Emergency Contraception Prevents Fertilization, not Implantation, Studies Show

Reprinted with permission of Population Council

NEW YORK (2 May 2005)--Recent research by members of the Population Council's International Committee for Contraception Research (ICCR) and other scientists shows that emergency contraceptive pills appear to work by interfering with ovulation, thus preventing fertilization of the egg. They do not appear to disrupt postfertilization events, such as the implantation of a fertilized egg in the uterus.

Emergency contraception prevents pregnancy most effectively when taken within 72 hours of unprotected intercourse. The researchers studied levonorgestrel, a progestin widely used for regular hormonal contraception that is also used for emergency contraception. Emergency contraception has been the subject of heated debate. At issue is the method's mechanism of action: does it prevent the meeting of egg and sperm, or does it prevent a fertilized egg from implanting in the uterus? A method that allows the fertilization of an egg but prevents the fertilized egg from implanting in the uterus may be considered abortifacient by some.

Over the past few years, reproductive physiologist Horacio B. Croxatto of the Chilean Institute for Reproductive Medicine in Santiago, Chile, and his colleagues have studied the effects of levonorgestrel on the reproductive cycles of female rats, monkeys, and humans. Croxatto and one of his study partners, biomedical researcher Vivian Brache of PROFAMILIA in Santo Domingo, Dominican Republic, are members of the ICCR.

Croxatto and his colleagues exposed female rats to very high doses of levonorgestrel at various stages of their reproductive cycles, either before or after ovulation or before or after mating. The researchers found that levonorgestrel inhibited ovulation totally or partially, depending on the timing of treatment and the dose administered. However, the drug had no effect on fertilization or implantation. This research was published in the May 2003 issue of the journal Contraception.

Next, Croxatto and his colleagues studied the effects of levonorgestrel given to Cebus monkeys either before ovulation or postcoitally. The reproductive cycle of each animal was monitored by ultrasound examination of  the ovaries, vaginal smears, and measurements of blood hormone levels, in order to time the administration of levonorgestrel. The researchers found that, when given before ovulation, levonorgestrel was able to inhibit or postpone ovulation. Alternatively, when it was given after mating-at a time when fertilization was believed to have occurred (on the basis of previous monitoring)-the pregnancy rates observed were identical in cycles treated with levonorgestrel or with a placebo. This indicates that levonorgestrel did not interfere with any postfertilization process required for embryo implantation. This research was published in the June 2004 issue of the journal Human Reproduction.

Women may become pregnant when they have intercourse in the five days before ovulation. This is because sperm can live in the female reproductive system for up to five days. An egg, however, is usually viable for only six to 12 hours after it is released. Croxatto, Brache, and their colleagues studied the effects of levonorgestrel administered during this fertile preovulatory period of women's menstrual cycles. The researchers used Plan BR, a levonorgestrel-containing emergency contraceptive product marketed in the United States and Canada.

Twenty-nine women in Santiago and 29 women in Santo Domingo were enrolled in the study. All of the women were protected from pregnancy by tubal ligation or a nonhormonal intrauterine device. The study was randomized, double-blind, and placebo-controlled. Women were treated with either a placebo, a full dose of Plan B emergency contraception, or a half dose of the drug. They were followed over several menstrual cycles and, by the end of the study, each woman had received all three of these treatments, separated by resting cycles. The women were randomly assigned to receive the treatments at specific times during the fertile preovulatory period, according to the diameter of the leading ovarian follicle, as determined by ultrasound. The leading ovarian follicle is the structure that ruptures to release the egg. In 82 percent of Plan B-treated cycles, follicles failed to rupture within the five-day period following treatment (the maximum time span sperm would survive in the female reproductive tract), or there was some significant abnormality in ovulation. These conditions occurred in only 41 percent of placebo cycles. The rate of failed or abnormal ovulation that was observed with Plan B treatment is identical with the estimated efficacy rate of Plan B emergency contraception. Blood tests on these women indicated that Plan B influences ovulation by suppressing the surge of luteinizing hormone (LH), the hormone that triggers ovulation.

"There is no doubt that fertilization would not have taken place in those women should they have had intercourse prior to treatment," says Croxatto. "We conclude that the effects exerted by Plan B, when it is taken before the onset of the LH surge, may fully explain the pregnancies averted by emergency contraception. Failure to affect the LH surge, because treatment was begun too late in the fertile preovulatory period, explains the 20 percent failure rate of this method. Our data presented in this paper suggest that emergency contraception using levonorgestrel works by disrupting ovulation, not by interfering with implantation." This research was published in the December 2004 issue of the journal Contraception.

The May 2005 Population Briefs is now available at http://www.popcouncil.org/pdfs/popbriefs/pbmay05.pdf

Other articles in this issue are:

* Postabortion Complications Prevalent in Pakistan
* Globalization Is Transforming Adolescence in the Developing World
* Guide for Improving Adherence to Drug Therapies
* Sperm with Bent Tails Point to Possible Male Contraceptive

Population Briefs highlights the Population Council's research in biomedicine, public health, and social science as well as its international collaborations. The free newsletter is available in print and electronically.

The Population Council (www.popcouncil.org) is an international, nonprofit, nongovernmental organization that seeks to improve the well-being and reproductive health of current and future generations around the world and to help achieve a humane, equitable, and sustainable balance between people and resources. The Council conducts biomedical, social science, and public health research and helps build research capacities in developing countries. Established in 1952, the Council is governed by an international board of trustees. Its New York headquarters supports a global network of regional and country offices.