Abstract
Objective. This study investigated whether women with a history of human papillomavirus (HPV) infection have an increased risk of infertility. Material and Methods. All patients with an HPV infection (n = 11,198) in Taiwan’s National Health Insurance Research Database (2000–2012) were propensity score matched with control subjects (n = 11,198) without an HPV infection by age, sex, index year, and relevant co-morbidities. Both groups were tracked until a diagnosis of infertility was recorded. The Chi-square test was used to analyze the distribution of demographic characteristics in the HPV group and non-HPV group. A Cox proportional hazards regression was used to estimate the hazard ratios (HRs) for the development of infertility, adjusting for age, sex, and co-morbidities. The Kaplan–Meier method was used to plot the cumulative incidence curves. We also performed negative controls to test for possible unmeasured confounding. Results. The HPV cohort had a higher risk of infertility. The adjusted HR (aHR) was found to be 1.39 (95% CI = 1.19–1.63) after adjusting for demographic characteristics and relevant co-morbidities. In the age subgroup analysis, patients with an HPV infection had an increased risk of infertility compared to the non-HPV cohort in the group aged 26 to 35 years (aHR, 1.53; 95% CI = 1.24–1.88). As we used propensity score matching to treat measurable confounders and negative controls to access unmeasured confounders, the findings of the study are robust. Conclusions. Among females of reproductive age, HPV infection is a potential risk factor that predisposes individuals to subsequent infertility.
Highlights
Infertility is defined as the inability to conceive after one year of regular intercourse without contraceptive measures involving both a male and a female partner [1]
Persistent human papillomavirus (HPV) infection has been linked to chronic inflammation [19], and during the HPV life cycle, the infectious virion-producing pathway may weaken the cells it resides in, which has been linked to infertility and early abortion [20]
The hazard ratios (HRs) adjusted for covariates was calculated for male and female patients and for the following age groups: 15–25, 26–35, and 36–45 years
Summary
Infertility is defined as the inability to conceive after one year of regular intercourse without contraceptive measures involving both a male and a female partner [1]. It is a complicated disorder affecting 8%–12% of reproductive-aged couples—estimated to be more than 48 million couples worldwide—which may lead to emotional and psychological distress [2,3]. The most common identifiable causes of female infertility are ovulatory disorders, endometriosis, pelvic adhesion, tubal abnormality, uterine abnormalities, hyperprolactinemia, and endometrial lesions [3,4,5,6]. Persistent HPV infection has been linked to chronic inflammation [19], and during the HPV life cycle, the infectious virion-producing pathway may weaken the cells it resides in, which has been linked to infertility and early abortion [20]
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