Comparison of the effectiveness of levonorgestrel intrauterine system and dienogest in the management of adenomyosis: A systematic review and meta-analysis.

BACKGROUND: Adenomyosis is a gynaecological lesion that impairs female fertility and contributes to reduced quality of life. There are several surgical and medical options for the management of this lesion; however, women who wish to conceive opt for medical therapies such as the levonorgestrel intrauterine device (LNG-IUS) and dienogest, which have various outcomes. To date, there is no consensus regarding which is more effective. OBJECTIVES: To compare the effectiveness of LNG-IUS and dienogest for the management of adenomyosis, and explore the risk of occurrence of known side effects for both treatments. DESIGN: Systematic review and meta-analysis exploring the effectiveness of LNG-IUS and dienogest for the management of adenomyosis. METHODS: A literature search was conducted using PICO guidelines and EMBASE, PubMed/MEDLINE, Scopus and Web of Science databases. Only clinical trials were collected and analysed. RESULTS: Of the 792 studies that were initially identified, six were eligible for inclusion in this study. The studies included a total of 707 women; of these, 270 were treated with LNG-IUS, 354 were treated with dienogest, and 83 were controls. All the studies were from Asia (Bangladesh n = 1, China n = 2, India n = 1, Japan n = 1, South Korea n = 1). Dienogest was found to reduce pelvic pain significantly, evidenced by a lower visual analogue scale score, compared with LNG-IUS. Also, dienogest led to a significant reduction in uterine volume compared with LNG-IUS. However, subjects in the LNG-IUS group had significantly higher levels of haemoglobin than those in the dienogest group. Nonetheless, the occurrence of side effects such as weight gain, breast tenderness/distension, headache, insomnia/sleep disorder, depression/mood disorder, skin disorder/acne, and coital discomfort/reduced libido were comparable in both treatment groups. CONCLUSION: Dienogest may be more effective than LNG-IUS for the management of adenomyosis, as it shows a superior effect in the reduction of pelvic pain and uterine volume. As only six studies were included in the present meta-analysis due to the paucity of data in the literature, it is recommended that well-designed randomized controlled trials comparing the effectiveness of dienogest with LNG-IUS should be conducted.

Cost-effectiveness analysis of levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg versus other long-acting reversible contraceptives for contraception in Spain.

INTRODUCTION: Condoms and combined oral contraceptive pills are widely used in Spain with high failure rates. Long-Acting Reversible Contraceptive (LARC) methods offer better efficacy and adherence and reduce unintended pregnancies (UP) compared with short-acting reversible contraceptive (SARC) methods. OBJECTIVE: To assess the cost-effectiveness of LNG-IUS 52 mg (Mirena®) versus other LARC for contraception in Spain. MATERIALS AND METHODS: A Markov model with annual cycles and an eight-year time horizon was developed from the Spanish national healthcare system (NHS) perspective, considering costs for contraceptive method acquisition, health care resources (HCR) and UP. Effectiveness was based on failure and discontinuation rates. Sensitivity analyses were performed to test the model's robustness. RESULTS: LNG-IUS 52 mg (Mirena®) resulted in lower costs and fewer UP versus LNG-IUS 13.5 mg (Jaydess®), Implant (Implanon®) and Copper IUD. LNG-IUS 52 mg (Levosert®) prevented the same UP events at a higher cost. LNG-IUS 19.5 mg (Kyleena®) was the most effective option, due to a lower discontinuation rate. CONCLUSIONS: LNG-IUS 52 mg (Mirena®) is the least costly LARC, driven by lower acquisition costs and reduced HCR utilisation. Increasing LNG-IUS 52 mg (Mirena®) uptake in contraception could generate further cost savings for the Spanish NHS and reduce economic burden of UP.

Levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena^®) is an effective and cost-saving long-acting reversible contraceptive (LARC) method compared with other similar methods in Spain over an eight-year time horizon, and Kyleena^® was the most effective option.

Long-term efficacy and safety of levonorgestrel releasing intrauterine system in the treatment of adenomyosis: evidence mapping.

PURPOSE: To summarize evidence on levonorgestrel releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis (AM) and to identify potential research gaps. METHODS: Search was conducted in MEDLINE, The Cochrane Library, EMBASE, CBM, CNKI, and Wanfang. We included studies investigating patients with AM treated with LNG-IUS combined with conservative therapy. RESULTS: Thirty-nine studies compared LNG-IUS with other conservative therapeutic drugs. The most common comparison was GnRH-a + LNG-IUS vs. LNG-IUS alone, followed by LNG-IUS vs. mifepristone, expected treatment, and GnRH-a. GnRH-a + LNG-IUS was more beneficial in reducing the intensity of dysmenorrhea than LNG-IUS alone at the 6-month follow-up in patients with an enlarged uterus and moderate to severe dysmenorrhea. Large and well-designed studies are needed to confirm the efficacy of LNG-IUS and GnRH-a on reducing uterine volume at 6-month follow-up. Thirty-two studies investigated LNG-IUS as the postoperative management. The most common comparison was surgical excision + LNG-IUS vs. surgical excision. Results showed VAS scores were lower in the surgical excision + LNG-IUS group than in the surgical excision group at the 1-year follow-up. Evidence on endometrial thickness, quality of life, adverse events and beneficial effect at 3 and 5 years are needed. CONCLUSIONS: Combined GnRH-a and LNG-IUS treatment was more efficacious than LNG-IUS alone for patients with an enlarged uterus and moderate to severe dysmenorrhea. Moreover, LNG-IUS seemed to show potential long-term benefits in postoperative therapy, warranting further meta-analysis for confirmation.

Feasibility and Effectiveness of Hysteroscopic Suture Fixation of the Levonorgestrel-Releasing Intrauterine System in the Treatment of Adenomyosis.

STUDY OBJECTIVE: To evaluate the feasibility and effectiveness of hysteroscopic suture fixation of the levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of adenomyosis. DESIGN: A retrospective case series. SETTING: Two teaching hospitals with the technology of hysteroscopic suture fixation of the LNG-IUS. PATIENTS: The study reviewed 79 adenomyosis patients who received the hysteroscopic suture fixation of the LNG-IUS from January 2021 to May 2022. INTERVENTION: Hysteroscopic suture fixation of the LNG-IUS to the posterior uterine wall with nondissolvable suture. MEASUREMENTS AND MAIN RESULTS: All patients underwent one-year postoperative follow-up to evaluate the LNG-IUS expulsion rate, postoperative efficacy, and side effects. Two patients (2.6%) experienced expulsion of the LNG-IUS at 8 months and 12 months postoperatively, respectively. The visual analog pain scale, pictorial blood loss assessment chart score and carbohydrate antigen 125 markedly decreased after the suture fixation of the LNG-IUS compared with baseline in all patients (p <.001). Hemoglobin increased significantly (p <.001). The most common side effect was irregular bleeding, which accounted for 44.3%. The second common side effect was weight gain, which accounted for 29.2%. The composite effectiveness based on pain and bleeding showed that the effective treatment rates at 1, 3, 6, and 12 months after surgery were 92.4%, 97.4%, 96.2%, and 97.4% respectively. CONCLUSIONS: Hysteroscopic suture fixation of the LNG-IUS to the uterine fundus was associated with low expulsion rates and significantly improved dysmenorrhea and bleeding.

Factors Predicting Removals of the Levonorgestrel-Releasing Intrauterine System in an Adolescent Cohort.

OBJECTIVE: Use of 52-mg levonorgestrel intrauterine system (LNG-IUS) in adolescents for heavy menstrual bleeding (HMB), dysmenorrhea, and contraception has increased, yet little is known about the factors predicting removal and dissatisfaction in adolescents. The aim of this study was to identify factors predicting LNG-IUS removal in adolescents. METHODS: This was a retrospective cohort study including all adolescents (9-19 years) who underwent LNG-IUS insertion between 2012 and 2021 (n = 536). A medical record review was conducted and data were collated on medical and gynecological history, age, indications for insertion, complications, expulsions, and removals. The data were analyzed using χ2 tests. RESULTS: Indications for LNG-IUS insertions (n = 536) among 517 individual patients (n = 517) included menstrual management (n = 142), HMB alone (n = 118), HMB and pelvic pain/dysmenorrhea (n = 105), dysmenorrhea/pelvic pain alone (n = 47), and contraception (n = 16). Associated diagnoses included intellectual disability (44.29%, 229/517), chronic pain conditions (12.77%, 66/517), and additional mental health concerns (24.37%, 126/517). Patient dissatisfaction with LNG-IUS led to removal in 61 (11.38%), mostly for pain or persistent bleeding. Higher removal rates occurred in those with associated chronic pain conditions (46.97%, χ2 = 55.9, P < .05), mental health concerns (16.67%, χ2 = 5.06, P < .05), and bleeding disorders (26.32%, χ2 = 5.09, P < .05). Among the cohort with an intellectual disability, lower rates of removal occurred (5.7%, χ2 = 11.2, P < .05). Whereas the LNG-IUS removal rate among gender-diverse youth was 23.07%, this was not statistically significant. Younger age was also not associated with a statistically significant increase in removals (13.72%, χ2 = 0.73, P > .05). DISCUSSION: Adolescents have a low dissatisfaction and removal rate (11.38%) of LNG-IUS. Chronic pain, bleeding tendency, and mental health concerns are associated with higher removal rates and intellectual disability with lower rates. These findings are useful in counselling patients and families about LNG-IUS.

Modified Fixation of Levonorgestrel-releasing Intrauterine System for the Treatment of Adenomyosis / 中山大学学报(医学科学版)

ObjectiveTo introduce a fixation technique with the modified levonorgestrel-releasing intrauterine system （LNG-IUS） and evaluate its efficacy in the treatment of adenomyosis patients with previous LNG-IUS expulsion. MethodsA retrospective analysis was done on 22 adenomyosis patients who underwent modified LNG-IUS fixation due to LNG-IUS expulsion at three hospitals from June 2022 to June 2023. The baseline clinical characteristics， operative and postoperative details were collected and analyzed. The Visual analogu scale （VAS） scores and pictorial blood loss assessment chart （PBAC） scores were measured and compared before， 3 and 6 months after the LNG-IUS fixation. ResultsThe mean operative time was （19.51±7.41） min and intraoperative bleeding was （6.71±5.30） mL. Of the patients， 13 were operated under local anaesthesia and the other 9 under intravenous anaesthesia. There were 4 operations performed by a resident doctor， 15 by an attending doctor and 3 by a senior doctor. No intraoperative or postoperative complication was found. The mean follow-up was 11.51 months and no patient had a recurrence of LNG-IUS expulsion during the follow-up period. The mean level of hemoglobin at 1 month after operation was significantly higher than that before （P<0.001）. VAS scores and PBAC scores at 3 and 6 months postoperatively were all improved significantly than those preoperatively （P<0.001）. ConclusionsEffectively preventing the recurrence of LNG-IUS expulsion， modified LNG-IUS fixation is a safe and efficient method for adenomyosis patients with previous LNG-IUS expulsion. Modified LNG-IUS fixation deserves the clinical application due to its easy operation and wide range of use on women.

Comparison of Bleeding Pattern and Quality of Life Before and After the Insertion of a Levonorgestrel Intrauterine System for Heavy Menstrual Bleeding: A Seven-Year Review.

Background This study aimed to examine the role of a levonorgestrel intrauterine system (LNG-IUS) in the treatment of heavy menstrual bleeding (HMB) regarding improvements in bleeding patterns and quality of life (QOL) and determine the reason for its failure or withdrawal from treatment in some patients. Methodology This retrospective study was conducted in a tertiary care center in eastern India. A seven-year assessment, with both qualitative and quantitative assessments, of the effect of LNG-IUS in women with HMB was performed using the Menorrhagia Multiattribute Scale (MMAS) and Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36) score as a tool to assess the QOL, and the pictorial bleeding assessment chart (PBAC) to assess bleeding patterns. The study population was divided into the following four groups based on duration: three months to one year, one to two years, two to three years, and more than years. The continuation, expulsion, and hysterectomy rates were evaluated. Results The mean MMAS and MOS SF-36 scores increased significantly (p < 0.05) from 36.73 ± 20.40 to 93.72 ± 14.62 and 35.33 ± 6.73 to 90.54 ± 15.89, respectively. The mean PBAC score decreased from 176.36 ± 79.85 to 32.19 ± 63.87. In total, 348 women (94.25%) continued the LNG-IUS, and 3.44% had uncontrolled menorrhagia. Furthermore, at the end of seven years, the expulsion rate was 2.28% due to adenomyosis and pelvic inflammatory disease, and the hysterectomy rate was 5.75%. In addition, 45.97% and 48.27% of the participants had amenorrhea and hypomenorrhea, respectively. Conclusions LNG-IUS improves bleeding and QOL in women with HMB. In addition, it requires less skill and is a non-invasive and nonsurgical option, which should be considered first.

Does Timing of Levonorgestrel Insertion in Women with Abnormal Uterine Bleeding Affect its Expulsion and Bleeding Pattern? A Follow-Up Study.

Background: Levonorgestrel Intra Uterine System insertion for contraception is preferred in the follicular phase. However, the ideal time of insertion for Abnormal Uterine Bleeding is not stated clearly. The aim of our study is to find out the effect of timing of insertion on expulsion and irregular bleeding pattern post insertion. Methods: A follow-up study of patients with LNG-IUS for AUB was conducted. They were grouped into four based on the day of insertion from Last Menstrual Period (LMP). The pattern of irregular bleeding post insertion was compared with odds ratio and the expulsion rate was compared with log rank test. Results: The most common indication for the 76 patients was ovulatory dysfunction (39.4%) followed by Adenomyosis (36.84%). Those who had LNG-IUS insertion from day 22-30 had quicker expulsions of 25% of patients by 3 months. By 6 months and later expulsion rate was much higher in the luteal phase than the follicular phase (p < 0.03). The least risk of moderate or heavy bleeding was for the 8-15 day group when compared to the 22-30 day group, the odds ratio being 0.03 [95% CI: (0.01-0.2)]. Conclusion: Based on expulsion rate alone, insertion of LNG-IUS at any time in the follicular phase is ideal. Considering both expulsion rate and pattern of bleeding the ideal time would be late follicular phase, that is 8-15th day.

Operative Hysteroscopy Versus Levonorgestrel-Releasing Intrauterine System (LNG-IUS) Insertion: A Prospective Observational Study on the Effect of Surgical and Medical Treatments on Sexual Functions in Women With Abnormal Uterine Bleeding.

Background This study aims to evaluate the effect of operative hysteroscopy and levonorgestrel-releasing intrauterine system (LNG-IUS) insertion for abnormal uterine bleeding on sexual function and, if it improves sexual function, to examine differences in sexual function between women undergoing hysteroscopy and women using LNG-IUS. Methods Ninety women aged between 25 and 52 enrolled in the study. Participants were divided into two groups, including 45 operative hysteroscopy patients and 45 LNG-IUS patients. All patients completed the Female Sexual Function Index (FSFI) questionnaire pre-treatment and after three months post-treatment. Pre- and post-treatment FSFI scores were compared both within and between groups. Results The mean FSFI scores at three months following both treatments were significantly higher than baseline in both groups (p<0.05). When the two groups were compared, no significant difference was observed between baseline and three-month post-treatment differences in FSFI scores except for the pain domain. In the pain domain of the FSFI questionnaire, a more significant improvement was found in the LNG - IUS inserted group compared to the operative hysteroscopy group. Conclusion Patients had improvement in sexual functions after both operative hysteroscopy and LNG - IUS insertion treatment. No significant difference was observed in hysteroscopy and LNG-IUS patients after both treatments in terms of sexual function according to scores calculated by FSFI, except for the pain domain. Significant improvement was observed in the pain domain of the FSFI for the LNG - IUS inserted group compared to the operative hysteroscopy group, thus demonstrating a significant effect and improvement for dyspareunia and chronic pelvic pain complaint in the LNG-IUS inserted group.

Assessment of pain and ease of intrauterine device placement according to type of device, parity, and mode of delivery.

OBJECTIVE: We compared pain and the ease of insertion of two different types of intrauterine devices (IUDs; the levonorgestrel intrauterine systems 52 mg (LNG-IUS 52 mg) and the copper-bearing IUD [TCu380A]) among nulligravidas and parous women with and without caesarean delivery. METHODS: A cross-sectional study assessed pain referred by women and ease of insertion of the two IUDs models. We applied a visual analogue scale (VAS) to assess pain, while the ease of insertion was defined by healthcare professionals. RESULTS: We assessed 1076 women, including 334 nulligravidas and 566 parous women who had had at least one caesarean delivery and 176 women with history of only vaginal delivery. Regarding pain at IUD placement, 26 (2.5%) women reported no pain, 167 (16.4%) light pain, 319 (31.3%) moderate and 506 (49.7%) intense pain. The highest scores for pain were reported by nulligravidas (67.2%, p = 0.001), while the mean pain score was higher in the LNG-IUS 52 mg group. Difficulties reported by healthcare providers were more frequent in the nulligravidas (21.2%) and women with previous caesarean delivery (16.9%). CONCLUSIONS: Our findings suggested differences between the two IUDs tested, with higher pain associated with the LNG-IUS 52 mg, and highlights the need for pain management, mainly among nulligravida and women with history of caesarean delivery.SHORT CONDENSATIONIntense pain at insertion was more related to nulligravida than parous women and more pain with placement of LNG-IUS 52 mg IUDs than TCu380A IUDs. Nevertheless, our results confirmed that ease of IUD placement was between 80% to 90% of all insertions, being more common in parous women without previous caesarean delivery.

Comparison of the treatment efficacies of HIFU, HIFU combined with GnRH-a, and HIFU combined with GnRH-a and LNG-IUS for adenomyosis: A systematic review and meta-analysis.

To compare the treatment efficacies of high-intensity focused ultrasound (HIFU), HIFU combined with gonadotrophin-releasing hormone agonist (GnRH-a), and HIFU combined with GnRH-a and levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis. We conducted a literature search in SCIENCE DIRECT, COCHRANE LIBRARY, WILLEY ONLINE LIBRARY, PUBMED, and TAYLOR FRANCIS. A total of 471 articles identified, 12 were included in a systematic review, and 11 of them deemed quantitively eligible included in the meta-analysis. The efficacies of the three treatment regimens were assessed using the dysmenorrhea and menstrual scores at 3, 6, 12, 24 months. Of the three regimens, HIFU combined with GnRH-a and LNG-IUS provides the best outcome. On dysmenorrhea score at 6 months there was significantly different higher heterogeneity with P < 0.00001 (I2 = 100% WMD 21.44 [6.34, 36.53]) with statistical significance P = 0.005. At 12 months there was significantly different higher heterogeneity P < 0.00001 (I2 = 100% WMD 23.47 [6.00, 40.94]) with statistically significant P < 0.008. At 24 months there was significantly different higher heterogeneity P < 0.0005 (I2 = 92% WMD 6.05 [4.81, 7.30]) with statistical significance P < 0.00001. HIFU combined with GnRH-a and LNG-IUS on menstrual score at 3 months was significantly different higher heterogeneity with P < 0.00001 (I2 = 100% WMD 56.23 [16.01, 96.45]) with statistical significance P = 0.006. At 6 months there was significantly different higher heterogeneity P < 0.00001 (I2 = 99% WMD 93.86 [64.15, 123.57]) with statistical significance P < 0.00001. At 12 months there was significantly different higher heterogeneity P < 0.00001 (I2 = 99% WMD 97.13 [67.81, 126.46]) with statistical significance P < 0.00001 compared to treatments with only HIFU and HIFU combined with GnRH-a. HIFU combined with GnRH-a and LNG-IUS treatment is more effective than only HIFU monotherapy and HIFU combined with GnRH-a.

Levonorgestrel-Releasing Intrauterine System Improves Menorrhagia-Related Quality of Life in Patients with Symptomatic Adenomyosis.

Levonorgestrel-releasing intrauterine system (LNG-IUS) relieves dysmenorrhea and heavy menstrual bleeding (HMB) in adenomyosis. However, its efficacy on health-related quality of life (HR-QOL) in patients with symptomatic adenomyosis remains unclear. The menorrhagia multi-attribute scale (MMAS), which measures HR-QOL improvement through the treatment of HMB, has never been used for evaluating menorrhagia-specific HR-QOL in patients with symptomatic adenomyosis. Hence, this study aimed to investigate the efficacy of LNG-IUS in improving menorrhagia-specific HR-QOL in these patients using the MMAS. The participants were diagnosed by magnetic resonance imaging. We also assessed the relationships between menorrhagia-specific HR-QOL, blood hemoglobin levels, and the degree of dysmenorrhea before and during LNG-IUS treatment. The LNG-IUS treatment improved the menorrhagia-specific HR-QOL more effectively in incipient type adenomyosis than in advanced type adenomyosis. The efficacy of LNG-IUS treatment on dysmenorrhea evaluated by the visual analog scale score tended to be better in the incipient type than in the advanced type. By the treatment of LNG-IUS, the blood hemoglobin level was not improved in the advanced type but in the incipient type. Furthermore, dysmenorrhea and HMB-related anemia were associated with HR-QOL impairment, and LNG-IUS treatment may improve the HR-QOL by relieving the symptoms. In conclusion, the effectiveness of LNG-IUS on HR-QOL is decreased by advanced adenomyosis. Thus, magnetic resonance imaging use should be reinforced to predict LNG-IUS efficacy in improving the HR-QOL of patients with adenomyosis.

Efficacy of high-intensity focused ultrasound combined with LNG-IUS for adenomyosis: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) combined with the levonorgestrel intrauterine system (LNG-IUS) for adenomyosis. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases from their inception to Nov 20, 2021 for relevant articles that compared HIFU combined with LNG-IUS vs. HIFU alone in patients with adenomyosis. RevMan5.4 software was used for the data analysis. The primary outcome was changes in volume of the uterine. Secondary outcomes included visual analog scale (VAS) scores for dysmenorrhea, serum CA125 level, recurrence rate, changes in volume of the adenomyotic lesion, menstrual volume scores, and adverse reactions. Data synthesis was conducted using a random-effects model with significant heterogeneity (I2 > 50%), and using a fixed-effects model otherwise. This study is registered on the PROSPERO platform (CRD42021295214). RESULTS: The final analysis included 13 studies, with a total of 1861 patients. Results of analysis revealed that there was no significant difference in uterine volume reduction between the HIFU control group and the HIFU/LNG-IUS group at 3 months after procedure (MD:30.63). Compared with the HIFU control group, the HIFU/LNG-IUS group had more pronounced reduction in uterine volume at 6 (MD:29.04) and 12 months (MD:22.10) after procedure. The HIFU/LNG-IUS group has lower VAS scores for dysmenorrhea than the HIFU control group at 3 (MD:1.68), 6 (MD:1.69), and 12 months (MD:1.30) after procedure. Serum CA125 level in the HIFU/LNG-IUS group decreased more significantly than the HIFU control group at 6 (MD:18.34) and 12 months (MD:18.49) after procedure. The recurrence rate in the HIFU/LNG-IUS group was lower than that in the HIFU control group (RR:0.20). CONCLUSIONS: Compared to HIFU control group, HIFU/LNG-IUS group for the management of adenomyosis had more advantages in alleviating symptoms and decreasing the volumes of the uterine and adenomyotic lesions. However, since the number of the included studies was too small and some of them were not RCT, this conclusion needs to be referenced with caution.

LNG-IUS vs. medical treatments for women with heavy menstrual bleeding: A systematic review and meta-analysis.

Introduction: To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with medical treatments for women with heavy menstrual bleeding. Materials and methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), and Wanfang databases for relevant randomized controlled trials (RCTs) in November 2021. All meta-analyses were performed using the random-effects model. PROSPERO registration number: CRD42021295379. Results: A total of trials (with 14 references) reporting on 1,677 women were included in this systematic review. The majority of the included RCTs were rated with low-to-unclear risk of bias in selection, detection, attrition, reporting, and other bias. All RCTs were rated as high risk in performance bias because blinding was difficult to ensure in the compared groups. Results of meta-analyses revealed that the number of clinical responders was greater in the LNG-IUS group than that in the medical treatments group at both 6-month (steroidal: five RCTs; n = 490; risk ratio [RR]: 1.72 [1.13, 2.62]; I 2 = 92%; nonsteroidal: one RCT; n = 42; RR: 2.34 [1.31, 4.19]) and 12-month (steroidal: three RCTs; n = 261; RR: 1.31 [1.01, 1.71]; I 2 = 74%) endpoints, with no clear differences on number of dropouts, and the incidence of adverse events. Conclusion: Evidence indicates that LNG-IUS is superior to the medical treatments in short-term and medium-term clinical responses, blood loss control, compliance, and satisfaction. Meanwhile, frequency of adverse events related to LNG-IUS is acceptable. Systematic review registration: PROSPERO, identifier CRD42021259335, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021295379.

Hormonal contraception and risk of breast cancer and breast cancer in situ among Swedish women 15-34 years of age: A nationwide register-based study.

Background: Evidence on a possible association between newer hormonal contraceptives (HC) and risk of breast cancer remains inconclusive, especially as concerns progestogen-only methods. Methods: In this nationwide prospective cohort study, all Swedish women aged 15-34 at study start on January 1st 2005, or who turned 15 years during the study period, were followed until December 31st 2017. Using information from seven National Registers, we assessed the risk ratio of developing breast cancer and breast cancer in situ in relation to different HC using Poisson regression. We adjusted the analyses for several known confounders of breast cancer. Findings: This cohort included 1.5 million women providing more than 14 million person-years. During the study period, 3842 women were diagnosed with breast cancer. Compared with never users of any HC, we found no increased risk of developing breast cancer among current users of any combined HC, IRR 1.03 (0.91-1.16), whereas current users of progestogen-only methods had an increased risk of developing breast cancer, IRR 1.32 (1.20-1.45). Across all types of HC, the risk of developing breast cancer appeared to be highest the first five years of use (combined HC IRR 1.39 (1.14-1.69); progestogen-only methods IRR 1.74 (1.44-2.10). The risk disappeared ten years after the women stopped using HC. The absolute risk of breast cancer per 100,000 women-years was 22.4 for never users, 10.9 for current users of combined HC, and 29.8 for current users of progestogen-only methods. Interpretation: Current use of progestogen-only methods is associated with a small increased risk of developing breast cancer, whereas we could only detect an increased risk among users of combined HC during the first five years of use. This may partly be explained by a selective prescription of progestogen-only methods to women with risk factors for breast cancer, like smoking or obesity. As the absolute risk of breast cancer was small, the many health benefits associated with HC must also be taken into account in contraceptive counselling. Funding: This study was funded by the Swedish Cancer Society and by the Uppsala County Council, the Faculty of Medicine at Uppsala University.

Levonorgestrel-releasing intrauterine system versus systemic progestins in management of endometrial hyperplasia: A systemic review and meta-analysis.

INTRODUCTION: Endometrial hyperplasia is associated with varying risk of endometrial cancer. The aim of this review is to assess effectiveness of levonorgestrel-releasing intrauterine system (LNG-IUS), compared to systemic progestins, in management of endometrial hyperplasia MATERIALS AND METHODS: A search on studies comparing LNG-IUS to systemic progestins was conducted on Scopus, Web of science, Cochrane, PubMed and Embase databases, from the date of inception to September 20th, 2020. Studies were excluded if they were non-comparative, animal studies, review articles, case reports, case series, and conference papers. Primary outcomes include resolution/regression rate, failure rate, and hysterectomy rate. Analysis was pooled using random effect model and was expressed as pooled odds ratios (OR) and 95% confidence interval (CI). Quality assessment was performed using Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale (NOS) assessment tool. MOGGE Meta-analysis Matrix was used to illustrate multiple subgroup analyses. RESULTS: Out of 341 studies retrieved from literature search, 12 were eligible. LNG-IUS yielded significantly higher resolution/regression rate (91.3% vs 68.6%, OR 3.42, 95% CI 1.86-6.30). Failure and hysterectomy rates were significantly lower in LNG-IUS group compared to systemic progestins' group (19.2% vs. 32.3%, OR 0.34, 95% CI 0.20-0.57 and 9.3% vs. 24.1%, OR 0.41, 95% CI 0.29-0.57, respectively). Subgroup analysis of studies including complex hyperplasia only did not show significant difference in resolution/regression rate was not statistically significant. CONCLUSION: LNG-IUS is associated with high success rate in management of women with endometrial hyperplasia. However, specific effectiveness of LNG-IUS on more advanced histologic subtypes is less studied.

Endometrial Cancer Following Levonorgestrel-Releasing Intrauterine System Insertion in Young Women with Atypical Hyperplasia: Two Case Reports and Literature Review.

Levonorgestrel-releasing intrauterine system (LNG-IUS) insertion is the first-line treatment for atypical hyperplasia (AH) in young women who wish to retain their fertility. However, the procedure is not always effective, and may allow AH to progress to endometrioid endometrial cancer (EEC). Two young women with AH who wished to preserve their fertility developed EEC following 52-mg LNG-IUS in insertion at our institution. One was a 34-year-old woman diagnosed with endometrial cancer 2 years after LNG-IUS insertion. The second was a 30-year-old woman diagnosed 17 months after LNG-IUS insertion. Proactive molecular risk classification for endometrial cancer (ProMisE) classification revealed that the first and second patients had p53-abnormal (p53abn) EEC and mismatch repair deficient (MMR-d) EEC, respectively. MMR-d and p 53abn were frequently observed in both AH and EEC specimens. Studies suggest that MMR-d and p53abn are predictors of the occurrence adverse effects after fertility-preserving treatment for EEC. AH is a precursor of EEC. Therefore, p53 and mismatch repair (MMR) mutation may be used to identify women with AH who will not likely benefit from progestin therapy. Molecular assays in women with AH will likely be useful for identifying novel predictive biomarkers of progestin resistance and to improve the safety of conservative treatment. Combined assessment of progesterone receptor (PR) with these predictive molecular markers may improve the predictive ability.

Effectiveness, safety and overall satisfaction of early postpartum placement of hormonal IUD compared with standard procedure: An open-label, randomized, multicenter study.

INTRODUCTION: In this open-label, randomized controlled, non-inferiority, multicenter study we aimed to study the risk of termination of pregnancy within 1 year postpartum, the safety profile and patient acceptability after early postpartum insertion of a hormonal intrauterine device (LNG-IUS, Mirena®) compared with standard placement 6-8 weeks postpartum. MATERIAL AND METHODS: April 2018 to January 2020 women with uncomplicated vaginal delivery at four urban birth centers in Sweden, were randomized to either early placement within 48 h after delivery (early group) or standard placement 6-8 weeks postpartum (standard group) of a hormonal intrauterine device. The main outcome measure was the proportion of terminations of pregnancies in each group during the first year after placement of the intrauterine device. Registration EudraCT database no. 2017-001945-29. RESULTS: The study was prematurely stopped according to the protocol due to an expulsion rate >20% in the early group. No pregnancies occurred. Fifty-two women were randomized to early and 49 women to standard insertion. In the early group, 23/52 (44.2%) of the intrauterine devices were expelled. After expulsion, 10 women chose to have another hormonal intrauterine device placed but still significantly fewer women (39/52, 75%, p = 0.22) in the early group used the hormonal intrauterine device method at study completion. No expulsions occurred in the standard group, but 5/49 (10.2%) requested removal and 41/49 (83.7%, p = 0.22) had used the hormonal intrauterine device method continuously for 1 year. CONCLUSIONS: Early hormonal intrauterine device insertion after vaginal delivery is associated with high expulsion rates. Despite this, a high continuation rate of the hormonal intrauterine device method is seen among women once choosing the method. In the light of high continuation rates, the advantages of early insertion could balance the risk of expulsion for well-informed women.

In-office hysteroscopic removal of retained or fragmented intrauterine device without anesthesia: a cross-sectional analysis of an international survey.

To investigate about the opinions of gynecologists regarding the in-office hysteroscopic removal of retained or fragmented intrauterine device (IUD) without anesthesia. An online survey was made available to gynecologists who routinely performed in-office hysteroscopy. Five areas of interest were analyzed: average number of hysteroscopic procedures performed without anesthesia, availability on their local market of the different types of hormonal and non-hormonal IUDs, reasons for the hysteroscopic removal of the IUD, types of IUDs that were more commonly found retained or fragmented and, overall difficulty of the hysteroscopic removal. A total of 419 surgeons voluntarily responded the survey, of which 19 were excluded for not performing in-office hysteroscopy. The most commonly available IUD was the Levonorgestrel-based Mirena (Bayer Healthcare, Germany) or similar, (399/400, 99.7%), followed by Copper T (Paragard, CooperSurgical INC, United States) (397/400, 99.2%), Multiload (234/400, 58.5%) and Jaydess (Bayer Healthcare, Germany) (227/400, 56.7%). The intracavitary retention of the IUD with (44.5%, 178/400) and without (42.2%, 169/400) visible strings accounted as the most common reason for undergoing hysteroscopic IUD removal. Copper T IUD was the most common intracavitary retained (297/400, 74.2%) as well as fragmented device (236/400, 59.9%). The in-office hysteroscopic removal of the IUD was considered an easy procedure by almost all the operators (386/400, 96.5%). In-office hysteroscopy without anesthesia is seen as a feasible and easy approach to remove retained or fragmented IUDs inside the uterine cavity or cervical canal. While the Levonorgestrel-based IUD is the most commercialized, Copper T IUDs are the most commonly found retained or fragmented.

Introducing the hormonal Intrauterine Device in Madagascar, Nigeria, and Zambia: results from a pilot study.

BACKGROUND: The hormonal Intrauterine Device (IUD) is a highly effective contraceptive option growing in popularity and availability in many countries. The hormonal IUD has been shown to have high rates of satisfaction and continuation among users in high-income countries. The study aims to understand the profiles of clients who choose the hormonal IUD in low- and middle-income countries (LMICs) and describe their continuation and satisfaction with the method after 12 months of use. METHODS: A prospective longitudinal study of hormonal IUD acceptors was conducted across three countries-Madagascar, Nigeria, and Zambia-where the hormonal IUD had been introduced in a pilot setting within the of a broad mix of available methods. Women were interviewed at baseline immediately following their voluntary hormonal IUD insertion, and again 3 and 12 months following provision of the method. A descriptive analysis of user characteristics and satisfaction with the method was conducted on an analytic sample of women who completed baseline, 3-month, and 12-month follow-up questionnaires. Kaplan-Meier time-to-event models were used to estimate the cumulative probability of method continuation rates up to 12 months post-insertion. RESULTS: Each country had a unique demographic profile of hormonal IUD users with different method-use histories. Across all three countries, women reported high rates of satisfaction with the hormonal IUD (67-100%) and high rates of continuation at the 12-month mark (82-90%). CONCLUSIONS: Rates of satisfaction and continuation among hormonal IUD users in the study suggest that expanding method choice with the hormonal IUD would provide a highly effective, long-acting method desirable to many different population segments, including those with high unmet need.