Breast Cancer Risk with Progestin Subdermal Implants: A Challenge in Patients Counseling

There is a steady global rise in the use of progestin subdermal implants, where use has increased by more than 20 times in the past two decades. BC risk has been reported with the older progestin only methods such as oral pills, injectables, and intrauterine devices, however, little is known about the risk with subdermal implants. In this review, we aim to update clinicians and researchers on the current evidence to support patient counseling and to inform future research directions. The available evidence of the association between the use of progestin subdermal implants and BC risk is discussed. We provide an overview of the potential role of endogenous progesterone in BC development. The chemical structure and molecular targets of synthetic progestins of relevance are summarized together with the preclinical and clinical evidence on their association with BC risk. We review all studies that investigated the action of the specific progestins included in subdermal implants. As well, we discuss the potential effect of the use of subdermal implants in women at increased BC risk, including carriers of BC susceptibility genetic mutations.

Wireless, battery-free, subdermally implantable platforms for transcranial and long-range optogenetics in freely moving animals

Wireless, battery-free, and fully subdermally implantable optogenetic tools are poised to transform neurobiological research in freely moving animals. Current-generation wireless devices are sufficiently small, thin, and light for subdermal implantation, offering some advantages over tethered methods for naturalistic behavior. Yet current devices using wireless power delivery require invasive stimulus delivery, penetrating the skull and disrupting the blood–brain barrier. This can cause tissue displacement, neuronal damage, and scarring. Power delivery constraints also sharply curtail operational arena size. Here, we implement highly miniaturized, capacitive power storage on the platform of wireless subdermal implants. With approaches to digitally manage power delivery to optoelectronic components, we enable two classes of applications: transcranial optogenetic activation millimeters into the brain (validated using motor cortex stimulation to induce turning behaviors) and wireless optogenetics in arenas of more than 1 m2 in size. This methodology allows for previously impossible behavioral experiments leveraging the modern optogenetic toolkit.

Safety and Benefits of Contraceptives Implants: A Systematic Review

Progestin-only contraceptive implants provide long-acting, highly effective reversible contraception. We searched the medical publications in PubMed, CENTRAL, and EMBASE for relevant articles on hormonal implants published in English between 1990 and 2021. Levonorgestrel (LNG) 6-capsule subdermal implants represented the first effective system approved for reversible contraception. The etonogestrel (ENG) single rod dispositive has been widely employed in clinical practice, since it is a highly effective and safe contraceptive method. Abnormal menstrual bleeding is a common ENG side effect, representing the main reason for its premature discontinuation. Emerging evidence demonstrated that it is possible to extend the use of the ENG implant beyond the three-year period for which it is approved. The ENG implant could be an effective and discrete alternative to the IUD in young girls, such as post-partum/post-abortion. Implants should be inserted by trained skilled clinicians who previously provide adequate counselling about their contraceptive effect, benefits, and any possible adverse events. More studies are needed to validate the extended use of the ENG implant for up to 5 years.

Evaluation of subdermal implants among family planning acceptors in a tertiary hospital, Nigeria

Background: Subdermal contraceptive implants are safe, convenient, very effective and reversible. Though they have numerous benefits, their use is still discontinued due to various reasons including side effects in the body of acceptors. Objective: To determine and compare the prevalence rates, side effects, discontinuation rates and indications for discontinuation of two subdermal implants (Jadelle and Implanon) at Rivers State University Teaching Hospital (RSUTH), Port Harcourt, Nigeria. Methods: A retrospective study of 874 clients attending family planning clinic at the RSUTH from 1st January, 2015 – 31st December, 2019 was conducted. Their records were retrieved from the clinic and reviewed. Data was extracted, coded and analyzed using the statistical package for social sciences (SPSS) IBM version 25.0 (Armonk, NY). Result: Four hundred and twenty five women used subdermal implants out of 874 acceptors of contraceptives within the study period giving an uptake rate of 48.6%. Implanon was more preferred accounting for 66.6% and Jadelle 33.4%. The mean age was 33.24+4.13 years. Most age group was 30-34 years accounting for 51.3%. Age range was 20-48 years and most (80%) were multiparous. Most (99.1%) were Christians and 98.4% were married. Only one client (0.2%) had no formal education. Seventy three (26.4%) acceptors discontinued the use. Most were due to desire for pregnancy (46.4%) and menorrhagia (24.1%). Four unintended pregnancies occurred giving a Pearl index of 0.9. Conclusion: Subdermal implants are safe and effective. Menstrual abnormality and desire for pregnancy were the commonest reasons for discontinuation.

Understanding the Acceptability of Subdermal Implants as a Possible New HIV Prevention Method: Multi-Stage Mixed Methods Study

Background A long-acting implant for HIV pre-exposure prophylaxis (PrEP) is in development in the Sustained Long-Action Prevention Against HIV (SLAP-HIV) trial. This could provide an alternative to oral PrEP. Objective Our mixed methods study aimed to understand (1) users’ experiences with a similar subdermal implant for contraception and (2) factors influencing the likelihood that gay and bisexual men (GBM) would use a proposed PrEP implant. Methods Work was completed in 4 stages. In stage 1, we conducted a scientific literature review on existing subdermal implants, focusing on users’ experiences with implant devices. In stage 2, we reviewed videos on YouTube, focusing on the experiences of current or former contraceptive implant users (as these implants are similar to those in development in SLAP-HIV). In stage 3, individuals who indicated use of a subdermal implant for contraception in the last 5 years were recruited via a web-based questionnaire. Eligible participants (n=12 individuals who liked implants a lot and n=12 individuals who disliked implants a lot) completed in-depth phone interviews (IDIs) about their experiences. In stage 4, results from IDIs were used to develop a web-based survey for HIV-negative GBM to rate their likelihood of using a PrEP implant on a scale (1=very unlikely and 5=very likely) based on likely device characteristics and implant concerns identified in the IDIs. Results In the scientific literature review (stage 1), concerns about contraceptive implants that could apply to the PrEP implants in development included potential side effects (eg, headache), anticipated high cost of the device, misconceptions about PrEP implants (eg, specific contraindications), and difficulty accessing PrEP implants. In the stage 2 YouTube review, individuals who had used contraceptive implants reported mild side effects related to their device. In stage 3, implant users reported that devices were comfortable, unintrusive, and presented only minor discomfort (eg, bruising) before or after insertion and removal. They mainly reported removing or disliking the device due to contraceptive-related side effects (eg, prolonged menstruation). Participants in the stage 4 quantitative survey (N=304) were mainly gay (204/238, 85.7%), white (125/238, 52.5%), cisgender men (231/238, 97.1%), and 42.0% (73/174) of them were on oral PrEP. Not having to take a daily pill increased the likelihood of using PrEP implants (mean 4.13). Requiring >1 device to achieve 1 year of protection (mean range 1.79-2.94) mildly discouraged PrEP implant use. Participants did not mind moderate bruising, a small scar, tenderness, or bleeding after insertion or removal, and an implant with a size slightly larger than a matchstick (mean ratings 3.18-3.69). Conclusions PrEP implants are promising among GBM. Implant features and insertion or removal-related concerns do not seem to discourage potential users. To ensure acceptability, PrEP implants should require the fewest possible implants for the greatest protection duration.

Microstructural Control of Polymers Achieved Using Controlled Phase Separation During 3D Printing with Oligomer Libraries: Dictating Drug Release for Personalized Subdermal Implants

<p>Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. In this study, we show that ink jet 3D printing of polymer blends gives rise to controllable phase separation that can be used to tailor the release of drugs. We predicted phase separation using high throughput screening combined with a model based on the Flory-Huggins interaction parameter, and were able to show that drug release from 3D printed structures can be predicted from observations based on single drops of mixtures. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be ‘dialed up’ without any manipulation of geometry. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be exploited, bringing a hitherto unseen level of understanding to emergent material properties of 3D printing.</p>

Microstructural Control of Polymers Achieved Using Controlled Phase Separation During 3D Printing with Oligomer Libraries: Dictating Drug Release for Personalized Subdermal Implants

<p>Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. In this study, we show that ink jet 3D printing of polymer blends gives rise to controllable phase separation that can be used to tailor the release of drugs. We predicted phase separation using high throughput screening combined with a model based on the Flory-Huggins interaction parameter, and were able to show that drug release from 3D printed structures can be predicted from observations based on single drops of mixtures. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be ‘dialed up’ without any manipulation of geometry. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be exploited, bringing a hitherto unseen level of understanding to emergent material properties of 3D printing.</p>

Uptake of hormonal implants contraceptives compared to other forms of contraceptives in Abuja, Nigeria

Background: Subdermal implants are a long-term, efficacious, and easily reversible contraceptive with few adverse effects that pose no risk to the health of the users. It is increasingly accepted as a method of contraception in sub-Sahara Africa like ours. Despite this, its uptake in Nigeria has not reached optimum level. This study is aimed at evaluating the socio-demographic characteristics of subdermal implants users in Abuja, Nigeria, its acceptance rate, efficacy, and discontinuation rate.Methods: The case notes of all the women from the family planning unit were studied. Data on socio-demographic characteristics, uptake rate, side effects profile and the discontinuation rates between January 2013 and December 2017 were retrieved and analyzed using SPSS software and results expressed in numbers and percentagesResults: Out of a total of 1,716 clients that were for contraception during the period under review, 786 accepted Jadelle/Implanon accounting for 45.8% of the implants acceptance rate. Of the 786 acceptors, 485(28.3%) chose Implanon, whereas 301(17.5%) preferred Jadelle. Discontinuation rate for both implants was 20.7%; the main reasons cited by the women were desire to have more children; 51(31.35%) and irregular vaginal bleeding; 30(18.4%). The Pearl Index for the implants in the study was zero. The peak parity for implant users was para 3. Approximately 72.1% the users of all forms of contraception were Christians, while 25.4% were Muslims. About 74.0% of the users had tertiary education.Conclusions: Jadelle/Implanon uptake was relatively high compared to other forms of contraception.