One of the most clinically challenging and controversial topics with 46,XY DSD is the practice of "sex assignment" or "sex of rearing". This is especially so in<unk> R2D, since most affected individuals have undervirilized genitalia at birth but virilize to varying degrees at puberty. Historically most<unk> R2D individuals have been "raised as females", but later reports show that over half of patients who underwent virilizing puberty adopted a male gender identity thus challenging historical practices. The goal of sex assignment/of rearing is to facilitate the greatest likelihood of a concordant gender identity in the patient's adulthood. The factors that contribute to gender identity are complex and not easy to report but some factors that contribute include sex chromosomes, androgen exposure, psychosocial development, cultural expectations, family dynamics and social situation. Female sex of rearing in<unk> R2D individuals involves surgical procedures such as childhood gonadectomy (to prevent virilization at puberty) and vaginoplasty. Life-long hormonal treatments as also required for the development and maintenance of female secondary sex characteristics. Male sex of rearing avoids lifelong hormonal treatments and allow for the potential of fertility. Cryptorchidism and hypospadias must be addressed to prevent damage to the seminiferous tubules that are essential for spermatogenesis and fertility. Diagnosis in infancy is essential before any gender assignment or surgical intervention since patients should be considered males at birth. The intersection of the child's well being, parental wishes, recommendations of the associated medical team and local laws makes decision making challenging in these cases. The necessity and ethics around consent and deception involved in administering such interventions has been seriously questioned. Fertility Spontaneous fertility in<unk> R2D affected males is usually not possible (though has been observed) due to semen abnormalities that include reduced sperm counts, high semen viscosity and, in some cases, lack of primary spermatocytes. This supports the notion that DHT has an important role in spermatocyte differentiation. The broad spectrum of presentation is consistent with highly varying sperm counts among affected males. Testicular function may also be impaired by incomplete descent as well as the genetic mutation itself. Assisted reproduction methods involving sperm extraction and concentration for intrauterine insemination, intracytoplasmic sperm injection, and in vitro fertilization have all demonstrated successful outcomes.
5α-Reductase 2 deficiency
Isolated 17,20-lyase deficiency
17β-Hydroxysteroid dehydrogenase III deficiency
Aromatase deficiency
Cortisone reductase deficiency
Androgen-induced hermaphroditism
Multiple sulfatase deficiency
Gonadotropin-releasing hormone insensitivity