Levonorgestrel-releasing Intrauterine System Research Articles

Etonogestrel-releasing subdermal contraceptive implant: Budget impact analysis based on the Brazilian private healthcare system.

High rates of unplanned pregnancies persist despite pharmacological developments and advancements in contraceptive methods. Here, we demonstrate that the etonogestrel-releasing subdermal contraceptive implant (IMP-ETN) may be an appropriate and cost-effective alternative to levonorgestrel-releasing intrauterine systems (LNG-IUSs) for women in Brazil. For our pharmacoeconomic analysis, we reviewed the literature on IMP-ETN regarding its acceptance, eligibility criteria, choice, relations with age, adverse events and, finally, the unmet need in the fee-for-service private healthcare sector. We considered qualitative observations in combination with quantitative analysis and performed a deterministic sensitivity analysis to investigate whether this technology can be self-sustainable over a period of five years. The target population for this analysis comprised 158,696 women. Compared with the continued use of LNG-IUSs, adopting the IMP-ETN can result in a cost avoidance of $ 7.640.804,02 in the first year and $ 82,455,254.43 in five years. Disseminating information among physicians will promote this change and strengthen the potential cost avoided by private health system payers. These savings can be used to improve other healthcare programs and strategies. Moreover, the principles of care can be promoted by improving and adapting healthcare systems and expanding treatment and follow-up strategies. This would also provide support to women's reproductive rights and improve their quality of life. Our results suggest that the IMP-ETN has a favorable cost-effectiveness profile. Given all its advantages and negative incremental cost impact over a period of five years, the IMP-ETN may be a more favorable alternative to LNG-IUSs. Therefore, it should be offered to beneficiaries with a private healthcare plan. This analysis overcomes previous barriers to the use of cost-benefit models, and our results may help balance decision-making by policymakers, technical consultants, and researchers.

Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis.

To evaluate the clinical efficacy of etonogestrel subcutaneous implant (ENG-SCI) with that of the levonorgestrel-releasing intrauterine system (LNG-IUD) for adenomyosis treatment. A prospective randomized cohort study was conducted including 108 patients (50 patients in ENG-SCI group and 58 in the LNG-IUD group) with adenomyosis from January 2019 to July 2021. After 3 months of treatment, both ENG-SCI group and LNG-IUD group showed significant improvement in patients' visual analog scale, pictorial blood loss assessment chart (PBAC), and uterine volume (P ＜ 0.05). The uterine volume of patients in LNG-IUD group decreased more significantly than that in the ENG-SCI group since 3 months of treatment. The PBAC score in the LNG-IUD group improved better than that in the ENG-SCI group since 6 months of treatment (P ＜ 0.05). No significant difference in the occurrence rate of ideal vaginal bleeding patterns and the hemoglobin levels between the two groups was observed. The ENG-SCI group had a higher probability of weight gain and progesterone-related side effects (P ＜ 0.05). Both ENG-SCI and LNG-IUD were effective in treatment of adenomyosis. However, LNG-IUD had a more significant effect in treating adenomyosis-related dysmenorrhea, excessive menstrual flow, anemia, and uterine enlargement, with relatively fewer side effects.

Association of vaginal oestradiol and the rate of breast cancer in Denmark: registry based, case-control study, nested in a nationwide cohort

ObjectiveTo estimate the rate of breast cancer associated with use of vaginal oestradiol tablets according to duration and intensity of their use.DesignRegistry based, case-control study, nested in a nationwide cohort.SettingBased...

Laparoscopic adenomyomectomy combined with levonorgestrel-releasing intrauterine system is effective for long-term management of adenomyosis

BackgroudLaparoscopic adenomyomectomy combined with intraoperative placement of levonorgestrel-releasing intrauterine device (LNG-IUS) is a novel conservative surgical procedure for adenomyosis. Our study aimed to compare the efficacy of surgery with or without intraoperative placement of LNG-IUS treatment in adenomyosis.MethodsWe retrospectively reviewed the medical records of adenomyosis patients who received laparoscopic adenomyomectomy from January 2014 to April 2020, finally including 70 patients undergoing surgery-LNG-IUS as group A and 69 patients undegoing surgery only as group B. Risk factors for three-year relapse were analyzed using Cox’s multivariate proportional hazard analysis.ResultsVisual analog scale and Mansfield-Voda-Jorgensen Menstrual Bleeding Scale scores of group A at 3, 6, 12, 24, and 36 months were significantly lower than those of group B at the corresponding points (P < .001 for both scales). Individuals in both groups showed statistically significant symptom relief. The recurrence rate in group A was significantly lower than that in group B at 36 months after the surgery (2.94% vs. 32.84%, P < .001). A cox proportional hazard model showed that relapse was significantly associated with coexisting ovarian endometriosis (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 1.33–7.02, P = .015). Patients who received surgery-LNG-IUS had a lower risk of recurrence than those with surgery-alone (aHR, 0.07; 95% CI, 0.016–0.31, P < .001).ConclusionsConservative surgery with intraoperative placement of LNG-IUS is effective and well-accepted for long-term therapy with a lower recurrence rate for adenomyosis. Coexistent ovarian endometriosis is a major factor for adenomyosis relapse.

Depression risk in users of different doses of levonorgestrel intrauterine systems: a nationwide prospective cohort study

Use of the high-dose levonorgestrel-releasing intrauterine system (LNG-IUS) has been associated with increased risk of incident depression. Evidence is lacking on the influence of use of two recently marketed low-dose LNG-IUS on risk of depression. This study aims to examine associations between use of different doses of LNG-IUS and risk of depression. We conducted a nationwide prospective cohort study involving all first-time users of an LNG-IUS among all Danish nulliparous women aged 15-34 years with no medical history of depression, major psychiatric diseases, endometriosis, heavy menstrual bleeding, polyp, myoma, dysmenorrhoea, iron supplement use, abortion, and infertility treatment. A total of 46,565 first-time users of LNG-IUS were followed for 80,516 person-years with 1,531 incident initiations of antidepressant use observed during follow-up. Use of the high-dose LNG-IUS containing 52mg levonorgestrel was initiated by 9,902 (21%) women, while 20,665 (44%), and 15,998 (34%) initiated use of the low-dose LNG-IUS containing 19·5 mg and 13·5 mg levonorgestrel, respectively.The age-, calendar-time-, and education-standardised incidence rates of first-time depression per 1,000 person-years at full LNG-IUS duration were 30.8 (95% CI 23·6-39·5) for the 52 mg LNG-IUS, 19·8 (95% CI 16·1; 24·0) for the 19·5 mg LNG-IUS, and 17·7 (95% CI 14·4-21·5) for the 13·5 mg LNG-IUS-. Compared to the high-dose 52 mg LNG-IUS, the adjusted number of avoided depressions per 1,000 person-years were 11·0 (95% CI 7·1-14·9) for the 19·5 mg LNG-IUS and 13·1 (95% CI 9·6-16·6) for the 13·5 mg LNG-IUS. The corresponding adjusted rate ratios were 0·77 (95% CI 0·68; 0·88) and 0·85 (95% CI 0·75-0·96). The reduced risk of depression with low-dose LNG-IUS compared to high-dose LNG-IUS was observable throughout duration of use. Use of low-dose LNG-IUS containing 19·5 mg and 13·5 mg levonorgestrel, respectively, were associated with a reduced risk of incident depression compared to use of the high-dose 52 mg LNG-IUS. The study suggests that low-dose LNG-IUS should be preferred over the high-dose LNG-IUS for contraceptive purpose. Sygeforsikringen "Danmark" grant: 2021-0128.

A 52-mg levonorgestrel-releasing intrauterine system vs bipolar radiofrequency nonresectoscopic endometrial ablation in women with heavy menstrual bleeding: long-term follow-up of a multicenter randomized controlled trial

BACKGROUNDThe symptom of heavy menstrual bleeding has a significant impact on professional, physical and social functioning. In 2021, results from a randomized controlled trial comparing a 52 mg levonorgestrel-releasing intrauterine system and radiofrequency non-resectoscopic endometrial ablation as treatments for women with heavy menstrual bleeding were published. Both treatment strategies were equally effective in treating heavy menstrual bleeding during a two-year follow-up. However, long-term results are also relevant for both patients and health care providers. OBJECTIVEThe aim of this study was to assess long-term differences in reintervention risk and menstrual blood loss in women with the symptom of heavy menstrual bleeding treated according to a strategy starting with a 52 mg levonorgestrel-releasing intrauterine system or radiofrequency non-resectoscopic endometrial ablation. STUDY DESIGNThis study was a long-term follow-up study of a multi-center randomized controlled trial (MIRA trial) in which women were allocated to either a 52 mg levonorgestrel-releasing intrauterine device (n=132) or radiofrequency non-resectoscopic endometrial ablation (n=138). Women from the original trial were contacted to fill out six questionnaires. The primary outcome was reintervention rate after allocated treatment. Secondary outcomes included surgical reintervention rate, menstrual bleeding measured by the Pictorial Blood Loss Assessment Chart, (disease-specific) quality of life, sexual function and patient satisfaction. RESULTSFrom the 270 women that were randomized in the original trial, 196 women (52 mg levonorgestrel-releasing intrauterine system group: n=94; radiofrequency non-resectoscopic endometrial ablation group: n=102) participated in this long-term follow-up study. Mean follow-up duration was 7.4 years (range 6-9 years). The cumulative reintervention rate (including both medical and surgical reinterventions) was 40.0% (34/85) in the 52 mg levonorgestrel-releasing intrauterine system group and 28.7% (27/94) in the radiofrequency non-resectoscopic endometrial ablation group (relative risk: 1.39; 95% confidence interval: 0.92-2.10). The cumulative rate of surgical reinterventions only was significantly higher for patients with a treatment strategy starting with a 52 mg levonorgestrel-releasing intrauterine system compared to radiofrequency non-resectoscopic endometrial ablation (35.3% [30/85] vs. 19.1% [18/94]; relative risk: 1.84; 95% confidence interval: 1.11-3.10). However, hysterectomy rate was similar: 11.8% [10/94] in the 52 mg levonorgestrel-releasing intrauterine system group and 18.1% [17/102] in the radiofrequency non-resectoscopic endometrial ablation group (relative risk: 0.65; 95% confidence interval: 0.32-1.34). Most reinterventions took place during the first 24 months of follow-up. A total of 171 Pictorial Blood Loss Assessment Chart scores showed a median bleeding score of 0.0. No clinically relevant differences were found regarding quality of life, sexual function and patient satisfaction. CONCLUSIONThe overall risk of reintervention after long-term follow-up was not different for women treated according to a treatment strategy starting with a 52 mg levonorgestrel-releasing intrauterine system as compared to a strategy starting with radiofrequency non-resectoscopic endometrial ablation. Yet, women allocated to a treatment strategy starting with a 52 mg levonorgestrel-releasing intrauterine system had a significantly higher risk for surgical reintervention, which was driven by an increase in subsequent endometrial ablation. Both treatment strategies remain effective in lowering menstrual blood loss over the long-term. The results of this long-term follow-up study help physicians to optimize counseling of women suffering from the symptom of heavy menstrual bleeding. Optimized counseling will enable women to make a well-informed choice regarding treatment.

Efficacy of fertility-sparing treatment with LNG-IUS is associated with different ProMisE subtypes of endometrial carcinoma or atypical endometrial hyperplasia.

To determine whether proactive molecular risk classifier for endometrial cancer (ProMisE) could be used to assess the prognosis of patients with atypical endometrial hyperplasia (AEH) or early-stage endometrial cancer (EC) treated with levonorgestrel-releasing intrauterine system (LNG-IUS). A retrospective cohort study was conducted among 93 AEH or early-stage EC patients who received LNG-IUS to preserve fertility . By immunohistochemistry and gene sequencing, 4 subtypes of ProMisE were identified (p53 wild type [p53 wt], mismatch repair-deficient [MMRd], p53-abnormal, and POLE-mutated). The primary outcome was the time to complete response (CR) after LNG-IUS therapy. Secondary outcomes included the recurrence rate after CR and success rate of conception. Among the 93 patients, 15 (16.1%) were classified as MMRd, 6 (6.5%) as POLE-mutated, 5 (5.4%) as p53-abnormal, and 67 (72.0%) as p53 wt. Comparison of serum cancer antigen 125, family history of tumor, and positive rates of programmed cell death 1 ligand 1 protein and Ki67 protein in 4 groups showed statistically significant differences (p<0.05). Patients with the p53-abnormal subtype had the lowest overall CR rate (40%) and the highest recurrence rate (2/2). Patients with POLE-mutated subtype had the best prognosis, and all 6 patients achieved CR. When patients achieved complete remission, assisted reproductive technology was more likely to help them conceive than natural conception (p<0.05). Patients with early-stage EC or AEH who are more likely to benefit from fertility-sparing treatment can be identified using ProMisE classifier. Patients with POLE-mutated are suitable for fertility-sparing treatment with LNG-IUS.

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

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. 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. 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). 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.

Laboratory evaluation of the hormonal agents effects on the plasma hemostasis system in women of reproductive age

Background: With the evolution of hormonal contraception, such as implementation of low dose agents, new regiments and administration routes of contraceptives, the risk of thrombotic complications persists, although is decreasing. The search for an available test for hemostasis assessment, which would allow for the prediction of thrombotic complications in high risk patients, remains relevant. Global tests for hemostasis assessment, such as thrombin generation test and thrombodynamics test, are attracting the specialists' attention due to the possibility of a quick integrative assessment of plasma hemostasis, especially during choice and tailoring of an optimal version of hormonal therapy.&#x0D; Aim: To assess the value of the integral thrombodynamics test in the multifactorial assessment of hemostasis system in women of reproductive age using hormonal contraceptives.&#x0D; Materials and methods: This observational prospective comparative study included 408 women aged 18 to 49 years followed from 2018 to 2022 in The Nikiforov Russian Center of Emergency and Radiation Medicine and Centre of Miscarriage Prevention and Treatment of the Maternity Hospital No. 1, St. Petersburg. From these, 208 women (mean age, 38.0 ± 7.0 years) were taking hormonal contraceptives (HC+ group), and 200 women (mean age, 37.5 ± 9.2 years) were in the control group (HC-). In the HC+ group, 163 women were taking combination oral contraceptives, 24 had an intrauterine levonorgestrel-releasing system, 8 used vaginal rings, and 13 were using progestin only oral contraceptives. Multifactorial clinical and laboratory assessment included taking past history, measurement of pro- and anticoagulation blood parameters, fibrinolysis, and endothelial function parameters (automatic coagulometer ACL TOP 500, Instrumentation Laboratory, USA). The integral assessment of the hemostasis system was performed with Thrombodynamics Registrator T-2 (Hemacor, Russia).&#x0D; Results: The groups were similar as per their age, chronic venous insufficiency and smoking. The HC+ group had significantly higher proportion of women with cardiovascular disorders (p = 0.0037), obesity (p = 0.0004), and headache (p 0.0001), compared to the HC- group. The thrombodynamics test showed a significantly higher rate of clot formation in the women taking hormonal contraception, compared to that in the HC- group (36.2 [30.1; 43.6] and 30.3 [28.0; 33.6] mcm/min, respectively, р 0.001). Hypercoagulation identified by the thrombodynamics test was associated with slowing down of XIIа-dependent fibrinolysis (6 [5; 8] min in the HC- and 12.8 [8; 16] min in the HC+ group, p 0,001) and higher levels of endothelial dysfunction markers (FVIII, 113 [85; 156] and 150 [107; 180]%, p = 0.015; vFW, 98 [85; 133] and 146 [95; 168]%, respectively, p = 0.003). The analysis of plasma hemostasis parameters depending on the presence of thromboembolic risk factors has shown that higher number of the risk factors is associated with higher velocity parameters in the thrombodynamics test in the range of chronometric hypercoagulation.&#x0D; Conclusion: The integral thrombodynamics test for the assessment of plasma hemostasis allows for identification of hemostasis dysfunction in women taking hormonal contraceptives. To prevent the risk of thromboembolic complications, it is desirable to assess blood coagulation system parameters before administration of hormonal agents.

#378 : Intrauterine Suture of Levonorgestrel Intrauterine Device Under Hysteroscopy

Background and Aims: Levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective and long-term treatment for adenomyosis, especially for patients who have severe dysmenorrhea symptoms but a strong desire to preserve their uterus. However, expulsion of the device for patients with an enlarged uterus remains a problem. In this study, an LNG-IUS was stitched on the posterior wall of the uterus under hysteroscopy, which can be an alternative method to this problem. Methods: 21 patients with adenomyosis who had previously been treated with the LNG-IUS and experienced expulsion for at least one time were enrolled. The fixation of the LNG-IUD on the posterior wall of the uterus was performed with a 4-0 Ethicon polypropylene non-absorbable suture through an endoscopic needle driver and a knot-pushing device. Results: During the postoperative follow-up, all patients experienced complete remission of their symptoms: a significant decrease in menstrual flow, relief of dysmenorrhea, and improvement in quality of life. No expulsion of device and other compilations were found. Conclusions: In patients with adenomyosis suffering from dysmenorrhea or heavy menstrual blood loss, suture fixation of an LNG-IUS using the hysteroscopic cold knife surgery system is a minimally invasive and effective alternative treatment for patients with an enlarged uterus and decreases the risk of LNG-IUS expulsion.

Levonorgestrel-releasing intrauterine system versus oral progestogens for non-atypical endometrial hyperplasia: predictors for treatment failure

Levonorgestrel-releasing intrauterine system versus oral progestogens for non-atypical endometrial hyperplasia: predictors for treatment failure

Five-year Contraceptive Use of 52-mg Levonorgestrel Releasing Intrauterine System in Young Women, Menstrual Patterns, and New Contraceptive Choice.

To evaluate the continuation rates of the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) during the first 5 years of use, reasons for its discontinuation, bleeding patterns, and new contraceptive choice after the 5th year, in adolescents and young women. The present study was a 5-year prospective cohort conducted in a Family Planning Service of a tertiary hospital in Brazil. We selected 100 healthy women between 15 and 24 years old who used 52-mg LNG-IUS for contraception. The clinical follow-up of these women took place from June 2017 to December 2022. The study evaluated the continuation rates of the method, reasons for its discontinuation, bleeding patterns, and new contraceptive choice after the 5th year. Continuous data were reported as mean ± standard deviation (SD) and range (minimum-maximum). Categorical variables were described as percentages. The continuation rates of LNG-IUS were 89.1% (82/92), 82.9% (72/87), 75.3% (64/85), 70.5% (60/85), and 64.2% (54/84) in the 1st, 2nd, 3rd, 4th, and 5th years of use, respectively. The main reason for discontinuation was acne (11/30). Amenorrhea rates were 50, 54.1, 39, 35.7, and 51.8% at 12, 24, 36, 48, and 60 months, respectively. All patients who completed the study and needed contraception after the 5th year opted for long-acting contraceptive methods (LARC). The LNG-IUS showed high continuation rates in adolescents and young women in the first 5 years of use. Most patients who completed the study chose a LARC method after the 5th year.

Current Medical Therapy for Adenomyosis: From Bench to Bedside.

Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on managing abnormal uterine bleeding (AUB) and dysmenorrhea, the main symptoms of adenomyosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid provide limited support for mild symptoms or symptom re-exacerbation during hormone therapy. The levonorgestrel-releasing intrauterine system (LNG-IUS) is commonly employed in adenomyosis management, showing promise in symptom improvement and reducing uterine size, despite the lack of standardized guidelines. Dienogest (DNG) also exhibits potential benefits, but limited evidence hinders treatment recommendations. Danazol, while effective, is limited by androgenic side effects. Combined oral contraceptives (COCs) may be less effective than progestins but can be considered for contraception in young patients. Gonadotropin-releasing hormone (GnRH) agonists effectively manage symptoms but induce menopausal symptoms with prolonged use. GnRH antagonists are a recent option requiring further investigation. Aromatase inhibitors (AIs) show promise in alleviating AUB and pelvic pain, but their safety necessitates exploration and limited use within trials for refractory patients. This review highlights the complexity of diagnosing adenomyosis, its coexistence with endometriosis and uterine leiomyomas, and its impact on fertility and quality of life, complicating treatment decisions. It emphasizes the need for research on guidelines for medical management, fertility outcomes, long-term effects of therapies, and exploration of new investigational targets. Future research should optimize therapeutic strategies, expand our understanding of adenomyosis and its management, and establish evidence-based guidelines to improve patient outcomes and quality of life.

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

To evaluate the feasibility and effectiveness of hysteroscopic suture fixation of the levonorgestrel-releasing intrauterine system (LNG-IUS) for the treatment of adenomyosis. A retrospective case series. Two teaching hospitals with the technology of hysteroscopic suture fixation of the LNG-IUS. The study reviewed 79 adenomyosis patients who received the hysteroscopic suture fixation of the LNG-IUS from January 2021 to May 2022. Hysteroscopic suture fixation of the LNG-IUS to the posterior uterine wall with nondissolvable suture. 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. Hysteroscopic suture fixation of the LNG-IUS to the uterine fundus was associated with low expulsion rates and significantly improved dysmenorrhea and bleeding.

Ulipristal acetate versus levonorgestrel-releasing intrauterine system for heavy menstrual bleeding: the UCON randomised controlled trial and mechanism of action study

Background Heavy menstrual bleeding affects one in four women and negatively impacts quality of life. The levonorgestrel-releasing intrauterine system is an effective long-term treatment but is discontinued by many due to unpredictable bleeding, or adverse effects. The selective progesterone receptor modulator ulipristal acetate is used to treat symptomatic fibroids but long-term efficacy for the symptom of heavy menstrual bleeding, irrespective of presence of fibroids, is unknown. Objectives To determine whether ulipristal acetate is more effective at reducing the burden of heavy menstrual bleeding than levonorgestrel-releasing intrauterine system after 12 months of treatment in women with and without fibroids. We investigated mechanism of action of ulipristal acetate in a subset of 20 women. Design Randomised, open-label, parallel group, multicentre trial with embedded mechanistic study. Setting Ten UK hospitals. Participants Women with heavy menstrual bleeding aged 18 and over with no contraindications to levonorgestrel-releasing intrauterine system or ulipristal acetate. Interventions Three 12-week treatment cycles of 5 mg ulipristal acetate daily, separated by 4-week treatment-free intervals, or continuous levonorgestrel-releasing intrauterine system following allocation in a 1 : 1 ratio using a web-based minimisation procedure. Main trial outcome measures Primary outcome was quality-of-life measured by menorrhagia multi-attribute scale at 12 months. Secondary outcomes included menstrual bleeding and patient satisfaction. Impact on fibroid size, endometrial appearance and liver function was also collected. Mechanistic study outcome Cellular markers for endometrial cell structure and function, determined from endometrial biopsies; volume of uterus and fibroids and microcirculation parameters were determined from magnetic resonance images. Results Sample size was increased from 220 to 302 as a result of temporary halt to recruitment due to concerns of ulipristal acetate hepatoxicity. Subsequent withdrawal of ulipristal acetate and the COVID-19 pandemic led to a premature closure of recruitment, with 118 women randomised to each treatment and 103 women completing 12-month menorrhagia multi-attribute scale scores prior to this point. Primary outcome scores substantially improved in both arms, but at 12 months there was no evidence of a difference between those receiving three cycles of ulipristal acetate [median score category: 76–99, interquartile range (51–75 to 100), n = 53] and levonorgestrel-releasing intrauterine system [median score category: 76–99, interquartile range (51–75 to 100), n = 50; adjusted odds ratio 0.55, 95% confidence interval 0.26 to 1.17; p = 0.12]. Rates of amenorrhoea were much higher in those allocated ulipristal acetate compared with the levonorgestrel-releasing intrauterine system (12 months: 64% vs. 25%, adjusted odds ratio 7.12, 95% confidence interval 2.29 to 22.2). There was no evidence of a difference in other participant-reported outcomes. There were no cases of endometrial malignancy and no hepatotoxicity due to ulipristal acetate use. Mechanistic study results Ulipristal acetate produced a reversible reduction in endometrial cell proliferation, as well as reversible alteration of other endometrial cellular markers. Ulipristal acetate did not produce a reduction in the volume of the uterus irrespective of coexisting fibroids, nor an effect on uterine microvascular blood flow. Limitations The urgent safety measures and premature closure of recruitment impacted final sample size. Conclusions We found no evidence of a difference in quality of life between the two treatments, but ulipristal acetate was superior to levonorgestrel-releasing intrauterine system at inducing amenorrhoea. Ulipristal acetate currently has restricted availability due to concerns regarding hepatotoxicity. Future work There is a need to develop new, safe, effective and fertility-sparing medical treatments for heavy menstrual bleeding. The observed acceptability and effectiveness of ulipristal acetate warrants further research into the selective progesterone receptor modulator class of pharmacological agents. Study registration This trial is registered as ISRCTN 20426843.

Risk of Hysterectomy After Endometrial Ablation: A Systematic Review and Meta-analysis

ABSTRACT A common gynecological problem for approximately 30% of women at reproductive age in European countries is heavy menstrual bleeding (HMB). Although hysterectomy is a highly successful treatment for this benign problem, it also risks serious complications due to its nature as a major operation. Less invasive HMB treatment options include insertion of a levonorgestrel-releasing intrauterine system, medical treatment (such as tranexamic acid and oral contraceptive pill), or endometrial ablation (which aims to destroy endometrial tissue and the superficial myometrium to reduce/stop menstrual bleeding). Endometrial ablation failure may result in the objective outcome of hysterectomy. This meta-analysis and review aimed to assess hysterectomy risk following nonresectoscopic endometrial ablation treatment to improve understanding and HMB patient counseling. Various nonresectoscopic ablation techniques versus their associated hysterectomy rates were investigated, and subgroup analyses were performed. Following a comprehensive and thorough search process of the MEDLINE, CENTRAL, and EMBASE databases, 53 articles ultimately met the inclusion criteria for inclusion in the systematic review. Between 1992 and 2017, in the included studies, 48,071 patients underwent endometrial ablation. A high risk of bias was found in 13 studies (mainly due to selection or reporting bias), whereas 12 studies maintained low risk of bias. However, exclusion of the 13 high-risk studies for a subgroup analysis yielded similar results to the original meta-analysis. Results of the analysis indicated a consistently increasing post–endometrial ablation hysterectomy, with 2% increments annually between 1 and 5 years following the procedure, rising to 4.3% after 1 year and 12.4% after 5 years. In 2 studies, a post–10-year follow-up found a mean hysterectomy rate of 21.3%. Between both various study designs and the different varieties of devices used, no major differences in hysterectomy rates were found, respectively. Limitations of the review include a high risk for heterogeneity found among studies in almost all analyses utilized by this analysis. Publication bias and methodological issues (variation of population size and study type) lent to the heterogeneity. Because of this variation, the authors performed analyses of subgroups with different study designs. In addition, of the 53 studies included, 15 of them included fewer than 50 participants, which was corrected in this analysis via an inverse variance. Overall, the study indicated that hysterectomy risk following endometrial ablation increases from 4.3% at the 1-year mark to 12.4% at the post–5-year mark. Neither differences in nonresectoscopic endometrial ablation techniques nor study design seemed to affect hysterectomy rates. This systematic review's data can be applied to clinical practice and used for counseling patients about hysterectomy risks within 5 years of endometrial ablation.

Hysteroscopic suture of levonorgestrel-releasing intrauterine system: learning curve for in vitro simulation training.

To simulate hysteroscopic suturing in vitro and analyze the learning curve of gynecologists with different experience levels. Three gynecologists were trained on uterine models in a circulating water box. The posterior uterine wall was sutured 10 times under hysteroscopy for 5 consecutive days, and the time of each suture procedure was recorded. Doctors A, B, and C completed 50 posterior uterine sutures. After Dr. C completed 50 sutures on the posterior wall, he added 50 sutures on the anterior wall (Group D). The mean suturing time was 71.54 ± 68.158 s in Group A, 50.10 ± 28.060 s in Group B, 34.04 ± 10.457 s in Group C, and 30.38 ± 8.734 s in Group D. The difference between Groups C and B and between Groups B and A was statistically significant. There was no statistically significant difference between Groups C and D. Simulation curves were created using the number of features as the abscissa and cumulative sum as the coordinate, with peak curves of 19, 27, and 18 cases for Group A, B, and C, respectively. Doctors with experience in single-hole laparoscopic surgery or hysteroscopic suture surgery can significantly shorten the hysteroscopic suturing time.

Preservation of the reproductive health of military women: global experience and realities of Ukraine

A review of world literature and Ukrainian researches on the most common requests to gynecologists among military women, on the structure of pathology and treatment methods was made. Special attention is paid to the hormonal contraception, namely combined oral contraceptives (COCs) in the usual and continuous regime (avoiding the hormone-free interval) and the levonorgestrel-releasing intrauterine systems (LNG-IUDs).Cases of global practice of using COCs in extended regimen were considered, which showed that 47.2% of 1156 women chose a prolonged regimen of COCs, the main reason for this was the desire to avoid symptoms associated with menstruation. We consider this option very positive for military women, because some studies show that military women who took COCs in a continuous regimen were almost twice as favorable to their reception as those who used them in a regular mode.The positive aspects of the LNG-IUDs use in military women are presented, as a factor in the prevention of abnormal uterine bleeding, reducing the risk of iron deficiency in case of possible blood loss, and reducing the intensity of dysmenorrhea as a negative factor in the military conditions.Ways to increase compliance between a gynecologist and a military woman are also considered, using the example of global studies, which prove that insufficient awareness of patients about the possible ways and positive effects of using COCs in extended regimen reduced patients’ commitment to choosing new regimens.Conclusions. In today’s realities, the gynecological service in our country faces a number of new problems that require a strategic approach and solution. World practice and national studies prove that stress-induced hormonal disorders in military women, such as abnormal uterine bleeding, menstrual cycle disorders, dysmenorrhea, are negative factors in combat conditions, require the attention and resolution by doctors. One of the options for solving this problem can be the appointment of COCs according to the usual and extended scheme or appointment of LNG-IUDs.

The impact of self-administered vaginal isonicotinic acid hydrazide (INH) administration 12 hours prior to levonorgestrel-releasing intrauterine system in women delivered only by elective cesarean section: A randomized double blinded clinical trial

The impact of self-administered vaginal isonicotinic acid hydrazide (INH) administration 12 hours prior to levonorgestrel-releasing intrauterine system in women delivered only by elective cesarean section: A randomized double blinded clinical trial

LEVONORGESTREL RELEASING INTRAUTERINE SYSTEM (MIRENA) FOR ABNORMAL UTERINE BLEEDING- A USEFUL TOOL IN THE COVID TIMES

Objectives: To assess the effectiveness of the Levonorgestrel-releasing intrauterine system (LNG-IUS) in improving heavy menstrual bleeding (HMB) and evaluate satisfaction rates among women with heavy menstrual bleeding, treated with LNG–IUS. Material and methods: This prospective observational study with a one-year follow-up included 73 women of reproductive age 20 – 50 years with complaints of heavy menstrual bleeding (HMB). They presented to the Gynae ward and the outpatient department (OPD) of Khyber Teaching Hospital, Peshawar, Pakistan. Patients with more than 3 cm fibroids, pelvic inflammatory disease, bleeding of unknown cause, and any known pelvic malignancy were excluded. LNG-IUS (Mirena) was inserted in OPD routinely and in Operation Theater under anesthesia where the cervix could not be dilated. Patients were followed up in OPD at one month, 3 months, six months, and one year. Improvement in symptoms, satisfaction level, and Hemoglobin (Hb) before and after the procedure was documented on a Proforma. RESULTS:  There was a progressive resolution in the amount of bleeding in patients followed at 1-month, 3-month, six months, and one year. The satisfaction rate was 92%. There was an improvement in Hb in 97% of patients. Only 04 out of 73 patients needed a hysterectomy. CONCLUSION: Levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective and tolerated treatment option for abnormal uterine bleeding. In the Covid times, it proved to be an effective first-line management of AUB. We recommend its use after careful selection of patients and also recommend a good counseling session before its use. Keywords: Abnormal uterine bleeding, heavy menstrual bleeding, LNG – IUS.