Comparison of menstruation recovery after ultrasound-guided suction curettage in patients with cesarean scar pregnancy pretreated using high-intensity focused ultrasound and uterine artery embolization

Abstract

Objectives

To investigate the menstruation recovery after two therapeutic regimens, high-intensity focused ultrasound (HIFU) or uterine artery embolization (UAE) combined with ultrasound-guided suction curettage, for premenopausal women with cesarean scar pregnancy (CSP).

Materials and methods

Seventy patients with CSP treated with HIFU followed by ultrasound-guided suction curettage and 63 patients with CSP treated with UAE followed by ultrasound-guided suction curettage in our hospital were retrospectively reviewed. The treatment parameters and the menstrual blood loss (MBL) volume at 6 months after the two therapeutic regimens were compared between the two groups.

Results

There was no significant difference in treatment results between the two groups. With regard to postoperative MBL volume, 5 out of 70 patients in the HIFU group and 22 out of 63 patients in UAE group exhibited a reduction in MBL, respectively. Multivariate logistic regression revealed that hypomenorrhea was more likely to occur in the UAE group than in the HIFU group (UAE group vs. HIFU group; OR 11.328, 95% CI 3.158–55.871; p < 0.001).

Conclusion

Compared to UAE, HIFU has less influence on postoperative MBL volume, which may be a fertility-sparing option for patients with CSP.

Keywords:

• Cesarean scar pregnancy
• high-intensity focused ultrasound
• uterine artery embolization
• menstrual blood loss
• ultrasound-guided suction curettage

1. Introduction

Cesarean scar pregnancy (CSP) is a significant and rare postoperative complication of cesarean section that accounts for 0.45% of postoperative complications [1]. Although CSP is rare, it may cause life-threatening hemorrhages and uterine rupture [2]. Currently, there is no consensus regarding the management of CSP. Recently, the Society for Maternal-Fetal Medicine (SMFM) suggested that the management of CSP should consider protecting maternal health and preserving women’s reproductive function as much as possible [3]. The previous studies have mainly focused on intraoperative blood loss during CSP surgery, but have ignored postoperative menstruation recovery [4–6]. For patients undergoing fertility-sparing surgery, poor postoperative menstruation recovery reflects insufficient fertility recovery.

Over the last few years, an increasing number of studies have demonstrated that uterine artery embolization (UAE) and high-intensity focused ultrasound (HIFU) are effective therapeutic options for CSP [7,8]. Although a study showed that there was no significant difference in postoperative menstruation recovery time between the HIFU and UAE groups [6], other studies indicated that UAE has negative effects on postoperative menstruation recovery due to the blocking of endometrial blood supply [9]. However, the effects of HIFU or UAE combined with ultrasound-guided suction curettage on postoperative menstrual recovery remain unknown. Consequently, this study aimed to investigate the menstruation recovery of two therapeutic strategies in CSP patients undergoing fertility-sparing surgery.

2. Materials and methods

This study was approved by the Ethics Committee of Shenzhen Maternity and Child Healthcare Hospital, Guangdong, China, (SFYLS [2022]012) and the requirement for an informed consent to do the research was waived.

2.1. Patients

Between October 2016 and June 2020, 70 patients treated with HIFU followed by ultrasound-guided suction curettage and 63 patients treated with UAE followed by ultrasound-guided suction curettage in the Department of Obstetrics and Gynecology of Shenzhen Maternity and Child Healthcare Hospital were retrospectively reviewed (Figure 1).

Figure 1. The study selection process for CSP.

The inclusion criteria were as follows: (1) history of cesarean section, (2) positive urine pregnancy test results, and (3) diagnosis of CSP confirmed by three-dimensional (3-D) ultrasound. The exclusion criteria were as follows: (1) other treatments (such as drugs or surgery), (2) gestational week >10 weeks.

2.2. Data collection

The characteristics of patients included age, interval from the last cesarean section, previous cesarean pregnancies, gestational age, number of abortions, gravidity, parity, scar thickness, pretreatment serum β-hCG level, largest diameter of the sac/mass, intraoperative blood loss, fetal heart activity detected, and direction of gestational sac growth were extracted from the hospital information system.

2.3. HIFU treatments

HIFU treatment was performed using a JC200 focused ultrasound tumor therapeutic system (Chongqing Haifu Medical Technology Co. Ltd., Chongqing, P.R. China). The patients were requested to undergo bowel preparation, including ingestion of a low-fiber diet, semi-liquid and liquid food, and oral administration of polyethylene glycol (PEG) the night before the treatment day, and fasting for 12 h. The abdominal wall from the umbilicus to the upper margin of the pubic symphysis was shaved first, and then degreased and degassed with degassed water. A catheter was inserted into the bladder to control the volume.

Patients were positioned prone on the HIFU table of the system, with the anterior abdominal wall in contact with degassed water. HIFU treatment was performed under conscious sedation. Sagittal ultrasound scanning mode was chosen for both pretreatment planning and sonication. A point scan was used, and the position of the focus was adjusted around the embedding area of the gestational sac. Contrast-enhanced ultrasound with a microbubble agent (Sonovue, Bracco, Milan, Italy) was performed 10 min before and immediately post-HIFU to evaluate the blood supply changes in the embedding area. The vital signs of patients were closely monitored during the procedure.

2.4. Procedure of UAE

The procedure of UAE was described previously [8]. Briefly, this procedure was performed under local anesthesia, and a right transfemoral approach was used for artery access. First, patients underwent bilateral uterine artery angiography before embolization. Subsequently, the bilateral uterine arteries were embolized using polyvinyl alcohol particles (with a diameter of approximately 0.5–0.7 mm), with 100 mg on each side. The embolization treatment was terminated when imaging showed that the branches of the main bilateral uterine arteries had disappeared. Hemostasis was applied to the puncture site and maintained under pressure for 24 h after the operation.

2.5. Ultrasound-guided suction curettage

All patients underwent ultrasound-guided suction curettage within 24–48 h after HIFU or UAE. Ultrasound-guided suction curettage was performed under general anaesthesia. The patient was placed in the bladder lithotomy position and a No.7 suction tube was used to suction the gestational sac. The negative pressure was set to exceed 400 mmHg. The procedure was stopped when the ultrasound showed no obvious abnormal uterine tissue. Intraoperative blood loss was collected throughout the curettage.

2.6. Menstrual blood loss evaluation

The Pictorial Blood Assessment Chart (PBAC) score was used to evaluate the postoperative MBL volume, with 80 ml of blood loss corresponding to a PBAC score of 100 [10]. Hypomenorrhea was defined as a PBAC score of <20 points.

2.7. Follow-up

All patients were scheduled for serum β-hCG monitoring weekly after they were discharged from the hospital until β-hCG returned to normal levels. During the visits to our outpatient clinic, the menstrual recovery time, postoperative MBL volume and adverse effects were monitored by self-report and face-to-face consultation. Postoperative MBL volume was scored using the PBAC score [11]. All patients were followed up for at least 6 months.

2.8. Statistical analysis

SPSS software (version 19.0; IBM, New York, USA) was used for statistical analysis. Normally distributed data are presented as mean ± standard deviation, and data with skewed distribution are presented as median (interquartile range). For continuous variables, the t-test and Wilcoxon rank-sum test were used for inter-group comparisons based on whether the variables followed a normal distribution and had equal variance. The chi-square test was used to analyze intergroup differences in the unordered categorical variables. The Wilcoxon rank-sum test was used to analyze intergroup differences in the ordered categorical variables. Univariate and multivariate logistic regression analyses were also conducted to analyze the risk factors for hypomenorrhea, including age, interval from the last CS, previous cesarean pregnancies, number of abortions, gravidity, parity, scar thickness, gestational age, pretreatment serum β-HCG, largest diameter of the sac/mass, intraoperative blood loss, intraoperative blood loss, time for β-HCG reduction to normal levels, menstrual recovery time, expenses, and length of hospital stay. Statistical significance was defined as a two-sided P-value of <0.05.

3. Results

3.1. Comparison of baseline characteristics between patients treated with HIFU and UAE

As shown in Table 1, the average age of patients treated with HIFU was 34.17 ± 4.11 years old, and it was 34.08 ± 4.97 years old in patients treated with UAE. The average interval from the last cesarean section to CSP was 5.18 ± 2.92 years in the HIFU group, and it was 5.13 ± 3.11 years in the UAE group. The average number of abortions was 1.77 ± 1.42 years in the HIFU group, and it was 1.87 ± 1.16 years in the UAE group. The average gravities was 4.21 ± 1.46, and it was 4.32 ± 1.32 in the UAE group. The average parities was 1.39 ± 0.55 in the HIFU group, and it was 1.48 ± 0.59 in the UAE group. The average gestational age was 49.84 ± 9.17 days in the HIFU group, and it was 49.9 ± 9.87 days in the UAE group. The average pretreatment serum β-hCG was 79248.90 ± 60780.57 mIU/mL vs 140803.79 ± 359103.67 mIU/mL in the two groups, respectively. The largest diameter of the sac/mass was 2.95 ± 1.19 mm in HIFU group, and it was 3.27 ± 1.54 mm in UAE group. The proportion of fetal heart activity detected in the HIFU and UAE groups was 59.2% and 40.8%, respectively. In HIFU group, the rate of endogenic type was 64.3%, and it was 69.8% in UAE group. There was no significant difference in baseline characteristics except in the thickness of the scar (0.26 ± 0.11 mm vs 0.20 ± 0.09 mm, p = 0.003) between the two groups.

Table 1. Comparison of baseline characteristics between patients with CSP treated with HIFU and UAE.

Characteristic	HIFU group (n = 70)	UAE group (n = 63)	T/X^2	P
Age, y	34.17 ± 4.11	34.08 ± 4.97	0.116	0.908
Interval from the last CS , y	5.18 ± 2.92	5.13 ± 3.11	0.098	0.922
Number of abortions, n	1.77 ± 1.42	1.87 ± 1.16	−0.445	0.650
Gravdities, n	4.21 ± 1.46	4.32 ± 1.32	−0.428	0.669
Parities, n	1.39 ± 0.55	1.48 ± 0.59	−0.913	0.363
Thickness of scar, mm	0.26 ± 0.11	0.20 ± 0.09	3.064	0.003
Gestational age , d	49.84 ± 9.17	49.9 ± 9.87	−0.047	0.963
Pretreatment serum β-HCG, mIU/mL	79248.90 ± 60780.57	140803.79 ± 359103.67	−1.343	0.184
Largest diameter of the sac/mass , mm	2.95 ± 1.19	3.27 ± 1.54	−1.348	0.180
Fetal heart activity detected, n (%)			1.840	0.175
With	29(59.2)	20(40.8)
Without	38(46.9)	43(53.1)
Types of CSP, n (%)			3.785	0.151
Endogenic type	25(35.7)	19(30.2)
Exogenic type	45(64.3)	44(69.8)

HIFU: high-intensity focused ultrasound; UAE: uterine artery embolization; CS: cesarean section; β-HCG: β-subunit of human chorionic gonadotropin.

3.2. Comparison of treatment efficacy between the two groups

All patients underwent ultrasound-guided suction curettage after HIFU or UAE treatment. As shown in Table 2, intraoperative blood loss (12.00 ± 23.58 ml vs. 15.08 ± 62.28 ml, p = 0.713) and time for β-hCG returned to normal level (25.64 ± 8.13 days vs. 26.70 ± 8.17 days, p = 0.457) did not exhibit any significant difference between the two groups. In addition, none had a uterus perforation. On the other hand, the length of hospital stay of HIFU group was significantly shorter than that of UAE group (3.84 ± 1.29 days vs. 5.11 ± 1.97 days, p < 0.001).

Table 2. Comparison of postoperative outcomes between HIFU group and UAE group.

Characteristic	HIFU group (n = 70)	UAE group (n = 63)	T/X^2	P
Intraoperative blood loss, mL	12.00 ± 23.58	15.08 ± 62.28	−0.369	0.713
Time for β-HCG returned to normal level, d	25.64 ± 8.13	26.70 ± 8.17	−0.746	0.457
Menstrual recovery time, d	37.50 ± 16.72	30.87 ± 7.73	2.880	0.005
Postoperative MBL volume, n (%)			15.813	<0.001
Hypomenorrhea	5	22
Eumenorrhea	65	41
Cost, yuan	12003.36 ± 1265.86	14786.90 ± 2890.84	−7.317	<0.001
Length of hospital stay, d	3.84 ± 1.29	5.11 ± 1.97	−4.433	<0.001

HIFU: high-intensity focused ultrasound; UAE: uterine artery embolization; β-HCG = β-subunit of human chorionic gonadotropin; MBL: menstrual blood loss.

3.3. The menstruation recovery results

In terms of postoperative outcomes, the menstrual recovery time in patients treated with HIFU was significantly longer than that of patients treated with UAE (37.50 ± 16.72 days vs.30.87 ± 7.73 days, p = 0.005) (Table 2). However, only 5 out of 70 (7.14%) patients had hypomenorrhea in the HIFU group, while 22 out of 63 (34.92%) were in the UAE group (p < 0.001) (Table 2).

3.4. The adverse effects after HIFU and UAE treatments

In the HIFU group, the visual analog scale (VAS) was 1.34 ± 1.67, with 6 patients (8.6%) experiencing sacrococcygeal pain and 3 patients (4.3%) developing subcutaneous induration. In the UAE group, the VAS was 5.92 ± 1.46, with 3 patients (4.8%) experiencing fever, 1 patient (1.6%) experiencing sacrococcygeal pain, 14 patients (22.2%) experiencing mild lower limb pain or numbness, 4 patients (6.3%) experiencing vomiting, and 1 patient (1.6%) developing venous thrombosis. Both groups of patients showed no statistically significant differences (p > 0.05) in terms of fever, sacrococcygeal pain, vomiting, subcutaneous nodules, and lower limb venous thrombosis. Patients treated with HIFU had a significantly lower abdominal pain score and a lower incidence of lower limb pain/numbness than that of patients in the UAE group (p < 0.05) (Table 3).

Table 3. Comparison of the adverse effects and complications between the two groups.

Variables	HIFU group (n = 70)	UAE group (n = 63)	p
Post-procedure pain score (point)	1.34 ± 1.67	5.92 ± 1.46	0.000
No. of patients with fever	0 (0%)	3 (4.8%)	0.104
Patients with sacrococcygeal pain	6 (8.6%)	1 (1.6%)	0.119
Patients with lower limb pain or numbness	0 (0%)	14 (22.2%)	0.000
Patients reported vomiting	0 (0%)	4 (6.3%)	0.048
Cases developed subcutaneous induration	3 (4.3%)	0 (0%)	0.246
Venous thrombosis	0 (0%)	1 (1.6%)	0.474

HIFU: high-intensity focused ultrasound; UAE: uterine artery embolization.

3.5. Risk factors for hypomenorrhea

Univariate logistic regression demonstrated that patients treated with UAE had a higher risk of hypomenorrhea than patients treated with HIFU (OR:6.976; 95%CI:2.624–22.141; p < 0.001). Similarly, on multivariate logistic analysis, the UAE group also had an increased risk of hypomenorrhea compared with the HIFU group (OR:11.328; 95% CI:3.158–55.871; p < 0.001) (Table 3). However, age (OR:1.099; 95%CI:0.981–1.243; p = 0.114), interval from the last cesarean section to CSP (OR:0.950; 95%CI:0.796–1.128; p = 0.561), number of pregnancies (OR: 2.132; 95%CI: 0.220–43.254; p = 0.518), number of abortions (OR: 1.950; 95%CI: 0.442–8.004; p = 0.360), gravidities (OR:0.606; 95%CI:0.155–2.679; p = 0.484), parity (OR: 0.379; 95%CI: 0.007–3.099; p = 0.447), thickness of scar (OR:8.189; 95%CI: 0.002–29522.000; p = 0.609), gestational age (OR:0.969; 95%CI: 0.905–1.031; p = 0.344), pretreatment β–HCG (OR:1.000; 95%CI: 0.999–1.000; p = 0.382), largest diameter of the sac/mass (OR:1.056; 95%CI: 0.687–1.635; p = 0.805), intraoperative blood loss (OR:0.996; 95%CI: 1.000–1.007; p = 0.688), time for β–HCG reduction to normal level (OR:1.058; 95%CI: 0.996–1.167; p = 0.236), menstrual return to normal (OR:0.990; 95%CI: 0.910–1.055; p = 0.776), and type of CSP (OR:1.005; 95%CI:0.197–4.485; p = 0.995) were not related to hypomenorrhea (Table 4).

Table 4. Univariate and multivariate analysis for hypomenorrhea.

Variable	Univariate analysis			Multiple analysis
	OR	95%CI	P	OR	95%CI	P
Age	1.069	0.972–1.179	0.175	1.099	0.981–1.243	0.114
Interval from the last CS	1.016	0.877–1.169	0.826	0.950	0.796–1.128	0.561
Previous cesarean pregnancies	0.852	0.364–1.863	0.698	2.132	0.220–43.254	0.518
Number of abortions	1.168	0.846–1.594	0.330	1.950	0.442–8.004	0.360
Gravdity	1.705	0.785–1.434	0.653	0.606	0.155–2.679	0.484
Parity	0.778	0.345–1.666	0.550	0.379	0.007–3.099	0.447
Thickness of scar	0.432	0.005–25.802	0.697	8.189	0.002–29522.000	0.609
Gestational age (d)	0.985	0.938–1.031	0.542	0.969	0.905–1.031	0.344
Pretreatment β-HCG	1.000	0.999–1.000	0.253	1.000	0.999–1.000	0.382
Largest diameter of the sac/mass	1.047	0.764–1.420	0.771	1.056	0.687–1.635	0.805
Intraoperative blood loss	0.988	0.914–1.006	0.620	0.996	1.000–1.007	0.688
Time for β-HCG reduction to normal level	1.039	0.990–1.089	0.107	1.058	0.996–1.167	0.236
Menstrual recovery to normal	0.993	0.953–1.023	0.672	0.990	0.910–1.055	0.776
Direction of the gestational sac growth	1.246	0.502–2.973	0.625	1.005	0.197–4.485	0.995
Treatment (UAE vs. HIFU)	6.976	2.624–22.141	0.000	11.328	3.158–55.871	<0.001

HIFU: high-intensity focused ultrasound; UAE: uterine artery embolization; CS: cesarean section; β-HCG = β-subunit of human chorionic gonadotropin; OR: odds ratio; CI: confidence interval.

4. Discussion

Despite CSP being a rare condition, delayed intervention may result in some life-threatening complications [1]. Currently, there is no consensus in the management of CSP. UAE is a treatment modality for CSP, but the adverse effects limit its role in the management of CSP. In our study, the results showed no significant differences in the intraoperative blood loss and time for β-hCG to return to normal levels between the patients treated with HIFU and patients treated with UAE. However, the length of hospital stay was significantly shorter in the HIFU group than in the UAE group. Patients in the UAE group had a significantly higher incidence of postoperative pain and lower limb numbness or pain than those in the HIFU group. Therefore, HIFU combined with ultrasound-guided suction curettage appeared to be as effective as UAE combined with ultrasound-guided suction curettage with less adverse effects.

Currently, CSP management is mainly aimed at protecting maternal health and maintaining fertility [3]. Previous studies have focused on reducing perioperative blood loss for maternal health; however, there are few reports on postoperative menstruation recovery [4–6]. Continuous and regular menstruation reflects normal reproductive function [12,13]. Therefore, a reduction in postoperative MBL should be recognized during follow-up visits. Xiao et al. reported that the HIFU procedure rarely affects postoperative MBL [7]. Consistently, our study also demonstrated that patients treated with HIFU had less influence on reproductive function than those treated with UAE, which may be suitable for fertility-sparing patients with CSP. HIFU treatment for CSP was performed under US guidance. The energy was delivered precisely to the implantation site of the gestational sac at the cesarean scar, which killed the trophoblastic cells and destroyed small blood vessels with a diameter of less than 2 mm by increasing the temperature from 60 − 100 °C [14]. Therefore, HIFU has a lower risk of intrauterine adhesions and has no negative effects on ovary function owing to precise sonication [15].

Our results showed that the hypomenorrhea rate in the HIFU group was 7.14% (5/70), which was significantly lower than that in the UAE group (34.92%). Additionally, the time to menstruation recovery in the UAE group was shorter than that in the HIFU group, because there was a slight impact of 6–7 days difference for an event that takes 30–40 days [16], the difference in time for menstruation recovery may not be clinically significant. The effects of UAE on fertility remain controversial. UAE can be used in CSP by blocking the uterine blood supply, resulting in the destruction of the surrounding endometrium[17]. Meanwhile, as some branches of the uterine artery supply blood to the ovaries, UAE may affect the blood supply from collateral vessels to the ovaries and induce a potential risk of ovarian ischemia[18]. Previous studies have shown that UAE causes partial endometrial necrosis in some patients and negatively affects ovarian function [19]. Permanent amenorrhea and ovarian failure, which are related to endometrial atrophy, may occur as serious complications after UAE [20,21]. Based on this retrospective cohort of premenopausal Chinese women, patients with CSP who underwent HIFU had a lower risk of hypomenorrhea than those who underwent UAE. This phenomenon may be due to the dual effects of rapid ovarian ischemia after UAE, which leads to decreased ovarian function and acute ischemic damage to the endometrium.

A strength of this study was that we first used PBAC score to evaluate the postoperative MBL volume on the quantitative assessment, rather than qualitative assessment, with a focus on menstrual volume changes after HIFU or UAE treatment in CSP patients. As patients with CSP are relatively young with a high fertility desire, we found HIFU had a lower risk of hypomenorrhea, which could protect maternal health and maintain fertility better. Our study provides important insights into the information needs of young CSP patients when making fertility decisions. Additionally, we believe that the harmlessness of postoperative MBL using the HIFU procedure will be of interest to clinicians.

Several limitations should be noted in this work. First, because of its retrospective nature, blood samples were lacking, making it impossible to measure indicators of ovarian function, such as AMH and FSH. Therefore, future prospective studies are required to compare the effects of HIFU and UAE on ovarian function. Second, the preoperative and postoperative blood supplies of the uterus and ovaries were not measured using Doppler ultrasonography. Nonetheless, the postoperative MBL measured using the PBAC score also reflected endometrial function. Moreover, this was a single-center study, and a potential selection bias was not completely excluded, but we tried to control the bias by comparing the baseline characteristics of two groups, which had no significant differences. Therefore, a prospective and randomized multi-center study will be performed in the future.

5. Conclusion

Based on our results, we concluded that HIFU has fewer negative effects on postoperative MBL, which may be a superior fertility-sparing modality to UAE in patients with CSP who wish to conceive in the future.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available upon request from the corresponding author, PJ. The data are not publicly available because they contain information that can compromise the privacy of the research participants.

Additional information

Funding

Chongqing Science and Technology Bureau (2021KFKT030).