The Impact of Oxidized Regenerated Cellulose Application during Cystectomy and Drainage in Endometrioma Patients: A Retrospective Cohort Study

Endometrioma is a cystic form arising from endometrial tissue that grows outside the uterus. Most endometriomas grow in the ovaries.[ 1 ] It is estimated that 17%–44% of endometriosis patients present with endometriomas.[ 2 3 ] About 50% of endometriosis patients experience infertility, and around 70% of patients experience pain.[ 4 5 ] Currently, endometriosis management has shifted from problem-oriented to patients-centered approach. Several goals in managing endometriosis are adapted to the patient’s needs, such as pain associated with endometriosis, infertility, and restoration of organ function.[ 6 ] Nonsteroidal anti-inflammatory drugs, combined oral contraceptives, and progestins are considered first-line therapy. In contrast, gonadotropin-releasing hormone analogs or antagonists and aromatase inhibitors are second-line treatments for endometriosis-associated pelvic pain (EAPP). Several nonhormonal drugs that have been developed, such as dopamine agonists and Janus kinase inhibitors, have shown promising results in reducing EAPP. Selective progesterone and selective estrogen receptor modulators have not provided significant benefits, so future research needs to be done.[ 7 8 9 ] Surgery is part of the management of endometrioma. Cystectomy is the first choice for conservative surgery for endometrioma.[ 10 ] This is because cystectomy is very good at suppressing postoperative recurrence but significantly reduces ovarian reserve. Drainage is another conservative surgical procedure for endometrioma that minimally impacts ovarian reserve. Currently, drainage only is no longer recommended; this is due to the very high recurrence rate after the procedure.[ 11 12 13 14 ] These are the reasons why future management of endometriosis will focus on techniques that preserve ovarian reserve while reducing recurrence rates. Oxidized regenerated cellulose (ORC) is a hemostatic agent widely used for surgery.[ 15 ] Shaltout et al. , in a previous study, concluded that there was a potential benefit from using ORC in suppressing endometrioma recurrence.[ 12 ] Our current study aims to evaluate the benefit of ORC in conservative endometrioma surgery in suppressing recurrence while preserving ovarian reserve.

All the patients were classified as Stage III/IV endometriosis based on the revised American Society of Reproductive Medicine classification. In this study, there were no significant differences in demographic data and cyst characteristics [ Table 1 ] between the two groups. Cystectomy with ORC was done in 20 patients, while drainage with ORC was done in 19 patients. Adenomyosis resection was done in 13 patients: 9 patients in cystectomy with ORC group and 4 patients in drainage with ORC group. Deep endometriosis excision was done in nine patients in cystectomy with the ORC group and 10 patients in drainage with the ORC group. The pain scale [ Table 2 ] decreased significantly in both groups before and after surgery, except for dyspareunia ( P = 0.79) in the drainage group with ORC. Seven recurrences of endometrioma [ Table 3 ] were found in this study, 4 recurrences in the drainage with ORC group, and 3 recurrences in the cystectomy group with ORC. There was no significant difference ( P = 0.622) in recurrence between the two groups. In both groups, recurrence was predominantly symptomatic (cystectomy: 10% and drainage: 15.8%) rather than asymptomatic (cystectomy: 0% and drainage: 5.3%). AMH was decreased [ Table 4 ] from 3.0 ± 1.8 to 2.1 ± 1.5 in cystectomy with the ORC group. Conversely, AMH decreased from 1.4 ± 1.25 to 1.1 ± 0.9 in the drainage with ORC group. AMH significantly reduced in the cystectomy with the ORC group ( P = 0.002), while those in the drainage with the ORC group did not ( P = 0.124). Patient Demographic and Cyst Characteristic Patients symptoms before and after surgery * P <0.05 Characteristics of Endometrioma Recurrence after 1-year follow up Pre and Post Operative AMH Level

Cystectomy with ORC significantly reduces ovarian reserve. Drainage followed by insertion of ORC to the cyst cavity can be an option to maintain ovarian reserve with a risk of recurrence that is not significantly different from cystectomy. MLS: conceptualization, study design, data collection, data analysis, writing. SME: data collection, data analysis, writing. EM, ASA, PAR, PRA: data collection. All authors read and approved the final script. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. There are no conflicts of interest.

Currently, the surgical management of endometrioma is still controversial. Several factors, such as recurrence and postoperative pain, to infertility, make it a challenge to perform surgery on patients with endometrioma. The dilemma currently faced by surgeons in managing endometrioma is whether to choose to maintain fertility or prevent recurrence. Most patients with endometriosis are associated with infertility.[ 16 17 ] In this study, most of the patients in both groups had primary infertility (cystectomy group; 85% vs. drainage group; 73.7%). At the same time, surgery can worsen fertility conditions in women with endometrioma due to decreased ovarian reserve after surgery. However, with the development of minimally invasive surgery and assisted reproductive technology, pregnancy can still occur in the advanced stages of endometriosis.[ 18 ] Several minimally invasive surgical procedures are being developed, such as ablation techniques with CO 2 or diode laser and sclerotherapy with ethanol. However, access and costs are a challenge for minimally invasive technology, which is difficult to reach.[ 19 20 21 ] Drainage-only procedures are widely discouraged for the surgical management of endometrioma. This is due to the very high rate of recurrence. Therefore, drainage is always followed by other procedures such as ablation using electrocautery, CO 2 laser, diode laser, and sclerotherapy using ethanol solution. However, drainage only has a better impact on reducing ovarian reserve than drainage followed by ablation.[ 12 ] Three-step surgery has been developed, which includes a drainage procedure. Tsolakidis et al. , in their research, compared three-step surgery with cystectomy. Six months after the procedure, AMH was significantly lower in the cystectomy group compared to the three-step surgery group.[ 22 ] This study found the AMH level of both groups decreased but significantly decreased in the cystectomy group. This finding aligns with two previous systematic reviews and one randomized control study about the impact of cystectomy on ovarian reserve.[ 12 13 14 ] Cystectomy can cause inadvertent removal of healthy ovarian tissue while removing endometriosis tissue. This mechanism is supported by several studies that found the presence of primordial follicles adjacent to the wall of endometriosis cysts.[ 23 24 25 ] In addition, damage to ovarian healthy tissue can be caused by inflammatory processes and vascular damage caused by the removal of the lesion.[ 26 ] Pain in endometriosis greatly reduces the patient’s quality of life and increases the prevalence of anxiety and depression.[ 27 28 ] Pain in endometriosis is caused by endometriosis lesions and secondary lesions originating from scar and fibrosis. These things trigger an inflammatory process that will be responded to with pro-inflammatory production and activate sensory nerves and nociceptive pathway.[ 29 30 31 ] In this study, we found that all patients experienced pain related to endometriosis, such as dysmenorrhea, CPP, dyspareunia, and dyschezia. Pain associated with endometriosis and did not resolve after medical treatment were indications for surgery in the patients in this study. Several previous studies recommended surgery as a solution to relieve pain after failed hormonal treatment.[ 10 32 33 34 35 ] In this study, there was a significant difference in pain (CPP, dysmenorrhea, dyspareunia, and dyschezia) between before and after surgery in both groups except dyspareunia in the drainage group. This reduction in pain correlates with the destruction of endometriosis lesions accomplished by both types of surgery and the absence of recurrence. There was no significant difference in dyspareunia before and after surgery in the drainage group related to postoperative recurrence, characterized by the appearance of dyspareunia in the drainage group. In this study, excision of all deep endometriosis lesions and adenomyosis resection was carried out to prevent the recurrence of postoperative endometriosis pain. Complete excision of all deep endometriosis lesions and adenomyosis resection is necessary to reduce the recurrence rate of postoperative endometriosis pain symptoms.[ 36 ] In addition, all patients in this study underwent ovarian suspension for 7 days to reduce the risk of postoperative adhesions. Giampaolino et al . in their research reported that ovarian suspension minimizes the risk of ovarian adhesions due to surgery.[ 37 ] Postoperative endometriosis recurrence is still a challenge for every surgeon until now. Several studies have defined recurrence differently; most have defined a definition based on symptoms, and several studies have determined a recurrence based on USG results. Previous studies have shown that recurrence is higher based on symptomatic criteria than in asymptomatic patients with endometriosis cysts on USG.[ 38 ] This aligns with our study result that found more symptomatic recurrence than the asymptomatic in both groups. However, in this study, there was no significant difference in recurrence between the two groups. Meanwhile, previous studies found that cystectomy significantly differed in the recurrence rate compared to drainage only.[ 39 40 ] The role of the ORC is believed to be the cause of the difference in the results of this study compared to previous studies. A survey by Shaltout et al . found that ORC insertion into the cyst significantly reduced the recurrence rate.[ 12 ] The underlying mechanism for this is that the acidic environment created by the ORC triggers a vasoconstriction process that makes residual endometriosis tissue experience anoxia.[ 15 41 ] The main limitation of this study is the small sample size, so in future studies, more samples from multicenter studies are needed to make this study more representative of the population. The heterogeneity of medical treatment before and after surgery is also a limitation in this study. In future studies, homogeneity must be considered to avoid bias. In addition, research over a year cannot conclude the best outcome from each surgical procedure, so conducting a study over a long period is necessary

This research was conducted with a retrospective cohort design. Thirty-nine women aged 18–45 years with pain-related endometriosis (dysmenorrhea or dyspareunia or dyschezia or chronic pelvic pain [CPP]) who underwent conservative laparoscopy surgery (cystectomy or drainage) using ORC at Fatmawati General Hospital Jakarta, Indonesia, from January 2020 to June 2023 were included in this study. We divided all patients into two groups: cystectomy with ORC and drainage with ORC. Cystectomy was performed on 20 patients in the cystectomy with ORC group, and drainage was performed on 19 patients in the drainage with ORC group. Complete excision of all endometriosis lesions, such as deep endometriosis lesions, was done in both groups. Adenomyosis resection was also done in both groups. All patients are evaluated for 1 year for symptoms (dysmenorrhea, CPP, dyspareunia, and dyschezia) every 3 months, and ultrasound (USG) examinations were performed at the 3 rd , 6 th , and 1 year after surgery. One surgeon did all the procedures. In cystectomy with the ORC group [ Figure 1 ], cystectomy begins by creating a small window in the ovarian cortex with scissors. Chocolate fluid from the cyst is aspirated with suction and then rinsed with saline solution. After that, a stripping technique is carried out by pulling the cyst tissue from the ovarian wall using a nontraumatic grasper. The ovaries are irrigated with saline solution, then, ORC (SURGICEL, Ethicon US, LLC.) is inserted into the ovaries. The ovaries were closed and suspended to the abdominal wall for 7 days with a monofilament suture. The drainage procedure with ORC [ Figure 2 ] begins by opening a window in the ovarian cortex with scissors. The chocolate fluid from the cyst was aspirated and rinsed with a saline solution. Then, ORC was inserted into the cyst cavity. The ovaries are closed and suspended for 7 days with monofilament suture. Cystectomy with oxidized regenerated cellulose (ORC) procedure. (a) Cystectomy begins by creating a small window in the ovarian cortex with scissors. Chocolate fluid from the cyst is aspirated with suction, then rinsed with saline solution; (b) A stripping technique is carried out by pulling the cyst tissue from the ovarian wall using a nontraumatic grasper; (c) ORC is inserted into the ovaries; (d) The ovaries are closed and suspended for 7 days with monofilament suture Drainage with oxidized regenerated cellulose (ORC) Procedure. (a) The drainage procedure with ORC begins opening a window in the ovarian cortex with scissors. The chocolate fluid that comes from the cyst will be aspirated out and irrigated with saline solution; (b) ORC is inserted into the cyst cavity; (c) The ovaries are closed and suspended for 7 days with monofilament suture Anti-Mullerian hormone (AMH) examination was carried out before the surgery and 6 months after surgery. Serum AMH was assayed by the electrochemiluminescence immunoassay technique, using Elecys AMH Plus kits (Roche Diagnostics International Ltd, Rothkreuz, Switzerland). Recurrence was assessed based on symptom and USG findings criteria. Symptoms criteria are defined as the presence of pain (dysmenorrhea, dyspareunia, CPP, and dyschezia) that appears after surgery with a Visual Analog Scale pain scale equal to 4 or higher than before surgery. USG criteria are defined by the appearance of an endometrioma of at least 3 cm after two menstrual cycles. In this study, data were analyzed with SPSS Version 26.0 (IBM Corp., Armonk, NY, USA). Chi-square was used to assess significant differences between categorical variables. We use the independent sample t -test to determine the mean, standard deviation, and differences in numerical data. For data before and after surgery, such as pain and AMH levels, first use Kolmogorov–Smirnov to assess the data distribution; after that, the dependent sample t -test is used on AMH and pain data, which are normally distributed. The study was conducted in accordance with the Declaration of Helsinki and was approved by Fatmawati General Hospital institution commission with (approval number: PL.04.02/DXXI.2/1143/2023; approval date: 12.April.2023). Informed consent was obtained from all participants.