Contraceptive failure is defined as:
“a conception that occurred during a month in which a woman (or her partner) was using a contraceptive method, as long as she did not report that she (or he) had stopped use before having become pregnant” (Fu, Darroch, Haas, & Ranjit, 1999:57).
In the developing world, 30% of the 74 million unwanted pregnancies that occur annually are due to failure of traditional or modern contraceptive methods (Polis et al. 2016), with Implanon® being a highly efficacious modern contraceptive, with a 0.05% failure rate in typical and perfect use (Trussell, 2011).
The Pearl Index is used to report efficacy and is calculated using the “expected number of pregnancies per100 woman-years of exposure” (Darney et al. 2009:1648). A woman year is defined as “a period of 365.25 days and this is the equivalence of roughly 13 cycles” (Pam et al.
2014:93). A study by Darney et al. (2009) on an Implanon® clinical trial study reported that: six pregnancies occurred during the clinical trials, resulting in a 0.38 cumulative Pearl Index. The pregnancies occurred within two weeks of discontinuation of Implanon® and, according to the FDA, any pregnancy within this time of a hormonal method is considered contraceptive method failure. The manufacturing company recorded 1 688 spontaneous pregnancies over a nine-year period, therefore resulting in a post-marketing Pearl Index of 0.024, which was based on voluntary reports. Additionally, the clinical trial did not include participants who weighed more than 130%
of their ideal body weight and who were using enzyme inducing drugs, these variables having been shown to affect Implanon® efficacy. The incidence of reported pregnancies in a study by Bensouda-Grimaldi, Jonville-Bera, Beau-Salinas, Llabres, and Autret-Leca (2005) is estimated to be 0.359/103 implants, and the estimated Pearl Index was 0.06. The approximate failure rate in the post-marketing phase in Australia is 0.1%, or 1 in 1000 insertions (Harrison-Woolrych & Hill, 2005). Similarly, the contraceptive method failure rate in the USA monitoring program was 0.17% (Creinin et al. 2017). The incidence of pregnancy in studies from Africa was low as shown in Table 2-9 (Tadesse et al. 2017; Pam et al. 2014; Muthir & Nyango, 2010) with the exception of Patel et al. (2015) who reported a total of 86 pregnancies in their study. The average time of onset of pregnancy in a French post-marketing study (n= 104) was 13 months (median 10.7 months) (Simon et al. 2016). Three pregnancies occurred in the first year of etonogestrel implant use and three in the second year in a USA monitoring program (Creinin et al. 2017).
Evidence from the literature in Table 2-9 indicates that pregnancies with etonogestrel implants can be due to reasons other than true contraceptive method failure. A notable reason for pregnancy, as established in several studies, was pregnancy prior to insertion. Practitioner-related reasons for pregnancy, such as insertion technique failure, and untimely insertion (Bensouda-Grimaldi et al. 2005; Harrison-Woolrych & Hill, 2005), were also cited. User-dependent reasons for pregnancy were noted in only two cases and included improper use of implant (Creinin et al.
2017) and unprotected sexual intercourse practiced in the first week of insertion (Obijuru et al.
2016). In studies from Africa, pregnancy was due to drug interaction, contraceptive method failure and pregnancy prior to insertion as highlighted in Table 2-9 Tadesse et al. 2017; Pam et al. 2014; Muthir & Nyango, 2010; Patel 2015).
One of the most common reasons for pregnancy was due to drug interaction with antiepileptics, ARVs, antituberculosis and St. John's wort (Simon et al. 2016, Harrison-Woolrych & Hill, 2005).
While some studies have reported pregnancy in etonogestrel implant use (Olowu, Karunaratne,
& Odejinmi, 2011; Rezai et al. 2018; Bouquier et al. 2012), others have particularly reported on failure of Implanon® in patients using efavirenz based therapy (Matiluko et al. 2007; Leticee, Viard, Yamgnane, Karmochkine, & Benachi, 2012; McCarty, Keane, Quinn, & Quah, 2011;
Lakhi & Govind, 2010). Patel et al. (2015) revealed a three times higher risk of implant contraceptive failure in efavirenz than nevirapine users.
Implanon NXT® efficacy may be affected by body mass index (BMI) however, there are contradicting arguments on this issue. The etonogestrel plasma levels is inversely related to body weight hence variations in serum concentration levels is possibly due to differences in body weight (Merck Sharp & Dohme, Australia, 2010). Creinin et al. (2017) suggested that BMI may influence failure and reported failure in one patient who was normal weight, two who were overweight and two who were obese. However, these results are insufficient to make a conclusion about possible effect of BMI on Implanon NXT® effectiveness. Xu et al. (2012) commented that one unwanted pregnancy over 1377 women-years resulted in an overall cumulative implant failure rate of 0.00 per 100-woman years, and 0.23 per 100-woman years in obese patients (2012).
Mornar et al. (2012) also established that the estimated etonogestrel exposure for obese women in a three-year period was found to be 40% lower than in those of normal weight. Projected plasma concentrations at one, two and three years after device insertion in the obese women were 133, 102, and 98 pg/mL respectively (2012). The projected etonogestrel concentrations for the third year was still above 90 pg/ml, which is an effective concentration to suppress ovulation. It is therefore evident that increased weight could be a factor in the contraceptive failure due to Implanon NXT®.
Table 2-9: Possible causes of pregnancy in etonogestrel implant use
Possible cause Frequency (n) References
Drug interaction 59 Simon et al. (2016)
57 Patel et al. (2015)
32 Australian Government (2010)
32 Commonwealth of Australia
(2007)
8 Harrison-Woolrych and Hill
(2005)
4 UK-MHRA (2014)
2 Bensouda-Grimaldi et al. (2005)
2 Lakhi and Govind (2010)
1 Schindlbeck, Janni, and Friese
(2006)
Method failure 13 Harrison-Woolrych and Hill
(2005)
1 Bensouda-Grimaldi et al. (2005)
1 Muthir and Nyango (2010)
1 Pam et al. (2014)
Insertion technique failure 203 Simon et al. (2016)
84 Harrison-Woolrych and Hill
(2005)
30 Bensouda--Grimaldi et al. (2005)
Pregnant prior to insertion 71 Simon et al. (2016)
46 Harrison-Woolrych and Hill
(2005)