Applicability of ultrasound-guided puncture and laparoscopic cystectomy for ovarian endometriosis cyst: a non-randomized trial

The present prospective study was a non-randomized trial conducted in Wuxi Maternity and Child Health Care Hospital (Wuxi, China). Patients were recruited from the gynecology department from March 2021 to November 2023 and followed up for 6 months after treatment. The study was approved by the Medical Ethical Committee of Wuxi Maternity and Child Health Care Hospital (Approval No. 2023–06–0421–11). All participants were given a detailed account of the study's purpose, methodology, and potential risks before they provided informed written consent. This study was registered on the Medical Research Registration and Filing Information System ( www.medicalresearch.org.cn ) and did not have a clinical registration number. The study was conducted following the CONSORT checklist, and the specific trial protocol is shown in Fig.  1 . Fig. 1 Flow diagram Flow diagram Women aged from 18 to 46 years diagnosed with endometriosis were included (ovarian cysts detected by ultrasound). Participants were measured with VAS scores, cyst numbers, cyst volume, AMH, and CA-125 before treatment. Patients with VAS ≤ 3 and mild clinical symptoms were allocated to the puncture group and underwent UGP intervention, while those with VAS scores ≥ 4 and severe clinical symptoms were allocated to the surgery group and underwent LC. UGP intervention: Under ultrasound guidance, an 18-gauge puncture needle was inserted into the cyst cavity. After the cystic fluid was aspirated, absolute ethanol (20–30% of the aspirated fluid volume) was injected into the cyst cavity. The sclerosing agent was retained for approximately 5–10 min before evacuating the ethanol. Successful cyst aspiration was defined by the absence of apparent residual fluid within the cyst cavity and the absence of significant discomfort in the patient. These procedural details have been comprehensively documented in the Methods section to ensure reproducibility and standardization of the study protocol. LC intervention: After anesthesia, a small incision was made and carbon dioxide gas was injected into the abdominal cavity to expand the abdominal cavity and provide operating space for the operation. The laparoscope and surgical instruments were inserted into the abdomen from other incisions. Then, an electric knife or ultrasonic knife was used to peel away the cyst from the ovary. The volume of ovarian cysts was calculated before and 3/6 months after procedure using the formula: volume (cm 3 ) = 0.5233 × anteroposterior diameter (cm) × transverse diameter (cm) × longitudinal diameter (cm). Pain was assessed by VAS preoperatively and 6 months postoperatively. The VAS ranged from zero to 10: zero indicated no pain and 10 indicated maximum pain. AMH and CA-125 were measured by ELISA in all patients preoperatively, and 6 months postoperatively. “Effectiveness” was defined as the removal of a cyst on imaging. “Cure” was defined as a shrinking cyst on imaging. “Recurrence” was measured by the reappearance of ovarian endometrioma on imaging after initial treatment. Statistical analysis was performed using SPSS 26. Numerical values were presented as mean ± standard deviation and intergroup differences were compared using the independent-samples Student t test and ANOVA. Multivariate regression analyses were carried out with cyst number and laterality as adjustment variables. A two-sided P value < 0.05 was considered statistically significant. Categorical data were presented as ratio or as number (%).

60 patients admitted were included in this trial. All procedures in the 60 patients were successfully performed. Patients received ultrasonography at 3 and 6 months postoperatively. Follow-up information of 4 patients was lost and the rest information of 56 patients was used for statistical analyses. There was no significant difference between the two groups in the average size of cysts preoperatively (Table  1 ). However, the surgery group exhibited more cysts and severe laterality status preoperatively (Table  1 ). These results suggest that patients with higher VAS scores tend to be associated with more cysts and a higher probability of bilateral morbidity, so they are more suitable for LC intervention. Table 1 Demographic, clinical, and sonographic patient characteristics Characteristics Laparoscopic cystectomy surgery ( n  = 28) Ultrasound-guided puncture intervention ( n  = 28) P value Age (y) 31.43 ± 7.88 31.25 ± 6.79 0.806 Cyst number  < 0.001 Single cyst ( n ) 11 26 Multiple cysts ( n ) 17 2 Laterality  < 0.001 Unilateral ( n ) 13 26 Bilateral ( n ) 15 2 Diameter of lesion (cm 3  ± SD) 100.32 ± 169.37 88.05 ± 54.93 0.464 Demographic, clinical, and sonographic patient characteristics The response rate was 100% at 3 months and 6 months in the surgery group, and the cure rate was 96.43% at 3 months and dropped to 85.71% at 6 months (Table  2 ), suggesting that LC had great effectiveness for patients with severe pain. The response rate was 100% at 3 months and dropped to 92.86% at 6 months, and the cure rate was 50% at 3 months and increased to 75% at 6 months in the puncture group (Table  2 ), indicating a lower response rate and slightly reduced cure rate compared to the surgery group. The recurrent rate was 14.92% in the surgery group and 7.14% in the puncture group (Table  2 ). To eliminate the bias caused by the number of cysts and laterality status, we analyzed the effect of treatment modes (laparoscopy/puncture) after adjusting for the baseline characteristics of cysts. The results showed that patients could still benefit more from LC at 3 months after adjusting for cyst number and laterality bias (Table  3 ). Table 2 Therapeutic effectiveness of ultrasound-guided puncture intervention and laparoscopic cystectomy surgery Group 3-month post-procedure Laparoscopic cystectomy surgery Ultrasound-guided puncture intervention Laparoscopic cystectomy surgery Ultrasound-guided puncture intervention Cure ( n ) 27 14 24 21 Cure rate (%) 96.43 50.00 85.71 75.00 Effective ( n ) 28 28 28 26 Effective rate (%) 100.00 100.00 100.00 92.86 Recurrent ( n ) 4 2 Recurrent rate (%) 14.92 7.14 Table 3 Adjusted cure 3-month post-procedure of ultrasound-guided puncture intervention and laparoscopic cystectomy surgery Cure B Degree of freedom P value Exp ( B ) 95% confidence interval of EXP ( B ) Before adjustment Operation(0) 3.296 1 0.002 27.000 3.212 226.968 Constant 0.000 1 1.000 1.000 After adjustment Operation(0) 2.869 1 0.014 17.624 1.798 172.737 Cyst number(0) 17.542 1 1.000 41553461.399 0.000 Laterality(0) − 18.392 1 0.999 0.000 0.000 Constant 0.791 1 0.524 2.206 Therapeutic effectiveness of ultrasound-guided puncture intervention and laparoscopic cystectomy surgery Adjusted cure 3-month post-procedure of ultrasound-guided puncture intervention and laparoscopic cystectomy surgery There was no significant difference in AMH levels before procedures between the puncture group and the surgery group (Table  4 ). AMH concentrations of patients in the surgery group decreased at 6 months postoperatively. In contrast, AMH concentrations of patients in the puncture group were increased at 6 months postoperatively, suggesting restored ovarian reserve function. CA-125 concentration was similar between the two groups preoperatively, while CA-125 decreased significantly 6 months after surgery (Table  4 ) compared with UGP, indicating improved endometriosis status. The VAS score of patients in the surgery group was also markedly decreased, indicating improved pain status. The VAS score of the puncture group dropped to 0 after procedures, due to lower baseline VAS scores preoperatively (Table  4 ). These results suggest that LC can better reduce CA-125 concentrations, while UGP intervention could slightly increase AMH levels. Table 4 Preoperative and postoperative between-group comparisons Group Laparoscopic cystectomy surgery ( n  = 28) Ultrasound-guided puncture intervention ( n  = 28) P value Pre-procedure AMH (ng/ml) 3.46 ± 2.79 2.51 ± 2.37 0.177 Post-procedure AMH (ng/ml) 2.08 ± 1.94 2.88 ± 1.77 0.111 Change in AMH (ng/ml) − 1.38 ± 1.44 0.38 ± 1.18  < 0.001 Pre-procedure CA-125 (UI/ml) 62.31 ± 148.62 44.32 ± 35.85 0.536 Post-procedure CA-125 (UI/ml) 18.59 ± 9.49 24.96 ± 11.90 0.031 Change in CA-125 (UI/ml) − 43.73 ± 150.11 − 16.85 ± 38.71 0.363 Pre-procedure VAS 5.96 ± 0.79 1.04 ± 1.10  < 0.001 Post-procedure VAS 0.39 ± 0.63 0.00 ± 0.00 0.003 Change in VAS − 5.57 ± 0.74 − 1.04 ± 1.10  < 0.001 Preoperative and postoperative between-group comparisons

Ovarian endometriosis cysts, also known as chocolate cysts of the ovary, are prevalent among women of reproductive age [ 1 ]. These cysts arise from ectopic endometrium outside the ovary, leading to blood accumulation in the cyst [ 2 ]. Chocolate cyst is also correlated with pelvic pain, dysmenorrhea, and infertility. Treatment strategies for chocolate cysts include oral progesterone drugs, surgery, and ultrasound-guided puncture (UGP) intervention [ 3 , 4 ]. Treatment strategies for ovarian endometriosis cysts depend on several factors, including the size, number, and laterality of the cysts, as well as classical symptoms. As the gold standard, laparoscopic surgery can completely clear the cyst walls and relieve pain. However, laparoscopic cystectomy (LC) may impair ovarian function and decrease ovarian reserve, thus increasing the risk of infertility [ 5 , 6 ]. UGP is minimally invasive, with no need for general anesthesia, and protects ovarian reserve [ 7 ]. Meanwhile, the clinical application of UGP is limited by the high recurrence rate, the inability to obtain pathology, and the possible need for repeated procedures. Recently, new treatment methods combined with surgery have also been developed and have achieved favorable results. The Dual Wavelength Laser System (DWLS) diode laser presents a good therapeutic option for ovarian endometrioma, demonstrating minimal impact on healthy ovarian tissue, favorable pregnancy rate, and low recurrence rates [ 8 ]. Laparoscopic laser vaporization is an effective treatment for superficial peritoneal endometriosis, which can relieve pain, improve quality of life, and enhance fertility outcomes [ 9 ]. Current guidelines lack consensus on optimal patient stratification. Decisions are often guided by pain severity, cyst size, and tumor markers. While ACOG (2022) recommends surgery for cysts > 5 cm or with malignant features, recent cohort studies suggest puncture may be effective for symptomatic relief in some cases [ 10 ]. The pain may reflect the severity of the cyst. For example, a larger cyst or a twisted cyst may cause more severe pain and require surgery. Patients with less severe pain may prefer puncture therapy. Therefore, visual analogue scores (VAS) score may be related to the pathology of the cyst and thus affect the treatment choice. This study aimed to compare the standard LC versus UGP for the treatment of ovarian endometriomas in a non-randomized study, with cyst cure rates as the primary outcome, and changed VAS scores, anti-Müllerian hormone (AMH), and cancer antigen 125 (CA-125) as the secondary outcomes.

LC outperformed UGP in reducing CA-125 concentration at the 6-month follow-up, while UGP showed higher AMH concentration, indicating less interference on reproductive function. For patients with more cysts, bilateral cysts, or severe pain symptoms, LC may be a better option, as it can remove the cyst more thoroughly and relieve pain. For patients with fewer cysts, unilateral cysts, and less painful symptoms, UGP intervention may be more suitable, because it is less damaging to ovarian reserve function. These conclusions may provide practical references for clinicians.

Treatment options for ovarian chocolate cysts include medications [ 11 ] and surgical procedures. However, surgical interventions can lead to open wounds and associated complications [ 12 ]. UGP intervention is recognized as a viable option for endometriosis therapy with many advantages, including non-interference wound, less invasiveness, and preservation of ovarian function [ 13 , 14 ]. In this study, we carried out a non-randomized trial of UGP intervention and LC for ovarian cyst treatment. We observed that LC eliminated ovarian cysts and reduced VAS scores to the greatest extent in patients than UGP, consistent with previous studies [ 15 , 16 ]. The surgery group exhibited more cysts and severe laterality status at baseline. Multivariate regression analysis showed that patients with more cysts and laterality status can benefit more from LC. It is well-established that non-excisional techniques are associated with increased recurrence rates [ 17 ]. Our findings revealed that UGP intervention was considerably effective, resulting in few recurrences among patients. The low recurrence rate in the puncture group did not align with previous studies [ 14 , 18 ], which may be due to the mild cyst status before procedures and the short follow-up period. Decreased AMH indicated that LC impaired ovarian reserve. AMH levels increased 6 months after UGP. By decompressing the cysts, UGP may mitigate mechanical stress on the ovarian stroma, thus preserving follicular pools. Cyst removal could restore blood flow to adjacent ovarian tissue, enhancing follicular activity. UGP may also reduce inflammatory cytokines that suppress AMH production [ 19 ]. Longer-term follow-up is needed to confirm the trends. Although elevated AMH may indicate improved ovarian reserve, its association with reproductive outcomes needs to be further validated. Future studies should consider sinus follicle count (AFC) and fertility endpoints for further validation. CA-125 decreased 6 months after surgery (Table  4 ) compared with UGP, as it may reflect inflammation, cyst burden, or comorbidities rather than direct treatment effects [ 20 ]. CA-125 trends in our cohort should be interpreted in conjunction with imaging and symptom outcomes, rather than as a standalone biomarker. This non-randomized trial suggests that patients with different clinical manifestations at admission and different therapeutic goals should opt for varied treatment modalities [ 21 ]. In this study, we used a non-randomized trial design to evaluate the efficacy of UGP intervention and LC in the treatment of ovarian endometriosis cysts. Although this approach is feasible in practical applications, it also brings some limitations. Importantly, VAS-driven grouping limits causal inference and results are only hypothetical. Reliable research must integrate multidimensional assessments (imaging, biomarkers, and patient goals) to reflect real-world practice and ensure valid conclusions. First, non-randomized grouping may introduce selection bias, thereby compromising the generalizability of the results. For example, significant differences were observed in the number of cysts and laterality status between the surgery and puncture groups. Second, the relatively small sample size constrains the robustness of the statistical analysis, potentially limiting the generalizability of the results. In addition, a follow-up period of 6 months may not be sufficient to fully evaluate the long-term effects and safety of both treatments. The loss of follow-up information for some patients has further affected data integrity and accuracy. In addition, as this study is conducted at a single center, our conclusions may be influenced by specific healthcare settings, thus limiting their broader applicability. Future studies should employ randomized methods, expand the sample size, ensure consistency and standardization of procedures, and involve multiple centers to improve the generalizability and reliability of the conclusions. Furthermore, it is vital to take steps to ensure the integrity of data collection and further explore the biological mechanisms behind the treatment. Addressing and overcoming these limitations will enable future investigations to provide a deeper understanding and more effective approaches for clinical practice.