Role of ultrasound-guided technique in the treatment of gynecologic diseases: A systematic review and meta-analysis

Background:

The efficacy and safety of ultrasound-guided interventional procedures for gynecologic diseases have not been evaluated comprehensively. Therefore, we aimed to provide an evidence-based medical reference for clinical treatment in this meta-analysis.

Methods:

The literature searches were conducted in databases of PubMed, Embase, and Web of Science for eligible studies published from 2002 to May 2022. All literature was searched, screened, and reviewed by 2 researchers separately. RevMan 5.3.0 was used to analyze the relevant data.

Results:

A total of 12 articles consisting of 2854 patients were included. Compared with the control group, meta-analysis showed that ultrasound-guided technique in the experimental group was associated with a higher effective rate [risk ratio = 0.84, 95% confidence interval (CI) (0.84, 0.84)], a lower probability of recurrence [odds ratio = 0.13, 95% CI (0.13, 0.13), P < .00001], and a greater effective reintervention rate [odds ratio = 3.39, 95% CI (1.29, 8.86), P = .01]. However, it was not significantly associated with fewer adverse reactions.

Conclusions:

Ultrasound-guided technique in treating gynecologic diseases exerted a positive effect and had fewer adverse reactions, which could be popularized and applied in clinical practice.

1. Introduction

As a disease treatment method, ultrasound-guided technique (USGT) has emerged with the development of medical technology. This technique is developed based on ultrasound imaging to further meet the needs of clinical diagnosis and treatment.^[1] Various needle biopsies, aspiration, intubation, and drug injection can be supervised or guided by ultrasound. The technique can avoid some surgical procedures and achieve the same effect as that of surgery.^[2] The principle of this technique is that ultrasound-guided fine-needle aspiration can directly reach the lesion area. Cyst fluid is then aspirated, or a drug is injected, causing the cyst to shrink and disappear. Subsequently, adenomyoma and fibroids immediately degenerate, shrink, and die. Therefore, clinical symptoms are relieved. The advantages of USGT are as follows: USGT requires no surgery and generally only requires local anesthesia, reducing the risk of general anesthesia^[3]; USGT induces slight damage, provides quick recovery, and exerts desirable effects, and it involves slight interference to the human body but protects normal organs the most; and USGT in the treatment can reduce the influence of drugs on lesions and minimize side effects on the body and other organs. The technique has become one of the most important treatment methods for gynecologic diseases (such as adenomyosis/tumor, uterine fibroids, chocolate cysts, ovarian cysts, polycystic kidneys, and aneurysms). Besides, it has gradually replaced or eliminated surgery as the original method.^[4]

An ovarian cyst is a gynecologic disease that more commonly occurs in women of reproductive age. Laparoscopic surgery is the recommended approach for ovarian cyst removal. However, complications, such as pelvic adhesions, also occur after laparoscopic surgery, affecting sterile women. USGT is particularly advantageous in the puncture and sclerotherapy of ovarian cysts. The method extracts cyst fluid via a puncture and then injects sclerosing agents, such as absolute ethanol and 50% high-sugar solution, to destroy the cyst intima and render it sterile. Inflammation can be cured by closing the cyst cavity. This technique has several advantages, such as the simplicity of operation, repeatability, reduced trauma, economic benefits, absence of severe complications, definite curative effect, and a mild impact on ovarian function.

A tubo-ovarian abscess is a severe gynecologic condition. Ultrasonography shows that the cyst wall is thick, the internal sound transmission is poor, and specificity is often accompanied by separation. Failure to promptly provide effective treatment can lead to chronic pelvic inflammation and atresia of the fimbria or lumen of the fallopian tube, increasing the risk of ectopic pregnancy or infertility. Surgical treatment is often used in clinical practice, including excision of abscesses or incision and drainage. However, insufficient preoperative preparation, unclear diagnosis, or unclear anatomy of surrounding organs and abscesses during surgery leads to side injuries and severe complications after surgery. Studies have found that ultrasound-guided puncture and drainage, as well as the application of antibiotics in the abscess cavity, can achieve the same level of efficacy as those of incision and drainage.^[5]

Chocolate cysts, also known as endometriosis, have considerably high clinical incidence and are challenging to treat. Although similar to malignant tumors, such as plant growth and tissue invasion, ovarian chocolate cysts are benign lesions. Infertility and dysmenorrhea are the most common clinical symptoms of patients with ovarian chocolate cysts. The condition seriously affects the quality of life and reproductive function of the patient. Therefore, effective treatment of ovarian cysts bears excellent significance. Laparotomy and laparoscopic surgery yield satisfactory results and can effectively remove ovarian chocolate cysts. However, surgery has postoperative complications, such as pelvic inflammatory disease and intestinal adhesions. These complications can delay postoperative recovery, seriously damage the reproductive function, and reduce ovarian reserve, leading to severe consequences. As a new minimally invasive technique, interventional ultrasound can be easily performed on patients with ovarian chocolate cysts, provide benefits, and exhibit safety. In addition, the incidence of postoperative bleeding and infection is relatively low.^[6,7]

Uterine fibroids are the most common benign tumors in the female reproductive system. Surgical treatment has been frequently used in the past. However, with improved requirements for the quality of life of individuals and changes in medical models, various minimally invasive interventional procedures, such as uterine artery interventional embolization, microwave coagulation, radiofrequency ablation, high-intensity focused ultrasound, and other treatment methods, are also increasingly used in the minimally invasive treatment of uterine fibroids. Uterine artery interventional embolization requires exposure to X-ray radiation, resulting in various complications, which limit its clinical application.^[8] In some studies,^[9–11] ultrasound-guided radiofrequency ablation is used to treat uterine fibroids, which is suggested to cause less trauma, significantly reduce tumor size, and markedly improve clinical symptoms and quality of life without serious complications.

Gynecological cysts are a common gynecologic disease, with the cyst being too large, causing compression symptoms prone to torsion. USGT is an ideal, minimally invasive, simple, economical, and effective treatment for patients with gynecologic cysts, who have experienced postoperative recurrence, received ineffective drug treatment, and refused surgery. In clinical practice, USGT in the treatment of gynecologic diseases has been reported to exhibit satisfactory clinical efficacy. However, in the early stages, there are no meaningful references for clinical practice because of the small sample size, and no reports of comprehensive evaluation using meta-analysis are retrieved. Therefore, we aimed to use meta-analysis to systematically evaluate the efficacy and safety of USGT for gynecologic diseases and thus provide an evidence-based medical reference for clinical treatment.

2. Materials and Methods

2.1. Literature search

The literature searches were conducted in databases of PubMed, Embase, and Web of Science for eligible studies published from 2002 to May 2022. A full-text search was conducted based on related subject terms as follows: “ultrasound-guided,” “interventional therapy,” “gynecology,” “cyst,” “gynecological disease,” “chocolate cyst,” “endometriosis,” “ovarian cyst,” “ovarian abscess,” “pelvic mass,” and “uterine fibroids.” A combination of keywords and subject words appeared in the retrieval form.

2.2. Inclusion criteria

Inclusion criteria were as follows: the language of publication was limited to English; the experimental design was scientific and reasonable, and the research designs and statistical methods were similar; outcome indicators included the following items: total effective rate, recurrence rate, occurrence of adverse reactions, and re-intervention rate; self-awareness of patients; voluntary participation of patients and their families in the research; and informed consent signed by the patient; and approval by the hospital ethics committee.

2.3. Exclusion criteria

The exclusion criteria were as follows: subjects with a severe infection, respiratory system disease, liver and kidney disease, blood disease, endocrine system disease, and digestive tract disease; review, systematic review, case analysis, and meta-analysis; duplicate publication; and presence of difficulties in data extraction.

2.4. Literature screening

All literature was searched, screened, and reviewed by 2 researchers separately. Disagreements during the review were resolved by a discussion or expert judgment. The data extracted from the article mainly included: authors and publication time; sample size, number of cases in each group, and average age of gynecologic disease types; specific intervention measures; and outcome indicators.

2.5. Statistical analysis

RevMan 5.3.0 was used to analyze the relevant data in the included articles. When the outcome variable was dichotomous, the relative risk ratio was calculated. When the outcome was a continuous variable, the mean difference was calculated. The results were presented using 95% confidence interval (CI). I² was used to assess heterogeneity among studies, and χ² was used for testing. If no statistical heterogeneity was found among the results of each study (I² < 50%, and P > .1), a fixed-effects model was used for meta-analysis. If statistical heterogeneity was indicated among the results of each study (I² ≥ 50%, or P ≤ .1), a random-effects model was used for the meta-analysis after the influence of apparent clinical heterogeneity was excluded. Subgroup and sensitivity analyses, or only descriptive analyses, were performed for studies with significant clinical heterogeneity. The meta-analysis was tested at α = 0.05. When the number of included studies exceeded 10, an inverted funnel plot was used for bias analysis.

3. Results

3.1. Literature search results

A total of 3748 articles were initially retrieved, among which 2673 duplicate articles, reviews, and abstracts were excluded, and 1075 articles remained. The articles for inclusion were screened by reading the titles and abstracts. Moreover, 1023 articles were initially screened, and 52 articles remained. The full text was read to screen out 40 articles that failed to meet the requirements, and the final study included 12 articles. The specific screening process is presented in Figure 1.

Figure 1.

Literature search.

3.2. Basic characteristics of the included studies

A total of 12 articles were included in the review,^[12–23] and Table 1 lists the basic characteristics of the included articles.

Table 1.

Basic characteristics of the 20 included articles.

Author(s), publication time	Sample size (cases)	Group (cases)	Disease type	Average age (yr)	Intervention measures	Outcome indicators
Cai et al, 2016[12]	79	Ultrasound intervention group (n = 37)	Ovarian cyst pediculotorsion	28.96 ± 3.59	Patients underwent emergency ultrasound intervention	b
		Laparoscopic group (n = 42)		29.25 ± 3.51	Patients underwent laparoscopic surgery
Mohr–Sasson et al, 2018[13]	132	Study group (n = 68)	Ovarian endometriomas	0.44 ± 0.77	5 mL of retention of ethanol transvaginal aspiration and sclerotherapy of endometrioma(s)	d
		Control group 1 (n = 64)	–	31.1 (19~44)	> 5 mL of retention
Goharkhay et al, 2007[14]	58	Ultrasound intervention group (n = 8)	Tubo-ovarian abscess	32.5 (18–44)	Primary image-guided drainage with concomitant intravenous antibiotics.	c
		intravenous antibiotics group (n 50)		31.7 (16–61)	Treatment with intravenous antibiotics alone
Chen et al, 2018[15]	1939	High-intensity focused ultrasound (HIFU) group (n = 1353)	Uterine fibroids	–	HIFU	c, d
		Control group (n = 586)		–	myomectomy.
Barnard et al, 2017[16]	83	Ultrasound intervention group (n = 43)	Uterine fibroids	–	Focused ultrasound surgery	D
		Control group (n = 40)			Embolization
Shawki et al, 2011[17]	86	Group I (n = 43)		(32 ± 12.24	Transvaginal ultrasound aspiration	b, c
		Group II (n = 43)	Ovarian endometriomas	(33 ± 45.30)	aspiration and in situ methotrexate injection
Visus et al, 2015[18]	50	50	Simple ovarian cysts	53.13 6 15.25	Ultrasound-guided fine-needle aspiration and ethanol sclerotherapy	b, c
Park et al, 2014[19]	79	79	Symptomatic uterine fibroid tumors with an immediate nonperfused volume (NPV) ratio of 80% or more.	43.6 4.4	MR-guided high-intensity focused US ablation	a
Wang et al, 2011[20]	68	68	For the ethanol short-time retention group, after washing with saline, the cyst was injected with 95% ethanol with a volume amounting to half of the fluid aspirated from the cyst. After 10 min, the remaining ethanol was aspirated.	–	Postoperative recurrent chocolate cysts	a
Kostrzewa, et al, 2019 [21]	84	84	Simple ovarian cysts		Transvaginal ultrasound-guided aspiration of SOC	b
De la Noval et al, 2020[22]	156	156	Low-risk adnexal cyst		Transvaginal US-guided aspiration	a, c
Zhang et al, 2011[23]	40	40	Symptomatic uterine fibroid		Percutaneous insertion of the microwave (MW) antenna into the fibroid, under US guidance, to perform the ablation.	c

a: total effective rate; b: recurrence rate; c: occurrence of adverse reactions; d: reintervention rate.

3.3. Meta-analysis results

3.3.1. Clinical efficacy.

Among the 12 included articles, 3 articles^[19,20,22] used clinical efficacy to evaluate the effect of USGT in the treatment of related gynecologic diseases. None of these 3 articles included controlled experiments, and all were self-descriptive experiments. The heterogeneity test yielded I² = 100% and P < .00001. USGT was found to significantly affect related gynecologic diseases [risk ratio = 0.84, 95% CI 0.84–0.84] (Fig. 2).

Figure 2.

Meta-analysis results for clinical efficacy.

3.3.2. Adverse reactions.

Among the 12 included articles, 6 articles^{[14,15,17,18,22,23]} used adverse reaction status to assess the safety of USGT for related gynecologic diseases, and the articles provided a specific number of adverse reactions after treatment. Among the 6 articles included, 3 articles^[14,15,17] were controlled studies, and 3^[18,22,23] were descriptive studies. The heterogeneity test for the controlled studies yielded I² = 92% and P < .00001. Therefore, a random-effects model was used to conduct a meta-analysis, and the results of the meta-analysis showed that the effect of USGT was more significant in the experimental group compared with the control group [OR = 0.21, 95% CI (0.14, 0.31), P < .00001]. The adverse reactions in the experimental group were significantly fewer compared with the control group (Fig. 3). The heterogeneity test for descriptive studies yielded I² = 100% and P < .00001. Therefore, a random-effects model was used to conduct a meta-analysis, showing that the therapeutic effect of ultrasound-guided interventional therapy on gynecologic diseases was significant [OR = 0.03, 95% CI (0.03, 0.03), P < .00001] (Fig. 3).

Figure 3.

Meta-analysis results for adverse reactions.

3.3.3. Recurrence rate.

Among the 12 included articles, 4 articles^{[12,17,18,21]} used the recurrence rate to assess the effect of USGT on related gynecologic diseases, and these articles specified the number of adverse reactions after treatment. Among the 4 included articles, 2 articles^[12,17] were controlled studies, and the other 2 articles^[18,21] were descriptive studies. The heterogeneity test for the controlled studies yielded I² = 0% and P = .60. Therefore, a fixed-effect model was used for meta-analysis, showing that after ultrasound guidance, no significant difference in the probability of recurrence was found between the experimental group and control group [OR = 1.04, 95% CI (0.59,1.83), P = .88] (Fig. 4). The heterogeneity test for descriptive studies yielded I² = 100% and P < .00001. Therefore, a random-effects model was used to conduct a meta-analysis, indicating that the therapeutic effect of USGT on gynecologic diseases was significant [OR = 0.13, 95% CI (0.13, 0.13), P < .00001] (Fig. 4).

Figure 4.

Meta-analysis results for recurrence rate.

3.3.4. Reintervention rate.

Among the 12 included articles, 3 articles^[12–23] used the re-intervention rate to evaluate the effect of USGT on related gynecologic diseases and specified the number of re-intervention treatments. The heterogeneity test of the studies yielded I² = 2% and P = .36. Therefore, a fixed-effect model was used for meta-analysis, revealing that the probability of re-intervention in the experimental group after ultrasound guidance was significantly higher compared with the control group [OR = 3.39, 95% CI (1.29,8.86), P = .01] (Fig. 5).

Figure 5.

Meta-analysis results for the reintervention rate.

4. Discussion

USGT refers to the ultrasound-guided puncturing of catheters and puncture needles into the body and various minimally invasive procedures. The method has become an important means of diagnosis and treatment in modern obstetrics and gynecology, which can guide the selection of puncture sites, accurately evaluate the effect of treatment, and provide an objective basis for further treatment.

Ovarian cysts are a common disease in women, especially those of childbearing age. If the symptoms are not promptly treated, subsequent fertility problems may occur. Using USGT to treat women with ovarian cysts can effectively avoid complications, such as pelvic adhesion, and prevent any impact on the reproductive function of nulliparous women. When treating patients with ovarian cysts using ultrasound, the cyst fluid needs to be extracted from the patient’s body first, usually by a puncture. After the extraction is completed, a sclerosing agent needs to be injected. Anhydrous ethanol is the most commonly used sclerosing agent, which destroys the cyst intima in the patient, inducing aseptic inflammation and finally reaching the cyst. Theoretically, the use of USGT in the treatment of ovarian cyst disease is not expected to cause complications affecting the reproductive function of female patients. Hsieh et al^[24] have demonstrated that ultrasound-guided interventional sclerotherapy for ovarian chocolate cysts is a practical treatment approach, and retaining a small amount of ethanol is more effective than pure ethanol irrigation. Koutlaki et al^[25] have introduced the experience of ultrasound-guided transvaginal ovarian cyst puncture and indicated that transvaginal ovarian cyst puncture is safe and reliable. Cho et al^[26] have suggested that repeatedly using high-intensity focused ultrasound to treat uterine fibroids is harmless and effective. USGT minimally invasive treatment of uterine fibroids is simple, safe, less traumatic, and effective. It is also associated with fewer complications and can preserve the integrity of the uterus. The appropriate minimally invasive treatment method should be selected based on the size of fibroids, particularly for patients with fertility requirements. Therefore, it has a good treatment prospect.

The functions of these treatment options in various clinical scenarios should be realized to perform appropriate consultation. Patients should be informed of potential benefits and harms and be actively involved in deciding on surgery. The treatment decision depends on the clinical symptoms, the desire of patients for subsequent fertility and pregnancy, as well as efficacy and the need for repeated interventions. In our systematic review, evidence for using interventional ultrasound is primarily available online in controlled and descriptive studies. In addition, evidence robustly assessing the comparative efficacy and safety of interventional ultrasound in these studies for the treatment of gynecologic disorders remains insufficient. However, randomized controlled trials are not always feasible in specific clinical settings. Therefore, descriptive studies are valuable for determining more accurate outcomes in clinical practice.

There were several limitations of this study as follows: we only included English literature reviews, and the influence of language factors could not be excluded; the literature included in this paper consisted of published literature reviews; unpublished related literature reviews, and reports, whereas other gray literature reviews were excluded, which might also affect the evaluation results. Therefore, high-quality clinical studies with large sample sizes and a long-term follow-up should be conducted to further evaluate the role of USGT in treating gynecologic diseases using advanced treatment protocols and equipment relative to other approaches.

Author contributions

Conceptualization: Fengsheng Zhou, Min Xuan.

Data curation: Chunyan Wu, Min Xuan.

Formal analysis: Chunyan Wu, Fengsheng Zhou, Jing Zhang, Min Xuan.

Funding acquisition: Fengsheng Zhou.

Project administration: Fengsheng Zhou, Min Xuan.

Resources: Chunyan Wu.

Software: Chunyan Wu, Jing Zhang, Min Xuan.

Supervision: Chunyan Wu.

Validation: Chunyan Wu, Fengsheng Zhou, Jing Zhang, Min Xuan.

Writing – original draft: Min Xuan.

Writing – review & editing: Fengsheng Zhou, Min Xuan.