General Medical Information

Surgical Management of Genital Ambiguity

Mark R. Feneley and John P. Gearhart

Management of the infant with ambiguous genitalia demands great care and skill. Gender assignment requires careful clinical evaluation and full understanding of its implications for future sexual and psychological development as well as fertility. The surgeon must be sensitive to concerns of the parents and the future development of the individual patient. This may pose great dilemmas, even for the infant with a normal 46,XX or 46,XY karyotype.

Ambiguous genitalia represents a spectrum of deviations of in utero sexual development, where the abnormal external genitalia range from predominantly male to predominantly female. These are manifestations of female pseudohermaphroditism, male pseudohermaphroditism, true pseudohermaphroditism, and mixed gonadal dysgenesis. Evaluation includes history, physical examination, and special investigations to define the phenotypic, gonadal, and chromosomal sex.

Maternal hormone therapy or intake of androgenic substances, medications that interfere with steroid metabolism, and excess steroid production secondary to maternal illness during pregnancy are etiologically important. The unexpected death of a sibling during the first weeks of life may alert the physician to the likelihood of adrenogenital syndrome with salt wasting. Family history of genital anomalies may indicate the possibility of 5a-reductase deficiency or androgen receptor insensitivity. Sterility, amenorrhea, and hernia containing a gonad also may be relevant.

On physical examination, the genitalia are ambiguous by definition and thus are neither clearly male nor female. Any of the following abnormalities may be present: (a) small phallus in the genetic male or enlarged clitoris in the genetic female, (b) inappropriately fused labioscrotal folds, (c) bifid scrotum, (d) labial rugae, (e) hypospadias, (f) chordee, (g) gonads above or below the inguinal ring, (h) palpable epididymis on the gonad, or (i) midline uterus on rectal examination. Recognizing the presence of vaginal epithelial cells in the smear of the perineal discharge obtained by milking the vagina during the rectal examination may be informative. Major anomalies involving other organ systems may be present and should be evaluated.

Blood draw for both biochemical studies and karyotyping are mandatory in all cases of genital ambiguity. Biochemical studies may reveal an underlying enzymatic defect and should include serum electrolyte analysis, 17-hydroxyprogesterone, pregnenolone, gonadotrophins, testosterone, and dihydrotestosterone, and quantification of urinary ketosteroids and pregnanetriol. Congenital adrenal hyperplasia, due to enzymatic defect that results in mineralocorticoid and glucocorticoid deficiency, leads to overproduction of adrenal androgens and masculinized genitalia in a genetic female. In the newborn, this may present as a medical emergency and early diagnosis will be life saving. Karyotype may distinguish mixed gonadal dysgenesis from true hermaphroditism. Laparotomy or laparoscopy and gonadal biopsy may be necessary in some cases to definitively diagnose mixed gonadal dysgenesis, male pseudohermaphroditism, or true hermaphroditism.

Initial evaluation of the internal genitalia includes retrograde genitogram and pelvic ultrasound examination. The genitogram will confirm the presence of müllerian structures and define the “takeoff” position of the vagina from the urogenital sinus (Fig. 6.1). These findings have significant implications for surgical reconstruction, and the surgeon will appreciate the need to be present at the time of these examinations. Müllerian duct structures may be identified by ultrasound or their absence confirmed. Magnetic resonance imaging may provide additional information. In cases where internal genital anatomy and gonadal sex remain undetermined, gonadal biopsy may be necessary.

Decisions on sex of rearing for an infant should be based on anatomy and potential for sexual function and not chromosomal karyotype or fertility potential alone. Genetic females almost invariably can be reconstructed and raised as female, whereas males with an inadequate phallus may be assigned the female sex. It is not difficult to create a vagina if one is absent, but it may be difficult to create a satisfactory penis. For genetic males with an adequate phallus, male sex assignment should be considered, but in general only patients with a stretched penile length of at least 2.5 cm who have responded to testosterone should be considered. When the phallus is particularly diminutive or rudimentary, female sex should be assigned regardless of gonadal or ductal sex of the infant. Despite major technical advances in penile reconstruction, it continues to appear that infants with a major intersex abnormality fare better psychologically and anatomically as females than as males. A contemporary long-term study recently completed at our institution has demonstrated highly favorable psychosexual and surgical outcomes in male pseudohermaphrodites following female reconstructive surgery, particularly when vaginoplasty is delayed until adolescence (1A).