Etonogestrel Implants Research Articles

Menstrual management using the etonogestrel implant in individuals with intellectual disabilities in Joinville, Brazil.

This study aimed to describe the use of etonogestrel (ENG) implants for menstrual management (i.e., management of bleeding and symptoms associated with menstruation) in individuals with intellectual disabilities. This study retrospectively analyzed a cohort of individuals with intellectual disabilities who began using ENG implants between 2003 and 2018, in Joinville, Brazil. We collected sociodemographic, clinical, and reproductive data from the medical records, along with information related to ENG implant use. In total, 369 implants were placed in 130 individuals with intellectual disabilities. The median age at the first implant was 20 (interquartile range [IQR], 17-26) years, and 43.8% of the patients were adolescents. By December 2018, 90 patients had received two or more subsequent implants. The median duration of current ENG implant use was 19 (IQR, 12.8-22) months. More than 40% of the patients had comorbidities, with epilepsy being the most common. During the use of the current implant, 80% of the patients had a favorable bleeding profile (no bleeding or ≤1 bleeding episode per month), and 53.8% (70/130) had no bleeding within 3 months before their last medical visit. Among patients experiencing dysmenorrhea and premenstrual syndrome (PMS), 79% (64/81) and 82% (54/66) reported complete improvement, respectively. The premature implant removal rate was 8.9% (33/369). Unfavorable bleeding was the main reason for premature implant removal (20 out 33 removals). ENG implants might be a suitable option for individuals with intellectual disabilities who require management of menstrual bleeding and symptoms associated with menstruation. Most patients had a favorable bleeding profile and experienced significant improvements in dysmenorrhea and PMS, contributing to the high continuation rates of ENG implants.

Manufacture, characterization, and elucidation of drug release mechanisms of etonogestrel implants based on ethylene vinyl acetate

In this work, etonogestrel implants were manufactured using coextrusion. The purpose of the study was to correlate changes in microstructure and transport properties that occurred in etonogestrel implants to drug release mechanisms. The implants consisted of an EVA 28 (28 % vinyl acetate) core containing dispersed and dissolved etonogestrel, and an EVA 15 (15 % vinyl acetate) skin. The drug release was determined to be via diffusion at a controlled rate and governed by implant dimensions. In-vitro release revealed evidence of supersaturation in the implant core and skin, likely from the intense mechanical energy input during the twin-screw manufacturing process. Subsequently during storage under ambient conditions, supersaturation resulted in recrystallization of drug crystals, preferentially in the implant core. Etonogestrel solubility and diffusivity in EVA were determined by permeation experiments and used for release modeling. Drug release from the EVA skin layer deviated from the predicted values due to 1) formation of a drug depletion zone in the core and 2) presence of a stagnant media layer adjacent to the skin. Drug release from implant ends was significantly faster than predicted. Air-filled pores were observed in the implant core using microCT which likely contributed to the faster release from implant ends.

P-607 Reproductive outcomes of oocyte donors using subdermal etonogestrel implants and levonorgestrel intrauterine devices

Abstract Study question Does the use of progesterone contraceptive devices during controlled ovarian stimulation (COS) affect ovarian response in oocyte donation cycles? Summary answer Progesterone contraceptive devices during COS did not impact ovarian response, measured by oocyte retrieval and maturity rates, in oocyte donation cycles. What is known already Subdermal etonogestrel implants and levonorgestrel intrauterine devices (L-DIU) are widely used contraceptives amongst oocyte donors. While the safe and effective use of L-DIU during COS has been documented, the impact of subdermal etonogestrel implants on ovarian response is less understood. Given their distinct mechanisms of action and varying local and systemic pharmacodynamics, a comprehensive understanding of the impact of these contraceptives on ovarian response during COS will be crucial for guiding informed clinical practice. Study design, size, duration In this retrospective cohort study, we analyzed 3,452 heterologous ICSI cycles from 1,975 oocyte donors (18-35 years), performed between March 2021 and September 2023, across two centers. We identified 40 COS in donors using contraceptive devices, either a subdermal etonogestrel implant (n = 18) or L-DIU, (n = 22). These were matched with 80 COS without a device. We primarily compared ovarian response amongst the two groups. Secondary outcomes included biochemical pregnancy, clinical pregnancy and live birth rates. Participants/materials, setting, methods We applied a propensity matching score model (PsmPy package, Python), trained on 3,388 oocyte donation cycles, for matching donors with and without contraceptive devices. Matching was based on age, BMI, anti-müllerian hormone (AMH) and antral follicle count (AFC), maintaining a 1:2 ratio. Ovarian response outcomes (oocyte retrieval and maturation rates) were analyzed using Student’s t-tests, while and clinical outcomes were evaluated using Fisher’s exact test. P-values <0.05 were considered significant. Main results and the role of chance Mean age was 26.22, BMI 24.7, AMH 2.63 ng/ml and AFC 18.77. We evaluated a total of 120 COS, leading to 176 heterologous ICSI cycles. The oocyte retrieval rate (total number of cumulus-oocyte-complexes (COCs) per total number of follicles > 14mm at final follicular scan), averaged 109.64%. We observed no differences in the number of COCs retrieved from donors with and without contraceptive devices (17.5 ±7.6 and 18.5 ± 9.6, respectively). Similarly, oocyte maturation rates (total number of MII oocytes per total number of COCs), were comparable amongst the two groups (78.6% overall, 77.6% with contraception device and 79.1% without contraception device, p > 0.05). The presence of the device did not affect biochemical pregnancy (69.7% with contraceptive device, 61.1% without contraceptive device, p > 0.05), clinical pregnancy (54.6% with contraceptive device, 52.9% with contraceptive device, p > 0.05) and ongoing pregnancy (36.4% with contraceptive device, 35.3% without contraceptive device). These results were consistent regardless of the type of device used. Limitations, reasons for caution The main limitation is the retrospective nature of the study, potentially influencing causal inferences, and that both devices were analyzed as one same group. The small subset of COS with contraceptive devices may impact statistical power. Perinatal outcomes were not analyzed. Wider implications of the findings This research provides clinicians with reassurance that the use of progesterone contraceptive devices during COS does not adversely affect clinical outcomes. These findings offer valuable insights for patient counseling, affirming the safety of contraceptive methods and encouraging further research for a more comprehensive understanding in diverse populations and clinical settings. Trial registration number not applicable

Efficacy of medication abortion with concurrent initiation of progestin contraceptives: A retrospective cohort study

ObjectivesTo evaluate medication abortion (MAB) outcomes for participants receiving intramuscular depot medroxyprogesterone acetate (DMPA) injections or subdermal etonogestrel implants concurrently with mifepristone compared to those who did not in a real-world setting. Study designThis retrospective cohort study included MAB patients from one Planned Parenthood health center in St. Paul, MN, between 2017 and 2019. We abstracted electronic health records and compared sociodemographic variables, clinical information, and treatment failure rates (primary outcome) between study groups with logistic regression (generating odds ratios [OR] and 95% confidence intervals [CI]). ResultsAmong 7296 MAB participants, 224 (3.1%) received DMPA injections and 309 (4.2%) received etonogestrel implants concurrently with mifepristone; 141 (62.9%) and 200 (64.7%) completed follow-up respectively. From a random sample of 1000, 990 comparison participants met inclusion criteria; 704 (71.1%) completed follow-up. Fourteen (9.9%) DMPA participants (aOR 4.26, 95% CI 1.87–9.68, p < 0.001) and 6 (3.0%) etonogestrel implant participants (aOR 1.38, 95% CI 0.48–3.55, p = 0.522) required additional treatment to empty the uterus and/or had an ongoing pregnancy, each contrasted with 15 (2.1%) comparison patients (models adjusted for gestational duration, patient age, parity, and race). ConclusionAlthough our study is limited by high rates of loss to follow-up, our analysis suggests that concurrent administration of DMPA with mifepristone may decrease MAB efficacy, while etonogestrel implant placement does not appear to alter MAB outcomes. These findings are overall consistent with prior literature and inform post-MAB contraception counseling. ImplicationsThis retrospective cohort study reinforces prior randomized controlled trial findings that concurrent depot medroxyprogesterone acetate injection with mifepristone administration may decrease medication abortion efficacy. Conversely, concurrent etonogestrel contraceptive implant placement with mifepristone administration does not appear to decrease medication abortion efficacy. These findings inform post-abortion contraception counseling.

A randomized trial of double vs single-dose etonogestrel implant to overcome the interaction with efavirenz-based antiretroviral therapy

BackgroundConcomitant use of efavirenz-based antiretroviral therapy and a standard-dose etonogestrel contraceptive implant resulted in 82% lower etonogestrel exposure compared to women not receiving antiretroviral therapy. The clinical impact of this reduced exposure is supported by retrospective cohort evaluations which demonstrated higher rates of unintended pregnancies when contraceptive implants were combined with efavirenz. We hypothesized that placement of two etonogestrel implants in those taking efavirenz-based antiretroviral therapy could increase etonogestrel exposure and improve measures of contraceptive efficacy. ObjectivesThis study compared the rate of ovulation and etonogestrel pharmacokinetics in women on efavirenz-based antiretroviral therapy receiving two etonogestrel implants (136mg, DoublET group) versus one etonogestrel implant (68mg, Control group). Study DesignThis randomized, open-label study enrolled Ugandan women with regular menstrual periods who were receiving efavirenz-based antiretroviral therapy for treatment of HIV. Participants were randomized 1:1 to the DoublET or Control group, and the etonogestrel implant(s) were placed in the same arm at enrollment. All participants used a copper intrauterine device to prevent pregnancy. Ovulation was evaluated by weekly serum progesterone concentrations measured over 4 consecutive weeks at months 3 (weeks 9-12), 6 (weeks 21-24), and 12 (weeks 45-48). Progesterone concentrations >3ng/mL were interpreted as ovulation. The ovulation rate in each group was compared using Fisher’s exact test by month and generalized estimating equations over 48 weeks. Plasma was collected at day 3 and weeks 1, 4, 12, 24, 36 and 48 after implant placement, and analyzed by a validated LC-MS/MS method for etonogestrel. Etonogestrel concentrations were summarized as median (interquartile range, IQR) and compared between groups by geometric mean ratio (GMR) with 90% Confidence Interval (CI). ResultsAll participants (n=72) were cisgender Ugandan women, median age 31 (IQR 29, 36), and 36 participants were enrolled in each study group. Two participants in the Control group were discontinued; one at week 1 due to undetected pregnancy at entry and another at week 45 due to clinically significant depression. There were 47 ovulations over 104 person-months (45%) in 25 of 34 participants in the Control Group, and 2 ovulations over 108 person-months (2%) in 2 of 36 participants in the DoublET group [Month 3: 11 (31%) vs 0 (0%); Month 6: 17 (49%) vs 0 (0%); Month 12: 19 (56%) vs 2 (6%), respectively (all p<0.001)]. The odds of ovulation were reduced by 97.7% (95% CI: 90.1- 99.5) in the DoublET group over 48 weeks. At each time point, etonogestrel was more than two-fold higher in the DoublET group compared to controls (GMR 2.30-2.83), with the GMR of 2.83 (1.89, 3.35 90% CI) at week 48. There were no differences in the adverse events between groups and no participant discontinued due to adverse events. ConclusionOver 48 weeks of combined use, placing two etonogestrel implants suppressed ovulation and increased plasma etonogestrel exposure compared to one etonogestrel implant among women on efavirenz-based antiretroviral therapy. Doubling the dose of etonogestrel with efavirenz-based antiretroviral therapy could improve contraceptive effectiveness.

Long-acting reversible contraception with etonogestrel implants in female macaques (Macaca mulatta and Macaca fascicularis).

Contraception is often required for management and population control purposes in group-housed and free-roaming non-human primates. Long-acting reversible contraceptives, including subdermal progestin-releasing implants, are preferred as they eliminate challenges associated with frequent administration. Etonogestrel (ENG)-releasing subdermal implants are reversible and long-acting for a minimum of 3 years, and are commercially available for human use as Implanon® or Nexplanon®. A retrospective analysis was performed detailing the contraceptive effectiveness and reversibility of subdermal placement of one-fourth or one-third of an ENG implant (68 mg/implant) in 129 female rhesus macaques (Macaca mulatta) and 67 cynomolgus macaques (Macaca fascicularis) at the Biomedical Primate Research Centre (Rijswijk, Netherlands). Furthermore, single cross-sectional ENG serum concentrations were measured for 16 rhesus and 10 cynomolgus macaques, and hemoglobin and blood chemistry pre-ENG and at timepoints >0.5, >1.5, and > 2.5 years post-ENG insertion were evaluated for 24 rhesus macaques. Finally, data were obtained using trans-abdominal ultrasound regarding the influence of ENG on uterine volume and endometrial thickness in 14 rhesus and 11 cynomolgus macaques. As a contraceptive ENG was in 99.80% (CI 93.50-99.99) and 99.95% (CI 99.95-100) effective in rhesus and cynomolgus macaques, respectively. Prolonged ENG durations of implant use in 14 rhesus macaques (range 3.1-5.0 years) and eight cynomolgus macaques (range 3.2-4.0 years) resulted in no unintended pregnancies. A total of 17 female macaques were allowed to breed after ENG removal, and among them, 14 female macaques (82%) had an uneventful delivery. Serum ENG concentrations with a median ENG duration of 1.2 years (range 0.1-6.0 years) and 1.9 years (range 0.6-4.7 years) resulted in median concentrations of 112 pg./mL (range 0-305 pg./mL) and 310 pg./mL (range 183-382 pg./mL) for rhesus and cynomolgus macaques, respectively. ENG had no clinical effect on hemoglobin and blood chemistry parameters nor on the thickness of the endometrial lining or uterus volume. This study indicates that both one-fourth and one-third of the ENG implants are effective, long-acting, reversible, and safe contraceptive to use in macaques.

Pharmacokinetic Study of Islatravir and Etonogestrel Implants in Macaques.

The prevention of HIV and unintended pregnancies is a public health priority. Multi-purpose prevention technologies capable of long-acting HIV and pregnancy prevention are desirable for women. Here, we utilized a preclinical macaque model to evaluate the pharmacokinetics of biodegradable ε-polycaprolactone implants delivering the antiretroviral islatravir (ISL) and the contraceptive etonogestrel (ENG). Three implants were tested: ISL-62 mg, ISL-98 mg, and ENG-33 mg. Animals received one or two ISL-eluting implants, with doses of 42, 66, or 108 µg of ISL/day with or without an additional ENG-33 mg implant (31 µg/day). Drug release increased linearly with dose with median [range] plasma ISL levels of 1.3 [1.0-2.5], 1.9 [1.2-6.3] and 2.8 [2.3-11.6], respectively. The ISL-62 and 98 mg implants demonstrated stable drug release over three months with ISL-triphosphate (ISL-TP) concentr54ations in PBMCs above levels predicted to be efficacious for PrEP. Similarly, ENG implants demonstrated sustained drug release with median [range] plasma ENG levels of 495 [229-1110] pg/mL, which suppressed progesterone within two weeks and showed no evidence of altering ISL pharmacokinetics. Two of the six ISL-98 mg implants broke during the study and induced implant-site reactions, whereas no reactions were observed with intact implants. We show that ISL and ENG biodegradable implants are safe and yield sufficient drug levels to achieve prevention targets. The evaluation of optimized implants with increased mechanical robustness is underway for improved durability and vaginal efficacy in a SHIV challenge model.

Novel Method for Management of Bothersome Bleeding Associated With Etonogestrel Drug Implant [ID: 1380127

INTRODUCTION: Nexplanon (etonogestrel drug implant [EDI]) is an effective, implantable subdermal contraceptive that releases progestin over 3 years for suppression of ovulation and thickening of cervical mucus. A significant portion of EDI patients will remove their device prematurely because of bothersome episodes of frequent/prolonged bleeding. In patients with abnormal uterine bleeding, induction of a withdrawal bleed, with the goal of reducing excessive bleeding, is a common approach. There is no standard approach to treating prolonged and/or excessive bleeding with EDI in place. METHODS: This is a randomized double-blinded placebo-controlled trial of 51 patients desiring EDI for contraception. Patients received norethindrone (NTA) 5 mg or placebo daily for 1 week every 4 weeks for a total of 6 months. RESULTS: No patients in the treatment arm requested removal because of bothersome bleeding as defined by International Federation of Gynecology and Obstetrics/World Health Organization criteria. In contrast, 24% of the placebo group participants requested removal of the device at or before 6 months from placement for a variety of reasons including bothersome bleeding. 9% from the treatment group requested early removal; however, none for bothersome bleeding. 80% of the treatment group participants had a satisfactory bleeding pattern. One participant in the treatment arm complained of unsatisfactory amenorrhea. CONCLUSION: We propose a novel method to manage bothersome bleeding associated with EDI. Our data suggest that cyclic NTA is an effective method to treat bothersome bleeding in patients using etonogestrel implants for contraception and warrants further study.

The effect of rifampin on serum etonogestrel concentrations and biomarkers of ovulation among contraceptive implant users: A pharmacokinetic and pharmacodynamic study

ObjectivesRifampin, a strong CYP3A inducer, is the gold standard for evaluating CYP3A-mediated drug-drug interactions. We aimed to evaluate the pharmacokinetic and pharmacodynamic effects of a short course (2 weeks) of rifampin on serum etonogestrel (ENG) concentrations and serologic measures of ovarian activity (endogenous estradiol [E2] and progesterone [P4]) among ENG implant users. Study designWe enrolled healthy females using ENG implants for 12 to 36 months. We measured baseline serum ENG concentrations using a validated liquid chromatography mass-spectrometry assay and baseline E2 and P4 concentrations using chemiluminescent immunoassays. After 2 weeks of rifampin 600 mg daily, we repeated ENG, E2, and P4 measurements. We compared pre- and post-rifampin serum measurements using paired Wilcoxon signed-rank tests. ResultsFifteen participants completed all study procedures. Participants’ median age was 28.2 years (range 21.8–34.1), median body-mass index was 25.2 kg/m2 (range 18.9–37.3), and median duration of implant use was 22 months (range 12–32). All participants experienced significant decreases from baseline ENG concentrations (median 164.0 pg/mL [range 94.4–265.0]) to post-rifampin measurements (median 47.8 pg/mL [range 24.7–82.8]) (p < 0.001). Serum E2 concentrations also significantly increased with rifampin exposure (median 73 pg/mL vs 202 pg/mL, p = 0.003); increases in serum P4 concentrations were not statistically significant (p = 0.19). Three participants (20%) experienced increased luteal activity, with one presumptively ovulating post-rifampin (P4 = 15.8 ng/mL). ConclusionsWith only short exposure to a strong CYP3A inducer, ENG implant users experienced clinically significant decreases in serum ENG concentrations that led to changes in biomarkers indicative of waning suppression of ovulation. ImplicationsEven a short, 2-week course of treatment with rifampin places etonogestrel contraceptive implant users at risk for decreased contraceptive efficacy. Clinicians should counsel patients using etonogestrel implants considering any duration of rifampin therapy on the need for backup nonhormonal contraception or the use of an intrauterine device to avoid unintended pregnancies.

Continuation Rates of the Etonogestrel Implant and Factors Associated With Early Discontinuation.

The etonogestrel implant is generally consideredaneffective, three-year, long-acting reversible contraceptive device. Previous research, such as the landmark CHOICE study, has reported a one-year continuation rate of 72% to 84%, however, in a real-world setting these rates may be significantly lower. To study etonogestrel implant continuation rates and factors associated with early discontinuation in a specific clinical setting. Single-center, retrospective cohort study of patients who received the etonogestrel implant between January 1, 2015, and December 31, 2017, at several practices at an academic community hospital network. Records were reviewed up to three years after implant insertion to determine continuation rates (oneto threeyears), early discontinuation rates (≤12 months), and reasons for early discontinuation. A sample size calculation was performed to guide a subanalysis of side effects. A total of 774 patients underwent etonogestrel insertion during the study period.The one-year continuation rate was lower than that of the CHOICE study (62% vs. 83%, P <0.001). A subanalysis (n=216) revealed that a majority (82%, n=177) of patients reported side effects. Side effects were more common in patients with early discontinuation compared with patients who continued use longer than one year (93% vs. 71%, P <0.001). The most common side effect, abnormal uterine bleeding, was not significantly associated with early discontinuation. A significant association (P=0.02) was found between early discontinuation and neurologic/psychiatric complaints. The one-year continuation rate of the etonogestrel implant inourpopulation is significantly lower than the value reported by CHOICE. Implant side effects are common and significantly affect rates of discontinuation. Our data suggest there is an opportunity for education and counseling for individuals opting for this method of long-acting contraception.

What is the most effective way to pharmacologically manage breakthrough bleeding in women with etonogestrel implants?

What is the most effective way to pharmacologically manage breakthrough bleeding in women with etonogestrel implants?

Single-visit long-acting reversible contraception provision and pregnancy rates within 3 months.

To assess the occurrence of pregnancy in a cohort of women who received a copper intrauterine device (IUD), hormonal IUDs or an etonogestrel (ENG) contraceptive implant at a single-visit practice. Prospective study conducted at the University of Campinas, Campinas, São Paulo, Brazil. We obtained data from four ongoing studies including both the date of the device placement, the first day of the last menstrual period, and the occurrence of pregnancy up to 3months after device placement. We included 2479 device placements (413 TCu380A IUDs, 1476 hormonal IUD and 590 ENG implants). Almost half of the device placements (1113/2479; 44.9%) were performed within the first 5 days of the menstrual cycle. We observed three pregnancies: one in an ENG implant user who received the implant within days 1-5 of the menstrual cycle; one in a woman who received a hormonal IUD during days 6-10 of the menstrual cycle; and one in a copper IUD user with placement during days 21-25 of menstrual cycle. Single-visit long-acting reversible contraception placements are a good strategy with overall very low pregnancy rates. This strategy has a potential to reduce unintended pregnancies and to reduce costs and barriers to both women and the healthcare system.

EE154 Reassessment of a Cost-Effectiveness Analysis of Etonogestrel Implant Compared to Other Contraceptive Methods Based on Real Life Data in France

To reassess the cost-effectiveness of etonogestrel implant compared to other contraceptive methods delivered in France.

P079Etonogestrel contraceptive implant users can experience breakthrough ovulation with only two weeks of exposure to a strong cyp3a inducer

<h3>Objectives</h3> Rifampin is a strong CYP3A inducer and the gold standard for evaluating CYP3A-mediated drug-drug interactions per the US Food and Drug Administration. We hypothesized that even a short course (two weeks) of exposure would lead to breakthrough ovulation-mediated changes in endogenous estradiol (E2) and progesterone (P4) concentrations among etonogestrel (ENG) implant users. <h3>Methods</h3> We enrolled healthy people using ENG implants for 12–36 months. We measured baseline serum concentrations of E2 and P4 as surrogate biomarkers for ovulation suppression using clinical chemiluminescent immunoassays. After two weeks of rifampin 600 mg daily, we repeated E2 and P4 measurements. We determined breakthrough ovulation based on pre-exposure P4 3.0ng/mL with concurrent rise in post-treatment E2. <h3>Results</h3> Fifteen participants completed all study procedures. Participants' median age was 28.2 (range, 21.8–34.1), median BMI was 25.2 kg/m2 (range, 18.9–37.3), and median duration of implant use was 22 months (range, 12–32). At baseline, median E2 concentrations were 73 pg/mL (range, 32–686) and median P4 concentrations were 0.3 ng/mL (range, 0.2–6.1). After concomitant rifampin, median E2 concentrations were 201 pg/mL (range, 59–951) and median P4 concentrations were 0.4 ng/mL (range, 0.2–15.8). Serum E2 concentrations significantly increased with rifampin exposure (p=0.003, paired Wilcoxon signed rank test), but the increases in serum P4 concentrations were not statistically significant (p=0.185). Three participants (20%) experienced breakthrough ovulation with the following P4 changes: 0.3>5.0, 0.8>7.3, 0.5>15.8 (pre>post; ng/mL). <h3>Conclusions</h3> With only a short exposure to a strong CYP3A inducer, ENG implant users experienced clinically significant changes in hormone biomarkers indicative of waning follicular development and ovulation suppression.

Prolonged hormonal contraception: current research and practice: A review

This review presents information on demographic processes in Russia and the relevance of highly effective contraception for the prevention of artificial abortion. We present data on the etonogestrel implant (68 mg), an innovative single-stranded subcutaneous implant, a long-acting reversible contraceptive option with high efficacy (Pearl index 0.05) with optimal and typical use of the product. We analyzed the results of the studies that showed a favorable safety profile of the etonogestrel implant with no significant effect on the risks of thrombotic events, metabolic processes, depression incidence, bone mineral density, and characteristics of reproductive function after discontinuation of the drug. The article presents data on possible side effects in the form of changes in the characteristics of menstrual bleeding and a slight increase in body weight, which is comparable with the natural gain in an adult with age. The importance of qualified counseling of patients before and during the use of etonogestrel implants is emphasized.

Pharmacokinetics of levonorgestrel and etonogestrel contraceptive implants over 48 weeks with rilpivirine- or darunavir-based antiretroviral therapy.

Pharmacokinetic data are lacking for progestin-releasing subdermal contraceptive implants when used with either rilpivirine- or darunavir/ritonavir-based ART. To characterize the pharmacokinetics of etonogestrel or levonorgestrel implants when administered with these ART regimens over 48 weeks. Two separate, parallel, three-group, non-randomized, pharmacokinetic studies evaluated either etonogestrel or levonorgestrel in women receiving rilpivirine- or darunavir-based ART compared with women without HIV (control group). Participants on ART were switched to rilpivirine-based ART with a run-in period of 6 weeks or darunavir-based ART with a run-in of 2 weeks prior to implant insertion. Plasma was collected on Day 0, and 1, 4, 12, 24, 36 and 48 weeks post-insertion. Plasma progestin concentrations were compared between ART and control groups by geometric mean ratio (GMR) and 90% CI. At the primary endpoint of Week 24, progestin concentrations were similar between the rilpivirine and control groups [etonogestrel: 1.18 (0.99-1.37); levonorgestrel: 1.16 (0.97-1.33)]. At Week 24, progestin exposure was higher in the darunavir groups compared with the control group [etonogestrel: 2.56 (1.69-3.28); levonorgestrel: 1.89 (1.38-2.29)]. Results remained consistent through to Week 48. No differences in etonogestrel-related adverse events were observed, but both ART groups experienced more menstrual abnormalities versus the control group with levonorgestrel. Etonogestrel and levonorgestrel concentrations were not altered by rilpivirine-based ART. Although progestin concentrations were higher in the ART groups containing ritonavir-boosted darunavir, no implant-related serious adverse events were observed. Both progestin-releasing implants are an appropriate contraceptive option with either rilpivirine- or darunavir/ritonavir-based ART.

Contraceptive implant use duration is not associated with breakthrough pregnancy among women living with HIV and using efavirenz: a retrospective, longitudinal analysis.

IntroductionContraceptive implants containing etonogestrel and levonorgestrel have emerged as popular contraceptive options among women in areas of high HIV burden in sub‐Saharan Africa. However, recent pharmacokinetic data have shown drug–drug interactions between implants and efavirenz‐containing antiretroviral therapy (ART), reducing the effectiveness of the implants. Here, we evaluated pregnancy incidence in 6‐month intervals following implant initiation among women using efavirenz and contraceptive implants to assess whether the risk of breakthrough pregnancy is higher after specific periods of implant use.MethodsWe used data from a retrospective longitudinal analysis of women living with HIV ages 18–45 years in western Kenya who attended HIV‐care facilities between 2011 and 2015. We used Cox proportional hazard models to compute hazard ratios (HRs) for breakthrough pregnancy by implant type and ART regimen. Depending on the model, we adjusted for socio‐demographic and clinical factors, programme, site and interaction between calendar time and ART regimen. We utilized inverse probability weights (IPWs) to account for three sampling phases (electronic medical record [EMR], chart review and phone interview) and calculated overall parameter estimates.ResultsWomen contributed 14,768 woman‐years from the largest sampling phase (EMR). The median age was 31 years. Women used etonogestrel implants for 26–69% of the time and levonorgestrel implants for 7–31% of the time, depending on the sampling phase. Women used efavirenz, nevirapine or no ART for 27–33%, 40–46% and 15–26% of follow‐ups, respectively. When combining sampling phases, there was little evidence to suggest that the relative hazard of pregnancy among efavirenz‐containing ART users relative to nevirapine‐containing ART changed with length of time on implants: IPW‐adjusted HR of 3.1 (CI: [1.5; 6.4]) at 12 months, 3.4 (CI: [1.8; 6.3]) at 24 months, 3.8 (CI: [1.9; 7.7]) at 36 months and 4.2 (CI: [1.6; 11.1]) at 48 months (interaction p‐value = 0.88). Similarly, no significant change in HRs over time was found when comparing women not using ART to nevirapine‐containing ART users (interaction p‐value = 0.49).ConclusionsWe did not find evidence to suggest implants being more fallible from drug–drug interactions with efavirenz at later time intervals of implant use. Thus, we would not recommend shortening the duration of implant use or replacing implants sooner when concomitantly used with efavirenz.

Effectiveness of training primary care internal medicine residents in etonogestrel implants and impact on their future practice: A cross-sectional study

ObjectiveTo evaluate the impact of an etonogestrel implant training program within a primary care Internal Medicine residency training program. Study designWe surveyed graduates of our primary care Internal Medicine residency program in the Bronx, New York who performed implant procedures though the first 32 months after implementation of a monthly faculty-supervised resident implant clinic. We assessed the number of implants placed and removed per graduate, and surveyed graduates’ satisfaction with the implant training program, perceived competence with implant procedures, and intent and ability to perform implant procedures and barriers to performing implant procedures postgraduation. ResultsBetween July 2017 and February 2020, 14 residents placed a total of 34 devices and removed four. All 14 program graduates completed the survey in August 2020. All but one respondent felt this training was valuable and 11 felt competent placing implants without supervision. Although 10 planned to provide implants following graduation, none have been able to, largely because of credentialing and clinic-practice level barriers. ConclusionsThe primary care Internal Medicine program graduates we surveyed (n = 14) valued our etonogestrel implant training program and perceived competence, particularly with implant placement. However, even those who intended to provide etonogestrel implants postgraduation were unable to do so. ImplicationsInternal Medicine residents trained to place and remove etonogestrel implants are most comfortable with implant placement. However, these physicians may face barriers related to credentialing and ambulatory practice scope when attempting to provide this care in clinical practice.

Early removal of etonogestrel subcutaneous contraceptive implant at a community health centre in Pretoria.

BackgroundThe etonogestrel subcutaneous contraceptive implant offers efficacy for three years, but some women remove it earlier than prescribed. This study discusses factors associated with the early removal of these implants at a Pretoria community health centre between 01 January 2020 to 30 June 2020.MethodsA cross-sectional study using a piloted and researcher assistant-administered questionnaire.ResultsOf the 124 participants who removed their etonogestrel subcutaneous contraceptive implant earlier than prescribed, most were single, unemployed, in the age group 30–39 years, Christian, with secondary level education and with parity one or more. Etonogestrel subcutaneous contraceptive implant pre-insertion counselling was given to all participants, most of whom had not previously used contraceptives. Those participants with previous contraceptive use had used injectables. Long-term contraception was the main reason for getting the etonogestrel subcutaneous contraceptive implant. Most participants did not attend post-insertion counselling. Heavy bleeding was the most common side effect and reason for early removal. Fifty-one participants kept the etonogestrel subcutaneous contraceptive implant in for a longer period of 12–23 months. From participants’ responses, it seems that Etonogestrel implants may be offered from as early as 15–20 years of age.ConclusionWomen having etonogestrel subcutaneous contraceptive implants removed early at a Pretoria community health centre tended to be young, single, unemployed, Christian, with a secondary level education and with parity one or more. All participants attended the etonogestrel subcutaneous contraceptive implant pre-insertion counselling services but not the post-counselling services. Heavy bleeding was the main reason for the early removal of the etonogestrel subcutaneous contraceptive implant.

Continuation Rates of the Etonogestrel Implant and Factors Associated With Early Discontinuation [A32

INTRODUCTION: The etonogestrel implant is a highly effective, 3-year, long acting reversible contraceptive (LARC) device. Studies report a 1-year continuation rate of 80%, with 10% of patients reporting abnormal uterine bleeding (AUB) leading to discontinuation. Our primary objective was to describe the continuation rates of the implant in our population. Secondarily, we aimed to identify factors associated with early discontinuation. METHODS: Single center retrospective cohort study of women with placement of the etonogestrel implant at Lehigh Valley Health Network Obstetrics and Gynecology department between January 1, 2015 and December 31, 2017. Institutional review board (IRB) approval was obtained. A sample size calculation was performed to guide a subanalysis of the implant side effect profile. RESULTS: From 2015-2017, 774 women had the etonogestrel implant inserted. The 1-year continuation rate was significantly less than the literature reported value (62% vs 80%, P&lt;.001). A subanalysis of 216 women revealed that 82% reported side effects (n=177) and 73% discontinued use due to side effects. Side effects were more common in women who discontinued use at 1 year compared to women who continued use (93% vs 71%, P&lt;.001). The most common side effect, AUB (n=115), was not associated with early discontinuation. Neurologic and psychiatric complaints were reported by 16.7% of patients (n=18), and associated with early discontinuation (P=.02). CONCLUSION: The 1-year continuation rate of the etonogestrel implant may be significantly lower than that reported in the literature. Side effects are common, and patients with psychiatric or neurologic side effects are more likely to discontinue. Future studies should examine this relationship.