Findings and interpretation
The results from KYSS demonstrate high satisfaction and continuation rates with LNG-IUS 12 across all countries included in this study. These rates compare favourably with both prior clinical trials of LNG-IUS 12 and rates reported in trials using other methods of reversible contraception [14, 16–18,37]. However, significant differences in these rates between countries in KYSS were observed. Belgium, Norway and Sweden had a lower proportion of satisfied women and a higher early removal rate than other countries.
It should be noted that of the 14% of discontinuations reported in this study, 50% were due to loss to follow-up and 50% for premature removal or expulsion. Thus, while the overall discontinuations for some countries may appear to be higher, the number of women choosing to have the device removed was low. Additionally, satisfaction data were not available for some participants, and therefore, satisfaction rates for these women were unknown. Although premature discontinuation and satisfaction did vary between countries, these results provide further evidence for the high continuation rate with LNG-IUS 12, which is another indicator of user satisfaction.
Population variances between the countries may account, at least in part, for the observed differences in satisfaction and continuation rates. The age and parity of women differed between countries, as well as the main reasons for choosing an LNG-IUS. In addition, although most women in the study had used a prior method of contraception, the most common method of contraception varied between countries. There are several potential reasons for these population variances. For example, some health care providers may have misplaced concerns, particularly surrounding the use of IUSs in nulliparous women, which may have led to a selection bias towards parous populations, who also tend to be older, in some countries [24,25]. In addition, government policies and costs may affect the study population included .
The variance in satisfaction and continuation rates between countries could also be due to the overall prevalence of use between countries. IUS use is common in some of the countries studied (such as the Nordic countries) and uncommon in others (such as Spain) [6,7]. Women from a low-use country who select an IUS for contraception may be more motivated to manage side-effects and to continue with that method compared with women in countries where IUS use is widespread. Sweden, in particular, had lower continuation rates in this study but also has a higher prevalence of IUS use in the general population .
In addition, differences in counselling between the participating countries and centres may also have led to the observed differences in satisfaction and continuation between countries. As the health care providers in this study were asked to simply provide women with their routine counselling, this was not standardised and therefore women in some countries and some centres may have received more thorough counselling than others. It is known that counselling can affect contraceptive acceptance and continuation rates [26–28]. Thus, this may also be a factor behind the country differences.
Interestingly, this study revealed that parity did not affect satisfaction or continuation rates. Similarly, age was not associated with satisfaction or continuation. This is important because it is a misconception among some health care providers and the public that IUSs are unsuitable for young, nulliparous women [8–11]. LNG-IUS 12 has previously been shown to be safe and efficacious in nulliparous women of all ages [14,17,18]. Furthermore, previously published data from the KYSS interim analysis have also demonstrated that insertion of LNG-IUS 12 is easy and results in none or mild pain even in young, nulliparous women where it is often (erroneously) assumed that insertion will be painful and difficult . The data presented here provide further evidence that LNG-IUS 12 is suitable for women irrespective of parity or age, by demonstrating high satisfaction and continuation across these subgroups.
Participants in this study had used a wide variety of prior contraceptive methods before switching to LNG-IUS 12. Regardless of the previous method used, satisfaction with LNG-IUS 12 was high; furthermore, previous IUS use was not associated with higher satisfaction rates than previous use of no or other contraceptive methods. Some differences in satisfaction were observed, but firm conclusions cannot be drawn from direct comparisons between the prior contraception subgroups due to the fact that some subgroups (such as the implant, transdermal hormonal contraception, or back-up contraception subgroups) contained an extremely small number of participants.
Satisfaction with LNG-IUS 12 was also high regardless of motivation for switching from the prior method of contraception. It is interesting to note that even those who chose to use LNG-IUS 12 due to a desire for an improved bleeding pattern had high satisfaction rates. This is despite the potential initial bleeding pattern changes associated with LNG-IUS, where bleeding may be more frequent and/or prolonged for the first 3 months of use . Unfavourable bleeding pattern changes are a common cause of dissatisfaction and discontinuation of LARCs [30–34], and concerns about these changes can prevent some women from considering using LARCs [25,35,36].
Although it is possible that irregular bleeding and spotting were underreported, the number of women reporting bleeding issues was low overall, and the number discontinuing due to this was even lower. The rate of device removal (for any reason) at 4–12 weeks as reported in the KYSS interim analysis was 2.2% compared with 8.3% at the end of 12-month observation period , demonstrating that discontinuation was not excessively high in the first 3 months of use. Women’s satisfaction with their menstrual bleeding profile was lower at 4–12 weeks of use than at the end of the observation period; however, at both follow-up time-points, most women were satisfied. Thus, for women with concerns about bleeding profile changes caused by usage of LNG-IUS, these findings should be reassuring.
This study builds on the already established favourable safety and efficacy profile of LNG-IUS 12 [14,17,18]. Adverse events, particularly serious adverse events or those leading to discontinuation, were uncommon and there were very few cases of contraceptive failure and expulsion, and no cases of uterine perforation.
Similarities and differences in relation to other studies
Prior clinical trials have demonstrated high satisfaction and continuation rates associated with LNG-IUS 12 use [14,17,18]. The results from KYSS build on this further and provide the first evidence in a real-world setting for satisfaction with LNG-IUS 12. Continuation was similar to that seen in other clinical trials of LNG-IUS 12 [14,17,18]. Satisfaction and continuation rates in this study compare favourably with those reported in trials using other methods of contraception [14,16–18,37]. The rate of adverse events, in particular expulsion, also compared favourably to rates reported in prior trials [14,17,18]. Real-world evidence bridges the gap between clinical trials and routine clinical practice, as the data from observational studies reflect the diversity of patients and clinical scenarios [38–40]. Thus, it is anticipated that the findings from KYSS will be applicable to an even larger, more inclusive, population of patients, providers, and health care systems and settings.