Intended for healthcare professionals

Rapid response to:

Clinical Review Regular Review

Ectopic pregnancy

BMJ 2000; 320 doi: (Published 01 April 2000) Cite this as: BMJ 2000;320:916

Rapid Response:

Association between the birth control pill and ectopic pregnancy

We were very pleased to see the excellent review of ectopic pregnancy
by Tay et al. In their otherwise accurate review, they report, "Previous
female sterilisation and current use of an intrauterine contraceptive
device are only risk factors when patients with ectopic pregnancy are
compared with pregnant controls and not with non-pregnant women."(1) We
feel that this statement is misleading.

Recently, we published a systematic review on the post-fertilization
effects of oral contraceptives,(2) in which we reviewed data indicating
that the ratio of extrauterine to intrauterine pregnancies is increased
for women on combined oral contraceptives (COCs) and progestin-only pills
(POPs), when compared to control groups of pregnant women not using oral
contraceptives (OCs).

The increased odds ratio (OR) of ectopic pregnancy in women on COCs
(compared to pregnant controls) was found in one study from seven
maternity hospitals in Paris, France, to be 4.5 (95%CI 2.1-9.6)(3) and in
another study from three maternity hospitals in Sweden to be 13.9 (95%CI
1.8-108.3).(4) These studies involved a total of 484 women with ectopic
pregnancies and 289 pregnant controls. We excluded three studies, for
reasons discussed in our review, which reported ORs of 1.7 (95%CI 1.1-
2.5), 1.8 (95% CI 0.9-3.4) and 4.3 (95% CI 1.5-12.6).(2)[NOTE - THESE

We used these ORs to estimate that in the studied populations that
the absolute rate of ectopic pregnancy in women using COCs would range
from 0.7 to 19.9 ectopic pregnancies per 1000 woman-years.(2) However, we
could only find one study which reported an absolute risk of ectopic
pregnancy in women on OCs. This study, from Zimbabwe, reported an ectopic
rate of 0.5 per 1000 women years.(5)

The increased OR of ectopic pregnancy for a woman on POPs (compared
to pregnant controls) was reported in one data set to be 79.1 (95% CI 8.5-
735.1)(6) which we used to estimate an absolute risk of 4 to 79 ectopic
pregnancies per 1000 woman-years.(2) This prediction is reasonably
concordant with the reported absolute rates of ectopic pregnancy in women
taking POPs, which have been reported in other populations to range from
about 3(7) to 20(8) per 1000 woman-years.

We recognize that studies that have used non-pregnant controls have
not shown a risk of increased ectopic pregnancy for users of OCs; however
like most researchers in this field, we restricted our review to studies
using pregnant controls because we concur with Tay and others(9,10) that
when considering the situation where a woman became pregnant during the
use of a birth control agent, one should focus on pregnant controls.

As the review so aptly pointed out, an ectopic pregnancy involves a
substantial risk to a woman. We believe that the association of ectopic
pregnancies with oral birth control pills has been overlooked in the
medical literature on ectopic pregnancy. Further, we believe most who
prescribe or dispense oral birth control pills are not aware of this
association. If a woman who is taking an oral birth control pill presents
with pelvic pain and unusual vaginal bleeding, we would recommend that the
possibility of ectopic pregnancy be ruled-out using the wise and practical
clinical approach suggested by Tay, et al.

Walter L. Larimore, MD

Associate Clinical Professor,
Department of Family Medicine, University of
South Florida, Tampa, Florida

email -

Joseph B. Stanford, MD, MSPH

Assistant Professor,
Department of Family and Preventive Medicine,
University of Utah, Salt Lake City, Utah

email -


1) Tay JI, Moore J, Walker JJ. Ectopic pregnancy. BMJ 2000 Apr

2) Larimore WL, Stanford JB. Postfertilization effects of oral
contraceptives and their relationship to informed consent. Arch Fam Med
2000 Feb;9(2):126-33.

3) Coste J, Job-Spira N, Fernandez H, Papiernik E, Spira A. Risk factors
for ectopic pregnancy: a case-control study in France, with special focus
on infectious factors. Am J Epidemiol 1991;133:839-49.

4) Thorburn J, Berntsson C, Philipson M, Lindbolm B. Background factors of
ectopic pregnancy. I. Frequency distribution in a case-control study. Eur
J Obstet Gynecol Reprod Biol 1986;23:321-331.

5) De Muylder X . Ectopic pregnancy in Zimbabwe. Int J Gynaecol Obstet

6) Liukko P, Erkkola R, Laakso L. Ectopic pregnancies during use of low-
dose progestogens for oral contraception. Contraception 1977;16:575-580.

7) Bonnar J. Progestagen-only contraception and tubal pregnancies. Lancet

8) Job-Spira N, Fernandez H, Coste J, Papiernik E, Spira A. Risk of
Chlamydia PID and oral contraceptives. J Am Med Assoc 1990;264:2072-4.

9) Mol BWJ, Ankum WM, Bossuyt PMM, and Van der Veen F. Contraception and
the risk of ectopic pregnancy: a meta analysis. Contraception 1995;52:337-

10) Coste J, Job-Spira N, Fernandez H, Papiernik E, Spira A. Risk factors
for ectopic pregnancy: a case-control study in France, with special focus
on infectious factors. Am J Epidemiol 1991;133:839-49.

Competing interests: No competing interests

05 April 2000
Walter L Larimore
Associate Clinical Professor of Family Medicine, University of South Florida, Tampa, Florida, USA
Heritage Family Physicians, Kissimmee, Florida, USA