Method of Hormonal Contraception and Protective Effects Against Ectopic Pregnancy: A Population-based Register Study

Background: Ectopic pregnancy is a major cause of maternal mortality, and it also causes significant morbidity in the form of surgical procedures, medication with methotrexate and reduced fertility. In Sweden the average incidence rate of ectopic pregnancy from 2008 to 2016 was approximately 0.83 cases per 1000 women-years for ages 15-49 years.

Objectives: To estimate the incidence rates for ectopic pregnancy by contraceptive method in a cohort of women using hormonal contraception in Sweden between 2005 and 2016.

Methods: Women aged 15-49 years with a filled prescription of a hormonal contraceptive in the Swedish Prescribed Drug Register between 2005 and 2016 were included. For each woman, all exposed women-time was allocated to treatment episodes depending on the method of contraception. Treatment time started on day of filled prescription and ended on the first day of end of supply, new eligible dispensing, pregnancy related diagnosis and its associated estimated date of last menstrual period, or removal procedure. Ectopic pregnancy was defined as having at least two recorded diagnoses of ectopic pregnancy within 30 days, or one diagnosis and one surgical procedure for ectopic pregnancy. Incidence rates per 1000 women-years and 95% confidence intervals (CI) were calculated for each method of contraception. A Cox regression model adjusted for age, history of endometriosis, previous ectopic pregnancy and contraceptive class was fitted to time to ectopic pregnancy. The fitted model was used for prediction of survival probabilities.

Results: The study included 1,663,242 women and 1,915 events of ectopic pregnancy. The estimated incidence rate per 1000 women-years for ectopic pregnancy per method of hormonal contraception (95% CI) was:
· Hormonal IUD 13.5 mg 2.76 (2.26 to 3.35),
· Hormonal IUD 52 mg 0.30 (0.28 to 0.33),
· Oral combined contraception 0.20 (0.19 to 0.22),
· Progestogen implants 0.31 (0.26 to 0.37),
· Oral medium dose progestogen 0.24 (0.21 to 0.27)
· Oral low-dose progestogen 0.81 (0.70 to 0.93).
The highest predicted risk for ectopic pregnancy was seen in women less than 40 years of age with a previous history of ectopic pregnancy using the IUD with 13.5 mg of progestogen. According to the model, approximately 9 cases of ectopic pregnancy in 100 treatments are expected during 2.5-3 years of use.

Conclusions: Hormonal contraception lowers the risk of ectopic pregnancy markedly. Women using a low-dose hormone IUD (13.5 mg levonorgestrel) had a substantially higher risk of ectopic pregnancy than women using other types of hormonal contraception. This study provides real-world evidence to inform best clinical practice for women-centered contraceptive counselling.