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Endometriosis is a relatively frequent pathology in gynecological practice. We performed an analysis to demonstrate the molecular changes that occur in endometriosis synthetic progestin-treated patients, hoping to sketch a possible pathophysiological pathway that will help us to better understand and treat this debilitating disease. We conducted a prospective study that included a group of 40 women, evaluated in our hospital between 2020-2021. We evaluated immunohistochemical tissue expression of estrogen receptor (ER), progesterone receptor (PR), B-cell lymphoma 2 (Bcl-2) protein, Ki-67, and serum levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in patients with ovarian endometrioma with and without progestin treatment. Our study revealed that Desogestrel treatment increases OPN serum levels, PR and Bcl-2 tissue expression and reduces VEGF serum levels and Ki-67 tissue expression. The results we have obtained are very interesting because the serum levels of OPN seem to be more influenced by progestin treatment, than by endometriosis itself. The study we have conducted gives a molecular complex view of what endometriosis represents and on how Desogestrel treatment works.

OBJECTIVE: To compare the risk of venous thromboembolism (VTE) among young women for nine combined oral contraceptives (COCs), including progestogens with an as yet unclear risk of VTE such as chlormadinone and nomegestrol, using COCs containing levonorgestrel with low ethinylestradiol (

To assess the variability of repeated measurements of serum etonogestrel concentration among contraceptive implant users.We measured 3 consecutive serum etonogestrel concentrations, drawn weekly, in women using etonogestrel implants for 12 to 36 months. We used a repeated measures test to evaluate differences.Among 20 participants, repeat serum etonogestrel concentrations did not differ from initial measurements (Friedman's test, p = 0.95). Mean serum etonogestrel concentrations had similar 95% confidence intervals at each time point: (134.09, 201.46), (135.08, 237.46), and (132.66, 192.45).We confirm that single-time measurements of serum etonogestrel concentration are acceptable pharmacokinetic outcomes for etonogestrel implant studies.Pharmacokinetic studies of the etonogestrel contraceptive implant assume single-time measurements are stable steady-state estimates based on small studies using older analysis methods. Our repeated measures study using modern liquid-chromatography mass-spectrometry analysis methods provides updated support for single-time pharmacokinetic measurements among etonogestrel implant users.

Progestin-only pills are associated with irregular bleeding patterns, including amenorrhea. Desogestrel (DSG) 75 mcg, a pill that inhibits ovulation, shows poor cycle control that may harm acceptability and compliance. A Drospirenone (DRSP)-only pill was developed with 244 days of activeplacebo days every 28-day cycle to improve cycle control.A phase III study in healthy women aged 18 to 45 years was performed to compare the bleeding profile of women taking a DRSP versus DSG over nine cycles. 249 women were older35 years: 173 using DRSP and 73 DSG. 259 women had a BMI25 kg/mAge: During cycles 2-4, the mean number of unscheduled bleeding days and spotting was 8.1 (SD10.53) for DRSP and 20.1 (19.41) for DSG;These analyses show the improvement in the bleeding profile of women with specific cardiovascular risk factors using the DRSP only oral contraceptive product compared to DSG.ImplicationsAn improvement in the bleeding profile of women with specific cardiovascular risk factors like age35 years, BMI25kg/m

Nexplanon is a single-rod contraceptive implant that should be placed subdermally at the inner side of the upper nondominant arm approximately 8-10 cm above the medial epicondyle of the humerus. Insertion guidelines were recently updated to place of insertion superficial of the triceps muscle to lower risk of insertion into vessels and nerves. If migration however occurs, it is most commonly around the insertion site. Migration above 2 cm is rarely reported [Ismail H, Mansour D, Singh M. Migration of implanon®. BMJ Sexual Reproduct Health. 2006;32:157-159]. This is a case report of a 24-year-old caucasian woman who presented with an impalpable Nexplanon implant that was, with the help of chest radiography and CT, located in a posterior basal subsegmental pulmonary artery in the left lower lobe of the lung. An attempt to remove the contraceptive implant by endovascular approach was unsuccessful. The implant remains

We aimed to compare low-level light therapy with oral contraceptive pills for pain relief and serum levels of nitric oxide and prostaglandin E2 in patients with primary dysmenorrhoea. This was a randomised, active comparator-controlled, multicentre study. In total, 156 patients were randomised to receive either low-level light therapy with light-emitting diodes (LED) applying on two acupoints, namely, conception vessel 4 (CV4) and CV6 or conventional treatment with oral Marvelon, 30 µg of ethinyl estradiol and 150 µg of desogestrel (DSG/EE), for three consecutive menstrual cycles. The main outcome was the proportion of patients who achieved 33% or more decrease in pain scores measured using the visual analogue scale, which was deemed as efficient rate. Absolute changes in visual analogue scale scores, serum levels of nitric oxide (assessed by nitrites and nitrates reflecting nitric oxide metabolism) and prostaglandin E2 (measured by enzyme-linked immunosorbent assay) were the secondary outcomes. A total of 135 patients completed the study (73 in the light therapy group and 62 in the DSG/EE group). The efficient rate at the end of treatment was comparable between the groups (73.6% vs. 85.7%, χ2 = 2.994, p = 0.084). A more significant reduction in pain scores was observed in the DSG/EE group (39.25% vs. 59.52%, p

ObjectivesLong-acting reversible contraceptives are effective contraceptives for women with HIV, but there are limited data on etonogestrel implant and antiretroviral therapy pharmacokinetic drug-drug interactions. We evaluated etonogestrel/antiretroviral therapy drug-drug interactions, and the effects of etonogestrel on ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, and efavirenz pharmacokinetics.Study designWe enrolled postpartum women using etonogestrel implants and receiving ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, or efavirenz-based regimens between 2012 and 2015. Etonogestrel implants were inserted 2 to 12 weeks postpartum. We performed pharmacokinetic sampling pre-etonogestrel insertion and 6 to 7 weeks postinsertion. We measured antiretroviral concentrations pre and postetonogestrel insertion, and compared etonogestrelconcentrations between antiretroviral regimens. We considered a minimum serum etonogestrelconcentration of90 pg/mLadequate for ovulation suppression.ResultsWe collected pharmacokinetic data for 74 postpartum women, 22 on ritonavir-boosted-atazanavir, 26 on ritonavir-boosted-lopinavir, and 26 on efavirenz. The median serum concentrations of etonogestrel when co-administered were highest with etonogestrel/ritonavir-boosted-atazanavir (604 pg/mL) and etonogestrel/ritonavir-boosted-lopinavir (428 pg/mL), and lowest with etonogestrel/efavirenz (125 pg/mL); p < 0.001. Minimum concentration (Cmin) of ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were lower after etonogestrel implant insertion, but overall exposure, predose concentrations, clearance, and half-lives were unchanged. We found no significant change in efavirenz exposure after etonogestrel insertion.ConclusionsUnlike efavirenz, ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were not associated with significant decreases in etonogestrel concentrations. Efavirenz was associated with a significant decrease in etonogestrel concentrations.ImplicationsThe findings demonstrate no interactions between etonogestrel and ritonavir-boosted-lopinavir or ritonavir-boosted-atazanavir, but confirm the decreased efficacy of etonogestrel with efavirenz-based antiretrovirals. This information should be used to counsel women with HIV who desire long-acting reversible contraceptives.

Study Objective Temporizing measures such as hormonal pills can temporarily improve the side effect of breakthrough bleeding in individuals using the etonogestrel implant. The aims of this study were to determine demographic factors that are associated with bothersome bleeding and to evaluate the impact of prescribing temporizing measures on implant continuation. Design Retrospective chart review. Setting The research was conducted in an adolescent medicine primary and specialty care clinic, an adolescent family planning clinic, and a clinic that cares for parenting adolescents. Participants A chart review was conducted on 1200 patients aged 12-24 years who received the implant in 2016. Interventions and Main Outcome Measures The primary outcome measure was removal of the implant within the first year of use. We followed each patient for 1 year to determine rates of removal, reasons for removal, and temporizing measures prescribed for bleeding. Results Younger age and lower body mass index were associated with reporting bothersome vaginal bleeding. Patients who were nulliparous or had bothersome bleeding were more likely to have the implant removed in the first year. Patients who received a temporizing measure for bleeding were more likely to retain the implant for 1 year than were those who did not receive one (67.1% vs 40%, P Conclusions Some patients are more likely to report concerns with bleeding or to have the implant removed in the first year after insertion. Prescribing temporizing measures to control bothersome vaginal bleeding may decrease rates of removal in the first year.

Background: Several studies have been published which stated that there is some connection between severe psychiatric disorders and contraceptive drug “desogestrel”. However, nothing in the summary of product characteristics (SmPC) or patient information leaflets of desogestrel about anxiety, more severe anxiety leading to panic attacks, or about risks of severe depression leading to suicidal thoughts or suicide attempts. Objective: To examine the safety and risk association between hormonal contraceptive desogestrel among women with psychiatric disorders using adverse drug reaction database of FDA Adverse Events Reporting System (FAERS) and EudraVigilance (EV). Methods: Individual case safety reports (ICSRs) of only female patients from Jan 1999 to Nov 2019 and Jan 2004 to Nov 2019 were downloaded from FAERS and EV database, respectively. Reports of drug desogestrel, dienogest, norgestimate, cyproterone acetate and drospirenone were downloaded. Disproportionality method of data mining was used to calculate the risk association. Results and Discusion: The lower limit of 95% CI of PRR is -0.28 and 2.02, PRR is 1.08 and 9.18, ROR is 1.09 (95%CI: 0.74, 1.59) and 9.26 (95% CI: 7.21, 11.89), Chi square value is 1.21 and 433.68, and IC-2SD is -0.27 and 2.60, respectively for data obtained from FAERS and EV. Conclusion: From this study, we conclude that there is no new emerging signal for the drug-event pair studied. Further study and continuous monitoring are required in future to know more about this drug-event pair association, as severe psychiatric disorders are not yet mentioned or included in SmPC and patient leaflet of desogestrel.

Objective To report our experiences with an extraction technique using a prebent, curved needle placed under deeply located single-rod implants to aid in removal. Study design We conducted a retrospective case series of all patients who were referred for removal of a deeply located or nonpalpable implant to one single specialized center between 2002 and 2019 by screening the database of the private office for “complex implants removals” or “nonpalpable implant” as a result for consultation. After implant-localization via high-resolution ultrasound, we performed a standard incision along the axis of the rod under local anesthesia. We fixed the rod by insertion of a curved needle directly beneath it piercing it through the tissue to the opposite side of the skin. After dissection of the subcutaneous tissue, we palpated the rod above the needle, grasped and removed it. In case of subfascial or intramuscular locations, we applied retractors and opened the fascia along the axis of the device to attempt removal. Results Of 117 referrals, medical records of 95 patients provided sufficient information to be included in our analysis. We could not palpate 81 (85%) devices and questionably palpate 14 (15%) implants. We successfully extracted all implants using this technique with an average removal duration of 30 minutes (SD +/- 6.8). Five (5.3%) patients noted intraoperative discomfort with 3 of them describing transient dysesthesia in the fingers innervated by the median nerve, which disappeared within a maximum of 48 hours. Conclusion Following the described protocol, this novel technique reliably facilitates removal of nonpalpable or deeply located etonogestrel implants. Implications This series of nonpalpable implants, all of which have been removed with the same standardized technique provides evidence that the given protocol permits successful extraction.

Purpose: Steroid hormones in hormonal contraceptives influence a variety of metabolic parameters. Mainly, ethinyloestradiol (EE) in combined hormonal contraceptives (CHC) is a potent inducer of hep...

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.

There is growing advocacy for use of long-acting reversible contraception among sexually active adolescents. Our primary aims were to evaluate the etonogestrel subdermal contraceptive implant (SCI) insertion trends among adolescents, as well as SCI retention at 1, 2, and 3 years, indications for removal, and to identify pregnancies that occurred during SCI use. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A retrospective cohort study was conducted of adolescents aged 13-19 years with SCI insertions in 2008-2014 within a large integrated health care system. Demographic and clinical characteristics included age, race/ethnicity, body mass index, gravidity, parity, insertions, reinsertions, indications for removal, and pregnancy. Electronic medical record review was conducted on a randomized sample of 540 adolescents with insertions during 2008-2011 for the retention objective to validate electronically extracted variables. Analyses included descriptive statistics, survival analysis with Kaplan-Meier estimates for implant retention and Cochran-Armitage trend test for insertions according to year during 2008-2014.Most adolescent SCI users were non-Hispanic white (43%), or Hispanic (34.2%) and 16 years or older (84.2%) at the time of insertion. Overall, 1-, 2-, and 3-year retention rates were 78.6%, 59.4%, and 26.2%, respectively, with retention at 44.3% at 2 years 9 months (indicative of removal of method for near expiration of 3-year device). The insertion rate trend showed statistically significant increases annually, from 0.14% in 2008 to 0.91% in 2014; P .0001. No pregnancies were documented during implant use. The most common indication for SCI removal was device expiration.SCI insertions increased annually among adolescents, with more than a sixfold increase over the 6-year study period, and more than half of the SCIs were retained through 2 years of use. The most common indication of SCI removal was completion of Food and Drug Administration-approved duration.

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

To estimate the cost-effectiveness (CE) of etonogestrel implants compared to other long-term and short-term reversible contraceptive methods available in France. 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. 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. 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.

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.

BackgroundUnintended 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.MethodsThe 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.ResultsThe 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.ConclusionESI 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.

Background Advocating for and promoting contraception use is critical in reducing mother and child morbidity and mortality. Early Implanon discontinuation may result in unwanted pregnancies and induced abortions. Although there has been research in Ethiopia on long-acting reversible contraceptives, there has been none on early Implanon removal among rural women who have used and removed it. Hence, this study aimed to investigate the magnitude of Implanon discontinuation and related characteristics among women who had the Implanon removed in central Ethiopian public health facilities. Methods A community-based cross-sectional study was conducted among all women of the reproductive age group who had removed Implanon after using it. A simple random sampling technique was used to select 373 women after proportional allocation to each health facility. Data were collected using a pretested semi-structured interviewer-administered questionnaire adapted from previous studies. Data were entered using EpiInfo and exported to SPSS version 21 for analysis. A binary logistic regression model was used to determine the association between the outcome variable and independent variables. A p-value less than 0.25 was used as a cutoff point to select candidate variables for the final model. Then, a p value less than 0.05, AOR, and a 95% confidence level were used to declare statistical significance. Result A total of 360 participants responded to the questionnaires, making a response rate of 96.5%. In this study, the early discontinuation rate was 42% (95% CI 36.9–47.7). No formal education (AOR = 0.53 [95% CI 0.3–0.94], having medium monthly income (AOR = 3.02 [95% CI 1.38–6.6]), inadequate pre-insertion counseling (AOR = 0.55 [95% CI 0.31–0.98]), lack of appointment for follow up (AOR = 0.16 [95% CI 0.05–0.54]), didn`t satisfy with service provided (AOR = 0.067 [95% CI 0.015–0.29] and developed side effect (AOR) = 4.45 [95% CI 2.37–8.36] were significantly associated with Implanon discontinuation. Conclusion The discontinuation rate of Implanon among those who removed it after using it in this study was high. Lack of formal education, having a medium-income, inadequate pre-insertion counseling, lack of appointments for the follow-up, poor satisfaction, and problems with side effects were the factors associated with early discontinuation rate. Hence, quality family planning service provision is essential to reduce the discontinuation rate.

To evaluate the different effects of a progestin-only contraceptive with desogestrel (DSG) vs combined oral contraceptives (COCs) for a first line long-term treatment of endometriosis-related pain among patients seeking hormonal contraception.An observational retrospective cohort study was conducted in collaboration with a local outpatient clinic for endometriosis among a group of nulliparous young women (No significant difference was found between the two groups in terms of clinical characteristics and pain scores before treatment. After 6 months both treatments were effective in reducing endometriosis-related pain, and those treated with DSG showed lower levels of dysmenorrhea, dyspareunia and nonmenstrual pelvic pain than COCs group (A progestin-only contraceptive with DSG is a valid option for long term management of endometriosis-related pain in patients seeking hormonal contraception.

Purpose In adolescents, concrete thinking may present as avoidance of an immediate, painful or uncomfortable experience despite long-term benefits, which may affect contraceptive choice. In this pilot study, we sought to better understand the pain that adolescents and young adults experience during contraceptive implant insertion. Materials and Methods In this cohort study, we surveyed 30 adolescents and young adults at their implant insertion visit about pre-procedure anxiety and pain experienced during lidocaine injection and Nexplanon™ placement. Results The average pre-procedure anxiety (Visual Analog Scale−Anxiety) score was 40 ± 29 mm. The average pain reported during lidocaine injection was 19 ± 21 mm and 6 ± 11 mm for implant insertion. Pre-procedure anxiety was not associated with pain during lidocaine injection (P = .61) or implant placement (P = .85). Conclusion Pain scores were low with both lidocaine injection and implant placement. Pre-procedure anxiety did not predict pain during lidocaine or implant placement. Patients considering an implant should be reassured by these data.

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.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.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.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.

To compare the efficacy and the tolerability of letrozole combined with oral contraceptives versus oral contraceptives alone in treating endometriosis-related pain.A total of 820 women with endometriosis presented with endometriosis-related pain were enrolled with this study. Patients were randomly treated either with letrozole (2.5 mg/day) combined with oral contraceptives (At completion of treatment, the intensity of chronic pelvic pain continued to decrease during treatment and at 1-month after treatment it was significantly lower than at 6-month follow-up and baseline level both in LE + oral contraceptives group (Mean ± SD,1.5 ± 1.4) and in oral contraceptives alone group(Mean ± SD,2.9 ± 1.2).The intensity of chronic pelvic pain and deep dyspareunia was significantly decrease at both 1-month after treatment and 6-month follow-up.This treatment for endometriosis is a promising new modality that warrants further investigation.

Background and purpose There is a lack of comparative safety data on the risk of pseudotumor cerebri syndrome (PTCS) associated with different hormonal contraceptives. We sought to quantify the risk of PTCS associated with eight different types of hormonal contraceptives compared with oral levonorgestrel. Methods We conducted a retrospective cohort study, with a case-control analysis of 4 871 504 women aged 15-45 years in the period 2008-2015, using IQVIA Ambulatory Electronic Medical Records data in the USA. Patients who used nine different contraceptive agents including intrauterine levonorgestrel, medroxyprogesterone injection, etonogestrel/ethinyl estradiol vaginal ring and combination oral contraceptives (COCs) that contained ethinyl estradiol and the progestins levonorgestrel, norgestimate, desogestrel, norethindrone and drospirenone, were included. Diagnosis of PTCS was defined using the first International Classification of Diseases, 9th or 10th revision, code for intracranial hypertension in patients who had also received an imaging code in the 30 days prior to the index date. Results A total of 3323 PTCS cases and 13 292 matched controls were identified. No increase in risk was found when analysing intrauterine levonorgestrel or COCs containing desogestrel, norethindrone, drospirenone, norgestimate or norgestrel versus COC levonorgestrel. The adjusted incidence rate ratio for etonogestrel/etonogestrel/ethinyl estradiol vaginal ring and medroxyprogesterone suspension compared with levonorgestrel COC was 4.45 [95% confidence interval (CI) 1.98-9.96] and 2.20 (95% CI 1.33-3.64), respectively. Conclusions This study found an elevated risk for PTCS among users of etonogestrel vaginal ring and medroxyprogesterone suspension when compared with oral levonorgestrel. Future studies are needed to confirm these findings.

To examine whether there is a positive association between sexual dysfunction (SD) and different types of progestin-based contraceptives. Nested case-control study in women of child-bearing age (15–45 years) from the IQVIA® Ambulatory electronic medical record database from 2008 to 2018. Cases defined by diagnosis of sexual dysfunction identified by international classification for disease clinical modification code 9th and 10th. Each case was matched to four controls and rates of prescriptions of the following were compared: levonorgestrel intra-uterine device (IUD), progestin, and ethinyl estradiol (EE) combined oral contraceptive (COC) formulations including levonorgestrel, norgestimate, drospirenone, desogestrel, norethindrone, and norgestrel; etonogestrel vaginal ring; and medroxyprogesterone injection. Overall, 6689 cases of patients with SD were matched to 26,756 matched controls. Compared with matched controls, more subjects with SD used levonorgestrel IUD (OR 1.24, 95% CI 1.08–1.44), EE-levonorgestrel COC (OR 1.18, 95% CI 1.00–1.41), EE-drospirenone (OR 1.28, 95% CI 1.00–1.67), and medroxyprogesterone (OR 1.38, 95% CI 1.12–1.70). The use of norgestrel exhibited a protective effect (OR 0.83, 95% CI 0.73–0.95). When using the EE-levonorgestrel COC as a comparator, norgestrel users exhibited a protective effect (OR 0.70, 95% CI 0.57–0.87) while no other contraceptives showed a statistically significant difference in association with SD. Our study found an increase in the use of levonorgestrel (COC and IUD), drospirenone, and medroxyprogesterone in subjects with SD. The risk of contraceptives did not differ when compared with oral levonorgestrel. The small association size and lack of difference between drug formulations suggest a minimal impact of progestin-based contraceptives on sexual dysfunction.

Objectives To assess etonogestrel contraceptive implant location and outcomes among women referred for “difficult” removal to a specialist clinic in South Africa. Study design We performed a retrospective review of cases referred to our clinic for removal of nonpalpable, deep, migrated, or damaged implants, or failed removals from March to August 2017. Results Most (n = 68, 92%) of the 74 referrals were nonpalpable in our clinic. We used ultrasound for localization and successfully removed 72 implants (97%) in the outpatient clinic. Conclusion With proper protocols and equipment, localization and removal of nonpalpable implants can be safely and effectively achieved in an outpatient African setting. Implications Access to providers specially trained in ultrasound localization should be available in all settings where implants are offered. Providing timely access to safe and effective implant removals in routine and difficult cases is essential to ensuring that implant programs are in alignment with rights-based, client-centered family planning principles.

Background: Rapid repeat pregnancy (RRP) is common among adolescents and is associated with adverse maternal and infant outcomes. Despite evidence that use of long-acting forms of contraception before hospital discharge can help minimize RRP rates, barriers to placement existed within the state of Indiana. We sought to determine state-specific RRP and induced abortion rates for adolescents based on chosen postpartum contraception to inform policy change. Methods: We examined a retrospective cohort of 227 adolescents (ages 12–18 years) who gave birth in Indiana between 2010 and 2012. Demographics, postpartum contraception, and subsequent pregnancies or abortions after the sentinel delivery were obtained. Rates of RRP based on type of immediate postpartum contraception, etonogestrel (ENG) contraceptive implant, depo-medroxyprogesterone acetate (DMPA) injection, and short-acting methods were compared. Bivariate and logistic regression analyses were conducted. Results: RRP rates were 3.7% for those with ENG contraceptive implant, 22.6% for those with DMPA, and 39.1% for those who choose short-acting methods (p = 0.01). Adolescents who did not choose an ENG contraceptive implant were significantly more likely to have an RRP (adjusted odds ratio [aOR] = 11.8, 95% confidence interval: 2.74–110.3), compared with other contraceptive methods, even after adjusting for covariates such as age, prior pregnancies, and postpartum visit attendance. Conclusions: Immediate postpartum receipt of ENG implant was significantly associated with a lower likelihood of RRP in adolescents in Indiana. These data facilitated state policy change regarding insurance reimbursement to improve statewide access for all women, regardless of age, showing how local data can inform policy change.

Background The use of implants has steadily increased in Kinshasa since 2013 but clinic-based access to this family planning method is limited due to distance and costs barriers. The objective of this study was to examine the feasibility and acceptability of providing Implanon NXT at the community level using medical and nursing students (M/N) as distributors, as part of a strategy to improve contraceptive uptake in the Democratic Republic of Congo. Methods A cohort of 531 women who chose to receive Implanon NXT from a M/N student during community-based campaign days participated in three rounds of a quantitative survey administered at the time of insertion of the method, and at 6 and 12 months later. We conducted descriptive analysis to assess the feasibility and acceptability of providing the method through M/N students in terms of method choice, user profiles, contraceptive history, experience with insertion and side effects, continuation / discontinuation of the method, and overall satisfaction with FP services as well as students’ preparedness and capacity to safely offer the method, and their satisfaction with the experience.. Results The study demonstrated the feasibility of training students for community-based provision of Implanon NXT and 95% of them were satisfied with their experience. Acceptability of both the method and the service delivery strategy was high among participants, including among young and first-time contraceptive users. Out of the 441 women with a known outcome at 12 months, 92% still had Implanon NXT inserted, despite some of them reporting experiencing side effects. The vast majority (79%) would “strongly recommend” obtaining NXT from a M/N student if a friend wanted to avoid pregnancies. Conclusions The provision of Implanon NXT at the community-level is a promising solution to address some of the barriers to accessing this method for women living in Kinshasa. However, strengthening pre-insertion counseling, particularly on expected side-effects and the possibility of early removal, is necessary to increase informed choice for the women and potentially limit method discontinuation.

OBJECTIVE To estimate the rate of readmissions for postpartum venous thromboembolism (VTE) during the first 30 days postdelivery between women with and without the immediate postpartum insertion of the etonogestrel contraceptive implant. METHODS The Nationwide Readmissions Database from 2016 was used to identify women with a singleton delivery, immediate postpartum insertion of the etonogestrel contraceptive implant, and readmission for VTE within 30 days of discharge. Those with a prior history of VTE or anticoagulant therapy were excluded. These women were compared with the number of women readmitted within 30 days for VTE who did not have the contraceptive implant placed during delivery admission. RESULTS Of 3,387,120 deliveries, 8,369 women underwent etonogestrel contraceptive implant placement during the delivery admission. There was no difference identified in the rate of readmission for VTE between exposed and unexposed women. Of these, seven had received a postpartum etonogestrel contraceptive implant (0.85/1,000; 95% CI 0.22-1.45/1,000 deliveries), compared with 1,192 without an etonogestrel contraceptive implant (0.35/1,000; 95% CI 0.33-0.37/1,000 deliveries); odds ratio (OR) 2.41; 95% CI 0.58-9.89. The rates of diabetes, thrombophilia, systemic lupus erythematosus, and cesarean birth did not differ between groups. Women who underwent etonogestrel contraceptive implant placement were younger and were more likely to have government-sponsored health insurance, a smoking history, hypertension, peripartum infection, or postpartum hemorrhage than women who did not receive an etonogestrel contraceptive implant (P

It is known that co‐administration of CYP3A inducers may decrease the effectiveness of oral contraceptives containing progestins as mono‐preparations or combined with ethinylestradiol. In a randomized clinical drug‐drug interaction study, we investigated the effects of CYP3A induction on the pharmacokinetics of commonly used progestins and ethinylestradiol. Rifampicin was used to induce CYP3A. The progestins chosen as victim drugs were levonorgestrel, norethindrone, desogestrel, and dienogest as mono‐products, and drospirenone combined with ethinylestradiol. Postmenopausal women (n = 12–14 per treatment group) received, in fixed sequence, a single dose of the victim drug plus midazolam without rifampicin, with rifampicin 10 mg/day (weak induction), and with rifampicin 600 mg/day (strong induction). The effects on progestin exposure were compared with the effects on midazolam exposure (as a benchmark). Unbound concentrations were evaluated for drugs binding to sex hormone binding globulin. Weak CYP3A induction, as confirmed by a mean decrease in midazolam exposure by 46%, resulted in minor changes in progestin exposure (mean decreases: 15–37%). Strong CYP3A induction, in contrast, resulted in mean decreases by 57–90% (mean decrease in midazolam exposure: 86%). Namely, the magnitude of the observed induction effects varied from weak to strong. Our data might provide an impetus to revisit the currently applied clinical recommendations for oral contraceptives, especially for levonorgestrel and norethindrone‐containing products, and they might give an indication as to which progestin could be used, if requested, by women taking weak CYP3A inducers—although it is acknowledged that the exact exposure‐response relationship for contraceptive efficacy is currently unclear for most progestins.

Subdermal contraceptive implant is approved in more than 60 countries and used by millions of women around the world. Although relatively safe in nature, their implantation and removal may be associated with potential complications, some of which may require surgical intervention. Two types of peripheral neurological complications are reported: complications related to compressive neuropathy caused by device decubitus and complications related to device improper removal. An healthy 35-year-old woman come to our attention for paresthesia from medial side of right elbow to fourth and fifth fingers. Tinel sign was positive on medial side of distal third of right arm, above the elbow, as well. Clinical history of patients revealed a subcutaneous placement of a etonogestrel implant 3 years before. Patients reported disappearing of tactile feeling of subcutaneous contraceptive implant since two months. At clinical examination, implant was not felt in its original subcutaneous place. X-rays control revealed its proximal and deep migration. Surgical exploration for subcutaneous contraceptive implant removal revealed it lying on the ulnar nerve. Patient referred immediate paresthesia disappearing after surgery. At 1 month follow up no motor or sensory alteration were evident. Removal of implants inserted too deeply must be carefully performed to prevent damages to nervous and vascular structures and it should be performed by operators who are very familiar with the anatomy of the arm. In case of chronic neuropathy caused by implant nerve compression only an appropriate patients information about rare but possible neuropathic symptoms related to device migration and a careful medical history collecting can avoid a mistaken diagnosis of canalicular syndrome. (www.actabiomedica.it)

It is not known whether the synergistic effect of genetic markers, increasing the risk of venous thrombosis (VT), and combined oral contraceptives (COC) use varies between different types of progestogens in these preparations. We investigated the joint effect of genetic risk factor, that is, F5 rs6025, F2 rs1799963, and FGG rs2066865 mutations, and different progestogens on the risk of VT. The constrained maximum likelihood estimation (CMLE) method was used to calculate joint effects, expressed as odds ratio (OR) with 95% confidence intervals [CI]. As the dose of estrogen is known to be a risk factor for VT, analyses were restricted to COC with 30 mu g estrogen and each progestogen. Overall, the joint effect of COC and genetic variants was lowest for COC containing the progestogen levonorgestrel, albeit CIs were wide. The OR (95% CI) of the four different analyses (i.e. joint effect with F5 rs6025, F2 rs1799963, F5 rs6025 or F2 rs1799963 and FGG rs2066865) ranged between 7 center dot 4 (5 center dot 4-10 center dot 2) and 24 center dot 8 (12 center dot 3-50 center dot 0) for levonorgestrel. For gestodene the joint effect ranged between 11 center dot 7 (7 center dot 2-19 center dot 1) and 30 center dot 9 (10 center dot 6-89 center dot 9). Desogestrel and cyproterone acetate had the highest risk estimates: 14 center dot 6 (9 center dot 7-21 center dot 9) and 32 center dot 6 (13 center dot 2-80 center dot 6) and 15 center dot 5 (9 center dot 7-24 center dot 9) and 44 center dot 4 (16 center dot 9-116 center dot 3) respectively. In women with inherited thrombophilia, COC containing levonorgestrel were associated with the lowest risk of VT, albeit the CIs were wide.

Women with chronic abnormal uterine bleeding-ovulatory dysfunction (AUB-O) are at increased risk of endometrial neoplasia. We conducted a non-inferiority randomized controlled trial to determine the effectiveness of two cyclic-progestin regimens orally administered 10 d/month for 6 months on endometrial protection and menstruation normalization in women with AUB-O. There were 104 premenopausal women with AUB-O randomized to desogestrel (DSG 150 µg/d, n = 50) or medroxyprogesterone acetate (MPA 10 mg/d, n = 54) group. Both groups were comparable in age (44.8 ± 5.7 vs. 42.5 ± 7.1 years), body mass index (24.8 ± 4.7 vs. 24.9 ± 4.7 kg/m2), and AUB characteristics (100% irregular periods). The primary outcome was endometrial response rate (the proportion of patients having complete pseudodecidualization in endometrial biopsies during treatment cycle-1). The secondary outcome was clinical response rate (the proportion of progestin withdrawal bleeding episodes with acceptable bleeding characteristics during treatment cycle-2 to cycle-6). DSG was not inferior to MPA regarding the endometrial protection (endometrial response rate of 78.0% vs. 70.4%, 95% CI of difference − 9.1–24.4%, non-inferiority limit of − 10%), but it was less effective regarding the menstruation normalization (acceptable bleeding rate of 90.0% vs 96.6%, P = 0.016).Clinical trial registration: ClinicalTrials.gov (NCT02103764, date of approval 18 Feb 2014).

Preventing new HIV infections, especially amongst young women, is key to ending the HIV epidemic especially in sub-Saharan Africa. Potent antiretroviral (ARV) drugs used as pre-exposure prophylaxis (PrEP) are currently being formulated as long-acting implantable devices, or nanosuspension injectables that release drug at a sustained rate providing protection from acquiring HIV. PrEP as implants (PrEP Implants) offers an innovative and novel approach, expanding the HIV prevention toolbox. Feedback from providers and future users in the early clinical product development stages may identify modifiable characteristics which can improve acceptability and uptake of new technologies. Healthcare workers (HCWs) perspectives and lessons learned during the rollout of contraceptive implants will allow us to understand what factors may impact the roll-out of PrEP implants. We conducted eighteen interviews with HCWs (9 Nurses and 9 Community Healthcare Workers) in rural KwaZulu-Natal, South Africa. HCWs listed the long-acting nature of the contraceptive implant as a key benefit, helping to overcome healthcare system barriers like heavy workloads and understaffing. However, challenges like side effects, migration of the implant, stakeholder buy-in and inconsistent training on insertion and removal hampered the roll-out of the contraceptive implant. For PrEP implants, HCWs preferred long-acting products that were palpable and biodegradable. Our findings highlighted that the characteristics of PrEP implants that are perceived to be beneficial by HCWs may not align with that of potential users, potentially impacting the acceptability and uptake of PrEP implants. Further our data highlight the need for sustained and multi-pronged approaches to training HCWs and introducing new health technologies into communities. Finding a balance between the needs of HCWs that accommodate their heavy workloads, limited resources at points of delivery of care and the needs and preferences of potential users need to be carefully considered in the development of PrEP implants.

OBJECTIVES Provision of reproductive health preventive services to adolescents is critical given their high rates of sexually transmitted infections and unintended pregnancies. Pediatricians are well positioned to provide these services but often face barriers. With this project, we aimed to build quality improvement (QI) capacity within pediatric practices to improve adherence to national guidelines for adolescent reproductive health preventive services. METHODS In 2016, an accountable care organization overseeing health care delivery for low-income children in the Midwestern United States used practice facilitation, a proven approach to improve health care quality, to support pediatric practices in implementing reproductive health QI projects. Interested practices pursued projects aimed at providing (1) sexual risk reduction and contraceptive counseling (reproductive health assessments [RHAs]) or (2) etonogestrel implants. QI specialists helped practices build key driver diagrams and implement interventions. Outcome measures included the proportion of well-care visits with RHAs completed and number of etonogestrel insertions performed monthly. RESULTS Between November 1, 2016, and December 31, 2019, 6 practices serving >7000 adolescents pursued QI projects. Among practices focused on RHAs, the proportion of well-care visits with completed RHAs per month increased from 0% to 65.8% (P < .001) within 18 months. Among practices focused on etonogestrel implant insertions, overall insertions per month increased from 0 to 8.5 (P < .001). CONCLUSIONS Practice facilitation is an effective way to increase adherence to national guidelines for adolescent reproductive health preventive services within primary care practices. Success was driven by practice-specific customization of interventions and ongoing, hands-on support.

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.

Objective To estimate associations between contraceptive failures and concomitant CYP3A4-inducing medications by route of administration. Study design Comparison of unintended pregnancy outcomes within U.S. Food and Drug Administration's Adverse Event Reporting System by couse of CYP3A4-inducing drugs and route of administration for levonorgestrel and etonogestrel/desogestrel. Results Among 14,504 levonorgestrel case reports, the reporting odds ratio (ROR) was increased for oral (ROR = 4.2 [3.0–5.7]), implants (ROR = 8.0 [5.8–11.0]), but not intrauterine (ROR = 0.9 [0.6–1.3]) levonorgestrel products. For 9348 etonogestrel/desogestrel case reports, oral and vaginal products were not associated with contraceptive failure. Etonogestrel containing implants (ROR = 4.9 [4.1–5.9]) were associated with increased contraceptive failure. Conclusion Levonorgestrel containing combination oral products and implants containing levonorgestrel or etonogestrel were prone to CYP3A4-inducing drug-drug interactions that may increase contraceptive failures. Implications The progestin components of hormonal contraceptives are susceptible to drug-drug interactions, but this susceptibility is influenced by route of administration. This study provides evidence from an Adverse Event Reporting System that CYP3A4-inducing medications increase the risk of unintended pregnancy for oral and implant contraceptives but not intrauterine or vaginal devices.