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Reproductive Health Oct 2022This study aimed to investigate the medroxyprogesterone acetate (MPA) + HMG protocol vs ultra-long gonadotrophin releasing hormone (GnRH) agonist protocol in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This study aimed to investigate the medroxyprogesterone acetate (MPA) + HMG protocol vs ultra-long gonadotrophin releasing hormone (GnRH) agonist protocol in patients with advanced ovarian endometriosis who received in vitro fertilization (IVF).
METHODS
Three hundred patients with advanced ovary endometriosis who underwent IVF were included, and embryological and clinical outcomes were assessed between March 2017 and September 2017. Patients were divided into MPA + HMG group and 1-month ultra-long GnRHa protocol group.
RESULTS
Lower hMG dose and shorter medication time were found in the MPA + HMG group than in the GnRHa group (P < 0.05). Follicle to-Oocyte Index was significantly different between MPA + HMG group and GnRHa group (P < 0.001). No differences were found in the ovary response and numbers of mature oocytes, fertilized oocytes and viable embryos. The clinical pregnancy and live birth outcomes were similar between MPA + HMG group and GnRHa group, and these outcomes were independent of fresh or frozen embryo transfer in the GnRHa protocol group. There were no significant differences in the time to embryo transfer, medical cost and adverse effects.
CONCLUSION
The number of oocytes retrieved and pregnancy outcomes after MPA + HMG protocol are similar to those after ultra-long GnRHa protocol in women with ovarian endometriosis. MPA + HMG protocol may be an alternative to ultra-long GnRHa protocol for IVF in ovary endometriosis patients. Trial registration The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INR-17010924) In conclusion, the administration of MPA in COH showed similar number of oocytes retrieved, no premature LH surge, and similar pregnancy and live birth outcomes in patients with advanced ovarian endometriosis undergoing IVF/ICSI as compared to the one-month long protocol. The use of MPA in COH appears to be promising although many questions remain to be elucidated, including the dose and time of progestin priming as well as its possible influence on the oocyte development potential and microenvironment. Given their good tolerability, few metabolic influence, and low cost, progestogens provide a novel alternative to the conventional protocol for patients with endometriosis.
Topics: Endometriosis; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Medroxyprogesterone Acetate; Ovulation Induction; Pregnancy; Progestins; Prospective Studies
PubMed: 36195878
DOI: 10.1186/s12978-022-01500-z -
Systematic Reviews Jul 2023Self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is registered in many countries. It shows great potential for... (Review)
Review
BACKGROUND
Self-administered depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) is registered in many countries. It shows great potential for improving contraceptive access, continuation, and autonomy. However, there are challenges in rolling out this new efficacious intervention, and major implementation problems have been encountered during scale-up.
OBJECTIVE
To describe the implementation strategies to scale up self-administered DMPA-SC and the barriers, facilitators, and outcomes of these programs.
METHOD
Recent guidelines, including the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews, were used to design and report this review. An article or report was eligible for inclusion if it reported interventions that could scale up self-administered DMPA-SC implementation or its facilitators, barriers, or outcomes. We searched six electronic databases and the grey literature for eligible articles and reports. Two reviewers independently screened the document titles, abstracts, and full texts to identify eligible documents. Data were extracted using structured forms. Using the Effective Practice and Organization of Care (EPOC) taxonomy of health systems framework for thematic analysis, data were presented in a narrative approach.
RESULTS
Of the 755 retrieved documents, 34 were included in this review. Most of the documents included were multi-country reports (n = 14), and all documents were published within the last 5 years (2018-2021). This review identified documents that reported interventions in all EPOC domains. The most-reported interventions were: task-sharing amongst health workforce cadres, engaged leadership, encouraging policies, training and education, DMPA-SC demand generation, integration into existing programs, improved funding mechanisms, collaboration with development partners, and supply chain strengthening. The main barriers were suboptimal funding, inadequate human resources, and poor logistics supply of DMPA-SC. There was minimal evidence of scale-up outcomes.
CONCLUSION
This scoping review reported a wide range of interventions employed by countries and programs to scale up DMPA-SC self-administration but minimal evidence of the scale-up outcomes. Evidence from this review can help design better programs that improves access to quality family planning services to achieve the Sustainable Development Goals (SDG) targets 3.7. However, efforts should focus on rigorous implementation research that assess scaled up self-administered DMPA-SC interventions and report their outcomes.
REGISTRATION
The protocol for this review was registered in the protocols.io repository ( https://www.protocols.io/view/a-protocol-for-a-scoping-review-of-implementation-x54v9yemmg3e/v1 ).
Topics: Female; Humans; Contraception; Contraceptive Agents, Female; Injections, Subcutaneous; Medroxyprogesterone Acetate; Self Administration
PubMed: 37403147
DOI: 10.1186/s13643-023-02216-2 -
Steroids Jun 2022The glucocorticoid receptor (GR) regulates transcription of genes involved in multiple processes. Medroxyprogesterone acetate (MPA), widely used in the injectable...
The glucocorticoid receptor (GR) regulates transcription of genes involved in multiple processes. Medroxyprogesterone acetate (MPA), widely used in the injectable contraceptive Depo-MPA (DMPA), has off-target effects via the GR, which may result in side-effects in endocrine therapy. However, very little is known about the GR activity of other progestins used in endocrine therapy. This study compared GR activities for several progestins, using whole cell binding, dose-response, and GR phosphorylation assays, in both a cell line model and peripheral blood mononuclear cells (PBMCs). MPA, etonogestrel (ETG) and nestorone (NES) exhibit greater relative binding affinities for the GR than levonorgestrel (LNG) and norethisterone/norethindrone (NET) and are partial GR agonists for transactivation but agonists for transrepression on synthetic promoters in COS-1 cells. MPA is a potent agonist for endogenous GR-regulated GILZ and IL6 genes in PBMCs. While ETG and NES also display agonist activity on IL6, they have little effect on GILZ. In contrast, LNG and NET exhibit little to no activity in transactivation models, while both exhibit some transrepressive activity but are generally less potent and/or efficacious than MPA. Antagonist and phosphorylation assays confirmed that MPA and NES act via the GR on endogenous genes in PBMCs. Our results suggest GR-mediated dose-dependent and gene-specific transcriptional side-effects are likely to occur at physiologically relevant concentrations in vivo for MPA, may possibly occur selectively for ETG and NES, but are unlikely to occur for LNG and NET. This suggests that these progestins will exhibit differential side-effects in endocrine therapy via the GR.
Topics: Animals; COS Cells; Chlorocebus aethiops; Glucocorticoids; Interleukin-6; Leukocytes, Mononuclear; Levonorgestrel; Medroxyprogesterone Acetate; Norethindrone; Progestins; Receptors, Glucocorticoid
PubMed: 35271867
DOI: 10.1016/j.steroids.2022.108998 -
Environmental Health Perspectives Nov 2020Injectable contraceptive use is common, with 74 million users worldwide. Use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) is associated with...
BACKGROUND
Injectable contraceptive use is common, with 74 million users worldwide. Use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) is associated with bone mineral density loss. We hypothesize that increased bone resorption with DMPA use allows for mobilization of the toxic metal lead stored in bone to blood, presenting users with increased systemic exposure to lead.
OBJECTIVE
The objective of our study was to investigate the association between current DMPA use and blood lead concentrations.
METHODS
We conducted a cross-sectional analysis using enrollment data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1,693 African-American women who were 23-35 years of age. Data on DMPA use were collected by computer-assisted telephone interview. Blood lead concentrations were measured in whole blood samples among 1,548 participants (91% of cohort). We estimated the adjusted percent difference in blood lead concentrations and 95% confidence intervals (CI) between current DMPA users and nonusers using multivariable linear regression.
RESULTS
Geometric mean blood lead concentration was (95% CI: 0.67, 0.71). After adjustment, current DMPA users (7% of cohort) had blood lead concentrations that were 18% higher than those of nonusers (95% CI: 8%, 29%). Similar associations were observed with additional analyses to assess for potential bias from smoking, DMPA-induced amenorrhea, use of estrogen-containing contraceptives, having given birth in the prior year, and history of medical conditions or current medication use associated with bone loss.
DISCUSSION
Our results indicate that current DMPA use is associated with increased blood lead concentrations. Further research, particularly in populations highly exposed to lead, is warranted to consider tradeoffs between the adverse effects of lead on human health and the importance of DMPA as a contraceptive option to prevent unintended pregnancy. https://doi.org/10.1289/EHP7017.
Topics: Adult; Bone Density; Cohort Studies; Contraceptive Agents, Female; Cross-Sectional Studies; Environmental Pollutants; Female; Humans; Lead; Medroxyprogesterone Acetate; Time Factors; Young Adult
PubMed: 33206002
DOI: 10.1289/EHP7017 -
AIDS (London, England) Apr 2020Depot medroxyprogesterone acetate (Depo-Provera) is the most commonly used injectable hormone contraceptive in Sub-Saharan Africa where HIV incidence is high. We...
OBJECTIVES
Depot medroxyprogesterone acetate (Depo-Provera) is the most commonly used injectable hormone contraceptive in Sub-Saharan Africa where HIV incidence is high. We determined the impact of Depo-Provera on cervical immune cells and mediators in healthy women.
METHODS
In this longitudinal study, vaginal, endocervical, and rectal swabs were collected at baseline (visit 1), 1 month (visit 2), and 3 months (visit 3) after Depo-Provera injection. Cervical cells were collected by cytobrush and immune markers on cervical CD4 T cells were analyzed by multicolor flow cytometry at three different visits. The levels of immune mediators in cytobrush supernatants as well as vaginal, cervical, and rectal secretions from swabs were analyzed by multiplex assays and ELISA.
RESULTS
Compared with baseline levels, we found a significant increase in the frequency of cervical CCR5CD4 T cells and a significant decrease in the frequency of cervical central memory CD4 T cells. Depo-Provera treatment had little effect on expression of immune mediators in rectal mucosa but significantly suppressed numerous immune mediators at cervicovaginal mucosa. Levels of MCP-1, G-CSF, IL-6, IL-10, GM-CSF, and IP-10 were significantly decreased in both vaginal and cervical secretions after Depo-Provera injection. In cervical samples collected by cytobrush, we found reduced levels of 22 of 25 immune mediators after Depo-Provera injection. Changes in immune mediators differed between vaginal and cervical mucosa, demonstrating compartment-specific responses.
CONCLUSION
Depo-Provera altered immune profiles of cervical CD4 T cells and suppressed host immune response at cervicovaginal mucosa, suggesting its likely effect on transmission of sexually transmitted infections including HIV.
Topics: Biomarkers; CD4-Positive T-Lymphocytes; Contraceptive Agents, Female; Female; Humans; Longitudinal Studies; Medroxyprogesterone Acetate; Mental Health; Mucous Membrane; Receptors, CCR5
PubMed: 31972606
DOI: 10.1097/QAD.0000000000002475 -
The Cochrane Database of Systematic... Dec 2012Health care providers often tell women to wait until the next menses to begin hormonal contraception. The intent is to avoid contraceptive use during an undetected... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Health care providers often tell women to wait until the next menses to begin hormonal contraception. The intent is to avoid contraceptive use during an undetected pregnancy. An alternative is to start hormonal contraception immediately with back-up birth control for the first seven days. Immediate initiation was introduced with combined oral contraceptives (COCs), and has expanded to other hormonal contraceptives. At the time of the initial review, how immediate start compared to conventional menses-dependent start was unclear regarding effectiveness, continuation, and acceptability. The immediate-start approach may improve women's access to, and continuation of, hormonal contraception.
OBJECTIVES
This review examined randomized controlled trials (RCTs) of immediate-start hormonal contraception for differences in effectiveness, continuation, and acceptability.
SEARCH METHODS
In August 2012, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP for trials of immediate-start hormonal contraceptives. We contacted researchers to find other studies. Earlier searches also included EMBASE.
SELECTION CRITERIA
We included RCTs that compared immediate start to conventional start of hormonal contraception. Also included were trials that compared immediate start of different hormonal contraceptive methods with each other.
DATA COLLECTION AND ANALYSIS
Data were abstracted by two authors and entered into RevMan. The Peto odds ratio (OR) with 95% confidence interval (CI) was calculated.
MAIN RESULTS
Five studies were included. No new eligible studies have been found since the review was initially conducted. Method discontinuation was similar between groups in all trials. Bleeding patterns and side effects were similar in trials that compared immediate with conventional start. In a study of depot medroxyprogesterone acetate (DMPA), immediate start of DMPA showed fewer pregnancies than a 'bridge' method before DMPA (OR 0.36; 95% CI 0.16 to 0.84). Further, more women in the immediate-DMPA group were very satisfied versus those with a 'bridge' method (OR 1.99; 95% CI 1.05 to 3.77). A trial of two immediate-start methods showed the vaginal ring group had less prolonged bleeding (OR 0.42; 95% CI 0.20 to 0.89) and less frequent bleeding (OR 0.23; 95% CI 0.05 to 1.03) than COC users. The ring group also reported fewer side effects. Also, more immediate ring users were very satisfied than immediate COC users (OR 2.88; 95% CI 1.59 to 5.22).
AUTHORS' CONCLUSIONS
We found limited evidence that immediate start of hormonal contraception reduces unintended pregnancies or increases method continuation. However, the pregnancy rate was lower with immediate start of DMPA versus another method. Some differences were associated with contraceptive type rather than initiation method, i.e., immediate ring versus immediate COC. More studies are needed of immediate versus conventional start of the same hormonal contraceptive.
Topics: Contraception; Contraceptives, Oral, Hormonal; Drug Chronotherapy; Female; Humans; Intrauterine Devices; Medroxyprogesterone Acetate; Menstruation; Pregnancy; Pregnancy, Unplanned; Randomized Controlled Trials as Topic
PubMed: 23235628
DOI: 10.1002/14651858.CD006260.pub3 -
Reproductive Health Aug 2013Use of depot medroxyprogesterone acetate (DMPA), often known by the brand name Depo-Provera, has increased globally, particularly in multiple low- and middle-income... (Review)
Review
BACKGROUND
Use of depot medroxyprogesterone acetate (DMPA), often known by the brand name Depo-Provera, has increased globally, particularly in multiple low- and middle-income countries (LMICs). As a reproductive health technology that has scaled up in diverse contexts, DMPA is an exemplar product innovation with which to illustrate the utility of the AIDED model for scaling up family health innovations.
METHODS
We conducted a systematic review of the enabling factors and barriers to scaling up DMPA use in LMICs. We searched 11 electronic databases for academic literature published through January 2013 (n = 284 articles), and grey literature from major health organizations. We applied exclusion criteria to identify relevant articles from peer-reviewed (n = 10) and grey literature (n = 9), extracting data on scale up of DMPA in 13 countries. We then mapped the resulting factors to the five AIDED model components: ASSESS, INNOVATE, DEVELOP, ENGAGE, and DEVOLVE.
RESULTS
The final sample of sources included studies representing variation in geographies and methodologies. We identified 15 enabling factors and 10 barriers to dissemination, diffusion, scale up, and/or sustainability of DMPA use. The greatest number of factors were mapped to the ASSESS, DEVELOP, and ENGAGE components.
CONCLUSIONS
Findings offer early empirical support for the AIDED model, and provide insights into scale up of DMPA that may be relevant for other family planning product innovations.
Topics: Contraceptive Agents, Female; Delayed-Action Preparations; Female; Health Services Accessibility; Humans; Medroxyprogesterone Acetate; Models, Theoretical; Reproductive Health Services
PubMed: 23915274
DOI: 10.1186/1742-4755-10-39 -
Reproductive Health Aug 2020Self-administered subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is poised to increase access to contraception; however, governments are concerned about the...
Adolescent and covert family planning users' experiences self-injecting contraception in Uganda and Malawi: implications for waste disposal of subcutaneous depot medroxyprogesterone acetate.
BACKGROUND
Self-administered subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is poised to increase access to contraception; however, governments are concerned about the waste management of used units. Self-injectors in Malawi and Uganda are currently instructed to store used units in containers and return them to health workers for disposal. However, this may not be feasible in low-resource settings, especially for younger or covert self-injectors. We describe adolescent (15-19 years) and adult (20-49 years) self-injectors' disposal experiences in Uganda and Malawi. When possible, we compare covert and overt users' experiences.
METHODS
We conducted cross-sectional qualitative studies in 2019 with 50 self-injectors in Uganda and 60 in Malawi. We purposively selected approximately half adolescents and included those trained by clinic-based providers and community health workers. We conducted semi-structured interviews and thematic data analysis and compared the findings across settings.
RESULTS
Just under half of both samples were adolescents, substantially more of whom were covert users in Uganda (68%) than Malawi (~ 10%). Most participants reported being told to store used units in a container and return them to health workers. About two-thirds of Uganda participants had disposed of at least one unit by the interview, most commonly returning them to health workers. Over one-third of Malawi participants had disposed of at least one unit by the interview, slightly more disposed into latrines compared to returning to health workers. Participants in both settings reported compliance with health workers' disposal instructions as a primary reason for their disposal method. One-fifth of Uganda participants, mostly adolescent covert users, and one-quarter in Malawi said they were told they could dispose into latrines, and often did so. The majority in both settings said they would prefer to dispose units in latrines because they worried about needlestick injuries to others and because it was convenient. Some Uganda adolescent covert users felt returning units to health workers was challenging due to privacy concerns.
CONCLUSIONS
While most self-injectors disposed of used units as instructed, findings from both studies suggest that returning units to health workers is not preferred and may not be feasible for some adolescent covert users. More convenient disposal solutions should be identified.
Topics: Adolescent; Adult; Community Health Workers; Contraception; Contraceptive Agents, Female; Cross-Sectional Studies; Family Planning Services; Female; Humans; Injections, Subcutaneous; Malawi; Medroxyprogesterone Acetate; Patient Satisfaction; Uganda; Young Adult
PubMed: 32746860
DOI: 10.1186/s12978-020-00964-1 -
Journal of Acquired Immune Deficiency... Jan 2023Depot medroxyprogesterone acetate (DMPA) is a widely used contraceptive method. HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate (F/TDF)...
Interaction of Depot Medroxyprogesterone Acetate and Tenofovir Disoproxil Fumarate/Emtricitabine on Peripheral Blood Mononuclear Cells and Cervical Tissue Susceptibility to HIV Infection and Pharmacokinetics.
BACKGROUND
Depot medroxyprogesterone acetate (DMPA) is a widely used contraceptive method. HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is highly effective in reducing HIV acquisition in women. We sought to determine the impact of DMPA on F/TDF pharmacokinetics and pharmacodynamics.
METHODS
Twelve healthy premenopausal cisgender women were enrolled and each completed 4 sequential conditions: (1) baseline, (2) steady-state F/TDF alone, (3) steady-state F/TDF + DMPA, and (4) DMPA alone. Assessments included clinical, pharmacokinetic, viral infectivity (ex vivo challenge of peripheral blood mononuclear cells by X4- and R5-tropic green fluorescent protein pseudoviruses and cervical tissue by HIV BaL ), endocrine, immune cell phenotyping, and renal function.
RESULTS
Compared with baseline, F/TDF (± DMPA) significantly decreased both %R5- and X4-infected CD4 T cells and F/TDF + DMPA decreased cervical explant p24 (all P < 0.05). The %R5- and X4-infected CD4 T cells were higher during DMPA alone than during F/TDF periods and lower than baseline (not statistically significant). Cervical explant p24 fell between baseline and F/TDF values (not statistically significant). There were neither statistically significant differences in F/TDF pharmacokinetics, including total or renal clearance of either antiviral drug, nor changes in glomerular filtration rate with the addition of DMPA. There were few immune cell phenotypic differences across conditions.
CONCLUSIONS
F/TDF decreased HIV infection in both challenge assays, whereas DMPA alone did not enhance HIV infection in either challenge assay. DMPA did not alter F/TDF pharmacokinetics or renal function.
Topics: Female; Humans; Emtricitabine; Tenofovir; HIV Infections; Medroxyprogesterone Acetate; Leukocytes, Mononuclear
PubMed: 36305827
DOI: 10.1097/QAI.0000000000003113 -
Contraception Nov 2018To describe women's experiences with subcutaneous depot medroxyprogesterone acetate (DMPA-SC) to inform scale-up of self-administered DMPA-SC. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To describe women's experiences with subcutaneous depot medroxyprogesterone acetate (DMPA-SC) to inform scale-up of self-administered DMPA-SC.
STUDY DESIGN
We conducted a 12-month randomized controlled trial in Malawi to measure DMPA-SC continuation rates. A total of 731 women presenting at six Ministry of Health clinics or to community health workers (CHWs) in rural communities were randomized to receive DMPA-SC administered by a provider or be trained to self-inject DMPA-SC. Data collectors contacted women after the reinjection window at 3, 6 and 9 months to collect data on satisfaction and use; self-injectors were also queried about storage and disposal of DMPA-SC. We compared frequencies of injection experiences and satisfaction by study group and over time.
RESULTS
Ninety-two percent of women who self-injected felt it was easy to do the first time. Women in the self-administered group primarily gave themselves the injection versus having someone else inject them; stored DMPA-SC mostly in bags, often in ways to keep the product away from others; and properly disposed of DMPA-SC in pit latrines. Women in both groups used printed calendars to remember when to get/be given their next injection. Both groups reported high satisfaction with DMPA-SC.
CONCLUSIONS
Women in low-resource settings can be successfully trained by public sector CHWs and clinic-based providers to self-inject and to appropriately store and dispose of DMPA-SC. DMPA-SC and self-injection are acceptable and feasible in a low-resource setting.
IMPLICATIONS
Self-administered and provider-administrated DMPA-SC should be scaled up, and the lessons learned during our trial should be applied to future scale-up efforts.
Topics: Adult; Contraceptive Agents, Female; Female; Humans; Injections, Subcutaneous; Medroxyprogesterone Acetate; Patient Satisfaction; Self Administration
PubMed: 29758176
DOI: 10.1016/j.contraception.2018.04.018