Single-Rod Implant: Efficacy

(Published July 2008)

Implanon™ has the highest efficacy among available contraceptive methods.¹ Optimal efficacy is due to the mechanism of action, which is principally ovulation inhibition, combined with the fact that the method is independent of user compliance.

The pregnancy rate is calculated from clinical trials involving 923 women and 1,854 women-years of Implanon use. The total number of 28-day cycles by year of use is:

Year 1: 10,867 cycles

Year 2: 8,595 cycles

Year 3: 3,492 cycles

Among women 18–35 years of age at entry into the clinical trials, six pregnancies occurred during 20,648 cycles of use. Two pregnancies occurred in each of Years one, two, and three. Each conception was thought to have occurred within two weeks after Implanon removal. The cumulative Pearl Index was 0.38 pregnancies per 100 women-years of use based on these six pregnancies. These clinical trials excluded women weighing more than 130 percent of their ideal body weight and women taking chronic medications that induce hepatic enzymes.

Post-marketing or real-life typical use trials have been conducted in developed countries. During the introduction of the product many insertion errors led to unanticipated pregnancies. In the first three years after introduction, 200 pregnancies were reported in an estimated 20,486 Australian women using Implanon. These unintended pregnancies were principally due to improper insertion technique, improper insertion timing in the menstrual cycle, or expulsion of the implant.³ An analysis of the findings from this study indicated:

• 46 women were already pregnant
• 84 implants were not actually inserted. With improper insertion training, the rod often fell out of the applicator or remained in the applicator, never reaching the arm.
• 19 were inserted at the wrong time leaving a gap for pregnancy to occur
• Three were expulsions
• Eight were drug-drug interactions
• The remaining cases had insufficient data to conclude the reason for pregnancy

Improved clinician training regarding insertion technique has appeared to greatly improve the failure rate of this contraceptive method.

Insertion errors led to a similar experience in France. Between May 2001 and September 2002, 39 pregnancies were reported in women using Implanon, which had been inserted incorrectly.⁴ The incidence of reported pregnancies was estimated at 0.359 per 10,000 implants. The majority of the unintended pregnancies were due to improper timing or failure to successfully implant the device:

• 30 implants were not actually inserted
• Two were drug-drug interactions
• Four were untimely insertions
• Two others were lost to follow-up

These real-life outcomes emphasize the need for health care providers to receive proper instruction on insertion techniques and timing for Implanon.

In other post-marketing studies of Implanon, no pregnancies occurred following insertion. Implanon users were followed for three years in a study of 417 women in Mexico City.⁵ The observation period totaled 958.5 woman-years of use (27.5 months per woman). No pregnancies occurred in this study for a pearl index of 0.0. The continuation rate was 61.4 percent. A United Kingdom study followed 106 women using Implanon for three years or until discontinuation.⁶ The continuation rate was 69.8 percent at 1 year, 44.1 percent at two years, and 30.2 percent at 3 years. No pregnancies occurred during this study. The United States clinical trial of 330 women who had Implanon inserted had an observation period of 474 woman-years representing 6,186 cycles.⁷ No pregnancies occurred in this clinical trial. Each of these studies further confirms the high efficacy rate of the Implanon single-rod implant when inserted properly.

There is no evidence that body weight affects the efficacy of Implanon, although clinical trials of this method included relatively few women who weighed more than 90 kg. Hence, the effect of increased body weight on efficacy is unknown. Serum concentrations of etonogestrel are inversely related to body weight and decrease with time after insertion. It is therefore possible that the Implanon implant may be less effective in overweight women, but data to substantiate this are lacking. The health care provider should discuss this aspect of Implanon efficacy when counseling overweight women. This is especially relevant in the presence of other factors that decrease etonogestrel concentrations, such as the concomitant use of hepatic enzyme inducers.

A few cases of ectopic pregnancy have been reported in women using Implanon, although there is no evidence of any causality. Concomitant use of an enzyme inducer (rifampin) resulted in ovulation and the subsequent ectopic pregnancy in one case report.⁸ The Implanon Physician Insert states:

“Be alert to the possibility of an ectopic pregnancy among patients using Implanon who become pregnant or complain of lower abdominal pain. Although ectopic pregnancies should be uncommon, a pregnancy that occurs in a patient using Implanon may be more likely to be ectopic than a pregnancy occurring in a patient using no contraception.”³

References:

1. Croxatto HB, Mäkäräinen L. The pharmacodynamics and efficacy of Implanon^®: An overview of the data. Contraception. 1998;58:(6):91S-97S.
2. Implanon (etonogestrel implant) Physician Insert. Organon USA, Inc. Roseland, NJ. 2006.
3. Harrison-Woolrych M, Hill R. Unintended pregnancies with the etonogestrel implant (Implanon): a case series from post-marketing experience in Australia. Contraception. 2005 Apr;71(4):306-8.
4. Bensouda-Grimaldi L, Jonville-Béra AP, Beau-Salinas F, Llabres S, Autret-Leca E; le réseau des centres régionaux de Pharmacovigilance. Insertion problems, removal problems, and contraception failures with Implanon]. Gynecol Obstet Fertil. 2005;33(12):986-90.
5. Flores JB, Balderas ML, Bonilla MC, Vázquez-Estrada L. Clinical experience and acceptability of the etonogestrel subdermal contraceptive implant. Int J Gynaecol Obstet. 2005;90(3):228-33.
6. Agrawal A, Robinson C. An assessment of the first 3 years’ use of Implanon in Luton. J Fam Plann Reprod Health Care. 2005 Oct;31(4):310-2.
7. Funk S, Miller MM, Mishell DR Jr, Archer DF, Poindexter A, Schmidt J, Zampaglione E; The Implanon US Study Group. Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel. Contraception. 2005;71(5):319-26.
8. Patni S, Ebden P, Kevelighan E, Bibby J. Ectopic pregnancy with Implanon. J Fam Plann Reprod Health Care. 2006 Apr;32(2):115.