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Table 1 Table describing salient features of included studies

From: A systematic review on clinical effectiveness, side-effect profile and meta-analysis on continuation rate of etonogestrel contraceptive implant

Author, country and year Type of study sample size Comparator (s) Effectiveness Effect(s) reported frequency (percentage) Continuation rate reported Follow-up period Reference number
Study design: cohort study
 Abraham M et al., USA, 2015 CHOICE cohort study n = 6106 Cu-IUD, Age and parity NA NA ENG implant continuation rate varied from 83 to 92% at 1 year and from 59 to 72% at 2 years. Nulliparous female were more likely to discontinue their LARC method among implant users adjusted HR 1.89, 95% CI 1.35–2.64 1, 2 years [53]
 Peipert et al., USA, 2011 CHOICE cohort study n = 5087 LNG IUS, Cu-IUD and Etonogestrel implant NA NA Continuation rate at one year for ENG implant was 83% 1 year [63]
 Neil O callahan et al., USA, 2013 CHOICE cohort study n = 9256 LNG IUS, Cu-IUD and Etonogestrel implant NA NA 24-month continuation rate for implant was 69% 2 years [72]
 Grunloh et al., USA, 2013 CHOICE cohort study n = 6167 LNG IUS, Cu-IUD and Etonogestrel implant NA NA Discontinuation rates was 6.9% for the implant 6 months [59]
 Vickery et al., USA, 2013 CHOICE cohort study n = 427 DMPA, LNG-IUS, Cu-IUD, ENG-implant NA No difference in weight gain NA 1 year [45]
 Agostini et al., France, 2018 Retrospective cohort study n = 42,365 COCs, progestin-only oral contraceptives, Cu-IUD, LNG-IUS and ENG implant NA NA 83.6% for the ENG implant Up to 2 years [54]
 Berenson et al., USA, 2014 Retrospective study LNG-IUS (n = 79,920) or ENG implants (n = 7374) inserted LNG-IUS and ENG implant 98.821% for ESI and 98.8713% in LNG-IUS The most frequent complications with both methods were related to abnormal menstruation, which was more likely to occur among ENG implant users 14.82% of ENG implant users discontinued within 1 year of insertion 1 year [38]
 Bitzer et al., Switzerland, 2004 Retrospective study n = 1183 None NA Side-effects (visit 1) included infrequent bleeding (28%), amenorrhea (33%), prolonged bleeding (15%), and metromenorrhagia (frequent and heavy bleeding) (16%). Other reported side-effects at visit 1 included dizziness (12%), acne (11%), mood swings (8%) and headache (5%) Implanon was removed prematurely in 235 women − 24%   [41]
 Chiles et al., USA, 2016 Retrospective cohort study  > 1.7 million women, aged 14–40 years LNG IUS, Cu-IUD and Etonogestrel implant NA NA Among women who selected the implant, 32.0% continued their method at 36 months 3 years [57]
 Sara e casey, Democratic Republic of Congo, 2017 Retrospective cohort study n = 548 Implant, IUD, Injection and Pill NA NA Discontinuation rate at one year for LARC users(IUD and implant) was 13.9% 1 year [42]
 Thamkantho et al., Thailand, 2008 Retrospective clinic based study n = 166 None 0 pregnancy in 1 year of use 30.3% had regular menstrual flow for a few months alternately with no menses for a few months; prolonged menstrual bleeding most common NA 1 year [33]
 Teunissen et al., Netherlands, 2014 Retrospective consecutive cohort design n = 230 None NA NA The continuation rate after 12 months was 72%; after 24 months, 53%; and after 36 months, 25%, with all women concerned having a new implant placed 1, 2, 3 years [69]
 Sznajder et al., USA, 2016 Retrospective cohort data n = 160 (12–24 years age) LNG-IUS and ENG implant NA NA Dis-continuation rate at one year for ENG implant was 22.68% 1 year [68]
 Howard et al., USA, 2017 Retrospective cohort study Retrospective cohort study based on billing records from a large multispecialty private practice in Las Vegas, Nevada None NA NA There was a progressive decrease in the 12-month continuation of implant from 2013 (95.7%) to 2015 (57.7%) 1 year [61]
 Aisien et al., Nigeria, 2010 Prospective Longitudinal n = 32 None 100% Oligomenorrhea: 18 (56.3%) Menorrhagia: 1(3.1%) and Combination: 13 (40.6%) Headache: 4 (12.5%) and Reduced libido: 3 (9.4%) Continuation rate at 1 year for ENG implant was 93.8% 12 months [27]
 Weisberg et al., Australia, 2014 Prospective Longitudinal n = 349 LNG-IUS and ENG implant NA NA 47% of implant users discontinued within three years 3 years [70]
 Rominski et al., Ghana, 2018 Pilot longitudinal study – Implant, IUD, Injection and Pill NA NA Continuation rate at one year for ENG implant was 95% 1 year [65]
 Arribas et al., Spain, 2009 Prospective n = 356 None 100% NA Continuation rates were 91.0% at 1 year, 74.7% at 2 years and 65.1% at 2 years and 9 months 1, 2, 2 year 9 months [28]
 Boas et al., Brazil, 2016 Prospective cohort study n = 213 healthy women None NA Increase in weight (63.3–66.1) and BMI (24.7–25.7) and a decrease in TC (172–161.5), TG (75–69.5), and LDL (100.5–98.5) (p > 0.05). Of the metabolic variables, FBG (85–88) and HDL (53–46) had significant differences (p < 0.002) NA 1, 2, 3 years [47]
 Guazelli et al., Brazil, 2010 Prospective study n = 47 None NA Increase in mean hemoglobin, hematocrit and indirect bilirubin concentrations and of the HDL-C/TC and HDL-C/LDL-C ratio. Decrease in mean TC level as well as LDL-C, very low-density lipoprotein cholesterol, TG, SGOT and SGPT NA 1 year [46]
 Hidalgo et al., Brazil, 2006 Prospective study n = 344 LNG implant, Cu-IUD NA Implanon, Jadelle and Cu-IUD, 12-month ovarian cyst incidence rates were 26.7%, 14.6% and 1.2%. They regress spontaneously and do not require further treatment NA 1 year [52]
 Iversen et al., Denmark, 2018 Prospective cohort study n = 1,879,227 Hormonal contraception NA Use of progestogen-only products was not associated with ovarian cancer risk NA 20 years [50]
 K Gezginc et al., Turkey, 2007 Prospective study n = 80 None 100% Amenorrhoea, infrequent bleeding and frequent bleeding were reported by 33(41.25%), 19 (23.75%) and 14 women (17.5%) 25% discontinuation in the study period of 2 years 2 years [29]
 Lidegaard et al., Denmark, 2012 Prospective cohort n = 1,626,158 OCP, LNG-IUD, Vaginal Ring, Patch and Implant NA No significant increase in the risk of thrombotic stroke or myocardial infarction NA 15 years [51]
 Modesto, Brazil, 2014 Prospective cohort n = 150 Cu-IUD, ENG-implant NA No significant differences on BMD. Increase in body weight (p 0.001) and an increase of 2% in the percentage of body fat, when compared with Cu-IUD users. Increase in lean mass (p = 0.020) NA 1 year [44]
 Morch et al., Denmark, 2017 Prospective cohort study n = 1.8 million OCP, LNG-IUD, Vaginal Ring, Patch and Implant NA As compared with never users of contraception, relative risk of breast cancer among implant users was 0.93 (0.48–1.79) NA Average of 10.9 years [49]
 Winner et al., USA, 2007 Prospective cohort n = 7486 DMPA and PPR (Pill, patch, ring) 0.27 per 100 participant-years in LARC as compared to 0.22 in DMPA and 4.55 in PPR NA NA 3 years for first 5090 participants and 2 years for those after [34]
 Birgisson et al., USA, 2015 Observational Cohort n = > 9000 LNG IUS, Cu-IUD and Etonogestrel implant, Patch, Pill and Ring Combined LARC (LNG-IUS, Copper- IUD and implant) failure rate at 1, 2 and 3 years was 0.3%, 0.6% and 0.9% as compared to 4.8%, 7.8% and 9.4% among short acting contraceptive users NA 12 and 24 month continuation rate was 83% and 68% 1, 2 years [39]
 Cea Soriano et al., UK, 2014 Prospective Observational study – Cu-IUD, LNG-IUS and DMPA injections NA NA 13.2% of ENG Implant users discontinued in first year of use 1 year [56]
 Short et al., 4 EU countries, 2012 Prospective Observational study n = 311 LNG-IUS and ENG implant NA NA Continuation rate at 1 year for ENG implant was 86% 1 year [67]
Randomised controlled trial
 Apter 2016 RCT Multicentre RCT n = 766 LNG-IUS and ENG implant The PIs for LNG-IUS and the ENG implant were 0.9 (95% CI 0.2–2.6) and 0.0 (95% CI 0.0–1.2), respectively The incidence of adverse events was 84.3% and 79.5% in the LNG-IUS 8 and the ENG implant groups, respectively. In LNG-IUS users: Dysmenorrhea (33.5%), uterine spasms (16.2%), procedural pain (13.6%), headache (11.3%), and acne (9.9%). In ENG implant users, acne (15.5%), headache (12.3%), dysmenorrhea (12.3%), nasopharyngitis (9.2%), and cervical dysplasia (8.9%) The 12-month discontinuation rates were 19.6% and 26.8% in the LNG-IUS 8 and ENG implant groups, respectively 1 year [35]
 Flores et al., Mexico, 2005 Multicenter trial n = 417 None The Pearl Index score was 0 NA The continuation rate at the end of 3 years was 61.4% 3 years [25]
 Bahamondes et al., Multicentre-seven countries, 2015 Open parallel group RCT n = 2963 Copper IUD-380A, LNG-implant and ENG implant 0.4 per 100 woman years (CI 0.1–1.4) in ENG implant; 2.8 ( CI 1.3–6.0) in Cu-IUD ENG implant: Amenorrhea: 38.9%, irregular bleeding: 86.0%, heavy bleeding: 35.38%, prolonged: 56.18%; acne: 45.23%; headache: 59.6% and lower abd pain: 50.35%; dizziness: 44.52% and PID: 1.21% Copper IUD: Amenorrhea: 8.65%, irregular bleeding: 38.93%, heavy bleeding: 49.85%, prolonged: 42.95%; acne: 32.23%; headache: 53.24% and lower abd pain: 61.17% dizziness: 39.96% and PID: 2.68% Method continuation rates for ENG implant at 2.5 years was 69.8 (95% CI 66.8–72.6) 2.5 years [37]
 Hubacher wt al, USA, 2016 randomized patient preference trial n = 916 OCP, DMPA, IUD and implant Implant and IUD (combined) was 0.7 (0.0–4.7) OC: 6.1 (4.3–8.6) DMPA: 4.6 (0.2–12.2) NA At one year, probability of continuation of implant was 77.5% (70.2–84.8) 1 year [36]
 Oderich et al., Brazil, 2010 Nonrandomized, open-label, prospective controlled tria n = 40 Cu IUD and implant NA Carbohydrate metabolism was not modified NA 6, 12 months [48]
 Study design: cross-sectional study
 Nageso et al., Ethiopia, 2018 Cross-sectional study design n = 711 None NA NA Early Implanon discontinuation rate in this study was 23.4% 1 year [73]
 Gupta et al.,Papua New Guinea, 2017 Cross sectional study n = 860 None 0.992 Irregular bleeding n = 178, 20.6% but only 7% (n = 13) said the bleeding was bothersome 97% (n = 836) still had the device in situ after 12 months 1 year [30]
 Medhin TG et al., Ethiopia, 2019 Cross sectional study n = 229 None NA NA Discontinuation: early Implanon discontinuation rate was 38%, 95% CI (32%, 44%).Discontinuation rate was (2.6%) within 6 months, (15.7%) 1 year, (19.7%) in 2 years and (62%) in 3 years At 6 months, 1, 2 and 3 years [71]
 Smith et al., USA, 2018 Pilot study n = 29 COCP, Progestin-only contraceptive, non-hormonal or no contraceptive NA Progestin-only-contraceptives users have a potential of developing depressive symptoms and have attenuated beta arrestin-1 protein levels in peripheral blood mononuclear leukocytes NA Unclear [76]
 Yildizbas et al., Turkey, 2007 A pilot study n = 41 None NA 34.1% had amenorrhea; 58.5% had some type of abnormal bleeding. Mood change in 17.1% and acne in 26.8% NA 6 months [40]
Study design: retrospective chart review
 Peterson et al., USA, 2019 Retrospective chart review n = 544 None NA NA Discontinuation rate at one year for ENG implant was 16% 1 year [64]
 Romano et al., USA, 2019 Retrospective chart review n = 197 Non-users of implant NA ENG implant users weight gain + 3.6 (± 7.8) kg vs + 3.1 (± 5.9) kg for controls (P = 0.43). Overall regression analyses showed no group differences among cases and controls The mean duration of ENG use was 24.5 (± 9.3) months with 21.8% of users (43/197) discontinuing the method early (before 3 years) 20 months [43]
 Mutihir et al., Nigeria, 2010 Retrospective review n = 669 None 98.51% NA 95.5% at the end of second year 2 years [31]
 Smith et al., UK, 2002 Retrospective record review and postal survey n = 190 None 100% NA Continuation rates were between 84 and 88% at 6 months and 67% and 78% at 12 months 6, 12 months [32]
 Berlan et al., USA, 2016 Retrospective chart review n = 750 adolescents None NA NA 77 (10.3%) had the device removed prior to 12 months of use 1 year [55]
 Griffith et al., Australia, 2016 Mixed method study; retrospective chart review – Cu-IUD, MPA injection, COCP and ENG-Implant NA NA Etonogestrel continuation rates at 1, 2 and 3 years were 87% (95% CI 81–92%), 72% (95% CI 64–78%) and 51% (95% CI 41–60%) respectively 1, 2, 3 years [58]
 Casey et al., USA, 2010 Retrospective review of medical records n = 151 None NA 39 (25.2%) women had abnormal bleeding Implant removal rate was 25.2% (mean interval, 9.8 months) 90 day reference periods. No fixed follow up [74]
 Harvey et al., Australia, 2009 Retrospective chart n = 767 None NA NA Continuation at 6 months after insertion was 94%. 74% continued at 1 year, 61% continued at 1.5 years and 50% continued at 2 years.1.2% continued beyond 3 years Every 6 months up to 3 years [60]
 Sanders et al., USA, 2017 Retrospective chart review n = 1008 LNG-IUS and Cu-IUD-T380A NA NA Two-year continuation rate 75.9%( 68-mg Etonogestrel implant) 2 years [66]
 Lakha et al., UK, 2006 Case notes Review n = 324 None NA NA Continuation rates were 89% (CI 84–91) at 6 months, 75% (CI 69–79) at 1 year, 59% (CI 52–63) at 2 years and 47% (CI 40–52) at 2 years and 9 months Every 6 months upto 3 years [62]
 Agrawal et al., UK, 2005 Case note-based study n = 106 None 100% NA The continuation rate at the end of 1 year was 69.8%, at 2 years was 44.1% and at 3 years was 30.2% 1, 2, 3 years [26]
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Reproductive Health

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