Ambiguous genitalia: an overview of 17 years' experience - SASSiT

Journal of Pediatric Surgery (2007) 42, 840–844
www.elsevier.com/locate/jpedsurg
Ambiguous genitalia: an overview of 17 years’ experience
Gülnur Göllü, Rahsan Vargün Yildiz, Meltem Bingol-Kologlu, Aydin Yagmurlu,
Mine Fedakar Senyücel, Tanju Aktug, I.Haluk Gökcora, Hüseyin Dindar*
Department of Pediatric Surgery, Ankara University School of Medicine, Ankara 06100, Turkey
Index words:
Ambiguous genitalia;
Vaginoplasty;
Female
pseudohermaphroditism;
Male
pseudohermaphroditism;
Intersex disorders
Abstract
Aim: The newborn with abnormal genital development presents a difficult diagnostic and treatment
challenge for the pediatric surgeon providing care. The purpose of this study was to evaluate the results
of surgical treatment for children with ambiguous genitalia.
Patients and Methods: The records of 85 children managed surgically for ambiguous genitalia in our
unit from 1988 to 2005 were reviewed retrospectively. Age at surgery, operative procedures, sex of
rearing, and outcome were recorded.
Results: The intersex committee’s decision concerning sex assignment was female for 62 children
(75%) and male for 23 children (25%). The etiologies of children reared as female were congenital
adrenal hyperplasia (n = 37), male pseudohermaphroditism (n = 12), mixed gonadal dysgenesis (n = 6),
true hermaphroditism (n = 4), and Mayer-Rokitansky syndrome (n = 3). Fifteen children with male
pseudohermaphroditism, 5 children with congenital adrenal hyperplasia, and 3 children with true
hermaphroditism were reared as male. The mean age at surgery was 4.4 years and follow-up period
averaged 7 years. Eighteen (29%) patients with feminization procedures and 8 (34%) of 23 patients with
masculinization procedures experienced complications and required redo operations. Vaginal stenosis
was the most common complication.
Conclusion: The surgical management of ambiguous genitalia has always been difficult, and it must be
performed by skilled pediatric surgeon. Genital surgery in infancy needs to be reassessed in the light of
literature findings revealing poor outcome. In patients who underwent feminizing genitoplasty, vaginal
reconstruction should be delayed until adolescence to achieve better cosmetic and functional results.
D 2007 Elsevier Inc. All rights reserved.
Ambiguous genitalia is one of the most distressing
problems encountered at birth. The overall management of
an infant with an intersex disorder is complex and requires
multidisciplinary approach. Genital appearance has been
cited as a fundamental factor in childhood sex and
psychosexual development, and has led to the current
* Corresponding author. Ankara Üniversitesi TVp Fakültesi, Çocuk
Cerrahisi Anabilim DalV, 06100 Dikimevi-Ankara, Turkey. Tel.: +90 312
5956228; fax: +90 312 362 6400.
E-mail address: dindar@medicine.ankara.edu.tr (H. Dindar).
management of infant genital cosmetic surgery for genital
ambiguity [1-6]. However, there is an increasing evidence
that, in the long term, there is patient dissatisfaction with
surgery outcomes, and debate over timing of reconstructive
surgery is ongoing [1-6]. Reasons for surgery in infancy
include maternal estrogen effect, better compliance with
dilations, lessening of the parents’ concerns regarding their
anomalous child, and the assumption that the child later in
life does not remember early interventions [2-5]. On the
other side, irreversible infant genital surgery may have lifelong
impact on social, psychologic, and sexual function.
0022-3468/$ – see front matter D 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.jpedsurg.2006.12.036

Ambiguous genitalia: an overview of 17 years’ experience 841
The current article presents our experience in children
with ambiguous genitale and discusses the management of
intersex patients with emphasis on timing of feminizing
genitoplasty.
1. Patients and methods
The records of 85 patients managed surgically for
ambiguous genitalia in our unit from 1988 to 2005 were
reviewed retrospectively with respect to diagnosis, age at
first presentation, age at surgery, diagnostic procedures,
sex assignment, surgical management, results, and complications.
In addition to history and physical examination,
the diagnostic studies included chromosomal analysis,
urine and blood steroid measurement, pelvic ultrasound,
genitogram, cystoscopy, laparoscopy, laparotomy, and
occasional gonadal biopsy. All patients were evaluated
and treated by a team consisting of a pediatric surgeon,
endocrinologist, and pediatric psychiatrist. Sexual identity
of child and psychiatric evaluation were regarded as the
most important factors for sex assignment. Final decision
of the sex was made by both intersex team and family. All
the newborns with 46,XX congenital adrenal hyperplasia
(CAH) and with 46,XY complete androgen insensitivity
syndrome were raised as females. The 46,XX CAH
children with delayed admission beyond infancy period
were raised as male because of developed male sex
identity. Most of the 5-a-reductase–deficient patients were
assigned female sex, but after the knowledge revealing
virilizing potential of these patients at puberty, assignment
of such individuals to the female sex by surgery has been
avoided and only undertaken with considerable caution
and after full multidisciplinary investigation and counseling
of the parents. The remaining undervirilized patients
with 46,XY genotype were raised as males. In patients
with ovotesticular gonad, the potential for fertility was
considered on the basis of gonadal differentiation and
genital development, and assuming that the genitalia are,
or can be made, consistent with the chosen sex. In the
case of mixed gonadal dysgenesis (MGD), prenatal
androgen exposure, testicular function at initial diagnosis
and after puberty, phallic development, and gonadal
location were considered.
Feminizing genitoplasty in our institution is done as a
2-staged or single-staged operation depending on the level
of vaginal insertion to the urogenital sinus. When the
vaginal insertion is low, clitoroplasty, vaginoplasty, and
labioplasty is done as early as 3 to 12 months of age. When
there is a high vaginal confluence, clitoroplasty is performed
early and vaginoplasty delayed until 2 to 4 years of age.
The reconstructive operations for masculinizing genitoplasty
begin at 6 months of age and consists of orchiopexy,
correction of chordee, staged hypospadias repair, and
removal of mqllerian structures and insertion of testicular
prosthesis when necessary.
2. Results
The intersex committee’s decision concerning sex assignment
was female for 62 children (75%) and male for
23 children (25%). The etiologies of children reared as
female were CAH (n = 37), male pseudohermaphroditism (n =
12) and MGD (n = 6), true hermaphroditism (n = 4), and
Mayer-Rokitansky syndrome (n = 3) (Table 1). The diagnoses
of the 12 children with 46,XY genotype and reared as
female were complete or partial androgen insensitivity
syndrome (n = 8), a-reductase deficiency (n = 4). Fifteen
children with male pseudohermaphroditism, 5 children with
CAH, and 3 children with true hermaphroditism were reared
as male (Table 1). The mean age at surgery was 4.4 F
2.3 years, and follow-up period averaged 7 years. Five
children with CAH were reared as male because of late admission
and psychiatric consultation, which demonstrated dominant
male behaviors. In addition to correction of chordee
and staged hypospadias repair, mqllerian ductal structures
were resected by laparotomy (n = 2) or laparoscopy (n = 3),
and testicular prostheses were placed in all 5 children.
Of the 62 children reared as females, 36 (58%) required
clitoral reduction plus perineal vaginoplasty, 14 (22%) had
both clitoral reduction and pull-through vaginoplasty, and
12 (20%) had colovaginoplasty.
Twelve children with male pseudohermaphroditism were
given a female sex assignment and underwent gonadectomy,
clitoral reduction, and vaginoplasty, and the remaining
15 children were given male sex assignment and underwent
orchiopexy, correction of chordee, and staged hypospadias
repair. All children with gonadal dysgenesis and 4 children
with true hermaphroditism (TH) were raised as girls, and
3 children with TH were raised as boys. Ovotestes were
removed and gonads and mqllerian structures were either
remained or removed because of the given sex assignment.
Eighteen (29%) of 62 children with feminization
procedures and 8 (34%) of 23 children with masculinization
procedures experienced complications and required redo
operations. Among 50 patients who underwent clitoroplasty,
cosmetic appearance was excellent in 35 (70%) patients,
satisfactory in 11 (22%) patients, and poor in 4 (8%)
(atrophic clitoris in 2 and clitoromegaly in 2) patients. The
Table 1 The distribution of etiologies in female and male sex
assignment groups
Diagnosis
Female sex
assignment
(n = 62)
Male sex
assignment
(n = 23)
CAH n = 37 (60%) n = 5 (21%)
MPH n = 12 (20%) n = 15 (65%)
MGD n = 6 (10%) –
TH n = 4 (6%) n = 3 (13%)
Mayer-Rokitansky
syndrome
n = 3 (4%) –
MPH indicates male pseudohermaphroditism.

842
labia minora were normal looking in 43 (86%) patients,
smaller than normal in 4 (8%), and larger than normal in 3
(6%) patients. Vaginal stenosis (associated with atrophic
clitoris and clitoromegaly in 4 patients) was the most
common complication (n = 10) followed by urethrovaginal
fistula (n = 4) in children who underwent feminization
genitoplasty. Although complications occurred in 6 (42%)
of 14 of pull-through vaginoplasties and 7 (19.4%) of 36 of
perineal vaginoplasties, only 1 of the 12 (8%) colovaginoplasties
required revision for stenosis of the introitus.
Although the mean operative age was 1.5 F 0.6 years in
children with complicated feminization genitoplasty, mean
operative age was 7.7 F 2.2 years in children with
uncomplicated feminization genitoplasty. The patients who
underwent sigmoid vaginoplasty had good cosmetic results
without the need for routine dilation or the problem of
excessive mucous production. Redo operations in masculinization
procedures were urethral fistula repair (n = 4),
redo hypospadias surgery (n = 3), and chordee repair (n =
1). Cosmetic appearance was excellent in 5 (21%),
satisfactory in 12 (52%), and poor in 6 (27%) of 23 patients
who underwent masculinization procedures.
3. Discussion
The management of intersex conditions frequently poses a
challenge to neonatologist, pediatric endocrinologist, and
pediatric surgeons. The ultimate goal in any management
strategy is to provide a framework that will allow the affected
child to develop into a well-adjusted psychosocially stable
individual who identifies with and is happy in the assigned
sex [4]. Factors that influence sex assignment include
diagnosis, genotype, genital appearance, surgical options,
need for lifelong replacement therapy, potential for fertility,
views of the family, and sometimes circumstances relating to
cultural practices [4-6]. Sexual identity of child and
psychiatric evaluation are the most important factors for sex
assignment. However, management of intersex patients is
associated with considerable ethical dilemmas such as there is
no guarantee that adult sex identity will developed as
assigned. Although standard protocols have stressed the need
for early diagnosis, sex assignment, and appropriate surgery
in infancy [1-3,6], in recent years, some authors have claimed
that such surgery is damaging or mutilating and, as it is
essentially cosmetic, should not be performed until the fully
informed consent of the patient could be obtained [7].
In our series, sex assignment was female in 75% and
male in 25%, whereas this ratio appears to be keeping with
many other reports [8-13]. Contrary to literature, nearly half
of the male pseudohermaphrodites consisted of all patients
with complete and partial androgen insensitivity syndrome,
and 4 patients with a-reductase deficiency were assigned
female sex because feminizing genitoplasty, as opposed to
masculinizing genitoplasty, requires less surgery to achieve
an acceptable outcome [8,9,14-19]. However, recent studies
G. Göllü et al.
on untreated 5-a-reductase–deficient patients have shown a
strong tendency to virilize at puberty and almost 100%
assumption of the male sex identity [2]. Approximately 60%
of 5-a-reductase–deficient patients assigned female in
infancy and virilizing at puberty live as males [6].
Therefore, assignment of such individuals to the female
sex by surgery should be avoided and only undertaken with
considerable caution and after full multidisciplinary investigation
and counseling of the parents.
The conditions that result in male pseudohermaphroditism
include partial androgen insensitivity syndrome,
5-a-reductase deficiency, testicular regression syndrome,
and severe hypospadias [2,18,19]. In these undervirilized
genetic males, correction of chordee, staged repair of
hypospadias, and orchiopexy is required [2,14-19]. The
outcome depends on the degree of hypospadias and the
amount of erectile tissue. Although some surgeons prefer
1-stage repair for chordee and proximal hypospadias,
reasonable incidence of major complications (20%-30%)
has been reported [15]. Besides excellent function, cosmesis
and patient satisfaction after puberty, with no chordee, has
been reported after a 2-stage approach for severe hypospadias
[16,19,20]. Contrary to this report, in the present series,
we experienced reasonable high incidence of complications
including urethral fistula and redo operations (34%).
For children raised as girls, surgery aims to promote
female sex development and avoid psychologic distress,
whereas long-term aims are to allow normal-looking and
functioning adult female genitalia [1,2,6]. The 2 essential
elements of feminizing genitoplasty are clitoral reduction
and vaginoplasty [1,2,6,10-13]. The surgical techniques
involved in feminizing genitoplasty have undergone considerable
change and refinement [2,21]. Previously described
techniques of clitorectomy and minor external skin
rearrangement have given way to more complex techniques
such as clitoroplasty, vaginoplasty, and labioplasty, aiming
for a better function and the creation of normal-appearing
female external genitalia [2]. Long-term data regarding
sexual function and quality of life among those assigned
female show great variability [1,2,6,10-13]. Although some
studies suggest satisfactory outcomes from early surgery
[8,21,22], the others indicate problems related to decreased
sexual sensitivity, loss of clitoral tissue, and cosmetic issues
[1,6,12,23]. In a recent cross-sectional study, 78% of the
adult intersex patients living as females and have undergone
clitoral surgery were found to experience nonsensuality
[23]. Our results regarding cosmetic appearance after
clitoroplasty and labioplasty were mostly satisfactory and
are in agreement with the previous reports.
The goals of therapy in vaginal reconstruction include
fertility, if possible, adequate sexual function without the
need for continual dilations, or lubrication [1,2,6,12].
The best timing for vaginoplasty remains controversial.
The suggested timing ranges between surgery in the
neonatal period to help parents accept the child more easily
to surgery at adolescence when the patient can give

Ambiguous genitalia: an overview of 17 years’ experience 843
informed consent [1,2,6,7,8,9,10,11,12,21,22]. Most authors
prefer to correct the external genitalia in a single-stage
procedure in the earlier period [6-8,21,22]. According to
some reports, initial surgery before or after 2 years of age
did not significantly affect outcomes [21]. However, some
long-term studies suggest that most of these girls who
underwent early vaginal reconstruction will require major
revisional surgery for vaginal stenosis in adolescence [1,2,6].
In a retrospective study of cosmetic and anatomical outcomes
in 44 adolescent patients who had ambiguous
genitalia in childhood and underwent feminizing genital
surgery, cosmetic result was judged as poor in 18 (41%) of
these patients [1]. Forty-three (98%) of 44 patients needed
further treatment to the genitalia for cosmetics or intercourse.
Twenty-three (89%) of 26 genitoplasties planned as 1-stage
procedures required further major surgery [1]. In patients
who underwent vaginal reconstruction in infancy, postoperative
vaginal stenosis has been reported to range between 0%
and 77% [1,2,6,7,8,9,10,11,12,21,22,24]. Our results confirm
the literature revealing high rate of vaginal stenosis in
prepubertal girls. We used to believe that reconstructive
surgery should take place from the newborn to the 3-year-old
period. Depending on our results and literature findings, we
decided to delay vaginal reconstruction until adolescence
period. Because early vaginoplasty confers no obvious
benefit in a young girl, delaying it until the onset of
menstruation makes it mandatory. The occasional patient
with a urogenital sinus complicated by urinary stasis and/or
infection may require an early surgical procedure.
In patients with absent vagina, a complete replacement is
necessary. Creation of a vagina is necessary for patients with
aplasia of mqllerian ducts, androgen insensitivity syndromes,
and some cases with 5a-reductase deficiency that
usually have a normal female external appearance
[2,6,12,25]. We performed colovaginoplasty at puberty with
low-rate complication in long-term follow-up. In agreement
with the literature [12,25], our experience revealed that
colovaginoplasty is an excellent procedure for patients with
absent vagina because the neovagina created with colon
usually has an adequate diameter and length, and has selfmoistening
property.
Most patients with 46,XX karyotype and CAH will be
raised as girls [2,6,26]. Rarely, the diagnosis may be missed,
and a severely virilized 46,XX individual may be raised as a
boy. In our series, 5 children who came to medical attention at
age of 5 to 7 years and diagnosed as CAH were reared as male
because of the developed male sexual identity. In those cases,
multiple-staged reconstructive procedures were required to
achieve an acceptable male phenotype [2,6,26]. The surgical
management of these patients consisted of laparoscopic
removal of mqllerian structures, correction of severe chordee,
staged hypospadias repairs preceded by testosterone therapy,
correction of bifid prepenile scrotum, and insertion of
testicular prostheses [2,6,26]. Assigning against genotype
brings potential problems such as no guarantee that adult sex
identity will develop as assigned and the patients will require
lifelong hormonal treatment and consistent surgical followup
[2,6,26]. Our follow-up period is not enough to address the
future problems of these patients.
In conclusion, sex assignment in cases of ambiguous
genitalia should be made by the intersex team and the family.
Genital surgery in infancy needs to be reassessed in the light
of literature findings revealing poor outcome in adult period.
In patients who underwent feminizing genitoplasty, vaginal
reconstruction should be delayed until adolescence to achieve
better cosmetic and functional results.
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