Levonorgestrel Intrauterine Device versus Combined Transcervical Resection of the Endometrium in the Management of Adenomyosis: A Randomized Clinical Trial

Adenomyosis is an important cause of abnormal uterine bleeding and dysmenorrhea in reproductive-aged women. Hysterectomy is the traditionally recommended definitive treatment. However, this may not be acceptable to many women. The levonorgestrel intrauterine device (LNG-IUD) effectively suppresses the endometrial glands and is widely used for treating heavy menstrual bleeding (HMB) and dysmenorrhea in women with adenomyosis.[ 1 2 ] It has good efficacy and has reduced hysterectomy rates in women with adenomyosis. However, the failure rate of LNG-IUD ranges from 20% to 30% in women with adenomyosis.[ 3 ] Transcervical resection of endometrium (TCRE) is an alternative treatment option in women with HMB when medical treatment is insufficient for the relief of symptoms.[ 4 ] Combining TCRE with LNG-IUD may reduce the failure rate of LNG-IUD in women with adenomyosis. Some studies have documented better responses in patients with adenomyosis when TCRE was combined with LNG-IUD.[ 5 6 7 ] More studies are needed to evaluate this combination of LNG-IUD and TCRE in women with adenomyosis. This randomized controlled trial was done to compare the treatment failure rates of combined TCRE and LNG-IUD versus LNG-IUD alone in women with adenomyosis.

A total of 158 women with adenomyosis were initially recruited and 12 were excluded [ Figure 1 ]. Baseline characteristics such as age, body mass index, and uterine volume were similar between the groups [ Table 1 ]. Most of the women had HMB alone (46%) or HMB and dysmenorrhea (46.5%). Only 7.5% of women had dysmenorrhea alone. Consort flow diagram Comparison of baseline characteristics between the two groups Values are presented as mean±SD or median (IQR) for continuous variables and numbers (percentage) for categorical variables. BMI: Body mass index, HMB: Heavy menstrual bleeding, LSCS: Lower segment cesarean section, MMAS: Menorrhagia Multi-attribute Scale, PBAC: Pictorial blood loss assessment chart, SD: Standard deviation, LNG-IUD: Levonorgestrel intrauterine device, TCRE: Transcervical resection of the endometrium, IQR: Interquartile range, WHO QOL: World health Organization Quality of life Seventy-three women were randomized to the combined TCRE and LNG-IUD group. All the women underwent the procedure as per allocation. There were no intraoperative complications in any women. No cervical ripening agent was used before TCRE. The mean fluid deficit was 806 ± 375 ml and the mean time of surgery was 21.23 ± 8.24 min. None of the specimens obtained through TCRE had evidence of endometrial hyperplasia or malignancy. None of the women in the LNG-IUD alone group needed cervical dilatation. No analgesics or cervical ripening agent was used in any women in this group. None of the women in the combined TCRE and LNG-IUD group had LNG-IUD expulsion at 12 months compared to the LNG-IUD expulsion rate of 8.8% in the LNG-IUD alone group ( P = 0.013). Women who had LNG expulsion had reinsertion of new LNG-IUD. At 12 months, five women in the LNG-IUD alone group and three women in the combined TCRE and LNG-IUD group were lost to follow-up. The primary outcome of treatment failure was significantly lower in the TCRE + LNG-IUD group (7.14% vs. 25%, P = 0.01; Risk ratio 3.45, 95% Confidence interval (1.35–8.83), as shown in Table 2 . Five (7.35%) women in LNG-IUD alone group and 2 (2.8%) women in combined TCRE and LNG-IUD group underwent hysterectomy ( P = 0.25). In the LNG-IUD alone group, 17 women had treatment failure; reason for treatment failure being persistent HMB in 16 (94.1%) and persistent dysmenorrhea in 1 (5.9%). In the combined TCRE and LNG-IUD group, only 5 women had treatment failure (3 due to persistent HMB and 2 due to persistent dysmenorrhea). Follow-up outcomes at 12 months Values are presented as mean±SD or median (IQR) for continuous variables and numbers (percentage) for categorical variables. IQR: Interquartile range, RR: Relative risk, CI: Confidence interval, LNG-IUD: Levonorgestrel intrauterine device, TCRE: Transcervical resection of the endometrium, MMAS: Menorrhagia Multi-attribute Scale, PBAC: Pictorial blood loss assessment chart, WHO QOL: World Health Organization Quality of life, SD: Standard deviation The quality-of-life score (WHO QOL-BREF) at 12 months was also significantly better in the TCRE + LNG-IUD arm with a mean score of 100.82 ± 11.56 compared to the LNG-IUD alone arm which had a mean score of 90.23 ± 14.47 ( P < 0.001). MMAS score was also found to be significantly better in the combined TCRE and LNG-IUD group. More women in the LNG-IUD alone arm needed additional medications for persistent symptoms compared to combined TCRE and LNG-IUD arm (20% vs. 4.4%, P < 0.05). Most of them received hormonal medications such as oral progesterone, Tranexamic acid, and analgesics. None of them received gonadotropin-releasing hormone agonists (GnRH-a). None of the women in the LNG-IUD alone arm underwent TCRE during the follow-up period. More women in the combined TCRE and LNG-IUD group rated their satisfaction as very satisfied or satisfied (92.85%) compared to the LNG-IUD alone arm (70.5%) ( P < 0.05).

In conclusion, a combination of TCRE with LNG-IUD has a lower failure rate at 12 months in women with adenomyosis compared to LNG-IUD alone. This combination also resulted in better patient satisfaction and quality of life and lowered the chance of LNG-IUD expulsion at 12 months. Conceptualization and Methodology- Murali Subbaiah and Yavana Suriya; Investigation-Murali Subbaiah, Yavana Suriya and Nevetha Selvarajan; Data Collection- Murali Subbaiah, Yavana Suriya and Nevetha Selvarajan; Original Draft Preparation-Murali Subbaiah; Review and Editing- Murali Subbaiah, Yavana Suriya and Nevetha Selvarajan; Supervision- Murali Subbaiah; All authors have read and agreed to the final version of the manuscript. The datasets generated during and analyzed during the current study are available in the Mendeley Repository with the following link: subbaiah, murali (2025), “Levonorgestrel intrauterine device versus combined transcervical resection of the endometrium and levonorgestrel intrauterine device in the management of Adenomyosis: A randomized clinical trial.”, Mendeley Data, V1, doi: 10.17632/xg2jrnb95x.1. There are no conflicts of interest.

Our present study showed that the combination of TCRE and LNG-IUD was superior to LNG-IUD alone at the end of 1 year in terms of reducing uterine bleeding and improving patient satisfaction and quality of life. The treatment failure rate was significantly lower in the combined TCRE and LNG-IUD group at the end of 1 year. Further, LNG-IUD expulsion rates were significantly lower in the combined TCRE and LNG-IUD group compared to the LNG-IUD alone group. The amenorrhea rate was also higher in the combined TCRE and LNG-IUD group compared to the LNG-IUD group. Although LNG-IUD is an effective method of treating adenomyosis, many women fail to respond to it, resulting in hysterectomy.[ 1 2 ] A combination of LNG-IUD with other medical methods such as GnRH-a has been tried in a few studies in women with adenomyosis.[ 3 ] Combining LNG-IUD with TCRE is another option. The advantage of this combination is that it combines two highly effective methods for reducing HMB. Very few studies have evaluated this combination in the treatment of adenomyosis.[ 5 6 7 ] In a prospective study by Chen et al ., 112 patients with adenomyosis were divided into two groups (combined TCRE and LNG-IUD versus LNG-IUD alone).[ 7 ] They were followed up for 36 months after treatment. The hysterectomy rate in the LNG-IUD group was significantly higher than that in the combined TCRE and LNG-IUD groups (12.50% vs. 5.36%); the LNG-IUD expulsion rate was 16.07% in LNG–IUD group and 5.36% in the combination group. Similar findings were found in our study; none of the women in the combined TCRE and LNG-IUD group had LNG-IUD expulsion at 12 months compared to the LNG-IUD expulsion rate of 8.8% in the LNG-IUD alone group. LNG-IUD is more prone to expulsion in women with adenomyosis. The LNG-IUD expulsion rates in women with adenomyosis have been reported to be 9.1% at 12 months and 11.1% at 36 months by Youm et al .[ 12 ] Most expulsions happen within 6 months of LNG-IUD insertion.[ 13 ] Combining TCRE with LNG-IUD insertion significantly reduced the LNG-IUD expulsion rates in our study. In our study, we combined TCRE and LNG-IUD and found this combination highly effective in reducing HMB. The disadvantage of this combination is the need for anesthesia to do TCRE and the risk of surgical complications and infection. TCRE is still used in many developing countries to treat HMB.[ 14 15 ] In our hospital, TCRE is the most commonly used ablation technique. Hence, we used the combination of TCRE and LNG-IUD in our study. A disadvantage of this combination is that it can be offered only to women who have completed their family, as TCRE causes permanent destruction of the endometrium. As TCRE causes intrauterine adhesions, there is a risk of LNG-IUD becoming irretrievable. These intrauterine adhesions may also interfere with adequate endometrial sampling in future, if needed. TCRE and other endometrial ablation methods alone have been evaluated in a few studies in women with adenomyosis with conflicting results.[ 16 17 18 ] Further, adenomyosis has been considered an important cause of ablation failure in women with HMB.[ 19 ] Hence, we used a combination of LNG-IUD and TCRE in our study. Hysteroscopic resection of focal and superficial adenomyosis has also been reported in some case series.[ 4 20 21 ] However, the safety and efficacy of these procedures need to be further evaluated. Hence, we did not use these techniques in our study. The merits of this study are its randomized design and the fact that quality of life and satisfaction were assessed in all the study participants. Earlier studies have not assessed the quality of life in these women. Another merit of the study was that the position of LNG-IUD was confirmed using ultrasonography immediately after insertion. Our study had some limitations. Although TVS was done in all women to diagnose adenomyosis according to the MUSA criteria, the type of adenomyosis was not documented (diffuse vs. focal vs. adenomyoma). Furthermore, the location of adenomyosis (outer myometrium vs. inner myometrium) was not documented. Recent evidence suggests that adenomyosis of outer and inner myometrium has different clinical profiles and responses to therapy.[ 22 23 ] Further, we did not assess the uterine volume at the end of 12 months as both groups received the same hormonal treatment, and we did not expect any difference in uterine volumes. Another limitation of the study was the relatively short follow-up period of 12 months. More extended follow-up studies are needed to evaluate this combination of TCRE and LNG-IUD further.

This randomized control trial was conducted at a tertiary care referral center in southern India. Women with adenomyosis were recruited from the outpatient department of our hospital between January 2021 and May 2023. The follow-up was done for 12 months after the intervention. The study was conducted in accordance with the Declaration of Helsinki. The study was done after approval by the Institutional Ethics Committee of JIPMER (JIP/IEC/2020/061) and after trial registration (CTRI/2020/09/027592). Women with adenomyosis were eligible for the study if they had HMB or dysmenorrhea and refractory to at least 3 months of medical management with hormonal pills. Only premenopausal women who had completed their family were included in this study. Exclusion criteria were women with chronic pelvic pain, patients not willing to follow-up in our hospital, acute pelvic inflammatory disease, and coexisting fibroid/endometriosis. Transvaginal ultrasound (TVS) was used to diagnose adenomyosis. Adenomyosis was defined by the presence of one or more of the following ultrasound features according to the Morphological Uterus Sonographic Assessment (MUSA) criteria: “asymmetrical thickness of the uterine wall, hyperechogenic islands within the myometrium, sub endometrial lines and buds, a globally enlarged uterus, presence of fan-shaped shadowing, myometrial cysts, translesional vascularity and/or irregular junctional zone.”[ 8 ] If the patients were eligible, they were randomized into two treatment groups: Either the combined TCRE and LNG-IUD group or the LNG-IUD alone group. Informed written consent was taken before randomization. Block randomization with a fixed block size of 4 was used to randomize the patients in the study arms in the ratio of 1:1 using Random Allocation Software Version 1.0 (M. Saghaei, Isfahan University of Medical Sciences, Isfahan, Iran), May 2004. Sequentially Numbered, Opaque, Sealed Envelope Allocation was used for concealment. Baseline characteristics of all patients, including menstrual blood volume using pictorial blood loss assessment chart (PBAC) score, dysmenorrhea (Visual Analog Scale-0 to 10; 0 rated as no pain and 10 as agonizing and unbearable pain), hemoglobin, uterine volume (using TVS) was noted down.[ 9 ] Baseline quality of life scores using World Health Organisation quality of life-BREF (WHO QOL-BREF) and menorrhagia multi-attribute scale (MMAS) scores were noted down before the intervention.[ 10 11 ] In the LNG-IUD alone group, LNG-IUD (Emily, HLL Lifecare Ltd, India) containing 52 mg Levonorgestrel was inserted into the uterine cavity under standard aseptic precautions. It was inserted in the minor operation theater immediately after periods. Patients in the combined TCRE and LNG-IUD group were admitted on the day of surgery. TCRE was done immediately after periods and under regional anesthesia. A standard 26 F bipolar resectoscope (Karl Storz, Germany) was used for the procedure, and normal saline was used as distension media. A 24F cutting bipolar loop was used to resect the endometrium and superficial myometrium using an Autocon II 400 high-frequency unit (Karl Storz, Germany), the effect setting being five for cut and six for coagulation. LNG-IUD was inserted into the uterine cavity after TCRE was completed. Patients were discharged the same day. Accurate LNG-IUD position was documented with abdominal ultrasound immediately after insertion in both groups. Patients in both groups were followed up after 3, 6, and 12 months of intervention. During each of these visits, the treatment failure rate and expulsion of LNG-IUD were documented. The primary outcome measure was treatment failure rate at 12 months and included any of the following: Hysterectomy for adenomyosis, persistent HMB, or persistent dysmenorrhea. PBAC score, rates of amenorrhea, patient satisfaction (5 point-LIKERT Scale; 1 rated as very satisfied and 5 as very dissatisfied), need for additional medications, WHO QOL-BREF score, and MMAS score were also noted down at 12 months. The treatment failure rate for LNG-IUD alone in adenomyosis was assumed to be 20%.[ 3 5 ] We considered a 10% difference in treatment failure rate to be clinically important. With a superiority margin of 5%, α error of 0.05, and power of 80% with 1:1 ratio between the two study groups, the minimum sample size required was 69 patients in each group. The sample size was calculated using nMaster 2.0. Expecting around 10% loss to follow-up, we calculated the sample size to be 75 in each group. The distribution of data on categorical variables such as parity, previous lower segment cesarean sections, treatment failure, amenorrhea rates, complications, and adverse effects was expressed as frequency and percentage, and their comparison between the groups was carried out by using the Chi-square or Fisher exact tests. The distribution of data on continuous variables such as age, BMI, PBAC score, WHO QOL-BREF score, and MMAS score was expressed as mean with SD or as median with range depending upon the normality of distribution. The comparison between these continuous variables was done with the independent Student’s t -test or Mann–Whitney U -test. P < 0.05 was considered statistically significant.