key: cord-0776586-1d1pysg0 authors: Fenizia, Claudio; Savasi, Valeria title: Sperm washing – yes or no? An open issue still to be debated date: 2020-08-21 journal: Reprod Biomed Online DOI: 10.1016/j.rbmo.2020.08.017 sha: 3e3f7b2c8a679c8d2fc7affe58a75e7d5ed47f1e doc_id: 776586 cord_uid: 1d1pysg0 nan This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo editing, typesetting, and review of the resulting proof before it is published in its final form. Please note that during this process changes will be made and errors may be discovered which could affect the content. Correspondence or other submissions concerning this article should await its publication online as a corrected proof or following inclusion in an issue of the journal. We are pleased that our recent publication (Fenizia et al., 2020) has opened a constructive discussion (Garolla et al., 2020) . We agree with Garolla and colleagues that there are detrimental effects of human papilloma virus (HPV) on fertility and pregnancy outcomes, which is why we feel it is important to investigate some potential countermeasures. As stated in our paper, further studies should be performed. However, we would like to reply to the authors' specific concerns as follows: (i) PCR is the preferred designated method for virus detection, including clinical diagnosis of HPV (Depuydt et al., 2019) , HIV (Fearon, 2005) and SARS-CoV-2 in the current COVID-19 pandemic (Sethuraman et al., 2020) . Highly specific and highly sensitive, PCR allows HPV-detection of only a few copies in the whole ejaculate, including cellfree HPV in seminal plasma. Moreover, we believe that consideration of the findings of Song et al. (2017) scarcely apply to HPV detection, given that the aim there was to investigate intra-clonal heterogeneity in cancer, making bulk analyses inappropriate in that case; (ii) notoriously, HPV is still detected upon 'standard' sperm-washing procedures (Foresta et al., 2011) , as confirmed in Figure 1 in Garolla et al. (2020) . However, we apply the 'combined' sperm-washing procedure, which differs from the 'standard' one (Fenizia et al., 2020; Savasi et al., 2007) ; (iii) thus far, there is no universal HPV-screening in assisted reproductive technology procedures and we aim to raise awareness of the potential importance of this step. We also recommend caution and we encourage other suitable beneficial approaches to be adopted, including an anti-HPV vaccine (Garolla et al., 2018) . Indeed, we believe that a joint, double-blinded study could be helpful in defining more appropriate guidelines, as proposed at the 2019 meeting of the Italian Society for the Study of Fertility and Sterility and Reproductive Medicine (SIFES-MR). Infectious human papillomavirus virions in semen reduce clinical pregnancy rates in women undergoing intrauterine insemination The laboratory diagnosis of HIV infections Human papillomavirus in spermatozoa is efficiently removed by washing: a suitable approach for assisted reproduction Semen washing procedures do not eliminate human papilloma virus sperm infection in infertile patients Human Papillomavirus Prophylactic Vaccination improves reproductive outcome in infertile patients with HPV semen infection: a retrospective study Caution in the use of standard sperm-washing procedures for assisted reproduction in HPV-infected patients Safety of sperm washing and ART outcome in 741 HIV-1-serodiscordant couples Interpreting Diagnostic Tests for SARS-CoV-2 Enrichment and single-cell analysis of circulating tumor cells