Long-term safety of human papillomavirus vaccination in relation to early pregnancy outcomes: registry-based follow-up of a community-randomized trial.

Despite the demonstrated safety of human papillomavirus vaccines, concerns have arisen regarding potential associations of human papillomavirus vaccination on reproductive health. The objective of this registry-based study was to compare overtime association of vaccination and early pregnancy outcomes. Twenty thousand four hundred twenty-six women born in 1992-1995, who participated in a Finnish community-randomized human papillomavirus vaccination trial, and age- and community-aligned unvaccinated controls born in 1990-1991 (n = 19 473) were followed up for 11 years. Data was obtained from the nationwide Finnish Care Register for Health Care. Incidence rates of adverse early pregnancy outcomes were compared between the human papillomavirus vaccinated and unvaccinated group. The mean age at first abnormal pregnancy result was 23.5 years in the human papillomavirus vaccinated group and 22.2 years in the unvaccinated group. 1.6% of human papillomavirus vaccinated women experienced a miscarriage compared with 5.3% of unvaccinated controls (P < .0001). No miscarriages occurred in close temporal proximity to vaccination. Rates of ectopic pregnancies were low and comparable across all groups (0.6-1.0%). Among women with a history of abnormal pregnancy outcomes, 55.6% of human papillomavirus vaccinated individuals had at least one live birth, compared with 70.3% of unvaccinated women. Human papillomavirus vaccination was not associated with an increased risk of miscarriage or other adverse early pregnancy outcomes. These results provide reassurance that human papillomavirus vaccination is safe with respect to reproductive outcomes, supporting its continued use in adolescent and young adult populations.