The Impact of Gonadotropin-releasing Hormone Agonist Combined with Lauromacrogol on Ovarian Reserve Function and Pain Scores in Patients with Ovarian Endometriotic Cysts

Manager Save my selection Original Article The Impact of Gonadotropin-releasing Hormone Agonist Combined with Lauromacrogol on Ovarian Reserve Function and Pain Scores in Patients with Ovarian Endometriotic Cysts The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China Address for correspondence: Dr. Ling-ling Lin, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China. E-mail: [email protected] This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License (CC BY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. To evaluate the efficacy of gonadotropin-releasing hormone agonist (GnRHa) combined with lauromacrogol sclerotherapy in preserving ovarian reserve and reducing pain in patients with ovarian endometriotic cysts (OECs).

Eighty OEC patients (Oct 2020–Oct 2024) were randomized into two groups (n = 40 each). The control group received laparoscopic cystectomy, and the observation group was treated with GnRHa plus lauromacrogol sclerotherapy. Curative effects were compared.

The total effective rate of the observation group (95.00%, 95% CI: 87.2–98.9) was higher than that of the control group (77.50%, 95% CI: 65.1–86.8; OR=5.51, 95% CI: 1.21–15.56, P < 0.05). After treatment, serum FSH, LH, E2, CA125, CA199 levels and VAS scores in the observation group were lower than those in the control group (all P < 0.05). The recurrence rate of the observation group (5.00%) was lower than that of the control group (17.<0.05).

The combination of GnRHa and lauromacrogol sclerotherapy has a significant effect on OEC, which can improve ovarian reserve function, reduce pain scores and recurrence rates.

Endometriosis (EM) is a common gynecological disease and the ovary is one of the most frequently involved sites. The incidence of ovarian endometriotic cysts (OEC) in EM patients can reach 17%–44%.[1] OEC mostly occurs in women of childbearing age.[2] Although the malignant transformation rate is very low, only 0.3%–0.8%,[3] the cysts will gradually increase, and the ovarian tissue will be compressed and damaged, resulting in dysmenorrhea, menstrual disorders, and even infertility.[4] Currently, laparoscopic cystectomy is the main treatment method for OEC, but there is a certain recurrence rate, and the surgery may damage the ovarian reserve function and affect the patient’s fertility. In recent years, ultrasound-guided sclerotherapy, as a minimally invasive treatment method, has gradually attracted attention.[5] Lauromacrogol, as a commonly used sclerosing agent, has a certain curative effect in the treatment of OEC. At the same time, gonadotropin-releasing hormone agonist (GnRHa) also plays an important role in the treatment of EM. Yen et al. reported in their study “Epidemiologic Factors Associated with EM in East Asia” that EM, with its perplexing pathogenesis, has an incidence rate of approximately 10% among women of reproductive age, and more women in Asia are affected by it than in any other continent. This study provides valuable insights into the epidemiological factors of EM, which is relevant to the background of our research on OECs.[6] This study investigated the combined sclerotherapy of GnRHa and lauromacrogol in the treatment of OEC and explored its effect on ovarian reserve function and pain scores.

General information: eighty patients with OEC admitted to our hospital from October 2020 to October 2024 were selected. Their ages ranged from 20 to 42 years, with an average of (30.25 ± 4.18) years; the disease course ranged from 3 to 18 months, with an average of (9.52 ± 2.36) months; the diameter of the cysts ranged from 3.5 to 8.0 cm, with an average of (5.25 ± 1.08) cm. Patients were included if they met the diagnostic criteria of OECs, were aged 20–45 years, had fertility requirements, and had not received hormone treatment in the past 3 months. Exclusion criteria included complications with other gynecological diseases, severe heart, liver, kidney and other organ diseases, and allergies to the drugs used in this study. According to different treatment methods, they were divided into two groups, with 40 cases in each group. In the control group, the ages ranged from 20 to 41 years, with an average of (30.18 ± 4.25) years; the disease course ranged from 3 to 17 months, with an average of (9.48 ± 2.42) months; the diameter of the cysts ranged from 3.5 to 7.5 cm, with an average of (5.18 ± 1.12) cm. In the observation group, the ages ranged from 21 to 42 years, with an average of (30.32 ± 4.05) years; the disease course ranged from 4 to 18 months, with an average of (9.58 ± 2.30) months; the diameter of the cysts ranged from 3.8 to 8.0 cm, with an average of (5.32 ± 1.05) cm. There was no statistically significant difference between the two groups (P > 0.05). This study was conducted in accordance with the Declaration of Helsinki and has been approved by the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University Ethics Committee with (approval number 2023079; approval date: Jun. 8, 2023), and all patients have signed the informed consent form.

The control group underwent laparoscopic cystectomy. Under general anesthesia, the pelvic cavity was explored with a laparoscope. According to the position, size, and relationship with surrounding tissues of the cysts, the cysts adhered to the surrounding tissues were separated and the cysts were completely removed. The observation group was treated with GnRHa combined with lauromacrogol sclerotherapy. Real-time ultrasound positioning puncture was used. Under local anesthesia, an 18G puncture needle was inserted under the guidance of ultrasound. After the cyst fluid was completely aspirated, the cyst cavity was rinsed with normal saline, and then, an appropriate amount of lauromacrogol (specification: 10 mL/bottle) injection was injected into the cyst cavity and retained. The injection volume was 10%–20% of the aspirated cyst fluid. In the observation group, a subcutaneous injection of goserelin acetate sustained-release implant (specification: 3.6 mg/stick) was given every 28 days after the operation for 3 consecutive months. Observation indicators Before treatment and 1 and 3 months after treatment, fasting venous blood was collected from patients to measure the levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, CA125, and CA199. Before treatment and 1 and 3 months after treatment, the pain degree of patients was evaluated by using the Visual Analog Scale (VAS). Among them, 0 points represented no pain and 10 points represented severe pain. Patients marked the score corresponding to their actual pain sensation on the corresponding scale. Twelve months after treatment, ultrasound reexamination was performed to observe the recurrence of cysts. The recurrence standard was that a cystic mass with a diameter of ≥3.0 cm was found in the ovary by ultrasound examination, and fine dotted echoes or septa could be seen in the mass. Evaluation criteria (1) Cure standard: after treatment, the clinical symptoms of the patient disappeared, and no recurrence of the cyst was confirmed by ultrasound examination. (2) Effective standard: After treatment, the clinical symptoms of the patient were significantly improved, and the reduction ratio of the cyst volume was >50%. (3) Ineffective standard: After treatment, the clinical symptoms of the patient were not improved or even aggravated, or the reduction range of the cyst volume was ≤50% or recurrence. The total effective rate = (number of cured cases + number of effective cases)/total number of cases × 100%. Statistical methods SPSS (the Statistical Package for the Social Sciences) (Version 22 for Windows, SPSS Inc, Chicago, IL, USA) statistical software was used to analyze the data. Measurement data were expressed as (mean ± standard) and tested by t-test; counting data were expressed as (n [%]) and tested by Chi-square test. P < 0.05 was considered statistically significant.

Efficacy rate The total effective rate in the observation group was 95.00% (95% confidence interval [CI]: 87.2–98.9), significantly higher than 77.50% (95% CI: 65.1–86.8) in the control group, with an odds ratio (OR) of 5.51 (95% CI: 1.21–15.56), indicating a 5.51-fold higher likelihood of positive treatment outcomes (P < 0.05). In the observation group, 25 cases (62.50%) were cured, 13 cases (32.50%) were effective, and 2 cases (5.00%) were ineffective; in the control group, 16 cases (40.00%) were cured, 15 cases (37.50%) were effective, and 9 cases (22.50%) were ineffective [Table 1]. Serum levels of follicle-stimulating hormone, luteinizing hormone, and E2 Pretreatment: no significant differences in FSH, LH, or E2 between groups (P > 0.05). Posttreatment: all hormone levels decreased in both groups, with greater reductions in the observation group (P < 0.05); FSH: Observation 4.05 ± 0.68 versu Control 5.08 ± 0.82 (Cohen’s d = 1.32). LH: Observation 2.56 ± 0.52 versus Control 3.25 ± 0.65 (Cohen’s d = 1.56). E2: Observation 25.12 ± 3.05 versus Control 35.08 ± 4.02 (Cohen’s d = 1.89) [Table 2]. Pretreatment: no significant group differences (P > 0.05). Posttreatment: both groups showed reductions, with greater declines in the observation group (P < 0.05); CA125: Observation 25.08 ± 5.12 versus Control 35.25 ± 6.05 (Cohen’s d = 1.18). CA199: Observation 15.05 ± 3.08 versus Control 20.12 ± 4.05 (Cohen’s d = 1.25) [Table 3]. The mean VAS scores decreased significantly in both groups posttreatment, with the observation group demonstrating greater pain relief (P 0.05; Observation: 7.52 ± 1.25 versus control: 7.48 ± 1.30). One month posttreatment: Observation: 3.05 ± 0.85 (reduction: 60.7%), Cohen’s d = 1.41 vs. control. Control: 4.58 ± 1.02 (reduction: 38.8%), P < 0.05 versus pretreatment. Three Months Posttreatment: Observation: 2.08 ± 0.65 (reduction: 72.4%), Cohen’s d = 1.63 versus control. Control: 3.52 ± 0.82 (reduction: 53.0%), P < 0.05 versus pretreatment [Table 4]. OECs are the most common type of EM, and the incidence is increasing year by year. OEC can damage normal ovarian tissue. The increasing cysts in the ovary can compress the normal ovarian tissue, gradually reducing the blood supply to the ovary. In severe cases, the blood supply may disappear completely, eventually leading to ovarian endocrine dysfunction and increasing the risk of infertility in patients.[7] The traditional treatment method is surgical treatment. Although surgical treatment can directly remove the lesions, the damage to ovarian tissue may affect the ovarian reserve function.[8] Especially for patients with fertility needs, the protection of ovarian function after surgery is crucial. In addition, the recurrence rate of surgical treatment cannot be ignored. Some patients still face the risk of disease recurrence after surgery. In recent years, minimally invasive treatment methods such as ultrasound-guided sclerotherapy have gradually developed, providing new options for the treatment of OEC. GnRHa can inhibit the secretion of gonadotropins by the pituitary gland, reduce the level of ovarian hormones, atrophy the ectopic lesions, relieve symptoms and reduce recurrence.[9] Lauromacrogol can destroy the endothelial cells of the cyst wall and cause fibrosis of the cyst wall to achieve the purpose of sclerosing the cyst. In clinical practice, the lauromacrogol sclerotherapy for the liver and kidney cysts has been recognized.[10] The combination of the two may have a synergistic effect, which can not only inhibit the recurrence of cysts but also protect the ovarian reserve function to a certain extent. Ovarian reserve function refers to the ability of follicles in the ovarian cortex to form fertilizable oocytes, which is closely related to female fertility. It plays a crucial role in ensuring ovarian ovulation and endocrine function.[11] Serum FSH, LH, and E2 levels are the important indicators for evaluating ovarian reserve function. Affected by EM, these hormone levels may abnormally increase.[12] The results of this study showed that after treatment, the serum FSH, LH, and E2 levels in both groups decreased, and those in the observation group were lower than those in the control group, indicating that GnRHa combined with lauromacrogol sclerotherapy is superior to simple laparoscopic cystectomy in improving ovarian reserve function. This may be because laparoscopic cystectomy causes greater direct damage to ovarian tissue, affecting the patient’s ovarian function and sex hormone levels,[13] while the combined treatment has less damage to ovarian tissue through puncture, and reduces ovarian hormone levels through drug action, thus better protecting the ovarian reserve function. The serum CA125 and CA199 levels in OEC patients often increase to varying degrees.[14] In this study, after treatment, the serum CA125 and CA199 levels in both groups decreased, and those in the observation group were lower than those in the control group, suggesting that GnRHa combined with lauromacrogol sclerotherapy is superior to simple laparoscopic cystectomy in reducing tumor marker levels. Pain is one of the main symptoms of OEC patients. According to the literature, about 80% of OEC patients have different degrees and natures of pain, including dysmenorrhea, chronic pelvic pain, and dyspareunia,[15] which have a serious negative impact on the patient’s quality of life. Li et al.[16] studied 43 patients with EM. All patients had different degrees of pain before surgery. The pain relief rate in the laparoscopic cystectomy combined with GnRHa group was 96.4%, which was significantly higher than that in the simple laparoscopic cystectomy group (60.0%). In this study, after treatment, the VAS scores in both groups decreased, and those in the observation group were lower than those in the control group, indicating that GnRHa combined with lauromacrogol sclerotherapy can more effectively relieve patient pain. This may be because GnRHa inhibits the secretion of estrogen and inflammatory mediators, reducing the activity of endometriotic lesions,[17] and lauromacrogol sclerotherapy destroys the endothelial cells of the cyst wall and reduces the secretion of cyst fluid. The combination of the two effectively relieves pain symptoms. The recurrence rate after OEC treatment is relatively high, reported to be about 24.6%.[18] How to reduce the recurrence rate after treatment is crucial. In this study, the recurrence rate in the observation group was lower than that in the control group, indicating that GnRHa combined with lauromacrogol sclerotherapy can reduce the recurrence risk of OEC. This is of great significance for improving the treatment effect of patients and reducing the possibility of reoperation. For patients with fertility needs, reducing the recurrence rate helps to improve their fertility opportunities and reduce further damage to ovarian function caused by the disease. Previous studies have reported that GnRHa may cause side effects such as hot flashes, night sweats, and bone loss due to reduced estrogen levels. Lauromacrogol may lead to local pain, allergic reactions, etc., In our study, although no severe adverse events were observed, we closely monitored patients for any potential side effects. Future research should pay more attention to these aspects to improve the safety of the treatment. In addition to serum FSH, LH, and E2 levels, anti-Müllerian hormone (AMH) and antral follicle count (AFC) are more sensitive indicators for evaluating ovarian reserve function and should be included in future studies to ensure comprehensive assessments. Yazawa et al.[19] reported a rare case of an extragonadal giant endometrial cyst with endometrioid borderline tumor, expanding the clinical spectrum of EM and highlighting the need for differential diagnosis in complex OEC cases. Kaseki et al.[20] conducted a study on risk factors for abscess development in endometrioma patients, identifying clinical predictors (e.g., elevated CRP and cyst size >5 cm) that inform preoperative risk stratification and infection prevention strategies in OEC management. Yu et al.[21] demonstrated that bilaterality of ovarian endometriomas does not impact in vitro fertilization/intracytoplasmic sperm injection outcomes after laparoscopic cystectomy, providing reassurance for infertile patients with bilateral lesions regarding their fertility prognosis. These studies collectively enhance our understanding of OEC complications, diagnostic challenges, and fertility implications, underscoring the importance of integrating advanced ovarian reserve markers (AMH and AFC) in future research to optimize treatment strategies for reproductive-aged women.

GnRHa combined with lauromacrogol sclerotherapy has a significant effect on OECs, can improve the ovarian reserve function of patients, reduce pain scores, and reduce recurrence, and has certain clinical application value. Author contributions The corresponding author (LLL) undertook the design of the project, selection of consenting patients, data collection andanalysis (SZW, ML, and YY), literature review, manuscript writing, and submission of the manuscript for publication. LLL had final responsibility for the decision to submit the manuscript for publication. All authors have read and agreed to the final version of the manuscript. Data availability statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Financial support and sponsorship This study was financially supported by Project of Wenzhou Science and Technology Bureau (Y2023532). Conflicts of interest There are no conflicts of interest.

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