The effectiveness of microwave endometrial ablation combined with hysteroscopic transcervical resection in treating submucous uterine myomas: A retrospective study

Submucous uterine myomas can be effectively and safely treated using microwave endometrial ablation (MEA). However, recurrence is common and requires additional treatment. This study investigated the ecacy of MEA combined with transcervical resection (TCR). Methods This retrospective study included 32 women who underwent MEA in addition to TCR for submucous uterine myomas at the International University of Medicine and Welfare Hospital between January 2016 and June 2020. All patients were followed up for ≥ 6 months after the procedure.


Results
The 32 women had a mean age of 45.2 ± 4.3 years. The myomas had a mean major diameter of 26.3 ± 12.3 mm and a protrusion degree of 51.3 ± 11.3%. The patients reported very severe hypermenorrhea/dysmenorrhea (10/10 points on the visual analogue scale) before the procedure. After the procedure, the hypermenorrhea scores decreased to 1.2 ± 1.3 and 0.9 ± 1.3 after 3 and 6 months, respectively (both p < 0.001). The dysmenorrhea scores also decreased to 1.3 ± 1.8 and 1.3 ± 1.8 after 3 and 6 months, respectively (both p < 0.001). Circulating hemoglobin concentrations improved signi cantly from 8.7 ± 1.9 g/dL to 13.5 ± 1.1 g/dL (p < 0.001). The mean follow-up duration was 33.8 ± 16.8 months and 10 women (31.3%) developed amenorrhea during this period, although none experienced recurrence of hypermenorrhea. No surgical complications were observed. The patients reported being highly satis ed with the ability of the combined treatment to relieve hypermenorrhea (mean visual analogue scale score: 9.5 ± 0.8).

Conclusion
Reducing the size of uterine broids via a combination of MEA and TCR can safely and effectively treat hypermenorrhea in patients with submucous myomas. Furthermore, the procedure's effectiveness is complemented by the patients' high satisfaction level.

Plain English Summary
The combination of MEA and TCR may safely, reliably, and effectively reduce the size of uterine broids and, thus, treat hypermenorrhea caused by submucous myomas.

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Hypermenorrhea is characterized by excessive menstrual bleeding that can cause severe anemia and interfere with everyday life. This condition can restrict women's social activities and decrease their quality of life. Microwave endometrial ablation (MEA) using a 2.45-GHz energy source, is a minimally invasive alternative to conventional hysterectomy for treating hypermenorrhea that is resistant to conservative treatment, triggered by systemic disease or medications, or caused by uterine myomas and brosis. 1,2 The popularity of MEA continues to increase worldwide, including in Japan where it has been covered by the national health insurance program since April 2012. This procedure has been performed at the International School of Medicine and Welfare Hospital since January 2016 and a previous report has demonstrated that it is reliable and effective in treating hypermenorrhea-induced anemia. 3 Although MEA can safely and effectively treat submucous myomas, some patients may still experience recurrent hypermenorrhea after the procedure and may require additional treatment. 4 Therefore, this study evaluated whether a combination of MEA and transcervical resection (TCR) was effective in treating submucous uterine myomas by reducing the size of uterine broids in patients with hypermenorrhea, thereby decreasing the possibility of recurrence and additional treatment.

Study design
The retrospective study protocol was approved by the ethics committee of the International University of Health and Welfare Hospital (20-B-399, date: May 7, 2020). All the patients provided written informed consent prior to the procedure. Patients were considered eligible if they underwent a MEA in addition to TCR for submucous uterine myomas after a primary complaint of hypermenorrhea between January 2016 and June 2020. All the patients were followed up for ≥ 6 months, and their medical records were reviewed to evaluate their outcomes.

Procedures
All the participants underwent cervical and endometrial cytological evaluations, as well as histological evaluations, if necessary, to exclude cases of uterine malignancies. In addition, magnetic resonance imaging and hysteroscopy were performed to evaluate the size and location of the myomas, as well as the degree of protrusion into the uterine cavity. Cervical dilatation was performed on the day before surgery using a cervical dilator (Lamicel; Japan Medtronic Co. Ltd., Tokyo, Japan).
The procedure was initiated under general anesthesia in the lithotomy position. The TCR procedure was performed before the MEA using a hystero-resectoscope (26-Fr outer sheath; Olympus Corp.), and Dsorbitol (3%) was used as the irrigation solution. Resected tissue specimens underwent histopathological examinations in all the cases. The MEA was then performed under transabdominal ultrasound guidance using the Microtaze AFM-712 unit (Alfresa Pharma Corp., Osaka) and a Sounding Applicator (CSA-40CBL-1006200C; Alfresa Pharma Corp.) (Fig. 1). The 2.45 GHz microwave Microtaze device was set to an output power of 70 W for 50-second cycles according to the guidelines. 5 Prior to terminating the MEA, the uterine cavity was evaluated using a hysteroscope to con rm that ablative necrosis at the endometrium did not extend to the internal ori ce or endocervix.

Study variables
The variables included operation time, number of ablation cycles, length of hospital stay, and visual analog scale (VAS) scores for hypermenorrhea, dysmenorrhea, and treatment satisfaction at 3 and 6 months after the procedure. In addition, we evaluated the postoperative incidence of amenorrhea, changes in hemoglobin (Hb) concentrations, and MEA-related complications.

Statistical analysis
Numerical data were reported as mean ± standard deviation (range). Statistical analysis consisted of single-factor ANOVA and parametric multiple comparisons. P values < 0.05 were considered statistically signi cant.

Results
A total of 34 women underwent a combination of MEA and TCR during the study period. Two patients were excluded from the study as their histopathological tests identi ed uterine malignancies (uterine sarcoma and endometrial cancer). The patients' characteristics are shown in Table 1. The 32 eligible women (6 nulliparous, 26 multiparous) had a mean age of 45.2 ± 4.3 years (range: 36-52 years). The cases included 10 cases of single myoma (only submucosal broids) and 22 cases of multiple myomas (submucosal and intramuscular broids) with a mean major axis diameter of 26.3 ± 12.3 mm and a mean protrusion degree of 51.3 ± 11.3%. According to the FIGO classi cation of submucosal broids, 6 cases presented with Type 1 and 26 cases presented with Type 2 broids. Multiple uterine broids (case) 22 The mean procedure duration was 45.5 ± 21.0 min (range: 19-110 min) and involved 7.0 ± 1.3 ablation cycles (range: 5-11 cycles). The mean postoperative hospital stay was 2.5 ± 0.5 days (range: 2-3 days).
The patients reported being highly satis ed with the procedure's ability to relieve hypermenorrhea, based on a mean VAS score of 9.5 ± 0.8 (range: 7-10) for satisfaction. The mean follow-up duration was 33.8 ± 16.8 months (range: 6-60 months). During follow-up, amenorrhea was reported by 10 patients (31.3%), and there were no instances of hypermenorrhea recurrence.

Discussion
Previous studies have indicated that MEA is an alternative to hysterectomy for patients requiring treatment for hypermenorrhea caused by submucous myomas. [1][2][3] This procedure has gained popularity in Japan, where it has been covered by the national health insurance program since 2012. Although MEA can safely and effectively treat submucous myomas, some patients may experience recurrent hypermenorrhea after the procedure and require additional treatment. This is believed to be caused by endometrial regeneration over time as the uterine cavity expands because of post-procedural broid growth. The present study evaluated the e cacy and safety of the combination of MEA and TCR under hysteroscopic guidance for women with submucous myomas. The patients experienced dramatic improvements in their hypermenorrhea symptoms and a signi cant increase in their circulating Hb concentrations. Furthermore, none of the women experienced recurrence of hypermenorrhea during the follow-up period.
Submucous myomas deform the uterine cavity, which can complicate the endometrial ablation process, depending on the shape of the microwave applicator. A resectoscope can be used for pre-ablation excision to improve the outcomes of MEA by smoothing the irregular inner surface, although it is important to be aware of potential issues regarding the scope of broid resection during this step. Problems are unlikely in patients who have a su ciently thick residual myometrium, even if the submucous myoma is completely removed, although excessive thinning is possible if complete myoma resection is attempted. Thus, the Japanese clinical practice guidelines indicate that MEA requires a myometrial thickness of ≥ 10 mm, which is intended to prevent damage to the surrounding organs. 5 Therefore, the scope of the TCR must be limited to partial resection before MEA if there is a risk of excessively thinning the uterine musculature. We reviewed the patients' TCR procedures and noted that only 6 patients underwent partial resection, although these patients experienced no recurrence and reported the same improvements in their clinical symptoms (vs. patients who underwent complete resection). The e cacy of the combined procedures can be attributed to the reduction in the broid mass and the use of a hysteroscope after the MEA to evaluate the uterine cavity and perform cauterization for sites with inadequate ablation.
The levonorgestrel-releasing intrauterine system (LNG-IUS) is another minimally invasive treatment for hypermenorrhea. This system provides promising outcomes, based on a > 50% reduction in menstrual ow (vs. the preoperative volume) experienced by 84.8% of patients and amenorrhea only occurring in approximately 20% of patients. 6 Based on our ndings, the MEA procedure appears to be more effective than the LNG-IUS, although a direct comparison is precluded because we only used subjective VAS ratings to evaluate menstrual ow. Nevertheless, from a long-term perspective, the effects of MEA may be more stable, as only 21% of patients who undergo MEA require another treatment for recurrent hypermenorrhea, while re-treatment is required for 42% of patients who receive the LNG-IUS. 6,7 Furthermore, the LNG-IUS could potentially slip out of place in a uterine cavity that has been deformed by the presence of submucous myomas. Therefore, we suggest that the combination MEA and TCR is a more effective treatment option for hypermenorrhea caused by submucous uterine myomas.
The concurrent use of a resectoscope with MEA permits a histopathological characterization of the lesion, which is not possible if MEA is performed alone. We have also previously reported that abnormal ndings were observed in endometrial specimens that were collected via endometrial total curettage during MEA, despite these patients having initially negative results for uterine malignancy from cytodiagnostic and histological screening before the MEA. 8 The present study also identi ed 2 patients with uterine malignancy, which was con rmed based on the histopathological ndings from specimens that were excised during the combination of TCR and MEA, despite the preoperative diagnosis being hypermenorrhea caused by submucous uterine myoma. Similarly, histopathological examinations of the TCR specimens can be useful for identifying uterine malignancies.
It is important to consider the safety of MEA, as complications include heat injury to the pelvic organs, uid retention in the uterus (because of cervical stenosis or the ablated endometrium), hematometra, pelvic in ammation (e.g., endometritis because of ascending infection), and pyometra. 9 However, we did not detect any of these complications, which may be related to the use of a resectoscope to evaluate the endometrial lining immediately after MEA. This step allowed for the maximum removal of the necrotic tissue left over by ablation, and we believe that it can improve the safety of MEA by reducing the rate of complications.
Although MEA is not indicated for treating dysmenorrhea and was not originally expected to alleviate its symptoms, some studies demonstrate its effectiveness in treating this condition. 10,11 Our patients reported improvements in dysmenorrhea as soon as their rst menses after MEA. We speculate that this was a secondary effect of improvements in hypermenorrhea, as reductions in menstrual volume were accompanied by less severe dysmenorrhea. Thus, MEA might be effective for reducing dysmenorrhea that is associated with hypermenorrhea caused by uterine myomas.
Our patients were highly satis ed with the MEA, based on an average VAS score of 9.5 ± 0.89 out of 10 points. Furthermore, most patients continued menstruating, although amenorrhea was reported by 10 patients (31.3%). Thus, we reckon that women with hypermenorrhea may desire a reduction, but not necessarily complete elimination, of menstrual ow while preserving their uterine function. The safety and e cacy of MEA in combination with TCR may also contribute to the patients' satisfaction.
Further studies are needed to consider various issues related to whether a combination of MEA and TCR can effectively treat hypermenorrhea secondary to uterine myomas. For example, hypermenorrhea outcomes should be considered in cases where the broids do not protrude into the uterine cavity. Furthermore, long-term follow-up is needed to clarify the hypermenorrhea recurrence rate and time to recurrence. Moreover, screening criteria are needed to identify women who are especially susceptible to hypermenorrhea recurrence. Finally, these studies could also consider novel ablation techniques.
In summary, the combination of MEA and TCR may safely and effectively reduce the size of uterine broids and, thus, treat hypermenorrhea caused by submucous myomas.

Figure 2
Changes in the visual analog scale score for hypermenorrhea after microwave endometrial ablation (MEA). Values are expressed as the mean and standard deviation (error bars). * P <0.01 relative to the result before surgery.
Page 12/13 Figure 3 Changes in the visual analog scale score for dysmenorrhea after microwave endometrial ablation (MEA).
Values are expressed as the mean and standard deviation (error bars). * P <0.01 relative to the result before surgery.

Figure 4
Comparing blood hemoglobin (Hb) concentrations before and after microwave endometrial ablation (MEA).

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