INTRODUCTION

Recent years have brought a significant change in the approach to benign gynecological disease putting emphasis on the symptomatic profile and reproductive needs rather than radicality in lesion removal. Women postponing their reproductive programs to within the same time frame that coincides with the peak incidence of fibroids represents a complex challenge for the obstetricians and gynecologists of today.

Management of uterine fibroids in women needs to offer an extensive evaluation of numerous aspects including previous obstetric history, future reproductive desire and overall symptomatology (bleeding pattern and anemia, compression symptoms and pain-related manifestations).

Radiofrequency thermal ablation (RFA) is a minimally invasive technique for conservative treatment of symptomatic fibroids which represents a promising alternative to standard surgical myomectomy.

Its application in gynecology is being refined as regards to procedure protocol and patient selection recommendations. Data on efficacy are promising while reproducibility aspects and associated complications still lack standardization.¹

RFA generates thermal effects (60°C–80°C) causing apoptosis of tissue cells by thermal coagulation and formation of vascular thrombosis in the blood vessels supplying the fibroid, which causes ischemic necrosis and atrophy along with inactivation of the estrogen and progesterone receptors within the fibroid owing to the thermal effect resulting in prevention of hormonal-dependent tissue proliferation.²

Different access techniques are available, including percutaneous, laparoscopic, hysteroscopic and transcervical/transvaginal approaches.³ All the different access routes can be performed as a single surgical step or combined with each other when the position of the fibroids to be treated allow the use of the same electrode through different routes.⁴ 

The overall advantages of myolysis in respect to surgical resection include reduced morbidity (operating time, blood loss, and length of hospital stay), preservation of the endometrial cavity, real-time imaging guidance, and the feasibility of undertaking as an outpatient procedure.⁴

LAPAROSCOPIC RADIOFREQUENCY ABLATION (LRFA)

Laparoscopic radiofrequency ablation (LRFA) received US Food and Drug Administration (FDA) clearance in November 2012. Indications include treatment of intramural, subserosal, submucosal and transmural fibroids in symptomatic premenopausal women. It is not recommended for pedunculated fibroids with a stalk <50% of the total myoma diameter; in cases of pedunculated myomas with a stalk >50% of the total myoma diameter, treatment with LRFA relies upon the surgeon’s discretion.⁵ Also, patients with a history of pelvic or cervical malignancy, prior treatment of fibroids should be excluded from treatment.^{6,7,8,9,10,11} The ideal condition for treatment would be a fibroid volume <300 cm³ and a maximum diameter <6 cm.¹²

TRANSVAGINAL RADIOFREQUENCY ABLATION (TRFA)

Transvaginal radiofrequency ablation (TRFA) is a more recent technique for radiofrequency myolysis using a vaginal ultrasound guided approach (Figures 1–3). While several studies have demonstrated the safety and efficacy of myolysis through the laparoscopic route, there is less experience using the transvaginal approach,³ although it is considered a safe and fast procedure with a short recovery period. It is effective in dimensional reduction of fibroid volume and improvement of menorrhagia.^6,12,13,14 The procedure is effortless and intuitive for professionals who are familiar with ultrasound and/or IVF procedures, i.e., ovarian pick-up practice. A 16–17 gage-thick 30–35 cm-long electrode with fixed or flexible active tip exposure (Figure 4) is inserted through an ultrasound guider on the transvaginal probe used for the fibroid identification and treatment.

To date, five prospective studies have been published describing the application of TRFA in symptomatic uterine fibroids. Mean initial fibroid volume ranged from 18.3 cm³ (SD 9.5) to 304.6 cm³ (SD 229.1), while postoperative mean volume ranged from 11.34 cm³ (SD 8.94) to 79.1 cm³ (SD 81.7). The fibroid reduction rate was calculated to range from 60% to 83% in the 12-month period of follow up, except for one study in which follow up was 18 months.³

In a systematic review published by Arnreiter et al. in 2021, ten studies using the transcervical approach with the Sonata system showed a reduction in total fibroid volume of 63.2% and a reduction in perfused fibroid volume of 64.5% at 12-month follow up, accompanied by improvements in symptoms and quality of life. The reintervention rate varied from 0.7% to 11.8% at 12 months. Forty-seven per cent of the patients experienced mild adverse events such as dysmenorrhea, abnormal uterine bleeding, pelvic pain, urinary tract infections, fibroid expulsion/sloughing, nausea/vomiting, flu-like symptoms, and other nongynecological symptoms such as constipation. Only four adverse events requiring inpatient treatment occurred, including one case of deep vein thrombosis.¹⁵

TRFA is preferable to other minimally invasive techniques such as cryotherapy or high intensity focused ultrasound (HIFU), because of its reliability, lower cost and shorter operating time.¹⁶ It is also preferable to laparoscopic myomectomy due to reduced median blood loss (20 mL versus 35 mL), and the ability to treat a higher percentage of fibroids.³

Rey et al., conducted a prospective observational study and described a sample population of women (n = 205) with symptomatic FIGO type 2–3 uterine submucosal or intramural cavity-distorting fibroids. An optimal volume is considered to be ≤39 cm³ with an expected volume reduction of 80% and disappearance in half of the cases, advising against utilization of TRFA in fibroids of a volume larger than 500 cm³, considering the possibility of incomplete myolysis.³

The SAGE registry is an ongoing large study collecting data on transcervical procedures and will generate up to 2500 patient-years of outcome data along 5 years of follow up. Preliminary results from the first 160 treated patients suggest broad applicability and a favorable safety profile.¹⁷

PREOPERATIVE WORK UP CONSIDERATIONS

Accurate node description and 2D/3D ultrasound mapping is of utmost importance for patient selection, treatment planning and follow up reducing the risk of complications. Volume calculation applying the ellipsoid formula (V = π/6 × L × S × LR), i.e., volume = length × width × height × 0.52 as well as baseline hemoglobin is useful to estimate symptom improvement and treatment efficacy. Myolysis does not allow histological confirmation of the fibroid compared to other traditional techniques and the potential role of presurgical biopsy has been addressed. As limitations in terms of sensitivity and specificity to exclude focal malignant alterations are noted, pre-surgical fibroid biopsy should not be considered as a standard management able to exclude enrolment of fibroids of doubtful nature.^18,19 Treatment with RFA can also create challenges in the histological distinction of leiomyosarcoma and benign fibroid due to the presence of coagulative necrosis and increased mitotic index due to tissue regeneration after thermal treatment.²⁰ The preoperative work up in terms of identifying typical nodules eligible for treatment should be rigorous and restricted in order to not promote ablative treatment in cases of controversial ultrasound criteria in typical fibroid diagnosis as well as the patient’s clinical history indicating doubtful disease origin. In the literature, a case of misdiagnosis of leiomyosarcoma after thermal ablation has been reported,¹⁶ which stresses the critical aspect of careful patient selection.

TECHNIQUE EFFICACY OUTCOME

Radiofrequency ablation has been shown to offer targeted treatment of fibroids, with size reduction of fibroids, and improvement of symptoms and quality of life, while maintaining a safe profile with few complications and low reintervention rates.

Volume and diameter of the fibroids are significantly reduced by −49.00% and −24.35%, −50.52% and 31,87%, −90.20% and −55,70%, respectively, at 12-, 24- and 36-months post-intervention (p <0.001). After LRA, overall uterine volume reduction was 69.17 cm³ (95% CI 35.87–102.46) at 12 months.^14,19

Compared to uterine artery embolization and magnetic resonance image–guided HIFU, RFA is shown to have significantly greater reduction in mean fibroid volume.²¹

Reduction in volume corresponds with symptom reduction (Figures 5 and 6). Significant improvement in symptoms for all bleeding-related variables (total days of bleeding, days of heavy bleeding, subjective reduction in bleeding) at 2, 6 and 12 months of follow-up has been demonstrated with transvaginal RFA, which also achieved a mean relative reduction in fibroid volume of more than 72% to more than 80% at 12 months’ follow up, depending on the initial size of the lesions.¹⁸ Studies showed similar improvement in symptoms after myomectomy and RFA. Based on validated questionnaires, quality of life improved significantly up to 36 months after laparoscopic radiofrequency ablation therapy with a maximum improvement at 12 months of 41.64 (95% CI 38.94–44.34) in Health-Related Quality of Life questionnaire score (HRQL), a reduction of 39.37 (95% CI 34.70–44.04) in transformed symptom severity score (tSSS) and by a percentage change of UFS-QOL symptom severity scores to −71.80% after 3 years with vaginal RFA.^14,19,22

TRFA is normally performed in an outpatient setting and is associated with mild-moderate pain and limited use of analgesics (mean of 3.8 days after discharge).^3,18

In the first comparative study evaluating myomectomy and RF with the Sonata system (CHOICES study) by Brooks et al., all stratified results for procedure costs, resource utilization and perioperative patient outcomes favored TFA over myomectomy, including operating room time, length of stay, sub-procedure costs regarding anesthesia, laboratory, pathology, pharmacy and facility procedure-related costs.²³ Furthermore, Chudnoff et al., reported, in their prospective trial, a significant reduction in fibroid-related symptoms with no device-related adverse events and a low surgical reintervention rate through 12-month follow up using same approach.²²

Overall need for reintervention rate due to persistent metrorrhagia ranged from 4.39% to 16.3%, including hysteroscopic removal of free intracavitary fibroids (1.46%), hysterectomy, hysteroscopic myomectomy and endometrial ablation.^19,24

The low reintervention rate suggests that a single intervention could be sustainable¹⁴ and rates are comparable with ranges seen with myomectomy and UAE.²⁵

PROGNOSTIC FACTORS FOR TREATMENT SUCCESS

Current data suggest that RFA is a promising minimally invasive option for conservative fibroid management; however, not all patients are ideal candidates for the approach. Accurate preoperative evaluation is fundamental for reaching optimal myolysis, and standardization of patient selection criteria still have to be refined as well as recommendations regarding women with a future pregnancy desire, although, these patients may benefit the most from minimally invasive treatments. For instance, pedunculated fibroids (International Federation of Gynecology and Obstetrics FIGO type 7) should be excluded along with giant fibroids.²⁵

In a case series of 59 patients treated with transvaginal RFA, in patients older than 40 years a more rapid and greater fibroid volume reduction was observed, compared to younger women (77.6% versus 59.7%). This could hypothetically be related to age-related differences in histological composition of the fibroid and the different hormonal milieu. In addition, larger fibroids showed a larger final volume: every 1-mL increase in initial fibroid volume was associated with a 0.12-mL increase in final volume and fibroids larger than 36.5 mL before treatment showed a mean reduction in volume at 12 months’ follow up of 65% vs. 85.6% of smaller fibroids.¹⁸

However, RFA, regardless of the access route or the fibroid type or position, turned out to be effective in the long term when the major fibroid to be ablated is no larger than 5 cm in diameter: the mean diameter of the dominant fibroid in the patients who required reoperation resulted greater than that of the successes.¹⁹

In addition, the degree of fibroid vascularization could influence the myolysis result, while final volume did not significantly depend on the type of fibroid (intramural or submucosal).¹⁸

FERTILITY OUTCOME

Present data on pregnancy outcome after RFA treatment are scant, since RFA devices approved by the FDA are not yet endorsed for women with fertility desire and the original clinical trials excluded this category from their study population. However, more and more case reports and small-size prospective studies are showing promising results.

Polin et al., conducted a systematic review of the literature to summarize the available data on pregnancy outcome after laparoscopic or transcervical RFA of uterine fibroids. The literature selected consisted of ten publications, including two clinical trials for a total of 923 patients of whom 550 patients underwent laparoscopic RFA and the other 364 transcervical RFA. Fifty pregnancies were reported, of which 40 were after laparoscopic RFA and 10 after transcervical RFA. Among the 50 pregnancies, 88% were full-term pregnancies (n = 44), among which there were no reported cases of uterine rupture, uterine window, invasive placentation (i.e., placenta accreta), placenta abruption or fetal growth restriction.²⁵ To note, there was one case of uncomplicated placenta previa and one case of delayed postpartum hemorrhage which required blood transfusion due to vaginal expulsion of a large degenerated fibroid. The fibroid was disrupted at the time of uterine closure during cesarean section.⁵

The mean number of fibroids treated was between 1 and 3 and the size varied from 0.9 cm up to 12.5 cm. Average age at ablation was calculated at 37 years. Great variability was found in the interval time between RFA and pregnancy, which ranged from 3 to 33 months, with a mean value of 16 months.²⁵

Spontaneous abortion occurred in 12% of the cases (n = 6), a rate that is in the lower range of the risk considered for the general obstetric population (11–22%).²⁵ Several transcervical procedures, including hysteroscopic myomectomy, dilation and curettage, and endometrial ablation can cause intrauterine adhesion formation that could cause a detrimental effect on menstrual cycle, successful conception rate and spontaneous abortion. Indeed, acquired uterine malformations, including adhesions or Asherman’s syndrome, have been found to be prevalent in women that suffered pregnancy loss, although the clinical relevance is unclear.²⁶ In the context of the OPEN clinical trial on transcervical uterine fibroid ablation with the Sonata system©, Bongers et al. compared baseline and post-ablation hysteroscopy in 37 patients and determined that RFA did not promote intrauterine adhesiogenesis, since RF energy is targeted to fibroids beneath the endometrium without involving significant areas of endometrium.²⁷

More than 50% of the women had uncomplicated vaginal births with a smaller proportion of patients having a cesarean delivery, even though the indication was not always specified. Standard myomectomy has always given rise to concerns about the risk for uterine rupture due to damage to uterine wall integrity. In the current literature, the overall uterine rupture rate after myomectomy during labor is 0.47% and 1.52% before labor.⁹ Uterine rupture is a rare, but significant, complication during pregnancy and labor and accurate risk rate after RFA is still to be defined due to the scarce population studied in literature.

Limitations to these studies relate to the small study population, the lack of standardized patient selection and potential bias due to limited information regarding the history of infertility and attempts to conceive of these women in most publications. Christoffel et al. in their 36 pregnancies after RFA report in which five women conceived more than once and four underwent assisted reproductive technology (ART).¹⁰

PROCEDURE-RELATED COMPLICATIONS

TRFA is reported to be associated with very low intra-operative and peri-operative, including 30-day readmission rates.²³ Nonspecific procedure-related are anesthesiologic complications and procedure related complications are estimated to be 1.78% and include infection (3.2%)^4,14 intestinal heat injury requiring surgery (1.69%)¹⁸ and vaginal discharge (15%) were also found. Pelvic organ thermal injury including intestine and bladder is a rare but serious complication: ablative energy spread to surrounding intestinal loops, especially after laparoscopic RFA, can lead to rectouterine fistula, intestinal necrosis, and need for demolitive surgery.²⁸

SUMMARY

Minimally invasive approaches in the management of common gynecological pathologies such as uterine fibroids are of utmost importance to offer fertility preservation and cost-effective solutions. Transvaginal radiofrequency ablation in a day-surgery setting offers an efficient volume reduction approach with improvement of fibroid-related symptoms in patients undergoing accurate preoperative selection. Radiofrequency ablation represents a valuable tool in tailoring treatment solutions along with conventional surgical and non-surgical techniques in managing fibroid-related symptoms.

PRACTICE RECOMENDATIONS