Pirjo Inki

Levonorgestrel-releasing Intrauterine System and Endometrial Ablation in Heavy Menstrual Bleeding: A Systematic Review and Meta-analysis

OBJECTIVE: To compare the effects of the levonorgestrel intrauterine system and endometrial ablation in reducing heavy menstrual bleeding. DATA SOURCES: Medline and EMBASE were searched online using Ovid up to January 2009, as well as the reference lists of published articles, to identify randomized controlled trials comparing the levonorgestrel intrauterine system with endometrial ablation in the treatment of heavy menstrual bleeding. METHODS OF STUDY SELECTION: This systematic review and meta-analysis was restricted to randomized controlled trials in which menstrual blood loss was reported using pictorial blood loss assessment chart scores. TABULATION, INTEGRATION, AND RESULTS: Six randomized controlled trials that included 390 women (levonorgestrel intrauterine system, n=196; endometrial ablation, n=194) were retrieved. Three studies pertained to first-generation endometrial ablation (manual hysteroscopy) and three to second-generation endometrial ablation (thermal balloon). Study characteristics and quality were recorded for each study. Data on the effect of treatment on pictorial blood loss assessment chart scores were abstracted, integrated with meta-analysis techniques, and presented as weighted mean differences. Both treatment modalities were associated with similar reductions in menstrual blood loss after 6 months (weighted mean difference, –31.96 pictorial blood loss assessment chart score [95% confidence interval (CI), –65.96 to 2.04]), 12 months (weighted mean difference, 7.45 pictorial blood loss assessment chart score [95% CI, –12.37 to 27.26]), and 24 months (weighted mean difference, –26.70 pictorial blood loss assessment chart score [95% CI, –78.54 to 25.15]). In addition, both treatments were generally associated with similar improvements in quality of life in five studies that reported this as an outcome. No major complications occurred with either treatment modality in these small trials. CONCLUSION: Based on the meta-analysis of six randomized clinical trials, the efficacy of the levonorgestrel intrauterine system in the management of heavy menstrual bleeding appears to have similar therapeutic effects to that of endometrial ablation up to 2 years after treatment.

The levonorgestrel-releasing intrauterine system in heavy menstrual bleeding: a benefit-risk review.

Heavy menstrual bleeding (HMB) is a common problem in women of reproductive age and can cause irritation, inconvenience, self-consciousness and fear of social embarrassment. Our objective was to review and appraise literature identified from the MEDLINE and EMBASE databases to evaluate the clinical evidence and provide an update on the risks and benefits of using the levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of HMB.The LNG-IUS consistently reduces menstrual blood loss (MBL) in women with HMB, including those with underlying uterine pathology or bleeding disorders. The available data suggest that it reduces MBL to a greater extent than other medical therapies, including combined oral contraceptives, oral progestogens (both short- or long-cycle regimens), tranexamic acid and oral mefenamic acid. In addition, the LNG-IUS and endometrial ablation appear to reduce MBL to a similar extent. The adverse effects reported with the LNG-IUS in women with HMB are similar to those typically observed in women using the system for contraception. Uterine perforations were not reported in any of the studies reviewed, but expulsion rates may be higher than in the general population of LNG-IUS users. Overall, the LNG-IUS has a positive effect on most quality-of-life domains, at least comparable to those achieved with hysterectomy or endometrial ablation, and is consistently a cost-effective option across a variety of countries and settings.In conclusion, the LNG-IUS is an effective treatment option for women with HMB, including those with underlying organic pathology or bleeding disorders.

Fertility after discontinuation of contraception: a comprehensive review of the literature

BACKGROUND Fear of adverse effects on subsequent fertility following reversible contraceptive use is an important concern for some women. STUDY DESIGN We undertook a comprehensive and objective review of the literature for prospective studies reporting pregnancy rates in women following contraceptive cessation. One-year pregnancy rates and pregnancy outcomes are summarized. RESULTS We identified and analyzed 17 studies according to preset criteria. Typical 1-year pregnancy rates following cessation of oral contraceptives or the levonorgestrel-releasing intrauterine system (LNG-IUS) ranged between about 79% and 96% and those for copper intrauterine devices (IUDs) were almost as high, ranging between about 71% and 91%. One-year pregnancy rates following cessation of contraceptive implants were between 77% and 86%, with one study showing a rate lower than 50%. For injectable contraceptives [(a) norethisterone enanthate and (b) 5 mg estradiol cypionate and 25 mg medroxyprogesterone (Cyclofem)], only two studies were reported, with 1-year pregnancy rates following cessation of 73% and 83%, respectively. There was no evidence of increased pregnancy complications or adverse fetal outcomes following cessation of any of the reversible methods reported. CONCLUSIONS Overall, 1-year pregnancy rates following cessation of oral contraceptives, contraceptive implants and monthly injections, copper IUDs and the LNG-IUS are broadly similar to those reported following discontinuation of barrier methods or use of no contraceptive method.

Use of contraceptive methods and contraceptive recommendations among health care providers actively involved in contraceptive counseling — results of an international survey in 10 countries☆

BACKGROUND This study was conducted to determine the personal choices of contraceptive methods among an international sample of contraception health care professionals (HCPs) and to determine if these choices are concordant with their recommendations to women. STUDY DESIGN In an anonymous online survey, 1001 HCPs actively involved in contraceptive counseling [obstetrician/gynecologists (OB/GYNs), general practitioners (GPs) and midwives (only in Sweden)] from 10 countries (Australia, Brazil, Canada, France, Germany, Korea, Mexico, Spain, Sweden and the United Kingdom) were asked about their personal use of contraceptive methods and their recommendations to women in two different clinical scenarios: for spacing between children (Group A) and after completion of the family (Group B). RESULTS The largest HCP group was OB/GYNs (67.1%), followed by GPs (31.4%) and midwives (1.5%). A total of 42.7% of respondents were male, and 57.3% were female. The majority of respondents were aged 36-45 years (38.9%) or 46-55 years (42.8%), 79.7% had children, and 53.9% were currently using contraception (by themselves or by their partners). Among 540 contraceptive users, the three most common methods were the levonorgestrel-releasing intrauterine system (LNG-IUS; 29.3%), combined oral contraceptives (COCs; 20.0%) and condoms (17.0%). OB/GYNs were more likely to be using the LNG-IUS than GPs (p=.014). Gender did not seem to influence contraceptive preference. Reasons for these choices were largely influenced by family situation and high contraceptive efficacy (for the LNG-IUS) or side effects caused by other methods (for condoms). The top contraceptive recommendation was COCs for Group A and the LNG-IUS for Group B. HCPs currently using COCs and the LNG-IUS were more likely to recommend these methods than other contraceptive methods for Group A and Group B, respectively. CONCLUSIONS The most popular contraceptive method in this sample of HCPs was the LNG-IUS. Choice of contraceptive method was driven by family situation, age and profession. It appears that, in this sample, personal contraceptive use influences contraceptive recommendations.

Vaginal sonosalpingography in the evaluation of tubal patency

BACKGROUND During the past few years, sonosalpingography has been suggested as the first-line method to study tubal patency. This study was launched in order to study the applicability of this method at our institution. METHODS Thirty-two patients suffering from primary or secondary infertility were evaluated for tubal patency with sonosalpingography using a pediatric Foley urinary catheter and a combination of air and saline solution as a contrast medium. The uterine tubes were evaluated separately and the results were compared to the findings at laparoscopy and chromotubation performed independently. Four patients conceived before their scheduled laparoscopy and were excluded from the study. In addition, the patency of three Fallopian tubes could not be adequately evaluated, leaving altogether 53 uterine tubes that were evaluated by both methods. RESULTS The findings of both methods agreed in 47 out of 53 tubes (concordance, 88.7%). The sensitivity of sonosalpingography in diagnosing tubal patency was 90.2% and the specificity 83.3%. The positive predictive value for tubal patency by sonosalpingography was 94.9% and the negative predictive value 71.4%. Adverse events of sonosalpingography included moderate to severe abdominal pain in three patients, one vasovagal reaction, and one case of shoulder pain. No infectious complications were recorded. CONCLUSIONS The results confirm that sonosalpingography utilizing air and saline as a contrast medium is a reliable, simple and well-tolerated method to assess tubal patency in an outpatient setting. In addition, the procedure can be performed without prophylactic antibiotics using a regular pediatric Foley urinary catheter instead of an expensive hysterosalpingography catheter.

Recent developments in the clinical use of the levonorgestrel-releasing intrauterine system

This overview focuses on recent developments in the clinical use of the levonorgestrel‐ releasing intrauterine system (LNG‐IUS) on established indications. Recent studies confirm that the LNG‐IUS is safe and equally effective for all age groups of women. All available studies showed that intrauterine contraception is more effective when compared to non‐intrauterine contraceptive methods to prevent repeat abortions. Furthermore, insertion in young nulliparous women is acceptable in the majority of women and associated with high continuation rates. The effectivity of LNG‐IUS appears to be similar in women with chronic medical conditions, including HIV infection or coagulation disorders, and healthy women. More and most importantly, it has no adverse effect on the underlying condition. We also discuss effects of LNG‐IUS on bone mineral density, vaginal flora, cardiovascular risk factors and breast cancer. In treatment of heavy menstrual bleeding, the LNG‐IUS appears to be one of the most effective and cost‐effective methods.

Management of Initial Bleeding or Spotting After Levonorgestrel-releasing Intrauterine System Placement: A Randomized Controlled Trial

OBJECTIVE: To assess the efficacy of tranexamic acid or mefenamic acid in the management of the initial “nuisance” bleeding or spotting in the period immediately after placement of the levonorgestrel-releasing intrauterine system. METHODS: Women were randomized after levonorgestrel-releasing intrauterine system placement to oral tranexamic acid (500 mg), mefenamic acid (500 mg), or placebo three times daily during bleeding or spotting episodes over a 90-day treatment period. Treatment was initiated from onset of a bleeding or spotting episode and continued until the first day after bleeding or spotting stopped and restarted with a new bleeding or spotting episode. The primary efficacy variable was reduction in the number of bleeding or spotting days. Tranexamic acid and mefenamic acid were compared with placebo using a one-sided Wilcoxon rank-sum test. Bonferroni-Holm adjustment was used to account for multiple testing. RESULTS: A total of 204 women were screened; 187 were randomized to tranexamic acid (n=63), mefenamic acid (n=63), or placebo (n=61). The median number of bleeding or spotting days experienced during treatment was 25, 29, and 33 days in the three groups, respectively. The median number of bleeding or spotting days was reduced by 6 days (95% confidence interval [CI] –14.0 to 1.0, P=.049) with tranexamic acid and by 3 days (95% CI –11.0 to 5.0, P=.229) with mefenamic acid compared with placebo. The relative risk of bleeding or spotting compared with placebo with tranexamic acid and mefenamic acid was 0.82 (95% CI 0.65–1.03) and 0.89 (95% CI 0.71–1.11), respectively. Most women (85% or more) were satisfied with the levonorgestrel-releasing intrauterine system across the groups. CONCLUSIONS: Tranexamic acid and mefenamic acid during the first 90 days after levonorgestrel-releasing intrauterine system placement do not alleviate “nuisance” bleeding or spotting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01295294. LEVEL OF EVIDENCE: I

Bleeding pattern and user satisfaction in second consecutive levonorgestrel-releasing intrauterine system users: results of a prospective 5-year study

STUDY QUESTION What is the bleeding pattern during second consecutive levonorgestrel-releasing intrauterine system (LNG-IUS) use? SUMMARY ANSWER Consecutive use of LNG-IUS is associated with a predictable bleeding pattern, characterized by the absence of the initial period of irregular bleeding seen after interval insertion of an LNG-IUS and a non-bleeding pattern in the vast majority of women. WHAT IS KNOWN ALREADY With increased popularity of the LNG-IUS for long-term birth control and treatment of heavy menstrual bleeding (HMB), consecutive use of the system is becoming more frequent. One previous study showed 60% amenorrhea rate in consecutive IUS users; however, the sample size was small. STUDY DESIGN, SIZE, DURATION A prospective multicenter study in four European countries recruited women who wished to continue with LNG-IUS use immediately after the first 5-year period. A total of 204 women were followed up until the end of the first year of the second IUS. Thereafter 170 women continued into the extension phase of the study up to the full 5 years of use of the second IUS and 144 women continued to the end of the study. PARTICIPANTS, SETTING, METHODS A total of 170 women (mean age 39 years) who had been using their first LNG-IUS for between 4 years 3 months and 4 years 9 months, either for contraception or for treatment of HMB, and who planned to replace the device with a new LNG-IUS, were recruited and followed up to 5 years of the second IUS use. A total of 17 centers in four European countries were involved in the study. Bleeding patterns were analyzed using daily bleeding diaries using 90-day reference periods (RP) for the first year of the second IUS use and for the last RP of each year during Years 2–5 of use. MAIN RESULTS AND THE ROLE OF CHANCE Approximately 70% of women were free of bleeding during Years 2–5 and up to 49% were amenorrheic. There was a slight increase in the number of bleeding/spotting days of ∼3 days during the first RP immediately after the placement of the second IUS, whereafter the number of bleeding/spotting days returned to the level preceding the second IUS insertion or below that. Absence of bleeding was associated with high overall satisfaction and continuation rates. No serious adverse events assessed as related to the LNG-IUS use occurred during the 5-year period. The cumulative expulsion rate during the 5-year study period was 1.2%. The sample size was large enough to study bleeding patterns, and subjects are likely to represent typical consecutive IUS users, and therefore, the role of chance is small. LIMITATIONS, REASONS FOR CAUTION The women represent a selected group as they had already successfully used their first IUS for almost 5 years and were willing to continue its use—however, this is currently a common clinical situation. The results may therefore not be extrapolated to first-time users of the LNG-IUS. WIDER IMPLICATIONS OF THE FINDINGS These data are of importance when counseling women who are making decisions concerning long-term contraception. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Bayer Pharma AG. P.I. and T.S. are full-time employees of Bayer Pharma AG. O.H. and K. G-D. have received consultancy fees from Bayer Pharma AG. The publication was developed jointly by all authors without third-party involvement and no honoraria were paid for any authors for their contribution to this manuscript. TRIAL REGISTRATION NUMBER NCT00393198.

Comment on ‘Incomplete IUS removal’

We would like to respond to the letter to the editor1 from Dr Agarwal that appeared in the July 2014 issue of this Journal. Dr Agarwal describes a case where an intrauterine system (IUS) was removed from a 51-year-old patient after it had been in situ for 8 years. Upon removal, it was thought that the transverse arms of the IUS were missing, and the patient subsequently underwent ultrasound and hysteroscopy examination, the latter failing to locate the IUS arms. On ultrasound, it was thought that a linear echogenicity at …

Continuation rates and satisfaction with the Levonorgestrel Intrauterine System. Letter to the Editor in response to an article published in volume 31, by Dr. Ewies

This letter to the editor comments on a publication which claims that the levonorgestrel intrauterine system (LNG-IUS) has high rates of sexual dissatisfaction high rates of discontinuation high rates of progestagenic side effects and high tissue and serum levels of LNG. It argues against these claims and explains the problems with the evidence and proposes solutions.