A randomised study comparing a low dose of mifepristone and the Yuzpe regimen for emergency contraception

Objective To compare 100 mg mifepristone with the standard Yuzpe regimen for emergency contraception.
Design Randomised controlled trial.
Setting Family Planning Clinic, Aberdeen.
Sample One thousand women seeking emergency contraception within 72 hours after an episode of unprotected sexual intercourse.
Methods Women were randomised to receive either 100 mg (half tablet) of mifepristone as a single dose or the Yuzpe regimen (two tablets each with 50 μg ethinyloestradiol and 0.25 mg levonorgestrel, to be repeated 12 hours later).
Outcome measures Crude pregnancy rates, proportion of pregnancies prevented, side effects and patient acceptability.
Results The crude pregnancy rates (95% CI) for the Yuzpe regimen and mifepristone were 3.6% (2.3–5.7) and 0.6% (0.2–1.8), respectively, with a significant difference between the two groups (RR 6.04; 95% CI 1.75–20.75). Mifepristone prevented 92% of pregnancies and the Yuzpe regimen preventing 56%. An increasing coitus to treatment interval was associated with contraceptive failure in the Yuzpe group (   P = 0.03  ) with no association seen with mifepristone. Following administration of mifepristone 24.5% and 13.1% given the Yuzpe regimen had a delayed period (RR 2.14; 95% CI 1.46–3.15). Overall, mifepristone was better tolerated than the Yuzpe regimen with significantly fewer side effects. More women were satisfied (   P < 0.0001  ) with mifepristone as an emergency contraceptive and would recommend it to a friend (   P = 0.02  ).
Conclusion Mifepristone administered in a 100 mg dose is a highly effective post-coital contraceptive with high patient acceptability and fewer side effects compared with the standard Yuzpe regimen. Delay in the onset of menstruation did not decrease patient acceptability.     

Levonorgestrel is more effective,has fewer side-effects,than Yuzpe regimen

This large-scale clinical trial compared the efficacy and side effects of 2 emergency contraceptive methods, the levonorgestrel and the Yuzpe regimen. A total of 1955 women, with a mean age of 27 years were studied, of whom 979 were randomly assigned to the Yuzpe regimen and 976 to the levonorgestrel group. Treatment began within 24 hours of unprotected sexual intercourse among nearly 50% of women in each group and within 48 hours in more than 80%. Findings showed that pregnancy occurred in 3.2% of women who received the Yuzpe regimen and in 1% of those assigned to the levonorgestrel regimen, with a crude relative pregnancy risk of 0.36. The levonorgestrel and Yuzpe regimen prevented 85% and 57% of expected pregnancies, respectively. Considering the side effects of the methods, the study found that levonorgestrel was better tolerated by women than was the Yuzpe regimen because of less significant occurrence of unpleasant reactions such as nausea, vomiting, dizziness and fatigue with levonorgestrel usage. An important finding of the study was the consistent linear relationship between efficacy and the time from intercourse to treatment where trends of rising pregnancy rates occur as treatment is being delayed. Both methods were more effective the sooner they were used after unprotected intercourse. From the findings, researchers suggest that replacement of the Yuzpe regimen with levonorgestrel should improve the acceptability of hormonal emergency contraception and should therefore be considered in family planning programs.     

A randomized trial of mifepristone (10 mg) and levonorgestrel for emergency contraception

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Emergency contraception: a review.

Emergency contraception (EC), also known as 'the morning after pill', or post-coital contraception, is a modality of preventing the establishment of a pregnancy after unprotected intercourse. Both a hormonal and an intrauterine form are available. Modern hormonal EC, with low side effects, was first proposed by Yuzpe in 1974. More recently, a new regimen, consisting of levonorgestrel administered alone, was introduced and found in clinical trials to be more effective (if taken as early as possible), and associated with less side effects than the Yuzpe regimen, which it has gradually replaced. The WHO developed another regimen based on the use of the selective progesterone receptor modulator (antiprogestin) mifepristone and conducted trials with different dosages. Intrauterine EC was first proposed by Lippes in 1976. It has the advantage of being applicable for almost a week and the disadvantage of a greater complexity. In addition, this modality is solely interceptive, acting by preventing implantation. Pregnancy rates reported following EC using an intrauterine device with more than 300 mm2 of copper are consistently low (0.1-0.2%).     

A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation

OBJECTIVE: To assess women's acceptability, the efficacy and side effects of sublingual versus vaginal administration of misoprostol in combination with mifepristone for medical abortion up to 13 weeks of gestation. DESIGN: Randomised controlled trial. SETTING: Aberdeen Royal Infirmary. POPULATION: Women undergoing medical abortion under the terms of the 1967 Abortion Act. METHODS: Mifepristone (200 mg) was given orally followed 36-48 hours later by misoprostol administration (sublingual: 600 microg; vaginal: 800 microg). A second dose of misoprostol 400 microg was given 3 hours later (sublingually or vaginally). Women between 9 and 13 weeks of gestation received a further (third) dose of misoprostol 400 microg (sublingually or vaginally), 3 hours later if abortion had not occurred. MAIN OUTCOME MEASURES: Women's acceptability, efficacy of the regimen and side effects experienced. RESULTS: A total of 340 women were recruited (171 sublingual and 169 vaginal). A total of 70% of women in the sublingual group expressed satisfaction with the route of misoprostol administration; 18% answered 'Don't know' while 12% were dissatisfied, compared with 68%, 28% and 4%, respectively, in the vaginal group (P= 0.02). There was no significant difference in the need for surgical evacuation for women in the sublingual (3/158, 1.9%) and vaginal groups (4/156, 2.6%) (P= 0.70). Women receiving misoprostol sublingually were more likely to experience diarrhoea (P < 0.01), shivering (P < 0.01) and unpleasant mouth taste (P < 0.01). CONCLUSIONS: Sublingual administration of misoprostol is an effective alternative to vaginal administration for medical abortion up to 13 weeks of gestation. The prevalence of prostaglandin-related side effects, however, was higher with this route of administration.     

Home use of two doses of misoprostol after mifepristone for medical abortion: a pilot study in Sweden and France.

OBJECTIVE: To test the feasibility, safety, and efficacy of home use of two doses of misoprostol for medical abortion (MA) in European settings. METHODS: One hundred thirty women (100 in Sweden, 30 in France) presenting for first-trimester MA were administered oral mifepristone in the clinic and sent home with two 400 microg doses of misoprostol, along with instructions to take the misoprostol at 24 h intervals. Women were also asked to complete a daily symptom diary. Outcomes of interest included effectiveness, side-effects, and adherence to and acceptability of the home-use regimen. RESULTS: Three women (all in France) were lost to follow-up. Of the remaining 127 women, 124 (98%) had a successful MA. All women adhered successfully to the home-use regimen, and satisfaction with home use was high (98%). Most women experienced noticeable, if transitory, side effects after both the first and second doses of misoprostol (97% and 94%, respectively). CONCLUSIONS: Misoprostol may successfully and satisfactorily be used at home as part of a MA regimen in European settings as it has been for years in the US. Further research to determine if two doses of misoprostol are more effective than a single dose would be useful.     

Emergency contraception: methods and efficacy

A number of effective and safe methods for emergency contraception are now available. High doses of oestrogens, although effective, are seldom used nowadays because of the high incidence of nausea and vomiting, and the need for administration for 5 days. The Yuzpe regimen, consisting of administration of two doses of combined oral contraceptive pills with a 12-h interval, can prevent more than 74% of expected pregnancies, but the incidence of side effects, mainly gastrointestinal side effects, is high. Levonorgestrel and mifepristone are more effective than the Yuzpe regimen and have a lower incidence of side effects. They can prevent about 85% of pregnancies. The efficacy of both the Yuzpe regimen and levonorgestrel decreased with increase in the intercourse-treatment interval. The dose of mifepristone can be reduced to 10 mg without loss of efficacy. Both levonorgestrel or mifepristone are not yet widely available, and the Yuzpe regimen remains the only hormonal method in many countries. The postcoital insertion of an intrauterine contraceptive device is also a highly effective method, which can prevent over 90% of pregnancies.     

人工流产妇女对紧急避孕法的可接受性研究

目的 :了解妇女对紧急避孕法的可接受性及其影响因素 ,以采取有效措施促进其使用 ,减少人工流产。方法 :用结构式调查表 ,对上海市三所妇幼保健院的 6 0 6名人工流产妇女进行了面对面的调查。有效的调查表编码后输入计算机 ,用 SAS软件对核对后的数据进行统计分析。结果 :妇女对紧急避孕法具有较高的可接受性 ,85.5%的对象表示需要时愿意使用。可接受性的影响因素包括妇女的人口学特征 (职业、年收入 )、孕次、常用避孕方法及对紧急避孕法的了解情况和健康状况。愿意使用者中 ,82 .6 %的对象愿意使用的是紧急避孕药 ,因此多数对象 (6 0 .1 % )认为药店是获得服务的理想地点 ,原因主要是到药店方便。结论 :通过知识宣传和服务改进可促进紧急避孕法的使用。避孕知识宣传和服务咨询一定要针对对象的个体需求。通过药店提供安全可靠的紧急避孕药是目前急需解决的问题     

Postplacental Insertion of Levonorgestrel Intrauterine System Versus Copper Intrauterine Device: A Prospective Study

PurposeTo compare between postplacental insertion of levonorgestrel intrauterine system versus copper intrauterine device regarding expulsion rates, patient satisfaction, complications, and continuation rates.MethodsThis prospective observational study was conducted on 1100 participants divided in to two groups: group (1) CU-IUD group and group (2) LNG-IUS group where women were assigned for postplacental insertion of either CU-IUD or LNG-IUS, respectively. Follow-up at 6 weeks, 3 and 6 months postpartum and data were collected and analyzed to evaluate outcomes.ResultsNo statistical difference between both groups regarding patients’ characteristics, the overall expulsion rate was higher in LNS-IUS group than CU-IUD group; 77 patients (14%) and 50 patients (9%), respectively, (P value < 0.05), odds ratio: 1.63 at CI: (1.12–2.37). No significant difference between the two groups regarding pain intensity, perforation, abnormal uterine bleeding, and clinical endometritis (P > 0.05). Overall satisfaction rate at six months was 478(87%) in the CU-IUD group and 472(85.8%) in the LNS-IUS group (P value > 0.05), odds ratio: 1.1 at CI: (0.78–1.55). Continuation rate at s6 months was comparable between the two groups 485 (88.2%) and 480 (87.3%) in CU-IUD group and LNS-IUS group respectively, (P value < 0.05), odds ratio: 1.09 at CI: (0.76–1.56).ConclusionThe rate of expulsion of LNG-IUS is higher than copper IUD when inserted postplacental, yet the continuation and acceptability rates were comparable between the two groups.     

Hormonal postcoital contraception with an ethinylestradiol-norgestrel combination and two danazol regimens

The ethinylestradiol-norgestrel combination (EE-NG) for postcoital contraception, as described by Yuzpe, has been shown to be an effective method but with frequent side effects. To overcome the problem of adverse effects a new approach using danazol was proposed, but the efficacy and acceptability of this treatment have not yet been tested in large studies. In a 5-year period at the AIECS Family Planning Centre in Milan we treated 2448 women requesting postcoital contraception using Yuzpe's regimen and two danazol regimens (800 mg/1200 mg). The patients' acceptability for danazol treatment was higher than for Yuzpe's regimen due to fewer, milder and shorter side effects. Nine pregnancies occurred in the EE-NG group (2.21%), 17 in the 800 mg group (1.71%) and 6 in the 1200 mg group (0.82%). Our study shows a statistically significant efficacy against expected pregnancy rates both with Yuzpe's regimen and with danazol. The 1200 mg danazol treatment seems to be more effective and can be considered a valid alternative to the EE-NG combination for hormonal postcoital contraception.     

Knowledge,attitude and practice of emergency contraception among health care providers in Ismailia,Egypt

ObjectiveTo explore the knowledge, attitude and practice of health care providers in Ismailia, Egypt regarding emergency contraception.Participants and methodA structured questionnaire was distributed to a total of 270 health care providers (obstetrics and gynecology specialists and general practitioners or family physicians). The questionnaire contained four main domains: demographic characteristics; knowledge about EC; attitude toward EC; and practice of EC.ResultsKnowledge of specialists was significantly higher than general practitioners/family physicians regarding the three most commonly used methods of EC, viz; combined oral contraceptive (Yuzpe) method, progesterone only pills (plan B) method and IUCD. Only 39.5% of specialists and 24.0% of GPs/family physicians had good knowledge of EC (p = 0.01). 45.7% of specialists and 42.6% of GPs/family physicians had favorable attitude toward EC with no significant difference. 39.5% of specialists and 26.6% of GPs/family physicians reported ever prescribing EC. Yuzpe method was the most commonly prescribed method by specialists (31.5%) and GPs/family physicians (27.0%) with no significant difference. Knowledge and favorable attitude were significantly associated in both groups. Age and years of experience significantly affected the three outcome measures.ConclusionA deficit in knowledge and a negative attitude shown by health care providers lead to an insufficient use of EC methods.     

Extending the time limit for starting the Yuzpe regimen of emergency contraception to 120 hours

OBJECTIVE: Current protocols state that the Yuzpe regimen of emergency contraception can be initiated up to 72 hours after unprotected intercourse. The purpose of this study was to determine whether the window for emergency hormonal contraception can be extended to 120 hours. METHODS: In an observational study, we tracked 111 women who requested emergency contraception between 72 and 120 hours after unprotected sex but refused postcoital copper intrauterine devices (IUDs), preferring instead the Yuzpe regimen. We compared failure rates for this group with rates among 675 otherwise similar women who started the same therapy within 72 hours. RESULTS: Both perfect use (1.9%) and typical use (3.6%) failure rates were low among women presenting between 72 and 120 hours after unprotected intercourse. These rates did not statistically differ from failure rates for the standard Yuzpe regimen (2.0% during perfect use and 2.5% during typical use). Our small sample size of 111, however, gave us just 25% power to detect a doubling in the failure rates (2% to 4%) and 59% power to detect a tripling in the failure rates (2% to 6%). CONCLUSION: The 72-hour cutoff for the Yuzpe regimen of emergency contraception appears needlessly restrictive. Women who request this therapy more than 72 hours after unprotected sex should be allowed to receive it, particularly if they decline postcoital insertion of a copper IUD and would otherwise have no options for reducing pregnancy risk.     

小剂量米非司酮用于紧急避孕的研究

目的：探讨一次性小剂量米非司酮25mg用于紧急避孕的效果及可接受性。方法：征集无保护性交或避孕措施失败后72小时内来院就诊的健康发女100例,单次口服米非司酮25mg,服药后按时随访并观察药物副反应及下次月经情况,保证月经复潮前禁欲或采用避孕套避孕。结果：根据Dixon方法计算,预期妊娠数为8．845,实际妊娠数为2例,避孕有效率为77．4％。实际妊娠与预期妊娠相比,有显著差异（P＜0．05）。结论：小剂量米非司酮用于紧急避孕是非常简便、安全、有效的方法。     

A multicentre,open-label,randomised phase III study comparing a new levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral contraception in young women of reproductive age

Objectives: To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8?μg/24?h over the first year [total content 13.5?mg]) and a 30?μg ethinyl estradiol/3?mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women.

Methods: Nulliparous and parous women (aged 18–29 years) with regular menstrual cycles (21–35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit.

Results: Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being ‘very satisfied’ or ‘satisfied’ with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p?=?0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group.

Conclusions: LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women.     

Medical abortion in women of less than or equal to 56 days amenorrhoea: a comparison between gemeprost (a PGE1 analogue) alone and mifepristone and gemeprost.

OBJECTIVE: To determine the efficacy of a new dose regimen of vaginal gemeprost (1 mg every 6 h up to three doses) in induction of abortion in women less than or equal to 56 days gestation, and to compare this regimen with mifepristone (200-600 mg) followed 48 h later by a single dose of gemeprost (1 mg). DESIGN: Two separate protocols, with 50% of the subjects randomized to one or other protocol. SETTING: The Royal Infirmary of Edinburgh, Scotland, UK. SUBJECTS: 301 referred by their general practitioner or local family planning clinic, requesting termination of pregnancy at less than or equal to 56 days amenorrhoea. INTERVENTIONS: Ongoing pregnancies and incomplete abortions were terminated surgically. MAIN OUTCOME MEASURES: Number of complete abortions, analgesic requirements and bleeding pattern following treatment. RESULTS: Complete abortion occurred in 87% of women treated with gemeprost alone and 98% of women treated with mifepristone and gemeprost (P = 0.0004). Analgesic requirements were greater in the group treated with gemeprost alone, compared with the group treated with mifepristone and gemeprost (P = 0.0001). CONCLUSION: The new dose regimen of gemeprost can be used for early induced abortion, but the use of mifepristone and gemeprost has several advantages over the use of gemeprost alone.     

Is home-based administration of prostaglandin safe and feasible for medical abortion? Results from a multisite study in Vietnam

OBJECTIVES: To study the efficacy and acceptability of a simplified medical abortion regimen in Vietnam. DESIGN: Open-label study. SETTING: One peri-urban and three urban hospitals and four urban maternal-child health family planning clinics located in Northern, Central and Southern Vietnam. SAMPLE: A total of 1601 women seeking abortion services from January 2001 to December 2001. METHODS: Consenting women presenting for abortion services with gestations less than 56 days LMP who met the inclusion criteria were given 200 mg mifepristone and offered the choice of either home or clinic administration of 400 microg oral misoprostol two days later. MAIN OUTCOME MEASURE: Complete abortion rate of 89.2% (n= 1395), with 1.5% (n= 24) of the women lost to follow up. The majority of women (>90%) reported that their medical abortion experience was either 'very satisfactory' or 'satisfactory'. RESULTS: There was a strong preference for home administration of misoprostol, with more than four-fifths of the study population selecting to administer the prostaglandin at home. Location of misoprostol administration did not affect efficacy rate. Regardless of location selected, women expressed a high degree of satisfaction with the medical abortion experience. CONCLUSIONS: Medical abortion with the option of home administration of misoprostol is safe and feasible for introduction into the Vietnamese healthcare system.     

延长米非司酮配伍米索前列醇序贯用药时间预防流产后出血的 …

目的 探讨米非司酮配伍米索前列醇终止早孕的最佳剂量方案,以预防流产后出血,方法 对１６１２例妊娠≤４９天,要求药物终止妊娠的妇女,按２：１随机分为观察组,对照组。观察组１１８例,米非司酮首次剂量５０ｍｇ,继后每１２ｈ１次,每次２５ｍｇ（共６ｄ）,总剂量３００ｍｇ,于用药第３天晨加用米索前列醇６００μｇ,第４￣６天晨各加服２００μｇ,总量１２００μｇ。对照组４９４例,米非司酮首次剂量５０ｍｇ,继后第     

Home use of two doses of misoprostol after mifepristone for medical abortion: A pilot study in Sweden and France

Objective To test the feasibility, safety, and efficacy of home use of two doses of misoprostol for medical abortion (MA) in European settings.

Methods One hundred thirty women (100 in Sweden, 30 in France) presenting for first-trimester MA were administered oral mifepristone in the clinic and sent home with two 400 μg doses of misoprostol, along with instructions to take the misoprostol at 24 h intervals. Women were also asked to complete a daily symptom diary. Outcomes of interest included effectiveness, side-effects, and adherence to and acceptability of the home-use regimen.

Results Three women (all in France) were lost to follow-up. Of the remaining 127 women, 124 (98%) had a successful MA. All women adhered successfully to the home-use regimen, and satisfaction with home use was high (98%). Most women experienced noticeable, if transitory, side effects after both the first and second doses of misoprostol (97% and 94%, respectively).

Conclusions Misoprostol may successfully and satisfactorily be used at home as part of a MA regimen in European settings as it has been for years in the US. Further research to determine if two doses of misoprostol are more effective than a single dose would be useful.     

米非司酮配伍米索前列醇终止10～16周妊娠的临床多中心随机比 …

目的 探讨米非司酮合并米索前列醇（米索）终止１０－１６周妊娠最佳剂量及最佳给药途径。方法 将来自上海２４所医院的２００７例孕１０－１６周要求药物终止妊娠的妇女,随机分成４种不同的治疗组。组Ｉ,５１１例,米非司酮７５ｍｇ每天１次,连服２天（总量１５０ｍｇ）第３天晨口服米索０．６ｍｇ,每３－４小时重复１次,最多３组,组ＩＩ：４９１例,非米司酮１００ｍｇ每天１次,连服２天（总量２００ｍｇ）米索用法同组Ｉ