UPDATE ON CONTRACEPTION
Why we have not yet reduced the unintended pregnancy rate
Skyla meets the prerequisites for rapid diffusion; it is highly compatible with current practice and easy to place and use. Of all these characteristics, the relative advantage granted by its size is most likely to promote its diffusion through the medical community.
Ease of placement versus Mirena
Clinical information about Skyla is currently available from two sources. The first is the product package insert, which includes selected data from the product’s Phase 3 study. This study included 1,432 participants, of whom 556 (38.8%) were nulliparous and 540 (37.7%) were treated in the United States.20
The second source is a published, peer-reviewed Phase 2 trial comparing Mirena with two smaller, lower-dose levonorgestrel-releasing devices, with the lowest-dose product corresponding to the marketed Skyla product.21 In the Phase 2 trial, all 738 women given Mirena or the smaller devices experienced successful placement, with 98.5% of placements achieved on the first attempt. Investigators rated placement for the smaller devices “easy” in 455 of 484 (94.0%) women, compared with 219 of 254 (86.2%) women given Mirena (P <.001). Most of the women given the smaller devices rated their pain with insertion as “mild pain” or “no pain,” compared with those given Mirena (72.3% vs 57.9%; P <.001). Adverse events were similar between users of the different products, except that significantly more women were classified as having an ovarian cyst among Mirena users than among users of the smaller, low-dose devices (22% vs 6%; P <.0001).
Little difference in "clinically relevant" effects
The claim that Skyla has an advantage over Mirena or ParaGard falls short on closer inspection. Although a clinician may prefer easy insertion and a patient with no pain, only very difficult or severely painful placements have clinical relevance.
Investigators rated only 4 of 254 (1.6%) Mirena insertions as “very difficult,” compared with 4 of 484 (0.8%) for the smaller devices (P=.46). Further, women found Mirena insertion to cause severe pain in only 17 of 254 (6.7%) insertions, compared with 21 of 484 (4.3%) placements of the smaller devices (P=.22). The smaller device and inserter, therefore, may have no clinical advantage.
Adverse events were similar
The data on adverse events are similarly misleading. Investigators in the Phase 2 study found that the lower-dose levonorgestrel-releasing IUDs had an 8.6% rate of ovarian cysts and the Mirena had a 22% rate (P <.0001). However, the Phase 2 study included a pelvic ultrasound examination at every visit, and ovarian cysts were included as an adverse event if the size was 3 cm or greater, regardless of symptoms.
Complaints of abdominal or low abdominal pain were as common among Mirena users as among users of the smaller devices, so this finding likely represents asymptomatic, clinically irrelevant cysts.
Most ovarian cysts found in users of the levonorgestrel-releasing intrauterine system are asymptomatic.22
Fewer Skyla users developed amenorrhea
Bleeding patterns differed between the products. Users of the smaller, low-dose device reported slightly more spotting and bleeding over the course of a month. In the Phase 2 trial, at the end of 3 years, only 12.7% of Skyla users achieved amenorrhea, compared with 23.6% of Mirena users. The amenorrhea rate for Mirena was very similar to the 20% rate reported in earlier studies,23,24 but the rate for Skyla was even lower (6%) in the larger Phase 3 study.
What about efficacy?
If there are no real advantages to be gained from the size of the device and inserter in terms of pain, and no real improvement in adverse effects or bleeding patterns, what about efficacy?
No direct comparisons are available, but if the devices are evaluated in terms of their first-year Pearl index rating from Phase 3 studies for approval in the United States, then among a cohort of 100,000 users, about 190 Mirena users would become pregnant in the first year, compared with 410 Skyla users.
All IUDs are considered highly effective contraceptives, but small relative differences can have a large impact on a population level if the methods are not used correctly or patients are not counseled appropriately. Although it is more effective than user-dependent contraceptives such as the pill, Skyla is the least effective of the highly effective methods available. If the device has any real benefits in comparison with the other IUDs, they must be better demonstrated with additional data.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
ObGyns have done much to increase the use of long-acting reversible contraceptives such as the IUD (Mirena, ParaGard), the etonogestrel implant (Implanon, Nexplanon), and the injectable contraceptive depot medroxyprogesterone acetate (Depo-Provera). We applaud this success and urge ObGyns to continue prescribing these options.
In addition, if we want to have a positive impact on the unintended pregnancy rate, we need to increase awareness of, access to, and use of the most effective contraceptive options in our community of providers and among our patients. We also need to eliminate barriers to use of the most effective methods—eg, discussing ulipristal acetate with our patients and providing advance prescriptions. We also need to be cautious about adopting some innovations, as the data for Skyla and Essure illustrate. They may be terrific options for very specific populations of women, but indiscriminate use may, paradoxically, increase the rate of unintended pregnancy.
