Intrauterine System Group Research Articles

Comparative assessment of the effects of two intrauterine systems for long-term contraception on some haematological, biochemical, and immunological markers

An intrauterine system (IUS) is a type of contraception tool that is used in order to control fertility and prevent concep¬tion in women for a long period. The aim of this study was to assess the influence of copper- versus levonorgestrel-releasing IUSs on women’s health. This is a descriptive cross-sectional study of 75 women that were randomly se¬lected (50 women that used a copper-releasing IUS and the remaining 25 that used a levonorgestrel-releasing IUS) amongst those attending out patient’s clinics at Hillah, Iraq, from March to July 2016. All women were between 18 to 46 years of age, and have had an IUS for at least three months. The measurement of serum ceruloplasmin (SCerP), haemoglobin, vitamin D (VD), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) levels was undertaken. Our results revealed that the copper-releasing IUS group has low haemoglobin and VD levels, along with high levels of SCerP and proinflammatory cytokines. One the other hand, the levonorgestrel-releasing IUS group displayed no significant changes on the above markers. We can conclude that the levonorgestrel-releasing IUS is free of any adverse effect when compared to a copper-releasing IUS, at least with regard to the parameters examined by our study.

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.

Comparison of the efficacy of oral contraceptives and levonorgestrel intrauterine system in intermenstrual bleeding caused by uterine niche.

This study aimed to compare the effectiveness of oral contraceptives and a levonorgestrel intrauterine system in treating intermenstrual bleeding due to uterine niche. We retrospectively analyzed 72 patients with intermenstrual bleeding due to uterine niche from January 2017 to December 2021, of whom 41 were treated with oral contraceptives and 31 with a levonorgestrel intrauterine system. Post-treatment follow-ups at 1, 3, and 6 months were conducted to compare the efficiency and adverse effects between the two groups. In the oral contraceptive group, the effectiveness rate was higher than 80% at 1- and 3-months post-treatment and higher than 90% at 6 months. In the levonorgestrel intrauterine system group, the effectiveness rates were 58.06%, 54.84%, and 61.29% at 1, 3, and 6 months of treatment, respectively. Oral contraceptives were more effective than the levonorgestrel intrauterine system in treating intermenstrual bleeding caused by uterine niche.

The effect of a combined indomethacin and levonorgestrel-releasing intrauterine system on short-term postplacement bleeding profile: a randomized proof-of-concept trial

Long-acting reversible contraceptives, including hormonal levonorgestrel-releasing intrauterine systems, are the most effective methods of reversible contraception. However, unfavorable bleeding, particularly during the first months of use, is one of the most important reasons for discontinuation or avoidance. Minimizing this as early as possible would be highly beneficial. Nonsteroidal anti-inflammatory drugs inhibiting prostaglandin synthesis are known to reduce bleeding and pain at time of menses. A levonorgestrel-releasing intrauterine system has been developed with an additional reservoir containing indomethacin, designed to be released during the initial postplacement period. This proof-of-concept study aimed to establish whether the addition of indomethacin to the currently available levonorgestrel-releasing intrauterine system (average invivo levonorgestrel release rate of 8 μg/24 h during the first year of use) reduces the number of bleeding and spotting days during the first 90 days of use compared with the unmodified system. The dose-finding analysis included 3 doses of indomethacin-low (6.5 mg), middle (12.5 mg), and high (15.4 mg)-to determine the ideal dose of indomethacin to reduce bleeding and spotting days with minimal side-effects. This was a multicenter, single-blinded, randomized, controlled phase II trial conducted between June 2018 and June 2019 at 6 centers in Europe. Three indomethacin dose-ranging treatment groups (low-, middle-, and high-dose indomethacin/levonorgestrel-releasing intrauterine system) were compared with the unmodified levonorgestrel-releasing intrauterine system group, with participants randomized in a 1:1:1:1 ratio. The primary outcome was the number of uterine bleeding and spotting days over a 90-day reference (treatment) period. Secondary outcomes were the number of women showing endometrial histology expected for intrauterine levonorgestrel application and the frequency of treatment-emergent adverse events. Point estimates and 2-sided 90% credible intervals were calculated for mean and median differences between treatment groups and the levonorgestrel-releasing intrauterine system without indomethacin. Point and interval estimates were determined using a Bayesian analysis. A total of 174 healthy, premenopausal women, aged 18 to 45 years, were randomized, with 160 women eligible for the per-protocol analysis set. Fewer bleeding and spotting days were observed in the 90-day reference period for the 3 indomethacin/levonorgestrel-releasing intrauterine system dose groups than for the levonorgestrel-releasing intrauterine system without indomethacin group. The largest reduction in bleeding and spotting days was achieved with low-dose indomethacin/levonorgestrel-releasing intrauterine system, which demonstrated a point estimate difference of-32% (90% credible interval,-45% to-19%) compared with levonorgestrel-releasing intrauterine system without indomethacin. Differences for high- and middle-dose indomethacin/levonorgestrel-releasing intrauterine system groups relative to levonorgestrel-releasing intrauterine system without indomethacin were-19% and-16%, respectively. Overall, 97 women (58.1%) experienced a treatment-emergent adverse event considered related to the study drug, with similar incidence across all treatment groups including the unmodified levonorgestrel-releasing intrauterine system. These were all mild or moderate in intensity, with 6 leading to discontinuation. Endometrial biopsy findings were consistent with effects expected for the levonorgestrel-releasing intrauterine system. All 3 doses of indomethacin substantially reduced the number of bleeding and spotting days in the first 90 days after placement of the levonorgestrel-releasing intrauterine system, thus providing proof of concept. Adding indomethacin to the levonorgestrel-releasing intrauterine system can reduce the number of bleeding and spotting days in the initial 90 days postplacement, without affecting the safety profile, and potentially improving patient acceptability and satisfaction.

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding

Heavy menstrual bleeding affects the physical functioning and social well-being of many women. The levonorgestrel-releasing intrauterine system and endometrial ablation are 2 frequently applied treatments in women with heavy menstrual bleeding. This study aimed to compare the effectiveness of the levonorgestrel-releasing intrauterine system with endometrial ablation in women with heavy menstrual bleeding. This multicenter, randomized controlled, noninferiority trial was performed in 26 hospitals and in a network of general practices in the Netherlands. Women with heavy menstrual bleeding, aged 34 years and older, without a pregnancy wish or intracavitary pathology were randomly allocated to treatment with either the levonorgestrel-releasing intrauterine system (Mirena) or endometrial ablation, performed with a bipolar radiofrequency device (NovaSure). The primary outcome was blood loss at 24 months, measured with a Pictorial Blood Loss Assessment Chart score. Secondary outcomes included reintervention rates, patient satisfaction, quality of life, and sexual function. We registered 645 women as eligible, of whom 270 women provided informed consent. Of these, 132 women were allocated to the levonorgestrel-releasing intrauterine system (baseline Pictorial Blood Loss Assessment Chart score, 616) and 138 women to endometrial ablation (baseline Pictorial Blood Loss Assessment Chart score, 630). At 24 months, mean Pictorial Blood Loss Assessment Chart scores were 64.8 in the levonorgestrel-releasing intrauterine system group and 14.2 in the endometrial ablation group (difference, 50.5 points; 95% confidence interval, 4.3-96.7; noninferiority, P=.87 [25 Pictorial Blood Loss Assessment Chart point margin]). Compared with 14 women (10%) in the endometrial ablation group, 34 women (27%) underwent a surgical reintervention in the levonorgestrel-releasing intrauterine system group (relative risk, 2.64; 95% confidence interval, 1.49-4.68). There was no significant difference in patient satisfaction and quality of life between the groups. Both the levonorgestrel-releasing intrauterine system and endometrial ablation strategies lead to a large decrease in menstrual blood loss in women with heavy menstrual bleeding, with comparable quality of life scores after treatment. Nevertheless, there was a significant difference in menstrual blood loss in favor of endometrial ablation, and we could not demonstrate noninferiority of starting with the levonorgestrel-releasing intrauterine system. Women who start with the levonorgestrel-releasing intrauterine system, a reversible and less invasive treatment, are at an increased risk of needing additional treatment compared withwomen who start with endometrial ablation. The results of this study will enable physicians to provide women with heavy menstrual bleeding with the evidence to make a well-informed decision between the 2 treatments.

Postplacental placement of intrauterine devices: A randomized clinical trial

ObjectiveTo compare the expulsion rate of the TCu380A intrauterine device (IUD) or levonorgestrel (LNG) 52 mg intrauterine system (IUS) up to 90 days after postplacental placement (10 min after delivery of the placenta). Study designRandomized trial (1:1) of women aged 18–43 years and ≥37 weeks pregnant enrolled during early or prodromal labor at the University of Campinas, Brazil. Follow-up was scheduled at 42 and 90 days after device placement. We confirmed the IUD or IUS location using ultrasonography. Multivariate logistic regression was used to assess variables associated with expulsion. ResultsWe enrolled 140 women, and assigned 70 to the TCu380A IUD and 70 to the IUS groups. By the 90-day follow-up visit, 22/60 women (36.7%) in the TCu380A IUD group had expelled the device, as had 12/60 women in the IUS group (20%). Thirty-three of the 34 expulsions had occurred by the 42-day visit. Multivariate analysis demonstrated that the expulsion odds ratio ([OR]; 95% confidence interval [CI]) was higher after vaginal delivery than after Cesarean delivery (OR 5.60; 95% CI 2.08–15.10; P < 0.00) and higher among women with one (OR 4.38; 95% CI 1.33–14.43; P 0.00) or three or more deliveries (including the present one) (OR 6.08; 95% CI 1.78–20.77; P 0.00) than those with two deliveries. ConclusionsPostplacental TCu380A IUD placement had a higher expulsion rate than the IUS, and the expulsion rate was higher among women who had a vaginal delivery than those who had a Cesarean delivery. Most of the expulsions occurred within 42 days. ImplicationsPolicy makers should increase the availability of both the TCu380A and the LNG intrauterine devices for the immediate postpartum period, even though the expulsion rate is higher than that after interval placement.

Postoperative Levonorgestrel-Releasing Intrauterine System for Pelvic Endometriosis-Related Pain

To estimate the effectiveness of a postoperative levonorgestrel-releasing intrauterine system for relieving pelvic pain in patients with endometriosis. A double-blind randomized controlled trial was conducted in 55 patients with endometriosis and moderate-to-severe dysmenorrhea (visual analog scale, greater than 50 mm) undergoing laparoscopic conservative surgery. After surgery, patients were randomized to a levonorgestrel-releasing intrauterine system (n=28) or expectant management (n=27) group. Primary outcome was the change of dysmenorrhea visual analog scale. Secondary outcomes included changes of pelvic pain and dyspareunia visual analog scale, Short Form-36 score, and adverse effects. The two groups were comparable in age, body mass index, parity, and baseline pain scores. At 12 months, the levonorgestrel-releasing intrauterine system group had a significantly lower median value of dysmenorrhea and noncyclic pelvic pain score. Compared with the control group, the levonorgestrel-releasing intrauterine system group had greater reduction in dysmenorrhea visual analog scale (-81.0 compared with -50.0 mm, P=.006) and pelvic pain visual analog scale (-48.5 compared with -22.0 mm, P=.038) but a comparable reduction in dyspareunia visual analog scale (-15.0 compared with -19.0 mm, P=.831). Two patients in levonorgestrel-releasing intrauterine system group (7.4%) and nine in the expectant management group (39.1%) had recurrent dysmenorrhea within 1 year postoperatively (P=.014). Number-needed-to-treat to prevent one case with recurrent dysmenorrhea within the first year was three cases. The Short Form-36 scores improved in the levonorgestrel-releasing intrauterine system group but did not change in the expectant management group. There was no serious adverse event during the study period. The levonorgestrel-releasing intrauterine system is effective and well accepted for long-term therapy after conservative surgery for patients with moderate to severe pain related to endometriosis. It can improve the patient's quality of life, including physical and mental health.

Puerperal and menstrual bleeding patterns with different types of contraceptive device fitted during elective cesarean delivery

Objective To evaluate the impact of a copper-containing intrauterine contraceptive device (IUCD) and the levonorgestrel-releasing intrauterine system (IUS) on puerperal and menstrual bleeding when fitted intraoperatively during scheduled elective cesarean. Methods Participants were allocated to 3 groups: cesarean with no device inserted; IUCD inserted during cesarean; and IUS inserted during cesarean. Results There was significantly shorter and lighter puerperium in the IUS group (20.2 ± 7.7 days and 3.1 ± 1.6 pads/day) than in the IUCD (33.4 ± 9.5 days and 4.9 ± 2.4 pads/day) and the control (27.0 ± 11.4 days and 4.9 ± 2.3 pads/day) groups ( P < 0.012 and P < 0.0001, respectively). At the end of puerperium, mean duration of amenorrhea was significantly longer in the IUS group than in the IUCD and control groups ( P < 0.0001). Menstrual periods were longer and heavier in the IUCD group than in the control group but the difference was not significant ( P > 0.07). In the IUS group, menstrual periods were significantly shorter and lighter than in the other groups ( P < 0.0001). Conclusion Intrauterine system fitting at the time of elective cesarean is associated with significant reductions in the duration and amount of puerperal blood loss, as well as a high incidence of amenorrhea and lighter periods thereafter.

Levonorgestrel-Releasing Intrauterine System or Medroxyprogesterone for Heavy Menstrual Bleeding

To compare the efficacy and safety of the levonorgestrel-releasing intrauterine system and oral medroxyprogesterone acetate in the treatment of idiopathic heavy menstrual bleeding. In this multicenter, randomized, controlled study, women aged 18 years or older with heavy menstrual bleeding (menstrual blood loss 80 mL or more per cycle) were randomly assigned to six cycles of treatment with either levonorgestrel-releasing intrauterine system or oral medroxyprogesterone acetate (10 mg daily for 10 days beginning on day 16 of each cycle). The primary efficacy variables were the absolute change in menstrual blood loss from baseline to end of study and the proportion of women with successful treatment (defined as menstrual blood loss less than 80 mL and a 50% or greater reduction in menstrual blood loss from baseline). Of 807 women screened, 165 were randomly assigned to treatment (levonorgestrel-releasing intrauterine system n=82, oral medroxyprogesterone acetate n=83). At the end of the study, the absolute reduction in median menstrual blood loss was significantly greater in the levonorgestrel-releasing intrauterine system group (-128.8 mL, range -393.6 to +1242.2 mL) than in the medroxyprogesterone acetate arm (-17.8 mL, range -271.5 to +78.6 mL, P < .001), and the proportion of women with successful treatment was significantly higher for the levonorgestrel-releasing intrauterine system (84.8%) than for medroxyprogesterone acetate (22.2%, P < .001). In women with idiopathic heavy menstrual bleeding, the levonorgestrel-releasing intrauterine system reduces menstrual blood loss more effectively and has a higher likelihood of treatment success than oral medroxyprogesterone acetate. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00360490. I.

Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial

Heavy menstrual blood loss is a common reason for women to seek medical care. The levonorgestrel-releasing intrauterine system (IUS) is an effective medical treatment for menorrhagia. We report a randomised comparison of this approach with hysterectomy in terms of the quality of life of women with menorrhagia and cost-effectiveness. Of 598 women referred with menorrhagia to five university hospitals in Finland, 236 were eligible and agreed to take part. They were randomly assigned treatment with the levonorgestrel-releasing IUS (n=119) or hysterectomy (n=117). The amount of menstrual blood loss was objectively measured. The primary outcome measure was health-related quality of life at 12-month follow-up. Analyses were by intention to treat. In the group assigned the levonorgestrel-releasing IUS, 24 (20%) women had had hysterectomy and 81 (68%) continued to use the system at 12 months. Of the women assigned to the hysterectomy group, 107 underwent the operation. Health-related quality of life improved significantly in both the IUS and hysterectomy groups (change 0.10 [95% CI 0.06-0.14] in both groups) as did other indices of psychological wellbeing. There were no significant differences between the treatment groups except that women with hysterectomy suffered less pain. Overall costs were about three times higher for the hysterectomy group than for the IUS group. The significant improvement in health-related quality of life highlights the importance of treating menorrhagia. During the first year the levonorgestrel-releasing IUS was a cost-effective alternative to hysterectomy in treatment of this disorder.