Am J Clin Exp Urol 2018;6(3):133-137

www.ajceu.us /ISSN:2330-1910/AJCEU0072410

Original Article
Post-operative use of human chorionic gonadotrophin
(u-hCG) inpatients treated for intrabdominal
unilateral undescended testes
Nicola Zampieri1, Virginia Murri2, Francesco Saverio Camoglio1

Departments of 1Pediatric Surgical Unit, 2Pediatrics, Azienda Ospedaliera Universitaria Integrata, University of
Verona, Woman and Child Hospital, Stefani 37100, Verona, Italy
Received January 9, 2018; Accepted April 23, 2018; Epub June 15, 2018; Published June 25, 2018

Abstract: Objective: To report our experience with post-operative use of human chorionic gonadotrophin to achieve
higher testicular volume and function, respect to untreated patients. Materials and methods: A prospective study
was done using subjects who underwent orchidopexy between Sptember 2010 and September 2016 for unilateral
intrabdominal undescended testes. All patients were treated by the same surgeon with laparoscopic one-stage
Fowler-Stephens technique. After surgery (2 weeks) those patient parents who accepted to use hormonal therapy,
had to follow a 6 weeks scheme. Patients received subcutaneous 500 UI (Gonasi-HP) weekly. A follow-up was per-
formed at the end of therapy and 6 months later. Testicular volume was measured at each visit by ultrasound and
by sonoelastography and compared with the untreated ones. Results: Forty-five patients were enrolled and treated
with a mean age of 18.0±9.7 months. 32 patients received post-operative hormonal therapy. There were no cases
of adverse effects nor droupout. All patients completed follow-up. There were no cases of testicular atrophy in both
groups. At 6 months among treated patients 26 (81%) subjects achieved normal testicular size while the other had
still smaller volume. Among untreated patients, 6 (46%) subject achieved normal testicular size (P < 0.05). Con-
clusion: Despite the role of hormonal therapy is still under discussion, especially for post-operative treatment, our
results suggest that it is safe and useful to improve testicular volume and morphology; treated testes have also a
good stiffness respect to untreated testes.

Keywords: Undescended testes, hormone, HCG, treatment

Introduction scended testis is the most frequently diag-

nosed andrological disease before 3 yrs of age;
Testicular growth depends on many different hormonal treatment has been used for years
factors. The normal development and function before surgery, but recently this treatment is
of the testis is strictly correlated with norm- under discussion [2-5].
al spermatogenesis and subsequent normal
fertility. Testicular size is highly correlated with The esticular volume and function improvement
fertility, poor fertility often being associated of intrabdominal testes after orchiopexy is still
with small testes. It is, therefore, vital to ensure the main outcome for surgeons. It was reported
the regular development of the testes at any that testicular volume and hormonal function at
stage. The regular development and function of
18 years in patients diagnosed and treated for
the testis in the fetus can be impaired by vari-
cryptorchidism during childhood are strongly
ous congenital malformations. In such cases,
influenced by the age at operation and whether
the imbalance in testicular hormonal stimula-
tion caused by many diseases results in dam- the undescended testis was unilateral or bilat-
age to the spermatogenesis and subsequent eral [1].
infertility [1].
The aim of this prospective study is to report
The testicular volume is strictly correlated to the Authors’ experience with the post-opera-
fertility potential and spermatogenesis; unde- tive use of human chorionic gonadotrophin to
 Undescended testes and hormonal therapy

achieve higher testicular volume and function with 5 to 10 MHz probes. With testicular US,
versus untreated patients. clinicians can assess the patients’ testicular
volume and parenchymal echostructure.
Materials and methods
In this study, US scans were performed by the
A prospective study was carried out on sub- same radiologist and the testes were scanned
jects treated with orchiopexy for unilateral with the same instrument described before
intrabdominal undescended testes between using a 7.5 MHz probe. Testicular length, width,
September 2010 and September 2016. All and height were measured using electronic cal-
patients were treated by the same surgeon lipers. The figures obtained were then substi-
using the laparoscopic one-stage Fowler-Ste- tuted into the formula of a prolate ellipsoid to
phens technique. estimate the testicular volume [Vol (ml) = .523
× L × W × H] [6].
Inclusion criteria for this study were as follows:
full term baby; unilateral non-palpable testes; Statistical analysis was performed using the
no genetic diseases; no other malformations. chi-square test, T-student test and Fischer ex-
act tests. P value < .05 was considered signifi-
Informed consent was obtained from all the
cant for the correlation between the variables.
parents and patients’ compliance with treat-
ment assessments was 100%. No dropouts Results
were recorded. The internal IRB approved the
study. During the study period, forty-five patients were
enrolled and treated, mean age of 18.0±9.7
Patients were divided into two groups: a study
months. 32 patients received post-operative
group and a control group. After surgery (2
hormonal therapy. There were no cases of
weeks), the patients whose parents had accept-
adverse effects including dropout or major sur-
ed to use the hormonal therapy had to follow a
gical complications (I.e. retracted testis or scro-
6-week scheme. Patients received subcutane-
tal bleeding). All patients completed follow-up.
ous 500 UI (human chorionic gonadotrophin
All data collected were monitored and recorded
extracted from human urine u-hCG) weekly.
in an electronic database. Before each visit,
Follow-up was performed at the end of the ther-
the patients were contacted by phone. For this
apy and 6 months hence after.
reason, compliance for this study was 100%.
Patients without hormonal therapy were includ- There were no cases of testicular atrophy in
ed in the control group. The testicular volume either group (P>0.05).
was measured at each visit by Ultrasound (US)
The injections were performed by the patients’
and sonoelastography and then compared with
parents at the samehour each week, with full
untreated patients (controlateral subjects and
study group vs control group). compliance with the procedure.

Sonoelastography is an imaging technique to At 6-month follow-up, treated patients showed

assess the elasticity of a tissue; results are different outcomes: 26 (81%) subjects achiev-
expressed following a color scale, where red ed normal testicular size versus the controlat-
shows well vascularized tissue with good elas- eral testis, while in the remaining subjects the
ticity, blue indicates stiffer tissue and green testis was still reduced in volume. In the group
represents mixed stiffness. The testicular elas- of untreated patients, 6 (46%) subjects achi-
ticity was expressed as a three-point scale (1: eved normal testicular size (P < 0.05).
normal; 2: mild to moderate stiffness; 3: severe
The mean testicular growth improvement in
stiffness) [6].
treated patients was 23% in volume versus
The advantage of this ultrasound technique lies untreated patients. Based on the elastosono-
in its real-time evaluation of the tissue, with any graphic results, treated patients had better
relevant stiff areas, allowing the operator to vascularizied testes with a soft pattern than
focus on a specific point. untreated patients. The mean score for each
testis at sonoelastography was 1.5±0.3 in the
Ultrasounds were performed using Siemens treated group and 2.1±0.3 in the untreated
Sonoline Elegra Ultrasound Imaging System, group (P < 0.05).

134 Am J Clin Exp Urol 2018;6(3):133-137

 Undescended testes and hormonal therapy

Treated testes were bigger and less stiff than the transabdominal migration of the testes into
the testes of the control group; considering the the inguinal region. Therefore, the transabdom-
controlateral testis per each group, the treated inal phase of the testicular descent is the result
group did not show significant statistical differ- of the vector sum of traction by the CSL and the
ences, while in the control group the operated gubernaculum. During the second inguinoscro-
testes were stiffer than their controlateral tal phase the testes move from the inguinal
(2.1±0.3 vs 1.4±0.5) (P < 0.05). region to the scrotum. This phase is due to the
shortening of the gubernacular cord and the
Discussion outgrowth of the gubernacular bulb. The trans-
abdominal stage occurs between 10 and 23
Many testes that are undescended at birth weeks of gestation in human embryos, while
reach the scrotum soon afterwards. It has been the inguinoscrotal phase starts at around 26
found that 2% of full-term and 18% of prema- weeks of gestation to end between 28 weeks of
ture babies have one or two undescended tes- gestation and birth.
tes at birth and that in 75% of these cases the
testes have descended by year 1, at which age Many studies found gonocytes (human testicu-
the overall incidence of undescended testes is lar tissue) in the testis of 2-year-old boys. At
1% [3]. the age of 3 years spermatogonia can be
observed on the basal lamina. Spermatocytes
Unilateral cryptorchidism accounts for about appear at 4 years, immature spermatids at 11
85% of all recoreded cases [5]. The incidence years, and mature spermatids at 13 years of
of this condition decreases to about 1% within age. Leydig cells are not recognized in the tes-
6 months of age because of spontaneous tes of 2- to 6-year-olds. Only fibroblast-like cells
descent. It has been estimated that a normal can be observed in the interstitial tissue. At the
testis results if descent occurs within 6 weeks age of 7 years, immature Leydig cells are recog-
from birth in a full-term infant or 3 months in a nized in the interstitial tissue. Mature Leydig
premature baby. With later descent the testis cells are also observed in the testes of 13-year-
fails to reach the bottom of the scrotum and old boys. All these results explain how impor-
remains smaller than the opposite scrotal tant the normal descent of the testes is for
organ [7]. spermatogenesis and how testicular failure or
disease during infancy may severly compro-
Evolutionarily speaking, testicular descent is a mise adult fertility [2].
costly process, and many developmental or
physiological difficulties might occur during its Many studies in humans and animals reported
course. The descent of the testis is a complex, the role of the gubernaculum: histologically, the
multistage process requiring the interaction of gubernaculum is composed of an abundant
both anatomical and hormonal factors [4-12]. extracellular matrix that is rich in glycosamino-
glycans and mesenchymal cells such as fibro-
The most accepted theory describes the blasts and smooth muscle cells. The connec-
descent from an intra-abdominal location into tive tissue of the gubernaculum undergoes
the bottom of the scrotum in two major phases, remodelling so that at the end of migration it
the transabdominal and the inguinoscrotal has essentially become a fibrous structure, rich
descent. This two-stage process is guided by in collagen and elastic tissue. But, as reported
two mesenteric ligaments: the cranial suspen- in animals, during this transformation, if treat-
sory ligament (CSL) and the caudal genitoingui- ed with hormone, the gubernaculum becomes
nal ligament or gubernaculum. rich in vessels under the effect of testosterone,
which increases the androgen receptor expres-
Under the effects of hormones, CSL regresses sion in the fibroblasts, with secondary guber-
whereas the gubernaculum develops its caudal nacular muscle contraction [8-11].
segment into the so-called gubernacular bulb,
a reaction called the “swelling reaction” or Chedane et al reported a link between low
“gubernacular outgrowth”, protruding into the maternal serum hCG level and cryptorchidism;
forming scrotal sac. The swelling reaction of the relative hCG insufficiency could contribute to
gubernaculum holds the testis very close to the cryptorchidism, as hCG is known to stimulate
developing internal inguinal ring; this causes fetal testicular androgen production with peak

135 Am J Clin Exp Urol 2018;6(3):133-137

 Undescended testes and hormonal therapy

hCG levels at weeks 8-11 of gestation. Start- surgery adds both improvement in interstitial
ing from week 20 of gestation hCG levels then tissue and in the stimulation of Sertoli cells.
drop to 10-15% of peak concentrations. For
this reason, for many years hormonal therapy Conclusions
was the first-line treatment for undescended
testes [15]. Despite the role of hormonal therapy being still
under discussion, especially as a post-opera-
If at present the standard goal still remains the tive treatment, the results collected in this
surgical procedure, less is known about the study, and confirmed by other authors [16-18],
role of hormonal therapy associated with orchi- suggest that this approach is simple (subcuta-
opexy. For intraabdominal undescended tes- neous injection), safe and useful to improve
tes, the first issue is whether or not surgeons testicular volume and morphology. Also, stiff-
should preserve the spermatic vessels. The ness in treated testes was milder than in
Fowler-Stephen technique, in which the testicu- untreated testes, due to improved vasculariza-
lar artery and vein are ligated, allows extensive tion. Further studies may show that such find-
mobilization of the testis, which then depends ings can be associated with enhanced testicu-
on the deferential artery and gubernaculum for lar function, thus preserving the patients’
blood flow. It was reported that pre-operative fertility potential.
human chorionic gonadotropin on intra-abdom-
inal rat testes undergoing orchiopexy doubled Disclosure of conflict of interest
the testicular blood flow [13].
None.
This technique can be performed in single or
two-staged procedure; at present, there are no Address correspondence to: Dr. Nicola Zampieri,
consistent data available to support either Pediatric Surgical Unit, Azienda Ospedaliera Uni-
option. However, all the series reported a suc- versitaria Integrata, University of Verona, Woman
cess rate between 80 and 85% with 20% of and Child Hospital Piazzale A. Stefani 37100,
atrophy [14]. Verona, Italy. Tel: +39458127129; E-mail: dr.zamp-
[email protected]
The aim of this study was to improve the tes-
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