Human Papillomavirus Prophylactic Vaccination improves reproductive outcome in infertile patients with HPV semen infection: a retrospective study

Abstract

In this study we aimed to evaluate the effect on reproductive outcome of HPV vaccination in male subjects of infertile couples with HPV semen infection. In this single-center study, we retrospectively enrolled 151 infertile couples with detection of HPV in semen, attending our Hospital Unit of Andrology between January 2013 and June 2015, counseled to receive adjuvant HPV vaccination. Seventy-nine accepted vaccination (vaccine group) whilst 72 did not (control group). Our protocol of follow-up, aimed to evaluate HPV viral clearance, consisted in semen analysis, INNO-LiPA and FISH for HPV in semen cells after 6 and 12 months from basal evaluation. Spontaneous pregnancies, miscarriages and live births were recorded. Progressive sperm motility and anti-sperm antibodies were improved in the vaccine group at both time points (p < 0,05 vs control arm). Forty-one pregnancies, 11 in the control group and 30 in the vaccine group, were recorded (respectively 15% and 38,9%, p < 0,05) and resulted into 4 deliveries and 7 miscarriages (control group) and 29 deliveries and one miscarriage (vaccine group, p < 0,05 vs control group). HPV detection on sperms was predictive of negative pregnancy outcome. Adjuvant vaccination associated with enhanced HPV healing in semen cells and increased rate of natural pregnancies and live births.

Figure 1

Flow diagram of the study showing the sample size of the study cohort, the proportion of patients accepting vaccination and the time-points for the clinical evaluation of viral healing.

Figure 2

Means (±standard errors) of total sperm count (A), progressive motility (B), normal morpholoy (C) and anti-sperm antibodies (D) observed in the control arm (blue bars) and in the vaccine arm (green bars) at the different time-points. T0: Baseline; T1: 6 months (at the end of HPV vaccination); T2: 12 months (after further 6 months from the end of HPV vaccination). *p < 0.05 vs control arm.

Figure 3

Mean percentage (±standard errors) of (A) HPV-infected sperm and (B) exfoliated cells (E.c.), observed by FISH analysis, in the control arm (empty bars) and in the vaccine arm (grey bars) at different time points. T0: Baseline; T1: 6 months (at the end of HPV vaccination); T2: 12 months (after further 6 months from the end of HPV vaccination). *p < 0.05 vs control arm.

Figure 4

Proportion of natural pregnancies (blue), deliveries (green) and abortions (purple) at T2 from couples of the control arm (A) and vaccine arm (B). *p < 0.05 vs control arm.