Early endovascular retrieval of a migrated Implanon NXT from a branch of the right pulmonary artery.

A woman in her 20s was referred to a tertiary hospital emergency department for management of a migrating Implanon NXT. The Implanon was inserted 1 week prior by the patient's general practitioner who was unable to palpate the Implanon after insertion and hence, ordered an ultrasound scan which showed an actively migrating Implanon in the left basilic vein. She had mild chest pain, and her physical examination, ECG and blood tests were unremarkable. A CT chest showed a 31 mm foreign body within the right lower lobar artery. The foreign body was removed by interventional radiology by accessing the right internal jugular vein under ultrasound guidance and inserting a 6 FR pig catheter into the pulmonary trunk. The position was confirmed with angiogram and the foreign body was removed using a goose neck snare. The patient was discharged the same day with no complications, and fell pregnant a few months afterwards.

Migration of a contraceptive implant to the lung.

This case report details a rare case of contraceptive implant migration in a young woman. The migration was discovered three years post-insertion during a routine replacement visit. Despite the absence of pulmonary symptoms, a CT scan revealed the implant in the inferior lobe of the right lung. The patient was referred for further evaluation, but immediate surgical removal was deferred. This case report highlights the importance of healthcare providers recognising migration as a rare complication during implantation and suggests self-examination as a potential preventive strategy.

Usage of the levonorgestrel releasing intrauterine system in perimenopause.

Levonorgestrel releasing intrauterine system have excellent contraceptive efficacy with simultaneous lowering of menstruation's blood loss. It could be used for therapy of endometrial hyperplasia in perimenopause. In position of gestagen part of the hormone replacement therapy it has high control of endometrial proliferation. It is conjoined with the zero increasing of risk of thromboembolic disease in combination with transdermal oestrogen's application.

Effect of progestin-based contraceptives on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls.

Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls. Fifty-nine sexually active, HIV-uninfected girls aged 15-19, were recruited from the Washington DC metro area and self-selected into Control (condoms only), combined oral contraceptive pills, LNG-IUD, ETNG and DMPA groups. Vaginal swabs were collected at baseline prior to contraceptive use and at 3-month follow-up visit. Vaginal secretions were tested for pro-inflammatory (IL-1α, IL-1ß, TNF-α, IL-6, IL-8, MIP-3α, IP-10, RANTES, MIP-1α, MIP-1ß) and anti-inflammatory/anti-HIV (Serpin-A1, Elafin, Beta-Defensin-2, SLPI) immune biomarkers using ELISA and for anti-HIV activity using TZM-bl assay. Vaginal microbiome was evaluated using 16S rRNA gene sequencing. Data were analyzed using SAS Version 9. Among the 34 participants who completed both visits, no significant changes in median biomarker concentrations, HIV inhibition and microbiome composition were observed between baseline and follow-up visits for any of the contraceptive groups. IL-8 (p<0.01), MIP-3α (0.02), Elafin (p = 0.03) and RANTES (p<0.01) differed significantly by race whereas IL-6 was significantly different by age (p = 0.03). We conclude that 3-month use of LNG-IUD, ETNG and DMPA have minimal effects on adolescent vaginal immune microenvironment, and therefore unlikely to impact HIV risk. Future studies with larger sample size and longer follow-up are recommended to continue to evaluate effects of contraceptives on the lower genital tract immunity and susceptibility to sexually transmitted infections.

Onset of Acute Intermittent Porphyria After Etonogestrel Implant Insertion: A Case Report.

A 17-year-old previously healthy female developed posterior reversible encephalopathy syndrome 1 week after etonogestrel implantation. She had a previous etonogestrel implant removed 4 months prior after unrelenting abdominal pain and hyponatremia with a negative workup for other etiologies, including hypercoagulable disorders and malignancy. This second insertion and resulting hospitalization allowed for the diagnosis of acute intermittent porphyria (AIP) to be confirmed. Progesterone can induce enzymatic activity upstream of porphobilinogen deaminase, the enzyme implicated in AIP, resulting in build-up of toxic metabolites. AIP requires high clinical suspicion for diagnosis but should be considered when hormonal triggers lead to unexplained neurovisceral symptoms.

Offering extended use of the contraceptive implant via an implementation science framework: a qualitative study of clinicians' perceived barriers and facilitators.

BACKGROUND: The etonogestrel contraceptive implant is currently approved by the United States Food and Drug Administration (FDA) for the prevention of pregnancy up to 3 years. However, studies that suggest efficacy up to 5 years. There is little information on the prevalence of extended use and the factors that influence clinicians in offering extended use. We investigated clinician perspectives on the barriers and facilitators to offering extended use of the contraceptive implant. METHODS: Using the Consolidated Framework for Implementation Research (CFIR), we conducted semi-structured qualitative interviews. Participants were recruited from a nationwide survey study of reproductive health clinicians on their knowledge and perspective of extended use of the contraceptive implant. To optimize the diversity of perspectives, we purposefully sampled participants from this study. We used content analysis and consensual qualitative research methods to inform our coding and data analysis. Themes arose deductively and inductively. RESULTS: We interviewed 20 clinicians including advance practice clinicians, family medicine physicians, obstetrician/gynecologist and complex family planning sub-specialists. Themes regarding barriers and facilitators to extended use of the contraceptive implant emerged. Barriers included the FDA approval for 3 years and clinician concern about liability in the context of off-label use of the contraceptive implant. Educational materials and a champion of extended use were facilitators. CONCLUSIONS: There is opportunity to expand access to extended use of the contraceptive implant by developing educational materials for clinicians and patients, identifying a champion of extended use, and providing information on extended use prior to replacement appointments at 3 years.

Mobilizing stakeholders for implant removals in Burkina Faso using landscape assessment data.

BACKGROUND: Successful efforts to encourage uptake of subdermal contraceptive implants, with a lifespan of three to five years, necessitate planning to ensure that quality removal services are available when desired. In Burkina Faso, implant use has tripled over the past 8 years and now comprises almost half of the contraceptive method mix. Population Monitoring for Action (PMA) surveys identified barriers to obtaining quality removal when desired, particularly when the implant is not palpable, or providers lack needed skills or supplies. The Expanding Family Planning Choices (EFPC) project supported ministries of health in four countries with evaluation and strengthening of implant removal services. METHODS: An implant removal landscape assessment was conducted at 24 health facilities in three regions of Burkina Faso with high implant use that included provider observations of implant removal, interviews with providers and health facility managers, and facility readiness surveys. The project used landscape data to mobilize stakeholders through a series of participatory workshops to develop a collaborative roadmap and commit to actions supporting quality implant removals. RESULTS: Landscape findings revealed key gaps in provision of quality removal services, including high levels of provider confidence for implant insertion and removal (82% and 71%, respectively), low competence performing simple and difficult removals (19.2% and 11.1%, respectively), inadequate supplies and equipment (no facilities had all necessary materials for removal), lack of difficult removal management systems, and a lack of standard data collection tools for removal. Exposure to the data convinced stakeholders to focus on removals rather than expanding insertion services. While not all roadmap commitments were achieved, the process led to critical investments in quality implant removals. CONCLUSION: Landscape data revealed that facilities lack needed supplies and equipment, and providers lack skills needed to perform quality implant removals, limiting client reproductive choice. Disseminating this data enabled stakeholders to identify and commit to evidence-based priority actions. Stakeholders have since capitalized on program learnings and the roadmap, including following MOH guidance for implant removal supplies and health provider training. Our experience in Burkina Faso offers a replicable model of how data can direct collective action to improve quality of contraceptive implant removals.

Nexplanonectomy-the surgical removal of an embolized implanted contraceptive device: a case report and review of the literature.

BACKGROUND: Nexplanon implants are a common hormonal contraceptive modality. Though rare, these devices can embolize into the injured wall of the basilic vein, through the right heart, and finally wedge itself into a pulmonary artery. With adherence to the arterial wall over time, it becomes less amenable to endovascular retrieval. Patients may present with symptoms mimicking a pulmonary embolism, or without any symptoms at all. In asymptomatic cases, endovascular retrieval and/or surgery is required when patients wish to begin having children prior to biological inactivity. The current literature showed as little as nine case reports detailing lung tissue removal in the aim of reversing a patient's implanted contraceptive device. CASE PRESENTATION: A 22-year-old asymptomatic active-duty Caucasian female presented for elective outpatient Nexplanon removal. The suspicion of possible implant migration arose when it was discovered to be non-palpable in her left arm. After plain film x-rays failed to localize the implant, a chest x-ray and follow-up Computed Tomography (CT) scan revealed that the Nexplanon had migrated to a distal branch of the left pulmonary artery. Due to the patient's strong desires to begin having children, the decision was made for removal. Initial endovascular retrieval failed due to Nexplanon encapsulation within the arterial wall. Ultimately, the patient underwent a left video-assisted thoracoscopic surgery (VATS) for exploration and left lower lobe basilar S7-9 segmentectomy, which successfully removed the Nexplanon. CONCLUSIONS: Implanted contraceptive devices can rarely result in migration to the pulmonary vasculature. These radiopaque devices are detectable on imaging studies if patients and clinicians are unable to palpate them. An endovascular approach should be considered first to spare lung tissue and avoid chest-wall incisions, but can be complicated by encapsulation and adherence to adjacent tissue. A VATS procedure with single-lung ventilation via a double-lumen endotracheal tube allows surgeons to safely operate on an immobilized lung while anesthesiologists facilitate single-lung ventilation. This patient's case details the uncommon phenomenon of Nexplanon migration, and the exceedingly rare treatment resolution of lung resection to remove an embolized device.

Risk of Stroke in Women Using Levonorgestrel-Releasing Intrauterine Device for Contraception.

BACKGROUND: The commonly used combined hormonal contraceptives with progestins and ethinylestradiol are associated with an increased risk of ischemic stroke (IS). Progestin-only preparations, including levonorgestrel-releasing intrauterine devices (LG-IUDs), are not associated with an increased risk, and in smaller studies, the risk is even reduced. The risk of intracerebral hemorrhage (ICH) has never been investigated. We studied the risk of IS and ICH in women using LG-IUDs compared with women not using hormonal contraceptives. METHODS: In this Danish historical cohort study (2004-2021), we followed nonpregnant women (18-49 years) registering incident IS and ICH in relation to use of LG-IUDs/nonuse of hormonal contraceptives utilizing Danish high-quality registries with nationwide coverage. Poisson regression models adjusting for age, ethnicity, education, calendar year, and medication use for risk factors were applied. RESULTS: A total of 1 681 611 nonpregnant women contributed 11 971 745 person-years (py) of observation. Mean age at inclusion was 30.0 years; mean length of follow-up was 7.1 years; 2916 women (24.4 per 100 000 py) had IS; 367 (3.1 per 100 000 py) had ICH. Of these, 364 784 were users of LG-IUD contributing 1 720 311 py to the investigation; mean age at start of usage was 34.6 years. Nonusers of hormonal contraceptives contributed 10 251 434 py; mean age at inclusion was 30.0 years. The incidence rate of IS/ICH among LG-IUD users was 19.2/3.0 and among nonusers, it was 25.2/3.1 per 100 000 py. After adjustment, incidence rate ratio for IS was 0.78 (CI, 0.70-0.88), and for ICH it was 0.94 (CI, 0.69-1.28). CONCLUSIONS: The use of LG-IUD was associated with a 22% lower incidence rate of IS without raising the incidence rate of ICH. The finding raises the question of whether levonorgestrel, in addition to its contraceptive properties, could have the potential to prevent IS.

Gene expression associated with unfavorable vaginal bleeding in women using the etonogestrel subdermal contraceptive implant: a prospective study.

To evaluate gene expression associated with unfavorable vaginal bleeding in users of the Etonogestrel (ENG) contraceptive implant. Prospective study involving 100 women who intended to use the ENG implant. Exclusion criteria included abnormal uterine bleeding, inability to attend a 1-year follow-up, and implant removal for reasons unrelated to vaginal bleeding or loss of follow-up. We obtained endometrial biopsies before implant placement and assessed the expression of 20 selected genes. Users maintained a uterine bleeding diary for 12 months post-implant placement. For statistical analysis, we categorized women into those with or without favorable vaginal bleeding at 3 and 12 months. Women with lower CXCL1 expression had a 6.8-fold increased risk of unfavorable vaginal bleeding at 3 months (OR 6.8, 95% CI 2.21-20.79, p < 0.001), while those with higher BCL6 and BMP6 expression had 6- and 5.1-fold increased risks, respectively. By the 12-month follow-up, women with lower CXCL1 expression had a 5.37-fold increased risk of unfavorable vaginal bleeding (OR 5.37, 95% CI 1.63-17.73, p = 0.006). Women with CXCL1 expression < 0.0675, BCL6 > 0.65, and BMP6 > 3.4 had a higher likelihood of experiencing unfavorable vaginal bleeding at 3 months, and CXCL1 < 0.158 at 12 months. Users of ENG contraceptive implants with elevated BCL6 and BMP6 expression exhibited a higher risk of breakthrough bleeding at the 3-month follow-up. Conversely, reduced CXCL1 expression was associated with an elevated risk of bleeding at both the 3 and 12-month follow-ups.

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.

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.

The personal experience of female obstetricians and gynaecologists with contraceptive use influences the guidance and prescription of contraceptive methods: a web-survey.

OBJECTIVE: To evaluate the influence of the personal experience of female obstetricians and gynaecologists (Obst/Gyns) who utilise contraceptive methods on the provision of these methods. METHODS: An anonymous online web-based survey was carried out with female Obst/Gyns. The instrument contained questions about their current and previous contraceptive methods use, factors that influenced the choice and satisfaction with the ongoing method, as well as the occurrence of adverse events. They were also asked whether the experience of any adverse events influenced their decision in prescribing any particular contraceptive method. RESULTS: 476/9000 (5.3%) female Obst/Gyns answered the survey. The most common contraceptive in use was the 52-mg levonorgestrel-intrauterine device (52-mg LNG-IUD) (34%), followed by non-Long-Acting Reversible Contraception hormonal methods (21.2%). More than half of the respondents (57.6%) reported having some adverse effects and 18.7% reported that the personal experience of an adverse effect with the use of a contraceptive method influenced the prescription of that method. CONCLUSION: Half of female Obst/Gyns encountered adverse events linked to contraceptive usage. Additionally, almost one-fifth believe that their own encounter with adverse effects from a contraceptive method impacts their decision to prescribe the same method.

Almost one-fifth of the female obstetrics and gynaecologists that answered the online survey reported that the personal experience of an adverse effect with the use of a contraceptive method influenced the prescription of that 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.

A retrospective analysis of factors associated with deep contraceptive implant removals compared to superficial removals.

OBJECTIVE: To identify factors associated with the need for a deep etonogestrel contraceptive implant removal as compared to superficial removal. STUDY DESIGN: We conducted a retrospective cohort study of patients undergoing contraceptive implant removal from January 2014 to January 2023. We extracted key patient characteristics from electronic health record review and compared patients requiring deep removal versus routine superficial removal using Chi-squared, Fischer's exact, and Mann-Whitney U test. A multivariate logistic regression identified variables associated with increased odds of requiring a deep implant removal. RESULTS: The deep and superficial removal groups included 162 and 585 patients, respectively. Deep removal was associated with younger age at removal (median 25.0 vs 26.0 years, p = 0.005), lower body mass index (BMI) at insertion (median 23.2 kg/m2 vs 26.6 kg/m2, p = 0.024), BMI≥ 40 kg/m2 at removal (15.2% vs 7.0%, p = 0.007), weight gain during implant use (median 6.6 vs 1.8 kg, p ≤ 0.001), longer duration of use (median 36.0 vs 27.5 months, p < 0.001), implant exchange (37.3% vs 17.4%, p < 0.001), and insertion by non-physician (43.3% vs 19.3%, p < 0.001) or non-obstetrican and gynecologist (31.4% vs 11.8%, p < 0.001). Lower BMI at insertion (aOR 0.92, [95% CI 0.87-0.98]), weight gain during use (aOR 1.06 [95% CI 1.02-1.10]), and longer duration of use (aOR 1.05 [95% CI 1.02-1.07]) remained significantly associated with deep removal in regression analysis. CONCLUSION(S): We identified lower BMI at insertion, weight gain during use, and longer duration of use as independent factors associated with increased likelihood of needing a deep contraceptive implant removal. IMPLICATIONS: Clinicians should utilize proper technique when inserting contraceptive implants, especially in patients at risk for deep insertion, and ensure immediate referral to Centers of Experience for patients with non-palpable implants.

Sexual behaviour among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Data from the ECHO randomized trial.

BACKGROUND: Contraceptive use has complex effects on sexual behaviour and mood, including those related to reduced concerns about unintended pregnancy, direct hormonal effects and effects on endogenous sex hormones. We set out to obtain robust evidence on the relative effects of three contraceptive methods on sex behaviours, which is important for guiding contraceptive choice and future contraceptive developments. METHODS: This is a secondary analysis of data from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial in which 7,829 HIV-uninfected women from 12 sites in Eswatini, Kenya, South Africa and Zambia seeking contraception were randomly assigned to intramuscular depot-medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. Data collected for 12 to 18 months using 3-monthly behavioural questionnaires that relied on recall from the preceding 3 months, were used to estimate relative risk of post-baseline sex behaviours, as well as sexual desire and menstrual bleeding between randomized groups using modified Poisson regression. RESULTS: We observed small but generally consistent effects wherein DMPA-IM users reported lower prevalence of specified high risk sexual behaviours than implant users than Cu-IUD users (the '>' and '<' symbols indicate statistically significant differences): multiple sex partners 3.6% < 4.8% < 6.2% respectively; new sex partner 3.0% < 4.0% <5.3%; coital acts 16.45, 16.65, 17.12 (DMPA-IM < Cu-IUD); unprotected sex 65% < 68%, 70%; unprotected sex past 7 days 33% <36%, 37%; sex during vaginal bleeding 7.1%, 7.1% < 8.9%; no sex acts 4.1%, 3.8%, 3.4% (DMPA-IM > Cu-IUD); partner has sex with others 10% < 11%, 11%. The one exception was having any sex partner 96.5%, 96.9% < 97.4% (DMPA-IM < Cu-IUD). Decrease in sexual desire was reported by 1.6% > 1.1% >0.5%; amenorrhoea by 49% > 41% >12% and regular menstrual pattern by 26% <35% < 87% respectively. CONCLUSIONS: These findings suggest that women assigned to DMPA-IM may have a modest decrease in libido and sexual activity relative to the implant, and the implant relative to the Cu-IUD. We found more menstrual disturbance with DMPA-IM than with the implant (and as expected, both more than the Cu-IUD). These findings are important for informing the contraceptive choices of women and policymakers and highlight the need for robust comparison of the effects of other contraceptive methods as well.

"My IUD is expiring": A national U.S. mystery client study regarding use of the LNG 52-mg IUD for pregnancy prevention beyond 5 years after multiple FDA extensions.

OBJECTIVES: Since 2020, the Food and Drug Administration has approved multiple extensions to the use of the levonorgestrel (LNG) 52-mg intrauterine device (IUD) for pregnancy prevention beyond 5 years. The accessibility of this information to patients calling a reproductive health clinic to schedule replacement remains unknown. We assess the patient experience in accessing information via phone call on the duration of pregnancy prevention for LNG 52-mg IUD. STUDY DESIGN: We utilized a mystery client study design to inquire about LNG 52-mg IUD use beyond 5 years. Purposeful sampling ensured clinic diversity. RESULTS: In June 2022, 18 (32%) clinics offered extended use beyond 5 years, 25 (44%) recommended replacement at 5 years, and 14 (25%) could not provide information. The number of clinics offering extended LNG 52-mg IUD use did not significantly increase in August 2023 (n = 22, 39%, p = 0.27). CONCLUSIONS: Patients scheduling a replacement of the LNG 52-mg IUD may not receive information about use beyond 5 years. IMPLICATIONS: Reproductive health clinics scheduling staff need further training on updated guidelines.

Tailoring drug release from long-acting contraceptive levonorgestrel intrauterine systems.

The wide array of polydimethylsiloxane (PDMS) variants available on the market, coupled with the intricate combination of additives in silicone polymers, and the incomplete understanding of drug release behavior make formulation development of levonorgestrel intrauterine systems (LNG-IUSs) formidable. Accordingly, the objectives of this work were to investigate the impact of excipients on formulation attributes and in vitro performance of LNG-IUSs, elucidate drug release mechanisms, and thereby improve product understanding. LNG-IUSs with a wide range of additives and fillers were prepared, and in vitro drug release testing was conducted for up to 12 months. Incorporating various additives and/or fillers (silica, silicone resins, silicone oil, PEG, etc.) altered the crystallization kinetics of the crosslinked polymer, the viscosity, and the microstructure. In addition, drug-excipient interactions can occur. Interestingly, additives which increased matrix hydrophobicity and hindered PDMS crystallization facilitated dissolution and permeation of the lipophilic LNG. The influence of additives and lubricants on the mechanical properties of LNG-IUSs were also evaluated. PDMS chemical substitution and molecular weight were deemed to be most critical polymer attributes to the in vitro performance of LNG-IUSs. Drugs with varying physicochemical characteristics were used to prepare IUSs, modeling of the release kinetics was performed, and correlations between release properties and the various physicochemical attributes of the model drugs were established. Strong correlations between first order release rate constants and both drug solubility and Log P underpin the partition and diffusion-based release mechanisms in LNG-IUSs. This is the first comprehensive report to provide a mechanistic understanding of material-property-performance relationships for IUSs. This work offers an evidence-based approach to rational excipient selection and tailoring of drug release to achieve target daily release rates in vivo. The novel insights gained through this research could be helpful for supporting development of brand and generic IUS products as well as their regulatory assessment.

Heavy menstrual bleeding in women with inherited bleeding disorders in use of LNG-IUS: A systematic review and single-arm meta-analysis.

OBJECTIVES: Inherited bleeding disorders may cause heavy menstrual bleeding in women, impacting quality of life and impairing daily and social activities. The levonorgestrel-releasing intrauterine system is a potential treatment for these women, which might reduce menstrual blood loss. STUDY DESIGN: We performed a systematic review and single-arm meta-analysis to examine the levonorgestrel-releasing intrauterine system in women with inherited bleeding disorders and heavy menstrual bleeding. RESULTS: A systematic search on PubMed, Embase and Cochrane yielded 583 results, of which six observational studies (n = 156) met inclusion criteria. Levonorgestrel-releasing intrauterine system use in patients with inherited bleeding disorders and heavy menstrual bleeding was associated with amenorrhea in 60% of patients and a significant increase of 1.40 g/dL in hemoglobin and of 19.75 ng/mL in ferritin levels when comparing post- and pre-treatment levels. The post-treatment mean hemoglobin was 13.32 g/dL and the mean ferritin was 43.22 ng/dL. The rate of intrauterine device expulsion or removal due to mal position was low (13%), as was the need for intrauterine device removal due to lack of efficacy (14%). CONCLUSION: The levonorgestrel-releasing intrauterine system may improve bleeding patterns and quality of life in patients with inherited bleeding disorders and heavy menstrual bleeding. IMPLICATIONS: Women with inherited bleeding disorders could benefit from levonorgestrel-releasing intrauterine system, so its use should be an option for this women.