Diethylstilbestrol Women exposed to DES in utero who subsequently conceive are at increased risk for ectopic pregnancy. In a review by Goldberg and Falcone, the pooled risk of ectopic pregnancy in DES-exposed women was nine times that of nonexposed women (65). Structural tubal abnormalities were found in DES-exposed women, including foreshortening, constrictions, and distortions (66). The Collaborative Diethylstilbestrol-Adenosis Project, which monitored 327 DES-exposed women, found that about 50% had uterine cavity abnormalities. In DES-exposed women, the risk for ectopic pregnancy was 13% in those who had uterine abnormalities compared with 4% in those who had a normal uterus. No specific type of defect was related to the risk for ectopic pregnancy (67).
Contraceptive Use It is not surprising that by reducing the overall likelihood of pregnancy, contraceptive use reduces the risk of ectopic pregnancy. There is concern that because of the various mechanisms of action of contraceptives, if a pregnancy were to occur, it might be more likely to be ectopic. In a meta-analysis of 13 studies examining the relationship between contraception and the risk of ectopic pregnancy, there was no increased risk in users of oral contraceptives or barrier methods compared with pregnant controls (40). There is no demonstrated increased risk in users of depomedroxyprogesterone injections, emergency contraceptive pills, or etonogestrel implants (68–70).
Hormonal and copper-containing IUDs are highly effective at preventing both intrauterine and extrauterine pregnancies. Women who conceive with an IUD in place are more likely to have a tubal pregnancy than those not using contraceptives. For women using the levonorgestrel intrauterine device, half of pregnancies will be ectopic, and 1 in 16 pregnancies in women with a copper IUD in place will be ectopic (71). The baseline risk of ectopic pregnancy in women not contracepting is 1 in 50. In a meta-analysis of studies investigating risk of ectopic pregnancy in IUD users compared with nonpregnant controls, IUD use had a protective effect with the exception of one study that showed no effect of IUD use (40). In the same meta-analysis, when IUD users were compared with pregnant controls, IUD use was associated with a significantly increased risk for ectopic pregnancy; the odds ratios ranged from 4.2 to 45. A common odds ratio could not be calculated because of heterogeneity between studies. The study with the most precise point estimate was a multinational case-control study conducted by the World Health Organization involving more than 2,200 women, which found an odds ratio of 4.2 (95% confidence interval, 2.5–6.9) (72). This suggests that while the intrauterine device decreases the risk of pregnancy overall, if a failure does occur, the device is more successful at preventing intrauterine pregnancy than tubal pregnancy. Past IUD use may slightly increase the risk of ectopic pregnancy. It should be noted that many of the studies that demonstrated this finding were conducted in the 1970s and 1980s, when women may have been using the Dalkon Shield, an IUD strongly associated with PID and ectopic pregnancy (73). The IUDs on the market in recent years are not associated with PID after the immediate insertion period (74).