Hormonal therapy or Surgery for undescended testis.

Hormonal therapy and surgical treatment for undescended testes.

Physiology of descent of the testis, development of sperm and physiological basis of hormone therapy:

Testicular descent is dependent on androgens. There are two phases of testis descent during gestation. The abdominal phase, the testis moving from the mid abdomen to the internal inguinal ring is mediated by the gubernaculum. The second phase, Inguinal phase is the testis moving from the internal ring, through the inguinal canal to the scrotum. This phase is mediated by androgens.

An understanding of the different types of germ cells observed in the process of spermatogonia in the foetus eventually transforming to mature sperm in the adult is essential to evaluate the studies on efficacy of hormonal therapy. When the gonad differentiates into a testis, gonocytes develop and move to the periphery of the seminiferous tubules. It is probably somewhere between 2-9 months of age that gonocytes develop into spermatogonia, dark type A, “Ad spermatogonia”, thought to be the stem cells crucial to having normal numbers and quality of sperm in the adult. The transformation is thought to be stimulated by gonadotropins and androgens, although not directly proven. Pale type A spermatogonia (Ap) produce type B spermatogonia, the cell type that is committed to become spermatocytes. This process is thought to occur around 4-5 years of age. Mature spermatocytes are the first type of germ cell to undergo meiotic division, beginning the transformation process to mature sperm in the adult male.

FSH stimulates Sertoli cells that support spermatogenesis and LH stimulates Leydig cells to produce testosterone. FSH and LH are produced by the pituitary gland and regulated by gonadotropin releasing hormone (GnRH) produced by the hypothalamus gland.

Human chronic gonadotrophin (HCG) produced by the human placenta with an α-subunit that is almost identical to the α-subunits of pituitary gonadotrophin has been shown to induce testicular descent, presumably by stimulating testosterone or by stimulating dihydrotesterone production. The stimulatory effect of this polypeptide hormone on testicular steroidogenesis has enabled it to be widely used for evaluating male Leydig cell function. The general goal of an HCG stimulation test is to increase serum testosterone levels. More than 10-20-fold baseline HCG has been used extensively in the preoperative period both as a stimulating test for identification of testicular presence in cryptorchidism and as a therapeutic measure to induce descent. The HCG induces a significant increase in the volume density of both interstitial tissue and blood vessels. The HCG should be given as per the WHO protocol.

HCG stimulation test: used to assess testicular function in undescended testis.

Dose Schedule

Age 250 IU Twice weekly x 5 weeks< 1 year

500 IU Twice weekly x 5 weeks for 1 – 5 years1000 IU Twice weekly x 5 weeks

> 5 years

Contraindications for hormone therapy:

1. Ectopic testes,

2. Retractile testis

3. non-descended testes with inguinal hernia or

4. after previous groin surgery.

HOW HORMONE THERAPY IS GIVEN

HCG is injected to the patients three times a week, in a 3-week period. The patients with a weight of less than 20 kg, will receive 750 units of HCG and those with weights of 20 kg and more, will receive 1500 units of HCG in 9 intramuscular injections at a two-day interval.

Different degrees of these short-term complications were observed in all the patients. They were asked to follow up visited at 1 month, 3 months and 12 months after the first injection.

A month after the first injection, 69.5% with abdominal testes had the descent of testes into the inguinal canal. Among the patients with inguinal testes, the testes descended to the scrotum in 69.7%. From supra inguinal testes, the testes descended to the scrotum in 78% of them. I don’t recommend any hormonal therapy for retractile testis.

One of the most important results of this study is that 20% of abdominal undescended testes descended into the inguinal canal, which eliminated the need for invasive laparoscopy and two-stage surgery.

I recommend only to patients with bilateral UDT, and certainly in all cases with local features of hormone deficiency ; and some cases of unilateral UDT with a non palpable testis prior to surgery .

Timing of surgery of undescended testis

Testosterone production is at least partly maintained even in a retained testis. Boys with bilateral cryptorchidism will go through normal male puberty. There is, however, convincing evidence that a testis situated in the abdomen or in the inguinal canal is unable to produce spermatozoa and that spermatogenesis is improved if such a testis can be placed in the scrotum. The small difference in temperature (2–3 °C) between the abdomen and the scrotum is detrimental to normal spermatogenesis. Unilateral UDT is four times more common than bilateral. In unilateral UDT, the descended, scrotal, testis might compensate for the poor sperm production in the retained testis. However, all studies of adult men with unilateral UDT show that the sperm count is lower than normal, even if conventional orchiopexy during childhood has been successful. On the other hand, fertility in this group of patients, defined as ever having fathered a child, may still approach that of the background population. We should, however, strive for optimization of spermatogenesis in every boy born with UDT.

There has been a long-standing debate over whether the increased incidence of malignancies in retained testes can be alleviated by bringing it into the scrotum. This has recently been shown to be the case; boys whose testes had been placed in the scrotum before 13 years of age showed a significantly reduced risk compared to those operated after that age.

Orchiopexy, results in about 95% anatomical success, with a low (about 1%) risk of complications. The optimal time for orchiopexy has also been debated. Surgery is generally the preferred mode of treatment, rather than hCG or GnRH treatments. Orchiopexy should be performed between 6 and 12 months of age, or soon after diagnosis, if that occurs later. If a testis is found to be undescended at any age after 6 months, the patient should be referred for surgery. Referral should be to paediatric rather than general surgeons/urologists if the boy is less than 1 year old, if he has bilateral or non-palpable testes.

Individual reports give very variable success rates after hormonal therapy, from 8 to 60% anatomical success (defined as scrotal position, without signs of atrophy).

This has also been a matter of controversy. The key issue is whether the testis is irreversibly damaged if left in a warmer than normal environment or whether it can recover fully once it is brought into the scrotum. And if recovery is possible, does the extent of recovery depend on the time spent above the scrotum?

At birth, 3–8% of all boys demonstrate uni- or bilateral UDT, but most of these retained testes descend into the scrotum during the first 3 months. Thus, there is presently consensus that the diagnosis should not be finally established before 6 months of age.

The first results from a randomized controlled study, comparing the testicular growth after surgery at 9 months or 3 years of age, were recently published. Orchiopexy at 9 months was followed by a partial catch-up growth, which was not seen after the late surgery. This suggests that the testis at least partly loses its capacity for recovery if left in the scrotum beyond 1 year of age. Early surgery therefore seems more advantageous.

The consensus group unanimously recommended surgery between 6 and 12 months of age, or soon after diagnosis, if that is made later in life.

Where, and by whom, should UDT be treated?

In skilled hands of a Paediatric Surgeon, complications from orchiopexy are not greater if done before 1 year of age than if done after. However, surgery of infants needs the facilities of a unit with personnel trained both in surgery and anaesthesia of infants. In most countries, this means that it should be done at centres for paediatric surgery.

After diagnosis of congenital cryptorchidism in a newborn boy, he should be referred to a paediatric surgeon no later than at 6 months of age. should schedule orchiopexy before 1 year of age.

One to two percent of males have an undescended testis(s) (UDT) that does not spontaneously descend by six months of age and requires treatment. In approximately 30% of cases of cryptorchidism the problem is bilateral. It is established beyond doubt that if an undescended testis does not spontaneously descend by the age of 6 months it will need treatment as early as possible. Childhood orchiopexy alone is an effective treatment for fertility in unilateral cryptorchidism.

Bilateral UDT with hypoplastic scrotum

Surgical therapy

If a testis has not descended by the age of 6months (corrected for gestational age), and as spontaneous testicular descent is unlikely to occur after that age, surgery should be performed within the subsequent year. Early orchidopexy can be followed by partial catch-up testicular growth, which is not the case in delayed surgery.

Palpable testes

Surgery for palpable testes includes adhesiolysis and orchidopexy via an inguinal incision. Inguinal orchidopexy is a widely used technique with a high success rate of up to 92%. Important inguinal orchidopexy steps include

(a) mobilization of the testis and spermatic cord to the level of the internal inguinal ring

(b)with dissection and division of all cremasteric fibres, to prevent secondary retraction, and (c) detachment of the gubernaculum testis. The patent processus vaginalis needs to be ligated proximally at the level of the internal ring, because an unidentified or inadequately repaired patent processus vaginalis is an important factor leading to failure of orchidopexy. Any additional pathology must be dealt with, such as removal of an appendix testis (hydatid of Morgagni). At this time the size of the testis can be measured and the connection of the epididymis to the testis can be judged and described in the protocol. Some boys have a significant dissociation between testis and epididymis which is prognostically bad for fertility. Finally, the mobilized testicle must be placed in a sub-dartos pouch within the hemi-scrotum without any tension. In case the length achieved using the above-mentioned technique is still inadequate, the Prentiss manoeuvre, which consists of dividing the inferior epigastric vessels and transposing the spermatic cord medially ( which can be done without deviding the inferior epigastric vessels), to provide a straight course to the scrotum due to reduction of triangulation might be an option.With regard to fixation sutures, if required, they should be made between the tunica vaginalis and the dartos musculature. Lymph drainage of a testis that has undergone surgery for orchidopexy may have changed from high retroperitoneal drainage to iliac and inguinal drainage, which might become important in the event of later malignancy.