{"paper_id":"c344fb3a-40d5-4909-b0c2-27dd33a750cb","body_text":"The effectiveness of ethanol sclerotherapy varies significantly depending on factors such as the volume of ethanol injected and retention time. Administering the minimum necessary volume of ethanol and retaining it without removal significantly reduces the recurrence rate while also minimising the impact on AMH.\n\nOvarian endometriomas are ovarian cysts lined with endometrial tissue, affecting up to 20% of women with infertility [ 1 ].These cysts present a unique challenge in treatment due to the lack of a clear cleavage plane between the cyst wall and the surrounding ovarian cortex.\nLaparoscopic cystectomy has traditionally been the most common treatment for ovarian endometrioma, effectively reducing recurrence and alleviating pain symptoms [ 2 ]. However, ovarian cystectomy carries the risk of decreased ovarian reserve, often due to inadvertent removal of healthy ovarian tissue adjacent to the cyst wall, as well as excessive coagulation for haemostasis [ 3 – 5 ]. These drawbacks have prompted the search for more conservative approaches that better preserve ovarian tissue. In this respect, sclerotherapy has emerged as a promising and cost-effective alternative for treating ovarian endometriomas [ 3 ,  6 ]. Sclerotherapy may be particularly beneficial for patients who wish to preserve ovarian function and fertility, as it is considered less damaging to the ovarian reserve compared to traditional surgical options [ 7 ,  8 ].\nSclerotherapy for ovarian endometriomas can be performed via either the transvaginal or laparoscopic approach. The transvaginal route is known to result in lower recurrence rates and may be beneficial for oocyte preservation when compared to cystectomy [ 9 ,  10 ]. However, a major limitation of transvaginal sclerotherapy is the difficulty in aspirating the highly viscous cystic content using a thin needle. Laparoscopic sclerotherapy, a more recent approach, provides the benefit of overcoming the limitations of the transvaginal method by allowing better access to the cystic content [ 11 ]. Despite its promise, laparoscopic sclerotherapy remains in the early stages of application, with relatively fewer clinicians having gained extensive experience. Furthermore, long-term data regarding its efficacy and safety remain insufficient, with only a limited number of studies having reported on its complication rates [ 12 ].\nSclerotherapy involves injecting sclerosing agents into endometriomas to denature the amino acid components of their pseudocapsules. Various sclerosing agents, including ethanol, tetracycline and methotrexate, have been used in the treatment; however, ethanol instillation remains the most commonly employed method [ 7 ,  13 ,  14 ]. High concentrations of ethanol can effectively denature proteins in the cyst’s inner epithelium without penetrating the surrounding healthy ovarian stroma. Most studies have utilised a treatment protocol of cyst aspiration followed by ethanol instillation, retention for a specific period, and subsequent removal of the ethanol [ 12 ,  15 – 18 ]. However, some studies have compared the effects of removing ethanol after retention for a set duration versus retaining the ethanol without removal, with results indicating that total retention without removal may be more effective in treating ovarian endometriomas [ 9 ,  19 – 21 ]. As a result, recent studies have favoured the technique of total ethanol retention without removal [ 22 ,  23 ]. These findings underscore the variability in the outcomes of ethanol sclerotherapy based on factors such as the volume and concentration of ethanol instilled, as well as the duration of treatment [ 7 ,  19 ,  20 ,  24 ].\nIf an effective technique for aspirating the viscous cystic content can be ensured, the transvaginal approach may offer more advantages than the laparoscopic approach. In this regard, this study aims to introduce an effective protocol for transvaginal ethanol sclerotherapy, focusing on the aspiration of viscous cystic content. The protocol is also designed to achieve a low recurrence rate and minimal impact on AMH levels by instilling minimal amounts of ethanol and leaving it in situ. This approach is based on over 10 years of experience with transvaginal sclerotherapy.\n\nBetween 2015 and 2022, we performed 421 cases of transvaginal sclerotherapy using 95% ethanol in patients with endometrioma at Good Moonhwa Hospital in Busan, Republic of Korea. Of these, 90 cases with available follow-up AMH results after sclerotherapy were included in the review. These women had at least one endometrioma larger than 2.5 cm, with cyst sizes ranging from 2.5 to 10.6 cm. If the cyst included echogenic portions within its cavity, Doppler ultrasound was used to differentiate between debris and tumour. MRI was performed in all patients prior to sclerotherapy to confirm that the cystic content was haemorrhagic and to rule out malignancy. Patients with recurrent cysts who had undergone an operation for endometrioma at other hospitals were also included. Patients without available AMH levels either before or after sclerotherapy were excluded from this study. Cases in which the ipsilateral ovary had multiple cysts were also excluded. Informed consent for possible conversion to laparoscopic cystectomy was obtained in the cases where 1. the cystic content was too viscous for aspiration, 2. internal bleeding occurred during the procedure, and 3. the aspirated content was inconsistent with an endometrioma. Patients were also informed of the possibility of aspiration alone without alcohol instillation if spillage of the cystic content into the pelvic cavity occurs. Regular follow-up after the procedure was recommended due to malignancy occurring in 0.8–1% of cases.\nAll patients were followed up on postoperative days 1 and 2, at 2 weeks, 4 weeks, 3 months, 6 months, 12 months, and then every 6 months to assess the ovary, AMH levels, complications, recurrence, pelvic pain and pregnancy outcomes. Serum AMH levels were assessed at 3 months after sclerotherapy. The mean follow-up period was 37.9 months (12–119 months).\nThe operation was performed by a single surgeon with over 30 years of experience in the field of endometriosis surgery. The procedure was performed in the operating room under sedation with intravenous administration of 100 μg of fentanyl and 200 mg of propofol. The patient was placed in a lithotomy position. With the bladder completely emptied, the cystic lesion was localised using a transvaginal ultrasound probe covered with a sterile glove. An 18-gauge long aspiration needle with a silicone plug attached at the end was used to collect the cystic content and the aspirated fluid was collected in a conical tube. The needle and the conical tube were connected via a flexible clear plastic tube which was flushed and filled with normal saline before starting the procedure. We could observe aspirate progression through the tube and grossly assess its appearance for consistency with endometrioma or mucinous cystadenoma. When aspirate was not observed, air bubbles within the saline in the plastic tube served as an indicator of ongoing, albeit slow, aspirate progression. This helped us determine whether to wait and continue with the aspiration or convert to laparoscopic surgery.\nUnder ultrasound guidance, the needle was carefully penetrated into the cystic cavity (Fig.  1 A–C). Constant negative pressure was maintained with a 50 cc syringe as thick, dark brown fluid, characteristic of an endometrioma, and was drained into the conical tube. Due to the viscous nature of the cystic fluid, a spare plunger was placed between the barrel and syringe’s primary plunger to maintain the necessary negative pressure throughout the procedure (Fig.  2 ). Fig. 1 Transvaginal ultrasound-guided aspiration and sclerotherapy.  A  Left endometrioma measuring 6.95 × 4.05 cm.  B  Needle (arrow) inserted under ultrasound guidance.  C  Shrinkage of cyst with needle still in it.  D  95% ethanol (30 cc) injected into the cystic space.  E  Needle removed from the cyst.  F  Normal ovary at 2 months postoperation Fig. 2 A spare plunger is placed between the barrel and the primary plunger of a 50 cc syringe to maintain constant negative pressure\nTransvaginal ultrasound-guided aspiration and sclerotherapy.  A  Left endometrioma measuring 6.95 × 4.05 cm.  B  Needle (arrow) inserted under ultrasound guidance.  C  Shrinkage of cyst with needle still in it.  D  95% ethanol (30 cc) injected into the cystic space.  E  Needle removed from the cyst.  F  Normal ovary at 2 months postoperation\nA spare plunger is placed between the barrel and the primary plunger of a 50 cc syringe to maintain constant negative pressure\nIf the viscosity of the cystic fluid was low enough to allow rapid flow into the collection tube, we measured the drainage speed in ml/min and substantial dilution was unnecessary. However, if the fluid was too viscous and collection slowed to a drop-counting rate, the dripping speed was determined by tallying droplets collected per minute. In such cases, normal saline was used to dilute the cystic content, facilitating aspiration, reducing procedure duration and ensuring successful sclerotherapy as we planned.\nNormal saline was injected into the cystic cavity, accounting for the volume within the long aspiration needle, the attached plastic tube, and the silicone plug, which was approximately 1 cc. This injection, equivalent to 1 cc plus the previously aspirated volume, ensured that the injected volume did not exceed the cystic capacity and prevented cyst rupture. For example, if 15 drops (approximately 1 cc) of fluid were collected, 2 cc (1 cc + 1 cc) of normal saline was injected into the cyst and an attempt was made to aspirate at least 2 cc. If the cystic content was too thick to become immediately visible within the plastic tube, the movement of saline and air within the tube under constant negative pressure indirectly indicated that the cystic content was slowly moving along the needle. Due to the cyclical size variations resulting from the postmenstrual absorption of its contents, the cystic cavity typically had capacity for extra saline. This irrigation process was repeated until the aspirate became nearly clear. Throughout the irrigation process, the needle tip was closely monitored via ultrasound to ensure it remained within the cyst and did not penetrate other parts of the cystic wall. Once the irrigate became clear, cysts with contents exceeding 10 cc were injected with 10 cc of 95% ethanol, and for cysts containing less than 10 cc, we instilled 95% ethanol in a volume 1 cc less than the aspirated fluid to assess the integrity of the cystic wall and to wash out residual saline from previous irrigation which might dilute the alcohol which is to be left within the cyst in the next stage. If the volume aspirated after ethanol instillation was significantly less than the injected volume, internal spillage was suspected, and ethanol instillation was held.\nThe volume of alcohol administered for sclerotherapy was tailored according to the cyst size. For cysts with 10 cc or less aspirated, an equal amount of 95% ethanol was instilled. For cysts with less than 30 cc of aspirated content, approximately 80% of the aspirated volume was injected. For cysts with more than 30 cc of aspirated content, 30–40 cc of alcohol was instilled (Fig.  1 D–F).\nAll statistical analyses were performed using Student’s t-test, Wilcoxon Signed Rank test, one-way ANOVA, and Pearson correlation using SPSS 25 (IBM Corporation, New York, USA). A  P -value < 0.05 was considered statistically significant.\n\nA total of 90 patients underwent ethanol sclerotherapy for endometriomas. The clinical characteristics of these patients are as presented in Table  1 . The mean age of patients was 30.1 ± 5.3 years (range 20–41 years) and their mean maximum cyst diameter was 5.07 ± 1.56 cm (range 2.5–10.6 cm). Forty-seven patients (52.2%) had unilateral endometriomas, while 43 patients (47.8%) presented bilateral endometriomas. The majority of the patients ( n  = 80, 88.9%) showed dysmenorrhea, but none complained of severe pelvic pain. Table 1 Patient characteristics Characteristics N  = 90 Age (mean, range) 30.1 ± 5.4 Pregnancy desire,  n  (%) 71 (78.9) Cyst size (cmSD) 5.07 ± 1.57 Localization Bilateral,  n  (%) 43 (47.8) Right,  n  (%) 24 (26.7) Left,  n  (%) 23 (25.5) Dysmenorrhea (%) 80 (88.9) Pre-OP AMH (ng/dL) (mean ± SD) 5.02 ± 3.68\nPatient characteristics\nAMH levels were evaluated at the 3-month follow-up after the procedure. AMH levels increased in 22 cases (24.4%) and decreased in 68 cases (75.6%). Cyst size consistently decreased after sclerotherapy and significantly decreased on postoperative day 9, with further reduction observed by 3 weeks postoperation, regardless of the initial cyst size or whether AMH levels decreased or increased (Table  2 ). The ovary returned to normal size on average 2.24 ± 0.97 (mean ± SD) weeks after sclerotherapy. Table 2 AMH levels and cyst size before and after ethanol sclerotherapy Decrease ( n  = 68, 75.6%) Increase ( n  = 22, 24.4%) AMH levels (ng/dL) Pre-OP 5.20 ± 3.99 a 4.45 ± 2.43 c POD 3 months 3.80 ± 2.96 b 5.67 ± 3.02 d Cyst size (cm) Pre-OP 5.03 ± 1.54 e, 5.21 ± 1.68 f POD9 2.80 ± 0.90 † 2.80 ± 0.76 † POD21 2.43 ± 0.78 † 2.32 ± 0.70 † † P , 0.05 (vs Pre-OP) a : b P  = 0.0000 c:d P  = 0.0001 e:f P  = 0.7059 g:h P  = 0.5093 i:j P  = 0.4311 All data are presented as mean ± SD. Wilcoxon singed rank test, Student t-test. POD: postoperative day\nAMH levels and cyst size before and after ethanol sclerotherapy\n† P , 0.05 (vs Pre-OP)\na : b P  = 0.0000\nc:d P  = 0.0001\ne:f P  = 0.7059\ng:h P  = 0.5093\ni:j P  = 0.4311\nAll data are presented as mean ± SD. Wilcoxon singed rank test, Student t-test. POD: postoperative day\nWhen analysing the effect of sclerotherapy on AMH levels in more detail, among the 22 cases in which AMH levels increased, 14 cases (about two-thirds) showed a significant increase of more than 20%. Among the 68 cases with decreased AMH levels, 38 cases (55.9%) showed a mild decrease of less than 30%, 18 cases showed a decrease of around 40%, and 12 cases showed a decrease of more than 40%. These findings suggest that our method of sclerotherapy had minimal impact on AMH levels in approximately two-thirds of patients (Table  3 ). Table 3 Distribution of the change rates of AMH before and 6 months after aspiration AMH Change rates No. of cases (%) AMH change rates No. of cases (%) Increase < 10% 4 (4.4) Decrease < 10% 14 (15.6 11 ~ 20% 4 (4.4) 11 ~ 20% 13 (14.4) 21 ~ 30% 4 (4.4) 21 ~ 30% 11 (12.2) 30% <  10 (11.1) 31 ~ 40% 18(20.0) subtotal 22 (24.4) 41 ~ 50% 4 (4.4) 50% <  8 (8.9) Subtotal 68 (75.6)\nDistribution of the change rates of AMH before and 6 months after aspiration\nWe then examined whether changes in AMH levels (increase or decrease) were associated with differences in cyst size, aspirated cyst volume, volume of alcohol instilled, operation time, recurrence rate, or pregnancy outcomes. As shown in Table  4 , none of these parameters differed significantly based on the rate of AMH change. The mean duration of follow-up was 37.9 ± 25.2 months (mean ± SD, range 2–119 months). During this period, recurrence assessed by ultrasound occurred in 6 cases (6.7%). The pregnancy rate was 31.4% among patients with increased AMH levels, compared to 25.4% among patients with decreased AMH levels, but this difference was not statistically significant. Table 4 Relationships between changes in AMH levels before and after, and cyst size, aspirated cyst volume, instilled ethanol volume, recurrence, and pregnancy outcomes Rate of change in AMH levels after OP No. of cases Age (years) Pre-OP AMH levels (mIU/ml) Cyst size (mm) Aspirated cyst volume (ml) Instilled ethanol volume (ml) Op time (min) No. of recurrence No. of those who wanted No. of pregnancy Range Mean + SD Decrease P  = 0.921 P  = 0.326 P  = 0.065 P  = 0.0210 P  = 0.047  < 10% 5.9 ± 2.3 14 30.9 ± 5.1 4.9 ± 3.8 5.3 ± 1.6 69.6 ± 70.3 16.7 ± 8.2 35.7 ± 17.2 1 10 2 (20.0%) 11 ~ 20% 15.7 ± 3.1 13 28.4 ± 6.4 5.3 ± 3.2 4.9 ± 1.3 37.8 ± 24.1 14.6 ± 6.6 36.8 ± 27.2 1 10 2 (20.0%) 21 ~ 30% 24.9 ± 3.1 11 29.7 ± 2.8 5.9 ± 5.0 4.3 ± 1.3 38.8 ± 31.8 14.3 ± 7.4 22.7 ± 6.8 2 11 2 (18.2%) 31 ~ 40% 34.9 ± 3.3 18 31.3 ± 5.8 5.2 ± 3.2 5.1 ± 1.8 51.9 ± 40.3 18.6 ± 7.1 32.6 ± 22.3 1 14 5 (33.7%) 41 ~ 50% 43.5 ± 2.9 4 30.2 ± 2.0 3.3 ± 2.2 6.3 ± 0.3 124.1 ± 15.2 25.7 ± 14.0 56.3 ± 21.3 0 4 1 (25.0%) 50% <  62.9 ± 9.8 8 31.9 ± 5.4 5.8 ± 6.6 5.1 ± 1.6 58.6 ± 54.5 18.3 ± 6.4 21.9 ± 9.2 0 6 2 (33.3%) Total 26.9 ± 19.3 68 30.3 ± 5.1 5.2 ± 4.0 5.0 ± 1.5 55.5 ± 48.1 17.1 ± 7.7 33.2 ± 21.1 5 55 14 (25.4%) Increase P  = 0.427 P  = 0.5684 P  = 0.070 P  = 0.5347  < 10% 4.9 ± 2.8 4 25.8 ± 2.7 4.9 ± 2.8 5.1 ± 1.3 55.5 ± 63.8 15.7 ± 9.0 22.5 ± 5.0 0 4 2 (50.0% 11 ~ 20% 5.0 ± 2.6 4 31.3 ± 4.9 5.0 ± 2.6 4.8 ± 1.4 49.1 ± 32.6 25.0 ± 5.0 32.5 ± 17.6 1 2 1 (50.0%) 21 ~ 30% 5.5 ± 1.8 4 33.3 ± 3.5 5.5 ± 1.8 6.7 ± 2.8 102.0 ± 81.7 28.3 ± 12.6 35.0 ± 13.3 0 2 0 (0.0%) 30% <  3.7 ± 2.5 10 28.7 ± 7.4 3.7 ± 2.5 5.0 ± 1.6 60.5 ± 44.6 14.9 ± 7.1 36.0 ± 21.3 0 9 2 (22.2%) Total 4.5 ± 2.4 22 29.3 ± 6.1 4.5 ± 2.4 5.2 ± 1.7 63.7 ± 50.3 18.7 ± 9.3 32.6 ± 17.3 1 16 5 (31.3%)\nRelationships between changes in AMH levels before and after, and cyst size, aspirated cyst volume, instilled ethanol volume, recurrence, and pregnancy outcomes\nAmong the 90 patients, 44 (48.8%) expressed a desire to become pregnant, and 17 (38.6%) had achieved pregnancy by the time of the last follow-up (Table  5 ). Of these 44 patients, 33 attempted natural conception and 12 (36.3%) conceived spontaneously. Eleven patients attempted to conceive via in vitro fertilisation and embryo transfer (IVF-ET), with 5 (45.5%) achieving pregnancy. Table 5 Fertility outcomes after sclerotherapy No. of those who wanted pregnancy 44 No. of pregnancies 17 (38.6%) No. of those who tried natural conception 33 No. of natural conception 12 (36.3%) No. of those who tried to IVF 11 No. of IVF pregnancy 5 (45.5%)\nFertility outcomes after sclerotherapy\nNext, we further analysed whether pregnancy outcomes were influenced by the rate of AMH change before and after sclerotherapy, cyst size, aspirated cyst volume, and instilled ethanol volume. In the group with an AMH increase of less than 20%, the pregnancy rate was 50%, which was significantly higher than that of other groups ( p  < 0.05). For patients with a cyst size between 5 and 6 cm, the pregnancy rate was 38.5%; however, no significant differences were observed among the other cyst size groups. In addition, neither the aspirated cyst volume nor the volume of ethanol injected had a significant impact on the pregnancy rate (Table  6 ). Table 6 Comparison of the recurrence and pregnancy outcomes after sclerotherapy according to changes in AMH levels, cyst size, aspirated cyst volume, and volume of alcohol instilled No. of cases Age (years) No. of recurrence No. of those who wanted No. of Pregnancy Change rates in AMH levels before and after OP  < (–)20% 27 29.7 ± 5.8 2 (7.7%) 20 4 (20.0%) (–) 21–40% 29 30.7 ± 4.94 1 (3.5%) 21 7 (33.3%) (–) 40% <  12 31.37 ± 4.5 0 (0.0%) 10 3 (30.0%)  < ( +)20% 8 28.5 ± 4.7 0 (0.0%) 6 3 (50.0%) ( +) 21–30% 4 33.3 ± 3.5 0 (0.0%) 2 0 (0.0%) ( +) 30% <  10 28.7 ± 7.4 0 (0.0%) 9 2 (22.2%) Subtotal 90 Cyst size 2–3 cm 8 33.6 ± 4.7 0 (0.0%) 6 2 (33.3%) 3–4 cm 18 31.0 ± 4.0 0 (0.0%) 14 3 (21.4%) 4–5 cm 17 27.1 ± 4.9 1 (5.9%) 16 3 (18.8%) 5–6 cm 28 31.3 ± 5.9 1 (4.3%) 13 5 (38.5%) 6 cm <  19 28.7 ± 5.1 1 (5.3%) 16 3 (18.8%) Subtotal 90 Aspirated cyst volume 1–20 ml 17 32.2 ± 6.1 1 (6.3%) 11 1 (9.1%) 21–40 ml 22 30.2 ± 4.6 1(4.8%) 18 6 (33.3%) 41–60 ml 24 30.7 ± 5.9 0 (0.0%) 18 4 (22.2%) 61–80 ml 6 30.0 ± 3.7 0 (0.0%) 3 0 (0.0%) 81–100 ml 10 27.9 ± 5.9 0 (0.0%) 8 3 (37.5%) 100 ml <  11 28.2 ± 4.6 1 (9.1%) 10 1 (10.0%) Subtotal 90 Instilled ethanol volume 1–10 ml 20 31.1 ± 5.2 0 (0.0%) 14 4 (28.6%) 11–20 ml 48 29.7 ± 5.7 2 (4.3%) 38 9 (23.7%) 21–30 ml 19 29.6 ± 4.9 1 (5.6%) 12 3 (25.0%) 30 ml <  3 31.0 ± 1.4 0 (0.0%) 2 0 (0.0%) Subtotal 90\nComparison of the recurrence and pregnancy outcomes after sclerotherapy according to changes in AMH levels, cyst size, aspirated cyst volume, and volume of alcohol instilled\nFirst, we investigated whether cyst size correlated with the change rate in AMH, aspirated cyst volume, volume of ethanol instilled, and operation time. As shown in Fig.  3 , cyst size demonstrated significant correlations with aspirated cyst volume, instilled ethanol volume, and operation time, but not with the change rate in AMH ( p  < 0.05). Fig. 3 Correlation between the cyst size and the change rate in AMH levels ( A ), the volume of cyst aspirated ( B ), the volume of alcohol instilled ( C ), and the operation time ( D ).  Vol  volume,  Op  operation\nCorrelation between the cyst size and the change rate in AMH levels ( A ), the volume of cyst aspirated ( B ), the volume of alcohol instilled ( C ), and the operation time ( D ).  Vol  volume,  Op  operation\nSecond, we evaluated whether the change rate in AMH correlated with aspirated cyst volume, instilled ethanol volume, and operation time. Contrary to expectations, the change rate in AMH, whether an increase or a decrease, showed no significant correlation with any of these variables (Fig.  4 ). However, there was a significant correlation between the instilled ethanol volume and operation time (Fig.  5 ). Fig. 4 Correlation between the change rate in AMH levels and the volume of cyst aspirated ( A ), the volume of alcohol instilled ( B ), and the operation time ( D ).  Vol  volume,  Op  operation Fig. 5 Correlation between the volume of alcohol instilled and the operation time ( D ).  Vol  volume,  Op  operation\nCorrelation between the change rate in AMH levels and the volume of cyst aspirated ( A ), the volume of alcohol instilled ( B ), and the operation time ( D ).  Vol  volume,  Op  operation\nCorrelation between the volume of alcohol instilled and the operation time ( D ).  Vol  volume,  Op  operation\nRecurrence occurred in 6 cases (6.67%). Recurrence was detected 46 months after the initial sclerotherapy with the recurrent endometrioma measuring 1.9 ‧ 2.2 cm. Six months later, the size of the endometriomas grew to 4.1 ‧ 2.8 cm, prompting a second sclerotherapy. Following the second procedure, no further recurrence has been noted.\n\nThe effectiveness of ethanol sclerotherapy varies considerably, depending on factors such as the injected ethanol volume and retention time [ 7 ,  20 ]. Studies have reported better outcomes when the injected ethanol is not withdrawn, compared to those with shorter retention times of less than 10 minutes [ 9 ,  19 ,  20 ]. Moreover, the meta-analysis by Kim et al .  concluded that sclerotherapy lasting under 10 minutes could be considered an incomplete treatment [ 8 ]. Recurrence rates have also been shown to increase in cases where ethanol volumes ranged from 100 to 540 ml [ 9 ,  12 ,  17 ].\nThus, the two critical factors in ethanol sclerotherapy are ensuring continuous ethanol retention without removal and minimising the injected volume to avoid ethanol intoxication [ 25 ,  26 ]. Miquel et al  . emphasised setting a strict limit on ethanol volume to prevent the risk of severe acute alcohol intoxication [ 12 ].\nTo address these challenges, we adopted a two-step protocol. First, we minimised the ethanol volume by basing it on the cyst volume reduced after aspirating its contents. As cyst size decreases significantly following aspiration, the volume of ethanol required for sclerotherapy also reduces. Second, we verified the integrity of the cyst wall and the absence of leakage by injecting alcohol before final instillation. Specifically, the cyst was diluted with an amount of normal saline equal to the volume of aspirated content, and the same volume was retrieved to confirm cyst wall integrity. For further verification, we injected 10 ml of ethanol and ensured that an equal 10 ml could be recovered before proceeding with the instillation of 95% ethanol. This is to reconfirm that the cyst wall is intact and to wash out any residual saline which might otherwise dilute the alcohol which is to be instilled and decrease its efficacy. Following this protocol, the ethanol volume injected did not exceed 30 ml in any case, except for one instance where 40 ml was used. In all cases, the ethanol was left in situ and not removed, ensuring effective treatment while minimising risks.\nSpillage during cyst procedures typically occurs in three main ways. First, the needle might penetrate the cyst wall instead of staying within the cyst itself. Second, over-dilution with normal saline can cause the cyst to rupture. Third, using more than one needle can lead to spillage. To prevent spillage, we take specific precautions for each scenario. For the first case, we continuously monitor the ultrasound screen during the procedure to ensure the needle remains securely inside the cyst. We also observe the monitor for any signs of spillage throughout the procedure. In most cases, spillage does not occur, and after the procedure, we perform another ultrasound check for free fluid in the pelvic cavity.\nRegarding the second case, it is crucial to carefully monitor the input and output when diluting with normal saline, ensuring that the volume does not exceed the cyst’s capacity. For the third case, using multiple needles can cause leakage through the insertion holes. Therefore, it is best to avoid using multiple needles and, as a rule, stick to one. If more than one needle is absolutely necessary, we recommend using an 18-gauge needle. Its smaller size significantly reduces the amount of content that can leak into the peritoneal cavity. Also, if a needle becomes blocked by the cyst’s contents, its patency can often be restored by flushing it with a small amount of normal saline (typically 10 cc or less, depending on the content volume).\nMaintaining an intact cyst wall is also crucial and requires additional considerations. It is generally easier to confirm an intact cyst for those of appropriate size, typically 5–7 cm or smaller. However, with larger cysts (8 cm or more), confirming an intact cyst can sometimes be ambiguous. If there is any doubt about the cyst wall’s integrity, we opt to perform only the aspiration and cancel the ethanol instillation. We then schedule a second procedure 1 or 2 months later. In cases where spontaneous cyst rupture occurs before the scheduled procedure date, we postpone the procedure. We wait for the perforated cyst wall to heal spontaneously and reschedule the procedure approximately 2 months later.\nThrough these methods of maintaining an intact cyst wall and preventing ethanol spillage, our study recorded no instances of alcohol intoxication during the research period.\nOur method appears to have yielded positive outcomes in three key aspects of ethanol sclerotherapy. First, our procedure had little impact on AMH levels, aligning with the findings of most studies, which have reported that sclerotherapy effectively preserves ovarian reserve over the long term [ 7 ,  18 ,  22 ,  23 ,  27 ]. Second, the recurrence rate was relatively very low (6.67%). Third, our ethanol sclerotherapy approach effectively preserves fertility.\nIn our study, AMH levels increased in 22 cases (24.4%), and among the 68 cases with decreased AMH levels, 38 cases (55.9%) showed a mild decrease of less than 30%. Overall, 60 cases (66.7%) experienced an AMH change, either an increase or a decrease, of 30% or less. Most studies, including several reviews, have reported an AMH reduction of at least 30%, often exceeding 50%, within 3 to 6 months following a cystectomy [ 4 ,  28 – 31 ]. Considering these findings, our results suggest that the sclerotherapy procedure had minimal impact on AMH levels in more than two-thirds of the patients.\nAs in our present study, some studies also showed only slight, non-significant increases in AMH levels following ethanol sclerotherapy [ 21 ,  32 ,  33 ]. Endometriomas themselves are known to compromise ovarian reserve through reduced circulation and inflammation within the cyst walls [ 34 ,  35 ]. Our sclerotherapy procedure may have mitigated these negative impacts, thereby facilitating improved follicular development and ovarian blood supply. Furthermore, the positive AMH shifts observed in this study are likely attributable to our practice of customising ethanol dosage according to each patient’s cyst size and content viscosity, which we believe significantly reduced ovarian exposure to and damage from ethanol.\nIn the present study, the recurrence rate was exceptionally low (6.67%, 6/90) even after a follow-up period of up to 119 months (mean: 37.9 months). This outcome compares favourably with recurrence rates reported in other ethanol sclerotherapy studies, which range from 13.3% to 75.0% [ 9 ,  18 ,  31 ,  36 ]. Notably, Noma & Yoshida and Hsieh et al .  observed that recurrence rates were significantly lower when ethanol was retained in the cyst cavity for more than 10 minutes [ 9 ,  36 ]. Hsieh et al .  noted, through personal communications with clinicians and literature reviews, that prolonged ethanol retention consistently demonstrated better treatment efficacy [ 9 ]. Since 2003, their team has strongly advocated for prolonged ethanol retention during sclerotherapy. Similarly, Chang et al .  reported lower recurrence rates in cases where ethanol was completely retained without removal, compared to cases where retention duration was less than 10 minutes [ 19 ].\nThe impact of ethanol sclerotherapy on pregnancy outcomes has shown significant variability across studies, likely due to the differences in study focus. Some studies reported outcomes exclusively from natural conception [ 9 ,  36 ,  37 ], others analysed results following the use of assisted reproductive technology (ART) [ 21 ,  38 – 40 ], and some presented combined data from both natural conception and ART [ 19 – 21 ]. Pregnancy rates following ethanol sclerotherapy have varied widely for each focus. For natural conception, rates range from 8.1% to 52.1% [ 9 ,  36 ,  37 ], while pregnancy rates via ART range from 4 to 47% [ 19 ,  38 ,  39 ,  41 ]. When combining outcomes from natural conception and ART, cumulative pregnancy rates have been reported to range from 15.8% [ 19 ] to around 44% [ 20 ,  21 ]. In our study, approximately 40% of patients who desired pregnancy achieved it, either naturally or through IVF-ET. Specifically, the pregnancy rate was 36.3% for natural conception and 45.5% for IVF-ET. These results align closely with previous findings, suggesting that our ethanol sclerotherapy approach effectively preserves fertility.\nAre pregnancy outcomes influenced by factors such as AMH change rates, cyst size, volume of cyst aspirated, or volume of alcohol instilled? In the present study, we investigated whether these variables impacted pregnancy outcomes. As shown in Table  6 , pregnancy rates were not significantly affected by any of these factors.\nAdditionally, we examined whether AMH change rates are significantly associated with other variables, including cyst size, volume of cyst aspirated, volume of alcohol instilled, operation time, and recurrence rate. As shown in Table  4 , none of these parameters varied significantly based on the rate of change in AMH levels, whether they increased or decreased. Furthermore, no significant relationships were observed between AMH change rates and variables such as the volume of cyst aspirated, and volume of alcohol instilled, or operation time (Fig.  4 ). However, cyst size showed a significant correlation with the volume of cyst aspirated, volume of alcohol instilled, and operation time, but not with AMH change rates (Fig.  3 ). Additionally, a significant correlation was found between the volume of alcohol instilled and operation time (Fig.  5 ), consistent with findings reported by Chang et al .  [ 19 ].\nThe treatment of endometriomas larger than 80 mm presents a significant challenge. While a laparoscopic approach can be complicated for these patients, a transvaginal approach offers a more feasible alternative. In the present study, four cases involved cysts exceeding 8 cm in size (8.4, 8.6, 9.5, and 10.6 cm). The aspirated cyst volumes for these cases were substantial, measuring 140 ml, 167 ml, 270 ml, and 193.5 ml, respectively. Despite the large cyst sizes and volumes of aspirated fluid, the corresponding volumes of ethanol instilled were relatively modest: 25 ml, 15 ml, 30 ml, and 40 ml, respectively. Furthermore, the operation times for these cases were 25 min, 75 min, 65 min, and 45 min, respectively, which were comparable to the average operation time for smaller cysts (< 8 cm), at 32.1 ± 19.7 min. These findings highlight the feasibility of ethanol sclerotherapy for large endometriomas, demonstrating that even with significant cyst sizes, the procedure remains efficient and manageable, with ethanol volumes and operation times similar to those required for smaller cysts.\nTransvaginal and laparoscopic approaches have been used for ethanol application, but their comparative superiority has not been established yet. Laparoscopic approach offers the advantage of allowing evaluation of the pelvis and potential surgical intervention for other pelvic pathologies. Conversely, the vaginal approach is generally considered a less costly and less invasive alternative with less damage to the ovaries. In addition, laparoscopic sclerotherapy still lacks long-term data on its safety and efficacy [ 12 ]. For this reason, our hospital mainly uses vaginal sclerotherapy due to its clear advantages, especially pertinent given our patient demographic. With a mean patient age of 30.1 years, and a substantial portion being either unmarried (45.6%) or subfertile (48.9%) with future pregnancy plans, prioritising fertility preservation was paramount. While laparoscopic cystectomy is considered in patients who have completed their childbearing or those with large cysts and viscous cystic content, transvaginal ethanol sclerotherapy is not only less invasive and more cost-effective, but crucially, it has less impact on AMH levels, a significant factor for fertility preservation [ 12 ,  42 ]. The success of vaginal sclerotherapy depends on how viscous the cystic content is and whether it can be easily aspirated, yet the viscosity cannot be predicted through ultrasound or MRI. From August 2009 to June 2025, we performed a total of 572 cases of vaginal sclerotherapy and only 19 cases were converted to laparoscopic cystectomy.\nThis study has clinical implications as it introduces a novel strategy for the transvaginal sclerotherapy approach, focussing on ethanol injection volume and retention time. Previous studies frequently involved injecting a large volume of ethanol, retaining it for a set period, and then removing it. In contrast, we propose determining the ethanol volume based on the reduction in cyst size following aspiration of its contents, with a recommended maximum of 30 cc. Importantly, the ethanol is retained fully without removal. This protocol aims to minimise ovarian cyst recurrence while preserving the ovarian reserve as much as possible. In addition, our findings reiterate the critical role of minimal ethanol injection and continuous retention without removal in enhancing the effectiveness of sclerotherapy, offering valuable insights for developing future ethanol sclerotherapy protocols.\nOn the other hand, this study has several limitations. First, its retrospective design and relatively small sample size may restrict the generalizability of the findings. To further validate these findings, additional prospective studies with a well-designed group are required. However, this study was conducted by a single surgeon with over 30 years of experience in endometriosis surgery, who has performed 421 cases of transvaginal ethanol sclerotherapy over the past 8 years. While the retrospective analysis included only 90 cases due to limited follow-up AMH data, the study remains significant because it is grounded in extensive clinical experience and features a long follow-up period ranging from 12 to 119 months. Second, this study is limited by the lack of a control group. This study aimed to complement this limitation by evaluating our results more objectively, citing and comparing the recurrence rate and AMH change rate reported in other previous studies. Finally, further research is needed to investigate the underlying mechanisms behind the observed changes in AMH levels following sclerotherapy.\nIn conclusion, this study demonstrates that our ethanol sclerotherapy procedure not only significantly reduces the recurrence rate but also minimises the impact on AMH levels. Notably, it highlights that the key to success lies in injecting the minimum effective volume of ethanol to avoid toxicity, while retaining it without removal. Achieving this requires meticulous monitoring for any leakage before the ethanol injection.","source_license":"public-domain-us","license_restricted":false}