Effect of human papilloma virus infection on in-vitro fertilization outcome: systematic review and meta-analysis

Objectives To identify, appraise and summarize the available data concerning the impact of human papilloma virus (HPV) infection on reproductive outcome following in-vitro fertilization (IVF). Methods We searched for studies in PubMed, EMBASE, Scopus, Lilacs and the Cochrane Central Register of Controlled Trials from inception to March 2017. Any type of HPV infection assessed through polymerase chain reaction, subfertility factors and IVF indications and protocols were considered. Our primary outcomes were live birth/ongoing pregnancy and miscarriage, while secondary outcomes included clinical and laboratory parameters. We planned subgroup analyses according to the status of cervical cytology and presence of infection in the male partner. We assessed the relative risk (RR), using a random-effects model; heterogeneity was assessed using the I2 statistic. Quality of the evidence was evaluated using the recommendations of the GRADE Working Group. Results From the 14 studies eligible for inclusion, quantitative data from 10, evaluating 299 women with HPV infection and 2049 women without HPV infection, were included in the analysis. The pooled results showed no significant difference between HPV-infected and non-infected women in rates of live birth/ongoing pregnancy (RR, 1.16 (95% CI, 0.88-1.53); I-2 = 0%; six studies, 983 women), clinical pregnancy (RR, 1.06 (95% CI, 0.74-1.54); I-2 = 61%; eight studies, 1173 women) or miscarriage (RR, 1.58 (95% CI, 0.93-2.69); I-2 = 8%; six studies, 290 clinical pregnancies). The overall quality of the evidence was very low, downgraded two levels because of serious limitations of the included studies (observational studies) and imprecision. In contrast, pooled results in the subgroup analysis based on the presence of infection in the male partner showed significant differences in rates of live birth/ongoing pregnancy (RR, 0.43 (95% CI, 0.23-0.82); I-2 = 0%; three studies, 429 participants; P= 0.01) and miscarriage (RR, 3.70 (95% CI, 1.94-7.05); I-2 = 0%; two studies, 90 participants; P< 0.0001). Conclusions The available evidence is still inadequate to enable us to draw firm conclusions regarding the effect of HPV infection in women on the most important reproductive outcomes following IVF; however, it suggests that the effect is not large for rates of live birth/ongoing pregnancy and clinical pregnancy. When infection is present in the male partner, it seems that there is a negative effect on live birth/ongoing pregnancy rate and an increase in miscarriage rate, a finding that should be interpreted with caution, owing to the very low quality of evidence supporting it. Copyright (C) 2017 ISUOG. Published by John Wiley & Sons Ltd.