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Purpose of Review: Injectable contraception is a highly effective form of birth control that is globally popular. Recent research has focused on ways to make injectables such as depot medroxyprogesterone acetate (DMPA) more accessible and to improve the side-effect profile of injectables. This review will focus on new directions and approaches to the use of injectable contraception., Recent Findings: Research in the area of injectable contraception has focused on improving access for women through home or self-injection, and also task-shifting and community-based distribution in low-resource areas. Specific to DMPA, studies have focused on lowering the overall dose of medication while maintaining efficacy, and improving drug-delivery systems. More research into the association between DMPA and HIV is needed, and also the effects of administration of DMPA at the time of medication abortion., Summary: Injectable contraceptives are an important part of the global method mix of highly effective birth control. Improving the accessibility and side effect profile of commodities such as DMPA will make injectables even more valuable for women seeking effective contraception.

Background: Use of contraception lowers a woman's risk of experiencing an ectopic pregnancy. In the case of method failure, however, progestin-only contraceptives may be more likely to result in ectopic pregnancies than some other methods such as combined hormonal and barrier contraceptives., Objective: To describe ectopic pregnancy risk associated with use of implants and progestin-only injectable contraceptives through a systematic review of published studies., Data Sources: We searched electronic databases for articles in any language published through May 2015 describing studies of progestin-only injectables and implants. We also searched bibliographies and review articles for additional studies., Study Selection and Extraction: Studies that reported any pregnancies were included in the review. Independent data extraction was performed by two authors based on predefined data fields, and where possible, we calculated the proportion of pregnancies that were ectopic and the ectopic pregnancy incidence rate per 1000 woman-years., Results: Fifty-three studies of implants and 28 studies of injectables were identified; 79% reported pregnancy location. The proportion of ectopic pregnancy ranged from 0 to 100% with an incidence of 0-2.9 per 1000 woman-years in studies of marketed levonorgestrel implants. Studies of etonogestrel implants and the injectables, depot-medroxyprogesterone acetate and norethisterone enanthate, reported few ectopic pregnancies., Conclusion: Progestin-only contraceptive implants and injectables protect against ectopic pregnancy by being highly effective in preventing pregnancy overall; however, the absolute risk of ectopic pregnancy varies by type of progestin. Risk of ectopic pregnancy should not be a deterrent for use or provision of these methods., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: A longer-acting injectable contraceptive that lasts for 6 months would be a valuable addition to the contraceptive method mix and ideal for women who are interested in spacing births and/or uncertain about their future reproductive plans. Here we review past applications of drug delivery technologies to injectable contraceptives as well as recent advancements in sustained drug delivery technologies that hold promise for the development of a new longer-acting injectable contraceptive product., Study Design: A global landscape analysis was conducted, promising sustained drug delivery technologies, and research opportunities and partnerships were established with experts in the fields of contraception and drug delivery to identify new approaches in developing a longer-acting injectable contraceptive product., Results: The landscape analysis confirmed that a number of existing polymer systems, such as poly-lactic-co-glycolic acid and poly(epsilon-caprolactone), remain promising candidates for application to a longer-acting injectable product. Novel polymers and materials also hold promise for achieving longer release profiles and/or having other advantages over existing polymer systems, but products using these materials could potentially have longer roads to regulatory approval. Additionally, recent advancements in the manufacturing process of microspheres may benefit the development of a longer-acting injectable contraceptive., Conclusion: The design of any new injectable product must take into account the limitations of current injectable contraceptives and address concerns that women may have for a longer-acting product. FHI 360 is supporting several research collaborations for proof of concept of various drug delivery approaches for achieving longer-acting product that fits an established target product profile., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and acceptability of these vaginal medications. Spermicides contain an active ingredient (most commonly nonoxynol-9) and a formulation used to disperse the product, such as foam or vaginal suppository., Objectives: This review examined all known randomized controlled trials of a spermicide used alone for contraception., Search Methods: In August 2013, we searched the following computerized databases for randomized controlled trials of spermicides for contraception: CENTRAL, MEDLINE, POPLINE, LILACS, EMBASE, ClinicalTrials.gov, and ICTRP. For the initial review, we examined the reference lists of trials found as well as those of review articles and textbook chapters., Selection Criteria: We included any trial of a commercial product used alone for contraception. Each included trial must have provided sufficient information to determine pregnancy rates., Data Collection and Analysis: Two authors independently extracted information from the trials identified. We did not conduct a meta-analysis, since most trials had large losses to follow up. We entered the data into tables and presented the results descriptively., Main Results: We located reports from 14 trials for the initial review, but have not identified any new trials since then. In the largest trial to date, the gel (Advantage S) containing the lowest dose of nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy than were gels with higher doses of the same agent (100 mg and 150 mg). Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three different vehicles with 100 mg of nonoxynol-9 had similar efficacy. Interpretation of these figures is limited, since 39% of participants discontinued the method or were lost from the trial. Few important differences in efficacy emerged in other trials., Authors' Conclusions: The probability of pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg was inferior to two other products tested in the largest trial. Aside from this finding, personal characteristics and behavior of users may be more important than characteristics of the spermicide products in determining the probability of pregnancy. Gel was liked more than the film or vaginal suppository in the largest trial. Spermicide trials have the dual challenges of difficult recruitment and high discontinuation rates; the latter threatens trial validity.

Background: Worldwide, hormonal contraceptives are among the most popular reversible contraceptives. Despite their high theoretical effectiveness, typical use results in much lower effectiveness. In large part, this disparity reflects difficulties in adherence to the contraceptive regimen and low rates for long-term continuation., Objectives: The intent was to determine the effectiveness of ancillary counseling techniques to improve adherence to, and continuation of, hormonal methods of contraception., Search Methods: Through August 2013, we searched computerized databases for randomized controlled trials (RCTs) comparing client-provider interventions with standard family planning counseling. Sources included CENTRAL, MEDLINE, EMBASE, POPLINE, ClinicalTrials.gov and ICTRP. Earlier searches also included LILACS, PsycINFO, Dissertation Abstracts, African Index Medicus, and IMEMR., Selection Criteria: We included RCTs of an intensive counseling technique or other client-provider intervention compared to routine family planning counseling. Interventions included group motivation; structured, peer, or multi-component counseling; and intensive reminders of appointments or next dosing. Outcome measures were discontinuation, reasons for discontinuation, number of missed pills or on-time injections, and pregnancy., Data Collection and Analysis: One author evaluated the titles and abstracts from the searches to determine eligibility. Two authors extracted data from the included studies. We calculated the Mantel-Haenszel odds ratio (OR) for dichotomous outcomes. For continuous variables, the mean difference (MD) was computed; RevMan uses the inverse variance approach. For all analyses, 95% confidence intervals (CI) were also computed. Since the studies identified differed in both interventions and outcome measures, we did not conduct a meta-analysis., Main Results: Nine RCTs met our inclusion criteria. Five involved direct counseling; of those, two also provided multiple contacts by telephone. Four other trials provided intensive reminders, two of which also provided health education information. Three trials showed some benefit of the experimental intervention. In a counseling intervention, women who received repeated structured information about the injectable depot medroxyprogesterone acetate (DMPA) were less likely to discontinue the method by 12 months (OR 0.27; 95% CI 0.16 to 0.44) than women who had routine counseling. The intervention group was also less likely to discontinue due to menstrual disturbances (OR 0.20; 95% CI 0.11 to 0.37). Another trial showed a group with special counseling plus phone calls was more likely than the special-counseling group to report consistent use of oral contraceptives (OC) at 3 months (OR 1.41; 95% CI 1.06 to 1.87), though not at 12 months. The group with only special counseling did not differ significantly from those with standard care for any outcome. The third trial compared daily text-message reminders about OCs plus health information versus standard care. Women in the text-message group were more likely than the standard-care group to continue OC use by six months (OR 1.54; 95% CI 1.14 to 2.10). The text-message group was also more likely to avoid an interruption in OC use longer than seven days (OR 1.53; 95% CI 1.13 to 2.07)., Authors' Conclusions: Only three trials showed some benefit of strategies to improve adherence and continuation. However, several had small sample sizes and six had high losses to follow up. The overall quality of evidence was considered moderate. The intervention type and intensity varied greatly across the studies. A combination of intensive counseling and multiple contacts and reminders may be needed to improve adherence and acceptability of contraceptive use. High-quality RCTs with adequate power and well-designed interventions could help identify ways to improve adherence to, and continuation of, hormonal contraceptive methods.

Background: Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and acceptability of these vaginal medications. Spermicides contain an active ingredient (most commonly nonoxynol-9) and a formulation used to disperse the product, such as foam or vaginal suppository., Objectives: This review examined all known randomized controlled trials of a spermicide used alone for contraception., Search Methods: In August 2013, we searched the following computerized databases for randomized controlled trials of spermicides for contraception: CENTRAL, MEDLINE, POPLINE, LILACS, EMBASE, ClinicalTrials.gov, and ICTRP. For the initial review, we examined the reference lists of trials found as well as those of review articles and textbook chapters., Selection Criteria: We included any trial of a commercial product used alone for contraception. Each included trial must have provided sufficient information to determine pregnancy rates., Data Collection and Analysis: Two authors independently extracted information from the trials identified. We did not conduct a meta-analysis, since most trials had large losses to follow up. We entered the data into tables and presented the results descriptively., Main Results: We located reports from 14 trials for the initial review, but have not identified any new trials since then. In the largest trial to date, the gel (Advantage S) containing the lowest dose of nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy than were gels with higher doses of the same agent (100 mg and 150 mg). Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three different vehicles with 100 mg of nonoxynol-9 had similar efficacy. Interpretation of these figures is limited, since 39% of participants discontinued the method or were lost from the trial. Few important differences in efficacy emerged in other trials., Authors' Conclusions: The probability of pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg was inferior to two other products tested in the largest trial. Aside from this finding, personal characteristics and behavior of users may be more important than characteristics of the spermicide products in determining the probability of pregnancy. Gel was liked more than the film or vaginal suppository in the largest trial. Spermicide trials have the dual challenges of difficult recruitment and high discontinuation rates; the latter threatens trial validity.

Background: Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so 'add-back' therapy is needed., Objectives: To summarize all randomized controlled trials (RCTs) of male hormonal contraception., Search Methods: In January and February 2012, we searched the computerized databases CENTRAL, MEDLINE, POPLINE, and LILACS. We also searched for recent trials in ClinicalTrials.gov and ICTRP. Previous searches included EMBASE. We wrote to authors of identified trials to seek additional unpublished or published trials., Selection Criteria: We included all RCTs that compared a steroid hormone with another contraceptive. We excluded non-steroidal male contraceptives, such as gossypol. We included both placebo and active-regimen control groups., Data Collection and Analysis: The primary outcome measure was the absence of spermatozoa on semen examination, often called azoospermia. Data were insufficient to examine pregnancy rates and side effects., Main Results: We found 33 trials that met our inclusion criteria. The proportion of men who reportedly achieved azoospermia or had no detectable sperm varied widely. A few important differences emerged. 1) Levonorgestrel implants (160 μg daily) combined with injectable testosterone enanthate (TE) were more effective than levonorgestrel 125 µg daily combined with testosterone patches. 2) Levonorgestrel 500 μg daily improved the effectiveness of TE 100 mg injected weekly. 3) Levonorgestrel 250 μg daily improved the effectiveness of testosterone undecanoate (TU) 1000 mg injection plus TU 500 mg injected at 6 and 12 weeks. 4) Desogestrel 150 μg was less effective than desogestrel 300 μg (with testosterone pellets). 5) TU 500 mg was less likely to produce azoospermia than TU 1000 mg (with levonorgestrel implants). 6) Norethisterone enanthate 200 mg with TU 1000 mg led to more azoospermia when given every 8 weeks versus 12 weeks. 7) Four implants of 7-alpha-methyl-19-nortestosterone (MENT) were more effective than two MENT implants. We did not conduct any meta-analysis due to intervention differences.Several trials showed promising efficacy in percentages with azoospermia. Three examined desogestrel and testosterone preparations or etonogestrel and testosterone, and two examined levonorgestrel and testosterone., Authors' Conclusions: No male hormonal contraceptive is ready for clinical use. Most trials were small exploratory studies. Their power to detect important differences was limited and their results imprecise. In addition, assessment of azoospermia can vary by sensitivity of the method used. Future trials need more attention to the methodological requirements for RCTs. More trials with adequate power would also be helpful.

Background: High pregnancy rates undermine the conduct and interpretation of HIV prevention trials. We performed this analysis to identify baseline participant characteristics associated with increased risk of pregnancy in recent vaginal microbicide trials., Study Design: We analyzed the data from four recently completed Phase III trials of candidate microbicides for prevention of HIV infection. Cox proportional hazard models, stratified by site nested within study, were used to determine the baseline factors that predict pregnancy. Six thousand seven hundred forty-eight women contributed data for this analysis., Results: Pregnancies were detected in a total of 1826 (27.1%) women. The hazard of pregnancy was higher for women who had a history of pregnancy, were living with a man or reported more sexual acts not protected by condoms in the week prior to enrollment. The risk of pregnancy was lower in older participants; in women with more years of education; in women who reported more sexual partners at baseline interview; in women who reported using intrauterine contraception, implants, sterilization or injectables and in women who reported use of a condom during their last act of vaginal intercourse., Conclusions: Our data suggest that current use or acceptance of intrauterine contraception, implants, sterilization or injectables is the most effective approach to reduce pregnancy rates and might be a useful eligibility criterion in future HIV prevention trials., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Worldwide, hormonal contraceptives are among the most popular reversible contraceptives in current use. Despite their high theoretical effectiveness, typical use results in much lower effectiveness. In large part, this disparity reflects difficulties in adherence to the contraceptive regimen and low rates for long-term continuation., Objectives: To determine the effectiveness of ancillary techniques to improve adherence to, and continuation rates of, hormonal methods of contraception., Search Strategy: We searched computerized databases for randomized controlled trials (RCTs) comparing client-provider interventions with standard family planning counseling. Sources included CENTRAL, MEDLINE, EMBASE, POPLINE, LILACS, PsycINFO, ClinicalTrials.gov and ICTRP., Selection Criteria: We included randomized controlled trials (RCTs) of an intensive counseling technique or client-provider intervention versus routine family planning counseling. Interventions included group motivation; structured, peer, or multi-component counseling; and intensive reminders of appointments or next dosing. Outcome measures were discontinuation, reasons for discontinuation, number of missed pills and on-time injections, and pregnancy., Data Collection and Analysis: The primary author evaluated all titles and abstracts from the searches to determine eligibility. Two authors independently extracted data from the included studies. With RevMan, we calculated the odds ratio for all dichotomous outcomes and the mean difference for continuous data. The studies were so different that we did not conduct a meta-analysis., Main Results: We found eight RCTs; only one showed a statistically significant benefit of the experimental intervention. In that trial, women who received repeated, structured information about the injectable contraceptive depo-medroxyprogesterone acetate (DMPA) were less likely to have discontinued the method by 12 months (OR 0.27; 95% CI 0.16 to 0.44) than were women who had routine counseling. The intervention group was also less likely to discontinue due to menstrual disturbances (OR 0.20; 95% CI 0.11 to 0.37). In another study, the intervention group was less likely to discontinue due to dissatisfaction with the contraceptive method (OR 0.61; 95% CI 0.38 to 0.98), but overall continuation was not affected., Authors' Conclusions: Most studies to date have shown no benefit of strategies to improve adherence and continuation. These trials have important limitations, however. Three had small sample sizes, four had high losses to follow up, and the intervention and its intensity varied across the studies. High-quality research is a priority, since adherence and continuation are fundamentally important to the successful use of hormonal contraceptives.

Background: Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so 'add-back' therapy is needed., Objectives: To summarize all randomized controlled trials of male hormonal contraception., Search Strategy: We searched the computerized databases CENTRAL, MEDLINE, EMBASE, POPLINE, and LILACS (each from inception to March 2006) for randomized controlled trials of hormonal contraception in men. We wrote to authors of identified trials to seek unpublished or published trials that we might have missed., Selection Criteria: We included all randomized controlled trials in any language that compared a steroid hormone with another contraceptive. We excluded non-steroidal male contraceptives, such as gossypol. We included both placebo and active-regimen control groups. All trials identified included only healthy men with normal semen analyses., Data Collection and Analysis: Azoospermia (absence of spermatozoa on semen examination) was the primary outcome measure. Data were insufficient to examine pregnancy rates and side effects., Main Results: We found 30 trials that met our inclusion criteria. The proportion of men who achieved azoospermia varied widely in reports to date. A few important differences emerged from these trials: levonorgestrel implants combined with injectable testosterone enanthate (TE) were more effective than levonorgestrel 125 microg daily combined with testosterone patches; levonorgestrel 500 mug daily improved the effectiveness of TE 100 mg injected weekly; desogestrel 150 mug was less effective than desogestrel 300 mug (with testosterone pellets); testosterone undecanoate (TU) 500 mg was less likely to produce azoospermia than TU 1000 mg (with levonorgestrel implants); norethisterone enanthate 200 mg with TU 1000 mg led to more azoospermia when given every 8 weeks versus 12 weeks; four implants of 7-alpha-methyl-19-nortestosterone (MENT) were more effective than two MENT implants. Several trials showed promising efficacy in terms of percentages with azoospermia. Three examined desogestrel and testosterone preparations or etonogestrel (metabolite of desogestrel) and testosterone, and two examined levonorgestrel and testosterone., Authors' Conclusions: No male hormonal contraceptive is ready for clinical use. Most trials were small exploratory studies. As a result, their power to detect important differences was limited and their results imprecise. In addition, the definition of oligozoospermia has been imprecise or inconsistent. To avoid bias, future trials need more attention to the methodological requirements for randomized controlled trials. More trials with adequate power would also be helpful.

Background: Worldwide, hormonal contraceptives are among the most popular reversible contraceptives in current use. Despite their high theoretical effectiveness, typical use results in much lower effectiveness. In large part, this disparity reflects difficulties in adherence to the contraceptive regimen and low rates for long-term continuation., Objectives: To determine the effectiveness of ancillary techniques to improve adherence to, and continuation rates of, hormonal methods of contraception., Search Strategy: We searched computerized databases for randomized controlled trials (RCTs) comparing client-provider interventions with standard family planning counseling. Sources included CENTRAL, MEDLINE, EMBASE, POPLINE, LILACS, and PsycINFO., Selection Criteria: Randomized controlled trials (RCTs) of an intensive counseling technique or client-provider intervention versus routine family planning counseling. Interventions included group motivation; structured, peer, or multi-component counseling; and intensive reminders of appointments. Outcome measures were discontinuation, reasons for discontinuation, number of missed pills and on-time injections, and pregnancy., Data Collection and Analysis: The primary author evaluated all titles and abstracts from the searches to determine eligibility. Two authors independently extracted data from the included studies. With RevMan 4.2, we calculated the odds ratio for all dichotomous outcomes and the weighted mean difference for continuous data. The studies were so different that we could not conduct a meta-analysis., Main Results: We found six RCTs; only one showed a statistically significant benefit of the experimental intervention. In that trial, women who received repeated, structured information about the injectable contraceptive depo-medroxyprogesterone acetate (DMPA) were less likely to have discontinued the method by 12 months (OR 0.27; 95% CI 0.16 to 0.44) than were women who had routine counseling. The intervention group was also less likely to discontinue due to menstrual disturbances. In another study, the intervention group was less likely to discontinue due to dissatisfaction with the contraceptive method, but overall continuation was not affected., Authors' Conclusions: Most studies to date have shown no benefit of strategies to improve adherence and continuation. These trials have important limitations, however. Two had small sample sizes, several had high losses to follow-up, and the intervention and its intensity varied across the studies. High-quality research is a priority, since adherence and continuation are fundamentally important to the successful use of hormonal contraceptives.

Background: Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and acceptability of these vaginal medications. Spermicides contain an active ingredient (most commonly nonoxynol-9) and a formulation used to disperse the product, such as foam or vaginal suppository., Objectives: This review examined all known randomized controlled trials of a spermicide used alone for contraception., Search Strategy: We searched the following computerized databases from inception to July 2004 for randomized controlled trials of spermicides for contraception: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, LILACS, and EMBASE. We examined the reference list of each trial found as well as that of review articles and textbook chapters., Selection Criteria: We included any trial of a commercial product used alone for contraception. Each included trial must have provided sufficient information to determine pregnancy rates. We located reports from 14 trials., Data Collection and Analysis: Two reviewers independently extracted information from the trials identified. We did not conduct a meta-analysis, since most trials had large losses to follow-up. We entered the data into tables and presented the results descriptively., Main Results: In the largest trial to date, the gel (Advantage S) containing the lowest dose of nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy than were gels with higher doses of the same agent (100 mg and 150 mg). Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three different vehicles with 100 mg of nonoxynol-9 had similar efficacy. Interpretation of these figures is limited, since 39% of participants discontinued the method or were lost from the trial. Few important differences in efficacy emerged in other trials., Authors' Conclusions: The probability of pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg was inferior to two other products tested in the largest trial. Aside from this finding, personal characteristics and behavior of users may be more important than characteristics of the spermicide products in determining the probability of pregnancy. Gel was liked more than the film or vaginal suppository in the largest trial. Spermicide trials have the dual challenges of difficult recruitment and high discontinuation rates; the latter threatens trial validity.