Open Journal of Pathology, 2012, 2, 159-161
Published Online October 2012 (http://www.SciRP.org/journal/ojpathology)
http://dx.doi.org/10.4236/ojpathology.2012.24030
1
Obstructive Azoospermia in a Patient with VATER
Association
Zhanyong Bing
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, USA.
Received May 23rd, 2012; revised June 21st, 2012; accepted June 29th, 2012
ABSTRACT
VATER association was first described in 1968 by Say and Gerald and is an association of congenital anomalies in-
cluding V (vertebral defect), A (anal atresia), TE (tracheoesophegeal fistula), and R (radial dysplasia and renal defects).
This report described a 26 year-old man with VATER association presented with infertility. Hormone tests including
follicular stimulating hormone, luteinizing hormone and testosterone were normal. Semen analysis showed azoospermia.
A testicular biopsy was performed and showed the presence of all of germinative components, germ cell sloughing, and
mild hypospermatogenesis. The findings were compatible with obstructive azoospermia. No evidence of intratubular
germ cell neoplasia unclassified was identified.
Keywords: VATER Association; Obstructive; Azoospermia
1. Introduction
Infertility can be attributed to men in 30% - 40% of in-
fertile couples, which may be du e to endocrin e disruption
of gonadal development during early pregnancy, environ-
ment pollution and genetic factors. Azoospermia can be
secondary to obstructive or non-obstructive etiologies.
Testicular biopsy plays a definitive role in confirming the
obstructive azoo spermia, which in turn leads to appropri-
ate management.
VATER association was first described in 1968 by Say
and Gerald [1] and is an association of congenital
anomalies including V ( vertebral defect), A (anal atresia),
TE (tracheoesophegeal fistula), and R (radial dysplasia
and renal defects) [2,3]. Since the introduction of the
acronym, various expansions in an effort to further define
the scope of the VATER association have been suggested,
such as V in VATER was expanded to include vascular
anomalies [4]. It has been suggested to expand the acro-
nym to VACTERL with the C denoting cardiovascular
anomalies and the L denoting limb anomalies [5]. About
half of the patients with VATER association also show
the urologic anomalies [6,7]. No obstructive azoospermia
has been reported in the patients with VATER associa-
tion. In this report a men with VATER association with
an obstructive azoospermia was describ ed.
2. Clinical Histor y
The patient was a 26 year old man who was born with an
imperforate anus and hypospadias. He had one functional
kidney. He had a colostomy from 1986 to 1997 and then
was reversed. He had fecal incontinence. Colorectal
evaluation showed minimal tone and no appreciable
functional sphincter. He developed hydrocele in 2005
and it was enlarged since then. He had no issues with
erection or orgasm. In 2 009 he had a semen analysis that
showed azoospermia. Hormone tests were done in 2011
and showed that follicular stimulating hormone, lu-
teinizing hormone and total testosterone were within
normal limits. He reported occasional dysuria and had to
strain to void at times. He had in intermittent stream. He
denied hematuria or urolithiasis. A testicular biopsy and
resection of hydrocele sac was performed.
3. Pathology
The testicular biopsy showed the presence of all germi-
native elements (Figures 1(a) and (b)). The majority of
the tubules showed sloughing of the immature germina-
tive elements. The modal Johnsen score was 9. The mean
spermatid count per tubules was 10. The tubular base-
ment membranes showed mild thickening. No Leydig
cell hyperplasia was seen. The vessels were unremark-
able. No morphological evidence for intratubular germ
cell neoplasia unspecificed was identified. Immunohis-
tochemical stains for OCT3/4 and PLAP were performed
and were negative.
4. Discussion
VATER association describes a non-random group of

Obstructive Azoospermia in a Patient with VATER Association
160
(a)
(b)
Figure 1. Testicular biopsy in a patient with VATER asso-
ciation. (a) Germ cell sloughing; (b) All of germinative
components were present.
vertebral, anal, radial and renal malformations. The inci-
dence ranges from 0.03 to 1.6/10,000 live birth [5,8]. The
underlying molecular mechanisms are yet to be deter-
mined. Chromosome studies done in 19 of the infants
were reported normal [9]. Population based study sug-
gests an association between maternal diabetes and mul-
tisystem anomalies. Incidence of VATER association in
infants of diabetic mothers was five times high er that that
of babies of nondiabetic mothers [10]. Interestingly, it
has been shown that a novel germ line mutation of the
PTEN gene in a patient with macrocephaly, ventricular
dilatation and features of VATER association [11].
Reported anomalies of VATER association in the
genitourinary tract include the malformation of male ex-
ternal genitalia [12], vaginal membranous septum [13],
and agenesis of the fallopian tubes, uterus, and vagina
[14]. Obstructive azoospermia in VATER association has
not been reported.
Obstructive azoospermia can be confirmed by testicu-
lar biopsy, which is usually performed for the following
reasons. First is to confirm the obstructive nature of
azoospermia, which may provide guidance for future
management, including surgical correction if appropriate.
Second is for sperm harvesting for in vitro fertilization.
In this scenario, a testicular biopsy is needed to estimate
the success rate for future sperm harvesting, and at same
time to diagnose intratubular germ cell neoplasia unclas-
sified (ITGCNU). Infertility, like other risk factors, such
as a history of cryptorchidism and testicular germ cell
tumor and gonadal digenesis has a higher chance for
ITGCNU [15].
As this patient was normal for hormone tests and se-
men analysis showed azoospermia. A testicular biopsy
was performed. In the biopsy, all germinative elements
were present. There were germ cell sloughing and mild
hypospermatogenesis. This report suggested that patients
with VATER association could present with azoospermia.
Testicular biopsy may be a useful tool to confirm the
obstructive nature of azoospermia. No morphological or
immunohistochemical evidences for ITGCNU were iden-
tified in this case.
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