Sperm human papillomavirus infection and risk of idiopathic recurrent pregnancy loss: insights from a multicenter case-control study

Objective: To test the hypothesis claiming an association between human papilloma virus (HPV) sperm infection and idiopathic recur-rent pregnancy loss (RPL).Design: Multicenter retrospective case-control studySetting: Three university hospitals. Patient(s): Cases included men belonging to couples affected by first trimester idiopathic RPL. Controls included men belonging to couples with proven fertility and no history of pregnancy loss; RPL was defined as the previous loss of 2 or more pregnancies. Couples were defined as "fertile"if they achieved a full-term pregnancy within the year before enrollment in the study. All participants conceived without assistance.Main Outcome Measure(s): The association between HPV DNA sperm infection, as identified using polymerase chain reaction, and RPL. Results: The HPV DNA sperm infection was detected in 23 of 117 cases (20%; 95% confidence interval [CI]: 13%, 28%) and in 3 of 84 controls (4%; 95% CI; 1%, 10%) (P< .001). A comparison across baseline characteristics and multiple regression analysis did not identify any potentially confounding factors. Multivariate regression models showed a significant association between HPV DNA sperm infec-tion and RPL (adjusted odds ratio, 7.44; 95% CI: 2.08, 26.58; P=.002 [Model 1]; adjusted odds ratio, 8.96; 95% CI: 2.41, 33.44; P=.001 [Model 2]).Conclusions: The prevalence of HPV sperm infection was significantly higher in couples affected by RPL than in their fertile counter-parts. Notably, the semen sample was infected by HPV in approximately 1 out of 5 patients. (Fertil Sterile 2023;119:410-8. (c) 2022 by American Society for Reproductive Medicine.)