A single dose of 10 mg mifepristone resulted in a pregnancy rate of 1. Mifepristone and levonorgestrel do not differ in efficacy as emergency contraceptives. 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. Researchers in Cochrane collected and analyzed all relevant studies to answer this question. We searched 10 English-language and three Chinese-language databases for published studies in any language, in February We also searched grey literature databases and websites and contacted experts and authors for eligible studies.
Studies had to report information on interventions to prevent pregnancy after a single act of unprotected intercourse.
We included randomized controlled trials with 60, women in this review. Ninety-two trials were conducted in China. The evidence is up-to-date to February The studies compared 25 different interventions of different types of emergency contraception. The studies showed the following. Levonorgestrel and mifepristone were more effective than Yuzpe regimen estradiol-levonorgestrel combination.
Our findings suggest that if 29 women per become pregnant with Yuzpe, between 11 and 24 women per will do so with the levonorgestrel, and that if 25 women per become pregnant with Yuzpe, between one and 10 women per will do so with mifepristone.
Mid-dose mifepristone 25 mg to 50 mg was probably more effective than levonorgestrel. Low-dose mifepristone less than 25 mg was probably less effective than mid-dose mifepristone, but both were more effective than levonorgestrel two doses of 0. Ulipristal acetate UPA was also more effective than levonorgestrel. The copper IUD inhibits fertilization through its toxic effects on the sperm and blocks implantation through the effects of the foreign body and trace mineral release on a changing endometrium.
Only mifepristone is effective once implantation has occurred, actually interrupting an early pregnancy. The effectiveness of these methods thus depends on the point in a woman's reproductive cycle at which emergency contraception is used. Physicians must understand the probability of conception when emergency contraception is considered. The average fertile period for a woman lasts only six days per menstrual cycle and ends the day she ovulates. Unprotected sex three days before ovulation results in an estimated 15 percent pregnancy rate; one or two days before ovulation, a 30 percent rate; and on the day of ovulation, an estimated 12 percent rate.
Sperm can survive in the female up to five days, and the mature egg may be fertilized over a hour period. The time period from ovulation to implantation is about seven days. This regimen remains the most commonly prescribed postcoital birth control method in the United States. A number of pills from different trade name birth control pill packages are used Table 2. More recently, a prepackaged, dedicated product consisting of four pills Preven has been developed.
Montvale, N. The other products listed are bioequivalents. Information from Twelve brands of emergency contraceptive pills in the United States.
J Am Med Womens Assoc ; If women have unprotected intercourse during the second or third week of their cycle, the probability is that eight will become pregnant. If the Yuzpe method is used, only two women will become pregnant about a 75 percent reduction. A recent review of eight studies showed a precise reduced risk of pregnancy of Common side effects include nausea 50 percent of women and vomiting 20 percent.
No studies have analyzed the effect of vomiting on the efficacy of this regimen. Some physicians prescribe antiemetics routinely with the hormone therapy or repeat the dose of medication if vomiting occurs within one to two hours of ingestion.
Others theorize that if nausea is experienced, the medication must already be absorbed systemically. Less common side effects include heavy menses and mastalgia. Withdrawal bleeding occurs within three weeks of treatment. Thirty-eight percent of women bleed before their menstrual period is due. Only 8 percent are estimated to be four or more days late.
No data support the occurrence of vascular complications in women resulting from this brief use of estrogen and progesterone therapy. There are no absolute contraindications to emergency contraception other than pregnancy. Furthermore, studies have shown no evidence of harm to the developing fetus. Investigators have not specifically examined the teratogenic effects associated with emergency contraceptive use, although a reasonable extrapolation may be made from extensive experience with prospective studies of unintended pregnancy in oral contraceptive users.
It is not known whether using estrogen-progestin combinations other than those described by Yuzpe would also be effective, whether the second dose given 12 hours after the first dose is necessary or whether the pills would be effective if started later than 72 hours after intercourse.
A recent analysis of the timing of pill use suggests an inverse linear relationship between efficacy and the time from intercourse to treatment. The earlier the pills were used, the more effective they were during the hour period studied. Delaying the first dose by 12 hours increased the odds of pregnancy by almost 50 percent. If a patient first contacts her physician more than 72 hours after unprotected intercourse takes place, the medication can still be prescribed, with reassurance that no harm will be done if she becomes pregnant and a discussion of the presumably reduced efficacy of this regimen beyond 72 hours.
Within the past few years, evidence has emerged to support the preferential use of the progestin-only regimen levonorgestrel, 0. The World Health Organization conducted a large, double-blind, randomized trial 9 involving 1, women from 14 countries, comparing the use of levonorgestrel with the Yuzpe estrogen-progestin combination. The levonorgestrel regimen decreased the average expected pregnancy rate by 85 percent 95 percent confidence interval; range: 74 to 93 percent compared with the Yuzpe regimen rate of 57 percent 95 percent confidence interval; range: 39 to 71 percent.
Although the decreased rate of pregnancy with use of the Yuzpe regimen in this study was less than that in the earlier review of 11 studies, 10 it was still within the range of pregnancy rates in previous individual studies. This large trial also demonstrated an improved side effect profile of the levonorgestrel protocol. Only Similarly, only 5. In both groups, the efficacy was inversely related to length of time from intercourse and commencement of medication within the hour window studied.
As in the Yuzpe regimen, the only absolute contraindication to the levonorgestrel protocol is pregnancy, because the medication would be ineffective.
Levonorgestrel in a two-pill sequential dosing packet Plan B is available in the United States and is labeled by the FDA for emergency contraceptive use. The more cumbersome regimen of 20 levonorgestrel pills Ovrette per dose may also be prescribed. Two randomized trials have compared mg of mifepristone with the Yupze regimen.
Most of these studies examined the potential of progestogens for regular postcoital use, an application for which they were found to be unsuitable, because of the high incidence of cycle disturbances. In EC, such menstrual irregularities are much less of an issue and, in fact, tablets or 0. One study, in which women received 1. Another study, which examined the effects of a daily dose of 0. When Levonorgestrel was given during the early follicular phase, the total cycle length was significantly prolonged due to the increased duration of the follicular phase.
Posttreatment biopsies taken on cycle days still showed proliferative endometrium in accordance with the delay in ovulation. When levonorgestrel was administered around the time of ovulation, the effects were variable: Ovulation was blocked in some women, while in others follicular activity was followed by deficient luteal function, and still other women ovulated normally.
On the other hand, administering levonorgestrel during the luteal phase did not affect cycle length or cause any significant endometrial changes. This last finding was somewhat unexpected in view of the proven effectiveness of levonorgestrel in emergency contraception [5]. Is Levonorgestrel an improved alternative to the Yuzpe regimen [11]? In Hong Kong the prospective randomized study was conducted, to compare the efficacy of Yuzpe regimen and levonorgestrel 0.
The failure rates were nearly similar 2. On , a study in South America reported of the hormonal and peripheral effects of d-Norgestrel, a synthetic progestational compound as postcoital contaception. It has been administered satisfactorily in oral doses of micrograms post-coitus, and has yielded a corrected treatment failure rate of 1,7 per woman years of use. The alteration consistently observed in the cervical mucus, with consequent prevention of sperm migration, has been suggested as the principal contraceptive mechanism table 2 , table 3 , table 4.
However, in postcoital contraception, treatment is applied to prevent conception when coitus already has occurred. Table 2. Cervical mucus in the ovulatory phase. Effect of a single dose of micrograms d-Norgestrel [6]. Table 3. Intercervical sperm penetration.
Effect of a single dose of m g d-Norgestrel [6]. Table 4. Recovery of intrauterin sperm. There are four randomized controlled trials of emergency contraception to present as practical part of the discussed treatment regimens to study the efficacy, the timing, and the dose-issue by comparing. Levonorgestrel is marketed in several countries for occasional postcoital contraception in packs containing 0.
The levonorgestrel regimen was better tolerated than the Yuzpe regimen. Efficacy was greater, in terms of both crude and adjusted pregnancy rates Lev: 1. The clustering of observed pregnancies around predicted ovulation Figure 3 validates our estimates of conception probabilities in this large sample.
Because of the biological variability in cycle length and the need to rely on calculated estimates of the day of ovulation, the occasional pregnancy after intercourse apparently outside the fertile period is to be expected. The second finding of public-health importance relates to the timing of the treatment. For both methods combined, efficacy was significantly and inversely related to time since unprotected coitus. A trend of decreasing efficacy with time for each regimen was described.
Different findings of importance to the timing lead to the proposal that women should receive treatment as soon, as is practicable after unprotected coitus. The sooner treatment starts, the better it works. Neither regimen substantially delayed the onset of next menses.
Mechanism of action: Little is known about, to explain why the Yuzpe regimen of levonorgestrel with ethinyloestradiol is less effictive than the regimen of levonorgestrel alone. The lower efficacy could be due to an interaction between the oestrogen and the progestagen as well as to the lower dose of levonorgestrel used in the Yuzpe regimen. Replacement of the Yuzpe regimen with levonorgestrel should improve the acceptability of hormonal emergency contraception.
Discussion: Regardless of the method, by which failure rates are calculated, the fact remains that none of the women and adolescents who were treated with mifepristone conceived. It was unquestionably as effective as the standard estrogen-progestogen regimen.
Mifepristone was associated with fewer side effects. Since it was taken as a single dose, there was no possibility of noncompliance if side effects occurred.
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