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.

Site necrosis at the insertion place of the single-rod subdermal contraceptive implant: report of five cases.

OBJECTIVE: Implant-site necrosis is a rare complication. We present a case-series of a necrosis as an adverse effect after the etonogestrel (ENG)-subdermal contraceptive implant placement. MATERIAL AND METHODS: Five women with site necrosis after the ENG-implant placement and their clinical manifestations and treatments. RESULTS: Local pain was the main symptom, appearing within 35 days of placement. Outpatient multidisciplinary treatment was undertaken. Local debridement and implant removal was performed in four out of the five women. Time to complete healing varied from 45 days to 12 months. CONCLUSION: Early diagnosis and multidisciplinary treatment are essential to avoid severe aesthetic or functional damages and major life-threatening complications.

We presented five cases with necrosis at the ENG-implant site of placement in which we proposed an early diagnosis and multidisciplinary treatment to avoid severe aesthetic or functional damages.

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.

LONG-TERM INCIDENCE AND RISK FACTORS OF OCULAR HYPERTENSION FOLLOWING DEXAMETHASONE-IMPLANT INJECTIONS: THE SAFODEX-2 STUDY.

PURPOSE: To analyze the incidence, risk factors, and time to onset of ocular hypertension (OHT) after intravitreal injections (IVI) of dexamethasone implant and to evaluate the long-term cumulative probability of intraocular pressure elevation. METHODS: Eyes of patients having received at least one dexamethasone implant IVI between October 2010 and February 2015 were included in the present study. Ocular hypertension was defined as intraocular pressure > 25 mmHg and/or an increase of 10 mmHg over the follow-up period compared with baseline intraocular pressure. RESULTS: Four hundred ninety-four eyes were studied in 410 patients. For a total of 1,371 IVI, the incidence of OHT was 32.6% in the study eyes with a mean follow-up period of 30 months (3-62.5) and a median follow-up of 29 months. Pressure-lowering treatment was introduced for 36.9% of eyes. Topical treatment alone was sufficient to manage OHT in 97%. Young age, male sex, uveitis and retinal vein occlusion, and glaucoma treated with a double- or triple-combination topical pressure-lowering medication were found to be risk factors for OHT. The incidence of OHT did not change with an increase in the number of IVI, and there was no cumulative effect, defining by an increase of the incidence of OHT in patients after repeated IVI (P = 0.248). CONCLUSION: This study confirmed that OHT is of moderate incidence, transient, controlled by topical treatment and provides data on the long-term cumulative probability of intraocular pressure elevation in a large cohort of eyes treated with dexamethasone implant IVI. Repeat injections of dexamethasone implant neither increase nor decrease the risk of OHT.

Major nerve injury in association with use of contraceptive implants. / Alvorlige nerveskader ved bruk av p-stav.

BACKGROUND: Subcutaneous contraceptive implants are recommended to be placed in the medial upper arm. Here, the implant lies close to important neurovascular structures. CASE PRESENTATION: We have treated two women with ulnar nerve injuries after removal of such implants. Patient 1 sustained a near complete nerve injury. Despite nerve grafting and a distal nerve transfer, she had a poor outcome. Patient 2 had a partial injury and has made a reasonable recovery after neurolysis of the ulnar nerve that was entrapped in scar tissue. INTERPRETATION: Prognosis after peripheral nerve injuries in the upper arm in adults is poor, and as such these injuries are particularly serious. Any patient with an implant that is not readily palpable in the subcutaneous tissue should be referred to a hand surgeon who has training in exploring peripheral nerves. If emergent nerve injury is suspected, referral to a department of hand surgery is vital.

The Rate of Infectious Complications After Intrathecal Drug Delivery System Implant for Cancer-Related Pain Is Low Despite Frequent Concurrent Anticancer Treatment or Leukopenia.

BACKGROUND: The efficacy of intrathecal drug delivery (IDD) for cancer-related pain is well established. Cancer therapies are often associated with immunosuppression and increased risk of infection, and the rate of infection after intrathecal drug delivery system (IDDS) implant in cancer patients has been reported as 2.4%-6.3%. Our objective is to report on the rate of surgical site infections (SSI) in patients implanted with IDDS for cancer-related pain and to provide a data-driven discussion on the relationship between antineoplastic treatment, leukopenia, and other clinical or demographic characteristics and SSI. METHODS: Following local institutional review board approval, we conducted a retrospective chart review of IDDS implants from May 2014 through December 2018. Data collected included demographic data, health status, prophylactic antibiotic administration, surgery duration, presence of leukopenia (white blood cell [WBC] count of <4.0 K/µL) or moderate neutropenia (absolute neutrophil count [ANC] of <1000/µL) within the 30 days before IDDS implant, and details of antineoplastic treatment or systemic corticosteroid use in the perioperative period. This information was assessed in relation to SSI incidence up to 6 months following implant. RESULTS: Two hundred seventeen IDDS implants were identified. A majority of patients (79.3%) received ≥1 form of antineoplastic therapy within 30 days before or after implant, and 42.4% received multiple forms of antineoplastic therapy. Therapies included chemotherapy in 46.5%, immunotherapy in 28.6%, systemic steroids in 32.3%, and radiation therapy in 28.1%. One-quarter of patients (25.8%) were leukopenic within 30 days before implant, with 3.2% having moderate neutropenia. There were 2 infectious complications representing an infection rate of 0.9% (95% CI, 0.1%-3.3%), with limited shared characteristics between those experiencing SSI. CONCLUSIONS: SSI risk after IDDS placement for cancer pain is low, despite frequent concurrent antineoplastic therapy and leukopenia in the perioperative period. Concomitant cancer therapies should not be a barrier to the implementation of IDD for cancer pain.

RETAINED, NONDISSOLVING, TUBULAR FOREIGN BODIES IN THE VITREOUS CAVITY AFTER INTRAVITREAL DEXAMETHASONE (OZURDEX) IMPLANTATION.

PURPOSE: To describe the retention of large, tubular, nondissolving foreign bodies because of a complication of the intravitreal dexamethasone implant (Ozurdex). METHODS: This is a single-center, retrospective chart review of patients who were found to have retained, nondissolvable tubular foreign bodies in the vitreous cavity for more than 6 months (the expected dissolution time of the implants) after Ozurdex injections. Ocular symptomatology and multimodal imaging were reviewed. RESULTS: Five patients had retained, nondissolvable tubular foreign bodies in the vitreous that persisted for months (mean 28.2 months, range 9-67 months) after intravitreal injection of Ozurdex. Two patients were symptomatic due to the foreign bodies and chose alternate local therapy, but none of the patients opted for surgical explantation. CONCLUSION: Persistent, nondissolving, tubular foreign bodies can be seen in the vitreous cavity for years after injection of the Ozurdex implant. Clinicians should be aware of this complication that has the potential to cause visual symptoms and ocular morbidity.

INTRAVITREAL DEXAMETHASONE IMPLANT MIGRATION INTO THE ANTERIOR CHAMBER: A Multicenter Study From the Pan-American Collaborative Retina Study Group.

PURPOSE: To establish the prevalence and risk factors for intravitreal dexamethasone implant migration into the anterior chamber in eyes with macular edema. METHODS: This was a multicenter, retrospective, observational chart review of data that included patients with macular edema who had been treated with at least one intravitreal dexamethasone injection. Patients with incomplete chart information during the follow-up period were excluded. RESULTS: The prevalence of implant migration in 468 patients, considering the number of injections, was 1.6%, with significant associations between implant migration and cataract surgery (P = 0.043) and intraocular lens status (P = 0.005) and a trend toward statistical significance (P = 0.057) with vitrectomy. A higher rate of implant migration into the anterior chamber was observed in vitrectomized eyes (4.8%) when compared with patients who did not undergo a vitrectomy (1.6%). The implants that migrated were removed with forceps with/without viscoelastic expression or with 20-gauge cannulas connected to the vitreous cutter machine. CONCLUSION: The risk of implant migration into the anterior chamber was 1.6%. Risk factors were a history of cataract surgery or vitrectomy and aphakia. When anterior migration occurs, rapid removal is advised, especially if corneal edema is present.

PERSISTENT REMNANTS OF DEXAMETHASONE INTRAVITREAL IMPLANT (OZURDEX).

PURPOSE: To describe persistent remnants of dexamethasone intravitreal implant (DEX implant) and evaluate the risk factors for remnant persistence in patients who received a DEX implant. METHODS: This retrospective observational study involved a retrospective chart review of 133 eyes from 129 patients who received DEX implant injection. RESULTS: Seventeen eyes of 17 patients (12.78%) exhibited remnant persistence >1 year after DEX implant injection; eight eyes (13.33%) were diagnosed with branching retinal vein occlusion, three eyes (14.28%) were diagnosed with central retinal vein occlusion, and six eyes (35.3%) were diagnosed with diabetic macular edema. The number of intravitreal DEX implant injections and triamcinolone acetonide injections administered to eyes with remnant persistence was significantly higher than that administered to the eyes without remnant persistence (P < 0.001 and P = 0.024, respectively). Remnants caused symptomatic floaters in 11.7% (2/17 eyes) of the patients with remnants and in 1.5% (2/133) of the entire patient cohort. CONCLUSION: DEX implant was not completely dissolved in the eyes that received multiple DEX implant or triamcinolone acetonide injections.

ENG-releasing subdermal implants in postpartum teenagers - an open-label trial study protocol.

BACKGROUND: Higher than expected adolescent pregnancy high rates continue globally, with repeated unplanned pregnancy (UP) in this age group is a public health problem. In Brazil, 16% of pregnancies occur in adolescents under 18 years old, with high maternal morbidity and mortality rates in this age group. Effective and safe contraception is required to reduce UP rates. The objective of our study is to evaluate acceptance of etonogestrel (ENG)-releasing subdermal contraceptive implant after childbirth, before discharge, as well as clinical performance up to one year after placement. Comparison between teenagers who opt for ENG-implant versus other contraceptive methods after childbirth will be also evaluated, specifically regarding UP, continuation and discontinuation rates and reasons, body composition, pelvic ultrasound characteristics and user satisfaction. METHODS: A non-randomized open-label trial will be conducted with teenagers after childbirth and followed up to one year at the Women's Hospital, University of Campinas (UNICAMP), Campinas, Brazil. The study group will consist of patients who accepted to use ENG-implant and placed before discharge. The comparison group will include adolescents who choose to use other contraceptive methods at the first postpartum visit (42 ± 3 days after childbirth). All women will follow-up at 40-60 days postpartum, as well as, at 6 and 12 months post-enrollment. Patient satisfaction, contraceptive effectiveness, reasons of discontinuation, continuation rate and body composition will be evaluated. Transvaginal ultrasound and electric bio impedance tests will be performed at all follow-up appointments. A 5% significance level was assumed, as well as, a sampling error (absolute) for 10% prevalence. The sample size was calculated at n = 100, obtaining an estimate of 50 to 70 adolescents who would accept the method offered, according to the prevalence and sample error assumed. DISCUSSION: Long-acting reversible contraceptive (LARC) methods include subdermal implants and intrauterine contraceptives, are considered first line contraception for teenagers. Immediate postpartum use is a safe option, which significantly reduces rates of repeated UP and all the undesirable consequences inherent to this process. TRIAL REGISTRATION: This study was approved by the Ethics and Research Commission of UNICAMP (CAAE: 92869018.5.0000.5404) and the Brazilian Registry of Clinical Trials (REBEC): http://www.ensaiosclinicos.gov.br/rg/RBR-4z7bc6, (number 2.901.752).

Predictors of Discontinuation of Subdermal Levonorgestrel Implants (Jadelle) at the Lagos University Teaching Hospital, Lagos, Nigeria: An Analytic Cohort Study.

Uptake and continuation of long acting reversible contraceptives (LARC) such as subdermal levonorgestrel implants are pivotal to the achievement of some sustainable development goals (SDG). We evaluated Jadelle uptake and factors affecting its discontinuation in the first three years of initiation at the Family Planning Clinic of the College of Medicine, University of Lagos (CMUL), Nigeria. A retrospective cohort study was conducted among 517 consecutive new Jadelle acceptors, at the family planning clinic of CMUL, between 1 October 2007 and 30 September 2010, who were followed up till 30 September 2011. Survival life table analysis, Kaplan-Meier plots and multivariable Cox proportional hazard regression were conducted to evaluate factors affecting time to Jadelle discontinuation. Stata version 13 statistical software (StataCorp USA) was used for analysis. The mean age of Jadelle acceptors was 32.9 (S.D: ±5.4) years and uptake rate of Jadelle was 61.8%. The overall discontinuation rate was 19 per 100 women-years while the 1-year, 2-year and 3-year Jadelle discontinuation rates were 7.1%; 27.0% and 58.1% respectively. Increased age, (P=0.047) and previous contraceptive use (P <0.001) were independent predictors of Jadelle discontinuation. Menstrual irregularity (51.4%) and intention to get pregnant (40.3%) were the commonest reasons for discontinuation. The failure rate was low at 0.27 per 100 women-years. This study showed that Jadelle had a high uptake rate complimented by a low failure rate; and is quite suitable for postpartum childbirth spacing as well as ongoing long term contraception.

Risk factors for and management of anterior chamber intravitreal dexamethasone implant migration.

BACKGROUND: This study aimed to investigate the incidence of and risk factors for the anterior chamber migration of an intravitreal dexamethasone implant (Ozurdex®). METHODS: A retrospective review of 640 consecutive intravitreal dexamethasone implant injections was conducted from February 2011 through February 2018 at the University Eye Hospital in Tübingen, Germany. Those patients who experienced anterior chamber dexamethasone implant migrations were identified, as well as the reasons for the anterior chamber migration. The surgical histories were obtained and comprehensive ophthalmic examinations were conducted for all of the eyes. Cross-tabulations, chi-squared tests, and Fisher's exact tests were used to assess the influences of different factors on the anterior chamber implant migrations. RESULTS: Overall, 4 eyes of four patients (0.63%) showed anterior chamber implant migrations. All four of the eyes were pseudophakic, and they had undergone prior vitrectomies. Three eyes had sclerally-fixated intraocular lenses, and one eye had a posterior chamber intraocular lens in the capsular bag, with a capsular tension ring due to partial zonular dehiscence. When comparing the vitrectomized eyes with reduced zonular/capsular bag complex integrity to the vitrectomized pseudophakic eyes with intact zonular/capsular bags, the former were significantly associated with an increased risk of anterior chamber implant migration (P = 0.008). The vitrectomized pseudophakic eyes, in contrast to the nonvitrectomized pseudophakic eyes, were significantly associated with an increased risk of anterior chamber implant migration (P = 0.009). CONCLUSIONS: The anterior chamber migration of an intravitreal dexamethasone implant is a serious complication. To minimize the risk of permanent corneal edema, immediate removal of the implant with a 20-gauge alligator forceps over a 2.75-mm long clear corneal tunnel is important. Those patients with insufficient zonular support, defects, or missing posterior capsular membranes and vitrectomy histories present a high risk of anterior chamber dexamethasone implant migration.

Promising Approach in the Treatment of Glaucoma Using Nanotechnology and Nanomedicine-Based Systems.

Glaucoma is considered a leading cause of blindness with the human eye being one of the body's most delicate organs. Ocular diseases encompass diverse diseases affecting the anterior and posterior ocular sections, respectively. The human eye's peculiar and exclusive anatomy and physiology continue to pose a significant obstacle to researchers and pharmacologists in the provision of efficient drug delivery. Though several traditional invasive and noninvasive eye therapies exist, including implants, eye drops, and injections, there are still significant complications that arise which may either be their low bioavailability or the grave ocular adverse effects experienced thereafter. On the other hand, new nanoscience technology and nanotechnology serve as a novel approach in ocular disease treatment. In order to interact specifically with ocular tissues and overcome ocular challenges, numerous active molecules have been modified to react with nanocarriers. In the general population of glaucoma patients, disease growth and advancement cannot be contained by decreasing intraocular pressure (IOP), hence a spiking in future research for novel drug delivery systems and target therapeutics. This review focuses on nanotechnology and its therapeutic and diagnostic prospects in ophthalmology, specifically glaucoma. Nanotechnology and nanomedicine history, the human eye anatomy, research frontiers in nanomedicine and nanotechnology, its imaging modal quality, diagnostic and surgical approach, and its possible application in glaucoma will all be further explored below. Particular focus will be on the efficiency and safety of this new therapy and its advances.

Management of Anterior Chamber Dislocation of a Dexamethasone Implant.

PURPOSE: To characterise the surgical removal technique of a dislocated dexamethasone implant in the anterior chamber and to gauge its success by analysing corneal transparency and subsequent visual acuity recovery in the postoperative phase. METHODS: Description of a patient who presented with an anterior chamber dexamethasone implant migration through an inferior iridotomy performed previously for a silicone oil fill in aphakia. Visual acuity had dropped to counting fingers due to marked corneal oedema. RESULTS: The implant was removed using a 23-g needle aligned with the axis of the implant through a paracentesis. After the clinical follow-up at 2 months, best-corrected visual acuity had returned to 0.2, which remained stable at the last follow-up at 14 months with an intraocular pressure of 10 mmHg. The corneal oedema resolved completely. CONCLUSION: This novel surgical management of a dexamethasone implant dislocation into the anterior chamber was successful and resulted in no long-term corneal damage when the implant was removed without delay. A repeated Ozurdex injection in patients with previous inferior iridotomy may require prior suturing of the iridotomy.

Embolization of a contraceptive implant into the pulmonary vasculature in an adolescent female.

Nexplanon is a long-acting 4cm radio-opaque rod shaped contraceptive device implanted in the subdermal layer of the inner, upper arm. Complications from implantation are uncommon and mostly local and minor, including infection at the implantation site with resulting cellulitis or abscess, hematoma, abnormal scar formation, or local damage to nerves and blood vessels. Intravascular insertion is estimated to be at 1.3 per million Nexplanon implants, and migration and embolization is a rare complication of this device. We present a case report of a 16year old female who presented to the pediatric emergency department with subjective dyspnea and an embolized contraceptive device within a subsegmental branch of the left lower lobe pulmonary artery. After discussion with consultants, interventional radiology was able to successful retrieve the device without complication.

Incomplete copolymer degradation of in situ chemotherapy.

In situ carmustine wafers containing 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are commonly used for the treatment of recurrent glioblastoma to overcome the brain-blood barrier. In theory, this chemotherapy diffuses into the adjacent parenchyma and the excipient degrades in maximum 8 weeks but no clinical data confirms this evolution, because patients are rarely operated again. A 75-year-old patient was operated twice for recurrent glioblastoma, and a carmustine wafer was implanted during the second surgery. Eleven months later, a third surgery was performed, revealing unexpected incomplete degradation of the wafer. 1H-Nuclear Magnetic Resonance was performed to compare this wafer to pure BCNU and to an unused copolymer wafer. In the used wafer, peaks corresponding to hydrophobic units of the excipient were no longer noticeable, whereas peaks of the hydrophilic units and traces of BCNU were still present. These surprising results could be related to the formation of a hydrophobic membrane around the wafer, thus interfering with the expected diffusion and degradation processes. The clinical benefit of carmustine wafers in addition to the standard radio-chemotherapy remains limited, and in vivo behavior of this treatment is not completely elucidated yet. We found that the wafer may remain after several months. Alternative strategies to deal with the blood-brain barrier, such as drug-loaded liposomes or ultrasound-opening, must be explored to offer larger drug diffusion or allow repetitive delivery.

Use of etonogestrel implant beyond approved duration: prolonged contraceptive effectiveness.

BACKGROUND: The subdermal etonogestrel contraceptive implant has a current approved duration of 3 years. There is, however, recent and strong evidence of its effectiveness for 2 additional years during which no pregnancies were documented. CASE: We report a case of a 28-year-old woman who had an etonogestrel implant inserted 4 years earlier and wished to get pregnant. The implant was, however, deep in the triceps muscle and could not easily be removed. Her serum levels of etonogestrel remained positive even 6 years after insertion. As infertility investigation revealed endometriosis and bilateral tubal obstruction she was referred for assisted reproduction. Despite obtaining oocytes during an ovarian stimulation cycle, the endometrium was never above 4 mm, precluding embryo transfer. It was decided to remove the implant in order to improve endometrial conditions, after which the patient achieved pregnancy. CONCLUSION: This case report suggests that the etonogestrel implant is effective for even longer than the most recent studies have shown.

Influence of age on tolerability, safety and effectiveness of subdermal contraceptive implants.

The use of long-acting contraceptive methods is on the rise. The aim of this study was to describe the main variables (effectiveness, tolerability, menstrual bleeding) associated with the use of subdermal contraceptive implants and to investigate the influence of age on these variables. This was a descriptive, retrospective, observational study of 221 cases of contraceptive implants inserted at a Spanish hospital between 2006 and 2015. The mean age of implant users was 31.2 ± 7.5 years. Effectiveness was 100% and good tolerability was recorded for 86.5%. Infrequent bleeding was the most common bleeding pattern, followed by amenorrhoea. Of the 221 implants inserted, 47.5% were removed. The main reasons were expiration (54.3%) and discomfort due to bleeding alterations and other adverse effects (25.7%). Nulliparity and weight gain were significantly associated with an increased probability of implant removal. This study shows that implants were highly effective, safe and well-tolerated in our population. The age of users had no influence on any of the study variables analysed. Impact Statement What is already known on this subject? Subdermal contraceptive implants are long-acting reversible contraceptives which are both safe and effective. What do the results of this study add? The age of users had no influence on any of the study variables analysed. Nulliparity and weight gain were significantly associated with an increased probability of implant removal. What are the implications of these findings for clinical practice and/or further research? Subdermal contraceptive implants were a safe and effective long-acting progestin contraceptive method for women from all age groups in our series because no significant age-related differences were observed for the tolerability, vaginal bleeding patterns, the effectiveness, the adverse effects or any other variables.