1.1. Significance of IVDs in the Clinic
IVD test is a crucial component of clinical care that performs a diagnostic test on biological samples that have been taken from a living body, such as blood, urine, and tissue.1 Such tests are usually performed to determine or confirm the presence of disease in an individual. “In vitro” literally means “within the glass”, which indicates that the test was historically conducted in glass test tubes. In contrast, in vivo tests, literally “within the living”, are conducted within a whole, living organism including human body.2 IVD tests have received much public attention because of their distinct features in the medical profession. First, IVD tests do not interact with the human body directly, making such diagnosis accessible without invasive surgeries and thus saving a great deal of suffering. Second, the procedures of IVDs are performed on samples rather than human body, avoiding the possible biological safety problems on patients that often take place in the in vivo diagnostics. Third, an IVD test can quickly provide valuable information on a patient’s healthcare conditions. On the basis of the information, physicians or patients are able to make a timely decision for patient care or treatment. Fourth, the application of IVDs enables early diagnosis and makes treatment of serious diseases easier. Generally, the cost of early testing is much lower than that of the later on extensive treatment. Last, IVDs play a particularly vital role in remote settings for managing outbreaks of acute infectious diseases, where effective but simple diagnostic systems are highly desirable. These features make IVDs unique and of great importance among medical technologies.

Gold Nanoparticles for In Vitro Diagnostics

BACKGROUND: Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. OBJECTIVES: To determine which EC method following unprotected intercourse is the most effective safe and convenient to prevent pregnancy. SEARCH METHODS: The search included the Cochrane Controlled Trials Register Popline MEDLINE PubMed Biosis/EMBASE Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database (July 2011). Content experts and pharmaceutical companies were contacted. SELECTION CRITERIA: Randomised controlled trials and controlled clinical trials including women attending services for EC following a single act of unprotected intercourse were eligible. DATA COLLECTION AND ANALYSIS: Data on outcomes and trial characteristics were extracted in duplicate and independently by two review authors. Quality assessment was also done by two review authors independently. Meta-analysis results are expressed as risk ratio (RR) using a fixed-effect model with 95% confidence interval (CI). In the presence of statistically significant heterogeneity a random-effects model was applied. MAIN RESULTS: One hundred trials with 55666 women were included. Most trials were conducted in China (86/100). Meta-analysis indicated that mid-dose mifepristone (25-50 mg) (20 trials; RR 0.64; 95% CI 0.45 to 0.92) or low-dose mifepristone (< 25 mg) (11 trials; RR 0.70; 95% CI 0.50 to 0.97) were significantly more effective than levonorgestrel (LNG) but the significance was marginal when only high-quality studies were included (4 trials; RR 0.70; 95% CI 0.49 to 1.01). Low-dose mifepristone was less effective than mid-dose mifepristone (25 trials; RR 0.73; 95% CI 0.55 to 0.97). This difference was not statistically significant when only high-quality trials were considered (6 trials; RR 0.75; 95% CI 0.50 to 1.10). Ulipristal acetate (UPA) appeared more effective (2 trials; RR 0.63) than LNG at a marginal level (P = 0.09) within 72 hours of intercourse.Regarding effectiveness in relation to the time of administration women who took LNG within 72 hours of intercourse were significantly less likely to be pregnant than those who took it after 72 hours (4 trials; RR 0.51; 95% CI 0.31 to 0.84). It was not evident that the coitus-treatment time affected the effectiveness of mifepristone and UPA.Single-dose LNG (1.5 mg) showed similar effectiveness as the standard two-dose regimen (0.75 mg 12 h apart) (3 trials; RR 0.84; 95% CI 0.53 to 1.33). This conclusion was not modified by the time elapsed from intercourse to treatment administration.Mifepristone (all doses) (3 trials; RR 0.14; 95% CI 0.05 to 0.41) and LNG (5 trials; RR 0.54; 95% CI 0.36 to 0.80) were more effective than the Yuzpe regimen in preventing pregnancy. One trial compared gestrinone with mifepristone. No significant difference of effectiveness was identified in this trial (996 women; RR 0.75; 95% CI 0.32 to 1.76).All methods of EC were safe. Nausea and vomiting occurred with oestrogen-containing EC methods and progestogen and anti-progestogen methods caused changes in subsequent menses. LNG users were more likely to have a menstrual return before the expected date but UPA users were more likely to have a menstrual return after the expected date. Menstrual delay was the main adverse effect of mifepristone and seemed to be dose-related. AUTHORS CONCLUSIONS: Intermediate-dose mifepristone (25-50 mg) was superior to LNG and Yuzpe regimens. Mifepristone low dose (< 25 mg) may be more effective than LNG (0.75 mg two doses) but this was not conclusive. UPA may be more effective than LNG. LNG proved to be more effective than the Yuzpe regimen. The copper IUD was the most effective EC method and was the only EC method to provide ongoing contraception if left in situ.

Interventions for emergency contraception

Emergency contraception is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for emergency contraception. Information on the comparative efficacy safety and convenience of these methods is crucial for reproductive health care providers and the women they serve. The objectives were to determine which emergency contraceptive method following unprotected intercourse is the most effective safe and convenient to prevent pregnancy. The search included the Cochrane Controlled Trials Register Popline MEDLINE PubMed Biosis/Embase Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database (December 2006). Content experts and pharmaceutical companies were contacted. Randomised controlled trials and controlled clinical trials including women attending services for emergency contraception following a single act of unprotected intercourse were eligible. Data on outcomes and trial characteristics were extracted in duplicate and independently by two reviewers. Quality assessment was also done by two reviewers independently. Meta-analysis results are expressed as relative risk (RR) using a fixed-effects model with 95% confidence interval (CI). In the presence of statistically significant heterogeneity a random-effect model was applied. Eighty-one trials with 45842 women were included. Most trials were conducted in China (70/81). There were more pregnancies with levonorgestrel compared to mid-dose (25-50 mg) (15 trials RR: 2.01; 95% CI: 1.27 to 3.17) or low-dose mifepristone (less than 25 mg) (9 trials RR: 1.43; 95% CI: 1.02 to 2.01). Low-dose mifepristone was less effective than mid-dose (20 trials RR:0.67; 95% CI: 0.49 to 0.92) but this effect was no longer statistically significant when only high quality trials were considered (6 trials RR: 0.75; 95% CI: 0.50 to 1.10). Single dose levonorgestrel (1.5 mg) administration seemed to have similar effectiveness as the standard 12 hours apart split-dose (0.75 mg twice) (2 trials 3830 women; RR: 0.77 95% CI: 0.45 to 1.30). Levonorgestrel was more effective than the Yuzpe regimen in preventing pregnancy (2 trials RR: 0.51; 95% CI: 0.31 to 0.83). CDB-2914 (a second-generation progesterone receptor modulator) may be as effective as levonorgestrel (1 trial 1549 women; RR:1.89; 95% CI: 0.75 to 4.64) but the conficence interval is wide and the result compatible with higher or lower effectiveness. Delay in the onset of subsequent menses was the main unwanted effect of mifepristone and seemed to be dose-related. Mifepristone middle dose (25-50 mg) was superior to other hormonal regimens. Mifepristone low dose (less than 25 mg) could be more effective than levonorgestrel 0.75 mg (two doses) but this was not conclusive. Levonorgestrel proved more effective than the Yuzpe regimen. The copper IUD was another effective emergency contraceptive that can provide ongoing contraception. (authors)

Interventions for emergency contraception (Review).

Background
Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins.

Objectives
To compare different medical methods for first trimester abortion.

Search methods
The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted.

Selection criteria
Types of studies 
Randomised controlled trials comparing different medical methods for abortion during first trimester (e.g. single drug, combination) were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant during the first trimester, undergoing medical abortion were the participants. The outcomes were mortality, failure to achieve complete abortion, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the procedure.

Data collection and analysis
Two reviewers independently selected trials for inclusion from the results of the search strategy described previously.The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. Data were processed using Revman software.

Main results
Fifty-eight trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. Sublingual and buccal routes were similarly effective compared to the vaginal route, but had higher rates of side effects. 2) Mifepristone alone is less effective when compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Five trials compared prostaglandin alone to the combined regimen (mifepristone/prostaglandin). All but one reported higher effectiveness with the combined regimen. The results of these studies could not be combined but the RR of failure with prostaglandin alone is reportedly between 1.4 to 3.75 with the 95% confidence intervals indicating statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference in effectiveness with use of a divided dose compared to a single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin demonstrates similar rates of failure to complete abortion when comparing intramuscular to oral methotrexate administration (RR 2.04, 95% CI 0.51 to 8.07). Similarly, day 3 vs. day 5 administration of prostaglandin following methotrexate administration showed no significant differences (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs. methotrexate and no statistically significant differences were observed in effectiveness between the groups.

Authors' conclusions
Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Vaginal misoprostol is more effective than oral administration, and has less side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all trials were conducted in settings with good access to emergency services, which may limit the generalizability of these results.

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Medical methods for first trimester abortion.

Background Improvements in vitrification now make frozen embryo transfers (FETs) a viable alternative to fresh embryo transfer, with reports from observational studies and randomized controlled trials suggesting that: (i) the endometrium in stimulated cycles is not optimally prepared for implantation; (ii) pregnancy rates are increased following FET and (iii) perinatal outcomes are less affected after FET. Methods This review integrates and discusses the available clinical and scientific evidence supporting embryo transfer in a natural cycle. Results Laboratory-based studies demonstrate morphological and molecular changes to the endometrium and reduced responsiveness of the endometrium to hCG, resulting from controlled ovarian stimulation. The literature demonstrates reduced endometrial receptivity in controlled ovarian stimulation cycles and supports the clinical observations that FET reduces the risk of ovarian hyperstimulation syndrome and improves outcomes for both the mother and baby. Conclusions This review provides the basis for an evidence-based approach towards changes in routine IVF, which may ultimately result in higher delivery rates of healthier term babies.

Fresh versus frozen embryo transfer: backing clinical decisions with scientific and clinical evidence

Emergency contraception: a review of the programmatic and social science literature.

Mifepristone and misoprostol compared with misoprostol alone for second-trimester abortion: a randomized controlled trial.

The role of emergency contraception.

Oral antihypertensive regimens (nifedipine retard, labetalol, and methyldopa) for management of severe hypertension in pregnancy: an open-label, randomised controlled trial.

Tara Shochet

Papers

Emergency contraception: a review of the programmatic and social science literature.

Mifepristone and misoprostol compared with misoprostol alone for second-trimester abortion: a randomized controlled trial.

The role of emergency contraception.

Oral antihypertensive regimens (nifedipine retard, labetalol, and methyldopa) for management of severe hypertension in pregnancy: an open-label, randomised controlled trial.

Modifying the Yuzpe regimen of emergency contraception: a multicenter randomized controlled trial.