Sertoli cell-only syndrome

Overview

Sertoli cell-only syndrome (SCOS), also known as Del Castillo syndrome, is a rare condition characterized by the complete absence of germ cells in the seminiferous tubules of the testes, leading to male infertility. Despite having a normal male karyotype (46,XY) and secondary sexual characteristics, affected individuals produce no sperm due to a lack of developing germ cells. The seminiferous tubules contain only Sertoli cells, which are responsible for nurturing and supporting germ cell development. SCOS is one of the causes of non-obstructive azoospermia, where no sperm are present in the ejaculate due to a production defect rather than a blockage.

Causes

The exact cause of Sertoli cell-only syndrome is not always identifiable, but it is believed to result from a combination of genetic, developmental, and environmental factors. Potential causes include:

• Genetic abnormalities: Microdeletions in the Y chromosome, particularly in the AZF (azoospermia factor) region, are commonly associated with SCOS

• Klinefelter syndrome mosaicism: Some patients may have mosaic forms of 47,XXY/46,XY

• Congenital developmental defects: Disruption in testicular development during fetal life

• Environmental exposures: Radiation, chemotherapy, toxins, or viral infections such as mumps orchitis during childhood

• Idiopathic: In many cases, no clear cause is identified

Symptoms

Sertoli cell-only syndrome often presents without any obvious physical symptoms and is usually discovered during an evaluation for infertility. However, some features may include:

• Primary infertility: Inability to conceive after 12 months of unprotected intercourse

• Azoospermia: Complete absence of sperm in the semen

• Normal male phenotype: Typical male external genitalia and secondary sexual characteristics

• Normal or small testicular volume: Testes may be slightly smaller in some men

In most cases, libido and erectile function are unaffected, and testosterone levels may be within the normal range, although mild hypogonadism can occur in some individuals.

Diagnosis

Diagnosis of Sertoli cell-only syndrome involves a thorough clinical evaluation, laboratory tests, imaging, and sometimes surgical biopsy. The key diagnostic steps include:

• Semen analysis: Repeated tests show azoospermia (no sperm in ejaculate)

• Hormonal profile: May show elevated follicle-stimulating hormone (FSH) due to lack of feedback from spermatogenesis; luteinizing hormone (LH) and testosterone may be normal or slightly altered

• Scrotal ultrasound: May reveal normal or reduced testicular volume; used to rule out structural abnormalities

• Genetic testing: Karyotyping and Y-chromosome microdeletion analysis, particularly for AZF regions (AZFa, AZFb, AZFc)

• Testicular biopsy: Confirms diagnosis by showing seminiferous tubules containing only Sertoli cells and no germ cells

A biopsy may also be done as part of a sperm retrieval procedure in fertility treatment.

Treatment

There is no curative treatment for Sertoli cell-only syndrome, but several options may help affected individuals manage their fertility and hormonal health.

Fertility Options:

• Testicular sperm extraction (TESE): In some rare focal cases, small areas of sperm production may exist; sperm retrieved can be used for intracytoplasmic sperm injection (ICSI) in assisted reproductive techniques

• Donor sperm: An option for achieving pregnancy when no sperm can be found

• Adoption or surrogacy: Alternative family-building options

Hormonal Management:

• In cases with low testosterone, hormone replacement therapy (HRT) may be prescribed

• Monitoring for bone density and other complications of hypogonadism if testosterone is deficient

Psychological Support:

• Counseling and support groups for men dealing with infertility

• Couples therapy may help partners cope with the emotional impact of infertility

Prognosis

The prognosis for general health in Sertoli cell-only syndrome is usually good, as it does not typically affect lifespan or cause systemic disease. However, the condition poses significant reproductive challenges.

Fertility prognosis depends on whether focal spermatogenesis is present. In rare cases where viable sperm are found through TESE, assisted reproductive techniques may result in biological children. For the majority of patients, biological fatherhood is not possible, and alternative reproductive methods are required.

With appropriate counseling and support, individuals with SCOS can lead healthy and fulfilling lives. Advances in genetic research and reproductive technologies continue to improve outcomes and understanding of this rare condition.