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

BACKGROUND: Concomitant use of efavirenz-based antiretroviral therapy and a standard-dose etonogestrel contraceptive implant led to 82% lower etonogestrel exposure when compared with women who do not receive antiretroviral therapy. The clinical impact of this reduced exposure is supported by retrospective cohort evaluations that demonstrated higher rates of unintended pregnancies when contraceptive implants were combined with efavirenz. We hypothesized that placement of 2 etonogestrel implants in those taking efavirenz-based antiretroviral therapy could increase etonogestrel exposure and improve measures of contraceptive efficacy. OBJECTIVE: This study compared the rate of ovulation and etonogestrel pharmacokinetics among women on efavirenz-based antiretroviral therapy who received 2 etonogestrel implants (136 mg; double implant group) in comparison with those who received 1 etonogestrel implant (68 mg; control group). STUDY DESIGN: This randomized, open-label study enrolled Ugandan women with regular menstrual periods who were receiving efavirenz-based antiretroviral therapy for the treatment of HIV. Participants were randomized 1:1 to the double implant 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 >3 ng/mL were interpreted as ovulation. The ovulation rate in each group was compared using Fisher's exact tests for each 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 using a validated liquid chromatography-triple quadrupole mass spectrometry method for etonogestrel. Etonogestrel concentrations were summarized as median (interquartile range) and compared between groups by geometric mean ratio with 90% confidence intervals. RESULTS: All participants (n=72) were cisgender Ugandan women with a median age of 31 years (interquartile range, 29-36), and 36 participants were enrolled in each study group. Two participants in the control group discontinued the trial; 1 at week 1 because of undetected pregnancy at entry and another at week 45 because of 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 double implant 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<.001). The odds of ovulation were reduced by 97.7% (95% confidence interval, 90.1-99.5) in the double implant group over 48 weeks. At each time point, etonogestrel concentration was more than 2-fold higher in the double implant group than in the controls (geometric mean ratio, 2.30-2.83) with a geometric mean ratio of 2.83 (90% confidence interval, 1.89-3.35) at week 48. There were no differences in the adverse events between groups and no participant discontinued because of adverse events. CONCLUSION: Over 48 weeks of combined use, placing 2 etonogestrel implants suppressed ovulation and increased plasma etonogestrel exposure when compared with 1 etonogestrel implant among women on efavirenz-based antiretroviral therapy. Doubling the dose of etonogestrel during efavirenz-based antiretroviral therapy could improve contraceptive effectiveness.

Use of etonogestrel subcutaneous implant in Sardinia, Italy: women's compliance and satisfaction.

PURPOSE OF THE ARTICLE: The main aim of the study was to analyze the population of women who used etonogestrel implant, the reason that led them to this type of contraception, and the degree of compliance with it. Materials and methods: We carried out a retrospective study on women who had etonogestrel subcutaneous implant placed (n°47) over a 6-year period (2015-2021). We submitted the women a series of questions by telephone questionnaire (range 10-72 months after placements, mean 40 months) that investigated the comorbidities and side effects related to etonogestrel implant. MATERIALS AND METHODS: We carried out a retrospective study on women who had etonogestrel subcutaneous implant placed (n°47) over a 6-year period (2015-2021). We submitted the women a series of questions by telephone questionnaire (range 10-72 months after placements, mean 40 months) that investigated the comorbidities and side effects related to etonogestrel implant. RESULTS: The average age of placement of etonogestrel implant was 33.8 ± 3.45 years. As regards level of education, 16/47 (34%) of the women had a university degree, 21/47 (44%) had a high school diploma and 10/47 (21%) had a secondary school diploma. The 12/47 (25%) of the women were, at the time of the counselling, unemployed and only 8% did not use in the past contraceptive methods other than etonogestrel implant. The 92% of women choose etonogestrel implant because it offered safe, comfortable and long-lasting contraception. Among the main side effects evaluated, we reported spotting in 24 out of 47 (51%), headache in 4 out of 47 (8.5%). The 85% of the women recommended etonogestrel implant to their friends as a contraceptive method, with an approval rating for the implant, expressed a rating from 1 to 10 with the mean that was 7.79, the median 8. CONCLUSIONS: Our results are of interest because they derive from a region of Italy in which the Long acting reversible contraception (LARC) is strongly underused. Etonogestrel implant was a safe and effective, long-acting, reversible hormonal contraception (LARC) and majority of women recommended the etonogestrel implant to their friends as a contraceptive method.

Etonogestrel implant is a safe and effective, long-acting, reversible hormonal contraception (LARC). The majority of women in our study choose the etonogestrel implant for its characteristics; among the main side effects evaluated we reported spotting and headache. The majority of women recommended the etonogestrel implant to their friends as a contraceptive method.

Nonpalpable implant removals at centre of experience in France: a cohort study.

OBJECTIVE(S): Management and localisation strategies to remove nonpalpable contraceptive implants may be difficult. We aimed to evaluate our imaging modalities to identify deep implant and patient outcomes related to removal. STUDY DESIGN: In this retrospective study, we reviewed all cases referred to our specialised centre for nonpalpable contraceptive implants from January 2018 to August 2022. RESULTS: Out of the cohort studied, 47 female subjects exhibited nonpalpable implants. The implant was nonpalpable for thirty-six patients (76,6%) immediately after the insertion whereas it was not palpable several months after the insertion for eleven patients (23.4%). Twelve patients (25.5%) had one or more failed removal attempts before referral.All 47 implants were successfully visualised via ultrasound in the upper arm: 40 implants (85.1%) were located in the subdermal tissue, 4 (8.5%) were intrafascial and 3 (6.4%) were intramuscular. Depth of the implant was 4.0 mm [1.7 - 12.0]. No clinical factors were statistically associated with differences in depth or location (subdermal vs subfascial). Removal procedures were mainly under local anaesthesia in 74.5% of cases in an outpatient setting. There were two Clavien-Dindo grade 1 complications (one case of cutaneous scar dehiscence and one transient postoperative neuropathic complaint in the upper arm resolved within 3 months under analgetics). CONCLUSIONS: Identification of deep implants requires following the ultrasound modality protocol. Ultrasound detection makes easy and safe implant removal. Training programs for the insertion as well as for the removal of correct and incorrect inserted implants should be continued and developed all around the world.

Migration of etonogestrel subcutaneous contraceptive implants: systematic review and recommendations for practice.

INTRODUCTION: Migration is a rare but serious complication of the etonogestrel contraceptive implant, and little is known about its extent. PURPOSE: To document and characterise cases of etonogestrel contraceptive implant migration in the scientific literature. METHODS: A systematic review of Medline, Embase and Global Health databases was carried out between January 2000 and January 2023 to identify articles presenting implant migrations. Narrative reviews, conference abstracts and articles not written in English or French were excluded. RESULTS: Forty-five articles, mostly published since 2016, were identified (eight case series and 37 case reports), for a total of 148 independent cases of migration: in pulmonary blood vessels (n = 74), in non-pulmonary blood vessels (n = 16) and extravascular (n = 58). Many patients are asymptomatic and migration is often an incidental finding. A non-palpable implant and symptoms related to implant location (intra- or extra-vascular) may be indicative of migration. Inadequate insertion and normal or underweight appear to increase the risk of migration. Scientific societies and authors offer practical strategies to deal with implant migration. CONCLUSION: Professionals who insert and remove contraceptive implants must be adequately trained. They need to be on the lookout for implant migration, and promptly refer patients to appropriate care if migration is suspected.

This systematic review documents and characterises 148 cases of vascular and extravascular etonogestrel contraceptive implant migration. Healthcare professionals must be aware of this rare but serious complication and be adequately trained to insert and remove contraceptive implants.

The role of progestin subdermal implant in the management of adenomyosis: a systematic review.

PURPOSE: The long-acting reversible contraception progestin subdermal implant (ENG implant) may be effective to improve endometriosis-related symptoms. Since adenomyosis is a histopathological form of endometriosis, we aimed to evaluate the effectiveness of ENG implant in adenomyosis management. MATERIALS AND METHODS: Electronic search in Medline, Scopus, Embase databases and Google Scholar using combinations of the following keywords: Progestin; subdermal implant; Implanon; Nexplanon; Adenomyosis; Endometriosis. RESULTS: Out of 889 articles in the initial database, 5 prospective observational studies were eligible for inclusion in our literature review. Our review involving 152 participants found a significant reduction in pelvic pain and dysmenorrhoea (baseline median VAS score ranged from 10 to 7.62 before implantation vs VAS score ranged from 1.81 to 0.1 after implantation) as well as an increase in the levels of haemoglobin after implantation of the device (from 86 g/L to 129 g/L after implantation). Moreover, the improvement may be sustained throughout the long-term follow-up visits (until 36 months). The most common adverse events were changes in bleeding patterns which were tolerable in most cases. CONCLUSION: ENG implant may be a relevant and promising medical option in the management of adenomyosis. Nevertheless, randomised controlled trials and prospective studies with larger cohorts are needed to confirm the potential role of ENG implant in the management of adenomyosis.

The etonogestrel-releasing subdermal contraceptive implant may be a relevant medical option in the management of adenomyosis.

Lactogenesis and breastfeeding after immediate vs delayed birth-hospitalization insertion of etonogestrel contraceptive implant: a noninferiority trial.

BACKGROUND: Initiating a progestin-based contraceptive before the drop in progesterone required to start lactogenesis stage II could theoretically affect lactation. Previous studies have shown that initiating progestin-based contraception in the postnatal period before birth-hospitalization discharge has no detrimental effects on breastfeeding initiation or continuation compared with outpatient interval initiation. However, there are currently no breastfeeding data on the impact of initiating the etonogestrel contraceptive implant in the early postnatal period immediately in the delivery room. OBJECTIVE: This study examined the effect of delivery room vs delayed birth-hospitalization contraceptive etonogestrel implant insertion on breastfeeding outcomes. STUDY DESIGN: This was a noninferiority randomized controlled trial to determine if time to lactogenesis stage II (initiation of copious milk secretion) differs by timing of etonogestrel implant insertion during the birth-hospitalization. We randomly assigned pregnant people to insertion at 0 to 2 hours (delivery room) vs 24 to 48 hours (delayed) postdelivery. Participants intended to breastfeed, desired a contraceptive implant for postpartum contraception, were fluent in English or Spanish, and had no allergy or contraindication to the etonogestrel implant. We collected demographic information and breastfeeding intentions at enrollment. Onset of lactogenesis stage II was assessed daily using a validated tool. The noninferiority margin for the mean difference in time to lactogenesis stage II was defined as 12 hours in a per-protocol analysis. Additional electronic surveys collected data on breastfeeding and contraceptive continuation at 2 and 4 weeks, and 3, 6, and 12 months. RESULTS: We enrolled and randomized 95 participants; 77 participants were included in the modified intention-to-treat analysis (n=38 in the delivery room group and n=39 in the delayed group) after excluding 18 because of withdrawing consent, changing contraceptive or breastfeeding plans, or failing to provide primary outcome data. A total of 69 participants were included in the as-treated analysis (n=35 delivery room, n=34 delayed); 8 participants who received the etonogestrel implant outside the protocol windows were excluded, and 2 participants from the delivery room group received the etonogestrel implant at 24 to 48 hours and were analyzed with the delayed group. Participants were similar between groups in age, gestational age, and previous breastfeeding experience. Delivery room insertion was noninferior to delayed birth-hospitalization insertion in time to lactogenesis stage II (delivery room [mean±standard deviation], 65±25 hours; delayed, 73±61 hours; mean difference, -9 hours; 95% confidence interval, -27 to 10). Onset of lactogenesis stage II by postpartum day 3 was not significantly different between the groups. Lactation failure occurred in 5.5% (n=2) participants in the delayed group. Ongoing breastfeeding rates did not differ between the groups, with decreasing rates of any/exclusive breastfeeding over the first postpartum year. Most people continued to use the implant at 12 months, which did not differ by group. CONCLUSION: Delivery room insertion of the contraceptive etonogestrel implant does not delay the onset of lactogenesis when compared with initiation later in the birth-hospitalization and therefore should be offered routinely as part of person-centered postpartum contraceptive counseling, regardless of breastfeeding intentions.

No-daily hormonal contraception today: general overview and application in specific clinical settings.

No-daily hormonal contraception includes short-acting reversible contraceptives (SARC), which contain estrogen and progestin (vaginal ring and transdermal patch), and long-acting reversible contraceptives (LARC), which contain only progestin (levonorgestrel-releasing intrauterine device and etonogestrel subdermal implant). No-daily hormonal contraceptives are reversible, avoid oral daily intake and have high contraceptive efficacy. They offer advantages over the traditional oral route, increasing user compliance, and reducing forgetfulness. Furthermore, they have several non-contraceptive benefits. This review aims to highlight the strengths of choices other than the traditional 'pill', with the goal of implementing contraceptive counseling, which should be personalized and tailored to each woman. Different subsets of patients may use no-daily contraception at different stages of their lives, with the option of either LARC or SARC. Specific contexts for its use are adolescence, perimenopause, obese women, eating disorders or intestinal malabsorption, breastfeeding, and post voluntary termination of pregnancy. Non-daily contraceptives can be an attractive alternative to the daily contraceptive pill, with benefits that are relevant to each woman desiring contraception, especially in unique and specific settings where customization of the contraceptive method is essential.

One-year follow-up of immediate postpartum contraceptive implant insertion in adolescents.

PURPOSE: Our study aimed to evaluate the acceptability, adverse effects and continuation rates among adolescents who accepted the etonogestrel (ENG) subdermal implant and compared to adolescents who chose other methods during the immediate postpartum period before hospital discharge, with one year follow-up up. MATERIALS AND METHODS: We conducted a cohort non-randomised study at the Women's Hospital, University of Campinas. All women up to 19 years of age, who gave birth at the hospital between July 2019 and April 2020, were invited to participate and were offered the ENG-implant or the routine contraceptive methods. They were followed for one year postpartum. RESULTS: We included 100 teenagers and 72 accepted the ENG-implant. Students are more likely to accept the ENG-implant than non-students (PR: 1.25 [95%CI 0.99-1.59]). Up to one year of follow-up, survival analysis showed that the time of adherence to the method was longer for the ENG-implant users (p = 0.0049). More than 90% of the adolescents were satisfied with the implant; however, five requested early removal due to menstrual irregularity and local discomfort. CONCLUSION: Provision ENG-implant for adolescents in the immediate postpartum demonstrated high acceptance and ensured effective contraception. After one year, most of them were satisfied, with a high continuation rate and without unplanned pregnancies.

Pharmacokinetics of levonorgestrel and etonogestrel in rat or minipig following intravenous, subcutaneous, or intradermal administration.

The objective of these studies was to determine the pharmacokinetics of levonorgestrel and etonogestrel in Sprague-Dawley rat or Göttingen minipig following various administration routes.Four sequential crossover studies were conducted: Study 1 administered levonorgestrel 30 µg intravenously and intradermally in four minipigs; Study 2 administered levonorgestrel 30 µg intravenously in 12 rats; Study 3 administered levonorgestrel 60 µg intravenously and subcutaneously in 12 rats; and Study 4 administered etonogestrel 30 µg intravenously in 12 rats. Samples were quantified using liquid chromatography-tandem mass spectrometry and pharmacokinetic parameters were estimated via noncompartmental analysis.Cmax and AUCinf for etonogestrel and levonorgestrel were similar following 30 µg intravenous bolus in rats, suggesting comparable pharmacokinetics. Levonorgestrel exposure was dose-proportional in rats, based on two-fold higher AUCinf following levonorgestrel 60 versus 30 µg. The bioavailability of intradermal and subcutaneous levonorgestrel was 97.7% (Study 1) and 90.3% (Study 3), respectively. The minipig levonorgestrel clearance was 21.5 L/hr, which was about 20-fold higher than both the rat levonorgestrel (range: 0.985-1.45 L/hr) and etonogestrel clearance (range: 0.803-0.968 L/hr).These studies contribute to the gap in knowledge of nonclinical levonorgestrel and etonogestrel pharmacokinetics, which is necessary for the ongoing development of long-acting reversible contraceptives.

Etonogestrel-releasing contraceptive implant in a patient using thalidomide for the treatment of erythema nodosum leprosum: a case report.

INTRODUCTION: Thalidomide is an immunomodulatory drug and first choice in the treatment of erythema nodosum leprosum. Given its teratogenic potential, it is essential that an effective contraceptive method is used, especially a long-acting reversible contraceptive (LARC) method. The subdermal etonogestrel (ENG)-releasing implant is an adequate method due to the high effectiveness and long-term use. However, interaction between thalidomide and ENG has not been well documented. Concern arises because thalidomide interacts with cytochrome P450 (CYP450) enzymes that metabolize sexual steroids. AIM: We aimed to study the effectiveness and safety of the ENG-implant in a thalidomide user. METHODS: Case report of a sexually active 21-year-old patient with both Hansen's disease and leprosy reaction type 2 treated with thalidomide requiring effective contraception. Follow-up was up to 36 months after implant placement. RESULTS: Contraception with ENG-implant was effective and safe, based on clinical parameters (reduction of menstrual flow and cervical mucus thickening) and laboratory parameters (gonadotropins and sexual steroids). CONCLUSION: To the best of our knowledge, this is the first case reported which presents a patient in simultaneous use of thalidomide and ENG-implant. Although this case report preliminary supports effectiveness and safety of ENG-implant as a contraceptive option in women using thalidomide, rigorous drug-drug interaction research is needed to better characterize the interaction between thalidomide and the ENG-implant.

Subcutaneous etonogestrel implant combined with endometrial ablation for the treatment of adenomyosis: two case reports.

Adenomyosis is a common disease that affects many premenopausal women. Two patients with adenomyosis, aged 51 and 42 years, presented with dysmenorrhea and increased menstrual volume. They refused laparoscopy or laparotomy surgery and were not eligible for the levonorgestrel-releasing intrauterine system (LNG-IUS). The first patient underwent endometrial ablation and subcutaneous etonogestrel (ENG)-releasing implant placement at the same time. Her symptoms of dysmenorrhea and heavy menstruation improved significantly. When serum follicle-stimulating hormone (FSH) and estradiol (E2) levels suggested menopause, the ENG-releasing implant was removed. However, her abdominal pain recurred and was relieved by medication. For the second patient, an ENG-releasing implant was placed first, and her dysmenorrhea and heavy menstrual volume were relieved. However, the bleeding pattern changed from regular bleeding to prolonged bleeding, which troubled the patient. Endometrial ablation was performed 4 months later to solve the problem. Both patients had improved symptoms and were satisfied with the treatment. For patients with adenomyosis who refuse surgery and are not candidates for the use of LNG-IUS, an ENG-releasing implant combined with endometrial ablation may be an effective alternative.

A rodent model of human dose-equivalent progestin-only implantable contraception.

BACKGROUND: Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use. METHODS: Intact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30µg/d, medium-0.17µg/d, low-0.09µg/d, placebo-0.00µg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA. RESULTS: Prior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation. CONCLUSION: Assessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.

Three-year observational study of immediate post-abortion insertion versus menstrual insertion of etonogestrel contraceptive implant.

OBJECTIVE: This study aimed to estimate the difference in vaginal bleeding pattern, discontinuation rate, and satisfaction between immediate after abortion and menstrual insertions of etonogestrel contraceptive implants. STUDY DESIGN: Between May 2013 and November 2015, 66 women were recruited in the abortion group who selected etonogestrel implants as their contraceptive immediately after induced abortion. 84 women who underwent the placement of the etonogestrel implant during their menstrual period were enrolled as the menstrual group. The two groups participated in 3-year follow-up outpatient visits at 1, 6, 12, 24, and 36 months after implantation. The vaginal bleeding pattern, discontinuation rate, satisfaction rate were recorded and compared. RESULTS: No woman had pregnancy over the study period of 3 years. The incidence of amenorrhea/infrequent bleeding did not differ between the two groups after 12, 24, and 36 months of implantation (53.0% vs. 58.4%, 47.8% vs. 51.6%, and 48.6% vs. 55.6%, respectively). In the abortion group, the incidences of frequent/prolonged bleeding were 15.1%, 32.6%, and 27.0% after 12, 24, and 36 months of implantation, respectively, while the other group showed 27.3%, 25.8%, and 20.4%, respectively. After 12 and 24 months, the continuation use rates were 69.7% and 56.1% in the abortion group and 73.8% and 64.2% in the menstrual group. The 12-month satisfaction rate between abortion group and menstrual group was 69.6% versus 72.6%. Statistical analyses show that there was no difference in vaginal bleeding pattern, discontinuation rate or satisfaction between the two groups. CONCLUSIONS: Immediately post-abortion may be also a favorable time to undergo etonogestrel implantation.

A clinical observational study on the efficacy of subcutaneous etonogestrel implants for adenomyosis in 20 patients.

Objective: To evaluate the efficacy of subcutaneous etonogestrel implants for adenomyosis.Methods: We conducted a clinical observational study of 20 patients suffering from adenomyosis treated with subcutaneous etonogestrel implants from August 2015 to July 2017 and followed up for 36 months. We evaluated the efficacy of subcutaneous etonogestrel implants primarily based on the following indicators: the pictorial blood loss assessment chart (PBAC) for menstrual blood volume, changes in bleeding patterns, the visual analog scale (VAS) pain score for dysmenorrhea, uterine volume, serum cancer antigen 125 (CA125) levels, hemoglobin levels and side effects.Results: During the 3 years of follow-up, subcutaneous etonogestrel implants were removed from six patients, among whom one was diagnosed with endometrial cancer, four had an increased menstrual blood volume, and one entered menopause. In total, 14 patients were treated with subcutaneous etonogestrel implants for 3 years. Among these patients, the number of patients with heavy menstrual bleeding and high PBAC and VAS scores and serum CA125 levels was significantly decreased after implantation compared with that before implantation. In the eight patients with anemia, hemoglobin levels increased gradually. However, the uterine volumes did not significantly change. Bleeding patterns were changed but were tolerable.Conclusion: Subcutaneous etonogestrel implants represent a new option for the clinical treatment of adenomyosis for patients who refuse surgery.

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

BACKGROUND: Unintended pregnancies (UIP) have a significant impact on health of women and the health budget of countries. Contraception is an effective way to prevent UIPs. The study objective was to collate evidence on clinical effectiveness of etonogestrel subdermal implant (ESI), continuation rate and side effect profile among eligible women of reproductive age group, as compared to levonorgestrel intrauterine system (LNG-IUS), copper intrauterine device (Cu-IUD) and depot medroxy progesterone acetate injections; other types of contraceptive implants were excluded as comparators. METHODS: The protocol of the systematic review was registered in Prospero (registration number: CRD42018116580). MEDLINE via PubMed, Cochrane library and web of science were the electronic databases searched. A search strategy was formulated and studies from 1998 to 2019 were included. Clinical trial registries and grey literature search was done. Critical assessment of included studies was done using appropriate tools. A qualitative synthesis of included studies was done and a meta-analysis was conducted in RevMan software for continuation rates of ESI as compared to other long acting reversible contraceptives (LARC) e.g. LNG IUS and Cu-IUD. RESULTS: The search yielded 23,545 studies. After excluding 467 duplicates, 23,078 titles were screened and 51 studies were included for the review. Eight of the 15 studies reporting clinical effectiveness reported 100% effectiveness and overall pearl index ranged from 0 to 1.4. One-year continuation rates ranged from 57-97%; 44-95% at the end of second year and 25-78% by 3 years of use. Abnormal menstruation was the most commonly reported side effect. There was no significant difference in bone mineral density at 1 year follow-up. The meta-analyses showed that odds ratio (OR) of 1-year continuation rate was 1.55 (1.36, 1.76) for LNG-IUS vs. ESI and 1.34 (1.13, 1.58) for copper-IUD vs. ESI; showing that continuation rates at the end of one-year were higher in LNG-IUS and copper-IUD as compared to ESI. CONCLUSION: ESI is clinically effective and safe contraceptive method to use, yet 1-year continuation rates are lower as compared to LNG-IUS and copper-IUD, mostly attributed to the disturbances in the menstruation.

Ovarian stimulation for fertility preservation in an oncology patient with etonogestrel implant in place.

PURPOSE: To describe a case of a young woman who presented for fertility preservation and underwent ovarian stimulation with an etonogestrel implant in place. METHODS: A 24-year old, gravida 0, with an etonogestrel implant and newly diagnosed lower extremity sarcoma and DVT desiring oocyte cryopreservation prior to adjuvant chemotherapy and radiation. To avoid delay in her oncologic care and allow for continued use of contraception post-retrieval, the patient underwent controlled ovarian hyperstimulation (COH) without removal of the etonogestrel implant. RESULTS: Baseline labs included follicle-stimulating hormone 9 mIU/mL, luteinizing hormone 4.9 mIU/mL, estradiol 42 pg/mL, anti-Müllerian hormone 5.1 ng/mL, and antral follicle count greater than 40. The patient was placed on an antagonist protocol and stimulated with 125 IU Gonal-F and 75 IU Menopur. She received a total of 12 days of gonadotropin stimulation. On the day of trigger, her estradiol was 1472 pg/mL, lead follicle 21.5 mm with a total of 25 follicles measured > 12 mm. She was triggered with 5000 U hCG. She had a total of 23 oocytes retrieved, 17 of which were metaphase II and vitrified. CONCLUSIONS: COH and successful oocyte cryopreservation can be achieved in patients with an etonogestrel implant in situ without apparent detrimental effects to oocyte yield or maturity. Due to the etonogestrel implant's inhibitory effects on LH, it is recommended to use an hCG trigger for final oocyte maturation.

Practical training of health care providers in insertion of contraceptive implants: findings from two Brazilian centres.

BACKGROUND AND OBJECTIVES: Lack of information and myths or inadequate training of health care providers in the guidance and management of contraceptives could negatively affect choice and eventually continuation rates. Our objectives were to evaluate the impact of clinical and theoretical training of health care professionals on insertion and removal of etonogestrel (ENG)-implant regarding this contraceptive, including pre- and post-training knowledge about insertion and removal techniques, clinical characteristics, side effects and outcomes. MATERIAL AND METHODS: We conducted a cross-sectional study in which a questionnaire was sent to health care providers after they received clinical training in the management of ENG-implant. RESULTS: After training, 78.2% of the 139 participants initiated to offer and inserted up to 5 implants/month and 17.6% between 6 to 10/month. None of the interviewees reported having difficulty with insertions after training, and 87.9% reported feeling very confident for removal. CONCLUSION: Theoretical and practical training appeared important to prepare health care professionals, clarify doubts and promote higher rates of use of contraceptive implants in Brazil, contributing to reduce the rates of unintended pregnancies.

An exploratory study on the association of lifestyle factors with serum etonogestrel concentrations among contraceptive implant users.

PURPOSE: To explore how diet and exercise habits associate with serum etonogestrel concentrations among contraceptive implant users. MATERIALS AND METHODS: We conducted a secondary analysis of healthy, reproductive-age women using etonogestrel implants. This study was registered on ClinicalTrials.gov, NCT03092037. We assessed diet and exercise habits with two validated surveys: Healthy Eating Vital Signs and the Stanford Brief Activity Survey. Participants previously had their serum etonogestrel concentrations measured using a validated liquid-chromatography mass-spectrometry assay. We then used linear modelling to test for associations between survey responses and serum etonogestrel concentrations. RESULTS: Among 129 participants, diet and exercise habits had no significant associations with serum etonogestrel concentrations (p = 0.22-0.72), with inconsistent effects found for increased caloric intake and sedentary lifestyle. CONCLUSION: This exploratory study found no significant effect of diet or exercise habits on steady-state pharmacokinetics among contraceptive implant users. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT03092037.

A prospective pilot study to assess the impact of the etonogestrel implant on postpartum depression.

OBJECTIVES: To assess the feasibility of comparing the rates of positive depression screens at 6 weeks and 3 months postpartum in women using immediate postpartum etonogestrel implant (ENG-implant) and women using non-hormonal contraception or sterilisation. METHODS: This was a pilot prospective cohort study performed to test the design adequacy of comparing the rates of positive postpartum PHQ-9 screens (≥10) in women using immediate postpartum ENG-implant and women using non-hormonal contraception or sterilisation. Participants were recruited during the third trimester of pregnancy or during delivery hospitalisation. They self-allocated to one of the two comparison groups. PHQ-9 surveys were administered during the third trimester of pregnancy, immediately postpartum, and at 6 weeks and 3 months postpartum. RESULTS: Between June 2017 and March 2018, 91 patients were recruited. Of these patients, 11 were excluded and the remaining 80 were split evenly into each cohort. The women in the ENG-implant group were younger, less educated, and more often publicly insured. The percentage of participants with positive PHQ-9 screens were: 3% during the postpartum hospitalisation, 6.2% at 6 weeks postpartum, and 10.2% at 3 months postpartum. PHQ-9 scores were similar between groups at both postpartum time points. CONCLUSION: The rates of positive PHQ-9 screens at 6 weeks postpartum were similar between groups. These preliminary data suggest that immediate postpartum placement of the ENG-implant does not negatively impact the risk for a positive depression screen. Larger-scale, adequately powered studies are warranted to further investigate this finding.

Real-world cost-effectiveness of etonogestrel implants compared to long-term and short term reversible contraceptive methods in France.

BACKGROUND: To estimate the cost-effectiveness (CE) of etonogestrel implants compared to other long-term and short-term reversible contraceptive methods available in France. RESEARCH DESIGN AND METHODS: A 6-year Markov model compared effectiveness between the implant and six other contraceptive methods in sexually active, not-pregnancy-seeking French females of reproductive age. Contraception efficacy, switch rates and outcomes were based on French current medical practice. Incremental CE ratios (ICERs) were calculated as incremental cost per unintended pregnancy (UP) avoided. Efficiency frontier was plotted to identify cost-effective methods. Uncertainty was explored through sensitivity analyses. RESULTS: The implant was on the efficiency frontier along with combined oral contraceptive pill (COC) and copper IUD. Implant avoids between 0.75% and 3.53% additional UP per person-year compared to copper IUD and second generation COC, respectively, with an ICER of €2,221 per UP avoided compared to copper IUD. For the 240,000 French women currently using the implant, up to 8,475 UPs and up to 1,992 abortions may be prevented annually. CONCLUSION: With more unintended pregnancies avoided and comparable costs to copper IUD, the implant is a cost-effective option among long-term and short-term reversible contraceptive methods.