Sertoli-Cell-Only Syndrome

Continuing Education Activity

Sertoli cell-only syndrome, also known as del Castillo syndrome or germ cell aplasia, typically occurs in males between the age of 20 and 40. In this syndrome, only Sertoli cells line the seminiferous tubules of the testis, and the patients have very low or absent spermatogenesis. These patients are typically normal on physical examination as this condition presents with infertility without sexual abnormality. Diagnosis is usually made based on testicular biopsy findings. Patients can still reproduce with assisted reproductive technology. This activity describes the diagnosis and treatment of Sertoli cell-only syndrome and highlights the role of the interprofessional team in the management of these patients.


  • Outline the cause of Sertoli cell only syndrome.
  • Describe the presentation of Sertoli cell only syndrome.
  • Summarize the treatment options for Sertoli cell only syndrome.
  • Review the importance of improving care coordination among the interprofessional team members to improve outcomes for patients affected by Sertoli cell only syndrome.


Sertoli cell-only syndrome (SCO) is also known as Del Castillo syndrome and germ cell aplasia. Sertoli cells are found in the convoluted seminiferous tubules and form part of the blood-testis barrier in males. They also play an important role in spermatogenesis which is sperm production. The cells respond to a hormone called follicle-stimulating hormone (FSH) that is released by the hypothalamus.[1] Patients with Sertoli cell-only syndrome are typically males between ages 20 to 40. In Sertoli cell-only syndrome, only Sertoli cells line the seminiferous tubules of the testis, and the patients have very low or absent spermatogenesis. These patients are typically normal on physical examination as this condition presents with infertility without sexual abnormality. Diagnosis is usually made based on testicular biopsy findings. Most cases are multifactorial and idiopathic. Patients can still reproduce with assisted reproductive technology.


Sertoli cells have multiple vital reproductive functions in males. They play an essential role in the proper growth and development of spermatogonia by secreting substances required for their growth and nourishment. Sertoli cells also secrete the anti-Mullerian hormone, AMH, that leads to the regression of Mullerian ducts in a male fetus. This hormone prevents the development of any internal female reproductive organs during the early stages of embryogenesis in a male fetus.

Sertoli cells also secrete inhibin-B which provides the down-regulatory effect of follicle-stimulating hormone secretion on the hypothalamus. Activin is another product secreted by Sertoli cells. It provides positive feedback on the hypothalamus for spermatogenesis and leads to a higher FSH level.


There are no exact figures for the prevalence of this condition, but it is estimated that less than 5% to 10% of infertile men may be having Sertoli cell-only syndrome. They present with only infertility. While there is no racial predilection, it is slightly more common in Caucasian males. The most commonly affected age group involves adults of 20 to 40 years old.


Sertoli cell-only syndrome most likely is a multifactorial and idiopathic condition. The diagnosis is often made when young male patients come for an evaluation for infertility. They present with reduced or absent spermatogenesis and usually have a normal physical examination.

Multiple possible pathways may be involved in the pathogenesis of this condition. Researchers hypothesize that congenital absence of germ cells can result from proper failure of migration of gonocytes. The Yq11 region is also known as the azoospermia factor region (AZF region). Microdeletions in the Yq11 region of the Y chromosome, especially in the AZFb/b+c region, have been found in some patients with SCO syndrome and is another possible cause of the disease. Deletions between palindromes P5 and P1 and between P4 and P1 have also been reported. Yang et al. also hypothesized that two deletions in the interval region between P4 and P3 might also be involved in the pathophysiology of the condition. Apoptotic elimination and altered maturation of germ cells through mutations of Fas, FasL, and active caspase-3 have also been reported recently in the literature.[2][3][4][5]

The patients present with normal levels of luteinizing hormone (LH) and testosterone. The low level of inhibin-B leads to a higher than normal level of follicle-stimulating hormone (FSH). A study conducted by Stouffs et al. showed that in Caucasian males with SCO syndrome, karyotype abnormalities, such as Klinefelter syndrome, were the most common abnormality seen.[6]

The pathophysiology of the disease can be summarized as follows:

  • Mostly idiopathic
  • Genetic as discussed above
  • Toxin exposure leading to lower spermatogenesis
  • Radiation exposure to the testicular region
  • History of trauma leading to decreased sperm cell production
  • Viral infection


According to Nistal et al., histology of biopsies can vary. They can appear as normal mature cells, while others might present as involuting, immature, or dysgenetic. The shapes of the cell and nucleus as well as changes in the cytoplasm are helpful for categorizing them.[7]

History and Physical

The patients are typically young males, aged 20 to 40, who come for an infertility evaluation. The testes can be normal or smaller in size. They have a normal consistency and shape. Some patients have been reported to show atrophy of the testes. On physical examination, no gynecomastia is seen, and patients present with normal virilization. No other physical abnormalities are usually reported.


Most patients with Sertoli cell-only syndrome are further evaluated by conducting a semen analysis. Azoospermia, which refers to the absence of sperm, is often seen in such patients. A very small percentage of patients may still have a low detectable level of sperm.

Treatment / Management

At present, there is no treatment for Sertoli cell-only syndrome (SCO). However, for some cases, patients with very low sperm counts can still be considered for testicular sperm extraction (TESE). TESE allows removal of the sperm from the patient's testes and the sperm can be used to fertilize an egg via intracytoplasmic sperm injection (ICSI). Some studies have shown that the recovery is better with higher FSH levels in the blood.[8][9]

The rate of successfully retrieving the sperm varies. Multiple factors such as the presence of sperm cells can influence the outcome of TESE and ICSI. Some studies have even suggested that only 13% of patients with Sertoli cell-only syndrome successfully managed to have a child via these procedures.[10]

Couples are also advised to undergo genetic testing to confirm if the children could also be at risk of the condition.

Differential Diagnosis

It is vital to properly rule out other conditions that may present with a low sperm count. Some of the differentials to consider are:

  • Azoospermia 
  • Leydig cell hyperplasia
  • Klinefelter syndrome 
  • End-stage testis failure 
  • Hypospermatogenesis 


The prognosis of the patients in terms of fertility varies and in some cases assisted reproductive technology can help with reproduction.


Patients should have proper follow-ups with their physicians. It is also strongly advised to avoid any gonadotoxins, such as chemotherapy, in order to preserve any remaining fertility.

Pearls and Other Issues

Sertoli cell-only (SCO) syndrome is a most often a multifactorial and idiopathic condition that leads to germ cells aplasia. Patients are sexually normal but have impaired spermatogenesis. Sperm analysis will usually show azoospermia. There are various techniques available to help patients who have some levels of sperms reproduce. The success rate, however, varies.

Enhancing Healthcare Team Outcomes

Sertoli cell only syndrome is best managed by an interprofessional team including nurses and pharmacists. While the diagnosis is not difficult the treatment is unsatisfactory for couples who want to conceive.

At present, there is no treatment for Sertoli cell-only syndrome (SCO). However, in some cases, patients with very low sperm counts can still be considered for testicular sperm extraction (TESE). TESE allows removal of the sperm from the patient's testes and the sperm can be used to fertilize an egg via intracytoplasmic sperm injection (ICSI). Some studies have shown that the recovery is better with higher FSH levels in the blood. However, patients need to be told that these procedures are prohibitively expensive and do not guarantee fertility.

Only about 10% of couples go on to conceive.

Article Details

Article Author

Kamleshun Ramphul

Article Editor:

Stephanie Mejias


3/7/2021 1:53:36 AM



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