What is Sertoli Cell-Only Syndrome

In Sertoli Cell-Only Syndrome (SCOS), males have normal secondary sexual features and genetic characteristics (karyotype) but still suffer from infertility due to oligozoospermia or azoospermia. SCOS falls into one of the two categories. The pure form of SCOS has no sperms. In the secondary form, laboratory tests may sometimes be able to detect some sperm.

Sertoli Cells and Spermatogenesis

Sperm cells develop in a process called spermatogenesis in the testes. Seminiferous tubules are the site of development of the human sperm that lasts two-and-a-half months. Cells begin by dividing to form two replicas (mitosis). Then each cell divides two times to make four copies but with only half of the genetic material or a single set of chromosomes (meiosis). Cells mature to form spermatocytes leading to mature spermatozoa.

Sertoli cells are present in the walls of the seminiferous tubules and provide nutrition from nearby capillaries to the sperm to help it grow and mature. Their tight packaging also creates the blood-testis barrier to shield the developing sperm from the blood. They also produce testicular fluid that binds to testosterone and concentrates it to promote the development of the sperm.

Causes and Symptoms of Sertoli Cell-Only Syndrome

Medical and scientific professionals speculate several causes of SCOS: genetic deletions, chemotherapy, exposure to toxins, a viral infection of the testicles, or exposure to radiation. These factors may lead to abnormal function of the Sertoli cells.
In Sertoli Cell-Only syndrome, the Sertoli cells exclusively line the seminiferous tubules. No sperm cells are present, leading to male infertility. SCOS is diagnosed between the ages of 20 and 40 years, when symptoms of azoospermia (no sperm production) surface. In some cases, Klinefelter syndrome (extra X chromosome in men) coexists with SCOS.
Most cases of SCOS happen because of genetic deletions on the long arm of the Y-chromosome. As a result, clinicians generally assume the cause of SCOS as non-obstructive azoospermia (NOA).
Genetic research studies have also indicated that several conditions occur in parallel with SCOS. Klinefelter syndrome, with up to seven Yq microdeletions, especially in the azoospermia factor (AZF) region, occurs in conjunction with SCOS. Further, varicocele (enlarged veins in the skin holding the testicles) or cryptorchidism (failure of the testes to descend into the scrotum) increases the risk of infertility in SCOS.
Another characteristic of SCOS is alteration in hormone levels. In affected males, although testosterone levels are normal, Sertoli cells secrete lower than normal levels of anti-Mullerian hormone (AMH) and inhibin B hormones. AMH is a protein that contributes to the development of the internal male reproductive organs, and Inhibin B participates in spermatogenesis.

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Risk Factors, Diagnosis, and Treatment for SCOS

The primary method to confirm SCOS is the diagnostic testicular biopsy (DTB). In general, testicular aspiration is the clinical standard for the diagnosis of azoospermia and oligospermia. Besides detecting azoospermia, a biopsy of the testicles is a common method to confirm no production of sperm. It is also important to undergo cancer screening (ultrasound or MRI) as SCOS raises the risk of developing testicular cancer.
Infertility due to SCOS is difficult to treat using artificial/ assisted reproduction techniques (ART) as no sperms are available for extraction. In some males, it may be possible to obtain sperm through testicular sperm extractions (TESE) and introduce sperms directly into the oocyte through intracytoplasmic sperm injection (ICSI). However, this raises the risk of fertility issues in subsequent generations. The combination of TESE-ICSI is promising for men with non-obstructive azoospermia but with 37% of the couples being able to eventually have a child. Other alternatives for couples trying to conceive include the adoption of a child or insemination of donor sperm.
Although men with SCOS face risks and infertility concerns, they can still father a child using the latest artificial insemination technologies. Counseling with a fertility expert is recommended to make a joint decision about the best option available.