title: Risk of miscarriage with bivalent vaccine against human papillomavirus (HPV) types 16 and 18: pooled analysis of two randomised controlled trials.
abstract: OBJECTIVE
  To assess whether vaccination against human papillomavirus (HPV) increases the risk of miscarriage.
  
  
  METHODS
  Pooled analysis of two multicentre, phase three masked randomised controlled trials
  
  
  METHODS
  Multicentre trials in several continents and in Costa Rica.
  
  
  METHODS
  26 130 women aged 15-25 at enrolment; 3599 pregnancies eligible for analysis.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  There is no evidence overall for an association between HPV vaccination and risk of miscarriage.
  
  
  BACKGROUND
  Clinical Trials NCT00128661 and NCT00122681.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Rockville, MD 20852, USA. WacholdS@mail.nih.gov
authors.forename: Sholom
authors.initials: S
authors.lastname: Wacholder
authors.forename: Bingshu Eric
authors.initials: BE
authors.lastname: Chen
authors.forename: Allen
authors.initials: A
authors.lastname: Wilcox
authors.forename: George
authors.initials: G
authors.lastname: Macones
authors.forename: Paula
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Brian
authors.initials: B
authors.lastname: Befano
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodríguez
authors.forename: Diane
authors.initials: D
authors.lastname: Solomon
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
mesh_terms: D000022:Abortion, Spontaneous / Q000139:chemically induced*; D000293:Adolescent; D000328:Adult; D019496:Cancer Vaccines / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D030361:Papillomavirus Infections / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000009:adverse effects*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control; D011252:Pregnancy Complications, Neoplastic / Q000517:prevention & control*; D011256:Pregnancy Outcome; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18