Male infertility and genitourinary birth defects: there is more than meets the eye

Male factor infertility is a significant problem present in up to 50% of infertile couples. The relationship between male infertility and systemic disease is of significant interest, and emerging evidence suggests a relationship between male infertility and male genitourinary (GU) birth defects (cryptorchidism, hypospadias, ambiguous genitalia, and congenital anomalies of the kidney and urinary tract). Many of these birth defects are treated in isolation by busy urologists without acknowledgment that these may be related to more global syndromic conditions. Conversely, geneticists and nonurologists who treat variable systemic phenotypes may overlook GU defects, which are indeed related conditions. Many of these defects are attributed to copy number variants dosage-sensitive genes due to chromosome microdeletions or microduplications. These variants are responsible for disease phenotypes seen in the general population. The copy number variants described in this review are syndromic in some cases and responsible for both GU birth defects as well as other systemic phenotypes. This review highlights the emerging evidence between these birth defects, male infertility, and other systemic conditions.