Clinical Articles Contraception and ectopic pregnancy risk Adele L. Franks, MD: Valerie Beral, MB, BS,b Willard Cates, Jr., MD, MPH,b and CarolJ. R. Hogue, PhD" Atlanta, Georgia Studies of the association of ectopic pregnancy with contraception have generated a conflicting array of results because of methodologic differences between studies. We estimated the absolute incidence rates of ectopic pregnancy for various contraceptives by multiplying the pregnancy rate by the proportion of pregnancies with ectopic implantation for each method. Our results indicated a more than SOO-fold difference in ectopic pregnancy incidence, from a low of 0.005 ectopic pregnancies per 1000 woman years of oral contraception or vasectomy to a high of 2.6 per 1000 woman years of no contraception. These estimated incidence rates should be useful for clinicians and patients seeking to beller understand the risks and benefits of contraceptives. (AM J OBSTET GYNECOL 1990;163:1120-3.)
Key words: Pregnancy, ectopic; contraception; intrauterine contraceptive device; family planning
The incidence of ectopic pregnancy has increased dramatically over the last 20 years.l~3 Possible explanations include the increased prevalence of pelvic inflammatory disease and sexually transmitted diseases, increased clinical suspicion and improved early diagnostic techniques for ectopic pregnancy (quantitative serum pregnancy hormone tests, ultrasonography, laparoscopy), the trend toward delaying childbearing until older ages when ectopic pregnancy becomes a greater risk, and the role of contraceptive practice. 1. 3~8 Studies of the association of ectopic pregnancy with contraceptive methods, in particular, the intrauterine contraceptive device (IUD)," 5, 6 have generated a conflicting array of results that may be a source of confusion for clinicians desiring to provide the best contraceptive alternatives to their patients. Most studies of the possible association of contraception and ectopic pregnancy have used the case-control study design because it is the most feasible method for studying rare diseases. 9 Such a study design compares persons who have the disease in question (cases) with persons free of the disease (controls). Crucial to interFrom the Division of Reproductive Health, Center for Chronic Disease Prevention and Health Promotion: and the Division of Sexually Transmitted Diseases, Center for Prevention Services,' Centers for Disease Control. Received for publication November 29, 1989; revised May 2, 1990; accepted May 18, 1990. Reprint requests: Adele Franks, MD, MailstopF05, OSAICCDPHP, Centersfor Disease Control, 1600 Clifton Road, Atlanta, GA 30333. 611/22474
1120
preting the results are that the controls be chosen from the same population of persons as the cases and that the controls have the potential for being exposed to the same risk factors as the case group. Selecting a control group for a case-control study of ectopic pregnancy is not a simple matter 10 • 11; some researchers have selected obstetric patients, and others nonpregnant women, as controls,3 leading to substantially different results.3. 5. 6.11 For example, in a study about the use of the IUD, the selection of the control group may determine whether the IUD appears to protect against ectopic pregnancy or to increase the risk of ectopic pregnancy; relative risk estimates range from 0.5 to 32, depending on study design. 3 To illustrate, if obstetric patients with intrauterine pregnancies are selected as controls, a low percentage of these women will have conceived while using the IUD because the IUD largely prevents intrauterine implantation. In addition, the spontaneous abortion rate is elevated among intrauterine pregnancies that result from IUD failure, and the likelihood of an induced abortion among IUD users who do not spontaneously abort also may be high. Thus women with second- or third-trimester intratuerine pregnancies are less likely than the general population to have been using an IUD. Comparing these women with those who have an ectopic pregnancy may therefore yield an elevated risk associated with IUD use among women in the case group, even if their prevalence of IUD use is not particularly high. In contrast, if nonpregnant
Contraception and ectopic pregnancy risk
Volume 163 Number 4, Part 1
1121
Table I. Estimated incidence rates of ectopic pregnancy by contraceptive method Contraceptive method
Oral contraceptivet Vasectomy Condom Diaphragm Tubal sterilization IUD* None
Lowest expected pregnancy rate per 1000 woman years* (A)
I I
20 30 2 20 520
Proportion ectopic implantation* (B)
Estimated ectopic pregnancy incidence rate per 1000 woman years (A x B)
0.005 0.005 0.005 0.005 0.159 0.051 0.005
0.005 0.005 0.100 0.150 0.318 1.020 2.600
*See material and methods section for origin of these numbers. tCombination estrogen-progestin only. *Unmedicated only.
women are selected as controls, the opposite conclusion is likely. Nonpregnant, sexually active women are more likely to be using contraception, and thus they may have a higher prevalence of IUD use than women in the case group, leading one to conclude that IUD use is protective against ectopic pregnancy. Interpretation of these results must be limited in scope to the comparisons actually studied. Thus no general statement may be made about whether IUD users are at increased or decreased risk of ectopic pregnancy. For an individual clinician or patient to use the information from case-control studies in selecting a contraceptive method would be, at best, a challenging endeavor. Instead, knowing the actual rates of ectopic pregnancy among cohorts of women using various contraceptive methods might prove more useful. Unfortunately, such information can be acquired only by follow-up oflarge numbers of women over time (cohort study design), a process that is expensive and timeconsuming. Such studies are therefore rare. Two cohort studies conducted in the 1960s and early 1970s in the United States and the United Kingdom provide sufficient information on ectopic pregnancy rates among IUD users.12. 13 Little information exists on ectopic pregnancy rates associated with other contraceptive methods. In this article we estimate the incidence rates of ectopic pregnancy per 1000 woman years of using various contraceptive methods to clarify the magnitude of ectopic pregnancy risk and to determine the relative ranking of risk for each contraceptive method. Material and methods
To calculate estimated rates of ectopic pregnancy per 1000 woman years of use for each contraceptive method, we assumed that the ectopic pregnancy rate was the product of two factors: (1) the incidence rate of pregnancy (i.e., the conception rate) per 1000 woman years and (2) the proportion of pregnancies implanting in an ectopic location (outside the uterine fundus). For women using contraception the pregnancy rate
per 1000 woman years was taken as the "lowest expected" ("method") failure rate associated with the use of each contraceptive method per 1000 women in the first year of use. I< This rate is based on the assumption of consistent and correct use of the method for the entire year. For women not using contraception, the pregnancy rate per 1000 woman years was taken as the average annual pregnancy rate per 1000 women not using contraception. IS For IUD users we derived the proportion of pregnancies that implant in an ectopic location from the two large cohort studies (mentioned earlier) in which, at the time of publication, more than 98% of the women enrolled used nonmedicated devices. 12. 13 The proportion of pregnancies that were ectopic among the women using IUDs (0.043 in the U.S. study and 0.072 in the U.K. study) were averaged (directly weighted by the number of woman years of IUD use in each study), yielding 0.051 for our calculations. For women who used combination oral contraceptives, who used barrier methods, and who were partners of vasectomized men, we assumed that the contraceptive method did not affect the site of implantation; therefore we assumed that the proportion of pregnancies implanting in an ectopic location was 0,005, approximately equal to the overall proportion among reported pregnancies in the U.S. population during the early 1970s.1 6 For women with tubal sterilization failures we obtained the proportion with ectopic implantation from literature reviews. 7 • 8 The IUD was the only contraceptive method for which actual observed rates of ectopic pregnancy per 1000 woman years of use were available from large cohort studies. 12. 13 These empiric rates were averaged (directly weighted by number of woman years of use in each study) and were compared with those calculated as described above. Results
The resulting estimated ectopic pregnancy rates by contraceptive method vary more than 500-fold from the lowest rate of 0.005 per 1000 woman years among
1122
Franks et al.
women who used combination oral contraceptives or who were partners of vasectomized men, to the highest rate of 2.6 per 1000 woman years among women using no contraception (Table I). Thus, although using an IUD carries a higher rate of ectopic pregnancy than using barrier methods, sterilization, or oral contraception, failure to use any contraception has the highest estimated rate of ectopic pregnancy. For IUD use, the calculated ectopic pregnancy rate can be compared with the actual rates of 1.0 per 1000 woman years in the U.S. study and 1.2 per 1000 woman years in the U.K. study referred to previously.I2. 13 On the basis of these numbers, the weighted average of 1.06 per 1000 woman years compares favorably with the calculated rate of 1.02 per 1000 woman years derived by multiplying the pregnancy rate and the proportion of resulting pregnancies that were ectopic (Table I). Comment
We believe that expressing risk of disease, whenever possible, in terms of absolute rates of occurrence, rather than only in relative terms, is more useful for clinical decision making. For ectopic pregnancy we believe relative risk estimates from case-control studies are especially confusing because the choice of control group profoundly affects interpretation of results. To estimate rates of occurrence of ectopic pregnancy in the absence of sufficient cohort data, we assumed that the proportion of pregnancies implanting in an ectopic location did not differ among women who used combination oral contraceptives, women who used barrier methods, women who were partners of vasectomized men, and women who used no contraception. If this assumption is incorrect, our resulting estimates of incidence rates for ectopic pregnancy might be incorrect as well; however, on the basis of current knowledge, we know of no reason to question this assumption. For those who prefer to make different assumptions regarding the likelihood of ectopic implantation, our methods may be easily applied, by substituting different numbers. Similarly, although we used the "lowest expected" ("method") failure rates for the various contraceptive groups for our calculations, one could easily use the "typical" ("user") failure rates among women using contraception instead. While the former is based on the assumption of consistent and correct use of the contraceptive method, the latter is based on "typical" couples, including those who do not use the contraceptive method consistently or correctly. To calculate ectopic pregnancy rates based on "typical" failure rates, one could substitute pregnancy rates of 30 per 1000 women for oral contraceptives, 1.5 per 1000 women for vasectomy, 120 per 1000 women for condoms, 180 per 1000
October 1990 Am J Obstet Gynecol
women for the diaphragm, 4 per 1000 women for tubal sterilization, and 60 per 1000 women for the IUD.I4 This substitution results in estimated "typical" ectopic pregnancy rates of 0.15,0.0075,0.60,0.90,0.64, and 3.06 per 1000 woman years of use, respectively. It should be noted that we used the first-year failure rates for women who used the various contraceptives while we used the average annual pregnancy rate for women who used no contraception. Because failure rates tend to decline over time for reversible contraceptives, our results may be biased in the direction of exaggerating the ectopic pregnancy risk among women using contraception. For women using sterilization to avoid pregnancy, failure rates over time may depend on method of occlusion and other factors that are not yet fully understood. Therefore predicting the direction of any potential bias in our calculations regarding sterilization is difficult. We also assumed the ectopic pregnancy rate to be the product of the pregnancy rate and the likelihood of ectopic implantation. Again, no data exist to challenge this assumption, and our own estimate of the ectopic prengancy rate among IUD users on the basis of this multiplicative assumption compares favorably with the actual rates reported in two large cohort studies. The only available cohort data reflect rates of ectopic pregnancy among IUD users during the 1960s and early 1970s. To make meaningful comparisons, we estimated the occurrence of ectopic pregnancy for other methods on the basis of data as close in time as possible to the IUD cohort studies. Note, however, that the currently used copper-containing IUDs have lower failure rates than the nonmedicated IUDs,I4 which were predominantly used in the 1960s and early 1970s. Thus the ectopic pregnancy rate associated with IUD use may be somewhat reduced in recent years. On the other hand, recent information suggests that the proportion of ectopic pregnancies among pregnancies resulting from tubal sterilization failure may vary according to method of occlusion and may be higher than previously believed, especially for pregnancies occurring after tubal sterilization by electrocoagulation. I7 Further research is necessary to clarify this issue. Though our estimates are imprecise, and changes in risk over time may have occurred, the differences in magnitude of ectopic pregnancy risk between contraceptives are so large that we believe the relative ranking of risk to be correct. We hope that expressing the risk of ectopic pregnancy associated with contraceptive methods as rates of occurrence rather than as relative risks will be meaningful in the clinical setting. In particular, the fact that ectopic pregnancy risk appears to differ little between women who use IUDs and women who use no contraception should be reassuring for
Volume 163 Number 4, Pan 1
those women for whom the IUD is otherwise the best contraceptive option. REFERENCES I. Lawson HW, Atrash HK, Saftlas AF, Franks AL, Finch EL, Hughes JM. Ectopic pregnancy surveillance, United States, 1970-1985. MMWR 1988;37(SS-5):9-18. 2. Beral V. An epidemiological study of recent trends in ectopic pregnancy. Br J Obstet GynaecoI1975;82:775-82. 3. Chow WH, Daling JR, Cates W Jr, Greenberg RS. Epidemiology of ectopic pregnancy. Epidemiol Rev 1987;9: 70-94. 4. Robinson N, Beral V. Risk of ectopic pregnancy. Lancet 1979;2: 1247-8. 5. Ory HW. Ectopic pregnancy and intrauterine contraceptive devices: new perspectives. Obstet Gynecol 1981;57: 137-44. 6. Marchbanks PA, Annegers JF, Coulam CB, Strathy JH, Leonard TK. Risk factors for ectopic pregnancy: a population-based study. JAMA 1988;259:1823-7. 7. Tatum HJ, Schmidt FH. Contraceptive and sterilization practices and extrauterine pregnancy: a realistic perspective. Ferti! Steril 1977;28:407-21. 8. DeStefano F, Peterson HB, Layde PM, Rubin GL. Risk of ectopic pregnancy following tubal sterilization. Obstet Gynecol 1982;60:326-30.
Contraception and ectopic pregnancy risk
1123
9. Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic research: principles and quantitative methods. New York: Van Nostrand Reinhold, 1982:62-70. 10. Weiss NS, Daling JR, Chow WHo Control definition in case-control studies of ectopic pregnancy. Am J Public Health 1985;75:67-8. II. Weiss NS, Daling JR. Risk factors for ectopic pregnancy. JAMA 1988;260:1553-4. 12. Vessey MP, Yeates D, Flavel R. Risk of ectopic pregnancy and duration of use of an intrauterine device. Lancet 1979;2:501-2. 13. Lehfeldt H, Tietze C, Gorstein F. Ovarian pregnancy and the intrauterine device. AM J OBSTET GYNECOL 1970; 108: 1005-9. 14. Trussell J, Kost K. Contraceptive failure in the United States: a critical review of the literature. Stud Fam Plann 1987;18:237-83. 15. Sheps MC. An analysis of reproductive patterns in an American isolate. Popul Stud 1965; 19:65-80. 16. Centers for Disease Control. Ectopic pregnancyUnited States, 1986. MMWR 1989;38:481-4. 17. Bhiwandiwala pp, Mumford SD, Feldblum PJ. A comparison of different laparoscopic sterilization occlusion techniques in 24,439 procedures. AM J OBSTET GYNECOL 1982; 144:319-31.
Bound volumes available to subscribers Bound volumes of the AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY are available to subscribers (only) for the 1990 issues from the Publisher, at a cost of $56.00 ($79.00 international) for Vol. 162 (January-June) and Vol. 163 (july-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram with the JOURNAL name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby-Year Book, Inc., Circulation Department, 11830 Westline Industrial Drive, St. Louis, Missouri 63146-3318, USA; phone (800) 325-4177, ext. 735l. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular JOURNAL subscription.
Key words: Pregnancy, ectopic; contraception; intrauterine contraceptive device; family planning
The incidence of ectopic pregnancy has increased dramatically over the last 20 years.l~3 Possible explanations include the increased prevalence of pelvic inflammatory disease and sexually transmitted diseases, increased clinical suspicion and improved early diagnostic techniques for ectopic pregnancy (quantitative serum pregnancy hormone tests, ultrasonography, laparoscopy), the trend toward delaying childbearing until older ages when ectopic pregnancy becomes a greater risk, and the role of contraceptive practice. 1. 3~8 Studies of the association of ectopic pregnancy with contraceptive methods, in particular, the intrauterine contraceptive device (IUD)," 5, 6 have generated a conflicting array of results that may be a source of confusion for clinicians desiring to provide the best contraceptive alternatives to their patients. Most studies of the possible association of contraception and ectopic pregnancy have used the case-control study design because it is the most feasible method for studying rare diseases. 9 Such a study design compares persons who have the disease in question (cases) with persons free of the disease (controls). Crucial to interFrom the Division of Reproductive Health, Center for Chronic Disease Prevention and Health Promotion: and the Division of Sexually Transmitted Diseases, Center for Prevention Services,' Centers for Disease Control. Received for publication November 29, 1989; revised May 2, 1990; accepted May 18, 1990. Reprint requests: Adele Franks, MD, MailstopF05, OSAICCDPHP, Centersfor Disease Control, 1600 Clifton Road, Atlanta, GA 30333. 611/22474
1120
preting the results are that the controls be chosen from the same population of persons as the cases and that the controls have the potential for being exposed to the same risk factors as the case group. Selecting a control group for a case-control study of ectopic pregnancy is not a simple matter 10 • 11; some researchers have selected obstetric patients, and others nonpregnant women, as controls,3 leading to substantially different results.3. 5. 6.11 For example, in a study about the use of the IUD, the selection of the control group may determine whether the IUD appears to protect against ectopic pregnancy or to increase the risk of ectopic pregnancy; relative risk estimates range from 0.5 to 32, depending on study design. 3 To illustrate, if obstetric patients with intrauterine pregnancies are selected as controls, a low percentage of these women will have conceived while using the IUD because the IUD largely prevents intrauterine implantation. In addition, the spontaneous abortion rate is elevated among intrauterine pregnancies that result from IUD failure, and the likelihood of an induced abortion among IUD users who do not spontaneously abort also may be high. Thus women with second- or third-trimester intratuerine pregnancies are less likely than the general population to have been using an IUD. Comparing these women with those who have an ectopic pregnancy may therefore yield an elevated risk associated with IUD use among women in the case group, even if their prevalence of IUD use is not particularly high. In contrast, if nonpregnant
Contraception and ectopic pregnancy risk
Volume 163 Number 4, Part 1
1121
Table I. Estimated incidence rates of ectopic pregnancy by contraceptive method Contraceptive method
Oral contraceptivet Vasectomy Condom Diaphragm Tubal sterilization IUD* None
Lowest expected pregnancy rate per 1000 woman years* (A)
I I
20 30 2 20 520
Proportion ectopic implantation* (B)
Estimated ectopic pregnancy incidence rate per 1000 woman years (A x B)
0.005 0.005 0.005 0.005 0.159 0.051 0.005
0.005 0.005 0.100 0.150 0.318 1.020 2.600
*See material and methods section for origin of these numbers. tCombination estrogen-progestin only. *Unmedicated only.
women are selected as controls, the opposite conclusion is likely. Nonpregnant, sexually active women are more likely to be using contraception, and thus they may have a higher prevalence of IUD use than women in the case group, leading one to conclude that IUD use is protective against ectopic pregnancy. Interpretation of these results must be limited in scope to the comparisons actually studied. Thus no general statement may be made about whether IUD users are at increased or decreased risk of ectopic pregnancy. For an individual clinician or patient to use the information from case-control studies in selecting a contraceptive method would be, at best, a challenging endeavor. Instead, knowing the actual rates of ectopic pregnancy among cohorts of women using various contraceptive methods might prove more useful. Unfortunately, such information can be acquired only by follow-up oflarge numbers of women over time (cohort study design), a process that is expensive and timeconsuming. Such studies are therefore rare. Two cohort studies conducted in the 1960s and early 1970s in the United States and the United Kingdom provide sufficient information on ectopic pregnancy rates among IUD users.12. 13 Little information exists on ectopic pregnancy rates associated with other contraceptive methods. In this article we estimate the incidence rates of ectopic pregnancy per 1000 woman years of using various contraceptive methods to clarify the magnitude of ectopic pregnancy risk and to determine the relative ranking of risk for each contraceptive method. Material and methods
To calculate estimated rates of ectopic pregnancy per 1000 woman years of use for each contraceptive method, we assumed that the ectopic pregnancy rate was the product of two factors: (1) the incidence rate of pregnancy (i.e., the conception rate) per 1000 woman years and (2) the proportion of pregnancies implanting in an ectopic location (outside the uterine fundus). For women using contraception the pregnancy rate
per 1000 woman years was taken as the "lowest expected" ("method") failure rate associated with the use of each contraceptive method per 1000 women in the first year of use. I< This rate is based on the assumption of consistent and correct use of the method for the entire year. For women not using contraception, the pregnancy rate per 1000 woman years was taken as the average annual pregnancy rate per 1000 women not using contraception. IS For IUD users we derived the proportion of pregnancies that implant in an ectopic location from the two large cohort studies (mentioned earlier) in which, at the time of publication, more than 98% of the women enrolled used nonmedicated devices. 12. 13 The proportion of pregnancies that were ectopic among the women using IUDs (0.043 in the U.S. study and 0.072 in the U.K. study) were averaged (directly weighted by the number of woman years of IUD use in each study), yielding 0.051 for our calculations. For women who used combination oral contraceptives, who used barrier methods, and who were partners of vasectomized men, we assumed that the contraceptive method did not affect the site of implantation; therefore we assumed that the proportion of pregnancies implanting in an ectopic location was 0,005, approximately equal to the overall proportion among reported pregnancies in the U.S. population during the early 1970s.1 6 For women with tubal sterilization failures we obtained the proportion with ectopic implantation from literature reviews. 7 • 8 The IUD was the only contraceptive method for which actual observed rates of ectopic pregnancy per 1000 woman years of use were available from large cohort studies. 12. 13 These empiric rates were averaged (directly weighted by number of woman years of use in each study) and were compared with those calculated as described above. Results
The resulting estimated ectopic pregnancy rates by contraceptive method vary more than 500-fold from the lowest rate of 0.005 per 1000 woman years among
1122
Franks et al.
women who used combination oral contraceptives or who were partners of vasectomized men, to the highest rate of 2.6 per 1000 woman years among women using no contraception (Table I). Thus, although using an IUD carries a higher rate of ectopic pregnancy than using barrier methods, sterilization, or oral contraception, failure to use any contraception has the highest estimated rate of ectopic pregnancy. For IUD use, the calculated ectopic pregnancy rate can be compared with the actual rates of 1.0 per 1000 woman years in the U.S. study and 1.2 per 1000 woman years in the U.K. study referred to previously.I2. 13 On the basis of these numbers, the weighted average of 1.06 per 1000 woman years compares favorably with the calculated rate of 1.02 per 1000 woman years derived by multiplying the pregnancy rate and the proportion of resulting pregnancies that were ectopic (Table I). Comment
We believe that expressing risk of disease, whenever possible, in terms of absolute rates of occurrence, rather than only in relative terms, is more useful for clinical decision making. For ectopic pregnancy we believe relative risk estimates from case-control studies are especially confusing because the choice of control group profoundly affects interpretation of results. To estimate rates of occurrence of ectopic pregnancy in the absence of sufficient cohort data, we assumed that the proportion of pregnancies implanting in an ectopic location did not differ among women who used combination oral contraceptives, women who used barrier methods, women who were partners of vasectomized men, and women who used no contraception. If this assumption is incorrect, our resulting estimates of incidence rates for ectopic pregnancy might be incorrect as well; however, on the basis of current knowledge, we know of no reason to question this assumption. For those who prefer to make different assumptions regarding the likelihood of ectopic implantation, our methods may be easily applied, by substituting different numbers. Similarly, although we used the "lowest expected" ("method") failure rates for the various contraceptive groups for our calculations, one could easily use the "typical" ("user") failure rates among women using contraception instead. While the former is based on the assumption of consistent and correct use of the contraceptive method, the latter is based on "typical" couples, including those who do not use the contraceptive method consistently or correctly. To calculate ectopic pregnancy rates based on "typical" failure rates, one could substitute pregnancy rates of 30 per 1000 women for oral contraceptives, 1.5 per 1000 women for vasectomy, 120 per 1000 women for condoms, 180 per 1000
October 1990 Am J Obstet Gynecol
women for the diaphragm, 4 per 1000 women for tubal sterilization, and 60 per 1000 women for the IUD.I4 This substitution results in estimated "typical" ectopic pregnancy rates of 0.15,0.0075,0.60,0.90,0.64, and 3.06 per 1000 woman years of use, respectively. It should be noted that we used the first-year failure rates for women who used the various contraceptives while we used the average annual pregnancy rate for women who used no contraception. Because failure rates tend to decline over time for reversible contraceptives, our results may be biased in the direction of exaggerating the ectopic pregnancy risk among women using contraception. For women using sterilization to avoid pregnancy, failure rates over time may depend on method of occlusion and other factors that are not yet fully understood. Therefore predicting the direction of any potential bias in our calculations regarding sterilization is difficult. We also assumed the ectopic pregnancy rate to be the product of the pregnancy rate and the likelihood of ectopic implantation. Again, no data exist to challenge this assumption, and our own estimate of the ectopic prengancy rate among IUD users on the basis of this multiplicative assumption compares favorably with the actual rates reported in two large cohort studies. The only available cohort data reflect rates of ectopic pregnancy among IUD users during the 1960s and early 1970s. To make meaningful comparisons, we estimated the occurrence of ectopic pregnancy for other methods on the basis of data as close in time as possible to the IUD cohort studies. Note, however, that the currently used copper-containing IUDs have lower failure rates than the nonmedicated IUDs,I4 which were predominantly used in the 1960s and early 1970s. Thus the ectopic pregnancy rate associated with IUD use may be somewhat reduced in recent years. On the other hand, recent information suggests that the proportion of ectopic pregnancies among pregnancies resulting from tubal sterilization failure may vary according to method of occlusion and may be higher than previously believed, especially for pregnancies occurring after tubal sterilization by electrocoagulation. I7 Further research is necessary to clarify this issue. Though our estimates are imprecise, and changes in risk over time may have occurred, the differences in magnitude of ectopic pregnancy risk between contraceptives are so large that we believe the relative ranking of risk to be correct. We hope that expressing the risk of ectopic pregnancy associated with contraceptive methods as rates of occurrence rather than as relative risks will be meaningful in the clinical setting. In particular, the fact that ectopic pregnancy risk appears to differ little between women who use IUDs and women who use no contraception should be reassuring for
Volume 163 Number 4, Pan 1
those women for whom the IUD is otherwise the best contraceptive option. REFERENCES I. Lawson HW, Atrash HK, Saftlas AF, Franks AL, Finch EL, Hughes JM. Ectopic pregnancy surveillance, United States, 1970-1985. MMWR 1988;37(SS-5):9-18. 2. Beral V. An epidemiological study of recent trends in ectopic pregnancy. Br J Obstet GynaecoI1975;82:775-82. 3. Chow WH, Daling JR, Cates W Jr, Greenberg RS. Epidemiology of ectopic pregnancy. Epidemiol Rev 1987;9: 70-94. 4. Robinson N, Beral V. Risk of ectopic pregnancy. Lancet 1979;2: 1247-8. 5. Ory HW. Ectopic pregnancy and intrauterine contraceptive devices: new perspectives. Obstet Gynecol 1981;57: 137-44. 6. Marchbanks PA, Annegers JF, Coulam CB, Strathy JH, Leonard TK. Risk factors for ectopic pregnancy: a population-based study. JAMA 1988;259:1823-7. 7. Tatum HJ, Schmidt FH. Contraceptive and sterilization practices and extrauterine pregnancy: a realistic perspective. Ferti! Steril 1977;28:407-21. 8. DeStefano F, Peterson HB, Layde PM, Rubin GL. Risk of ectopic pregnancy following tubal sterilization. Obstet Gynecol 1982;60:326-30.
Contraception and ectopic pregnancy risk
1123
9. Kleinbaum DG, Kupper LL, Morgenstern H. Epidemiologic research: principles and quantitative methods. New York: Van Nostrand Reinhold, 1982:62-70. 10. Weiss NS, Daling JR, Chow WHo Control definition in case-control studies of ectopic pregnancy. Am J Public Health 1985;75:67-8. II. Weiss NS, Daling JR. Risk factors for ectopic pregnancy. JAMA 1988;260:1553-4. 12. Vessey MP, Yeates D, Flavel R. Risk of ectopic pregnancy and duration of use of an intrauterine device. Lancet 1979;2:501-2. 13. Lehfeldt H, Tietze C, Gorstein F. Ovarian pregnancy and the intrauterine device. AM J OBSTET GYNECOL 1970; 108: 1005-9. 14. Trussell J, Kost K. Contraceptive failure in the United States: a critical review of the literature. Stud Fam Plann 1987;18:237-83. 15. Sheps MC. An analysis of reproductive patterns in an American isolate. Popul Stud 1965; 19:65-80. 16. Centers for Disease Control. Ectopic pregnancyUnited States, 1986. MMWR 1989;38:481-4. 17. Bhiwandiwala pp, Mumford SD, Feldblum PJ. A comparison of different laparoscopic sterilization occlusion techniques in 24,439 procedures. AM J OBSTET GYNECOL 1982; 144:319-31.
Bound volumes available to subscribers Bound volumes of the AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY are available to subscribers (only) for the 1990 issues from the Publisher, at a cost of $56.00 ($79.00 international) for Vol. 162 (January-June) and Vol. 163 (july-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue in the volume. The binding is durable buckram with the JOURNAL name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby-Year Book, Inc., Circulation Department, 11830 Westline Industrial Drive, St. Louis, Missouri 63146-3318, USA; phone (800) 325-4177, ext. 735l. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular JOURNAL subscription.
