Fertility in adult men born with hypospadias: A nationwide register-based cohort study on birthrates, the use of assisted reproductive technologies and infertility

摘要

Background: Fertility in men with hypospadias may be affected due to anatomical, surgical, or etiological factors and associated conditions. Fertility is further influenced by psychosocial and genetic factors, often shared within families. Objective: To evaluate fertility in men born with hypospadias and assess confounding by familial factors. Materials and methods: A population-based cohort of 1.2 million men born in Sweden 1964-1998, identified through national demographic and healthcare registers. Associations between hypospadias and (a) being a biological father, (b) conceiving through ART, and (c) diagnosis of male infertility were investigated in the full cohort with logistic regression models and Cox proportional hazard models, expressed as odds ratios (ORs) and hazard ratios (HRs), respectively, with 95% confidence intervals (CIs). A stratified proportional hazard model, conditional on sibling group, was used to control for shared familial confounding. Results: Men with hypospadias, as a whole group, had a lower probability of having biological children (adjusted HR0.87,95% Cl 0.83-0.92). Asignificant association was present in both distal (adjusted HR 0.90, 95% Cl 0.85-0.96) and proximal hypospadias (HR 0.59, 95% Cl 0.42-0.81). Men with hypospadias more often became fathers through ART, regardless of concomitant cryptorchidism. The initial association between hypospadias and the diagnosis of infertility disappeared in sensitivity analyses excluding cryptorchidism. Discussion: Men with hypospadias displayed lower birthrates as compared to their brothers and the general population. Mere birthrates may, however, be a questionable measure of fertility in a population using family planning. However, men with hypospadias were also at higher risk of reproducing through ART and did more often receive a diagnosis of male infertility. Altogether, these findings indicate impaired fertility in men with hypospadias. Conclusions: Fertility in men with hypospadias is impaired, as shown by lower birthrates, increased use of ART and higher risk of receiving a diagnosis of male infertility.