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Postfertilization Effects of Oral Contraceptives and Their Relationship to
informed
consent
Walter L. Larimore,
MD; Joseph B. Stanford, MD, MSPH
Arch Fam Med. 2000;9:126-133.
ABSTRACT
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The primary
mechanism of oral contraceptives is to inhibit ovulation, but
this mechanism is not always operative. When breakthrough ovulation
occurs, then secondary mechanisms operate to prevent clinically
recognized pregnancy. These secondary mechanisms may occur either
before or after fertilization. Postfertilization effects would
be problematic for some patients, who may desire information
about this possibility. This article evaluates the available
evidence for the postfertilization effects of oral contraceptives
and concludes that good evidence exists to support the hypothesis
that the effectiveness of oral contraceptives depends to some
degree on postfertilization effects. However, there are insufficient
data to quantitate the relative contribution of postfertilization
effects. Despite the lack of quantitative data, the principles
of informed
consent
suggest that patients who may object to any postfertilization
loss should be made aware of this information so that they can
give fully informed
consent
for the use of oral contraceptives.
INTRODUCTION
Oral contraceptives (OCs) are among the most extensively studied
and used medications in the world,1 and are accessible
without a prescription in some countries, although still virtually
unavailable in others. In America, OCs have contributed
to an increased acceptability of birth control,2 although,
for many patients, decisions about contraception still have moral,
ethical, and religious implications.3-4 For patients
who believe that human life begins at fertilization (conception),
a method of birth control that has the potential of interrupting
development after fertilization (a postfertilization effect)
may not be acceptable.5-6 Postfertilization effects are
operative for emergency (postcoital) contraception (when it is
administered too late to prevent ovulation),7-8 luteolytic
agents (ie, RU-486),9 and intrauterine devices,5 and
these methods therefore are unacceptable to some patients. Although
postfertilization effects have been cited as a secondary mechanism
of OCs,10-12 the evidence
for such effects has not been systematically reviewed. The purpose
of this article was to review and grade the available evidence
for postfertilization effects of OCs and discuss the implications
for informed
consent,
based on the premise that patients to whom postfertilization
effects are important have the right to make decisions
based on the best available evidence.13-15
Our analysis of the evidence involved a review of the abstracts
of all studies of OCs published since 1970 available on
MEDLINE that discussed the commonly used OCs, including low-dose
(<50 µg of estrogen) phasic combined oral contraceptives
(COCs), low-dose monophasic COCs, and progestin-only OCs (progestin-only
pills [POPs]). We also reviewed the patient handouts provided
by OC manufacturers and the most recent editions of several
medical textbooks and reference books.
Since there is variability in the definitions and use of terminology
in reproductive medicine, we used the American Academy
of Obstetrics and Gynecology Committee on Ethics' definitions
for fertilization, implantation, embryo,
and preembryo.16 Preembryo is a general term
that includes the human developmental stages that occur after
fertilization but prior to the appearance of the primitive streak
about 14 days after fertilization. From that point until the end
of the eighth week after fertilization, the term embryo is
used. Implantation is the process whereby the preembryo attaches to
the endometrial lining of the uterus. This process begins 5 to
7 days after fertilization and may last several days. For this
review, we defined postfertilization effects to include mechanisms
of action that operate after fertilization to prevent a clinically
recognized intrauterine pregnancy. We looked specifically for
studies referencing any postfertilization effects of OCs. When
many studies indicated similar findings, we listed the most recent
or most methodologically sound references or other systematic
or general reviews of particular subjects.
MECHANISMS
OF OCs
The literature discusses several mechanisms for OCs. While the primary
effect of OCs is the inhibition of ovulation via suppression of
pituitary gonadotropin secretion (this mechanism is operative most
of the time),1,
10,
12
secondary effects are implicated at times of breakthrough ovulation
to prevent clinically recognized pregnancy.17-18 We classified
these secondary effects as occurring either prefertilization
or postfertilization. Secondary prefertilization effects may
include alterations in cervical mucus that limit sperm penetration2, 17-20 and changes
in the endometrium and fallopian tube that may impede normal
sperm transport.2, 17-18,21
Breakthrough ovulation rates vary by the form and the dose of
the OC used.2, 10, 12, 18, 22 With OCs, breakthrough ovulation
is more likely with lower doses of estrogen and with imperfect
rather than perfect use.10, 12, 16-17,23-25 Perfect
use of OCs implies taking them consistently and correctly (ie,
in the correct order, on time, each and every day, and without
other medications that might diminish the effectiveness of OCs).
Typical use is described as the full range
of usage patterns for OCs that actually occur in women.1, 11-12,18 While
some smaller studies that evaluated small numbers of women for
6 or fewer cycles have reported breakthrough ovulation rates of
near 0, studies that evaluated women for at least 6 cycles demonstrated
ovulation rates ranging from 1.7%25 to 28.6%23 per cycle.
For POPs, reported breakthrough ovulation rates range from 33%26 to 65%.20, 27-28
Obviously, breakthrough ovulation can result in unintended pregnancy1, 17-18; however,
the pregnancy rates with typical use vary widely and are often
underestimated.29 Unadjusted analyses of unintended
pregnancies while using COCs report rates of 0.1 to 1.0
per 100 woman-years of use in perfect use and 3 per 100 woman-years
in the first year of typical use.1, 10, 12, 17-18,20 Most of
these data do not account for elective abortions. One
national analysis that accounted for the underreporting
of elective abortions estimated that the unintended pregnancy
rates during the first year of OC use were 4% for "good compliers,"
8% for "poor compliers," and up to 29% for some users.29 Rates
of pregnancy are higher with POPs than with COCs.1, 17-18 Unadjusted
analyses of pregnancies while taking POPs reported rates of 0.5
to 1.0 per 100 woman-years of perfect use and 3 to 7 per 100
woman-years in the first year of typical use.1, 10, 12, 17-18,20 However,
these rates have not been adjusted for elective abortions and
are almost certainly underestimated.29 Progestin-only
pills are reported to have potent effects on both cervical mucus
and the endometrium.19-21,30-31 While this has led to speculation
that "the principal mode of action is . . . to make the cervical
mucus hostile to the transport of the sperm,"17 animal
model data32
and data on ectopic pregnancy rates (reviewed below) suggest
that postfertilization effects also play a role.
In theory, postfertilization effects of OCs could involve any
1 or more of the following 3 mechanisms of action: (1)
A postfertilization preimplantation effect would consist of a
slower transport of the preembryo through the fallopian tube,
preventing the preembryo from implanting in the uterus; this could
result either in the unrecognized loss of the preembryo or in
an ectopic (tubal) pregnancy if the preembryo had slower tubal
transport and ended up implanting in the fallopian tube. (2) A
peri-implantation effect would be the alteration of
the endometrium, such that a preembryo that reached the uterus
was unable to successfully implant into the endometrial
lining of the uterus. (3) A postimplantation effect could result
from alteration of the endometrium not sufficient to prevent implantation
but unfavorable for maintenance of the pregnancy; a preembryo
or embryo already implanted in the endometrial lining of the uterus
would be unable to maintain itself long enough to result in a
clinically recognized pregnancy.
EVIDENCE
FOR POSTFERTILIZATION EFFECTS
Direct evidence of postfertilization preimplantation and peri-implantation
effects would require methods that directly measured the
rate of fertilization and the loss of the preembryo in women
taking OCs. Transcervical tubal washings have been
used in women using intrauterine devices to quantify the rate
of ova fertilization33 and could theoretically
be done for women taking OCs. However, there is no proven method
to measure the loss of the preembryo prior to implantation, even
though a number of possible methods have been investigated that
involve maternal hormones that may be produced or altered after
fertilization.34-36 Probably the most promising
method is the isolation of "early pregnancy factor."37-39
Direct evidence of a postimplantation effect on the preembryo
or embryo prior to clinically recognized pregnancy would
require measurement with ultrasensitive assays for 
–human chorionic gonadotropin (
-HCG) or other pregnancy-related hormones.40 Although
ultrasensitive assays for
-HCG have been done with normally fertile women not using OCs,41-44 as well
as with women using nonhormonal methods of contraception,45 we could
find no such studies in women using OCs. Despite the lack of
these data, at least 3 lines of evidence have been suggested
to support the hypothesis that 1 or more postfertilization
effects are operative in at least some women taking OCs. Using
a standard quality of evidence table46 (Table 1), we graded the available evidence.
Endometrial
Changes That May Affect Endometrial Receptivity
Oral contraceptives directly affect the endometrium.1, 10, 12, 20-21 These
effects have been presumed to render the endometrium relatively
inhospitable to implantation or to the maintenance of the preembryo
or embryo prior to clinically recognized pregnancy by producing
a predecidual or decidualized endometrial bed with diminished
thickness and with widely spaced, exhausted, and atrophied glands;
by altering the cellular structure of the endometrium, leading
to the production of areas of edema alternating with areas of
dense cellularity18, 20-21; and by altering the biochemical
and protein composition of the endometrium.47
Although these changes are consistently seen in women taking
OCs, there is currently no direct evidence to link these
changes to preembryo or embryo loss in women taking OCs. However,
this hypothesized postfertilization effect seems to be so well
accepted that in many medical articles and textbooks it has been
explicitly listed as the third mechanism of OCs (after suppressing
ovulation and prefertilization effects).1, 10, 17-18 For example,
the Food and Drug Administration–approved product information
for OCs in the Physicians' Desk Reference states,
Although the primary mechanism
of this action is inhibition of ovulation, other alterations
include changes in the cervical mucus, which increase the difficulty
of sperm entry into the uterus, and changes in the endometrium,
which reduce the likelihood of implantation.11
An independent clinical pharmaceutical reference also contains
this assertion.12 We considered this level III (poor to
good) evidence (Table 1).
To assess the clinical significance of an altered endometrium,
it was helpful to examine data that compared endometrial
thickness with the receptivity of the endometrium to preembryos
during in vitro fertilization procedures. Magnetic resonance
imaging scans of the uteri of women reveal that the
OC users have endometrial linings that are consistently thinner
than the endometrial linings of nonusers,48-50 up to
58% thinner.51
Of the first 4 ultrasound studies published, the first did not
find a relationship between endometrial thickness and in vitro
fertilization implantation rates52; however,
subsequent studies noted a trend,53-54 and one demonstrated
that a decreased thickness of the endometrium decreased
the likelihood of implantation.55 Larger, more recent, and
more technically sophisticated studies56-65 all concluded that
endometrial thickness is related to the functional receptivity of
the endometrium. Furthermore, when the endometrial lining becomes
too thin, then implantation does not occur.56-58,64-65 The
minimal endometrial thickness required to maintain a pregnancy in
patients undergoing in vitro fertilization has been reported, ranging
from 5 mm55
to 9 mm65
to 13 mm,53
whereas the average endometrial thickness in women taking OCs
is 1.1 mm.50
These data would seem to lend credence to the Food and Drug Administration–approved
statements that " . . . changes in the endometrium . .
. reduce the likelihood of implantation."11 We considered
this level II.2 (good to very good) evidence (Table 1).
Integrin
Changes Affecting Fallopial Tube and Endometrial Receptivity for Implantation
Integrins are a family of cell adhesion molecules that are accepted
as markers of uterine receptivity for implantation.66-67 Temporal
and spatial expression of these endometrial peptides is
believed to contribute to the establishment and maintenance of
a cyclical endometrial receptivity. Three cycle-dependent integrins
(
1
1,
4
1,
V
3) have been shown to be " . . . coexpressed apparently only
for a brief interval of the cycle that corresponds with the putative
window of maximal uterine receptivity" and " . . . have emerged
as reliable markers of normal fertility."68 Of these 3, the
V
3 integrin seems "to be an excellent marker to study the molecular
events leading to the establishment of uterine receptivity and
successful implantation."68-69 These 3 integrins are conspicuously
absent in the endometrium of most patients with luteal phase
deficiency, endometriosis, and unexplained infertility.68
In addition, integrin expression is significantly changed by
OCs. Integrins have been compared using endometrial biopsy
specimens from normally cycling women and women taking OCs. In
most OC users, the normal patterns of expression of the integrins
are grossly altered, leading Somkuti et al68 to conclude
that the OC-induced integrin changes observed in the endometrium
have functional significance and provide evidence that reduced
endometrial receptivity does indeed contribute to the contraceptive
efficacy of OCs. They hypothesized that the sex steroids in OCs
alter the expression of these integrins through cytokines and
therefore predispose to failure of implantation or
loss of the preembryo or embryo after implantation.
We considered this level II.3 (good) evidence (Table 1).
Integrins have also been identified in the fallopian tube.69 Of
interest, the
V subunit is expressed in the fallopian tube epithelium throughout
the cycle, but the
3 subunit is only upregulated during the period of endometrial
receptivity. Therefore, it has now been postulated that the normal
tubal epithelium also has an implantation window that " . . .
affords the opportunity for trophoblast attachment should a 5-7
day preembryo be unduly retained in the tube."69 As discussed
earlier, one of the postulated actions of the OCs is a slowing
of tubal peristalsis (via smooth muscle relaxation)70; therefore,
a reduction in tubal peristalsis that is associated with an upregulation
of the
V
3 integrin in the epithelium of the fallopian tube could theoretically
lead to an increased risk of ectopic pregnancies in women taking
OCs.
If breakthrough ovulation occurs while using the COC, then to
some extent ovarian and blastocyst steroidogenesis could
theoretically "turn on" the endometrium, causing it to normalize
prior to implantation in the ovulatory cycle. However, after
discontinuing use of COCs, it usually takes several
cycles for a woman's menstrual flow to approach the volume of
women who have not taken hormonal contraception,71 suggesting
that the endometrium is slow to recover from its COC-induced
atrophy. Furthermore, in women who have ovulated
secondary to missing 2 low-dose COCs, the endometrium in the
luteal phase of the ovulatory cycle has been found to be nonsecretory.23
Increased
Extrauterine Pregnancy to Intrauterine Pregnancy Ratio
If the action(s) of OCs on the fallopian tube and endometrium
were such as to have no postfertilization effects, then
the reduction in the rate of intrauterine pregnancies in women
taking OCs should be proportional to the reduction in the rate
of extrauterine pregnancies in women taking OCs. If the effect
of OCs is to increase the extrauterine-to-intrauterine pregnancy
ratio, this would indicate that one or more postfertilization
effects are operating. All published data that we could review
indicated that the ratio of extrauterine-to-intrauterine
pregnancies is increased for women taking OCs and exceeds that
expected among control groups of pregnant women not
currently using OCs. These case-controlled series come from 33
centers in 17 countries and include more than 2800
cases and controls.72-77 The odds ratios
in these studies ranged from 1.7 (95% confidence interval [CI],
1.1-2.5)72
to 1.8 (95% CI, 0.9-3.4)73 to 4.3 (95% CI, 1.5-12.6)74 to 4.5
(95% CI, 2.1-9.6)75 to 13.9 (95% CI, 1.8-108.3).76 The
letter by Job-Spira et al74 seems to represent the same data
set of 279 cases and controls as the study by Coste et al.76 The meta-analysis
by Mol et al73
includes 2 of the publications,72, 75 but one of these may include women taking
POPs.72
Therefore, of the 5 publications, only 2 allow review of the
association of COCs with ectopic pregnancy.75-76 These
2 studies from 7 maternity hospitals in Paris, France, and 3 in
Sweden involved 484 women with ectopic pregnancies and 289 pregnant
controls and suggest that at least some protection
against intrauterine pregnancy is provided via postfertilization
preimplantation effects. We recognize that studies
that have used nonpregnant controls have not shown
a risk of increased ectopic pregnancy for users of
COCs. In our review, we restricted our analysis to
studies using pregnant controls, because we concur with researchers73,
76
in this field that " . . . when considering the situation where
a woman became pregnant during contraceptive use, one should
focus on pregnant controls."73 Therefore, COC use seems to
be associated with an increased risk of ectopic implantation or
unrecognized loss of preembryos. We considered this level II.2
(good to very good) evidence (Table 1).
Ectopic pregnancy is a particular form of postfertilization
loss that involves substantial risks to the woman, and
thus the absolute risk of ectopic pregnancy for women
taking OCs will be of interest to clinicians and patients.
Converting a relative risk of ectopic pregnancy to an absolute
risk has many inherent difficulties that have been
reviewed elsewhere.78 Nevertheless, adapting
the method suggested by Franks et al78 would allow one to predict
that the ectopic pregnancy rate for women taking OCs would be the
product of 3 factors: (1) the overall pregnancy rate per 1000 woman-years
among those taking OCs, (2) the proportion of extrauterine pregnancies
compared with all pregnancies for a comparable control population
not taking OCs, and (3) the relative risk for ectopic
pregnancy in women taking OCs compared with the control population,
which may be estimated by the odds ratio from case-control studies.
For factor 1, Potter29 suggests 40 for
good compliers and 80 for poor compliers. For factor 2,
the proportion of ectopic pregnancies in the 1990s is estimated to
range from 1 in every 5679 to 6480-81 pregnancies (0.0156 to 0.0179).
A reasonable range for factor 3 would be 1.1 to 13.9, based on
the studies discussed above. This model would predict
an absolute risk ranging from 0.7 (40 x
0.0156 x 1.1) to 19.9 (80
x 0.0179 x 13.9) ectopic pregnancies per 1000 woman-years.
We could only find one study, from Zimbabwe, which reported
an absolute risk of ectopic pregnancy in women taking OCs
of 0.582 per 1000 woman-years.
The risk of ectopic pregnancy is higher with POPs, and ectopic
pregnancy has been discussed at length by a number of
investigators as a clinically significant potential
complication of POPs.82-84 The odds ratio of an extrauterine
pregnancy for a woman taking a POP (compared with pregnant controls)
was reported in only one study and was 79.1 (95% CI, 8.5-735.1).74 Assuming
an overall clinical pregnancy rate of 30 to 70 per 1000 woman-years,
this equates to a predicted absolute risk of 4 to 99 ectopic pregnancies
per 1000 woman-years ([30 or 70] x [0.0156 or 0.0179] x [8.5 or 79.1]) in women taking
POPs. This is reasonably concordant with absolute rates of ectopic
pregnancy in women taking POPs, which have been reported to range
from about 382-83,85 to about
2084, 86 per 1000 woman-years.
Data from case-controlled series demonstrate that women with
clinically recognized pregnancy are no more or less likely
to miscarry based on whether they were taking an OC after their
pregnancy was clinically recognized.87-90 However,
the epidemiology, biology, and recognized risk factors of clinically
recognized embryo or fetal loss (spontaneous abortion after clinically
recognized pregnancy) do not seem to apply to early (unrecognized)
preembryo or embryo loss, as the available evidence suggests
that the mechanisms of early establishment and maintenance
of pregnancy and later maintenance of pregnancy are qualitatively
and substantially different.90
COMMENT
We found the evidence supporting postfertilization effects for OCs
in the prevention of clinically recognized pregnancy to range
from poor (level III) to very good (level II.2). Specifically, evidence
based on alterations in endometrial biochemistry and histology
(level III), evidence based on endometrial thickness and endometrial
receptivity from research studying in vitro fertilization (level
II.2), and evidence based on endometrial integrins (level II.3)
all support the possibility of peri-implantation or postimplantation
effects. Furthermore, evidence based on ectopic-to-intrauterine
risk ratios from multiple case-control studies (level II.2) supports
the possibility of postfertilization preimplantation, peri-implantation,
or postimplantation effects. However, we could identify few data
that would assist in quantifying these postfertilization effects.
It seems likely that for perfect use of COCs, postfertilization
mechanisms would be likely to have a small but not negligible
role. For POPs, COCs with lower doses of estrogen, and imperfect
use of any OCs, postfertilization effects are likely to have an
increased role. In any case, the medical literature does not support
the hypothesis that postfertilization effects of OCs do not exist.
Despite the evidence, which suggests that postfertilization
effects for OCs are operational at least some of the time,
and the fact that a postfertilization mechanism for OCs is described
in the Physicians' Desk Reference,11 in Drug
Facts and Comparisons,12 and in most standard gynecologic,
family practice, nursing, and public health textbooks, we anecdotally
find that few physicians or patients are aware of this possibility.
Therefore, we believe that the potential for postfertilization
effects is probably not routinely presented to patients as part
of their informed
consent
to use an OC. Furthermore, it is of concern to us that only one
of the many OC patient information handouts we and others5 have reviewed,
including those produced by the OC manufacturers, mentions the
possible postfertilization mechanism, despite the fact that this
information is nearly always included in the professional labeling
of these same OCs.
Since there is evidence to support the existence of postfertilization
effects and because it is impossible to know in advance
which patients would find the potential for this effect objectionable,
we believe that the lack of information regarding postfertilization
effects in patient information materials about OCs represents
a potential failure to provide complete Informed
consent.
Furthermore, if this mechanism of an OC violates the moral requirements
of a woman, then failure to disclose this information seriously
jeopardizes her autonomy. If information about the mechanism
of an OC is deliberately withheld or misstated, then an
unethical deception occurs. Failure to disclose information that
might lead a patient to choose a different method of treatment
is generally considered to be unethical.12-13 Therefore,
it seems clear to us that failure to inform patients of a possible
postfertilization mechanism of an OC is a failure to provide
informed
consent.
PROVIDING
informed
consent
Many reproductive scientists have defined pregnancy as occurring
at the point of or at some point after implantation.16, 91-92 However,
this definition does not change the fact that some patients,
for personal, scientific, moral, or religious reasons, identify
the start of human life at fertilization. For such patients,
a form of contraception that allows fertilization and then causes
loss of the preembryo or embryo may be unacceptable. Regardless
of the personal beliefs of the physician or provider about the
mechanism of OCs, it is important that patients have information
relevant to their own beliefs and value systems.
However, the objective presentation of the potential for postfertilization
effects of OCs may be complex; there are a variety of
potential interpretations of the postfertilization
effects depending on which aspect is emphasized: (1) One could
state that OCs may significantly reduce the absolute
risk per woman-year of any possible postfertilization loss in
the same way that they reduce the absolute clinical
pregnancy rate.78 For some women or medical personnel
who believe that human life begins at fertilization, this view
might render OCs, even with postfertilization loss, morally acceptable.
(2) One could emphasize that once fertilization has
occurred, OCs may cause at least an occasional postfertilization
loss, regardless of the rate of fertilization. For some women
or medical personnel who believe that human life begins
at fertilization, the view that any postfertilization loss could
be attributed to the effects of OCs and therefore could be considered
induced rather than natural may render OCs morally unacceptable
to use, even if the absolute frequency of such an event is very
low.
Medical colleagues have suggested to us that postfertilization
loss attributed to OCs would not need to be included in
informed
consent
until it is either definitely proven to exist or proven to be
a common event. However, rare but important events are an essential
part of other informed
consent
discussions in medicine, primarily when the rare possibility
would be judged by the patient to be important. For example,
anesthesia-related deaths are extremely rare for elective surgery
(<1:25,000 cases); nevertheless, it is considered appropriate
and legally necessary to discuss this rare possibility with patients
before such surgery because the possibility of death is so important.
Therefore, for women to whom the induced loss of a preembryo
or embryo is important, failure to discuss this possibility,
even if the possibility is judged to be remote, would
be a failure of informed
consent.
Others feel that an overemphasis of possible postfertilization
effects might make women choose a less-effective method
of contraception and therefore increase the incidence of unplanned
pregnancy. Both of these views fail to acknowledge the value
of a woman's autonomy in making decisions based on Informed
consent.
During informed
consent
discussions, overemphasis of any single possible risk may not
result in appropriate informed
consent;
however, neither does choosing to not mention the possible risk
result in adequate informed
consent.
Therefore, discussion of this potential risk should occur and
should be kept within the perspective of the available medical
evidence.
One possible approach to this complex issue might be to inquire
of the patient whether she desires this information. The
physician or provider might say, for example: "Most of the time,
the pill acts by preventing an egg from forming. This prevents
pregnancy. However, women on the pill can still sometimes get
pregnant. Some doctors think that the pill may cause
the loss of some of these pregnancies very early in the pregnancy,
before you would even know you were pregnant. Would
knowing more about this possibility be important
to you in your decision about whether to use the
pill?"
If the answer is yes, further explanation of the issues would
be indicated and should occur in terms that are as understandable
as possible. Proper informed
consent
requires patient and physician comprehension of information,
the disclosure of this information, and the sharing of interpretations.14-15 If any
mechanism of any OC violates the morals of any particular woman,
the failure of the physician or care provider to disclose this
information would effectively eliminate the likelihood that the
woman's consent
was truly informed13-14,93 and would
seriously jeopardize her autonomy.13
Furthermore, there is a potential for negative psychological
impact on women who believe human life begins at fertilization,
who have not been given informed
consent
about OCs, and who later learn of the potential for postfertilization
effects of OCs.94 The responses to this could include
disappointment, anger, guilt, sadness, anger, rage, depression,
or a sense of having been violated by the provider.5 Further research
is necessary to identify the exact frequency of postfertilization
effects of OCs.
CONCLUSIONS
The available evidence supports the hypothesis that when ovulation
and fertilization occur in women taking OCs, postfertilization
effects are operative on occasion to prevent clinically
recognized pregnancy. Physicians should understand and respect
the beliefs of patients who consider human life to be present
and valuable from the moment of fertilization. Since it would
be difficult to predict which patients might object
to being given an OC if they were aware of possible postfertilization
effects, mentioning the potential for postfertilization
effects of OCs to all patients and providing detailed information
about the evidence to those who request it is necessary for adequate
informed
consent.
AUTHOR
INFORMATION
Accepted for publication March 18, 1999.
We thank John R. Hartman, MD, Chris Kahlenborn, MD, G. Gayle
Stephens, MD, William Toffler, MD, and Randy Alcorn, MS,
for their help with conceptual development of this article and
for identifying important references.
Reprints: Joseph B. Stanford, MD, MSPH, Department of Family
and Preventive Medicine, University of Utah, 50 North
Medical Dr, Salt Lake City, UT 84132 (e-mail: jstanford@dfpm.utah.edu).
From the Department of Family
Medicine, University of South Florida, Kissimmee (Dr Larimore),
and Department of Family and Preventive Medicine, University of Utah, Salt
Lake City (Dr Stanford).
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