INTERNATIONAL CONFERENCE

ICOMESH 2023

AMBIGUOUS GENITALIA: A CASE REPORT

FONDA OCTARIANINGSIH SHARIFF

OBSTETRICS DAN GYNECOLOGY DEPARTMENT FACULTY OF MEDICINE

UNIVERSITAS MALAHAYATI, LAMPUNG, INDONESIA
A. INTRODUCTION
The term "intersex traits" refers to a broad category of diagnoses known as
"differences of sex development" (DSD), wherein the external genital
appearance, internal reproductive anatomy hormone levels, and sex chromosomes
deviate from the conventional binary male or female developmental routes.(Lee
and others, 2006) The incidence of DSD can range from 1 in 100-200 individuals,
depending on how broadly the disorder is defined. This estimate takes into
account congenital adrenal hyperplasia (CAH) and other sex chromosome
aneuploidies (SCA) like Turner syndrome (TS) and Klinefelter syndrome (KS),
as well as other congenital genital variants like cryptorchidism and hypospadias.
(Blackless et al. 2000)
The sex of a baby is usually defined without difficulty, male or female,
shortly after birth. Using prenatal ultrasonography (USG), the sex can be
recognized intrauterine, even from the second trimester. Gender is also generally
immutable and becomes one of the personal identities from birth. In some
conditions, clinician sometimes finding difficulty in defining fetal external genital
forms to indicate male or female sex. This condition is called ambiguous
genitalia. Ambiguous genitalia or sex ambiguity is a disorder in which the patient
has questionable genetic, anatomical and/or physiological characteristics between
male and female. In Indonesian this is referred to as dubious or confusing gender.
It is also called double sex because sometimes the clitoris is so large that it looks
like there are two sexes.
This disorder is also known in other scientific terms as intersexual, a term
that refers to the notion that the sexes are divided into two poles, male or female,
so the questionable sex form falls between the two poles. However, nowadays
endocrinologists more often use the term Disorders of Sexual Development
(DSD). Diagnosis, monitoring, treatment planning, and genetic counseling as well
as the growth and development of the baby later is very important so that it can be
done immediately to minimize medical, psychology and social complications.
Medical attempts to adjust or correct genital shape are often followed by several
related problems from medical, psychosocial, legal, environmental to religious
aspects.

B. CASE PRESENTATION
1. Identification
Name : Mrs Al
Age : 29 years old
Marital status : Married
Menarche : 13 years old
Last Menstrual Period : 26/03/2022
Reproduction status : G3P1A1
Admission : Barokah Medika Clinic (October 28th 2023)
2. Anamnesis/Subjective
Patient came to Clinic for antenatal care. This was the third visit, and early
October visit suspected no abnormalities was found intrauterine. The fetal
growth was within normal status and female sex was suspected. In this visit,
physician suspected the fetal labias enlarged and might be an ambiguity for the
fetal sex. Then the patient was referred to Fetomaternal Subdivision
consultation.
3. Physical Examination/Objective
Status Present:
General condition : normal
GCS : 15
Blood pressure : 120/80 mm/Hg
Pulse : 89 x/m
RR : 21 x/m
Organ Examination :
Face/Neck : within normal condition
Thorax : within normal condition
Abdomen : within normal condition (pregnancy bump)
Obstetrics Examination:
Leopold I : enlarged abdomen, symmetrical, fundal height estimated
equal to 30 weeks GA, suspected breech at fundus
Leopold II : extremities at left side, fetal HR 134x/m
Leopold III : head presentation, 5/5
Leopold IV : floating
Vaginal toucher : not indicated
4. Diagnosis : G3P1A1 30 weeks pregnancy single life fetus cephalic presentation
 5. Management :
- Antenatal care
- Ultrasound examination
USG result :
Fetal biometries equal to 30 weeks 3 days, EFW 1534 grams, amniotic fluid
sufficient, baby movement active, placenta implantation at anterior corpus,
fetal sex suspected ambiguous.
6. Planning:
Consultation to Fetomaternal Subspecialist
7. Follow up:
Fetomaternal consultation result:

Picture 1. USG Result for Fetal Genital

Rounded/blunt appearance of penis tip, short penis shaft tip down and bifid
scrotum suspected to be hypospadias.
Suggestion : Follow up within 2 weeks, if the genital suspected to
ambiguous, further examination for phenotype after birth is needed.

C. DISCUSSION
a. Disorders of Sex Development
The three primary components of somatic sex development are gonadal sex
(testes and/or ovaries), anatomic sex (male and/or female internal and external
genitalia), and chromosomal sex (the complement of X and Y chromosomes).
Two successive stages, each governed by a separate mechanism, go into the
evolution of sexuality (Chan et al. 2020). Human embryos are identical five
weeks after conception and can develop either male or female anatomy (i.e.,
we are all identical at birth).
Human embryos are identical five weeks after conception and can
develop either male or female anatomy (i.e., we are all identical at birth). Chan
and colleagues, 2020).Six weeks is when sex determination starts: Bipotential
gonads are guided to become either ovaries or testes by sex chromosomes (XX
or XY). The gene known as SRY (sex-determining region Y) is located on the
Y chromosome. It is responsible for initiating a sequence of genetic signaling
processes that ultimately lead to the creation of the testes.
Previously, ovary would considered develop, even in the absence of a Y
chromosome and SRY, automatically in ovarian development. However,
research now indicates that ovarian development involves active process with
activation of genes that support ovarian development while interfering
testicular development. The development of atypical sex anatomy is one of the
main effects of divergence from usual sex determination. Associated
characteristics may include an increased risk of gonadal cancer (Hersmus et
al., 2017), infertility, and insufficient sex hormone production for either a
spontaneous puberty or the preservation of secondary sex traits.
The development of the external and internal genitalia is a component of
the second stage of sex development, known as sex differentiation. The uterus,
upper two-thirds of the vagina, the primordia of fallopian tubes, and Müllerian
structure development are all suppressed by the peptide anti-Müllerian
hormone (AMH) produced by the testes. When AMH is absent, as occurs
when an ovary forms from a bipotential gonad, multiple genes will regulate
the differentiation of female-typical interior tissues. Additionally, testosterone
produced by the testes separates the Wolffian structures into the seminal
vesicles, vasa deferentia, and epididymides. Unlike the two ducts of the
internal genitalia, the Müllerian and Wolffian ducts, the external genitalia are
not a single organ. The usual development of the penis and scrotum is caused
by the conversion of testicular testosterone into dihydrotestosterone. When
there is no testosterone present, or when there is insufficient androgen action
at the end organ, the genital tubercle matures into the clitoris. In contrast, the
labia minora and majora are formed by labioscrotal swellings.
 DSDs are categorized by karyotype; when the disorder's genetic
foundation is known, clinically descriptive terms are added along with the
disorder's molecular basis (e.g., "46, XY complete gonadal dysgenesis with
SF1 variant" or "46, XX testicular DSD, SRY +"). According to Lee et al.
(2006)'s Consensus Statement, DSDs are categorized as follows:
1. 46, XY DSD: includes disorders of testis development (e.g., partial or
complete gonadal dysgenesis, or the presence of both ovarian and
testicular tissue, i.e., ovotesticular DSD), as well as defects in androgen
synthesis (e.g., 5α-reductase 2 deficiency) and action (e.g., partial or
complete androgen insensitivity syndrome).
2. 46, XX DSD: including conditions related to excess androgen (e.g., CAH)
or ovarian development (e.g., gonadal dysgenesis).
3. Examples of sex chromosome DSD include chimerism (46, XX/46, XY),
Klinefelter syndrome and variants (47, XXY), Turner syndrome and
variants (45, X), sex chromosome mosaicism and variants (45, X/46, XY),
and other changes in the normal sex chromosomal complement.
When sex chromosomes, gonads, hormones, and the anatomy of the
reproductive organs develop abnormally, ambiguous genitalia result. A
congenital defect is the cause of this ailment. (Lee and others, 2006)

b. Prenatal Sexual Determination

Prenatal sex determination is often done by ultrasonography assessment of
the external genitalia beginning in the second trimester. When there is a
discrepancy between the chromosomal sex and the external genitalia or when
the external genitalia are unclear, an evaluation of the internal genitalia is
essential. It is possible to make a non-invasive prenatal diagnosis of the fetal
phenotypic sex using prenatal ultrasonography or, less frequently, magnetic
resonance imaging (MRI). Even while advances in ultrasound technology have
made it possible to diagnose patients earlier and with greater assurance, these
limitations still affect evaluation. Transvaginal sonography between weeks 12
and 23 of pregnancy
Bronshtein et al. were able to accurately determine the fetal sex in 76% of
cases at 13–14 weeks' gestation and in 88% of cases at 15–16 weeks' gestation.
Additionally, they discovered that the detection rate rose with experience: after
two years, 80% at 13–14 weeks' gestation and 96.7% at 15–16 weeks'
gestation. The male genitalia in this study were determined sonographically
based on the identification of a non-septate, dome-shaped structure at the base
of the penis, called the "dome sign," which indicates a scrotum. The labia
majora and minora were described by two or four parallel lines, used to
identify the external genitalia of females. The longitudinal, midline, echogenic
line at the base of the fetal penis in the tangential plane, which represents the
median penile raphe, is another crucial indicator for the precise prenatal
detection of male genitalia. (Brohnstein, 1990)
In 2006, Efrat et al. used transabdominal ultrasound to identify the fetal
sex in 656 singleton pregnancies at 12–14 weeks of gestation. The technique
was measuring the angle of the genital tubercle to a horizontal line along the
mid-sagittal plane of the lumbosacral skin surface. Male sex fetus was
suggested if the angle was greater than 30° and female sex if the angle was less
than 10°. The gender could not be determined if the angle fell between 10 and
30°. With the use of this technique, the phenotypic sex of 555 infants was
determined with 99–100% accuracy for male gender throughout all gestational
ages. The detection rate in females varied considerably with gestational age
and was less precise: 91.5% at 12 + 0 to 12 + 3 weeks, 99% at 12 + 4 to 12 + 6
weeks, and 100% at 13+0 to 13+6 weeks. (Efrat and others, 2006) Chelli et al.
correctly diagnosed 87.9% of males and 83.3% of females at 11–14 weeks
gestation using the same technique. (Chelli, 2009)
The visibility of the penis and scrotum in males and the two or four
parallel labial lines in females can be used to determine gender. In comparison
to the first trimester, the second trimester offers better visualization. Finding
these genital cues can increase normal gender identity to 100% in the second
trimester. By measuring the transverse diameter and circumference of the
uterus between 19 and 38 weeks of gestation, Soriano et al. were able to report
the normal values of the uterus and detect the intraabdominal fetal ovaries
since 19 weeks. The uterine circumference expanded from 20.5 mm at 19
weeks to 58.2 mm at 38 weeks, and the mean transverse diameter increased
from 6 mm at 19 weeks to 20 mm at 38 weeks. (Soriano, 1999) But in 40/180
(22%) of the female fetuses, the uterus was invisible.
 Determining sex can be made easier if the fetal gonadal sex is identified.
Before 25 weeks of gestation, the testes do not descend to the scrotum.
According to Birnholz, 12.5% of male fetuses at 26.0–27.9 weeks, 60% of
cases at 28.0–31.6 weeks, 85.7% of cases at 32.0–33.6 weeks, and 94.7% of
cases beyond that had descending testes. (Birnholz, 1983). In 1998, Achiron et
al. used improved ultrasound resolution to find that 30% of male fetuses at
25.0–16.0 weeks gestation and 70% of fetuses at 26 weeks gestation had at
least one descending testis. In 97% of cases, bilateral testicular descent was
seen by 32 weeks. (Achiron, 1998).

c. Prenatal Sex Abnormality

Diagnostic methods for fetal gender abnormalities include fetal

ultrasonography, MRI, and difference between chromosomal sex and
phenotypic traits. Confusing names like "intersex," "hermaphrodite," and
"pseudo-hermaphrodite" are used to characterize this complex scenario, which
only serves to increase the fear and uncertainty of parents.

The ability of the radiographer to accurately detect the phenotypic and

gonadal sex, as well as the ultrasound resolution, make accurate categorization
of the DSD difficult. Furthermore, only invasive techniques like cordocentesis,
amniocentesis, or chorionic villus sampling (CVS) can determine
chromosomal sex. These techniques have a risk of miscarriage or early birth,
depending on the gestational age at the time of the surgery. Thus, the
chromosomal sex is not always readily available.

Unlike other fetal abnormalities, the most severe aberration could seem
normal even if it is of the opposite sex, which could lead to it going unnoticed.
In contrast, severe masculinization of the female external genitalia, as in 21
hydroxylase deficiency, which causes Prader-four, will look as normal female
external genitalia in cases of severe incomplete masculinization of the male
external genitalia, as observed in androgen insensitivity syndrome. Fetal DSD
must be evaluated step-by-step to obtain as much information as possible and
identify the most likely diagnosis to provide the woman with the knowledge
she needs to make an informed decision regarding the trajectory of her
pregnancy.

Once the development of the unborn external genitalia is complete, genital

anomalies can be identified by fetal ultrasound and/or MRI examination from
approximately 13 to 14 weeks of gestation. (Hamiel and Pinhas, 2002) They
might also be mentioned if there is a difference in the chromosomal (found by
CVS or amniocentesis) and fetal phenotypic (found by ultrasound
examination) sex.

Incomplete masculinization of the external genitalia is suspected

prenatally if the fetal ultrasound/MRI examination reveals abnormal phallic
structure (absent, short, or abnormal shape) and/or scrotum (absent or bifid)
with absent or undescended testes later in the pregnancy, or if there is a
discrepancy between the assessment of external fetal gender and internal fetal
gender by assessment of the pelvic organs and the distance between the
anterior wall of the rectum and the posterior wall of the bladder. It is assumed
that the female external genitalia have become masculinized when a prenatal
ultrasound or MRI shows an expanded phallic structure, deformed or fused
labia instead of a scrotum, a detectable uterus, or a relatively considerable
rectovesical distance.

The history of pregnancy should include information about maternal

diseases that cause virilization (such as hirsutism, excessive cystic acne,
enlarged clitoris from tumors producing testosterone or placental aromatase
deficiency), or about maternal exposure to teratogens (pesticides, isotretinoin),
endocrine disruptors (phenytoin, aminoglutethimide), or androgens. (Spritzer
et al, 2007) To determine whether the mother's serum unconjugated estriol
level is low, which is typical in fetal conditions like Smith-Lemli-Opitz
syndrome, CAH, and placental amino acid deficiency as well as chromosomal
abnormalities like trisomy 18, the results of the Down syndrome screening
should be reviewed. Moreover, low levels of pregnancy-associated plasma
protein-A and high levels of human chorionic gonadotropin and alpha-
fetoprotein may suggest placental insufficiency, which is linked to a higher
risk of hypospadias in male fetuses. (Yinon et al, 2010) It is necessary to get a
three-generation family history using standardized pedigree symbols. It is
important to find out about any family members who have inherited diseases,
repeated miscarriages, stillbirths, mental retardation, or other anomalies.
(Benjamin et al., 2008)

Consanguinity in the family may indicate recessive illnesses such Fraser

syndrome, CAH, and problems with testosterone biosynthesis. Moreover, it
raises the possibility of multifactorial conditions such hypospadias. The
potential of androgen insensitivity is suggested by a family history of
infertility or females with amenorrhea, and the possibility of salt-losing CAH
is increased by an unexplained baby death. To look for recurrence, similar
anomalies in siblings or other family members should be considered during the
fetal ultrasound screening and other tests.

When looking at fetal genital abnormalities, chromosomal analysis and, if

necessary, microarray analysis should be part of the first study. The results of
the fetal ultrasonography can be used to determine whether the amniotic fluid
contains any more hormones, such as testosterone, androstenedione, 17-
hydroxy-progesterone, 11-dexoycortisol, and 7-dehydrocholesterol2. Fetal
DNA can be used for specific condition mutation analysis, such as 21
hydroxylase deficiency, 5α reductase deficit, or SRY mutation, based on the
family history and/or fetal ultrasound abnormalities. When no particular
mutation is examined based on family history, mutation analysis is a time-
consuming process, and the results could not be accessible until much later in
the pregnancy or after delivery. To reduce the amount of blood drawn from the
baby, an effort should be made to retrieve a portion of chord and a cord blood
sample, preserved in tubes containing EDTA and sodium heparin, as
additional study will typically be needed after delivery.

Non-isolated DSD may indicate a chance of maternal exposure to

teratogens, fetal chromosome abnormalities, and single gene illnesses. It may
also indicate spontaneous disorders such as cloacal dysgenesis and
omphalocele–exstrophy of the bladder–imperforate anus–spine abnormality
(OEIS). Since most DSD cases that are discovered during pregnancy have
isolated genital abnormalities, and since multiple conditions can cause the
 same phenotype, the woman should be offered additional investigation, such
as amniocentesis for chromosome analysis and amniotic fluid hormonal
studies, if she wants to know with certainty what the etiology and
consequently the prognosis.

d. DSD Findings

Most of the time, intrauterine exposure to high levels of androgens is the

cause of the fetal anomalies in the individuals in the XX DSD group. This may
be intrinsic, resulting from fetal CAH or placental aromatase insufficiency, or
extrinsic, resulting from the ingestion or synthesis of androgen by the mother.
Prenatal ultrasound findings include redundant, incompletely separated, or
merged labia majora, as well as an enlarged phallic structure (clitoris). Over
90% of these instances are caused by CAH, and over 90% of these cases are
caused by a deficit in 21 hydroxylases. In CAH, the fetal adrenal glands can be
shown to have a large hypoechogenic cortex, a discoid form instead of a
triangular one, and an expanded volume throughout the third trimester.

Two further, while far less frequent, causes of CAH include deficiencies
in 3β-hydroxysteroid dehydrogenase and 11β-hydroxylase. Notably, extreme
cases (Prader Stage 4) exhibiting urogenital opening at the base of the phallic
shaft and full labial fusion can mimic isolated hypospadias in males or 46, XY
DSD. Therefore, one of the most crucial ultrasonography findings to
distinguish XX DSD from XY DSD in the absence of a known fetal karyotype
is the direct visualization of the uterus or an accurate measurement of the
distance between the bladder and rectum, using the method developed by
Glance et al. (Glance, 2007). It is imperative to consider CAH since, in the
postnatal period, it may pose a life-threatening hazard requiring prompt
diagnosis and treatment for neonates. Moreover, early prenatal detection in
impacted families would enable dexamethasone-based maternal prenatal
treatment to lessen genital virilization in impacted female babies.

The first step in identifying the disease is figuring out the chromosomal
sex (46, XY) and whether or not a normal SRY gene exists. Fetal
ultrasonography can differentiate these cases from XX DSD and is essential in
 the diagnosing process when fetal karyotyping is not available. This can be
derived from:

a. defects in testicular development caused by deletion or mutation of the

SRY gene (rarely, DAX-1 duplication and SF-1 mutations), abnormalities
in sex chromosomes 45, X/46, and XY mosaicism, testicular regression
syndrome, and disappearing testes syndrome (unknown etiology);
b. abnormal testosterone production resulting from luteinizing hormone
deficiency or a lack of testicular response to pituitary hormones;
c. abnormal conversion of testosterone to DHT in the external genitalia (5α
reductase deficiency);
d. abnormal/lack of response to testosterone (partial or complete androgen
insensivity); (5) abnormal synthesis of testosterone due to testicular
enzyme deficiency (steroidogenic acute regulatory protein deficiency, 3β-
hydroxysteroid dehydrogenase, 17β hydroxysteroid dehydrogenase, or 17
lyase deficiency).
Lack of testicles, inadequate testosterone, DHT deficiency, and complete
androgen insensitivity cannot be distinguished in pregnancy from normal
female genitalia, and if the fetal karyotype is unknown, these disorders will not
be suspected in utero.

e. Differential Diagnosis of Prenatal Abnormal Findings

1. Hypospadias

Hypopadias is thought to affect 1 in 500 live male infants. (Andersen,

2001) The meatal location is used to classify the ailment and indicates the
severity of the illness. The urethra opens below the tip of the penis in
first-degree (also known as glandular/coronal) hypopadias; in second-
degree hypopadias, opens along the penile shaft; third-degree
hypospadias (20% of cases) often referred to as perineal hypopadias, as
most severe variety and causes the urethra to open below the penis or at
the penoscrotal junction. Due to atresia of the corpus spongiosum distal
to the urethral meatus, the penis in second- and third-degree chordee
variations exhibits a ventral curve, which facilitates the prenatal
 diagnosis. A ventral urine stream, which is also typical of the illness, is
seen in some of these instances.

Resulting to the genital tubercle's downward trend at roughly 13 to

15 weeks of pregnancy and the observation of the scrotum and penile
shaft later on, some instances with severe hypopadias are originally
identified as female genitalia. Meizner et al. described the "tulip sign," a
sonographic feature associated with penoscrotal transposition resulting
from a bifid scrotum that occurs in cases of severe hypospadias. Meizner
(2004) Because 3D ultrasound displays the penis' downward orientation,
it can aid in the diagnosis of hypospadias. Recent research has shown a
correlation between hypospadias and intrauterine growth restriction
(IUGR), suggested involvement of placental function in the development
of the male external genitalia. Therefore, in cases of IUGR, hypospadias
should be sought.

2. Exstrophy-epispadias complex (EEC).

A range of genitourinary abnormalities, such as OEIS, bladder exstrophy,

cloacal exstrophy, and epispadias, are included in EEC. The prevalence
of this disorder is 1/30000 for bladder exstrophy and 1/200000 for cloacal
and OEIS exstrophy at birth. This complex is uncommon and more
prevalent in boys than in girls. The cloacal membrane is mechanically
disrupted to cause EEC, and the period of the rupture determines how
severe the malformation is. Majority of cases appear to be complex, and
the etiology is unknown. Prenatal ultrasound can identify EEC; the most
common finding is a non-visualized fetal bladder with the umbilical
arteries running alongside a mass in the abdominal wall below the
insertion of the umbilicus; other common findings include abnormal
external genitalia and normal amniotic fluid volume; in the case of OEIS,
additional findings include omphalocele and lower spine segmentation.
(Ben-Neriah et al., 2007)

f. Management of Pregnancy
 The discovery of fetal genital abnormalities during pregnancy is a
medical and psychosocial emergency that needs to be investigated and
discussed with the family by a multidisciplinary team consisting of social
workers, psychologists, endocrinologists, neonatologists, urologists, and
medical geneticists with specialized training in this area. It is important to
share details about the anomaly, differential diagnosis, postnatal care, and
prognosis. It should be made clear that not all abnormalities can be detected by
ultrasound, and that the results at delivery may not match the description
provided by prenatal ultrasonography. It is important to describe the
embryology of both normal and abnormal external genitalia and to stress that
the abnormality was not caused by anything the parents did or did not do. The
conversation should be geared at the parents' level of cognition while taking
their cultural and religious background into account. It is important to provide
parents the choice of decision whether to end the pregnancy or not. In
addition, they may choose to proceed with the pregnancy and get maternal
prenatal care if necessary, or they may choose to conduct additional
investigations to determine the etiology before planning. Before making this
choice, the parents ought to have some time to acclimate.
The mode of delivery is unaffected by the diagnosis of DSD. If the
choice is continuing pregnancy to term, the prenatal care team should continue
postnatal care to determine the baby's gender and provide any necessary
treatment. To minimize the amount of blood for analysis from the newborn, a
portion of the cord should be obtained to create a cell line for additional
research to examine hormone studies, DNA extraction (in an EDTA tube), and
chromosome analysis (in a sodium heparin tube).
The initial investigation should be guided to define chromosome analysis
and physical examination. This usually include laboratory studies
(determination of sex chromosomes, if not done prenatally, and determination
of levels of 17-hydroxyprogesterone, serum electrolytes and serum glucose)
and neonatal imaging such as ultrasonography of the abdomen and pelvis to
determine the presence of gonads, a uterus, and/or a vagina (neonatal adrenal
glands may be assessed at this time; abdominal/pelvic MRI may play a role in
inconclusive or challenging cases); retrograde urethrogram and/or
cystoscopy/vaginoscopy. Laparoscopic if possible may help visualization to
 delineate the internal reproductive organs/anatomy including gonadal biopsy
for histological/genetic evaluation.
The first line examination to determine whether the uterus, ovaries,
and/or testes is ultrasound. Examining the inguinal area and the iliopsoas
muscle should be done if the testes are not descended. It is important to
evaluate the adrenal glands for hyperplasia and hypertrophy. Perineal
examination for the presence of fistulous tracts may be necessary in more
complex cases of DSD.

g. Postnatal Management

Infants that are prone to have ambiguous genitalia may have the following
external genitalia forms or manifestations:
1. Appears to be masculine.
- Testicles in preterm newborns are not palpable
- Hypospadias with divided scrotal sac; and
- Cryptorchidism along with hypospadias
2. Indeterminate or doubtful, ndeterminate genitalia
3. A female's appearance:
- Variable degrees of clitoral enlargement
- A shallow vulva with a single aperture
- An inguinal hernia containing gonads.
Anamnesis of the baby's parents, including family history and genetics;
history of disease, nutrition, and drug use during pregnancy; history of past
diseases, daily routine, and so forth, is necessary for the diagnosis of this
ambiguous genitalia issue. John (2012) It is challenging to confirm the
diagnosis because of the wide range of diagnoses and the lack of particular
examination techniques. Due to the vast range of diagnoses for abnormalities
of the external genitalia, it is necessary to carefully choose the supporting
exams for diagnosis, which takes time and money. If possible,
comprehensive testing, including around molecular genetics, will result in
more accurate and certain diagnosis.
 Figure 2. Prader Scale
Determining the karyotype is the initial step in the examination of a
patient with confusion over their genitalia. The ability of an individual's
gonads, internal genitalia tracts, and external genitalia to distinguish between
male and female sexual characteristics is essential. There are multiple stages
to normal sexual development, and chromosomes have an impact on how the
gonads develop into the testes or ovaries based on genetics. The initial steps
of the physical examination involve evaluating the overall health and vital
signs, as well as looking for any unusual characteristics. To ascertain the
Prader-degree of virilization, the external genitalia are inspected. Since the
ventral curve (chordee) and excess suprapubic fat frequently conceal the true
size of the penis, the length of the phallus is measured by lifting the corpus
between the examiner's two fingers. The penis should be extended to a
minimum of 2 cm in term newborns.
The urethral meatus's location, which is occasionally only known after
the infant has urinated, is used to calculate the degree of urogenital sinus
closure. It is necessary to look for symmetry and the presence of rugae in the
labioscrotal folds. Inguinal hernia is frequently linked to palpable gonads on
the more virilized side of the folds if they are asymmetrical. The gonads on
both sides must be palpated. To do this, move the examining finger along the
inguinal canal line in the direction of the labia or scrotum, holding the
palpable gonads in the other hand. Use patience and warm hands when doing
this. Additionally, keep an eye out for genital and nipple hyperpigmentation.
(Houk, 2006).
Additional imaging studies and laboratory testing are required to confirm
the diagnosis. To view the internal genitalia's anatomical features, undergo
pelvic and abdominal imaging.
1. An ultrasound examination can detect intra-abdominal molecular
structures and gonadal structures, as well as aberrant kidneys and
adrenals.
2. Intra-abdominal organs can be found, and molecular structures can be
assessed using MRI and CT scans.
3. The urogenital sinus's anatomy can be ascertained using retrograde
genitogram testing.
4. Laboratory tests, including hydroxy progesterone, chromosomal analysis,
FSH, LH, testosterone, DHT, and hCG testing, as well as serum
electrolytes.
A multidisciplinary team comprising professionals from the
psychosocial, medical, and surgical domains as well as subspecialty fields
like neonatology, endocrinology, urology, gynecology, genetics, counseling,
psychiatrists or psychologists, nurses, and social workers is necessary for the
best management of disorder of sex development (DSD). Hormonal
treatment is one aspect of medication management. Examining DSD in
accordance with its classification includes hormonal therapy as part of the
diagnostic process. The basis for hormone therapy for DSD is the idea that
pubertal growth requires sex hormones.
When the DSD patient reaches puberty, they can begin this hormonal
therapy. Future quality of life may be impacted and delays in genitalia
development, sexual and reproductive function, and reproductive function
may result from protracted hormone therapy delays. (Anthol, 2022).
If the patient turns male, treatment aims to encourage masculinization
while inhibiting feminization. Treatment aims to repress masculine
development and encourage feminine sexual features if the development is
female. Hormones for salt retention and glucocorticoids are administered in
congenital adrenal hyperplasia (CAH). Sex hormone therapy is often initiated
at puberty, whereas glucocorticoids can be started sooner, if necessary,
usually as soon as a diagnosis is made. (Diamond, 2006)
As an illustration, we have included a case study on timeline
management using ambiguous genitalia below.
 Figure 3. Timeline management for suspected ambiguous genitalia case
(Sato, et al, 2021)

D. CONCLUSION
This case needs more follow up for fetal sex determination. Hypospadias as a
differential diagnosis for the fetal is highly suggested with also better prognosis.
Further observation for phenotype and other abnormality for genitourinary disorder
and other organs are recommended. Noninvasive Prenatal Test or Chorionic Villous
Sampling may be indicated if in follow-up the abnormalities continue.

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