Emergency contraception

Emergency contraception (EC), or emergency postcoital contraception, refers to contraceptive measures that, if taken after sex, may prevent pregnancy.

Forms of EC include:

• Emergency contraceptive pills (ECPs)—sometimes simply referred to as emergency contraceptives (ECs) or the "morning-after pill"—are drugs that act both to prevent ovulation or fertilization and possibly post-fertilization implantation of a blastocyst (embryo). ECPs are distinct from medical abortion methods that act after implantation.^[1]
• Intrauterine devices (IUDs)—usually used as a primary contraception method, but sometimes used as emergency contraception.

As its name implies, EC is intended for occasional use, when primary means of contraception fail. Since EC methods act before implantation, they are medically and legally considered forms of contraception. Some pro-life groups define pregnancy as beginning with fertilization, and consider those forms of EC that act after fertilization to be abortifacients (See Mechanism of action section).

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Emergency contraceptive pills (ECPs)

See also: Emergency contraceptive availability by country

Emergency contraceptive pills (sometimes referred to as emergency hormonal contraception (EHC) in the U.K.) may contain higher doses of the same hormones (estrogens, progestins, or both) found in regular combined oral contraceptive pills. Taken after unprotected sexual intercourse, such higher doses may prevent pregnancy from occurring. Mifepristone is another kind of ECP, but is considered an anti-hormonal drug, and does not contain estrogen or progestins.

The phrase "morning-after pill" is figurative; ECPs are licensed for use up to 72 hours after sexual intercourse.

Types of ECPs

The progestin-only method uses the progestin levonorgestrel in a dose of 1.5 mg, either as two 750 μg doses 12 hours apart, or more recently as a single dose. Progestin-only EC is available as a dedicated emergency contraceptive product under many names worldwide, including: in the U.S., Canada and Honduras as Plan B; in the U.K., Ireland, Australia, New Zealand, Portugal and Italy as Levonelle; in 44 nations including France, most of Western Europe, India, and several countries in Africa, Asia and Latin America as NorLevo; and in 44 nations including most of Eastern Europe, Mexico and many other Latin American countries, Portugal, Australia and New Zealand, Israel, China, Hong Kong, Taiwan and Singapore as Postinor-2.^[2]

The combined or Yuzpe regimen uses large doses of both estrogen and progestin, taken as two doses at a 12-hour interval. This method is now believed to be less effective and less well-tolerated than the progestin-only method.^[3] It is possible to obtain the same dosage of hormones, and therefore the same effect, by taking several regular combined oral contraceptive pills. For example, 4 Ovral pills are the same as 4 Preven pills.^[4][5] The FDA approved this off-label use of certain brands of regular combined oral contraceptive pills in 1997.^[4][6][7]

The drug mifepristone may be used either as an ECP or as an abortifacient, depending on whether it is used before or after implantation. In the USA, it is most commonly used in 200- or 600-mg doses as an abortifacient,^[8] but in China it is commonly used as emergency contraception. As EC, a low dose of mifepristone is slightly less effective than higher doses, but has fewer side effects.^[9] As of 2000, the smallest dose available in the USA was 200 mg.^[10] Mifepristone, however, is not approved for emergency contraceptive use in the United States.^[11] A review of studies in humans concluded that the contraceptive effects of the 10-mg dose are due to its effects on ovulation,^[12] but understanding of its mechanism of action remains incomplete. Higher doses of mifepristone can disrupt implantation and, unlike levonorgestrel, mifepristone is effective in terminating established pregnancies.

Morning-after pills (ECPs) are not to be confused with the “abortion pill”, otherwise known as RU486, mifestone, or Mifeprex. According to the International Federation of Gynecology and Obstetrics, “EC is not an abortifacient because it has its effect prior to the earliest time of implantation.” Since they act before implantation, they are considered medically and legally to be forms of contraception.

Effectiveness of ECPs

Progestin-only (levonorgestrel) regimen:

The original (1999) FDA-approved U.S. product labeling for Plan B said:

Plan B reduces the risk of pregnancy following a single act of unprotected sex from about 8% down to 1%. This represents an 89% reduction in risk of pregnancy for this single act of unprotected sex.^[13]

The current (2006) FDA-approved U.S. product labeling for Plan B says:

Plan B works best the sooner you use it. If it is taken within 72 hours (3 days) after sex, it will significantly decrease the chance that you will get pregnant. Seven out of every eight women who would have gotten pregnant will not become pregnant. Plan B works even better than this if taken within the first 24 hours after sex.^[14]

Combined (Yuzpe) regimen:

The original (1998) FDA-approved U.S. product labeling for Preven (the Yuzpe regimen), referring to Yuzpe regimen ECPs, said:

If one hundred women used ECPs correctly in one month, about two women would become pregnant after a single act of intercourse. If no contraception is used about eight women would become pregnant after a single act of intercourse. Therefore, the use of ECPs results in a 75% reduction in the number of pregnancies to be expected if no ECPs were used after unprotected intercourse. Notably some clinical trials have shown that efficacy was greatest when ECPs were taken within 24 hours of unprotected intercourse, decreasing somewhat during each subsequent 24-hour period.^[15]

The effectiveness of emergency contraception is expressed as a percentage reduction in pregnancy rate for a single use of EC. A review article in American Family Physician explains the 75% effectiveness rate of the Yuzpe regimen thus:

... these numbers do not translate into a pregnancy rate of 25 percent. Rather, they mean that if 1,000 women have unprotected intercourse in the middle two weeks of their menstrual cycles, approximately 80 will become pregnant. Use of emergency contraceptive pills would reduce this number by 75 percent, to 20 women.^[16]

Mifepristone regimen:

In three randomized trials providing individual data of mifepristone 10 mg taken up to 120 hours (5 days) after intercourse, the combined estimate of pregnancies prevented was 83%.^[17] In high quality trials, mifepristone 10 mg had similar effectiveness to mifepristone 25-50 mg, which had similar effectiveness to levonorgestrel 1.5 mg.^[18][19]

The effectiveness of emergency contraception is highest when taken within 12 hours of intercourse and declines over time.^[20][21] The limit of 72 hours is based on a study by the World Health Organization (WHO).^[3] A subsequent WHO study has suggested that reasonable effectiveness continues for up to 120 hours (5 days) after intercourse.^[19]

Effectiveness estimate calculation

Early studies of emergency contraceptives did not attempt to calculate a failure rate, they simply reported the number of women who became pregnant after using an emergency contraceptive. Since 1980, clinical trials of emergency contraception have estimated effectiveness using: observed pregnancies divided by the estimated (by cycle day) number of women who would have become pregnant without treatment.^[22]

In their April 2007 emergency review article, Trussell and Raymond note:

Calculation of effectiveness, and particularly the denominator of the fraction, involves many assumptions that are difficult to validate. Therefore, reported figures on the efficacy of emergency contraception may be underestimates or, more probably, overestimates. Yet, precise estimates of efficacy may not be highly relevant to many women who have had unprotected intercourse, since ECPs are often the only available treatment. A more important consideration for most ECP clients may be the fact that data from both clinical trials and mechanism of action studies clearly show that at least the levonorgestrel regimen of ECPs is more effective than nothing.^[23]

It's important to remember that this kind of effectiveness measurement is of the number of women who would have gotten pregnant but for the medical intervention, but did not. For instance, an effectiveness of 89% doesn’t mean that 11 percent of women will get pregnant. It instead would mean that emergency contraception prevents 89% of the pregnancies researchers would expect to happen when women don’t use birth control. Usually, if 100 women have unprotected sex one time during the second or third week of their monthly menstrual cycle, 8 of them will get pregnant. If a particular form of emergency contracpetion were 89% effective, that would mean that if those same 100 women used that form of emergency contraception, only 1 would get pregnant. Put another way, this is an 89% reduction in the expected number of pregnancies. ^[24]

• Eight studies of the progestin-only (levonorgestrel) regimen, that included more than 9,500 women, reported effectiveness estimates between 59% and 94%.^[23]
• A meta-analysis of eight studies of the combined (Yuzpe) regimen, that included more than 3,800 women and reported effectiveness estimates between 56% and 89%, concluded that the best point estimate of effectiveness was 74%.^[23][25]
• A more recent analysis of two of the largest combined (Yuzpe) regimen studies, using possibly more accurate estimates of conception probabilities by cycle day, found effectiveness estimates of 47% and 53%.^{[3][23][26][27]}
• Combined data from two randomized trials that directly compared the two regimens, found the levonorgestrel regimen was twice as effective as the Yuzpe regimen.^{[3][18][23][28][29]}

Placebo-controlled trials that could give a precise measure of effectiveness for EC would be unethical, so the effectiveness percentage is estimated. This is currently done using variants of the calendar method.^[30] Women with irregular cycles for any reason (including recent hormone use such as oral contraceptives and breastfeeding) must be excluded from such calculations. Even for women included in the calculation, the limitations of calendar methods of fertility determination have long been recognized. Recently, hormonal assay has been suggested as a more accurate method of estimating fertility for EC studies.^[31]

Safety

Existing pregnancy is not a contraindication in terms of safety, as there is no known harm to the woman, the course of her pregnancy, or the fetus if progestin-only or combined emergency contraception pills are accidentally used, but EC is not indicated for a woman with a known or suspected pregnancy because it is not effective in women who are already pregnant.^{[23][32][33][34][35][36][37][38]}

The WHO Medical Eligibility Criteria for Contraceptive Use list no medical condition for which the risks of emergency contraceptive pills (using progestin-only or combined oral contraceptive pills) outweigh the benefits, specifically noting breastfeeding and history of ectopic pregnancy as conditions where there are no restrictions on use of ECPs, and history of severe cardiovascular disease (heart attack, stroke, blood clots), angina, migraine, and severe liver disease (including jaundice) as conditions where the advantages of using emergency contraceptive pills generally outweigh the theoretical or proven risks.^[36] The American Academy of Pediatrics (AAP) and experts on emergency contraception say progestin-only ECPs may be preferable to combined ECPs containing estrogen in women with a history of blood clots, stroke, or migraine.^[23][32][33]

The AAP, American College of Obstetricians and Gynecologists (ACOG), U.S. Food and Drug Administration, the WHO, the Royal College of Obstetricians and Gynaecologists's Faculty of Family Planning & Reproductive Health Care (FFPRHC) and other experts on emergency contraception state that there are no medical conditions in which progestin-only ECPs are contraindicated.^{[23][32][33][34][35][36][37]} The FFPRHC UK Medical Eligibility Criteria for Contraceptive Use specifically note current venous thromboembolism, current or past history of breast cancer, inflammatory bowel disease, and acute intermittent porphyria as conditions where the advantages of using emergency contraceptive pills generally outweigh the theoretical or proven risks.^[37]

The herbal preparation of St John's wort and some enzyme-inducing drugs (e.g. anticonvulsants or rifampicin) may reduce the effectiveness of ECP, and a larger dose may be required.^[39][40]

The AAP, ACOG, FDA, WHO, FFPRHC and experts on emergency contraception say that ECPs, like all other contraceptives, reduce the absolute risk of ectopic pregnancy by preventing pregnancies, and that the best available evidence, obtained from over 7,800 women in randomized controlled trials, indicates there is no increase in the relative risk of ectopic pregnancy in women who become pregnant after using progestin-only ECPs.^{[23][32][33][34][35][36][37][38][39][41]}

Side effects

The most common side effect reported by users of emergency contraceptive pills was nausea (50.5% of 979 Yuzpe regimen users and 23.1% of 977 levonorgestrel-only users in the 1998 WHO trial; 14.3% of 2,720 levonorgestrel-only users in the 2002 WHO trial); vomiting is much less common and unusual with levonorgestrel-only ECPs (18.8% of 979 Yuzpe regimen users and 5.6% of levonorgestrel-only users in the 1998 WHO trial; 1.4% of 2,720 levonorgestrel-only users in the 2002 WHO trial).^[3][19][39] Anti-emetics are not routinely recommended with levonorgestrel-only ECPs.^[39][42] If a woman vomits within 2 hours of taking a levonorgestrel-only ECP, she should take a further dose as soon as possible.^[39][43]

Other common side effects (each reported by less than 20% of levonorgestrel-only users in both the 1998 and 2002 WHO trials) were abdominal pain, fatigue, headache, dizziness, and breast tenderness.^[3][19][39] Side effects usually do not occur for more than a few days after treatment, and they generally resolve within 24 hours.^[23]

Temporary disruption of the menstrual cycle is also commonly experienced. If taken before ovulation, the high doses of progestogen in levonorgestrel treatments may induce progestogen withdrawal bleeding a few days after the pills are taken. One study found that about half of women who used levonorgestrel ECPs experienced bleeding within 7 days of taking the pills.^[44] If levonorgestrel is taken after ovulation, it may increase the length of the luteal phase, thus delaying menstruation by a few days.^[45] Mifepristone, if taken before ovulation, may delay ovulation by 3-4 days.^[46] (Delayed ovulation may result in a delayed menstruation.) These disruptions only occur in the cycle in which ECPs were taken; subsequent cycle length is not significantly affected.^[44] If a woman's menstrual period is delayed by a week or more, it is advised that she take a pregnancy test.^[47] (Earlier testing may not give accurate results.)

Intrauterine device (IUD) for emergency contraception

An alternative to emergency contraceptive pills is the copper-T intrauterine device (IUD) which can be used up to 5 days after unprotected intercourse to prevent pregnancy. Insertion of an IUD is more effective than use of Emergency Contraceptive Pills - pregnancy rates when used as emergency contraception are the same as with normal IUD use. IUDs may be left in place following the subsequent menstruation to provide ongoing contraception (3-10 years depending upon type).^[48]

Postcoital high-dose progestin-only oral contraceptive pills as ongoing contraception

One brand of levonorgestrel pills, Postinor, is marketed as an ongoing method of postcoital contraception.^[49] However, there are serious drawbacks to such use of postcoital high-dose progestin-only oral contraceptive pills, especially if they are not used according to their package directions, but are instead used according to the package directions of emergency contraceptive pills:

• Due to the increasing severity of side effects with frequent use, Postinor is only recommended for women who have intercourse four or fewer times per month.^[49][50]
• If not used according to their package directions, but instead used according to the directions of levonorgestrel emergency contraceptive pills (up to 72 hours after intercourse), they would be estimated to have a "perfect-use" (when not used according to their package directions but used as directed on the package directions for levonorgestrel emergency contraception pills) pregnancy rate of 20% per year when used as the sole means of contraception (as compared to a 40% annual pregnancy rate for the Yuzpe regimen).^[24] These failure rates would be higher than those of almost all other birth control methods, including the rhythm method and withdrawal.^[51]
• Like all hormonal methods, postcoital high-dose progestin-only oral contraceptive pills do not protect against sexually transmitted infections.^[52]

ECPs are generally recommended for backup or "emergency" use, rather than as the primary means of contraception. They are intended for use when other means of contraception have failed—for example, if a woman has forgotten to take a birth control pill or when a condom is torn during sex.^[24]

History

Interest in synthetic hormones as postcoital contraceptives originated several decades ago, with the first published study on the subject appearing in 1967.^[53] A few different drugs were studied, with a focus on high-dose estrogens, and it was originally hoped that postcoital contraception would prove viable as an ongoing contraceptive method.^[54]

The first widely used methods were five-day treatments with high-dose estrogens, using diethylstilbestrol (DES) in the US and ethinyl estradiol in the Netherlands.^[55][56]

In the early 1970s, the Yuzpe regimen was developed by AA Yuzpe (1974);^[57] progestin-only postcoital contraception was investigated (1975);^[58] and the copper IUD was first studied for use as emergency contraception (1975).^[59] Danazol was tested in the early 1980s in the hopes that it would have fewer side effects than Yuzpe, but was found to be ineffective.^[60]

The Yuzpe regimen became the standard course of treatment for postcoital contraception in many countries in the 1980s. The first prescription-only combined estrogen-progestin dedicated product, Schering PC4 (ethinylestradiol and norgestrel), was approved in the UK in January 1984 and first marketed in October 1984.^[61] Schering introduced a second prescription-only combined product, Tetragynon (ethinylestradiol and levonorgestrel) in Germany in 1985.[1] By 1997, Schering AG dedicated prescription-only combined products had been approved in only 9 countries: the UK (Schering PC4), New Zealand (Schering PC4), South Africa (E-Gen-C), Germany (Tetragynon), Switzerland (Tetragynon), Denmark (Tetragynon), Norway (Tetragynon), Sweden (Tetragynon) and Finland (Neoprimavlar); and had been withdrawn from marketing in New Zealand in 1997 to prevent it being sold over-the-counter.[2][3][4] Regular combined oral contraceptive pills (which were less expensive and more widely available) were more commonly used for the Yuzpe regimen even in countries where dedicated products were available.^[62]

Over time, interest in progestin-only treatments increased. The Special Program on Human Reproduction (HRP), an international organization whose members include the World Bank and World Health Organization, "played a pioneering role in emergency contraception" by "confirming the effectiveness of levonorgestrel."^[63] After the WHO conducted a large trial comparing Yuzpe and levonorgestrel in 1998,^[64][65] combined estrogen-progestin products were gradually withdrawn from some markets (Preven in the United States discontinued May 2004, Schering PC4 in the UK discontinued October 2001, and Tetragynon in France) in favor of progestin-only EC, although prescription-only dedicated Yuzpe regimen products are still available in some countries.

In 2002, China became the first country in which mifepristone was registered for use as EC.

United States

• DES
  • In 1971, a New England Journal of Medicine editorial calling attention to previously published studies on the use of DES as a postcoital contraceptive at Yale University, and a large study published in JAMA on the use of DES as a postcoital contraceptive at the University of Michigan, led to off-label use of DES as a postcoital contraceptive becoming prevalent at many university health services.^[66][67]
  • In May 1973, in an attempt to restrict off-label use of DES as a postcoital contraceptive to emergency situations such as rape, a FDA Drug Bulletin was sent to all U.S. physicians and pharmacists that said the FDA had approved, under restricted conditions, postcoital contraceptive use of DES.^[68] (In February 1975, the FDA Commissioner testified that the only error in the May 1973 FDA Drug Bulletin was that the FDA had not approved postcoital contraceptive use of DES.)^[69]
  • In September 1973, the FDA published a proposed rule specifying patient labeling and special packaging requirements for any manufacturer seeking FDA approval to market DES as a postcoital contraceptive, inviting manufacturers to submit abbreviated new drug applications (ANDAs) for that indication, and notifying manufacturers that the FDA intended to order the withdrawal of DES 25 mg tablets (which were being used off-label as postcoital contraceptives).^{[70][71][72][73]}
  • In late 1973, Eli Lilly, the largest U.S. manufacturer of DES, discontinued its DES 25 mg tablets and in March 1974 sent a letter to all U.S. physicians and pharmacists telling them it did not recommend use of DES as a postcoital contraceptive.^[69]
  • Only one pharmaceutical company, Tablicaps, Inc., a small manufacturer of generic drugs, ever submitted (in January 1974) an ANDA for use of DES as an emergency postcoital contraceptive, and the FDA never approved it.^[69][74]
  • In February 1975, the FDA said it had not yet approved DES as a postcoital contraceptive, but would after March 8, 1975 permit marketing of DES for that indication in emergency situations such as rape or incest if a manufacturer obtained an approved ANDA that provided patient labeling and special packaging as set out in a FDA final rule published in February 1975.^[75] To discourage off-label use of DES as a postcoital contraceptive, in February 1975 the FDA ordered DES 25 mg (and higher) tablets removed from the market and ordered the labeling of lower doses (5 mg and lower) of DES still approved for other indications be changed to state: "THIS DRUG PRODUCT SHOULD NOT BE USED AS A POSTCOITAL CONTRACEPTIVE" in block capital letters on the first line of the physician prescribing information package insert and in a prominent and conspicuous location of the container and carton label.^[76][77]
  • In March 1978, a FDA Drug Bulletin was sent to all U.S. physicians and pharmacists which said: "FDA has not yet given approval for any manufacturer to market DES as a postcoital contraceptive. The Agency, however, will approve this indication for emergency situations such as rape or incest if a manufacturer provides patient labeling and special packaging. To discourage 'morning after' use of DES without patient labeling, FDA has removed from the market the 25 mg tablets of DES, formerly used for this purpose."^[78]
  • In the 1980s, off-label use of the Yuzpe regimen superseded off-label use of DES for postcoital contraception.^[74][79][80]
  • DES is no longer commercially available in the U.S.; Eli Lilly, the last U.S. manufacturer, ceased production in spring 1997.^[81]

• Yuzpe regimen & Preven
  • On February 25, 1997, the FDA posted a notice in the Federal Register saying it had concluded that the Yuzpe regimen was safe and effective for off-label use as postcoital EC, was prepared to accept NDAs for COCPs labeled as ECPs, and listed 6 then available COCPs (there are now 22) that could be used as ECPs.^[4]
  • On September 1, 1998, the FDA approved the prescription Yuzpe regimen Preven Emergency Contraception Kit (which contained a urine pregnancy test and 4 COCPs).^[82] Preven was discontinued in May 2004.^[83]

• Plan B
  • On July 28, 1999, the FDA approved the prescription progestin-only Plan B (two 750 µg levonorgestrel pills) emergency contraceptive.^[84]
  • On August 24, 2006, the FDA approved nonprescription behind-the-counter access to Plan B from pharmacies staffed by a licensed pharmacist for women 18 or older; a prescription-only form of Plan B will remain available for young women aged 17 and younger.^[85]
  • On November 6, 2006, Barr Pharmaceuticals announced that its subsidiary, Duramed Pharaceutials, had initiated shipment of dual-label Plan B OTC/Rx and it would be available in pharmacies across the U.S. by mid-November 2006.^[86]

International Consortium for Emergency Contraception

In 1995, the Rockefeller Foundation convened a meeting to discuss emergency contraception. After the meeting, a group of seven international organizations formed The International Consortium for Emergency Contraception (ICEC) to promote EC as a part of mainstream reproductive health care worldwide.^[87] Dedicated products for EC were "virtually unknown" in 1995, there was little awareness of EC as an option, and EC was not used as public health measure.^[88]

The seven founding member organizations were the Concept Foundation, the International Planned Parenthood Federation (IPPF), the Pacific Institute for Women's Health, the World Health Organization (WHO), the Population Council, Population Services International, and the Program for Appropriate Technology in Health (PATH).^[87]

The Concept Foundation is the distribution arm of ICEC; its funding for the development of Postinor-2 came from the Rockefeller Foundation and the David and Lucile Packard Foundation, as well as the other ICEC organizations.^[89]

The Consortium helped promote the availability of EC by:^[88]

• Manufacturing an EC product. The ICEC worked with the Hungarian pharmaceutical firm Gedeon Richter to repackage its contraceptive Postinor as an emergency contraceptive, called Postinor-2. Distributing Postinor-2, principally in developing countries, was the primary work of the ICEC.
• Facilitating product registration in two ways. First, the ICEC encouraged interest in EC products through meetings with public-sector agencies and non-governmental organizations (NGOs) who they perceived would benefit from adding EC to the products they distribute. Second, by helping organizations applying for EC registration through the country-specific approval process, including lobbying of local leaders who may be influential in the registration decision.
• Negtiotiating a public-sector price. The ICEC's agreement with Gedeon Richter provided a discount price at which EC could be obtained by public-sector agencies in developing countries.
• Marketing and social marketing.

An ICEC member organization, the International Planned Parenthood Federation (IPPF), has launched its own dedicated levonorgestrel EC product, Optinor.^[90]

Relationship to risky sex and abortion

The current (October 2005) AAP Policy Statement on Emergency Contraception states: "The concern that widespread emergency contraception use would encourage unprotected coitus in teens is not supported in the literature."^[32]

The current (December 2005) ACOG Practice Bulletin on Emergency Contraception states: "A prominent concern among both women and health care providers is that making emergency contraception more readily available could encourage irresponsible sexual behavior, which would increase the risks of both unintended pregnancy and sexually transmitted diseases. However, numerous studies have shown that this concern is unfounded."^[34]

The latest (April 2007) review by emergency contraception experts Trussell and Raymond^[23] states: "Reported evidence demonstrates that making ECPs more widely available does not increase risk-taking^{[91][92][93][94][95][96][97][98][99][100][101]} and that women who are the most diligent about ongoing contraceptive use are those most likely to seek emergency treatment."^[102]

However, the availability of ECPs has not been shown to lower abortion rates. In France, Sweden, and Britain—where Yuzpe-regimen EC had been available by prescription for more than a decade and progestin-only EC has been available without a prescription for 8, 6, and 2 years respectively—the abortion rate was stable or higher during that time period.^[103] Another study concluded that distribution of free, advance supplies of EC to large numbers of women in Scotland did not reduce abortion rates.^[104] A randomized controlled trial of 2000 women in China compared women with advance access to EC to women without access, and noted that the pregnancy rate was the same between the two groups. The study observed that "...providing EC in advance increases use, but there is no direct evidence that it reduces unintended pregnancy" and concluded that EC may not lower abortion rates.^[105]

In September 2006, emergency contraception expert Anna Glasier wrote a BMJ editorial entitled "Emergency Contraception. Is it worth all the fuss?" that said in closing: "So is emergency contraception worth the fuss? If you are a woman who has had unprotected sex then of course it is, because emergency contraception will prevent pregnancy in some women some of the time—and if you don’t want to get pregnant anything is better than nothing. If you are the CMAJ’s editor or FDA commissioner then yes, because scientific freedom is worth the fight. If you are looking for an intervention that will reduce abortion rates, emergency contraception may not be the solution, and perhaps you should concentrate most on encouraging people to use contraception before or during sex, not after it."^[106]

EC and sexual assault

Before EC was used in the general population or defined as "emergency contraception," it was used, beginning in the 1960s and 70s, specifically as a treatment for victims of sexual assault.^[107][108] Although EC is in wide use as an option for victims of sexual assault, some researchers believe it is underutilized as a public health measure.^[109] Abortions because of rape account for less than one percent of all annual abortions.^[110]

Mechanism of action

The United States FDA states that progestin-only ECPs like Plan B work by preventing ovulation. It also says "it is possible" that progestin-only ECPs may interfere with the embryo implanting in the uterine lining, and that they have no effect on pregnancies if taken after implantation.^[111][112]

A number of studies in the 1970s and 80s concluded that emergency contraception could cause changes in the endometrium^[113] that would prevent implantation of an early-stage embryo in the uterus. This research led many pro-life advocates, who believe that pregnancy begins at fertilization, to oppose ECPs as an abortifacient.

In recent years--especially in light of U.S. ethical controversy over the research's claims--the scientific community has begun to critically reevaluate the early studies, introducing doubt into the argument that ECPs prevent implantation. Recent studies in rats and monkeys have shown that post-ovulatory use of progestin-only and combined ECPs have no effect on pregnancy rates.^[114][115] Studies in humans have shown that the rate of ovulation suppression is approximately equal to the effectiveness of emergency contraceptive pills,^[116][117] suggesting that might be the only mechanism by which they prevent pregnancy.

However, these studies have also shown that, in women who ovulate despite taking ECP before ovulation, there are changes in certain hormones such as progesterone and in the length of luteal phase.^[116] These secondary changes might inhibit implantation in cases where fertilization occurs despite ECP use. Because of the difficulty of studying embryos inside the uterus and fallopian tubes prior to implantation, both sides of this debate concede that completely proving or disproving the theory may be impossible.^[118][114]

When used as a regular method of contraception, IUDs have been proven to act primarily through spermicidal and ovicidal mechanisms, but it is considered possible that these same mechanisms are also harmful to embryos that have not yet implanted.^[119]

Hormonal progestin-only and combined estrogen-progestin emergency contraceptives such as Yuzpe regimen or Plan B are different from the anti-hormonal drug mifepristone (also known as Mifeprex and RU-486), an abortifacient which can induce abortion if taken after implantation. Yuzpe and progestin-only emergency contraception will have no effect if taken after implantation.

United States legal and ethical controversies

• A great deal of controversy accompanied the FDA approval of over-the-counter (OTC) access to Plan B. Supporters of over-the-counter access believe that easier access will reduce unintended pregnancy and abortion rates; some pro-life opponents believe that EC itself is a form of abortion.^[120] The American Medical Association, the American Academy of Family Physicians, the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and other leading U.S. medical organizations all supported OTC access.^[121] An advisory committee to the FDA recommended that Plan B be made available over the counter in 2003.^[122] In 2004, the FDA refused the advisory board's recommendation and prohibited over-the-counter sale, citing insufficient evidence that ECPs could be used safely by adolescents without medical supervision. Reproductive rights supporters accused the FDA of basing the decision on political pressure from the pro-life lobby. The Center for Reproductive Rights filed a lawsuit regarding the approval process, which has not been resolved as of December 2006. In the legal proceedings, two senior FDA officials have alleged in depositions that the decision to reject the OTC application was made on political, rather than scientific, grounds to "appease the administration's constituents".^[123][124] Depositions taken from other FDA officials do not indicate White House involvement.^[123] In 2006, the FDA approved over-the-counter access to Plan B for women 18 years of age and older.^[125]

• A Massachusetts law that went into effect on 14 December, 2005, requires all hospitals in the state to provide emergency contraception to any "female rape victim of childbearing age"^[126] including Catholic Hospitals who oppose the provision of emergency contraception. In a letter criticizing the joint UN/WHO Inter-agency Field Manual on Reproductive Health in Refugee Situations, the Catholic Church explains its belief that emergency contraception, along with IUDs and hormonal contraception, cannot be considered "solely contraceptive because in the case of effective fertilization a chemical abortion would be carried out during the first days of pregnancy."^[127] The Catholic position on family planning is explained further in Ethical and Religious Directives for Catholic Health Care Services.^[128] Because of this expressed moral stance against emergency contraception, the Massachusetts Catholic Conference opposed this law, stating interference with religious freedom. According to The New England Journal of Medicine, "compelling arguments can be made both for and against a pharmacist's right to refuse prescriptions for emergency contraception."^[129]

• In isolated instances across the United States, pharmacists have refused to dispense emergency contraception even when presented with a legal prescription.^[130] In addition, Wal-Mart, the nation's fifth-largest distributor of pharmaceuticals, refused to stock EC, beginning with Preven in 1999.^[131] However, Wal-Mart reversed this position when it was announced that stores would sell Plan B in March of 2006.^[132]