Sexually transmitted infections among women randomised to depot medroxyprogesterone acetate, a copper intrauterine device or a levonorgestrel implant.

OBJECTIVES: Reproductive aged women are at risk of pregnancy and sexually transmitted infections (STI). Understanding drivers of STI acquisition, including any association with widely used contraceptives, could help us to reduce STI prevalence and comorbidities. We compared the risk of STI among women randomised to three contraceptive methods. METHODS: We conducted a secondary analysis to assess the risk of chlamydia and gonorrhoea in a clinical trial evaluating HIV risk among 7829 women aged 16-35 randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) or a levonorgestrel (LNG) implant. We estimated chlamydia and gonorrhoea prevalences by contraceptive group and prevalence ratios (PR) using log-binomial regression. RESULTS: At baseline, chlamydia and gonorrhoea prevalences were 18% and 5%, respectively. Final visit chlamydia prevalence did not differ significantly between DMPA-IM and copper IUD groups or between copper IUD and LNG implant groups. The DMPA-IM group had significantly lower risk of chlamydia compared with the LNG implant group (PR 0.83, 95% CI 0.72 to 0.95). Final visit gonorrhoea prevalence differed significantly only between the DMPA-IM and the copper IUD groups (PR 0.67, 95% CI 0.52 to 0.87). CONCLUSIONS: The findings suggest that chlamydia and gonorrhoea risk may vary with contraceptive method use. Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use.

The new contraceptive revolution: developing innovative products outside of industry†,‡.

A significant global unmet need for new contraceptive options for both women and men remains due to side effect profiles, medical concerns, and inconvenience of many currently available products. The pharmaceutical industry has largely abandoned early research and development for contraception and will not likely engage to bring new products to the market unless they have been significantly de-risked by showing promise in early phase clinical trials. This lack of interest by big pharma comes at a time when scientific and technological advances in biology and medicine are creating more opportunities than ever for the development of new and innovative drug products. Novel partnerships between the academic sector, small biotechnology companies, foundations, non-government organizations (NGOs), and the federal government could accelerate the development of new contraceptive products. We discuss the challenges and opportunities that we have encountered as an NGO with a mission to develop novel contraceptive products for low- and middle-income countries and how it differs from developing products for higher-income markets. We hope that our experiences and "lessons learned" will be of value to others as they proceed down the product development path, be it for female or male or for hormonal or nonhormonal contraceptives.

Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review.

OBJECTIVE: The purpose of this study was to determine whether interactions between non-rifamycin antibiotics and hormonal contraceptives result in decreased effectiveness or increased toxicity of either therapy. STUDY DESIGN: We searched MEDLINE, Embase, clinicaltrials.gov, and Cochrane libraries from database inception through June 2016. We included trials, cohort, case-control, and pharmacokinetic studies in any language that addressed pregnancy rates, pharmacodynamics, or pharmacokinetic outcomes when any hormonal contraceptive and non-rifamycin antibiotic were administered together vs apart. Of 7291 original records that were identified, 29 met criteria for inclusion. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors independently assessed study quality and risk of bias using the United States Preventive Services Task Force evidence grading system. Findings were tabulated by drug class. RESULTS: Study quality ranged from good to poor and addressed only oral contraceptive pills, emergency contraception pills, and the combined vaginal ring. Two studies demonstrated no difference in pregnancy rates in women who used oral contraceptives with and without non-rifamycin antibiotics. No differences in ovulation suppression or breakthrough bleeding were observed in any study that combined hormonal contraceptives with any antibiotic. No significant decreases in any progestin pharmacokinetic parameter occurred during co-administration with any antibiotic. Ethinyl estradiol area under the curve decreased when administered with dirithromycin, but no other drug. CONCLUSION: Evidence from clinical and pharmacokinetic outcomes studies does not support the existence of drug interactions between hormonal contraception and non-rifamycin antibiotics. Data are limited by low quantity and quality for some drug classes. Most women can expect no reduction in hormonal contraceptive effect with the concurrent use of non-rifamycin antibiotics.

Preexposure prophylaxis for HIV infection among African women.

BACKGROUND: Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others. METHODS: In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety. RESULTS: HIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04, P<0.001, and P=0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo group (3.0%, P=0.051). Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy. CONCLUSIONS: Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.).

Chikungunya virus host range E2 transmembrane deletion mutants induce protective immunity against challenge in C57BL/6J mice.

A vaccine against Chikungunya virus (ChikV), a reemerging pathogenic arbovirus, has been made by attenuating wild-type (WT) virus via truncation of the transmembrane domain (TMD) of E2 and selecting for host range (HR) mutants. Mice are a standard model system for ChikV disease and display the same symptoms of the disease seen in humans. Groups of mice were inoculated with one of three ChikV HR mutants to determine the ability of each mutant strain to elicit neutralizing antibody and protective immunity upon virus challenge. One mutant, ChikV TM17-2, fulfilled the criteria for a good vaccine candidate. It displayed no reactogenicity at the site of injection, no tissue disease in the foot/ankle and quadriceps, and no evidence of viral persistence in foot/ankle tissues 21 days after infection. Upon challenge with a highly pathogenic strain of ChikV, the mutant blocked viral replication in all tissues tested. This study identified a ChikV HR mutant that grows to high levels in insect cells but was restricted in the ability to assemble virus in mammalian cells in vitro. The study demonstrates that these HR strains are attenuated in the mammalian host and warrant further development as live-attenuated vaccine strains.

Drug-drug interactions between antiretrovirals and hormonal contraception: An updated systematic review.

OBJECTIVE: To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). STUDY DESIGN: Systematic review. RESULTS: We included 49 articles, with clinical, ARV, or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations. CONCLUSION: TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counseling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice. IMPLICATIONS: Most ARVs and HCs may be used safely and effectively together. Efavirenz-based ART requires careful counseling and data for possible interactions between HCs and new ARV classes are anticipated.

Menstrual cup use and intrauterine device expulsion in a copper intrauterine device randomized trial.

OBJECTIVE: To evaluate menstrual cup use and intrauterine device (IUD) expulsion. STUDY DESIGN: We performed a secondary analysis of a 3-year contraceptive efficacy trial comparing two copper 380 mm2 IUDs. Investigators randomized participants approximately 1:4 to the TCu380A or NTCu380-Mini IUD. Approximately 12 months after enrollment began, we advised participants against menstrual cup use due to observed IUD expulsions in cup users. We evaluated IUD expulsion (including spontaneous partial and complete expulsion and accidental self-removal) at 12 and 36 months. We used multivariable logistic regression to evaluate IUD expulsion by age, baseline menstrual volume, body mass index, IUD type, menstrual cup use, parity, and uterine length. RESULTS: This analysis included 1046 participants (203 TCu380A and 843 NTCu380-Mini), with 879 (84.0%) nulliparas. Through 12 and 36 months, expulsion occurred in 74 (7.1%, 95% CI 5.5-8.6%) and 133 (12.7%, 95% CI 10.7-14.7%) participants, respectively. Overall, 250 (23.9%) reported menstrual cup use. More menstrual cup users than non-users experienced expulsion through 12 months (32/203 [15.8%] vs. 42/843 [5.0%]) and 36 months (58/250 [23.2%] vs. 75/796 [9.4%]). Through 36 months, NTCu380-Mini menstrual cup users had higher expulsion odds, while TCu380A cup users did not. Menstrual cup users more frequently experienced accidental self-removal than non-users in participants using the TCu380A (3/53 [5.7%] vs. 0/150 [0.0%]) and the NTCu380-Mini (20/197 [10.2%] vs. 7/646 [1.1%]). In multivariable regression, we found increased odds of expulsion through 36 months in participants using menstrual cups with the NTCu380-Mini (aOR 3.13, 95% CI 1.16-8.46) and <25 years (aOR 1.59, 95% CI 1.07-2.34). CONCLUSIONS: We found higher odds of IUD expulsion with menstrual cup and concurrent NTCu380-Mini IUD use over 36 months of use, but not with concurrent TCu380A IUD use. Menstrual cup users experienced higher likelihood of accidental self-removal regardless of IUD type. IMPLICATIONS: Menstrual cup and NTCu380-Mini use may increase IUD expulsion risk and may increase accidental self-removal risk with TCu380A and NTCu380-Mini use. Clinicians should advise patients of these risks and consider warning patients using an IUD shaped like the NTCu380-Mini (Nova-T frames) of expulsion risk with menstrual cup use.

Spermicide used alone for contraception.

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.

Spermicide used alone for contraception.

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.

20 µg versus >20 µg estrogen combined oral contraceptives for contraception.

BACKGROUND: Concern about estrogen-related adverse effects has led to progressive reductions in the estrogen dose in combination oral contraceptives (COCs). However, reducing the amount of estrogen to improve safety could result in decreased contraceptive effectiveness and unacceptable changes in bleeding patterns. OBJECTIVES: To test the hypothesis that COCs containing ≤ 20 µg ethinyl estradiol (EE) perform similarly as those containing > 20 µg in terms of contraceptive effectiveness, bleeding patterns, discontinuation, and side effects. SEARCH METHODS: In July 2013, we searched CENTRAL, MEDLINE, and POPLINE, and examined references of potentially eligible trials. We also searched for recent clinical trials using ClinicalTrials.gov and ICTRP. No new trials met the inclusion criteria. Previous searches included EMBASE. For the initial review, we wrote to oral contraceptive manufacturers to identify trials. SELECTION CRITERIA: English-language reports of randomized controlled trials were eligible that compare a COC containing ≤ 20 µg EE with a COC containing > 20 µg EE. We excluded studies where the interventions were designed to be administered for less than three consecutive cycles or to be used primarily as treatment for non-contraceptive conditions. Trials had to report on contraceptive effectiveness, bleeding patterns, trial discontinuation due to bleeding-related reasons or other side effects, or side effects to be included in the review. DATA COLLECTION AND ANALYSIS: One author evaluated all titles and abstracts from literature searches to determine whether they met the inclusion criteria. Two authors independently extracted data from studies identified for inclusion. We wrote to the researchers when additional information was needed. Data were entered and analyzed with RevMan. MAIN RESULTS: No differences were found in contraceptive effectiveness for the 13 COC pairs for which this outcome was reported. Compared to the higher-estrogen pills, several COCs containing 20 µg EE resulted in higher rates of early trial discontinuation (overall and due to adverse events such as irregular bleeding) as well as increased risk of bleeding disturbances (both amenorrhea or infrequent bleeding and irregular, prolonged, frequent bleeding, or breakthrough bleeding or spotting). AUTHORS' CONCLUSIONS: While COCs containing 20 µg EE may be theoretically safer, this review did not focus on the rare events required to assess this hypothesis. Data from existing randomized controlled trials are inadequate to detect possible differences in contraceptive effectiveness. Low-dose estrogen COCs resulted in higher rates of bleeding pattern disruptions. However, most trials compared COCs containing different progestin types, and changes in bleeding patterns could be related to progestin type as well as estrogen dose. Higher follow-up rates are essential for meaningful interpretation of results.

Clinical outcomes of intrauterine device insertions by newly trained providers: The ECHO trial experience.

Objectives: To assess the rates of failed insertion, expulsion, and perforation when intrauterine device (IUD) insertions were done by newly trained clinicians, and to examine factors that may affect these outcomes. Study design: We evaluated skill-based outcomes following IUD insertion at 12 African sites in a secondary analysis of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial. Before trial initiation, we provided competency-based IUD training to clinicians and offered ongoing clinical support. We used Cox proportional hazards regression to examine factors associated with expulsion. Results: Among 2582 IUD acceptors who underwent first attempted IUD insertion, 141 experienced insertion failure (5.46%) and seven had uterine perforation (0.27%). Perforation was more common among breastfeeding women within three months postpartum (0.65%) compared with non-breastfeeding women (0.22%). We recorded 493 expulsions (15.5 per 100 person-years, 95% confidence interval [CI] 14.1─16.9): 383 partial and 110 complete. The risk of IUD expulsion was lower among women older than 24 years (aHR 0.63, 95% CI 0.50─0.78) and may be higher among nulliparous women. (aHR 1.65, 95% CI 0.97─2.82). Breastfeeding (aHR 0.94, 95% CI 0.72─1.22) had no significant effect on expulsion. IUD expulsion rate was highest during the first three months of the trial. Conclusions: IUD insertion failure and uterine perforation rates in our study were comparable to those reported in the literature. These results suggest that training, ongoing support, and opportunities to apply new skills were effective in ensuring good clinical outcomes for women receiving IUD insertion by newly trained providers. Implications: Data from this study support recommendations to program managers, policymakers, and clinicians that IUDs can be inserted safely in resource-constrained settings when providers receive appropriate training and support.

Prevalence and incidence of sexually transmitted infections among South African women initiating injectable and long-acting contraceptives.

BACKGROUND: South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). In 2017, there were an estimated 6 million new CT, 4.5 million NG and 71 000 Treponema pallidum infections among South African men and women of reproductive age. METHODS: We evaluated STI prevalence and incidence and associated risk factors in 162 women aged 18-33 years old, residing in eThekwini and Tshwane, South Africa who were part of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomised to use depot medroxyprogesterone acetate (n = 53), copper intrauterine device (n = 51), or levonorgestrel (n = 58) implant. Lateral vaginal wall swab samples were collected prior to contraceptive initiation and at months one and three following contraceptive initiation for STI testing. RESULTS: There were no significant differences in STI incidence and prevalence across contraceptive groups. At baseline, 40% had active STIs (CT, NG, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) or herpes simplex virus-2 shedding across all age groups- 18-21 years (46%), 22-25 years (42%) and 26-33 years (29%). The incidence of STIs during follow-up was exceptionally high (107.9/100 women-years [wy]), with younger women (18-21 years) more likely to acquire CT (75.9/100 wy) compared to 26-33 year olds (17.4/100 wy; p = 0.049). TV incidence was higher in the 26-33 year old group (82.7/100 wy) compared to the 18-21 year olds (8.4/100 wy; p = 0.01). CONCLUSIONS: Although the study participants received extensive counselling on the importance of condom use, this study highlights the high prevalence and incidence of STIs in South African women, especially amongst young women, emphasising the need for better STI screening and management strategies.

MIT CAACB Risk Assessment Case Study: Assessing Virus Cross-Contamination Risk between Two Simultaneous Processes in an Open Biomanufacturing Facility.

Some members of MIT's Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) previously published content on the "Quality Risk Management in the Context of Viral Contamination", which described tools, procedures, and methodologies for assessing and managing the risk of a potential virus contamination in cell culture processes. To address the growing industry interest in moving manufacturing toward open ballrooms with functionally closed systems and to demonstrate how the ideas of risk management can be leveraged to perform a risk assessment, CAACB conducted a case study exercise of these new manufacturing modalities. In the case study exercise, a cross-functional team composed of personnel from many of CAACB's industry membership collaboratively assessed the risks of viral cross-contamination between a human and non-human host cell system in an open manufacturing facility. This open manufacturing facility had no walls to provide architectural separation of two processes occurring simultaneously, specifically a recombinant protein perfusion cell culture process using the human cell line, HEK-293 (Process 1) and a downstream postviral filtration unit operation (Process 2) of a recombinant protein produced in CHO cells. This viral risk assessment focused on cross-contamination of the Process 2 filtration unit operation after the Process 1 perfusion bioreactor was contaminated with a virus that went undetected. The workflow for quality risk management that is recommended by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) was followed, which included identifying and mapping the manufacturing process, defining the risk question, risk evaluation, and risk control. The case study includes a completed Failure Mode and Effects Analysis (FMEA) to provide descriptions of the specific risks and corresponding recommended risk reduction actions.

Immediate start of hormonal contraceptives for contraception.

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.

Expectant care versus surgical treatment for miscarriage.

BACKGROUND: Miscarriage is a common complication of early pregnancy that can have both medical and psychological consequences such as depression and anxiety. The need for routine surgical evacuation with miscarriage has been questioned because of potential complications such as cervical trauma, uterine perforation, hemorrhage, or infection. OBJECTIVES: To compare the safety and effectiveness of expectant management versus surgical treatment for early pregnancy failure. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (9 February 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2011, Issue 4 of 4), PubMed (2005 to 11 January 2012), POPLINE (inception to 11 January 2012), LILACS (2005 to 11 January 2012) and reference lists of retrieved studies. SELECTION CRITERIA: Randomized trials comparing expectant care and surgical treatment (vacuum aspiration or dilation and curettage) for miscarriage were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial quality and extracted data. We contacted study authors for additional information. For dichotomous data, we calculated the Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI). For continuous data, we computed the mean difference (MD) and 95% CI. We entered additional data such as medians into 'Other data' tables. MAIN RESULTS: We included seven trials with 1521 participants in this review. The expectant-care group was more likely to have an incomplete miscarriage by two weeks (RR 3.98; 95% CI 2.94 to 5.38) or by six to eight weeks (RR 2.56; 95% CI 1.15 to 5.69). The need for unplanned surgical treatment was greater for the expectant-care group (RR 7.35; 95% CI 5.04 to 10.72). The mean percentage needing surgical management in the expectant-care group was 28%, while 4% of the surgical-treatment group needed additional surgery. The expectant-care group had more days of bleeding (MD 1.59; 95% CI 0.74 to 2.45). Further, more of the expectant-care group needed transfusion (RR 6.45; 95% CI 1.21 to 34.42). The mean percentage needing blood transfusion was 1.4% for expectant care compared with none for surgical management. Results were mixed for pain. Diagnosis of infection was similar for the two groups (RR 0.63; 95% CI 0.36 to 1.12), as were results for various psychological outcomes. Pregnancy data were limited. Costs were lower for the expectant-care group (MD -499.10; 95% CI -613.04 to -385.16; in UK pounds sterling). AUTHORS' CONCLUSIONS: Expectant management led to a higher risk of incomplete miscarriage, need for unplanned (or additional) surgical emptying of the uterus, bleeding and need for transfusion. Risk of infection and psychological outcomes were similar for both groups. Costs were lower for expectant management. Given the lack of clear superiority of either approach, the woman's preference should be important in decision making. Pharmacological ('medical') management has added choices for women and their clinicians and has been examined in other reviews.

Steroid hormones for contraception in men.

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.

Contraceptive method preference and reasons for contraceptive discontinuation among women randomized to intramuscular depot medroxyprogesterone acetate, a copper intrauterine device or a levonorgestrel implant: Findings from Durban, South Africa.

OBJECTIVES: The use of intrauterine devices (IUDs) and contraceptive implants in South Africa is low with limited data on patterns of use and reasons for discontinuation. We describe contraceptive preferences and reasons for discontinuation among women enrolled in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial from one trial site. STUDY DESIGN: ECHO, conducted between 2015 and 2018, enrolled and randomized sexually active women, aged 16 to 35, and desiring contraception, to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (copper-IUD) or a levonorgestrel (LNG) implant; follow-up was 12 to 18 months. We interviewed 829 women at the Durban, South Africa trial site at ECHO Trial exit to ascertain contraceptive preferences at randomization. Reasons for randomized contraceptive discontinuation were collected at ECHO Trial exit and 6 months later. Data were analyzed descriptively. RESULTS: At the final ECHO Trial visit, among women using their randomized contraceptive method (n = 757), 21% discontinued DMPA-IM, 20% discontinued LNG implant and 22% discontinued the copper-IUD. About a quarter from each group discontinued due to problems with bleeding. Among women continuing their randomized contraceptive at trial exit (n = 597), 25% discontinued DMPA-IM within 6 months of exiting the study, 8% discontinued LNG implant and 4% discontinued copper-IUD. A third of women reported wanting to be assigned DMPA-IM at randomization, 20% wanted the LNG implant and 18% the copper-IUD. CONCLUSIONS: Despite some women having preferences about which contraceptive they might be randomized to, discontinuation rates for all three methods at ECHO Trial exit and 6-month post-trial follow-up were low. IMPLICATIONS: Despite limited prior use of IUDs and implants among women enrolled in this study, and a desire by some women to not receive these methods at randomization, discontinuation rates remained low. The provision of quality contraceptive counselling and support may increase uptake and continued use of implants and IUDs.

Remediation of noxious wastewater using nanohybrid adsorbent for preventing water pollution.

Removal of toxic elements from wastewater effluent has got a lot of attention because of their severe negative effects on human and environmental health. In the past few years, rapid urbanization and industrial activities in developing countries have exacerbated the destruction of the environment. Most of the wastewater effluents are discharged untreated or inadequately treated, which has become a major concern due to its impact on sustainability and the environment. This is imperative to implement, innovative and resourceful wastewater treatment technologies requiring low investment. Among the various treatment technologies, cutting-edge processes in nano-material sciences have recently piqued the interest of scientists. Nanohybrid absorbents have the potential in improving wastewater treatment and increase water supply by utilizing unconventional water resources. Carbon nanotubes, titanium oxide, manganese oxide, activated carbon (AC), magnesium oxide, graphene, ferric oxides, and zinc oxide are examples of nano-adsorbents that are used to eliminate pollutants. This also demonstrated the effective removal of contaminants along with the harmful effects of chemicals, colorants, and metals found in wastewater. The present manuscript examines potential advances in nanotechnology in wastewater treatment for the prevention of water and soil pollution. This systematic review aims to highlight the importance of nanohybrid absorbents treatment technology for wastewater treatment and to explain how nanohybrid absorbents have the potential to revolutionize industrial pollution. There are also other published review articles on this topic but the present review covers an in-depth information on nano-adsorbents and their targeted contaminants.

Genital inflammatory status and the innate immune response to contraceptive initiation.

PROBLEM: Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence immune mediator changes in response to contraceptive initiation. METHODS: This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation. Women were grouped according to an overall baseline inflammatory profile. We evaluated modification of the relationships between contraceptives and immune mediators by baseline inflammation, demographic, and clinical factors. RESULTS: Overall, LNG implant and copper IUD initiation were associated with increases in inflammatory cytokines, while no changes were observed following DMPA-IM initiation. However, when stratifying by baseline inflammatory profile, women with low baseline inflammation in all groups experienced significant increases in inflammatory cytokines, while those with a high baseline inflammatory profile experienced no change or decreases in inflammatory cytokines. CONCLUSION: We conclude that pre-contraceptive initiation immune profile modifies the effect of contraceptives on the FGT innate immune response.