Reproductive outcomes in couples affected by human papillomavirus infection undergoing in vitro fertilization procedures

Abstract

Reproductive outcomes in couples affected by human papillomavirus infection undergoing in vitro fertilization procedures G. Ruvolo1, L. Giovannelli2, R. Schillaci3, P. Alimondi3, A. Pane1, A. Perino3, E. Cittadini1 1Centro di Biologia della Riproduzione, Centro di Biologia della Riproduzione, Palermo, Italy 2Dipartimento di Scienze per la Promozione della Salute, Dipartimento di Scienze per la Promozione della Salute, Palermo, Italy 3Dipartimento Materno Infantile University of Palermo, Dipartimento Materno Infantile University of Palermo, Palermo, Italy Introduction: Genital human papillomavirus (HPV) infection is the most common sexually transmitted viral infection worldwide, and has been associated with precancer and cancer of the male and female anogenital mucosa. Although it is well known that sexually transmitted infections are the primary cause of infertility few studies have investigated the effect of HPV infection on human reproduction. It has been designed a prospective study to investigate the role of HPV infection in infertile couples undergoing assisted reproductive technology (ART) cycles. The objectives of this study were to assess the prevalence of HPV infection in infertile couples, and to evaluate the correlation between HPV infection and ART outcome. Material and Methods: A total of 199 couples were enrolled from May 2008 to May 2009. The mean age of women and men were 34.7 ± 5.01 and 38.0 ± 6.36 years, respectively. Types of infertility were female (tubal occlusion, chronic anovulation, 24.1%), male (severe oligoasthenoteratozoospermia, 58.6%), couple (6.8%), and idiopathic (10.5%). The exclusion criteria were: cases of azoospermia, couples with repeated implantation failures and cases of endometriosis. All women had undergone cervical cytologic screening within the previous 12 months, with no cytologic abnormality reported. No patients tested were positive for microbiological and viral infections. Patients were treated with standard ovulation induction protocols and underwent cycles of ART. Cervical cells were obtained with the combined use of an Ayre’s spatula and an endocervical cytobrush before oocyte recovery by transvaginal ultrasound-guided follicular puncture, and were placed in 20 mL of PreservCyt Solution (Cytyc Corp,). Total DNAwas extractedwith the QIAampMiniKit (Qiagen,Germany). All investigations, both for IVF and ICSI procedures, were carried out on spermatozoa prepared with the swim-up technique. The association between pregnancy and miscarriage for demographic and clinical variables was assessed using the Chi-square test or Fisher’s exact test, as appropriate. A P value %.05 was considered statistically significant. Results: Out of the 199 couples, the male partner was HPV positive in 9.5% of couples (19/199), whereas the female partner had a positive HPV DNA test in 17.5% of couples (35/199). Both partners were HPV positive in 4.5% (9/199) of couples. Statistical analysis showed no differences in the rate of pregnancy in terms of HPV status. When considering the HPV infection of couples, the PR was 33.3% and 31.6%, respectively, in HPV negative and HPV positive men, and 31.1% and 42.9%, respectively, in HPV negative and HPV positive women. Conversely, miscarriage rates showed statistically significant differences. Couples who underwent ART cycles experienced an increased risk of pregnancy loss when HPV DNA testing was positive in the male partner, compared with non infected patients (66.7%–15%, P < 0.01. It is worth noting that all pregnanciesin HPV-positive couples resulted in miscarriage, whereas there was a 15.9% overall miscarriage rate in HPV-negative couples (P < 0.001). Discussion: Several studies have shown that infected spermatozoa may play a role as carriers of HPV DNA both in the reproductive tract and within the oocyte, with the possibility of detrimental effects during emb