Genetic aspects of fertility disorders

Genetic disorders of fertility can occur at the level of gonadal differentiation or function, germ cell production or function, and the genital ducts. In gonadal dysgenesis, the differentiation of testes or ovaries is impaired. Gonadal dysgenesis can be caused by chromosome aberrations or monogenetic defects in XY or XX gonadal dysgenesis. For the biosynthesis of sexual hormones, a normal development of the gonads and an intact hypothalamic-pituitary-gonadal axis is necessary. Disorders of steroid hormone synthesis are associated with an increased or diminished production of sexual hormones. Clinical and genetic aspects of adrenogenital syndrome are discussed here. Mutations of the androgen receptor cause a spectrum of androgen insensitivity ranging from women with female external genitalia through patients with genital ambiguity to men with infertility. Disturbed spermatogenesis is heterogeneous and can be the result of chromosome aberrations such as Klinefelter syndrome or structural aberrations as translocations and microdeletions of the Y chromosome. Premature ovarian failure is characterized by amenorrhea and hypergonadotropic hypogonadism before 40 years of age. Beside nongenetic factors, premature ovarian failure can be caused by chromosome aberrations or monogenetic defects. Disorders of the genital ducts such as anomalies of the mullerian ducts in females and of the wolffian ducts in males can be associated with sterility or infertility.