Oskari Heikinheimo

Double-blind, randomized, placebo-controlled study on the effect of misoprostol on ease of consecutive insertion of the levonorgestrel-releasing intrauterine system

BACKGROUNDnMisoprostol has been studied intensively to produce cervical dilatation. To date, no studies have evaluated the effectiveness, safety or acceptability of this treatment for repeat intrauterine device insertions.nnnSTUDY DESIGNnThis study was a randomized, double-blind, placebo-controlled trial on the consecutive use of the levonorgestrel-releasing intrauterine system (LNG-IUS). Women who had used their first LNG-IUS for 4 years and 3 to 9 months and opted for an immediate replacement with a second LNG-IUS received a single sublingual dose of 400 mcg misoprostol or placebo 3 h prior to the LNG-IUS insertion.nnnRESULTSnThe proportion of easy insertions as judged by the investigator was 93% (40/43) in subjects randomized to misoprostol and 91% (42/46) in the placebo group (p=1.0 for the difference of proportions). No or mild pain at insertion was reported by 37% and 35% of subjects in the misoprostol and placebo groups, respectively. However, adverse events related to the study drug were more common in the misoprostol group.nnnCONCLUSIONnSublingual misoprostol did not have a significant effect on the ease of insertion in subjects having a repeat insertion of the LNG-IUS.

Intrauterine contraception: incidence and factors associated with uterine perforation—a population-based study

STUDY QUESTIONnWhat are the incidence and factors associated with uterine perforation by modern copper intrauterine device (Cu-IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS)?nnnSUMMARY ANSWERnPerforation incidence was similar to that reported in prior studies and did not vary between Cu-IUD and LNG-IUS groups. Lactation, amenorrhoea and a post-partum period of <6 months were common.nnnWHAT IS KNOWN AND WHAT THIS PAPER ADDSnThe study supports findings in prior studies. The incidence rate was low and factors associated with uterine perforation were similar to those in earlier reports. DESIGN AND DATA COLLECTION METHOD: This retrospective population-based registry study included 68 patients surgically treated for uterine perforation by an intrauterine device (IUD)/intrauterine system (IUS) at clinics in the Helsinki and Uusimaa hospital district.nnnPARTICIPANTS AND SETTINGnRecords of 108 patients with probable uterine perforation by an IUD/IUS were analysed, leaving 68 patients treated for uterine perforation. RECRUITMENT/SAMPLING STRATEGY: Patients with diagnostic and surgical treatment codes indicating uterine perforation by an IUD/IUS between 1996 and 2009 were retrospectively selected from the Finnish National Hospital Register.nnnDATA ANALYSIS METHODnPatients with Cu-IUDs (n = 17) and the LNG-IUS (n = 51) were analysed as one group and also compared using Mann-Whitney and chi-square tests. IUD/IUS sales numbers were used to calculate incidences.nnnMAIN FINDINGSnThe overall incidence of perforation was 0.4/1000 sold devices, varying annually from 0 to 1.2/1000. The proportion of both sold and perforating LNG-IUSs increased during the study period, but perforation incidence was not affected. Demographic characteristics in the Cu-IUD and LNG-IUS groups were similar. More than half of the devices (55%) were inserted at <6 months post-partum. Breastfeeding at the time of insertion was common, comprising 32% of all patients. Moreover, of the breastfeeding women, 90% had delivered within 6 month prior to insertion.nnnIMPLICATIONSnThe population-based study setting represents a good overview of patients experiencing uterine perforation with an IUD/IUS. As previously reported, the post-partum period, lactation and amenorrhoea may increase the risk of perforation.nnnBIAS, LIMITATIONS AND GENERALIZABILITYnAs the study setting revealed only symptomatic patients or those attending regular follow-up, the true incidence might be somewhat higher. As there is no specific diagnostic code for uterine perforation or treatment, it is unlikely that all cases of uterine perforation can be identified in a retrospective study.

The levonorgestrel-releasing intrauterine system in human immunodeficiency virus-infected women: a 5-year follow-up study.

OBJECTIVEnWe sought to assess the effects of long-term use and safety of the levonorgestrel-releasing (LNG)-intrauterine system (IUS) among human immunodeficiency virus (HIV)-infected women in comparison with HIV-infected women not using the device.nnnSTUDY DESIGNnFifteen women using the LNG-IUS and their 25 age- and CD4(+) lymphocyte count-matched control subjects with annual follow-up data were followed up for 5 years.nnnRESULTSnNo unplanned pregnancies or pelvic infections occurred among the LNG-IUS users. Altogether, 12 (80%) of the LNG-IUS users continued its use up to 5 years. Annual CD4(+) lymphocyte counts were similar in the LNG-IUS users and control subjects throughout the follow-up period. The hemoglobin levels increased initially (P < .005) and remained higher among the LNG-IUS users (P < .02). Pap smears displayed non-squamous intraepithelial lesion cytology in ≥ 85% of cases in both groups.nnnCONCLUSIONnNo unfavorable effects on the course of HIV infection were noted during long-term use of the LNG-IUS. Dual protection by means of an LNG-IUS and condoms might be an ideal contraceptive strategy for HIV-infected women.

Bleeding pattern and safety of consecutive use of the levonorgestrel-releasing intrauterine system (LNG-IUS)—a multicentre prospective study

BACKGROUNDnThe LNG-IUS has increasingly been used for contraception, treatment of menorrhagia and endometrial protection during hormone replacement therapy since mid-1990s. Thus, many women use the LNG-IUS consecutively. However, published data on the bleeding pattern regarding consecutive use of the LNG-IUS is scarce.nnnMETHODSnWe performed a prospective 15-month multicentre study on the bleeding profile, removal and insertion procedures and safety of the second LNG-IUS in fertile-aged women who had used their first LNG-IUS between 4 years 3 months and 4 years 9 months and who opted for the insertion of a second IUS immediately after removal of the first IUS. Bleeding data were reported descriptively starting from the last 90 days of the first IUS use and continuing for up to 1 year.nnnRESULTSnOf the 234 subjects screened, 204 (87%) entered the trial. The median number of bleeding/spotting days during the last 90 days of the first LNG-IUS was 7 (25 and 75% percentiles 0 and 15). Due to bleeding associated with the insertion procedure, this increased to 8 days (4 and 18) during the first 90-day reference period, thereafter decreasing to 4 (0 and 10) days during the second to fourth reference periods. Only one expulsion and no pregnancies, pelvic inflammatory diseases or perforations occurred. A total of 12 subjects (5.9%) prematurely discontinued the study: five due to an adverse event and seven due to other reasons (inclusive of loss to follow-up).nnnCONCLUSIONSnThis study confirms the favourable bleeding profile and safety of consecutive use of the LNG-IUS.

Comparison of rates of adverse events in adolescent and adult women undergoing medical abortion: population register based study.

Objective To determine the risks of short term adverse events in adolescent and older women undergoing medical abortion. Design Population based retrospective cohort study. Setting Finnish abortion register 2000-6. Participants All women (n=27u2009030) undergoing medical abortion during 2000-6, with only the first induced abortion analysed for each woman. Main outcome measures Incidence of adverse events (haemorrhage, infection, incomplete abortion, surgical evacuation, psychiatric morbidity, injury, thromboembolic disease, and death) among adolescent (<18 years) and older (≥18 years) women through record linkage of Finnish registries and genital Chlamydia trachomatis infections detected concomitantly with abortion and linked with data from the abortion register for 2004-6. Results During 2000-6, 3024 adolescents and 24u2009006 adults underwent at least one medical abortion. The rate of chlamydia infections was higher in the adolescent cohort (5.7% v 3.7%, P<0.001). The incidence of adverse events among adolescents was similar or lower than that among the adults. The risks of haemorrhage (adjusted odds ratio 0.87, 95% confidence interval 0.77 to 0.99), incomplete abortion (0.69, 0.59 to 0.82), and surgical evacuation (0.78, 0.67 to 0.90) were lower in the adolescent cohort. In subgroup analysis of primigravid women, the risks of incomplete abortion (0.68, 0.56 to 0.81) and surgical evacuation (0.75, 0.64 to 0.88) were lower in the adolescent cohort. In logistic regression, duration of gestation was the most important risk factor for infection, incomplete abortion, and surgical evacuation. Conclusions The incidence of adverse events after medical abortion was similar or lower among adolescents than among older women. Thus, medical abortion seems to be at least as safe in adolescents as it is in adults.

Emerging indications for the levonorgestrel-releasing intrauterine system (LNG-IUS).

The levonorgestrel intrauterine system (LNG‐IUS), originally designed for long‐term contraceptive use, has been on the Scandinavian market for approximately 20 years. Novel clinical indications for the LNG‐IUS, derived mainly from investigator‐initiated studies, are emerging. These include heavy menstrual bleeding associated with uterine fibroids, endometriosis, adenomyosis, as well as endometrial hyperplasia. In both cohort and randomized studies, the LNG‐IUS is effective in decreasing heavy menstrual bleeding, also in women diagnosed with uterine fibroids. In randomized studies the LNG‐IUS has shown comparable clinical efficacy to GnRH analogues or progestins for the symptomatic treatment of endometriosis. Experience with LNG‐IUS in adenomyosis is based on prospective cohort studies. Dysmenorrhea has been reported to decrease in all women, and uterine volume was seen to diminish in some of these studies. In the treatment of endometrial hyperplasias, including atypical hyperplasia, the LNG‐IUS is equal or superior to treatment with systemic progestins. Further studies are needed to examine the full potential of the LNG‐IUS in such common clinical situations.

Uterine perforation caused by intrauterine devices: clinical course and treatment

STUDY QUESTIONSnWhat are the symptoms of uterine perforation caused by modern copper intrauterine devices (Cu-IUDs) and the levonorgestrel-releasing intrauterine system (LNG-IUS); how is perforation detected and what are the findings in abdominal surgery?nnnSUMMARY ANSWERnSymptoms are mostly mild and ∼30% of women are asymptomatic. Surgical findings are mainly minimal; no visceral complications were found in this study. However, adhesions as well as pregnancies seem to be more common among women using Cu-IUDs.nnnWHAT IS KNOWN ALREADYnPrior studies and case reports have suggested that uterine perforation by modern IUDs/IUSs is rarely serious.nnnSTUDY DESIGN, SIZE, DURATIONnA retrospective study of 75 patients (54 LNG-IUS and 21 Cu-IUD) treated surgically for uterine perforation between 1996 and 2009.nnnPARTICIPANTS/MATERIALS, SETTING, METHODSnThe patients treated for uterine perforation by an IUD/IUS at clinics of the Helsinki and Uusimaa Hospital District were identified using the National Care Register for Health Institutions in Finland. The clinical data were collected from individual patient records.nnnMAIN RESULTS AND THE ROLE OF CHANCEnThe majority of patients (n = 53; 71%) had mild symptoms of abnormal bleeding or abdominal pain or both, in combination with missing IUD/IUS threads. Asymptomatic patients (n = 22; 29%) were examined because of missing threads or pregnancy. Failure to remove the IUD/IUS by pulling visible threads was the reason for referral in seven women (9%) requesting removal of the device. Eleven women (15%) were pregnant. Misplaced IUDs/IUSs were localized by a combination of vaginal ultrasonography (US) and X-ray, hysteroscopy or curettage. Only after this were patients treated by means of laparoscopy. The majority (n = 44; 65%) of the 68 intra-abdominal devices were located in the omentum, the remaining 24 (35%) around the uterus. Partial perforation or myometrial embedding was diagnosed in all seven cases (9%) with visible threads, but unsuccessful removal by pulling. During laparoscopy, filmy adhesions were found in 21 patients (30%). Pregnancy (33 versus 7%, P = 0.009) and intra-abdominal adhesions (58 versus 20%, P = 0.002) were significantly more common in the Cu-IUD group. Infections were rare; one non-specific acute abdominal infection, later found to be unrelated to the IUD, led to laparoscopy and in four cases the IUD was surrounded by pus, but there were no symptoms of infection.nnnLIMITATIONS, REASONS FOR CAUTIONnThe study setting revealed only surgically treated symptomatic patients and asymptomatic women attending regular follow-up. Women not treated, but only followed or not attending follow-up, were not identified, excluding the possibility to analyse missed undiagnosed perforations, or conservative follow-up as a treatment option.nnnWIDER IMPLICATIONS OF THE FINDINGSnAs surgical findings are minimal, asymptomatic women may need no treatment at all. An alternative form of contraception is, however, important as pregnancies do occur. If a woman plans a pregnancy, a misplaced LNG-IUS should be removed, as it may act as a contraceptive.

High Prevalence of Sacrococcygeal Teratoma in Finland – A Nationwide Population‐Based Study

The birth prevalence of sacrococcygeal teratoma (SCT) has been reported to range from 1:27 000 to 1:40 000. We assessed the population‐based prevalence and clinical presentation of SCT over 22 years.

One- and two-day dosing intervals between mifepristone and misoprostol in second trimester medical termination of pregnancy—a randomized trial

BACKGROUNDnThe recommended time interval between mifepristone and misoprostol in medical second trimester termination of pregnancy (TOP) has been 36-48 h. However, a more flexible interval would be of value. The aim of this investigation was to compare one- and two-day intervals in second trimester medical TOP. The main outcome measures were induction-to-abortion time and the rate of surgical evacuation.nnnMETHODSnThis open randomized trial included 227 women undergoing TOP between gestational weeks 13-24. Mifepristone (200 mg) was followed by misoprostol (400 mcg) after one (17-28 h) or two (41- 45 h) days.nnnRESULTSnIn intention-to-treat analysis, the median induction-to-abortion interval was 1h longer in the one-day group (8.5 versus 7.2 h, P = 0.038), but in per-protocol analysis, the rate of surgical evacuation was higher in the 2-day group [30/115 (25%) versus 40/112 (37%); 95% confidence interval 0.3-24.1, P = 0.044]. A subgroup analysis showed that the median induction-to-abortion interval was 3h longer in the one-day group, amongst women without previous vaginal deliveries (10.1 versus 7.6, P = 0.013) and when gestation exceeded 16 weeks (10.8 versus 7.2, P = 0.024).nnnCONCLUSIONSnBoth one- and two-day dosing intervals seem to be suitable for second trimester medical TOP, but women with no previous deliveries and those whose gestation exceeds 16 weeks may benefit from the longer interval. However, evaluated on the basis of surgical evacuation, the one-day interval could be supported as an option for second trimester medical TOP. Effective use of both one- and two-day dosing intervals is important when optimizing clinical service.nnnTRIAL REGISTRATIONnISRCTN09944151.

Hormonal contraception and mental health: results of a population-based study

BACKGROUNDnThe effects of oral contraceptives (OCs) on mental health are not clear, and no study has been focused on the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on mental health. The aim of this study was to analyse the association between the use of OCs and the LNG-IUS and psychological well-being and psychopathology.nnnMETHODSnThe associations between the current use of OCs and the LNG-IUS, and their duration versus mood symptoms [Beck Depression Inventory (BDI)], psychological well-being [(General Health Questionnaire-12 (GHQ-12)] and recent psychiatric diagnoses [(Composite International Diagnostic Interview (CIDI)] were examined among women who participated in the Finnish-population-based Health 2000 study. Analyses were performed on the 30- to 54-year-old sample (n = 2310); some of the analyses were extended to include the younger age group (18- to 54-year-old sample; n = 3223).nnnRESULTSnOverall, hormonal contraception was well tolerated with few significant effects on psychological well-being. The length of OC use was inversely associated with some BDI items (dissatisfaction, irritability, lost interest in people, earlier waking and lost interest in sex), and directly associated with worries about ones health (BDI) and with a current diagnosis of alcohol dependence (CIDI). The current use of the LNG-IUS was inversely associated with earlier waking (BDI) and with impaired concentration (GHQ), while the length of LNG-IUS use was inversely associated with strain (GHQ).nnnCONCLUSIONSnThe influence of hormonal birth control on mental health is modest and mainly favourable. The length of current OC use seems to have some beneficial effects on mood although the longer the duration of use, the greater the association with a diagnosis of alcohol dependence. Knowledge of the use of hormonal contraception might be of value when assessing psychopathology in women. The cross-sectional design, with partly retrospective data collection, precludes any causal conclusions.