Prior Abdominal Surgery Many patients with ectopic pregnancies have a history of previous abdominal surgery. The role of abdominal surgery in ectopic pregnancy is unclear. In one study, there appeared to be no increased risk for cesarean delivery, ovarian surgery, or removal of an unruptured appendix (75). Other studies showed that ovarian cystectomy or wedge resection increases the risk for ectopic pregnancy, presumably because of peritubal scarring (76,77). Although there is agreement that an increased risk for ectopic pregnancy is associated with a ruptured appendix, one study did not confirm this finding (75).
Infertility The incidence of ectopic pregnancy increases with age and parity, and there is a significant increase in nulliparous women undergoing infertility treatment (27,32,49). For nulliparous women, conceptions after at least 1 year of unprotected intercourse are 2.6 times more likely to be tubal (78). Additional risks for infertile women are associated with specific treatments, including reversal of sterilization, tuboplasty, ovulation induction, and in vitro fertilization (IVF). Various studies examining risk factors for ectopic pregnancy found that infertility increased the odds of tubal pregnancy at least 2.5 times and perhaps as much as 21 times (32).
Hormonal alterations characteristic of clomiphene citrate and gonadotropin ovulation-induction cycles may predispose to tubal implantation. About 1.1% to 4.6% of conceptions associated with ovulation induction are ectopic pregnancies (78–80). In many of these patients, the results of hysterosalpingography are normal, and there is no evidence of intraoperative tubal pathology. Hyperstimulation, with high estrogen levels, may play a role in tubal pregnancy; however, not all studies showed this relationship (81–83).
When the first pregnancy obtained with IVF was a tubal pregnancy; about 2% to 8% of the conceptions are tubal (84). Tubal factor infertility is associated with a further increased risk of 17% (85–88). Predisposing factors are unclear but may include placement of the embryo high in the uterine cavity, ﬂuid reﬂux into the tube, and a predisposing tubal factor that prevents the reﬂuxed embryo from returning to the uterine cavity.
Smoking Cigarette smoking is associated with an increased risk for tubal pregnancy in a dose-dependent fashion. A case-control study showed a dose relationship: smokers of more than 20 cigarettes a day had a relative risk of 3.5 compared with nonsmokers, whereas smokers of up to 10 cigarettes had a risk of 2.3 (89). A case-control study in France found similar relative risk estimates (90). Alterations of tubal motility, ciliary activity, and blastocyst implantation are associated with nicotine intake.
Abortion Multiple studies suggest an association between ectopic pregnancy and spontaneous abortion (79,91). With recurrent spontaneous abortion the risk may be increased up to four times (92). This may reﬂect a shared risk factor, such as with luteal phase defect. Substantial evidence found no increased risk with elective abortion; one study did find a slightly increased risk, particularly with multiple abortions (93–96).