Postfertilization Effects of Oral Contraceptives
and Their Relationship to Informed Consent

Walter L. Larimore, MD; Joseph B. Stanford, MD, MSPH Theprimarymechanismoforalcontraceptivesistoinhibitovulation,butthismecha-
nism is not always operative. When breakthrough ovulation occurs, then secondarymechanisms operate to prevent clinically recognized pregnancy. These secondary mecha-nisms may occur either before or after fertilization. Postfertilization effects would be problematic for some patients, who may desire information about this possibility. This article evalu-ates the available evidence for the postfertilization effects of oral contraceptives and concludes thatgood evidence exists to support the hypothesis that the effectiveness of oral contraceptives de-pends to some degree on postfertilization effects. However, there are insufficient data to quanti-tate the relative contribution of postfertilization effects. Despite the lack of quantitative data, theprinciples of informed consent suggest that patients who may object to any postfertilization lossshould be made aware of this information so that they can give fully informed consent for the useof oral contraceptives.
such effects has not been systematically re- viewed. The purpose of this article was to cations in the world,1 and are accessible review and grade the available evidence for postfertilization effects of OCs and dis- tries, although still virtually unavailable in uted to an increased acceptability of birth to whom postfertilization effects are im- control,2 although, for many patients, de- based on the best available evidence.13-15 moral, ethical, and religious implica-tions.3,4 For patients who believe that hu- For Author’s Comment
man life begins at fertilization (concep- see page 133
tion), a method of birth control that hasthe potential of interrupting develop- ment after fertilization (a postfertiliza- volved a review of the abstracts of all stud- tion effect) may not be acceptable.5,6 Post- ies of OCs published since 1970 available (when it is administered too late to pre- µg of estrogen) phasic combined oral con- vent ovulation),7,8 luteolytic agents (ie, RU- 486),9 and intrauterine devices,5 and these gestin-only pills [POPs]). We also reviewed some patients. Although postfertilization tions of several medical textbooks and ref-erence books.
Since there is variability in the defini- 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). 2000 American Medical Association. All rights reserved.
Typical use is described as the full tions for fertilization, implantation, embryo, and preembryo.16 Preembryo week after fertilization, the term em- bryo is used. Implantation is the pro- fined postfertilization effects to in- the first year of typical use.1,10,12,17,18,20 EVIDENCE FOR
the first year of typical use.1,10,12,17,18,20 ising method is the isolation of “early tilization effects also play a role.
2000 American Medical Association. All rights reserved.
Quality of Evidence*
tain a pregnancy in patients under-going in vitro fertilization has been Evidence obtained from at least one properly randomized Evidence obtained from well-designed controlled trials Evidence obtained from well-designed cohort or case-controlled analytic studies, preferably from more than one center or research group.
Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolledexperiments could also be regarded as this type Opinion of respected authorities based on clinical experience, descriptive studies and case reports, Integrin Changes Affecting
Fallopial Tube and Endometrial
OCs in the Physicians’ Desk Refer- Receptivity for Implantation
ity of evidence table46 (Table), we
culty of sperm entry into the uterus, and Endometrial Changes That May
Affect Endometrial Receptivity
integrins (␣1␤1, ␣4␤1, ␣V␤3) have III (poor to good) evidence (Table).
ers of normal fertility.”68 Of these 3, sion is significantly changed by OCs.
2000 American Medical Association. All rights reserved.
dow that “ . . . affords the opportunity tubal peristalsis that is associated with Increased Extrauterine
Pregnancy to Intrauterine
Pregnancy Ratio
2000 American Medical Association. All rights reserved.
for OCs is described in the Physi- cians’ Desk Reference,11 in Drug (level III) to very good (level II.2).
d e n c e b a s e d o n e n d o m e t r i a l til it is either definitely proven to ex- 2000 American Medical Association. All rights reserved.
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94. Cruz P. Angry over withheld information. Life Ad- 79. Storeide O, Veholmen M, Eide M, Bergsjo P, Sand- I haveprescribed“thePill”since1978.MywifeandIusedthePillforyears,havingnomoralconcernsaboutit.Then,
in 1995 my friend and practice partner John Hartman, MD, showed me a patient information brochure—given to himby a friend—that claimed the Pill had a postfertilization effect causing “ . . . the unrecognized loss of preborn chil- dren.” John asked me if I had ever heard of such a thing. I had not. I did read the brochure and its claims seemed to beoutlandish, excessive, and inaccurate. So, I decided to begin a literature search to disprove these claims to my partner, my-self, and any patients who might ask about it. The more research I did, the more concerned I became about my findings. Icalled researchers around the country and interviewed them. During this process I met Joe Stanford, MD. Joe volunteered toassist in the research that ultimately became this systematic review. We were concerned enough about our findings and aboutthe fact that so many of our colleagues and patients seemed to share our ignorance about this potential effect that we pre-sented the preliminary results of our research at a number of research forums, just to see if we were off base. Most of thereviewers suggested that, although this evidence was new to them (as it was to us), it seemed accurate and not off target.
Furthermore, several said that they thought it would change the way family physicians informed their patients about the Pilland its potential effects.
The most difficult part of this research was deciding how to apply it to my practice. I discussed it with my partners, my patients, ethicists I know and respect, and pastors in my community. I studied the ethical principle of double effect anddiscussed the issue with religious physicians of several faiths. Finally, after many months of debate and prayer, I decided in1998 to no longer prescribe the Pill. As a family physician, my career has been committed to family care from conception todeath. Since the evidence indicated to me that the Pill could have a postfertilization effect, I felt I could no longer, in goodconscience, prescribe it—especially since viable alternatives are available. The support and encouragement that my part-ners, staff, and patients have given me has been unexpectedly affirming. It seems that my patients have appreciated the in-formation I have given them. Many have been surprised or even shocked (as I was) to learn about this potential effect. Manyof my patients have chosen to continue taking the Pill, and we have physicians in our practice and community who willprescribe it for them. Patients who take the Pill tell me that they are much more careful with their compliance. Others havechosen other birth control options—especially one of the modern methods of natural family planning. So, this is researchthat has changed my soul and my practice. It has been an extraordinarily difficult issue with which I have had to wrestle. Isuspect it will be so for many who thoughtfully read and consider the evidence contained in this review.
Walter L. Larimore, MDKissimmee, Fla 2000 American Medical Association. All rights reserved.


Management of Complex Ovarian Cysts in Women with Management of Complex Ovarian Cysts in women with Postmenopausal Bleeding Abstract Introduction : Transvaginal ultrasound (TVS) to determine endometrial thickness is recommended in women with postmenopausal bleeding (PMB). TVS may also detect extra-endometrial pathology including ovarian cysts. National guidelines exist regarding ma

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