Spontaneous reports of primary ovarian insufficiency after vaccination: A review of the vaccine adverse event reporting system (VAERS)

Background: Since 2012, reports of primary ovarian insufficiency (POI) temporally associated with receipt of human papillomavirus (HPV) vaccine have been published leading to questions about a potential cau-sal association. A Vaccine Safety Datalink study did not find an increased risk for POI after vaccination. We reviewed the Vaccine Adverse Event Reporting System (VAERS) to describe POI reports. Methods: We searched VAERS, a U.S. passive surveillance system, for domestic POI reports received from 01/01/1990 to 12/31/2017 after any vaccination. The search used both Medical Dictionary for Regulatory Activity Preferred Terms and a text-based search for POI and its symptoms. All reports were reviewed, and the American College of Obstetricians and Gynecologists (ACOG) guidelines for POI diagnosis were applied. Data mining for disproportionate reporting was conducted. Results: Six hundred fifty-two reports met the search criteria and clinical review identified 19 POI reports. Most reports (n = 16) were received between 2013 and 2017. The median age at vaccination was 14.5 years (range 10-25 years) and the median interval between first dose of vaccination and report-ing the event to VAERS was 43 months (range 4-132 months; mean 59.6 months). Four reports met ACOG diagnostic criteria; one with an underlying cause (47XXX chromosomal abnormality) reported. Eleven reports documented menstrual irregularity >= 3 months; 5 had >= 1 laboratory test result used to diagnose POI. Eighteen of 19 reports described receipt of HPV vaccine with or without other vaccines. Other vac-cines reported were meningococcal conjugate vaccine, hepatitis A, varicella and tetanus toxoid, reduced diphtheria toxoid and acellular pertussis. Disproportionate reporting was found for three relevant coding terms after HPV vaccination. Conclusions: POI is rarely reported to VAERS. Most reports contained limited diagnostic information and were submitted after published cases of POI following HPV vaccination. Results of our review do not sug-gest a safety concern.Published by Elsevier Ltd.