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Population Council, May 2, 2005
Emergency Contraception
Prevents Fertilization, not Implantation, Studies
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NEW YORK --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 B®, 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
thatruptures 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.
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