Helena Kopp Kallner

Use of Contraception and Attitudes towards Contraceptive Use in Swedish Women - A Nationwide Survey

Objective To describe contraceptive use and attitudes towards contraceptive use in Sweden which has the highest abortion rate in Western Europe. Secondary objectives were to investigate knowledge of contraceptive methods and outcomes of unplanned and unwanted pregnancies. Design Telephone survey. Setting National survey of women living in Sweden. Population Women between 16 and 49 years. Methods The survey contained 22 questions with free text and multi choice answers on demographics, contraceptive use, knowledge of and attitudes towards contraception, the importance of monthly bleeding and experience of unintended pregnancy. Main Outcome Measures Distribution of use of contraceptive methods and non-use of contraception among Swedish women. Prevalence and outcome of unintended pregnancies. Results A total of 1001 women participated in the survey. Of all women, 721/1001 (72.1%) currently used contraception whereas 268/1001 (26.8%) women did not. Long acting reversible contraception, (LARC; implant and intra uterine contraception) was used by 24.3% of women. The unmet need of contraception in Sweden was estimated at 8.9% (89/1001 women). A total of 781 (78%) women had never experienced an unintended pregnancy whereas 220 (22%) women had had at least one unintended pregnancy. Users and non-users alike stated that one of the most important characteristics of a contraceptive method is its effectiveness. Conclusions Sweden has a large unmet need for contraception. Furthermore, a large proportion of women have experienced at least one unintended pregnancy. Increasing contraceptive use and promotion of LARC is a possible way forward in the effort to reduce the rates of unwanted pregnancies.

Sublingual versus vaginal misoprostol for cervical dilatation 1 or 3 h prior to surgical abortion: a double-blinded RCT

STUDY QUESTION Can sublingual administration of misoprostol 1 h prior to vacuum aspiration be more effective than vaginal administration and as effective as either route three 3 h prior to surgery? SUMMARY ANSWER Sublingually administered misoprostol is superior to vaginally administered misoprostol when given 1 h pre operatively, and it is as effective as after a three 3 h priming interval with either route of administration. WHAT IS KNOWN ALREADY Misoprostol reduces complications and morbidity when used for cervical priming prior to surgical dilatation and vacuum aspiration in first trimester pregnancy. Despite the widespread use and extensive studies, the optimal route of administration of misoprostol before surgical abortion remains to be defined. The optimal priming interval after vaginal and sublingual administration of 400 mcg misoprostol has been reported to be 3 h. A longer interval will not improve dilatation but will increase the risk for bleeding and expulsion of the uterine contents before surgical evacuation. The pharmacokinetic properties of misoprostol indicate that sublingual compared with vaginal administration of misoprostol may result in a more rapid cervical priming effect. STUDY DESIGN, SIZE, DURATION Women were randomized to four treatment groups and received 400 mcg misoprostol sublingually, or vaginally, 1 or 3 h prior to surgery. The study was a double-blinded RCT with regard to route of misoprostol administration but not the timing interval. The primary outcome was baseline cervical dilatation after misoprostol priming. The study was conducted between June 2007 and March 2014 and 184 women aged 18 years or older were recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS Women were recruited among nulliparous women undergoing elective surgical first trimester abortion. Exclusion criteria were any contraindication for misoprostol, untreated genital infection, previous history of surgery to the cervix, or abnormal pregnancy. Gestational age was established by endovaginal ultrasound examination. The trial was conducted in a university hospital outpatient clinic. The allocated medication (misoprostol and placebo) was self-administered 1 h or 3 h prior to surgery. All women received 2 tablets of 200 mcg misoprostol and 2 identical looking placebo tablets. Prophylactic pain medication, 100 mg oral diclofenac, was administered at the time of misoprostol. Side effects were recorded immediately before surgery and women were asked which administration route of administration they found most convenient and which they would have preferred. The exact priming time (from misoprostol administration to initiation of dilatation) and signs of bleeding prior to dilatation were recorded. Vacuum aspiration was performed under general anaesthesia according to clinical routine. Dilatation was performed using tapered Pratt-dilatators and the resistance of the cervix was assessed objectively using a tonometer. All surgery was performed by two investigators, experienced in using the tonometer. The cumulative force required to dilate the cervix was calculated by adding the peak force needed for each dilatator up to 9.7 mm. The time needed for surgery including cervical dilatation and vacuum aspiration, was recorded. Intra-operative blood loss was measured and any surgical complications noted. MAIN RESULTS AND THE ROLE OF CHANCE Six women were excluded retrospectively from the analysis. Multivariate analysis of the primary outcome baseline dilatation showed a significant influence on route of administration (P = 0.034, 95% confidence interval (CI) -2.202, -0.086) as well as the interaction variable between route of administration and total priming time (P = 0.042, 95% CI 0.00, 0.016), with the vaginal route becoming more effective with longer priming time. These factors also had a significant influence on the peak force (administration route P = 0.042, 95% CI 0.221, 12.427, interaction P = 0.049, 95% CI -0.089, 0.000) and cumulative force (administration route P = 0.023, 95% CI 3.142, 40.877, interaction P = 0.026, 95% CI -0.293, -0.019) used for dilatation. The total priming time had a significant influence on bleeding before surgery, with more women bleeding the longer the total priming time (P = 0.003, 95% CI 2.203, 49.706). For abdominal pain before surgery there was a significant influence of administration route (P = < 0.001 95% CI 0.028, 0.235) and the interaction variable between administration route and priming time (P = 0.003, 95% CI 2.005, 30.757) with more women in the sublingual group experiencing abdominal pain the longer the priming time. The groups did not differ regarding duration of surgery, amount of bleeding and rate of side effects, such as nausea and shivering. Women in our study preferred vaginal treatment, as they disliked the taste of the misoprostol tablets. Vaginal treatment was also perceived as quicker to administer (P = 0.0001). LIMITATIONS, REASONS FOR CAUTION The cervical tissue has viscoelastic properties, i.e. tissue resistance to mechanical dilatation depends also on the rate at which dilatation is performed. The ideal measurement of dilatation force should therefore also record the rate and time of dilatation. To ensure comparability, only nulliparous women without prior cervical surgery were recruited. In addition, time of dilatation was recorded and did not differ between the groups, and it is therefore assumed that dilatation took place at approximately the same rate. A limitation is that the study was conducted over a long time period because there was only one tonometer, decreasing numbers of surgical abortions and the fact that the main author was on a rotation schedule. In addition, the study was not powered to detect differences in side effects. WIDER IMPLICATIONS OF FINDINGS Priming with misoprostol is recommended prior to surgical abortion. The priming interval of misoprostol may be reduced to 1 h after sublingual administration but not after vaginal administration. The results of the present study will increase choice and flexibility in cervical priming. STUDY FUNDING/COMPETING INTERESTS The Swedish research council (521-2009-2605), Swedish Council for Working Life and Social Research (1404/08), Stockholm County Council and Karolinska Institutet (ALF 2009-2012). All authors declare that they have no conflicts of interest. TRIAL REGISTRATION NUMBER www.clincaltrials.gov, NCT 01933360.

Medical Abortion Provided by Nurse-Midwives or Physicians in a High Resource Setting: A Cost-Effectiveness Analysis.

Objective The objective of the present study is to calculate the cost-effectiveness of early medical abortion performed by nurse-midwifes in comparison to physicians in a high resource setting where ultrasound dating is part of the protocol. Non-physician health care professionals have previously been shown to provide medical abortion as effectively and safely as physicians, but the cost-effectiveness of such task shifting remains to be established. Study design A cost effectiveness analysis was conducted based on data from a previously published randomized-controlled equivalence study including 1180 healthy women randomized to the standard procedure, early medical abortion provided by physicians, or the intervention, provision by nurse-midwifes. A 1.6% risk difference for efficacy defined as complete abortion without surgical interventions in favor of midwife provision was established which means that for every 100 procedures, the intervention treatment resulted in 1.6 fewer incomplete abortions needing surgical intervention than the standard treatment. The average direct and indirect costs and the incremental cost-effectiveness ratio (ICER) were calculated. The study was conducted at a university hospital in Stockholm, Sweden. Results The average direct costs per procedure were EUR 45 for the intervention compared to EUR 58.3 for the standard procedure. Both the cost and the efficacy of the intervention were superior to the standard treatment resulting in a negative ICER at EUR -831 based on direct costs and EUR -1769 considering total costs per surgical intervention avoided. Conclusion Early medical abortion provided by nurse-midwives is more cost-effective than provision by physicians. This evidence provides clinicians and decision makers with an important tool that may influence policy and clinical practice and eventually increase numbers of abortion providers and reduce one barrier to women’s access to safe abortion.

Effect of letrozole on uterine tonus and contractility: A randomized controlled trial☆

BACKGROUND Letrozole inhibits estrogen production. It has been shown to increase efficacy in medical abortion when used with misoprostol. This study investigated if letrozole acts as an abortifacient due to a synergistic effect with misoprostol on uterine contractility. STUDY DESIGN Sixteen healthy women requesting surgical abortion were randomized to receive either no pretreatment or treatment with letrozole 7.5 mg daily for 3 days prior to the abortion. All women received misoprostol 400 mcg vaginally 3.5 h prior to surgery. Intrauterine pressure was measured for 30 min before and 3.5 h after misoprostol was given using an intrauterine pressure catheter. Main outcome measure was uterine contractility analyzed by repeated-measures analysis of variance. RESULTS At baseline, uterine contractions were absent and tonus was low. No significant difference was seen between the two groups in tonus (p=.818) or in contractility (p=.423) after misoprostol administration. CONCLUSION Letrozole does not appear to act as an abortifacient through an effect on uterine contractility or increased sensitivity to misoprostol of the uterine myometrium.

Safety and efficacy of mirabegron in daily clinical practice: a prospective observational study.

OBJECTIVE To determine risks associated with prescribing mirabegron, the first-in-class β3-adrenoreceptor agonist, to non-selected female patients with overactive bladder. STUDY DESIGN Routine female patients seeking treatment for overactive bladder (n=221) in a urology/gynecology outpatient clinic. Data on adverse events, cardiovascular outcomes, condition specific symptoms and drug discontinuation was collected at two months follow-up (FU). Non-parametric statistics was used as appropriate. Odds ratios (ORs) with 95% confidence intervals (CIs) for outcome association analyses using logistic regression. RESULTS 16 patients (7.2%) discontinued treatment because of side effects. There were no significant associations between cardiovascular adverse events and pre-existing cardiovascular disease (OR 0.3, 95% CI 0.3-2.6), or pre-existing ECG abnormalities (OR 2.3, 95% CI 0.3-16.3). At FU ECGs there were no de novo cases of tachyarrhythmias and no significant difference in mean QTc between baseline (403ms, SD 21.7) and the 2 months follow-up ECG (403ms, SD 20.3) (p=0.75). There was a significant decrease in the mean systolic blood pressure (p=0.03) but no significant change in mean diastolic pressure (p=0.8) or heart rates (p=0.2) from baseline to FU. Overactive bladder specific symptoms and quality of life improved significantly (p<0.001 respectively). CONCLUSIONS Mirabegron treatment is associated with a satisfactory cardiovascular safety profile, as well as, significant symptomatic improvement also in a heterogeneous population of non-selected women with overactive bladder presenting in everyday clinical practice.

Investigating the loss of work productivity due to symptomatic leiomyoma

Introduction Leiomyoma affects up to 50% of fertile women, leading to morbidity such as bleeding or pain. The effect of symptomatic leiomyoma on the productivity of employed women is understudied. The present study investigates productivity loss in a Swedish setting in women with symptomatic leiomyoma compared to healthy women. Material and methods Women seeking care for leiomyoma and heavy menstrual bleeding (HMB) were recruited at nine Swedish sites. Healthy controls with self-perceived mild to normal menstruation were recruited at routine visits. Cases and controls were employed without option to work from home. After recruitment, all women reported the work productivity and activity impairment (WPAI) questionnaire, the pictorial blood assessment chart (PBAC) and pain on the visual analog scale (VAS). Results Women with symptomatic leiomyoma (n = 88) missed more working time during menses compared to asymptomatic controls (n = 34): 7.6 vs 0.2% p = 0.003. The proportion of impairment while working was also significantly higher in women with symptomatic leiomyoma (43.8 vs 12.1% p<0.001). Moreover, cases reported greater activity impairment outside office hours (43.9 vs 12.1%, p<0.001). Among healthy controls, 69.5% reported symptoms of HMB (PBAC>100). Conclusions Symptomatic leiomyoma leads to loss of working hours as well as loss of productivity during working hours, and affects women in other daily activities. Increased awareness of the impact of leiomyomas on womens lives is needed, and timely and appropriate management of the symptomatic leiomyomas could improve work productivity and quality of life.

Cost‐effectiveness analysis of a low‐dose contraceptive levonorgestrel intrauterine system in Sweden

To evaluate the cost‐effectiveness of a novel intrauterine system, levonorgestrel intrauterine system 13.5 mg vs. oral contraception, in women at risk of unintended pregnancy.

Mifepristone treatment prior to insertion of a levonorgestrel releasing intrauterine system for improved bleeding control – a randomized controlled trial

STUDY QUESTION Does pre-treatment with a low dose of mifepristone improve irregular vaginal bleeding patterns during the initial 3 months after LNG-IUS placement? SUMMARY ANSWER Mifepristone treatment prior to LNG-IUS insertion results in significantly lower bleeding and spotting rates for the first month post insertion but no significant reduction at 3 months post insertion. WHAT IS KNOWN ALREADY One of the leading causes of premature discontinuation of the LNG-IUS is unscheduled bleeding in the first months following its insertion. Up to now, there has been no effective treatment to prevent this side effect which reduces continuation rates for one of the most effective contraceptives. STUDY DESIGN, SIZE, DURATION This randomized, double blinded, controlled trial was conducted between 2009 and 2015. In total, 68 women opting for a LNG-IUS were screened for eligibility, of whom 58 were randomized at a ratio of 1:1 in blocks of 10 to pre-treatment with mifepristone or a comparator. The main outcome was the rate of bleeding and spotting days reported during the first 3 months post LNG-IUS 52 mg placement. PARTICIPANTS/MATERIALS, SETTING, METHODS Healthy women with regular and normal menstrual cycles aged 18-43 years were enrolled at a single center in a university hospital; 29 were allocated to 2 months pre-treatment with a low dose mifepristone and 29 to the comparator prior to insertion of the LNG-IUS. Women were advised to use barrier methods during the pre-treatment period. Bleeding diaries were collected for the pre-treatment period and for the first 6 months after the LNG-IUS placement. MAIN RESULTS AND THE ROLE OF CHANCE There were no differences in demographic or baseline characteristics between the study groups. Data for analysis of the main outcome were contributed by a per protocol population of 19 women per group. There was a significant lower bleeding and spotting rate in the mifepristone group (-17.8% points, P < 0.001) after 2 months of pre-treatment and during the first month after the LNG-IUS insertion. In the following months, no significant difference could be seen. While no pregnancies occurred prior to LNG-IUS insertion in the mifepristone group, there were three unintended pregnancies in the comparator group which emphasizes the need for a reliable contraceptive potential in any pre-treatment regimen used in clinical practice. LIMITATIONS, REASONS FOR CAUTION The use of mifepristone prior to the LNG-IUS insertion in this trial was used as prophylaxis against unscheduled bleeding after the placement of the device. Although this side effect constitutes a major concern in a clinical setting, only a subset of women are at risk. This is the first study using pre-treatment to attempt improved bleeding control. The differences were small and the effect was short lasting but the reduced rate of bleeding and spotting observed during the first month following LNG-IUS insertion indicates that this approach may be further explored. The fact that there were three pregnancies in the comparator group stresses the need for any pre-treatment to also protect against unplanned pregnancy. WIDER IMPLICATIONS OF THE FINDINGS Modified treatment protocols of mifepristone could be used prior to the LNG-IUS insertion to investigate possible further improvement of the outcome. The effect size of the current dose used might have been more prominent in women with LNG-IUS if the treatment also continued some weeks after the placement of the device. Although the low dose of mifepristone used in this trial is not available in Europe, other progesterone receptor modulators currently available could be investigated in larger clinical trials. To avoid unintended pregnancy in the pretreatment period, the dosage used should, ideally, also be effective for contraception and the pretreatment period should be kept as short as possible. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Swedish Research Council (2012-2844, 2017-00932), Stockholm County Council and Karolinska Institutet (ALF). Conflicts of interests for K.G.D. and H.K.K. are listed at the end of the paper. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER EudraCT number 2009-009014-40. Regional ethical review board at Karolinska Institutet permit 2009/144-31/4. TRIAL REGISTRATION DATE 20 July 2009. DATE OF FIRST PATIENT’S ENROLMENT 24 November 2009.

Cost of unintended pregnancy in Sweden — a possibility to lower costs by increasing LARC usage

OBJECTIVES The objective of this study was to determine the cost of unintended pregnancy (UP) in Sweden and savings generated by a switch of 5% of women from short-acting reversible contraception (SARC) and other methods to long-acting reversible contraceptives (LARCs). STUDY DESIGN We constructed an economic model to estimate the number and costs of UPs and contraceptive use over a 1-year period. The population consisted of all women aged 15-44years requiring reversible contraception and at risk of UP. UPs could result in birth, spontaneous abortion, induced abortion, and ectopic pregnancy. The model included costs incurred by the healthcare payer or out-of-pocket expenses by women, and indirect costs, i.e., foregone wages from time away from work. RESULTS We estimated 73,989 unintended pregnancies yearly, amounting to costs of almost €158 million. A 5% switch from non-LARCs to LARCs would generate more than 3500 fewer UPs yearly with savings of nearly €7.7 million. The majority of these savings would arise from reduced costs for UPs. CONCLUSIONS UPs are costly for society and women. A small change in the proportion of women using the most effective methods generates substantial cost savings due to fewer UPs and thus fewer abortions. A switch in 5% of women using non-LARCs could prevent more than 3500 UPs yearly, generating savings of more than SEK 70 million (€7.7 million) or of 2.4% of costs for UPs.

Colposcopy telemedicine: live versus static swede score and accuracy in detecting CIN2+, a cross-sectional pilot study

BackgroundThis cross-sectional pilot study evaluates diagnostic accuracy of live colposcopy versus static image Swede-score evaluation for detecting significant precancerous cervical lesions greater than, or equal to grade 2 severity (CIN2+).MethodsVIA or HrHPV positive women were examined using a mobile colposcope, in a rural clinic in Kolkata, India. Live versus static Swede-score colposcopy assessments were made independently. All assessments were by gynecologists, junior or expert. Static image assessors were blinded to live scoring, patient information and final histopathology result. Primary outcome was the ability to detect CIN2+ lesions verified by directed biopsies. Diagnostic accuracy was calculated for live versus static Swede-score in detecting CIN2+ lesions, as well as for interclass correlation.Results495 images from 94 VIA positive women were evaluated in this study. Thirteen women (13.9%) had CIN2+ on biopsy. No significant difference was found in the detection of CIN2+ lesions between live and static assessors (area under curve = 0.69 versus 0.71, p = 0.63). A Swede-score of 4+, had a sensitivity of 76.9% (95% CI 46.2–95.0%) and 84.6% (95% CI 54.6–98.1%), for live- and static-image assessment respectively. The corresponding positive predictive values were found to be 90.9% (95% CI 75.7–98.1%) and 92.6% (95% CI 75.7–99.1%). The interclass correlation was good (kappa statistic = 0.60) for the senior static assessors.ConclusionsSwede-score evaluation of static colposcopy images was found to reliably detect CIN2+ lesions in this study. Larger studies are needed to further develop the colposcopy telemedicine concept which may offer reliable guidance in management where direct specialist input is not available.Trial registrationEthical approval of the study was obtained by the Chittaranjan National Cancer Institute (CNCI) Human Research Ethics Committee (4.311/27/2014). The trial was retrospectively registered in the Clinical Trails Registry of India CTRI/2018/03/012470.