Changes in symptoms and fibroid characteristics in women treated with ultrasound-guided high intensity focused ultrasound (USgHIFU) at Chris Hani Baragwanath Academic Hospital.

This report was originally submitted to the University of the Witwatersrand as an undergraduate research report. Raphaela Setzen, Claire O'Donoghue, Nico Van Dyk, Ayanda Sengane, Nomvuyo Manyatsi and Shalya Sarubdeo contributed to the development of the protocol, assisted with data collection, and contributed to the research report. Raphaela Setzen wrote the first draft of the research report for submission to the journal. Raymond Setzen developed the original database, introduced the topic and did almost all the treatments. Yasmin Adam and Raymond Setzen supervised the project. Yasmin Adam revised the research report and did the analysis of the data.

The study was self‐funded.

There were 345 women who were seen at the HIFU treatment center between November 2015 and December 2018. A total of 14 (4.06%) were untreated (6 due to treatment abandonment) and eight (2.32%) had adenomyosis. There were therefore 331 women who were part of this study. The mean age of the patients was 34.95 years (SD ± 5.43; range: 18–49). The median height was 162 cm (IQR: 158–167; range: 148–180), the median weight was 68 kg (IQR: 58–76; range: 38–157) and the median BMI was 25.30 (IQR: 22.31–29.05; range: 13.46–56.29). The median parity was 0 (IQR: 0–1; range: 0–6) and the median gravidity was 1 (IQR: 0–2; range: 0–6). The median abdominal thickness was 1.8 cm (IQR: 1.3–2.8; range: 0.2–6.5). One of the patients had an abdominal thickness of ≥6.0 cm. However, at the clinician's discretion, she was treated due to the position of the fibroids (anterior and easily observable) and lower risk for side effects. There were 199 patients (61.12%) who had more than one fibroid and 132 (39.88%) who had a single fibroid. The median number of fibroids was 2 (IQR: 1–3; range: 1–8); 132 (39.88%) had a single fibroid. There were 730 fibroids diagnosed in 338 patients. The mean size of the fibroids measured on MRI was 172.91 cm 3 (SD ± 54.89) and the median was 53.06 cm 3 (IQR: 22.01–174.31) ( n  = 354) The mean uterine size measured on MRI was 859.68 cm 3 (SD ± 14.26) and the median size was 680.15 cm 3 (IQR: 373.26–986.54). In terms of the fibroid position in the uterus, there were a total of 460 (63.10%) fibroids that were intramural, 181 (24.83%) subserosal and 88 (12.07%) that were submucosal. There were 499 (68.28%) fibroids in the anterior wall of the uterus, 232 (31.72%) in the posterior wall of the uterus. The baseline characteristics are summarized in Table  1 . The presenting symptoms were dysmenorrhea in 281/329 (85.41%), menorrhagia in 219/325 (67.38%) and infertility in 166/326 (50.92%). The symptoms at presentation are shown in Table  2 . Patients and characteristics of fibroids. Note : BMI, calculated as weight in kilograms divided by the square of height in meters. Abbreviations: BMI, body mass index; IQR, interquartile range; MRI, magnetic resonance imaging; SD, standard deviation. Presenting symptoms. Note : n is the number of patients where the data was collected, some patients had more than one symptom. Abbreviations: HIFU, high intensity focused ultrasound. The MRI intensity of the fibroids was hypointense in 675 (91.16%), 38 (5.16%) were hyperintense and 3.67% (28 fibroids) were isointense. The intensity of fibroids is described in relation to the surrounding myometrium, and it affects the likelihood of treatment success. Hypointense fibroids are most effectively treated followed by isointense with hyperintense fibroids being the most difficult to treat. However, this does not exclude any patients from treatment. A total of 86% of women ( n  = 283) had follow‐up data. The median follow‐up time was 28 weeks (IQR: 16–52; range: 4–156). The change in symptoms before and after treatment is shown in Table  3 . Given the relatively short follow‐up period infertility was not evaluated post treatment. Symptoms in 283 patients before and after USgHIFU. Abbreviation: USgHIFU, ultrasound‐guided high intensity focused ultrasound. McNemar's χ 2 test. There were 50 women who had a repeat MRI after HIFU treatment (as close to 6 months as possible after treatment). Table  4 shows the mean difference of the fibroid size before and after treatment as measured on the MRI. The size of the fibroid(s) before and after USgHIFU treatment. Size of the fibroid N  = 129 Abbreviations: IQR, interquartile range; USgHIFU, ultrasound‐guided high intensity focused ultrasound. Paired t ‐test. Wilcoxon signed‐rank test: n  = number of fibroids. This mean difference in size of the fibroid was calculated in 50 women who had 129 fibroids.

This is the first study using USgHIFU in South Africa and Africa looking at outcomes after treatment. In line with prior literature and clinical experience, in this study dysmenorrhea was the most frequent presenting symptom in women followed by menorrhagia. 11 There was a reduction of dysmenorrhea and menorrhagia in 30% and 25% of women, respectively. However, we did not quantify the severity of symptoms at follow‐up. A study in Finland with 175 women who were treated with MR‐HIFU showed a mean symptom severity score of 56 (IQR: 44–69) at baseline to 25 (IQR: 16–38) at 12 months. 12 HIFU has been shown to be the most effective non‐invasive treatment for uterine fibroids. 13 , 14 In studies where HIFU was compared to abdominal myomectomy, HIFU has demonstrated an improved quality of life in patients in the short term. 5 Other procedures have also been shown to reduce symptoms. First, with regards to uterine artery embolization, clinical symptoms (menorrhagia, dysmenorrhoea and uterine bulk symptoms) improved by 78%–90% after the procedure. 15 Lastly, both laparoscopic and abdominal myomectomy showed an 80% success rate in the relief of symptoms. 16 A study conducted in Taiwan showed a significant 40.2% reduction in fibroid size on MRI imaging post‐HIFU treatment. 17 Our study shows a 30% reduction of the mean volume. Another retrospective study reported a reduction in the size of fibroids in approximately 78% of patients who followed up after 70.1 (IQR: 58–88) months as shown on post‐treatment MRI. 18 HIFU is therefore an option in the management of women with symptomatic fibroids. However, the effect is only modest in this South African population as compared to other settings and other treatment options. CHBAH is the only hospital in South Africa offering HIFU for uterine fibroids. Given the short follow‐up period we did not evaluate infertility. A systematic review on reproductive outcomes after HIFU showed pregnancy rates between 7% and 36%. 19 The other methods of treatment of fibroids at CHBAH is myomectomy, and uterine artery embolization and hysterectomy. This study may not be generalizable to all women with fibroids as only women who met the clinical criteria for treatment with HIFU at our institution were included. MRI measurement of fibroids post‐treatment was not available for all women and symptom severity was not measured objectively. Fibroids were measured using MRI. Although the reduction in the volume was less than previously reported, the improvement in menorrhagia and dysmenorrhea is important. There is now local evidence that HIFU at CHBAH is a treatment that can be included in the armamentarium in the treatment of fibroids in this community.

This is the first study of HIFU to be conducted in a South African population reporting outcomes after treatment. HIFU has not only shown to be a reasonably beneficial alternative in the treatment of uterine fibroids but has also shown clinical benefit. Finally, it is recommended that HIFU for the treatment of fibroids be considered as an option, and it is recommended that future long term follow‐up studies be conducted.

Uterine fibroids are the most common benign tumor of the reproductive tract with an incidence of 20%–40% in women during their reproductive years. 1 , 2 The highest burden of this condition affects black women, occurring at rates 3–4 times greater as compared to other races. 3 A South African study on pathology specimens obtained at hysterectomy in a single institution showed that the proportion of fibroids over a 6‐month period was 64.6%. 4 Symptoms of fibroids include menorrhagia, dysmenorrhea, pelvic pain, Infertility, urinary and bowel symptoms. Treatments range from medical management, surgical procedures including hysterectomy and myomectomy and non‐invasive techniques such as uterine artery embolization and high intensity focused ultrasound (HIFU). The choice of treatment method needs to be tailored to a woman's individual characteristics. Several key considerations must be taken into account including the need for anesthesia, the risk of blood loss, the expected hospital stay, the likelihood of recurrence and the implications of fertility. 5 , 6 , 7 , 8 HIFU is a thermal ablation technique using ultrasound beams that are focused onto a single point and converted to heat; it penetrates the tissue and targets the tumor. 9 HIFU can be performed under the guidance of ultrasound (USgHIFU) or magnetic resonance imaging (MRI) (MRgHIFU). Ultrasound allows monitoring in real‐time grayscale changes which indicate the tumor's response to the HIFU treatment. A meta‐analysis including 4450 women comparing HIFU with surgical treatment found an improved quality of life at 6 and 12 months in the HIFU group. 5 Patients treated with HIFU had fewer post‐procedure complications, less pain and experienced a faster recovery; a shorter hospital stay. Medical treatments such as gonadotropin releasing hormone antagonists and selective progesterone receptor modulators are only used for short‐term therapy because of the significant risks with long‐term therapy, or lack of evidence regarding the benefits. USgHIFU was introduced at Chis Hani Baragwanath Academic Hospital (CHBAH) and South Africa (SA) in 2015. The present study was performed to evaluate women who were treated with HIFU. The objectives were to describe patient characteristics and symptoms, fibroid characteristics, and the impact of USgHIFU on symptoms and fibroid size.

The authors have no conflict of interest to declare.

This study was a single center (CHBAH, Soweto) retrospective study using data in women treated between November 2015 and December 2018. Soweto is a suburb in the South of Johannesburg which serves mostly Black women and women of a low socioeconomic status. Initially only women of reproductive age were treated, but as the success of treatment was noted older women were offered treatment. The fibroids were mapped using MRI in all women prior to treatment. USgHIFU was only offered to women who had general good health, had a hemoglobin count of ≥8 g/dL (this was not an absolute contraindication, it was the standard of care adopted in this unit), abdominal wall thickness ≤6 cm, uterine size ≤20 weeks, fibroids visible on ultrasound (US) (≥2 cm), had a normal cervical smear, and no intrauterine device present. The use of HIFU in women with a high body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) (>30) and with abdominal scars were individualized according to abdominal wall thickness and visibility of the fibroid. Fibroids that were within 0.5 cm from the endometrium (especially in women desiring fertility) were not treated. However, patients with symptoms related to submucosal fibroids who did not desire fertility were offered USgHIFU if they accepted the risk after being extensively counseled that the procedure could result in Ashermans syndrome. The procedure was performed under conscious sedation and women had to be able to lie prone for 2 h or longer without moving. The primary characteristic of conscious sedation is that the patient remains awake and maintains the ability to respond purposefully and can communicate with the doctor about pain. The procedure was carried out in the HIFU unit which is situated in the Department of Radiology. The amount of energy used was dependent on the number, size and vascularity of fibroids. The greater the number and size as well as the increased vascularity of the fibroid(s), the greater the amount of energy used. Energy used can vary anywhere between 20 000 to 40 000 J for smaller fibroids and more than 100 000 J for larger fibroids. Complications that occur during the HIFU procedure include abdominal pain, burning sensation on the skin surface as well as nerve pain down the legs. Since the patient was awake, and was warned beforehand of such complications, the patient was able to inform the treating doctor of such burning sensation and this was managed by stopping the high‐frequency ultrasound waves and decreasing the amount of energy being delivered, as well as increasing the level of the water inside the transducer dish to cool the skin. Should the patient experience nerve pain down the legs during the treatment, the patient is given dexamethasone 8 mg immediately (stat) and the amount of energy being delivered is also decreased. The data analyzed for this study was extracted from the HIFU clinical database (maintained by the Department of Gynecology) and from medical files and then exported to an Excel spreadsheet for data cleaning and then exported to Stata14.2 (StataCorp, 4905 Lakeway Drive, College Station, Texas, USA) for statistical analysis. The following data were retrieved for this study; demographic information (age, parity, gravidity, weight, height); symptoms before and after the procedure (dysmenorrhea, menorrhagia, infertility), details of the fibroid (size, number, position, location, MRI intensity [hypoechoic, isoechoic, hyperechoic]). Weinreb 10 defined diagnostic criteria for a leiomyoma to include a uterine mass that is predominantly hypointense compared to the myometrium on T2W imaging and predominantly hypointense on T1W imaging. Infertility was by self‐report. The severity of dysmenorrhea or menorrhagia was not assessed. The fibroid size was calculated based on the MRI scan using a caliber measurement tool on PACS (South Africa's Public Hospital imaging system). Categorical variables are described using frequencies and percentages. Continuous variables are described using means (±standard deviation [SD]), medians (interquartile range [IQR]) or both. Comparisons were made in 283 women who had a follow‐up visit. A comparison in fibroid size was made in 50 women who had an MRI post treatment. The unit stopped performing MRI's post treatment due to resource constraints. Follow‐up evaluation was performed using ultrasound. Comparisons of categorical variables were made using a McNemar's chi2 and continuous variables using either a paired t ‐test or Wilcoxon sign rank test. Permission was obtained from the CEO of CHBAH and the gate keeper of the database (Dr R Setzen). No individual consent was obtained as the data used was from a clinical database and patient files in the unit. Ethics clearance for this study was obtained by the Human Research Ethics Committee (University of the Witwatersrand) (certificate no: M190903).