OBJECTIVE:

To assess whether vaccination against human papillomavirus (HPV) increases the risk of miscarriage.

DESIGN:

Pooled analysis of two multicentre, phase three masked randomised controlled trials

SETTING:

Multicentre trials in several continents and in Costa Rica.

PARTICIPANTS:

26 130 women aged 15-25 at enrolment; 3599 pregnancies eligible for analysis.

INTERVENTIONS:

Participants were randomly assigned to receive three doses of bivalent HPV 16/18 VLP vaccine with AS04 adjuvant (n=13 075) or hepatitis A vaccine as control (n=13 055) over six months.

MAIN OUTCOME MEASURES:

Miscarriage and other pregnancy outcomes.

RESULTS:

The estimated rate of miscarriage was 11.5% in pregnancies in women in the HPV arm and 10.2% in the control arm. The one sided P value for the primary analysis was 0.16; thus, overall, there was no significant increase in miscarriage among women assigned to the HPV vaccine arm. In secondary descriptive analyses, miscarriage rates were 14.7% in the HPV vaccine arm and 9.1% in the control arm in pregnancies that began within three months after nearest vaccination.

CONCLUSION:

There is no evidence overall for an association between HPV vaccination and risk of miscarriage.

TRIAL REGISTRATION:

Clinical Trials NCT00128661 and NCT00122681.