Comment: The quality of evidence is upgraded by large magnitude of effect.
A multinational, prospective, non-interventional cohort study «Heinemann K, Reed S, Moehner S et al. Risk of uter...»1 with new users of levonorgestrel-releasing intrauterine systems (LNG-IUD, releasing 20 mcg LNG daily) and copper IUDs (Cu-IUD) assessed the incidence of uterine perforation and other adverse events. In addition to a baseline questionnaire, women and their treating health care professional completed a single follow-up questionnaire after 12 months. A total of 61448 women in 6 European countries (Germany, Austria, the United Kingdom, Finland, Sweden, Poland) were followed between 2006 and 2013 (70% LNG, 30% copper devices). Overall, 81 uterine perforations were reported: 61 for LNG-IUDs (1.4 per 1000 insertions (95% CI 1.1-1.8)) and 20 for copper IUDs (1.1 per 1000 insertions (95% CI 0.7-1.7), for an adjusted risk ratio of 1.6 (95% CI 1.0-2.7) when adjusted for age, BMI, breastfeeding at time of insertion and parity. Breastfeeding at time of insertion was associated with a 6-fold increase (RR 6.1, 95% CI: 3.9-9.6), with no differences between LNG and copper IUD users. Seventy eight per cent (63/81) of perforations were associated with previously suspected risk factors (e.g. breastfeeding, time since last delivery ≤ 36weeks). No perforations led to serious illness or to injury of intra-abdominal or pelvic structures.
An additional follow-up and analysis «B...»6 at 60 months in 39 009 women of the above described assessed the rate of perforations following IUD insertion. The overall perforation rate was 2.1 per 1000 insertions (95% CI 1.6 to 2.8) for LNG-IUS users (40 + 19 perforations/27 630 insertions) and 1.6 per 1000 insertions (95% CI 0.9 to 2.5) for copper-IUD users (14 + 4 perforations/11 379 insertions). LNG-IUS users had a borderline higher risk of perforation compared with copper-IUD users (ORadj 1.7; 95% CI 1.0 to 2.8). 58% of the 77 perforations were associated with suspected risk factors. Breastfeeding (RR 4.9, 95% CI 3.0 to 7.8) and time since delivery (RR 3.0, CI 1.5 to 5.4) remained significant risk factors. No perforations resulted in serious injury to intra-abdominal or pelvic structures.
A retrospective population-based registry study «Kaislasuo J, Suhonen S, Gissler M et al. Intrauter...»2 in Finland assessed the incidence and factors associated with uterine perforation by modern Cu-IUD and LNG-IUD. 68 patients surgically treated for uterine perforation by an intrauterine device were analysed (17 with Cu-IUDs and 51 with LNG-IUDs). The overall incidence of perforation was 0.4/1000 sold devices, varying annually from 0 to 1.2/1000. Demographic characteristics in the Cu-IUD and LNG-IUD groups were similar. More than half of the devices (55%) were inserted at < 6 months post-partum and 22% were inserted < 3 months post-partum. Breastfeeding at the time of insertion was common, comprising 32% of all patients. Moreover, of the breastfeeding women, 90% (n=19) had delivered within 6 month prior to insertion and 17 of them were amenorrhoeic (P < 0.001).
In a retrospective study «van Grootheest K, Sachs B, Harrison-Woolrych M et ...»3 National pharmacovigilance centres in the Netherlands, New Zealand, Switzerland and Germany did a search on their adverse drug reaction databases for reports of cases of uterine perforation after insertion of a LNG-IUD. The number of women affected and patient characteristics such as age, parity and breastfeeding status were examined. Between years 1990 and 2007 701 cases of uterine perforation with a LNG-IUD were reported; 8.5% of the perforations were detected at the time of insertion. Abdominal pain and control/check-up visits were the most common events that lead to the detection of a perforation. Of 462 women known to be parous, 192 (42%) were breastfeeding at the time the perforation was discovered.
A prospective follow-up study «Caliskan E, Oztürk N, Dilbaz BO et al. Analysis of...»4 in Turkey determined the risk factors for IUDs being displaced into the abdominal cavity. All 8343 women who had a copper T-380A IUD inserted between 1996 and 2002 underwent ultrasound examination after 1 year. Eighteen uterine perforations occurred, giving an incidence of 2.2 per 1000 insertions. When the time elapsed after the last delivery until IUD insertion is considered, postplacental insertion and insertion after 6 months postpartum were found not to increase the risk of uterine perforation. However, IUD insertion 0-3 months postpartum increased the risk of uterine perforation (odds ratio (OR) 11.7, 95% CI 2.8-49.2) as did insertions at 3-6 months postpartum (OR 13.2, CI 2.8-62). Increasing parity decreased the risk (OR 0.04, CI 0.01-0.1) and increasing number of abortions increased the risk (OR 2.1, CI 1.2-3.6).
Another survey «Andersson K, Ryde-Blomqvist E, Lindell K et al. Pe...»5 comprised 50 consecutive perforations occurring with intrauterine devices (IUD) reported to the National Patient Insurance Scheme Register of Sweden during 1990 to 1993. All 50 women were parous and over 20 years of age at the time of IUD insertion. A total of 45 women (90%) had their IUD inserted under 1 year after a full-term pregnancy and 31 women (62%) had their IUD inserted at or under 12 weeks after delivery. Of the 50 women, 27 (54%) reported that they were breastfeeding at the time of IUD insertion. No particular IUD was overrepresented in relation to its share on the market.