Surgery to Correct Ambiguous Genitalia (46XX Disorder of Sexual Development)

ANTHONY J. CASALE

Ambiguous genitalia and intersex are historical terms used to describe a congenital condition where the appearance of the genitalia is neither classically male nor female. Modern nomenclature has been proposed to replace the old, and this group of disorders is now described as disorders of sexual development (DSD). The condition affects both external genitalia (phallus, labia, scrotum, and introitus) and internal reproductive structures (vagina, urethra, urogenital sinus). In these cases, there is usually a conflict between the genetic sex, gonadal sex, and apparent gender as based on genital appearance. The genital appearance may be gender neutral and give little indication of the genetic or gonadal sex. On the other hand, the genitalia may have an appearance more consistent with the opposite gender, as with females with severely virilized congenital adrenal hyperplasia (CAH). When patients with these conflicts reach adulthood, they face significant hurdles in both reproduction and sexual activity.

The historical goal of surgery for ambiguous genitalia has been to provide the child with genitalia that have the appearance of and are functional as either male or female gender and that are consistent with the genetic and gonadal sex when possible. Feminizing genitoplasty is the term used to describe a series of surgical procedures designed to create classic female genitalia from a truly ambiguous genital state. This surgery has usually been applied to female patients with partially masculinized genitalia, and in those cases, surgery brings the genetic, gonadal, and genital sex back into alignment. Rarely, this surgery has been used to reassign the gender of genetic and gonadal male patients with what was felt to be inadequate phallic tissue to the female gender. It is this later group of patients who have had more difficulties with gender dissatisfaction and their experience has brought the principle of gender assignment under question. This chapter will discuss the technical aspects of feminizing genitoplasty.

Society dictates that the appearance of the infant’s genitals and therefore its apparent gender is the subject of great and urgent interest for the immediate and extended family and friends, making ambiguous genitalia a cause of intense concern and confusion for all. It is this powerful interest that has driven physicians and families to treat the condition as an emergency, even though there are often no immediate health risks. The historical approach to this issue has been to assign gender based on several factors, including the potential for reproduction, the technical limits of surgical reconstruction (i.e., our limited ability to create a male phallus without adequate corpora), and the belief that gender was determined by genital appearance and role assignment in childhood. The validity of this approach has recently been questioned and is the subject of widespread study at this time. At present, intrauterine and postpartum androgen exposure of the central nervous system seems to be the dominant factor in determining gender identity. Exactly how to reliably measure the gender of the brain remains an unsolved question.

Genital ambiguity is a result of an abnormality in sexual determination resulting from a defect in genetic, gonadal, or genital tissue differentiation and has been classified historically into four categories: female pseudohermaphrodite (now called 46XX DSD), male pseudohermaphrodite (46XY DSD), mixed gonadal dysgenesis (sex chromosome DSD), and true hermaphrodite (ovotesticular DSD). Female genital reconstruction, also called feminizing genitoplasty, is restricted to female pseudohermaphrodite (46XX DSD), mixed gonadal dysgenesis (sex chromosome DSD), and true hermaphrodite (ovotesticular DSD) individuals who have the potential to have normal female sexual function. CAH is a form of 46XX DSD and is by far the most common condition causing ambiguous genitalia. CAH is responsible for over 70% of cases of ambiguous genitalia and the vast majority of patients treated with feminizing genitoplasty.

Candidates for feminizing genitoplasty have two distinct problems: (a) the fusion of their internal reproductive system with the urinary tract as a urogenital (UG) sinus with a single external orifice and (b) the virilization of the external genitalia, with fused labioscrotal folds and clitoral enlargement. The internal anatomy can cause problems by pooling of urine within the vagina and uterus and inadequate vaginal drainage for secretions and menses. There is no adequate external vaginal orifice for sexual intercourse. Infants with a UG sinus may present with urinary infection or an abdominal mass from a poorly drained vagina or uterus. Today, many present on prenatal ultrasound screening that reveals a dilated bladder, vagina, or upper urinary tract. The external genitalia are a concern primarily for sexual function and the potential psychological damage that may result from gender ambiguity.

There have been great advances in the surgical technique of feminizing genitoplasty over the past half century, resulting in more normal appearance and sexual function. Despite apparently successful surgery, some adult patients have expressed profound dissatisfaction with their childhood genital reconstruction and gender. Because of this concern, more long-term outcome studies that include all patients with these rare conditions must be undertaken in order to understand the most appropriate management of these complex patients. The challenge of these studies is to make them comprehensive in surveying medical, sexual, and psychological health.

FIGURE 105.1 A and B: These intersex female patients demonstrate labial/scrotal fusion and a hypertrophied phallus with a distal UG sinus opening.

The first task for the physician faced with a child with intersex is to correctly diagnose the underlying condition responsible for the appearance of the genitalia. A team including a pediatric urologist, pediatric endocrinologist, neonatologist, and either pediatric psychologist or psychiatrist provides the best approach for this complex process.

The first step in diagnosis is a thorough physical examination. The initial caregivers in the nursery are usually alerted to the possibility of gender ambiguity if the phallus is small or curved and if the labioscrotal folds are partially fused (Fig. 105.1). The pediatric urologist should then document the length and diameter of the phallus and the position and number of external perineal openings, including the position of any potential UG orifices as well as the rectum. The state of fusion of the labioscrotal folds and their location are important, as is the presence or absence of palpable gonads. The presence of a palpable gonad almost always is consistent with male gender. Hyperpigmentation of the labioscrotal skin is common in cases of CAH. The blood pressure should be measured carefully because of the threat of hypertension with CAH.

Chromosomal studies should be sent immediately. In the immediate newborn period, the presence of functioning testicular tissue can be determined by measuring serum testosterone, which is elevated in the first few days of life. CAH is diagnosed by finding elevated plasma levels of 17-hydroxyprogesterone and androstenedione and urine levels of pregnanetriol and 17-ketosteroids. CAH can be a life-threatening condition because adrenal insufficiency commonly causes salt wasting leading to hyponatremia and hyperkalemia and could result in lethargy, vomiting, and eventual hypotension.

Imaging studies of the infant should include a pelvic ultrasound looking for the presence of a uterus and retrograde injection of contrast into the UG sinus (genitogram) to identify the presence of a vagina and uterus. The uterus can usually be identified on pelvic ultrasound of the newborn as a 1-cm solid midline mass just posterior to the bladder (Fig. 105.2). The uterus can often be identified on a genitogram with a cervical impression outlined by the contrast in the vagina.

During the initial investigation, the family is advised to delay naming the child and reporting the child’s gender to others until the gender is established and to state only that the child had some developmental problems that need to be investigated. It is during this period that the gender assignment team should carefully educate and counsel the family about the nature of their child’s problem and the limitations and potential inherent in the exact condition. The family should be prepared to face the options of therapy, including reconstructive
surgery, so that when the diagnosis is clear, they can make an informed decision. This is a difficult and often painful process for both family and team, and it is critical that every option be explored and discussed with the family and that this counseling is documented in the medical record.

FIGURE 105.2 Pelvic ultrasound demonstrates the uterus in the midline position posterior to the urinary bladder.

There are actually two decisions to be made by the parents: the gender that they will raise the child and whether to have reconstructive surgery. Gender decisions have always been considered urgent, while surgical reconstruction decisions may be made later as long as there is not a health concern because of inadequate drainage of urine. The medical team must explain the surgical options, including advantages, risks, and potential complications of delaying surgery, performing the external genital reconstruction (clitoroplasty), and performing the internal genital reconstruction (UG sinus repair).

TIMING OF SURGERY

Once the decision for feminizing genitoplasty has been made, the timing of the procedure is of some importance. In cases of CAH, glucocorticoid and mineralocorticoid replacement therapy will diminish androgen production by the adrenal and lead to partial reversal of the clitoral hypertrophy. For this reason, the external genital surgery should be delayed until at least 6 months of age. In some cases, hormone replacement therapy decreases the size of the clitoris so that surgery on this structure is not necessary. Since most complaints about childhood genital surgery involve dissatisfaction with clitoral reconstruction, most surgeons have currently limited this surgery to the most extreme cases of enlargement and with the family’s clear support. Some surgeons have refused to perform clitoral reconstructive surgery altogether. The decision about clitoral reconstruction is the most difficult issue to face in the care of these children and must be considered carefully by the family and medical team.

Some surgeons prefer to delay reconstruction of the internal structures until adolescence if the child does not have problems with urine retention and urinary tract infections because historically, patients who had reconstruction early in life might require a secondary procedure at adolescence to correct vaginal stenosis. On the other hand, those children who have early reconstruction need only dilations or simple revisions of the vagina at adolescence, in contrast to the child who delays the major reconstruction until later in life. We prefer to do a complete reconstruction at 6 months of age and explain to the family that a second minor procedure may be needed later.

PREOPERATIVE EVALUATION

Each child suspected to have ambiguous genitalia should have a complete anatomic, endocrine, and genetic evaluation. A karyotype is necessary not only to determine the correct genetic sex but also to look for other chromosomal errors that may be present. A complete endocrine evaluation should focus on potential gonadal function as well as concerns related to the endocrinopathy of CAH.

A comprehensive definition of the anatomy is imperative in planning for and accomplishing the reconstruction. The upper urinary tract should be imaged with ultrasound and, if the kidneys are not normal, a diuretic (Lasix) renal scan. The lower urinary tract should be imaged with a retrograde genitogram (Fig. 105.3). This is performed by placing a catheter in the most distal portion of the UG sinus and injecting contrast while imaging from the anterior, lateral, and oblique perspectives. This gives the surgeon important information about the length of the UG sinus, the point of confluence of the vagina and urethra, and their relative lengths and position within the pelvis. The level of this confluence, either high (UG sinus over 3 cm) or low (UG sinus <3 cm), ultimately determines the surgical approach. Further imaging of the pelvic organs may be necessary in complex cases and can be done with magnetic resonance imaging or computerized tomographic scanning with good visualization.

FIGURE 105.3 Genitogram demonstrates confluence of the urethra anteriorly and vagina posteriorly. Note cervical impression at the apex of the vagina and contrast within the cervix.

Finally, an examination under anesthesia is needed, including cystoscopy and vaginoscopy. It is often easier to measure the length of the UG sinus and determine the height of the confluence with the scope than with imaging. The length of the UG sinus can be measured by placing the tip of the scope at the point of confluence and marking the scope at the level of the external meatus. When the scope is withdrawn, the length of the UG sinus is estimated by measuring the distance from the mark on the barrel to the tip of the scope. These measurements of the UG sinus, vagina, and urethra, along with the position of the confluence of all three, are important in order to plan what techniques may be necessary for repair.

SURGICAL POSITIONING

Most of the surgery for ambiguous genitalia can be performed in the lithotomy position. The lithotomy position is ideal for the clitoroplasty and reconstruction of the labia and introitus. The lithotomy position, however, does not always provide adequate exposure of the higher forms of UG sinus. Hendren and Atala (1), Peña (2), and Rink and Adams (3) have demonstrated the superior exposure provided by the posterior prone
approach to the pelvic organs. We follow Hendren’s recommendations to prepare the patient circumferentially while applying sterile wrapping to the lower legs to allow the patient to be turned from the lithotomy to the prone position as necessary during the operation. It is wise to have all positioning options available for this challenging surgery. Surgery usually begins in the lithotomy position and the clitoroplasty is done first, followed by the vaginoplasty, and finally the labioplasty.

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