Obstructive Azoospermia in a Patient with VATER Association

doi:10.4236/ojpathology.2012.24030

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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

Obstructive Azoospermia in a Patient with VATER

Association

Zhanyong Bing

Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, USA.

Email: [email protected]

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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