Update on risk of uterine perforation with intrauterine devices

HSA would like to inform healthcare professionals about the final findings from the European Active Surveillance Study for Intrauterine Devices (EURAS-IUD), which showed a higher risk of uterine perforation associated with both levonorgestrel-intrauterine system (LNG-IUS) and copper intrauterine devices (Cu IUDs) in breastfeeding women, as well as in women who are up to 36 weeks post-partum at time of insertion. The uterine perforation rate with the devices in the entire study population was classified as uncommon (1.3 per 1,000 insertions).

The LNG-IUS registered in Singapore since 1994 is Mirena® (Bayer (South East Asia) Pte Ltd), and the Cu IUDs, registered locally since 2005 and 2010, respectively, are Nova T® (Bayer (South East Asia) Pte Ltd) and Multilan AG Multiload cu250 and cu375 (MSD Pharma (Singapore) Pte Ltd). All the IUDs are indicated for contraception, with Mirena® having additional indications of idiopathic menorrhagia and protection from endometrial hyperplasia during oestrogen replacement therapy.

Background

Uterine perforation is a rare but serious complication of IUD insertion. The rate of uterine perforation per 1,000 insertions has been reported at 0.9 with LNG-IUS¹ and 0.6–1.6 with Cu IUDs.^2,3 Potential risks of uterine perforation such as insertion of IUDs in the first six months post-partum, lactation, and women with an atypical uterine anatomy (such as fixed retroverted uterus) have been reported.^2,4

Breastfeeding has been reported in the literature as a potential risk factor for uterine perforation because of low serum oestrogen levels and therefore a more contracted uterus. A pooled analysis of uterine perforation after insertion of LNG-IUS from four national pharmacovigilance centres from 1990 to 2007 found that 42% of 462 women were breastfeeding at the time the perforations were discovered.⁵

Findings from the EURAS-IUD study

The EURAS-IUD is a prospective, non-interventional cohort study conducted from 2006 to 2013 in over 61,000 IUD users (70% LNG-IUS, 30% Cu IUDs) from six European countries. The study found that the incidence rate of uterine perforation was 1.3 per 1,000 insertions (95% CI 1.1, 1.6) in the whole study population. Breastfeeding at time of insertion led to a six-fold increase in total perforation risk, regardless of time interval since last delivery (risk ratio 6.1; 95% CI 3.9, 9.6). Insertion up to 36 weeks post-partum was also independently associated with an increased risk of perforation. The incidence of perforation with IUDs inserted at 36 weeks or less after delivery was 5.6 per 1,000 insertions (95% CI 3.9, 7.9) in breastfeeding women and 1.7 (95% CI 0.8, 3.1) in non-breastfeeding women, and dropped to 1.6 (95% CI 0.0, 9.1) and 0.7 (95% CI 0.5, 1.1), respectively when the insertions were performed at more than 36 weeks after delivery. These risks were independent of the type of IUD inserted.

Local situation

To date, two reports of uterine perforation associated with Mirena® were reported to HSA in 2011 and 2013. One case presented with heavy menstrual bleeding, while another case reported that Mirena® could not be located by thread pulling during its removal procedure. In both cases, the breastfeeding status of the patient was unknown. There were no local reports of uterine perforation associated with Cu IUDs. A Dear Healthcare Professional Letter was issued on 14 May 2014 by Bayer, who funded the EURAS-IUD, to update healthcare professionals on the study findings.⁶

HSA's advisory

Healthcare professionals are advised to take the above information into consideration when selecting IUDs for use in women who are less than 36 weeks post-partum or breastfeeding at time of insertion.

References

1. Pharmacoepidemiology and Drug Saf 2003; 12: 371

2. Contraception 2003; 67: 53-6

3. J Obstet Gynaecol Can 2004; 26: 219-96

4. http://www.bayer.ca/files/announcements/Mirena%20Final%20HPC%2010June10_EN.pdf ↗ (opens in new tab)

5. Drug Saf 2011; 34: 83-8

6. https://www.hsa.gov.sg/announcements/Dear-Healthcare-Professional-Letters