Role of sclerotherapy in treatment of non-neoplastic ovarian cysts

Fluid-filled sacs that develop on or within an ovary are called ovarian cysts. These cysts are fairly typical. Most are benign and go away on their own . Symptoms of the peritoneum, abdominal distension and bleeding, an irregular menstrual cycle, abnormal vaginal bleeding, and dull bilateral pelvic pain can all be brought on by a ruptured cyst . There is still some debate surrounding how to treat women who have benign ovarian cysts. Medical treatment, ultrasound-guided (US-guided) aspiration, and laparoscopy are some of the treatment options . Sclerotherapy has been used to try to prevent ovarian cysts from coming back. Despite the simplicity and safety of US-guided aspiration, the recurrence rate is high, ranging from 28.5 to 100% . Polidocanol is a nonionic sclerosing surfactant composed of 5% ethanol and 95% hydroxypolyethoxydodecane. Polidocanol was developed for use as an anesthetic. Polidocanol is a liquid surfactant with the ability to kill endothelial cells . The majority of people believed that a local chemical irritation or inflammatory response was the cause of the sclerosing effect. Ethanol is responsible for cell dehydration, cytotoxic damage, and the production of mediators for inflammation and fibrosis . This study aimed to evaluate the role of sclerotherapy (injection of Polidocanol) in treatment of non-neoplastic ovarian cysts. Patients and methods A cohort study enrolled 52 patients who presented with non-neoplastic ovarian cysts based on transabdominal US and/or transvaginal US findings and tumor markers analysis conducted at Al-Azhar University Hospital at Assiut, Diagnostic and Interventional Radiology Department, Faculty of Medicine from September 2022 to January 2024. Aspiration was done using either percutaneous transabdominal US-guided technique or using transvaginal US-guided technique according to Preprocedure US images to determine the access route: as percutaneous transabdominal US was used with well-visible cyst and/or virgin patients. While with a visualized cyst located deep within the pelvic cavity, when transabdominal access was not technically feasible, obese and/or nonvirgin patients, transvaginal US was used. Inclusion criteria were diagnosed with non-neoplastic ovarian cysts, all patients from 15 to 48 years old, cyst size (from 5 to10 cm) and wall thickness(<5 mm), Negative tumor markers (cancer antigen 125 (CA125), carcinoembryonic antigen (CEA), CA19.9 and alpha fetoprotein), Persisted for more than 3 months, normal color Doppler blood flow analysis and Resistant to hormonal treatment combined oral contraceptive (COCs). A family history of ovarian cancer, Ultrasound Sonography (USG) features suggesting malignancy, papillary projections or mural nodule, cyst wall thickness greater than 5 mm, low Doppler indices, known allergy to sclerosing agent, and bleeding tendency were excluded. Ethical consideration The study was approved by Al-Azhar Assiut University and informed written consent was obtained from all participants. The study was conducted according to Helsinki standards, as revised in 2013. Clinical trials registration number: NCT06399744. US-guided aspiration (without cytological examination as all cases included were negative for tumor markers as well as US examination before the procedure which showed benign criteria included in the study while suspicious cases with US examination were excluded), was performed with electronically focused transducers ranging in frequency from 1 to 6 MHz for convex transducer on an US equipment model (LOGIQ XDclear, Siemens ACUSON X300 or LOGIQ C5 Premium) in Percutaneous transabdominal US technique. The standard practice for needle aspiration in our study used a 18-gouge Chiba biopsy needle (CHIBA IGNE, Egemen). The participant was put in a supine position, the puncture site was completely exposed, and Povidone Iodine 10% was used to sterilize it. Before the cysts were punctured transabdominal, local Lidocaine HCL 2% (from 3 to 6 ml) was injected transabdominally under USG into the wall of the cyst. The fluid’s granular appearance was recorded. However, much liquid as could reasonably be expected was suctioned, and 1 ampule of Polidocanol (Docavarico 20 mg/2 ml AMOUN) −95% hydroxypolyethoxydodecane and 5% ethanol-was infused into the cyst and left forever in situ, then, at that point, the catheter was eliminated and site of suction was cleaned. Before injecting, we left a small amount of fluid in each cyst to ensure that the needle would remain there after aspiration. Utilizing the same US model and the same needle was used, with electronically focused transducers ranging in frequency from 4 to 9 MHz for vaginal transducer on Transvaginal US Technique, the participants were positioned for a lithotomy. A clean condom was used to cover the transvaginal probe. Local Lidocaine HCL 2% (from 3 to 6 ml) was injected transvaginally under USG into the vaginal wall as well as the cyst wall. The 18-gauge Chiba biopsy needle was mounted onto the transducer after the vagina was sterilized with Povidone Iodine 10%. Until the contents of the cyst were completely removed, negative pressure was applied. 1 ampule of Polidocanol (Docavarico 20 mg/2 ml AMOUN)—95% hydroxypolyethoxydodecane and 5% ethanol—was injected into the cyst and left permanently in place after the macroscopic appearance of the fluid was recorded. The catheter and the vaginal transducer were then taken out. Follow-up after the procedure: the targeted organ was evaluated using US and Color Doppler to see if there were any signs of hemorrhage. The accumulation of fluid is another alarming sign. The patient would be admitted until their condition improved if any complications were discovered. Long-term follow-up: US and Color Doppler sonography was performed on all patients 1, 3, and 6 months after the procedure. In some cases of cyst persistence, a second aspiration and re-injection with Polidocanol were attempted (n=9), while the rest refused repeated aspiration and needed medical management or surgery. The main outcome measure was the disappearance of the cyst and the avoidance of surgery. The cyst was considered resolved if follow‑up revealed either no cystic lesion or only a follicle‑like cyst no more than 30 mm in diameter. Sample size calculation Sample size calculation was carried out using G*Power 3 software (China) Faul et al.. A calculated minimum sample of 48 women with recurrent or persisting non-neoplastic ovarian cysts underwent sclerotherapy injection of Polidocanol to detect an effect size of 0.25 in the rate of cyst recurrence, with an error probability of 0.05 and 80% power. Statistical analysis The computer received the data and used IBM SPSS version 20.0 to analyze them. (IBM Corp., Armonk, New York, US) numbers and percentages were used to describe qualitative data. The range (minimum and maximum), mean, standard deviation, median, and interquartile range were used to describe quantitative data. The obtained results were deemed significant at the 5% level.

The mean age of the studied cases was 29.44 (±9.34 SD) with a range (16–48) as shown in (Table 1). The mean international normalised ratio (INR) of the studied cases was 0.97 (±0.11 SD) with range (0.7–1.2), the mean prothrombin time was 12.6 (±1.19 SD) with range (10.5–14.7), the mean prothrombin concentration was 86.63 (±7.25 SD) with range (70–97), the mean CA19.9 was 24.28 (±6.28 SD) with range (12.1–36.3), the CEA was 2.28 (±3.51 SD) with range (0.04–19.4), the mean CA125 was 15.91 (±16.86 SD) with range (2–95.2) and the mean AFP was 6.77 (±2.74 SD) with range (1.9–10) as shown in (Table 2). According to US findings, there were 23 (44.2%) with left ovarian cyst and 29 (55.8%) with right ovarian cyst, the mean size of lesion was 6.22 (±1.51 SD) with a range (5–10), according to the type of lesion there were 46 (88.5%) with simple lesion, three (5.8%) with complicated lesion and three (5.8%) with hemorrhagic lesion, the mean ovarian volume was 9.95 (±1.86 SD) with range (6–16) and all the cases had normal Doppler color as shown in (Table 3). There was only one case with rupture as complication as shown in (Table 4). Table 1 Distribution of the studied cases according to age | Patients (n=52) | | |---|---| | Age | | | Range | 16–48 | | Mean ± SD | 29.44±9.34 | Table 2 Distribution of the studied cases according to laboratory data | Patients (n=52) | | |---|---| | INR | | | Range | 0.7–1.2 | | Mean ± SD. | 0.97±0.11 | | Prothrombin time (s) | | | Range | 10.5–14.7 | | Mean ± SD | 12.6±1.19 | | Prothrombin conc. (%) | | | Range | 70–97 | | Mean ± SD | 86.63±7.25 | | CA19.9 (U/ml) | | | Range | 12.1–36.3 | | Mean ± SD | 24.28±6.28 | | CEA (ng/ml) | | | Range. | 0.04–19.4 | | Mean ± SD. | 2.28±3.51 | | CA125 (U/ml) | | | Range | 2–95.2 | | Mean ± SD | 15.91±16.86 | | AFP (ng/ml) | | | Range. | 1.9–10 | | Mean ± SD | 6.77±2.74 | Table 3 Distribution of the studied cases according to ultrasound findings | Patients (n=52) | | |---|---| | US findings | N (%) | | Left ovarian cyst | 23 (44.2) | | Right ovarian cyst | 29 (55.8) | | Size of lesion in (cm) | | | Range | 5–10 | | Mean ± SD | 6.22±1.51 | | Type of lesion | N (%) | | Simple | 46 (88.5) | | Complicated | 3 (5.8) | | Hemorrhagic | 3 (5.8) | | Ovarian volume | | | Range | 6–16 | | Mean ± SD | 9.95±1.86 | | Color doppler | N (%) | | Normal | 52 (100.0) | Table 4 Distribution of the studied cases according to complications | Patients (n=52) | | |---|---| | Complications | N (%) | | Non | 51 (98.1) | | Rupture | 1 (1.9) | According to follow-up in the first month, there were 41 (78.8%) with no recurrence and 11 (21.2%) with cyst recurrence after excluding the 11 who had recurrence we were left with 41 in the third month among them there were 32 (78%) with no recurrence, six (14.6%) with cyst recurrence and three (7.3%) were pregnant and after excluding the six with recurrence and three pregnant women we were left with 32 in the sixth month all the patient did not have recurrent cyst as shown in (Table 5). Table 5 Distribution of the studied cases according to recurrent follow-up | Patients (n=52) | | |---|---| | 1st month | N (%) | | No | 41 (78.8) | | Recurrent cyst | 11 (21.2) | | 3rd month | (n=41) | | No | 32 (78.0) | | Recurrent cyst | 6 (14.6) | | Pregnant | 3 (7.3) | | 6th month | (n=32) | | No | 32 (100.0) | | Recurrent cyst | 0 | According to follow-up of cases who had re-injection with ethanol in the first month there were six (66.7%) with no recurrence and three (33.3%) with cyst recurrence after excluding the three who had recurrence, we were left with six in the third months all the cases had recurrent cyst as shown in (Table 6). Table 6 Distribution of the studied cases according to recurrent follow-up in the re-injected cases | Patients (n=9) | | |---|---| | 1st month | N (%) | | No | 6 (66.7) | | Recurrent cyst | 3 (33.3) | | 3rd month | (n=6) | | No | 0 | | Recurrent cyst | 6 (100.0) | According to the total recurrence of cases, there were 35 (67.3%) with resolved cysts, 11 (21.2%) with persistent cysts, and six (11.5%) with recurrent cysts as shown in (Table 7). Table 7 Distribution of the studied cases according to total recurrence | Subjects (n=52) | | |---|---| | N (%) | | | Resolved | 35 (67.3) | | Persistent | 11 (21.2) | | Recurrent | 6 (11.5) | There was high statistically significant relation between recurrence and cyst size as shown in (Table 8). Table 8 Relation between recurrence and cyst size | Resolved | Persistent and recurrent | t | P value | | |---|---|---|---|---| | Size of lesion | |||| | Range | 5–8 | 5–10 | 5.453 | <0.001* | | Mean ± SD | 5.59±0.69 | 7.53±1.88 | Case (1): A 27-year-old female para2 presented with irregular menses in the last 6 months. The results of the coagulation profile (INR 1.08, prothrombin time of 11.6 s, prothrombin concentration of 80%), CEA 1.2 ng/ml, CA19.9 level of 23.7, CA125 U/ML level of 20.1, AFP ng/ml level of 5.4. Abdominal US with Color Doppler revealed: (Fig. 1A) showed: right intraovarian anechoic cystic lesion, imperceptible wall with posterior acoustic enhancement measuring +/–5×5.5 cm (arrowheads). Fig. (1B) showed: no internal vascularity of the cyst (black arrow). Fig. (1C) showed: The needle inside the cyst during aspiration (line arrows). Fig. (1D) revealed: clear yellowish content of the cyst (bold arrow). Abdominal US followed percutaneous transabdominal aspiration-injection of Polidocanol as a sclerosing agent was done directly after the procedure: Fig. (1E) showed: The remnant of the cyst after aspiration-injection directly after the procedure (measured +/–34 × 9 mm) (short arrow) as well as right ovary after intervention (black arrows). Follow-up abdominal US and Color Doppler was done after the procedure: Figs (1F) and (G) showed: no right ovarian cysts as well as normal ovarian blood flow at 1 month follow-up. Figs (1H) and (I) showed: small right ovarian functional cyst with normal ovarian blood flow (measured 2.4×2.5 cm) at 3 months follow-up (white arrows). Figs (1J) and (K) showed: no right ovarian cysts with normal ovarian blood flow at 6 months follow-up (black arrows).

Ovarian cysts, fluid-filled sacs, are common, benign, and typically go away on their own. Ovarian cysts can be diverse, including, theca-lutein, follicular, polycystic, peritoneal inclusion, and hemorrhagic cysts . This study aimed to investigate the role of sclerotherapy (injection of Polidocanol (Docavarico) − (95% hydroxypolyethoxydodecane and 5% ethanol) in the treatment of recurrent or persisting non-neoplastic ovarian cysts. In this study, the mean age of the studied cases was 29.44 (±9.34 SD) with range (16–48). This agreed with Aflatoonian et al. who stated that the average age of the patients was 31.47 4.93 years. On the other hand, Han et al. reported that the participants ranged in age from 20 to 44 years, with a mean age of 32. In this study, we found that among the studied cases there were 15 (28.8%) virgin, six (11.5%) nullipara, one (1.9%) para 1, 10 (19.2%) para 2, six (11.5%) para 3 and 14 (26.9%) para 4 or more, and there were 20 (38.5%) complain of irregular menses, 11 (21.1%) complain of irregular pain and 35 (67.3%) complain of regular pain. This matched with García-Tejedor et al. who stated that cyst aspiration was very effective for the prompt resolution of symptoms in ten patients, six of whom were admitted with acute lower abdominal pain. Cyst aspiration has a significant advantage in this regard as a means of relieving acute pain. Additionally, it prevents symptomatic functional cysts that are intended to resolve on their own from necessitating an emergency operative procedure. Visus et al. 100% of patients were satisfied or very satisfied, 88.3% reported experiencing mild or moderate pain during the procedure, and 96.7% stated that they would undergo the procedure once more. In this study, the mean INR of the studied cases was 0.97 (±0.11 SD) with range (0.7–1.2), the mean prothrombin time was 12.6 (±1.19 SD) with range (10.5–14.7), the mean prothrombin concentration was 86.63 (±7.25 SD) with range (70–97), the mean CA19.9 was 24.28 (±6.28 SD) with range (12.1–36.3), the CEA was 2.28 (±3.51 SD) with range (0.04–19.4), the mean CA125 was 15.91 (±16.86 SD) with range (2–95.2) and the mean AFP was 6.77 (±2.74 SD) with range (1.9–10). All were within the normal range as any abnormality were excluded from this study. This was consistent with García-Tejedor et al. who discovered that the mean number of cysts was 14%, or 1.7 0.9, and the mean CA-125 level was 14%, or 51.7 54.3, before treatment. Hagras et al. stated that there was no difference between the two groups in either demographic information (age, gravidity, parity, history of abortion, and curettage) or tumor markers (transvaginal aspiration and tetracycline sclerotherapy versus only aspiration). In this study, we demonstrated that there were 23 (44.2%) with a left ovarian cyst and 29 (55.8%) with a right ovarian cysts, the mean size of ovarian cysts was 6.22 (±1.51 SD) with range (5–10), also there were 46 (88.5%) with simple cyst, 3 (5.8%) with complicated cyst and 3 (5.8%) with hemorrhagic cyst, the mean ovarian volume was 9.95 (±1.86 SD) with range (6–16) and all the cases had normal doppler color. This agreed with Hagras et al. who reported that the distribution of small and large cysts (‘transvaginal aspiration and tetracycline sclerotherapy’ versus ‘only aspiration’) and initial cyst sizes did not differ between the two groups. On contrary, Aflatoonian et al. reported a cyst size of 4.52 1.27 cm on average, which is slightly smaller than the one measured in this study. In this study, only 8 (15.4%) had previous surgical or laparoscopic intervention. Injection of sclerosing agent directly into the cystic cavity after aspiration, this minimally invasive procedure offers several advantages, including high efficacy rates, low complication rates, and minimal invasiveness. It also noted that sclerotherapy of ovarian cysts can affect on pregnancy rate and represents a good alternative way. This was in coordination with Visus et al. who demonstrated that adhesions or previous surgeries may prevent some patients from benefiting from operative laparoscopy. In addition, it has been hypothesized that a cystectomy might reduce folliculogenesis significantly. Okasha et al. the use of a sclerosing agent is associated with a lower rate of recurrence when compared with aspiration without sclerotherapy for the treatment of ovarian cysts. The success of this study’s decision to use sclerotherapy instead of aspiration to treat ovarian cysts was demonstrated by these results. In this study, we found that the most common content of cysts was clear content in 40 (76.9%), and the most common content color of the cysts was transparent in 24 (46.2%) and we had only one case with rupture cyst as a complication. In line with Okasha et al. when compared aspiration with the use of sclerosing agent to aspiration without sclerotherapy for the treatment of ovarian cysts, the use of a sclerosing agent is associated with a lower rate of recurrence. These results demonstrated that the decision made in this study to treat ovarian cysts with sclerotherapy rather than aspiration only was successful. In this study, the only major complication was a case of self-limiting hemoperitoneum, which was managed in the usual manner. Similarly, Han et al. stated that there were two patients with significantly lower abdominal tenderness after the procedure were admitted to the hospital for parenteral antibiotic treatment. This study showed that out of 52 women, cysts disappeared in 35 (67.3%) patients, cases and persistent or recurrent in 17 (32.7%) cases that needed repeated aspiration or medical management or surgery non had major problems. Followed-up cases who had re-injection 9 cases were all had recurrent cyst, (P<0.001). We can attribute recurrence here to long-standing of these cysts more than 6 months and its relative larger size (≥8 cm). Similarly, Visus et al. demonstrated that one of the drawbacks of simple aspiration is the high recurrence rate, which prevents cyst fluid from being treated at its source. Injecting sclerosing agents into the cyst to cause fusion of the cyst walls, which will reduce the likelihood of recurrence, is a plausible alternative strategy. Because it destroys the epithelial lining of the cyst walls, which is the source of the fluid, aspiration sclerotherapy eliminates the cavity of the cyst and prevents the fluid from reaccumulating. By increasing the volume of alcohol injected (from 50% of the aspirated volume to 75%. Okasha et al. were able to significantly reduce the rates of recurrence for large ovarian cysts with a volume between 100 and 300 ml and the amount of time this was left in place (from 5 to 10 to 20 min).

Sclerotherapy emerges as effective therapeutic option for the management of non-neoplastic ovarian cysts. Through the injection of sclerosing agents directly into the cystic cavity, this minimally invasive procedure offers several advantages.

Firstly, a larger sample size was better to provide strong conclusions. Secondly, patients were not easily convinced with the procedure. Recommendations Antral follicle count and serum anti-Müllerian hormone measurement before and after the procedure will be useful to see the correlation between ovarian reserve and sclerotherapy. Sclerotherapy will be helpful and of high value for cases with cyst size less than 8 cm not larger to diminish recurrence rates, as well as virgins to avoid unnecessary interventional methods and their complications (surgery or laparoscopy). Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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