Chapter 86: The Testis and Scrotum

Embryology and Anatomy of the Testis

The testes originate from two types of cells in the embryo:

• The primordial germ cells (PGC) will form the gametes (sperm). These cells come from the ectoderm, but they separate themselves from it at the early stages of development.
• The somatic cells that surround the PGCs are the supporting Sertoli cells and the interstitial Leydig cells. These cells are thought to arise from the mesonephros, local mesenchyme and/or superficial epithelial cells (coelomic epithelium).

At 4–6 weeks of gestation, paired urogenital ridges develop as outgrowths of coelomic epithelium, the medial part forming gonadal ridges, where the PGCs migrate from the yolk sac in the sixth week. From the seventh week, in male embryos with a normal sex-determining region on the Y chromosome (SRY), the PGCs coalesce to form the primordial testis. The differentiation of pre-Sertoli cells forms the first step of this process, surrounding the PGCs and eventually becoming testicular cords from which the seminiferous tubules eventually develop in the mature testicles.

After the eighth week mesenchymal cells between the testicular cords differentiate to become interstitial Leydig cells, which produce testosterone. These cells are thought to be derived from the ventral part of the mesonephros (the origin of the adrenal cortex). The mesenchyme between the testicular cords forms connective tissue that subdivides the testicles into lobules, as well as the future tunica albuginea.

At about 9 weeks of development, the labioscrotal swellings fuse to form the scrotum. Testosterone induces development of the mesonephric (Wolffian) duct to form the epididymis, vas deferens and seminal vesicles. During this stage, the testis migrates from the gonadal ridges to lie at the internal inguinal ring owing to a combination of growth processes, hormones and the gubernaculum (a fibrous cord from the testis that inserts around the labioscrotal swellings). Between the seventh and the 12th week the gubernaculum shortens and pulls the testis and its vessels downwards.

At the same time, adjacent to the lower portion of the gubernaculum, an evagination of the parietal peritoneum, the processus vaginalis, pushes through the abdominal wall, creating the inguinal canal and taking the internal oblique and transversus abdominis muscle fibres with it, eventually forming the cremasteric layer of the scrotum. The transversalis fascia forms the internal spermatic fascia deep to the cremaster, and the superficial aponeurosis of the external oblique muscle forms the external spermatic fascia. Between the third and seventh months of gestation the testes stay in the area of the inguinal canal. They descend during the seventh to ninth months to reach the scrotum at roughly the time of birth under the influence of androgens and insulin-like peptide 3 (INSL3). The process is also dependent on the abdominal wall musculature generating intra-abdominal pressure. In the first year of life the upper part of the processus vaginalis obliterates, the lower portion persisting as the testicular tunica vaginalis.

During the eighth to ninth months of gestation, the epididymis follows the testis into the processus vaginalis. As the mesonephric duct develops into the epididymis, a proximal remnant may persist as the appendix epididymis (most often at the head of the epididymis). Simultaneously, the paramesonephric structures (Müllerian) regress under the influence of Müllerian inhibiting substance secreted by the Sertoli cells of the developing testis. The proximal remnant of the Müllerian duct persists as the appendix testis.

The anatomy of the adult testis reflects its embryonic development. The testicular arteries originate in the retroperitoneum from the abdominal aorta just below the renal arteries. The testicular veins drain into the renal vein on the left and the inferior vena cava on the right. For much of their course the testicular artery and vein run parallel to the ipsilateral ureter, for which they may be mistaken during retroperitoneal surgery. Lymphatic drainage also follows this route – the paraaortic nodes are the draining lymph nodes for the testes, which is important in the staging of men with testicular cancer.

The epididymis lies on the posterior aspect of the testis and is palpable as a separate structure, with a head, a body and a tail. The seminiferous tubules enter the epididymis at the upper end of the epididymis (the head). From the head, sperm travel through the body and tail of the epididymis to enter the vas/ductus deferens at the lower pole of the testis. The vas lies behind the testis and can be felt above the testis as a firm tubular structure entering the external inguinal ring (Figure S86.1).

Figure S86.1

Diagram of the genital ducts after descent of the testis. The paradidymis is formed by remnants of the paragenital mesonephric tubules. (Reproduced from Docimo SG. The Kelalis–King–Bel-man textbook of clinical paediatric urology, 6th edn. Boca Raton, FL: Taylor & Francis Group, 2020.)

Filarial Elephantiasis of the Scrotum

Filarial elephantiasis of the scrotum is caused by obstruction of the pelvic lymphatics by worms such as those of W. bancrofti (90% of cases), Brugia malayi and Brugia timori. The condition is common in the tropics and is transmitted by mosquitoes. It is often accompanied by secondary infection and lymphangitis, resulting in swelling of the genitals and lower limbs. In chronic cases, the swollen scrotum may bury the penis (Figure S86.2). Associated symptoms and signs include fever, epididymitis, hydrocele and chyluria. The diagnosis is usually made clinically, although immunological testing can be helpful.

Medical treatment involves the use of diethylcarbamazine (DEC), ivermectin and albendazole, depending upon geographical location. Surgical treatment is rarely helpful, although redundant skin can be removed and the scrotum reconstructed.

Non-filarial elephantiasis

Elephantiasis can occur in the absence of filariasis, most notably in sub-Saharan Africa. Non-filarial elephantiasis can result from fibrosis of the lymphatics caused by lymphogranuloma venereum, but in many cases it is thought to arise as a consequence of persistent contact with irritant soils.

Sebaceous cysts

Sebaceous cysts are common in the scrotal skin. They are usually small and multiple (Figure S86.3). If troublesome, then surgical excision is necessary.

Male Factor Infertility

For couples of unknown fertility status, approximately 15% are unable to achieve a pregnancy within 1 year. The inability to conceive may be due to female factor infertility, male factor infertility or a combination of these two factors; approximately 20% of cases of infertility are caused entirely by the male factor.

Aetiology

Male infertility is a symptom of underlying disease. The two main causes of male factor infertility are either failure of sperm production or failure of sperm delivery.

Failure of sperm production can reflect:

• endocrinological abnormalities such as hypogonadism, which can be hypergonadotropic (testicular failure) or hypogonadotropic (pituitary failure);
• genetic problems (e.g. Klinefelter’s syndrome), microdeletions of the Y chromosome;
• infection, e.g. mumps orchitis;
• anatomical/congenital issues (varicoceles, cryptorchidism);
• social causes (smoking, excess alcohol);
• drugs, chemotherapy or radiation damage;
• malignancy (testis cancer).

In most cases however, the cause is unclear. In these cases, there may be reduced numbers of sperm in the ejaculate (oligozoospermia) or a complete absence of sperm in the ejaculate (azoospermia).Failure of sperm delivery includes obstructive or coital issues.

• Obstructive causes can be:
  • genetic, e.g. congenital absence of the vasa (often in association with cystic fibrosis);
  • iatrogenic (surgical damage to the vasa following inguinal surgery/vasectomy);
  • infection (epididymitis causing epididymal obstruction);
  • anatomic (ejaculatory duct obstruction).
• Coital causes can be erectile dysfunction, ejaculation issues or penile deformity.

The top causes of male infertility as a whole are varicoceles (38%), idiopathic causes (23%), obstructive causes (13%) and endocrinopathies (2%).

Assessment and investigation

Given the interplay between male and female factors, the man should not be investigated in isolation from his female partner. A careful history is the mainstay of the assessment with a careful search for aetiological factors. Physical examination is usually normal, but occasionally the testes may feel small (suggestive of a testicular cause), the vasa may be absent, there may be evidence of endocrine abnormalities (gynaecomastia or abnormal hair distribution) or there may be a varicocele.

The partner should also be assessed. It is important to remember that female fertility declines earlier and at a faster rate than male fertility after the age of 35. The age of the woman is therefore important.

The assessment of the man includes semen analysis, which should be tested within 1 hour of the semen being produced. If abnormal, a second sample should be tested. The volume of the ejaculate, the number of sperm, their motility and the percentage of morphologically abnormal or dead sperm are all predictive of male fertility. An endocrine screen should be performed, including serum testosterone, prolactin, folliclestimulating hormone (FSH) and luteinising hormone (LH). In obstructive cases, the FSH is typically normal.

An ultrasound of the scrotum is recommended to exclude testicular lesions, varicoceles and signs of obstruction (dilated rete testis, absent vasa). For patients with a low seminal volume and in whom distal obstruction is suspected, transrectal ultrasound or MRI is essential to assess the genital tract.

Infections of the male urogenital tract are potentially curable causes of male infertility; if there is a history suggestive of this, semen and urine cultures should be done. Bilateral epididymitis can result in obstructive infertility.

The incidence of chromosomal abnormalities in infertile men is between 6% and 10% and testing for karyotype anomalies, Y chromosome microdeletions and cystic fibrosis gene mutations is performed depending on the degree of oligozoospermia and clinical examination.

Treatment

Sperm counts of less than 15 million sperm per millilitre are defined as oligozoospermia. If there is a reversible cause, it should be treated. However, in many cases, some form of assisted conception is required.

Azoospermia (the complete absence of sperm in the ejaculate) is either due to obstruction of the pathway of spermatozoa from the testis to the ejaculatory ducts or due to severe testicular failure. For non-obstructive azoospermia, surgical sperm retrieval is indicated, of which microsurgical testicular sperm extraction (micro-TESE) is the gold standard procedure, with a success rate of 50% (Figure S86.4). A testicular biopsy is performed during the harvest to establish histological characteristics (the only predictor of finding viable sperm) and Johnsen score.

Figure S86.4

The microdissection testicular sperm extraction (micro- TESE) procedure. Visible tubules are biopsied with a micro-forceps to look for sperm (courtesy of the author and Dr Mohamed Abdellatif).

For obstructive azoospermia, reconstruction (vasovasostomy/vasoepidymovasostomy) may be possible if the site of the obstruction can be identified. Occasionally a midline prostatic cyst that is obstructing the ejaculatory ducts can be deroofed. An alternative to reconstruction would be surgical sperm retrieval, which may be preferable if the female partner is older as the return of sperm to the ejaculate may take longer than 6–12 months.

Assisted conception, including in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), and advanced sperm retrieval techniques, such as micro-TESE, have changed the management of male factor infertility. In ICSI, spermatozoa harvested from the ejaculate or by surgical sperm retrieval in azoospermic men can be injected in vitro into ova obtained from the mother. The embryo is then transferred into the mother’s uterus at the 100- to 125-cell stage, when it is known as a blastocyst.

Vasectomy

Vasectomy for sterilisation is a common and effective contraceptive procedure. It should be undertaken only after the couple has been carefully counselled. Both partners need to know that the operation is performed to make the man permanently sterile. They should be warned that normal contraceptive precautions should continue until the success of the operation is confirmed by semen analysis performed 12–16 weeks after surgery after 20 ejaculations. They should also be warned of the possibility of spontaneous recanalisation (1:2000), which may restore fertility unexpectedly, and of the possibility of chronic testicular pain, which may occur in up to 5% of men. Vasectomy is easily and painlessly performed under local or general anaesthetic. The vasa are delivered through tiny bilateral scrotal incisions or through a single midline scrotal incision. For medicolegal reasons it is wise to remove a segment of each vas to prove that it has been successfully divided. Ligation, diathermy and burying the cut ends with fascial interposition helps to prevent them rejoining.

Acute postprocedure pain usually resolves after about 4 weeks. Postvasectomy pain syndrome is defined as at least 3 months of chronic scrotal pain after surgery, with theories of its causation ranging from damage to the scrotal and spermatic cord nerve structures via inflammatory effects of the immune system, back pressure effects in the obstructed vas and epididymis, vascular stasis, nerve impingement or perineural fibrosis. Therapeutic options include antibiotics if signs of infection are present; analgesia, including neuropathic pain medication; chronic pain strategies such as spermatic cord blocks and surgery, including excision of sperm granuloma; microdenervation of the spermatic cord; epididymectomy; orchidectomy; or vasectomy reversal.

Reversal of vasectomy may not restore fertility even if the surgery is technically successful because of damage to the testis secondary to the vasectomy. Although patency rates of 80% or more are commonly reported at short durations (<10 years) post vasectomy, successful fertility rates are much lower and diminish with increasing delay from the time of vasectomy.