Role of pre-operative gonadotropin in orchidopexy

Role of pre-operative gonadotropin in orchidopexy

El-sayedH.  Abdallah, MI>; MohammedA.Abdelkhalekb, MIP; Guindy, MD:; AmrA.Mostafa, MlJd

a) Departments of General Surgery (Pediatric Surgery Unit), Al-Azhar University b) Departments of Urology, Al-Azhar University

c) Department of Paedistues, Al-Azhar University d) Department of Radiology, Al-Azhar University

Background: To evaluate the role of human chorionic gonadotropin  (HCG) in cryptorchid boys regarding testis position and size in treatment of palpable undescended testis (UDT).

Patients and methods:  One hundred children presented with unilateral palpable UDT were studied in the period from May 2007 to May 2010. Their ages ranged from2-12 years with mean age 6.4 years SD ±2.1 and were divided into two equal groups: Group A- {control group) in which surgical orchidopexy was done without preoperative hormonal  preparation and Group B- {studied group) in which the patients received preoperative intramuscularinjection of HCG

30-50IU(Pregnyl) per kilogram ofbodyweight, two times a week for five succeeding weeks. The patients were subjected to clinical examination, laboratoryinvestigationsincluding testosterone level pre- and post- HCG therapy, ultrasound (UIS) and color Doppler ultrasound (CDUS). The results were assessed clinically, hormonal level, and CDUS  Standard orchidopexy was done in all cases. Both groups were assessed in teims  of testicular size and vascularity by CDUS  The mean basal and post-HCG stimulation  serum testosterone level were also compared in both groups. Both groups were also followed up postoperatively, clinically and by UIS

Results:   found sizable testis, long cord withgood vascularity, easily dissectible associated hernial sac and more capacious scrotum with good post-operative results in group B patients.

Conclusion: Preoperative HCG treatment is a safe effective tool to increase testicular size and viability which improve the results of orchiopexy

Key words: Undescended testis, orchiopexy, human chorionic gonadotropin(HCG).

Introduction:

Cryptorchidism  is the most common urogenital birth defect in males necessitating surgery. The importance of cryptorchidism treatment concerns with the possibility of diminishing  risk  of  malignant  degeneration and improving  fertility.! Malignant  changes and degeneration  in UDT  is 4-40%  higher than normal testes.3 Testicular descent occurs late in fetal life and is regulated by many factors including intra-abdominal pressure, hormonal, neurologic influence and presence of gubernaculum. The absence of any of these elements may contribute to cryptorchidism. The   incidence   of   undescent   depends   on fetal age, up to 30% of premature boys have

either  one  or  both  undescended  testes.  In boys born at term the  incidence  is between

3-4%.4 Approximately atthe age of3 months,

transient increase in serum gonadotropin and testosterone occurs which is responsible for spontaneous  descent  in  more than  one  half of boys with cryptorchidism.  The incidence of cryptorchidism in untreated adults is approximately 1%.5

Success   rate   of   hormonal   treatment varies from 0-55% with human chorionic gonadotropin (HCG) and 9-87% with gonadotropin releasing hormone (Gn-RH). Surgical     interference     for     undescended testes  still  is  the  main  way  for  treatment to  avoid  complications.   Shortening  of  the

spermatic   cord  and  under-development   of the  scrotum  are  still  the  main  problem  in surgical treatment  of UDT. The use of HCG as a preoperative preparation for orchidopexy helps the  surgeon  by  increasing  the  length and the vascularity  of the cord and increase size  of the testis  and the  scrotum  becomes more   capacious   and   well         developed   in addition to help the dissection of hernia sac. 7

The  proper  treatment  of  cryptorchidism   is still  controversial.  In the  past,  it  has  been dictated by experts in hormonal therapy. By ascertaining  the  cause  of  UDT, the  action of  gonadotropin  factor  and  the  efficacy  of surgical  procedures,  the surgeon  is enabled to reconstruct a rationale form of treatment. Currently, most pediatric  urologists  suggest treatment  of cryptorchidism  before the child is 2 years old, preferably when he is between

6-18  months.8  The surgeon  is able to place

the UDT into the scrotum however, surgical treatment is difficult and complications range from   1.5%  to  12.2%.  Certain  outstanding difficulties               are           encountered in            surgical procedures   when   the   scrotum   is   under­ developed and the testis is malformed, small and   associated   with   short   vessels.9   The modalities available for surgical or hormonal therapy   are   performed   on   an   outpatient basis.  Hormonal  manipulation  is  based  on the  observation  that  increased  testosterone may encourage  testicular  descent.l2  Human chorionic        gonadotropin    HCG     produced by human  placenta with a a-subunit  that  is almost  identical to the a-subunit of pituitary gonadotropin   has   been   shown   to  induce testicular  descent presumably  by stimulating either   testosterone or   dihydrotestosterone production  by Leydig's  cells.l3 Immediately after   treatment   with   HCG,  there   was   a large  increase  in the  conversion  of 3-(0H) progesterone       and       3-(0H)pregnenolone by     17-alphahydroxilase                and                 3-beta­ hydroxysteroid dehydrogenase. Considerable amount of testosterone was formed especially from  pregnenolone  within  2 weeks  of  last HCG   injection   and  steroidogenic   activity has decreased. These observations  indicated that HCG treatment of boys with UDT does

not result in irreversible or even long lasting stimulation  of their steroidogenic  activity.l4

Hawkin's  in 1995  stated  that  no long term ill effects have been in association with this short   term   hormonal   therapy.   The  mean goal of HCG therapy is to increase serum testosterone level. More than  10-20-fold baseline  HCG  has  been  used  extensively in the preoperative period as a therapeutic measure to induce testicular descent.l5 HCG induces a significant increase  in the volume and  density  of  both  interstitial  tissue  and blood vessels.ll

Patients and methods:

The study included one hundred children who suffered from unilateral palpable UDT attending   outpatient  clinics  of  Al-Hussein and Bah El-shairia Hospitals, Al-Azhar University, in the period from  May 2007 to May 2010. Their ages ranged from 2-12 years with mean age 6.4 years SD ±2.1 years. All patients subjected to full history taking & clinical examination, complete laboratory investigations and Doppler U/S examination for evaluation of size, site and vascularity of the UDT. Those children were genotypically and phenotypically normal.

Exclusion          criteria:          Non-palpable

undescended testes, bilateral palpable undescended  testes  and abnormal  genotype and phenotype (ambiguous genitalia).

These patients were grouped into two groups:

Group A: 50 patients operated without hormonal therapy and

Group B: 50 patients prepared by hormonal therapy (HCG) pre-operatively.

The HCG was given according to the body weight as shown in Table (1).

Preoperatively,  testicular  size  was measured  clinically   by  orchidometer   with slide calibers. The volume V (ml) was calculated  by V = length  L (em)  x breadth B (em) x diameter D (em) x 0.523. Color Doppler ultrasound  was done in all cases to localize the testes,  measure its size and note its vascularity. Re-measurement was done for both groups. Standard orchidopexy was done in all cases.

Results:

This study was done on 100 patients who suffered from  unilateral  palpable  UDT. The left side is more commonly affected as shown in Table (2).

The  patient  ages  range from  1-12  years with mean age 6.6/12  years. Table (3) show age at presentation ofUDT.

In our study, we measured serum testosterone  level  in  both  groups  and  after HCG therapy for group B only and we found that   serum  testosterone   level   was  at  the low normal value before HCG therapy and increased significantly in group B after HCG therapy as shown in Table (4).

In our study, as regard U/S findings, we

found that the site of the undescended testis was the  inguinal  canal  (30%),  external inguinal ring (50%) and at the neck of scrotum (20%). After  hormonal therapy  in group  B, we found  increased  size  of testes  by about

10-15%  based on the first U/S examination, increased vascularity by Doppler U/S and scrotal  development  by clinical  observation in addition to increased activity and increased appetite as observed by parents. As regard the site ofthe testis, in 8 out of 15 cases of group B (16%) with testicles at the site of inguinal canal, the testicles reached the site of external inguinal ring.

In 10 out of 25 cases of group  B (20%)

with testicles  at the site of external inguinal ring, the testicles reached the site of scrotal neck.

In  7 out  of  10  cases of  group  B (10%)

with testicle at the scrotal neck, the testicles reached at the bottom of scrotum.

In 25 cases of group B (50%) the site of the testes did not change after HCG therapy but  their  size  increased  by  10-15%  of  the first U/S measure  with increased vascularity by  Doppler  U/S.  On  surgical  orchidopexy, the surgery was more easy, the testis was sizable, the  cord was longer, the hernia  sac was thicker and easier dissectible from the cord, tissue plane was good and the scrotum was well developed and capacious as shown in Figure (1).

Follow up after orchidopexy, the testicular size was good.

Discussion:

One hundred children suffering from unilateral palpable UDT attending the outpatient  clinics  of  Al-Hussein  and  Bah El-shaaria Hospitals,  Al-Azhar  University, in the period from  May 2007 to May 2010, their ages ranged from 1-12 years with mean age  6.6112 years  with  60  cases  presented with  left  unilateral   palpable  UDT  and  40 cases presented with right unilateral palpable UDT. Serum testosterone level was measured in all patients and we found that basal level was at the low normal value (4.2-4.3  ng/dl) [Normal value: 3-10 ng/dl] (Nicholson and Pesce  2000). After HCG therapy  for  group B  we  re-estimate  hormonal  level  and  we found   significant   increase   in  testosterone level (91ng/dl) and this coincided with Gangopadhyay et al. 2005. The testicular site and size were measured by Doppler U/S for all cases at the start of the study and we found that the site of the undescended testis was at the inguinal canal in (30%), external inguinal ring in (50%) and at the neck of scrotum in (20%) and the testicular volume ranged from

0.8-0.9 cm3. After HCGtherapy in group Bas

regard the site of the testis we found a change in the site in 50% as follows: 16% in whom testicles at the inguinal canal, the testicles reached the external inguinal ring, (20%) in whom testicles at the external  inguinal ring, the  testicles   reached  the  scrotal  neck  and (14%) in whom testicle  at the scrotal  neck, the testicles reached at the bottom of scrotum. However, in 50% the site of the testes did not change after HCGtherapy by Doppler U/S but the size oftestis increased by 10-15% ofthe first U/S measure with increased vascularity by  Doppler  U/S.  On  surgical  orchidopexy, the surgery was more easy, the testis was sizable, the  cord was longer, the hernia  sac was thicker  and easier  dissectible  from  the cord, tissue plane was good and the scrotum was well developed and capacious. We hypothesized that HCG may prevent ischemic damage during orchidopexy by increasing collateral flow and this is in agreement  with Geesman  et  al.  1992.  The  ultimate  aim  of all  therapeutic   approaches   to  UDT  is  to achieve  intrascrotal  fertile  testis.  This  can

Figure {1):A: The scrotum is well developed and capacious. B: the cord is longer. C: the hernia sac is thicker and easier dissectible  from the cord. D: the testis easily reaches the scrotum.

Table (1): Doses of  HCG therapy for UDT

Table (2): Distribution of unilateral palpable UDT as regard the affected side

Table (3): Age distribution of the patients

Table (4): Serum testosterone level during the study

be achieved either by hmmonal therapy only (HCG or Gn-RH), or hormonal therapy as a preoperative preparation. In our study, success rate ofhmmonal-induced intrascrotal descent  14%. The  most  st:Iiking result of

our work is the evidence of the efficacy of early hmmonal n·eatment in improving the n·ophism of  Clyptorchid testes.  Hormonal n·eatment, when administered at the end of the first 6 months of life, can be considered

an  effective  and  timely  substitution  of  the gonadotropin  and  testosterone  insufficiency of  the   cryptorchid   infant.   Therefore,   we propose this therapeutic procedure combined with surgery. LHRH nasal treatment was not difficult to  administer,  even  in  very  young infants, and did not cause any distinct adverse events   with   the        exception   of   increased excitability in about 25% of cases. Treatment with (Gn-RH) as nasal spray was introduced in  Europe  in  1975  and  proved  successful although  the  pathophysiologic   background has  been  questioned   and  success  rate  has been   variable.21  HCG  caused   mild   signs of        androgeniz\Zation     (hyperpigmentation of  genital  skin,  erections,  moderate  penile growth) in almost all patients. Orchidopexy in the 1st year oflife does not pose any significant problem to a competent pediatric surgeon and there are important anatomic advantages: the inguinal  channel  is shorter  and it  is  easier to  place  a  very  high  intra-abdominal  testis into the scrotum.  Many data in the literature indicate a good correlation between germ-cell count in childhood and semen quality as an adult.7 In our study, HCG as an intramuscular injection  was  used  with  slight  psychologic side effect instead of Gn-RH as the last drug is not available and is more expensive. Lala study  in  Switzerland  1993  with  HCG  500

I.U. I.M. three times weekly for three weeks

showed that 37.8% of testes descended  into scrotum.  Lala  study  showed  also  testicular descent occurred more often in patients with testes were located in lower position.l2 In our study, the results are less than Lala 14% as the regimen ofHCG is different. Nowadays, there must not be debate on the choice of medical or  surgical   approach  for  the  management of UDT and on their  efficacy in preventing long term complications. It must be a matter of synergism of both hormonal  HCG and/or followed by surgical orchidopexy to help and improve  the  surgical  orchidopexy.  In cases of failure that require surgery, the HCG will stimulate tissue growth enhancing the success of orchidopexy. The result that HCG is useful in testicular descent is also verified by another study  carried  out  by Zucchini  and  Cacciari in1982.  The  rationale  for  giving  HCG  is

that it stimulates  Leydig cells that results in an increase in plasma testosterone, which promote testicular descent. In our study, we found that HCG therapy stimulates testicular secretion, increases the size & vascularity of scrotum,  testes  and  vas  deference,  enlarges the inguinal canal, and causes differentiation of the epididymis and this coincided with Hadiselimovic and Gangopadhyay et al.23

Conclusion :

Preoperative   HCG treatment   is a safe effective  tool  to     increase   testicular   size and viability which improves the results of orchiopexy.

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