy after Cesarean Section (2016)
proposes that all patients with CSP (including patients with CSP diagnosed before
2016) should be divided into three types according to the growth direction of the
gestational sac at the scar as well as the thickness of the uterine scar. Type I (26 patients): a small part of the fetal sac implants at the scar,
and the thickness of the scar is
All pregnant patients with scarred uterus were treated with surgical abortion,
and CSP patients voluntarily chose treatment options according to their general
conditions and economic conditions. Accordingly, 154 CSP patients underwent UAE
followed by uterine curettage (49 cases, including 2 cases of type I, 40 cases of
type II and 7 cases of type III), MTX followed by uterine curettage (33 cases,
including 6 cases of type I, 26 cases of type II and 1 case of type III) and
uterine curettage alone (72 cases, including 18 cases of type I, 52 cases of type
II and 2 cases of type III). Patients who received UAE treatment completed
uterine curettage surgery within 72 hours following intervention. For patients
with blood HCG
(1) Preoperative conditions: age, number of pregnancies, number of cesarean
sections, gestational age, time from this pregnancy to the previous cesarean
section, size of gestational sac, serum
(2) Intraoperative conditions in CSP patients: duration of surgery, intraoperative blood loss;
(3) Therapeutic effect indicators in CSP patients: time for serum
All data were statistically processed using SPSS 16.0. The test values of the
measured data among the CSP groups were expressed as mean
The age, number of miscarriages, number of cesarean sections, time to previous
cesarean section and other indicators of the 154 CSP patients were compared to
155 pregnant women with scarred uterus termination of pregnancy in the same
period, in which a significant difference in the distribution of “Time to
previous cesarean section” was found (P
Variable | CSP Group, n = 154, (100%) | Pregnant with scarred uterus Group, n = 155, (100%) | P value | |
Age | ||||
64 (41.56) | 63 (40.65) | 0.027 | 0.870 | |
90 (58.44) | 92 (59.35) | |||
Number of miscarriages | ||||
0 | 1 (0.65) | 3 (1.94) | 1.307 | 0.860 |
1 | 30 (19.48) | 28 (18.06) | ||
2 | 36 (23.38) | 35 (22.58) | ||
3 | 42 (27.27) | 46 (29.68) | ||
45 (29.22) | 43 (27.74) | |||
Number of cesarean sections | ||||
1 | 89 (57.79) | 90 (58.06) | 0.002 | 0.961 |
65 (42.21) | 65 (41.94) | |||
Interval (month) | ||||
29 (18.83) | 16 (10.32) | 16.661 | 0.000 | |
24–60 | 71 (46.10) | 107 (69.03) | ||
54 (35.06) | 32 (20.65) |
No significant difference in age, times of pregnancy, times of cesarean section,
gestational age, time from this pregnancy to previous cesarean section, blood
Category | UAE + uterine curettage Group (n = 49) | MTX + uterine curettage Group (n = 33) | The uterine curettage alone Group (n = 72) | P value |
Age (year) | 32.33 |
31.85 |
32.11 |
0.931 |
Number of pregnancies | 4.27 |
4.94 |
4.64 |
0.410 |
Number of CS | 1.49 |
1.48 |
1.50 |
0.968 |
Gestational age (days) | 52.96 |
50.21 |
50.79 |
0.520 |
Time since last cesarean section (months) | 57.47 |
46.27 |
54.99 |
0.610 |
Pre-treatment serum |
64081.54 |
43285.09 |
47289.57 |
0.117 |
Progesterone level (ng/mL) | 52.96 |
50.21 |
50.79 |
0.520 |
Diameter of gestational sac (mm) | 29.35 |
28.42 |
27.58 |
0.798 |
Uterine scar thickness (mm) | 2.27 |
2.98 |
2.78 |
0.002 |
The operation time among the three groups of patients with CSP was shortest in
the MTX + uterine curettage group and longest in the uterine curettage alone
group, which was observed to be statistically significant (P
Two patients with MTX + uterine curettage more than 10 weeks were present; both were type II, had intraoperative blood loss of more than 200 mL, and underwent emergency Foley catheter balloon compression hemostasis. Six patients had intraoperative blood loss of more than 200 mL (2 cases of type III, 4 cases of type II) and were more than 8 weeks of gestational age, of which 2 cases (all type III) were given emergency interventional therapy and 4 cases (type II) were given Foley catheter balloon compression hemostasis. None of the patients who underwent UAE + uterine curettage had blood loss greater than 200 mL. The bleeding volume of the three groups was least in the UAE + uterine curettage group and most in the uterine curettage alone group, which was found to be statistically significant.
The most direct indicators in evaluating the success of treatment were found to
be the presence or absence of residual uterine cavity, whether blood
Groups | Operation time (min) | Hospital day (days) | Hospital costs (RMB) | Intraoperative blood loss (mL) | Time for serum |
Time to resumption of menses (days) |
UAE + uterine curettage Group (n = 49) | 16.94 |
8.24 |
18581.78 |
17.76 |
12.53 |
40.80 |
MTX + uterine curettage Group (n = 33) | 14.42 |
15.12 |
9929.80 |
57.85 |
20.85 |
43.73 |
uterine curettage alone Group (n = 72) | 19.26 |
6.28 |
5233.14 |
113.18 |
20.25 |
42.58 |
Note: * P |
In the UAE + uterine curettage group, 36 patients (73.47% in UAE group) had different degrees of lower abdominal pain following intervention, of which seven patients required analgesic drugs. Twenty patients in the UAE + uterine curettage group had irregular vaginal bleeding following interventional surgery, and all patients in the MTX + uterine curettage group had irregular small amount of vaginal bleeding during chemotherapy, with no special treatment. Furthermore, 12 patients that underwent MTX + uterine curettage had different degrees of liver function impairment and were given liver protection treatment, which did not cause irreversible damage. No complications such as uterine perforation occurred during uterine curettage among the three groups.
A correlation analysis was performed between pretreatment indicators (age,
number of pregnancies, number of cesarean sections, gestational age, time from
previous cesarean section) and bleeding volume among the 72 patients in the
simple uterine curettage group. After analysis, it was found that the gestational
age, blood
Variable | P value | Correlation coefficient |
Gestational age | 0.031 | 0.254 |
Blood β-hCG level | 0.044 | 0.238 |
Gestational sac diameter | 0.043 | 0.239 |
Thickness of uterine scar | 0.026 | -0.263 |
Due to the adjustment of China’s “second child policy”, drawbacks in the history of high cesarean section rate began to appear, and the incidence of CSP began to increase annually. In the present study, 154 cases of CSP were evaluated, of which 108 patients accounted for 70.13% of the total in the past four years. Since CSP may lead to uterine rupture, uncontrollable bleeding and even loss of fertility [3, 4], it is particularly important to determine its etiological factors and early diagnosis as well as provide active and effective treatment.
At present, the pathogenesis of CSP is not clear. Various scholars hold the
opinion that multiple cesarean sections increase the damage done to the
endometrium as well as the scar area, thereby increasing the probability of
gestational sac implantation in the endometrium [5, 6]. The findings of this
study demonstrate that undergoing multiple cesarean sections does not
significantly increase the occurrence of CSP, which is in contrast to the above
assertion. However, the incidence of CSP significantly increased when the time
from previous cesarean section was
The diagnosis of CSP mainly relies on medical history, clinical manifestations
and auxiliary examinations. There may be no clear history of menopause at the
onset of CSP, and most patients present with painless vaginal bleeding [12].
In this study, serum
Principles of treatment of CSP is removal of the lesion, reduction of bleeding and preservation of reproductive function [3]. Moreover, treatment methods include interventional therapy, drug therapy, surgical treatment and combined therapy. Uterine artery embolization (UAE) blocks the blood supply of the gestational sac by selectively embolizing the uterine artery, resulting in ischemic necrosis of the embryo and significantly reducing bleeding during embryo dissection and abortion [3, 16, 17]. This study found that the bleeding volume of patients in the UAE + uterine curettage group was significantly less than that of patients in the other two groups, and no patients in the UAE + uterine curettage group underwent hysterectomy due to massive hemorrhage. However, Cao et al. [16] reported that two patients with CSP had uncontrollable bleeding following UAE treatment. Therefore, the following points must be considered prior to commencing UAE: (1) Definite diagnosis: CSP is not only often misdiagnosed as a cervical pregnancy, but it is also confused with normal intrauterine pregnancy. If uterine artery embolization is performed in a normal pregnancy, wastage of medical resources as well as an increase in economic burden for patients occurs, and complications following embolization may be encountered, leading to ischemic injury of non-target tissues. Therefore, a definitive diagnosis is a prerequisite for the successful treatment of UAE; (2) Timing of surgery: In this study, all patients who underwent UAE underwent uterine curettage within 72 hours after embolization to avoid failure of surgery due to the establishment of collateral circulation. In regard to patients with special circumstances requiring subsequent uterine curettage, it was necessary to perform a second embolization in order to avoid massive hemorrhage; (3) Check: In patients with CSP more than 10 weeks pregnant, the placenta has already been formed. Considering that the blood supply of uterus is partly from the communication branches of ovarian vessels and internal pudendal artery, simple embolization of the uterine artery still risks massive hemorrhage, hence, planning for laparotomy or balloon tamponade hemostasis should be done for such patients; (4) Fully inform the relevant risks of interventional therapy such as premature ovarian failure, abdominal pain, uterine ischemic necrosis, and uncontrollable bleeding following interventional therapy. Premature ovarian failure is mainly caused by embolic agents that block blood vessels supplying the ovary with blood circulation. Whether menstruation resumes after surgery is an important evaluation index. No significant difference in the onset time of menstruation between patients treated with UAE and the other two groups were present, however, 36 patients (73.47% in UAE group) had different degrees of abdominal pain after UAE, which may be related to transient uterine ischemia, hypoxia, edema, hyperkalemia and histamine stimulation of pain sensation in muscle fiber cells.
MTX is currently the first-line drug for conservative treatment, which inhibits
trophoblastic cell division in order to kill embryos and may be administered
locally and systemically. Jin li et al. found that no significant difference in
the treatment success rate between the two routes of administration [18]. In
this group of data, 33 patients were treated with MTX + uterine curettage, and
the MTX dosing regimen was calculated as 50 mg/m
Patients with a bleeding volume greater than 200 mL in simple uterine curettage and MTX + uterine curettage were more than 8 weeks or even more than 10 weeks of gestational age. Reasons for this may be that after 8 weeks of pregnancy, the placental villi’s development flourishes and are firmly connected to the decidua basalis, having branches of umbilical artery and umbilical vein in each villous trunk. The increase in maternal uterine spiral blood into the intervillous space while the cesarean scar was relatively poor, resulted in the stimulation of villous trophoblasts that invade the scar and its surrounding deep uterus, causing a significant increase in bleeding volume after 8 weeks of pregnancy. After 10 weeks of pregnancy, the placenta was preliminarily formed, the dissection area following uterine curettage was large, and the scar did not contract. Even after MTX treatment, a risk of massive hemorrhage was still present.
In order to explore which factors were related to the severity of bleeding
during CSP treatment, this study conducted a dedicated analysis and found that
the three indicators of menopause time, serum
Regardless of the method used to treat CSP, a preemptive plan for massive hemorrhage and persistent ectopic pregnancy should be made. According to the data of this study, in order to minimize the risk of residual uterine cavity and avoid massive hemorrhage caused by repeated scratching and scarring, the operation was performed by experienced senior surgeons under the guidance of color Doppler ultrasound. Accordingly, 154 patients had only 4 cases of residual uterine cavity (3 in the simple uterine curettage group and 1 in the MTX + uterine curettage group), where the diameter of residues was less than 1.5 cm. For the 4 patients with residual uterine cavity, MTX treatment was given while inducing uterine contractions, which were all successful. UAE and uterine cavity balloon compression hemostasis were remedial measures in controlling intraoperative bleeding. Since the materials required for balloon compression hemostasis are available at all hospitals, are easy to operate and have good hemostatic effect, they could be popularized in primary hospitals, saving valuable time in the transfer treatment of such patients.
In summary, gestational age, pretreatment serum
This study attempted to compare the surgical effect and safety of the three treatment schemes and further clarified that pretreatment is recommended for patients with more than 8 weeks of gestation and rich blood flow around the gestational sac. MTX pretreatment may be considered for patients between 8 and 10 weeks of gestation, whereas UAE pretreatment is recommended for patients who are over 10 weeks of gestation. Emergency uterine cavity balloon compression is beneficial for hemostasis during operation if much bleeding is present. The limitations of this study are that the sample size was relatively small. Moreover, CSP termination of pregnancy also includes other methods such as hysteroscopic surgery and laparoscopic surgery, which were not included in the scope of this study. Therefore, treatment choice still requires further elucidation.
JX and XJH conceived and designed the experiments; JL and YYX analyzed the data; JX and XJH wrote the paper. FF, WZ and LLL critically revised the manuscript.
The study protocols were approved by the Ethical Committee of the Second Affiliated Hospital of Nanchang University. Written consent to participate was obtained from the patient in this study.
I would like to express my gratitude to all those who helped me during the writing of this manuscript. Thanks to all the peer reviewers for their opinions and suggestions.
This work was supported by the Science and Technology Plan Fund of Jiangxi Provincial Health and Family Planning Commission (No. 20185244), Construction project of 2018 Postgraduate Teaching Case Base of Nanchang University, the Jiangxi Province Natural Science Foundation of China (S2019ZRMSB1793), Chinese National Natural Science Foundation (81760277).
The authors declare no conflict of interest.