The World Health Organization includes oral emergency contraception (EC) in the list of essential medicines. Ulipristal acetate (UPA) and levonorgestrel (LNG) are the recommended oral methods. UPA has superior efficacy and a comparable side effect profile compared with LNG. Both work by inhibiting or delaying ovulation, so that sperm present in the reproductive tract will have lost their fertilising ability by the time the oocyte is eventually released. Neither LNG nor UPA at the EC doses have significant effects on the endometrium and are unable to prevent implantation. Mifepristone can also be used for EC but its availability is limited to few countries. LNG is less effective in women with a body mass index over 26 kg/m2 or weight over 70 kg. Hormonal contraception can be quickstarted immediately following LNG, or five days following UPA. LNG-releasing intrauterine devices and cyclo-oxygenase inhibitors are promising options for EC to be further studied.

A comprehensive profile of danazol describing the nomenclatures, formulae, elemental composition, appearance, uses and applications is presented. The profile contains the method which was utilized for the preparation of the drug substance and its respective scheme is outlined. The physical characteristics of the drug including the solubility, X-ray powder diffraction pattern, differential scanning calorimetry, thermal behavior and spectroscopic studies are described. The methods which were used for the analysis of the drug substance in bulk drug and/or in pharmaceutical formulations including the compendial, spectrophotometric, electrochemical and the chromatographic methods are reported. The stability, toxicity, pharmacokinetics, bioavailability, drug evaluation and monitoring, comparisons, pharmacology, in addition to several compiled reviews on the drug substance which were involved. Finally, two hundred and seventy-nine references are listed at the end of this profile.

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. This is an update of a review previously published in 2009 and 2012.

To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.

In February 2017 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database. We also searched ICTRP and ClinicalTrials.gov as well as contacting content experts and pharmaceutical companies, and searching reference lists of appropriate papers.

Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible.

We used standard methodological procedures recommended by Cochrane. The primary review outcome was observed number of pregnancies. Side effects and changes of menses were secondary outcomes.

We included 115 trials with 60,479 women in this review. The quality of the evidence for the primary outcome ranged from moderate to high, and for other outcomes ranged from very low to high. The main limitations were risk of bias (associated with poor reporting of methods), imprecision and inconsistency.Comparative effectiveness of different emergency contraceptive pills (ECP)Levonorgestrel was associated with fewer pregnancies than Yuzpe (estradiol-levonorgestrel combination) (RR 0.57, 95% CI 0.39 to 0.84, 6 RCTs, n = 4750, I2 = 23%, high-quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000.Mifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I2 = 0%, high-quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000.Both low-dose mifepristone (less than 25 mg) and mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I2 = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I2 = 0%, moderate-quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low-dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1000.Ulipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I2 = 0%, high-quality evidence).Comparative effectiveness of different ECP dosesIt was unclear whether there was any difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I2 = 0%, moderate-quality evidence).Mid-dose mifepristone was associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I2 = 0%, high-quality evidence).Comparative effectiveness of Cu-IUD versus mifepristoneThere was no conclusive evidence of a difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence).Adverse effectsNausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I2 = 59%, moderate-quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I2 = 0%, high-quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I2 = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I2 = 78%, moderate-quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I2 = 0%, high-quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu-IUD versus no events in 190 women using mifepristone, low-quality evidence).

Levonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid-dose (25 mg to 50 mg) and low-dose mifepristone(less than 25 mg) were probably more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25 mg) was less effective than mid-dose mifepristone. UPA may be more effective than levonorgestrel.Levonorgestrel users had fewer side effects than Yuzpe users, and appeared to be more likely to have a menstrual return before the expected date. UPA users were probably more likely to have a menstrual return after the expected date. Menstrual delay was probably the main adverse effect of mifepristone and seemed to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than ECPs.

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. This is an update of a review previously published in 2009 and 2012.

To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.

In February 2017 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database. We also searched ICTRP and ClinicalTrials.gov as well as contacting content experts and pharmaceutical companies, and searching reference lists of appropriate papers.

Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible.

We used standard methodological procedures recommended by Cochrane. The primary review outcome was observed number of pregnancies. Side effects and changes of menses were secondary outcomes.

We included 115 trials with 60,479 women in this review. The quality of the evidence for the primary outcome ranged from moderate to high, and for other outcomes ranged from very low to high. The main limitations were risk of bias (associated with poor reporting of methods), imprecision and inconsistency. Comparative effectiveness of different emergency contraceptive pills (ECP)Levonorgestrel was associated with fewer pregnancies than Yuzpe (estradiol-levonorgestrel combination) (RR 0.57, 95% CI 0.39 to 0.84, 6 RCTs, n = 4750, I2 = 23%, high-quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000.Mifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I2 = 0%, high-quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000.Both low-dose mifepristone (less than 25 mg) and mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I2 = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I2 = 0%, moderate-quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low-dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1000.Ulipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I2 = 0%, high-quality evidence). Comparative effectiveness of different ECP dosesIt was unclear whether there was any difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I2 = 0%, moderate-quality evidence).Mid-dose mifepristone was associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I2 = 0%, high-quality evidence). Comparative effectiveness of Cu-IUD versus mifepristoneThere was no conclusive evidence of a difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence). Adverse effectsNausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I2 = 59%, moderate-quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I2 = 0%, high-quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I2 = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I2 = 78%, moderate-quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I2 = 0%, high-quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu-IUD versus no events in 190 women using mifepristone, low-quality evidence).

Levonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid-dose (25 mg to 50 mg) and low-dose mifepristone(less than 25 mg) were probably more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25 mg) was less effective than mid-dose mifepristone. UPA was more effective than levonorgestrel.Levonorgestrel users had fewer side effects than Yuzpe users, and appeared to be more likely to have a menstrual return before the expected date. UPA users were probably more likely to have a menstrual return after the expected date. Menstrual delay was probably the main adverse effect of mifepristone and seemed to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than ECPs.

Emergency contraception (EC) is a way to significantly reduce the chance of becoming pregnant after an episode of unprotected intercourse. Considerable data support the safety of all available and emerging options for EC. Areas covered: This review presents a comprehensive summary of the literature regarding the safety of EC as well as directions for further study. PubMed was searched for all relevant studies published prior to June 2017. Expertopinion: All available methods of EC (i.e., ulipristal acetate pills, levonorgestrel pills, and the copper-IUD), carry only mild side effects and serious adverse events are essentially unknown. The copper IUD has the highest efficacy of EC methods. Given the excellent safety profiles of mifepristone and the levonorgestrel IUD, research is ongoing related to use of these products for EC.

The World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) provide recommendations for use of emergency contraceptive pills (ECPs), including levonorgestrel (LNG) and combined oral contraceptives (COCs). A new ECP formulation, ulipristal acetate (UPA), is now available worldwide. To determine whether LNG, UPA or COC (Yuzpe) ECPs are safe for women with certain characteristics or medical conditions, we searched the PubMed and Cochrane databases for articles published from date of inception until May 2015 pertaining to the safety of LNG, UPA or Yuzpe ECP use. For direct evidence, we considered studies that looked at safety outcomes among women with certain medical conditions or characteristics taking ECPs compared with women not taking ECPs. For indirect evidence, we considered studies that reported pharmacokinetic (PK) data for ECP use among women with certain medical conditions or characteristics and studies that reported safety outcomes among healthy women taking ECPs. Five studies provided direct evidence; of these five studies, four examined LNG or Yuzpe use among pregnant or breastfeeding women, and one reported risk of ectopic pregnancy among women repeatedly using LNG ECPs. Poor pregnancy outcomes were rare among pregnant women who used LNG or Yuzpe ECPs during the conception cycle or early pregnancy. Breastfeeding outcomes did not differ between women exposed to LNG ECP and those unexposed, and there was no increased risk of ectopic pregnancy versus intrauterine pregnancy after repeated use of LNG ECPs compared with nonuse. Forty-five studies provided indirect evidence. One PK study demonstrated that LNG passes into breastmilk but in minimal quantities. In addition, nine studies examined pregnancy outcomes following ECP failure among healthy women, and 35 articles reported adverse events. Studies suggest that serious adverse events are rare among women taking any of these ECP formulations.

Evidence on safety of ECPs among women with characteristics or medical conditions listed within WHO and CDC family planning guidance is limited. However, both direct and indirect evidence for our study question did not suggest any special safety concerns for the use of ECPs among women with particular medical conditions or personal characteristics, such as pregnancy, lactation or frequent ECP use.

The main goal of this study was to assess worldwide research activity in emergency contraception (EC) using bibliometric indicators.

Data in SciVerse Scopus were searched for documents pertaining to emergency contraception. Data obtained were then exported to Microsoft Excel and analyzed using Statistical Package for Social Sciences.

A total of 2142 documents were published about EC worldwide. Documents were written in 27 different languages and were published from 78 countries. Publications in EC started on late 1960s. Total number of citations for published EC documents was 30154 while median citation per document was six. The h-index of the retrieved documents was 58. The leading country in EC research was United States of America with a total of 559 documents (26.10%). One hundred and ninety five (9.10%) documents were published in Contraception journal. The leading institution in EC research and publications was Princeton University (50; 2.33%) followed by University of California, San Francisco (34; 1.59%).

The present data revealed that there is a worldwide increasing interest in EC research. Willingness of health policy makers to make EC accessible to the public will determine the future of EC research activity and future of EC as a contraceptive method.

We aimed to compare acceptability of Levonorgestrel with the Yuzpe regimen among Iranian women based on their side-effects and resulting changes in the amount and pattern of menses.

Five hundred twenty nine participants aged 15-49 having regular menses and one act of unprotected intercourse within 72 h were included in the double-blind, controlled trial in 2006-2007 and randomly assigned into LNG (n=263) and HD (n=266) groups, receiving Levonorgestrel 0.75 mg given 12 h apart and ethinyl estradiol 100 μg plus 0.5 mg Levonorgestrel 0.5 mg repeated after 12 h, respectively.

The participants receiving Levonorgestrel experienced significantly lower side-effects in the case of nausea, vomiting, and dizziness (P<0.05). The changes occurred in the amount and pattern of menses were the same for both groups (P>0.05). No significant difference was observed between the efficiencies of the treatments.

Significantly lower side-effects of Levonorgestrel can be considered as greater acceptability and translated to higher efficiency.

Emergency post-coital contraception (EC) is an effective method of preventing pregnancy when used appropriately. EC has been available since the 1970s, and its availability and use have become widespread. Options for EC are broad and include the copper intrauterine device (IUD) and emergency contraceptive pills such as levonorgestrel, ulipristal acetate, combined oral contraceptive pills (Yuzpe method), and less commonly, mifepristone. Some options are available over-the-counter, while others require provider prescription or placement. There are no absolute contraindications to the use of emergency contraceptive pills, with the exception of ulipristal acetate and mifepristone. This article reviews the mechanisms of action, efficacy, safety, side effects, clinical considerations, and patient preferences with respect to EC usage. The decision of which regimen to use is influenced by local availability, cost, and patient preference.

This review will focus on the available methods for emergency contraception (EC), efficacy, side effects and mechanisms of action. Copper intrauterine device (IUD) has been shown to be the most effective method for EC which can be continually used for regular contraception. However, this possibility is seldom used and may be little known. Among the hormonal EC methods 1.5 mg levonorgestrel is the most widely used EC pill while the more recently developed Ulipristal acetate (UPA) has been shown to be the most effective option. This is probably due to a more pronounced prevention of follicular rupture compared with other hormonal EC methods. Knowledge is needed to better advise lactating women and obese women on optimal EC method. Furthermore a possible interaction of UPA with regular hormonal contraception and possibilities for "bridging" from EC to regular contraception needs to be explored. To increase efficacy future studies should focus on EC methods that target the endometrium.

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.

To determine which EC 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 (July 2011). Content experts and pharmaceutical companies were contacted.

Randomised controlled trials and controlled clinical trials including women attending services for EC following a single act of unprotected intercourse were eligible.

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.

One hundred trials with 55,666 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.

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.

Selective progesterone receptor modulators (SPRMs) have been developed since the late 70s when mifepristone was first described. They act through nuclear progesterone receptors and can have agonist or mixed agonist antagonist actions depending on the cell and tissue. Mifepristone has unique major antagonist properties allowing its use for pregnancy termination. Ulipristal acetate has been marketed in 2009 for emergency contraception and has been recently approved for preoperative myoma treatment. Further perspectives for SPRMs use include long term estrogen free contraception, endometriosis treatment. However long term applications will be possible only after confirmation of endometrial safety.

To evaluate the existing data to estimate the rate of ectopic pregnancy among emergency contraceptive pill treatment failures.

Our initial reference list was generated from a 2008 Cochrane review of emergency contraception. In August 2009, we searched Biosys Previews, the Cochrane Database of Systematic Reviews, Medline, Global Health Database, Health Source: Popline, and Wanfang Data (a Chinese database).

This study included data from 136 studies, which followed a defined population of women treated one time with emergency contraceptive pills (either mifepristone or levonorgestrel) and in which the number and location of pregnancies were ascertained.

Data from each article were abstracted independently by two reviewers. In the studies of mifepristone, 3 of 494 (0.6%) pregnancies were ectopic; in the levonorgestrel studies, 3 of 307 (1%) were ectopic.

The rate of ectopic pregnancy when treatment with emergency contraceptive pills fails does not exceed the rate observed in the general population. Because emergency contraceptive pills are effective in lowering the risk of pregnancy, their use will reduce the chance that an act of intercourse will result in ectopic pregnancy.

III.

This survey was conducted to determine the knowledge, and prescribing attitudes of emergency contraception among healthcare professionals in Ibadan, Nigeria. A questionnaire was administered to 735 health care professionals in selected healthcare facilities in Ibadan. These facilities were randomly selected as part of an ongoing programme designed to introduce emergency contraceptive pills (ECPs) as a clinic based method of family planning in service delivery outlets in the city. The response rate was 87.5%, comprising nurses (59.3%) and physicians (25.0%). Others were pharmacists, social workers and administrators. The results revealed that healthcare professionals' knowledge of various methods that can be used emergency contraception is very low. Less than half (35.1%) of the respondents were aware that combined oestrogen/progestin or progestin-only pills can be used as emergency contraception. Similarly, only 26.7% and 13.3% of the respondents were aware that intrauterine contraceptive devices and mifepristone respectively could be used as emergency contraception. While only 16.3% of the respondents had ever prescribed the combined pills as emergency contraception, 10.9% and 8.2% had prescribed progestin-only pills and intrauterine contraceptive devices for this purpose in the past. Circumstances under which emergency contraception could be used vary among the respondents but 71.4% and 64.4% were of the opinion that condom breakage and sexual assault would be appropriate indications for its use. Two main sources, hospitals (68.4%) and pharmacies (8.8%) were identified by participants. It is apparent that one of the major barriers to frequent use of emergency contraception in Ibadan is the lack of awareness of its use by healthcare professionals. Therefore, there is an urgent need to educate these practitioners and include emergency contraception in the family planning curriculum of nursing and medical schools.

This study was conducted to assess the knowledge of family medicine providers and their attitudes towards emergency contraception in a teaching hospital in Karachi, Pakistan. A 21-item questionnaire containing the demographic profile of respondents and questions concerning knowledge of and attitudes towards emergency contraception was distributed among participants. In total, 45 interviews were conducted, with a response rate of 100%, with faculty physicians (33%), residents (27%), medical officers (40%), 36% male and 64% female physicians; of them, the majority (64%) were married. Although the large majority (71%) of the respondents reported considerable familiarity with emergency contraception, objective assessment revealed deficiencies in their knowledge. About 38% of the participants incorrectly chose menstrual irregularity as the most common side-effect of progestin-only emergency contraception pills, and only 33% answered that emergency contraception was not an abortifacient while 42% were unsure. Forty percent of the physicians prescribed emergency contraception in the past. The large majority (71%) of the physicians were familiar with emergency contraception, yet deficiencies in knowledge inaccuracies were identified. Barriers to its use were identified as 'it will promote promiscuity' (31%), religious/ethical reasons (27%), liability (40%), teratogenicity (44%), and inexperience (40%). Overall attitudes regarding emergency contraception were positive; however, most (82%) physicians were unsatisfied with their current knowledge of emergency contraception, and there was a discrepancy between perceptions of physicians and actual knowledge. Interventions providing education to family physicians regarding emergency contraception is strongly recommended.

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.

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 45,842 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 (<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 confidence 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 (<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.

This study explored the potential of beta-cyclodextrin to improve the aqueous solubility and dissolution of danazol, investigated a simple and less expensive method for preparation of a danazol-beta-cyclodextrin binary system, and explored the potential application of a danazol-beta-cyclodextrin binary system as a single-dose emergency contraceptive. Phase solubility analysis indicated formation of a first-order soluble complex with stability constant 972.03 M(-1), while Job's plot affirmed 1:1 stoichiometry. The hyperchromic shift in the UV-Vis spectrum of danazol in the presence of beta-cyclodextrin indicated solubilization capability of beta-cyclodextrin for danazol. The extrinsic Cotton effect with a negative peak at 280.7 nm confirmed the inclusion of danazol in the asymmetric locus of beta-cyclodextrin. (1)H-nuclear magnetic resonance analysis suggested that the protons of the steroidal skeleton of danazol display favorable interactions with the beta-cyclodextrin cavity. The danazol-beta-cyclodextrin binary system was prepared by kneading, solution, freeze-drying, and milling methods. The extent of the enhancement of dissolution rate was found to be dependent on the preparation method. Dissolution studies showed a similar relative dissolution rate (2.85) of the danazol-beta-cyclodextrin binary system prepared by the freeze-drying and milling (in the presence of 13% moisture) methods. In a mouse model, the danazol-beta-cyclodextrin binary system at 51.2 mg/kg (equivalent to a 400-mg human dose) showed 100% inhibition of implantation when given postcoitally. Moreover, the danazol-beta-cyclodextrin binary system is safe up to 2000 mg/kg in the mouse (15.52 g/70 kg human) as a single oral dose. Thus, the danazol-beta-cyclodextrin binary system could serve as a new therapeutic application: an oral emergency contraceptive at a physiologically acceptable single dose.

Mifepristone is a progesterone antagonist that has been studied for a number of clinical applications. It is a well-known abortifacient that is effective for both first- and second-trimester medical abortion when used with a prostaglandin analog. It is also an effective cervical priming agent that can be used to soften the cervix before surgical evacuation. Its clinical efficacy as an emergency contraception has been proven. Other applications including treatment for fibroids, endometriosis and various cancers have been explored. However, its association with abortion limits the applications of mifepristone in many of these areas.

Mifepristone is a potent glucocorticoid and progesterone receptor antagonist. The pathophysiology of a number of neuropsychiatric disorders implicates abnormalities in glucocorticoid function. These include mood disorders such as psychotic major depression and bipolar depression. In addition, cognitive disorders such as Alzheimer's disease might also be partially mediated by abnormalities in the hypothalamic-pituitary-adrenal axis. Preliminary studies suggest that mifepristone might have a role in the treatment of a number of neuropsychiatric disorders.

This is an analysis of the Australian component of a large World Health Organization multicentre dose-finding study of mifepristone for emergency contraception and the first clinical study of this controversial drug in Australia.

To compare the effectiveness and side-effects of three single doses of mifepristone taken within 120 h after unprotected coitus as emergency contraception.

Double-blind, randomised controlled trial.

One hundred fifty healthy women with regular menstrual cycles who requested emergency contraception. Participants were allocated randomly to one of the three doses (10, 50 and 600 mg). The primary outcome was confirmed pregnancy, and secondary outcome measures included side-effects and delay in the onset of the next menses.

Pregnancy rates for mifepristone 10, 50 and 600 mg were 2.0, 2.1 and 2.1%, respectively, with no significant difference between groups. No major side-effects occurred, except an unpredictable delay in the onset of the next menses. Mifepristone 600 mg caused a significantly longer delay in the onset of the next menses than either the 10 or the 50 mg dose.

Lowering the dose of mifepristone from 600 to 10 mg did not significantly impair its effectiveness as an emergency contraceptive, and caused less delay in the onset of the next menses. Therefore, a dose as low as 10 mg may be preferable to 600 mg for emergency contraception. This is very much lower than the dose required to terminate a pregnancy.

Teen birth rates in the United States have declined during the last decade but remain much higher than rates in other developed countries. Reduction of unintended pregnancy during adolescence and the associated negative consequences of early pregnancy and early childbearing remain public health concerns. Emergency contraception has the potential to significantly reduce teen-pregnancy rates. This policy statement provides pediatricians with a review of emergency contraception, including a definition of emergency contraception, formulations and potential adverse effects, efficacy and mechanisms of action, typical use, and safety issues, including contraindications. This review includes teens' and young adults' reported knowledge and attitudes about hormonal emergency contraception and issues of access and availability. The American Academy of Pediatrics, as well as other professional organizations, supports over-the-counter availability of emergency contraception. In previous publications, the American Academy of Pediatrics has addressed the issues of adolescent pregnancy and other methods of contraception.

To determine pregnancy and neonatal outcome after the failure of levonorgestrel as an emergency contraceptive.

A retrospective observational cohort study.

Telephone consultations concerning reproductive risk factors conducted by Telefono Rosso-Teratology Information Service, Catholic University of Sacred Heart, Rome, Italy.

Women exposed to levonorgestrel (36 cases) compared with a control group (80 cases).

Teratological counseling.

The rate of congenital anomalies, the prepartum or peripartum complications, and the pregnancy outcomes.

Twenty-five exposed newborns with length and weight identical to that of the control group were shown to be without increased risk of congenital malformation. No statistical differences were observed in terms of spontaneous or legal abortion and pregnancy and neonatal complications, and there was no ectopic pregnancy in either group.

Although the sample size was small, in our experience, the failure of levonorgestrel as an emergency contraceptive was not associated with an increased risk of major congenital malformations, prepartum or peripartum complications, or an adverse pregnancy outcome.

Since the discovery of the antiprogestin mifepristone, hundreds of similar compounds have been synthesized, which can be grouped in a large family of progesterone receptor ligands. This family includes pure agonists such as progesterone itself or progestins and, at the other end of the biological spectrum, pure progesterone receptor antagonists (PA). Selective progesterone receptor modulators (SPRM) have mixed agonist-antagonist properties, and occupy an intermediate position of the spectrum. These compounds have numerous applications in female health care. Mifepristone is used to terminate pregnancy, and as such is commercially available in many countries. The negative abortion-related image of mifepristone has clearly limited the involvement of the major pharmaceutical companies in the development of PA and SPRM. Many PA and SPRM display direct antiproliferative effects in the endometrium, although with variable actions which seem product- and dose-dependent. This property justifies their use in the treatment of myomas and endometriosis. PA also suppress late follicular development, block the LH surge and retard endometrial maturation, which renders them potential estrogen-free contraceptive drugs. SPRM such as asoprisnil are not as effective in blocking the LH surge and appear to target the endometrium directly and produce amenorrhoea. Interestingly, clinical data show that treatment with these compounds is not associated with hypo-estrogenism and bone loss. The potential clinical applications of these compounds cover a broad field and are very promising in major public health areas. These include emergency contraception, long-term estrogen-free contraception (administered alone, or in association with a progestin-only pill to improve bleeding patterns), myomas (where they induce a marked reduction in tumour volume and produce amenorrhoea) and endometriosis. Further developments might also include hormone replacement therapy in post-menopausal women, as well as the treatment of hormone-dependent tumours.

The potential of mifepristone to be an emergency contraceptive is reviewed. Mifepristone prevents 92-100% of pregnancies with an acceptable side-effect profile on oral intake of a 10-600-mg dose within 72 h of unprotected intercourse. A single dose of 10 mg mifepristone resulted in a pregnancy rate of 1.5%, similar to a 1.5-mg single dose or two doses of 0.75 mg levonorgestrel 12 h apart, administered within 120 h (current standard) of unprotected sexual intercourse. Mifepristone and levonorgestrel do not differ in efficacy as emergency contraceptives. The mode of action of emergency contraception (EC) with mifepristone or levonorgestrel is primarily associated with inhibition of ovulation rather than prevention of implantation. Different doses of mifepristone appear to have similar effects. However, delay in the onset of subsequent menstruation caused by mifepristone is dose dependent and is reduced with a lower dose without affecting its efficacy. Patient acceptability of mifepristone as EC is high. However, the optimum standard dose of mifepristone is yet to be established for its application as an effective and acceptable emergency contraceptive drug for ordinary clinical use or practice.

Since the discovery of the antiprogestin RU 486 (mifepristone), other compounds have been synthesised that function as pure progesterone antagonists or progesterone receptor modulators. The latter are mixed agonists-antagonists. Mifepristone is usually used to terminate pregnancy but these compounds have numerous other applications in female healthcare. Mifepristone is an excellent agent for emergency contraception. Many progesterone antagonists and progesterone receptor modulators display antiproliferative effects on the endometrium and thus have application in the treatment of endometriosis and uterine myoma without being associated with hypoestrogenism and bone loss. They also have contraceptive potential by suppressing follicular development, blocking the luteinising hormone surge and retarding endometrial maturation. Finally, they have clinical application in GeneSwitch system, a plasmid-based method enabling controlled expression of specific genes (e.g., erythropoietin) using a progesterone antagonist as the inducer.

To compare the efficacy, patient acceptability and adverse effects of low-dose mifepristone (10 mg) with the levonorgestrel regimen (2 doses of 750 microg given 12 hours apart) for emergency contraception.

This randomized controlled trial compared mifepristone (10 mg) to levonorgestrel (2 doses of 750 microg given 12 hours apart) in the context of emergency contraception within 120 hours of unprotected intercourse. The primary outcome measure was unintended pregnancy. Secondary outcomes included adverse effects experienced by women, acceptability of the method of emergency contraception used, and the timing of the first menstrual cycle after treatment.

The total number of women recruited was 2,065. The crude pregnancy rates were 1.3% and 2.0% for mifepristone and levonorgestrel (P = .46), with 77% and 64% of expected pregnancies prevented, respectively. Women receiving mifepristone were more likely to have a delayed onset of the subsequent menstrual cycle after treatment (P < .001), whereas those having levonorgestrel were more likely to have an early onset of the subsequent menstrual cycle (P < .001). Acceptability levels were high for both methods, with 94% of women receiving mifepristone and 91% receiving levonorgestrel expressing satisfaction. There was no difference in adverse effects (nausea, vomiting, breast tenderness, abdominal pain, lethargy, headache, hot flushes, and dizziness) experienced by women in the 2 groups.

This study suggests that a small dose of mifepristone is not less effective than levonorgestrel for emergency contraception. Both regimens were highly acceptable to women.

To compare side effects, women's acceptance and satisfaction with mifepristone (100 mg) versus the Yuzpe regimen for emergency contraception (EC).

A total of 1000 women requesting EC within 72 h of unprotected intercourse were randomized to receive mifepristone 100 mg or the standard Yuzpe regimen. Outcome measures included patient acceptability and satisfaction.

A total of 620 (62%) questionnaires were returned, 64% in the mifepristone group and 60% in the Yuzpe group. Mifepristone was better tolerated than the Yuzpe regimen. The rates of nausea (P<0.0001), abdominal pain (P=0.001), tiredness (P<0.0001), lethargy (P=0.001), hot flushes (P<0.0001) and dizziness (P<0.0001) were all significantly higher in women given the Yuzpe regimen compared to those who received mifepristone. Of these 94% and 80% in the mifepristone and Yuzpe groups, respectively, were satisfied with treatment (P<0.0001). Of women in the mifepristone group, 56% (181/321) had used the Yuzpe regimen of EC in the past and of these, 93.6% (161/172) indicated they would use mifepristone in the future. A total of four women in the Yuzpe group had mifepristone in the past and all four said they would use mifepristone in the future.

Mifepristone has high patient acceptability and few side effects compared to the standard Yuzpe regimen for EC.

In this randomized pilot study, we compared the contraceptive efficacy, safety and side effect profiles of weekly versus planned postcoital regimens of low-dose mifepristone. Forty participants were randomized to receive mifepristone 10 mg weekly or planned postcoitally (to be used no more frequently than once every 5 days), for 12 consecutive months. Participants were evaluated monthly to determine pregnancy, ovulation status and acceptability of physical side effects. We ended this pilot study prematurely due to low efficacy and predetermined stopping rules. Three pregnancies during 56 woman-months occurred in the weekly group and three pregnancies during 68 woman-months occurred in the planned postcoital group. Almost half of the participants ovulated monthly on either regimen. The majority of the participants found the physical side effects of these regimens acceptable. Participants in the planned postcoital group, however, found adhering to the regimen more difficult than those in the weekly group. Mifepristone 10 mg used weekly or planned postcoitally did not adequately prevent pregnancy in our pilot study population. Although the concept of intermittent low-dose mifepristone is appealing, the contraceptive effectiveness was disappointing.

The concept of luteal phase contraception and the use of mifepristone in clinical trials, which allows for testing of its validity, as well as clinical pharmacological research designed to understand its mode of action, are reviewed. Early luteal phase administration has a variety of morphological, physiological and biochemical effects on the endometrium that are likely to interfere with embryonic-endometrial interactions. In fact, specifically designed pilot clinical trials as well as data derived from emergency contraception studies indicate that early luteal phase administration of mifepristone is highly effective in preventing pregnancy, with minimal disturbance of hormonal parameters or menstrual cyclicity. Mid and late luteal phase administration of mifepristone at doses above 25 mg are highly effective in inducing endometrial bleeding in nonconceptional cycles. However, administration of mifepristone within the period between implantation and expected menses fails to induce bleeding in a significant proportion of cases, and furthermore the bleeding induced does not insure the termination of pregnancy. While the data suggest there is potential for a once-a-month contraceptive pill, it is likely that no molecule endowed with partial agonistic properties, like mifepristone, will completely and reliably suppress the essential functions of progesterone in order to achieve contraceptive efficacy comparable to that of modern contraceptive methods.

Emergency contraception (EC) consists of either 1.5 mg of levonorgestrel (LNG) in one or two doses, or a combination of LNG with ethinylestradiol, administered for up to 5 days after unprotected intercourse. Clinical studies indicate that LNG alone is more effective and has less side effects. Its effectiveness decreases the longer after coitus it is taken. EC is indicated when there is non-compliance or accidents with the use of regular methods of contraception, or when women have had voluntary or imposed unprotected intercourse. The ethics of providing EC has been questioned by some, arguing that it acts by preventing implantation. Scientific evidence does not support this concept, but shows that EC acts mostly before fertilization. Placing obstacles to the access of EC is unethical as it transgresses the ethical principles of autonomy, non-maleficence beneficence and justice. Far from inducing abortions, EC reduces unwanted pregnancies and prevents abortion.

Spotting following the use of emergency contraception is not unusual, nor is anxiety in women waiting to see if the treatment has worked. It is not known whether such spotting should bring worry or relief. We, therefore, wished to see if there was any correlation between bleeding pattern and treatment outcome. Using data from a large multicenter efficacy trial, we examined bleeding patterns post-emergency contraception. The earlier in the cycle the pills were taken, the more likely the next bleed was to be early and the less likely it was to be on time. There was no observable difference in spotting rates between women who got pregnant and those who did not. The occurrence of spotting did not influence whether the next period was lighter or heavier.

In emergency contraception a drug or IUD is used to prevent pregnancy shortly after unprotected intercourse. Except for some Western-European countries and China, emergency contraception is largely under-utilised worldwide. In many developing countries lack of access to emergency contraception may subject women to unsafe abortions, which contribute significantly to maternal mortality and morbidity. Currently, several interventions (IUD, the Yuzpe regimen, levonorgestrel, mifepristone, danazol and some combination regimens) 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.

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, Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database (July 2003). 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 significant heterogeneity a random-effect model was applied.

Forty-eight trials with 33110 women were included. Most trials were conducted in China (37/48). Levonorgestrel is more effective than the Yuzpe regimen in preventing pregnancy (2 trials, RR: 0.51; 95% CI: 0.31 to 0.83). Single dose (1.5 mg) administration seems to have similar effectiveness as the standard 12 hours apart split-dose (0.75 mg twice) of levonorgestrel (2 trials, RR: 0.77, 95% CI: 0.45 to 1.30). Levonorgestrel has similar effectiveness to mid-dose (8 trials, RR: 1.64; 95% CI: 0.82 to 3.25) or low-dose (7 trials, RR: 1.38; 95% CI: 0.93 to 2.05) mifepristone. Low-dose (=< 10 mg) mifepristone is similarly effective as mid doses (25-50 mg) when only high quality trials are considered. Delay in the onset of subsequent menses is the main unwanted effect of mifepristone and seems to be dose-related. The Yuzpe regimen can be used when levonorgestrel and mifepristone are not available. Half-dose Yuzpe with single administration is associated with fewer side-effects but it is not clear whether it is as effective as the standard Yuzpe regimen (RR: 1.41; 95% CI: 0.76 to 2.61).

Levonorgestrel 1.5 mg (two split doses or a single dose) and low and mid-doses (25-50 mg) of mifepristone offer high efficacy with an acceptable side-effect profile. Single dose simplifies the use of levonorgestrel for emergency contraception without an increase in side-effects. However, mifepristone might delay the following menstruation, which could increase anxiety, particularly in higher doses. The Yuzpe regimen could be used if levonorgestrel or mifepristone are not available. The intrauterine device (IUD) is another effective emergency contraceptive, and can be kept for ongoing contraception.

The conference on the use of mifepristone to reduce unwanted pregnancy, sponsored by the World Health Organization, Concept Foundation and the Rockefeller Foundation, took place in Bellagio, Italy, between 24 and 28 September 2001. The objective of the conference was to review the scientific information and to evaluate the use of mifepristone for emergency contraception, luteal contraception and menstrual induction. Mifepristone is highly effective for emergency contraception but its advantages and disadvantages in comparison with levonorgestrel need to be further studied. Data indicate that mifepristone alone or in combination with misoprostol has potential for occasional use for women seeking help following repeated unprotected intercourse and/or when the interval between intercourse and treatment is more then 120 h. Administration of mifepristone immediately after ovulation seems to be an effective contraceptive method. However, before it can be used commonly, there is a need for a simple and inexpensive method to identify the right time in the cycle. Once-a-month treatment with mifepristone and misoprostol at the expected time of menstruation is not a practical method due to bleeding irregularities and timing of treatment. Menstrual induction with mifepristone and a suitable prostaglandin analogue is highly effective. A randomized comparison with manual vacuum aspiration is, however, needed before it can be recommended for routine use.

Mifepristone is a potent agent used in emergency contraception (EC). In the present study, we examined the contraceptive efficacy of mifepristone used in EC and then, using the model of mifepristone-based EC, we investigated its mechanism of action in the rhesus monkey. Sexually mature females were allowed to cohabitate with male animals from 1600 to 900 h of any one day of days 8-17 of cycle without (Group I; n = 6) and with a single dose of mifepristone (Group II, n = 31, 25 mg per animal, subcutaneous) 72 h postcoitus. Blood samples from all animals of Groups I and II were used to determine the concentrations of estradiol (E), progesterone (P) and chorionic gonadotrophin in peripheral circulation for retrospective analysis of the days of ovulation and blastocyst implantation. Four out of six animals (66.6%) in Group I became pregnant, while all 31 monkeys in Group II failed to establish pregnancy along with marginal changes in serum concentrations of E and P. In the second part of the study, animals were subjected to the same experimental protocol followed by collection of endometrial tissue samples on cycle day 22 from animals of both Group I (n = 6) and Group II (n = 24). Endometrial samples were subjected to morphological analysis including mitotic index, immunohistochemistry for vascular endothelial growth factor (VEGF), leukemia inhibitory factor (LIF), transforming growth factor beta1, estradiol receptor (ER), progesterone receptor (PR), proliferating cell nuclear antigen, placental protein 14 (PP 14) and detection of apoptosis by terminal nick end labeling method followed by histometric analysis. The results were retrospectively analyzed between the two groups on the basis of the day of treatment after ovulation: early luteal phase (days 0-3 postovulation) and mid-luteal phase (days 4-7 after ovulation). Mifepristone used in EC in the present study resulted in general loss of functional integrity of epithelial compartment characterized by loss of secretory maturation, increased apoptosis and higher degree of degeneration along with decreased expression of VEGF, LIF, PP14 and ER, while PR level increased as compared to control samples. The vascular compartment appeared to be compromised along with affected morphological features and decreased expression of VEGF, LIF, ER and PR following the administration of mifepristone. It appears that mifepristone used in EC alters the physiological homeostasis in epithelial and vascular compartments of implantation stage endometrium rendering it hostile to blastocyst implantation. Furthermore, the degree to which the endometrial function is affected largely depends on the day of mifepristone treatment in a parameter-specific manner resulting in a higher degree of degenerative changes in samples obtained from animals who received mifepristone during mid-luteal phase of cycles.

An emergency contraceptive method is used after coitus but before pregnancy occurs. The use of emergency contraception is largely underutilized worldwide. Recently, treatment with 10 mg mifepristone as a single dose has emerged as one of the most effective hormonal methods for emergency contraception, with very low side effects. However, the mechanism of action of mifepristone in humans when used for contraceptive purposes and especially for emergency contraception remains largely unknown. The objective of this review is to summarize available data on the effect of mifepristone on female reproductive functions relevant to emergency use of the compound. Taken together, available data from studies in humans indicate that the contraceptive effect of mifepristone used as a single low dose for emergency contraception is mainly due to impairment of ovarian function, either by blocking or postponing the luteinizing hormone surge, rather than to inhibiting of implantation.