THE ROLE OF HUMAN CHORIONIC GONADOTROPIN IN THE TREATMENT OF RETRACTILE TESTIS

A retractile testis is the testis that can be brought down into the scrotum but then after a period retract upward outside the scrotum by the action of cremasteric muscle. The aim of this study is to identify the effect of age of the patient, location of the RT, and whether unilateral or bilateral on the response to HCG therapy. This is a prospective study conducted in the pediatric surgery compartment in Basrah Children Hospital over 3 years (2013-2016). Thirty two boys with a diagnosis of retractile testis (RT) are included in this study. All cases were treated with intramuscular injection of HCG as following: in boys aged 1-4 years: 1000 IU twice weekly for 3 weeks (total 6000 IU) and in those aged more than 4 years: 1500 IU twice weekly for 3 weeks (total 9000 IU). The response to treatment was evaluated in 2 weeks, one month, and 6 months after completing the course of treatment of HCG. In this study, the diagnosis of retractile testis was confirmed in 32 boys aged (1.25-9.5) years (mean: 5.28 years). Ten boys (31%) were with unilateral retractile testis. Twenty two boys (69%) were with bilateral retractile testis, 15 (27.7%) testes in the prescrotal area, and 39 (72.2%) testes in the inguinal area. From a total 54 retractile testes; 40 (74%) testes respond (descended into the scrotum). The mean age for responder was 5.49 years and the mean age for boys who did not respond was 4.69 years. Six (60%) of 10 unilateral retractile testes and 34 (77.3%) of 44 bilateral retractile testes respond to HCG treatment. Response to HCG occurred in 12 (80%) of the pre-scrotal retractile testes, and in 28 (71.8%) of the inguinal retractile testes. Re-ascending (recurrence) occurred in 6 (15%) testes. In conclusion, HCG treatment is an effective way of treatment of retractile testis especially in preschool children, bilateral cases, and in those with prescrotal testicular position. Introduction retractile testis is a normally descended testis that move outside of the scrotum but it can be brought down manually into the scrotum during physical examination without pain or tension on the spermatic cord and remain in the scrotum for a while after release. This upward movement of the testis is by the action of the cremasteric muscle (cremasteric reflex). The function of cremasteric muscle is to regulate the temperature of the testis in cold weather by elevating the testis to become closer to the body core temperature. The cremasteric muscle is most active in children especially between 2-7 years. Boys with retractile testis are usually referred to pediatric surgery or pediatric urosurgery outpatient clinic as a cases of cryptorchidism. Retractile testis is relatively common in pediatric population; the prevalence is recorded as 1.68% in children up to 14 years. The prevalence is also reported to be 3.9% of schoolchildren (7-12) years old. Some regarded retractile testis as a normal variant need only follow up because they often descend at puberty and there is no effect on testicular size or future fertility. Others considered retractile testis as a true pathological condition because of the following points: A


Introduction
retractile testis is a normally descended testis that move outside of the scrotum but it can be brought down manually into the scrotum during physical examination without pain or tension on the spermatic cord and remain in the scrotum for a while after release [1][2][3] .This upward movement of the testis is by the action of the cremasteric muscle (cremasteric reflex).The function of cremasteric muscle is to regulate the temperature of the testis in cold weather by elevating the testis to become closer to the body core temperature.The cremasteric muscle is most active in children especially between 2-7 years 4 .
Boys with retractile testis are usually referred to pediatric surgery or pediatric urosurgery outpatient clinic as a cases of cryptorchidism 5 .Retractile testis is relatively common in pediatric population; the prevalence is recorded as 1.68% in children up to 14 years 6 .The prevalence is also reported to be 3.9% of schoolchildren (7-12) years old 7 .Some regarded retractile testis as a normal variant need only follow up because they often descend at puberty and there is no effect on testicular size or future fertility [8][9][10][11] .Others considered retractile testis as a true pathological condition because of the following points: A There is gubernaculum defect in majority of cases; in addition, associated undescended testes are present in 42% of unilateral retractile testes 12 .Ascending testes (acquired cryptorchidism) can developed in 6%-32% of retractile testis cases carrying the same risk of complications occurring in congenital cryptorchidism 6,13,14 .Histological changes (tubular degeneration, germ cells maldevelopment) are present in retractile testes and ascending testis in a nearly similar degree as in undescended testis [15][16][17][18][19][20] .The size of retractile testes is significantly affected as compared with normal testes 7,21 .The presence of retractile testis in the inguinal region for prolong period with higher temperature than the scrotal position is the main cause of complications that may affect future fertility especially in bilateral cases 3,15,22,23 .The proper management of retractile testes still controversial; some prefer surgical correction in form of orchiopexy 20,24 , others prefer conservative management either wait and see 25 or hormonal therapy.Many studies evaluate hormonal therapy using Human chorionic gonadotropin (HCG) to stimulate testicular descent and the results were encouraging [26][27][28][29] .The action of Human chorionic gonadotropin (HCG) is similar to that of luteinizing hormone; it stimulate the leydig cells to produce androgen 1 , in addition it increase vascularity and weight of the testis 30 .In general; HCG treatment is regarded a safe treatment way; however, it may cause increase in penile size, painful erection, increase in pubic hair, and behavioral changes during the time of treatment and shortly after that 31 .This study is conducted to identify the effect of age of the patient, location of the retractile testis, and whether unilateral or bilateral on the response to HCG therapy.

Materials and methods
A prospective study conducted in the pediatric surgery compartment in Basrah Children Hospital over 3 years (2013-2016).Thirty two boys with a diagnosis of retractile testis are included in this study.The diagnosis of retractile testis is confirmed depending on history and physical examination.The parents of all boys confirmed that the affected testis was in the normal position within the scrotum then started to retract frequently outside the scrotum especially when it exposed to cold environment.The boys were examined in frog-leg position.The examination was in worm room, started with inspection then palpation with worm hand to avoid cremasteric muscle stimulation ,the testis was regarded as a retractile if it can be pushed from the inguinal region to the scrotum without pain or tension and remain there after that for a period at least one minute until cremasteric muscle activation.The examination was repeated two to three times for each boy before the final decision regarding the diagnosis, In some cases continuous pulling of the testis for 30 seconds was required to make the cremasteric muscle in fatigue status to maintain the testis within the scrotum after hand release 1 .Cases with ipsilateral inguinal hernia in association with retractile testis or those with history of ipsilateral inguinal surgery were excluded from this study.Data was collected regarding the age of the patient, unilateral or bilateral, and pretreatment and post-treatment location of the testis (prescrotal or inguinal) All cases were treated with intramuscular injection of HCG, the regimen of treatment was according to the patients age as following:  1-4 years: 1000 IU twice weekly for 3 weeks (total 6000 IU)  More than 4 years: 1500 IU twice weekly for 3 weeks (total 9000 IU) Two weeks after completing HCG treatment course; each patient was The role of human chorionic gonadotropin in the treatment of retractile testis Sadik Hasan Kaddim 98 Bas J Surg, December, 2016 evaluated for the response to treatment, the position of the testis was recorded again 1 month and 6 months later on.

Results
In this study, the diagnosis of retractile testis was confirmed in 32 boys aged (1.25-9.5)years (mean: 5.28 years) Ten boys (31%) were with unilateral retractile testis.Twenty two boys (69%) were with bilateral retractile testis.Of unilateral cases (7) were on the right side and (3) were left sided.The distribution of retractile testes according to their location at diagnosis was 15(27.7%)testes in the prescrotal area, and 39(72.2%)testes in the inguinal area.The response to HCG treatment of a total 54 retractile testes is evaluated, the results was as following: From a total 54 retractile testes; 40(74%) testes respond (descended into the scrotum).The mean age for responder was 5.49 years and the mean age for boys who did not respond was 4.69 years (Table I) .

Discussion
In 1988; Elder JS recommend the usage of HCG in the treatment of retractile testis 32 , also Ashcraft mention that retractile testis can be differentiated from cryptorchidism by HCG administration meaning that the response of retractile testis to HCG is well established 33 .
According to the Guidelines on Pediatric Urology 2013; the HCG dose 6000-9000 IU h given in four doses over 2-3 weeks 34 , while WHO recommends the following regimen: 250 IU/dose in boys less than one year, 500 IU/dose in those of ages 1-5 years, and 1000 IU/dose in those of ages more than 5 years given biweekly for five weeks 28,35 .In this study the total HCG dose is 6000 IU and 9000 IU according to the age of the patient, the total dose of HCG is the same of that mentioned in the Guidelines on Pediatric Urology 2013 but divided into six rather than four doses.In this study the overall response of retractile testis to HCG treatment (success rate) is 74%, which is nearly similar to reported success rate by two previous studies: Ezzat A, et al (76%) 28 , and Metin A, et al (82%) 27 .Bilateral cases in Ezzat A 28 , et al study were 60% of total case.Our study confirmed the higher prevalence of bilateral cases (69%).The same previous study revealed the mean age of those who respond to HCG was7.5 years, in our study the mean age was l (5.5 years).The least success rate is reported to be in boys less than 2 years (3%-15%) 27,36 .
In this study the success rate of HCG treatment was higher in bilateral cases than in unilateral cases 77.3% and 60% respectively, while in a study by Ezzat et al 28

Table ( III): Response to HCG according to the pretreatment location of the testis Response to HCG Location of the testis Respond Did not respond Total
27study by Metin A et al27recurrence occurred in 11 (8.9%) of 123 retractile testes.The increment of recurrence rate in present study may be because more than two third of retractile testes located in the inguinal region, in addition; in the Metin A study; a total HCG dose was 9000 IU used in all cases while in the present study the total dose was (6000-9000) IU according to patient age.