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Urology > Male Infertility
Sertoli-Cell-Only Syndrome
Article Last Updated: Feb 1, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Edward David Kim, MD, FACS, Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center
Edward David Kim is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, and Tennessee Medical Association
Coauthor(s):
Joe D Mobley III, MD, MPH, Resident Physician, Department of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine/University of Tennessee Medical Center
Editors: Erik T Goluboff, MD, Assistant Professor, Program Director, Department of Urology, Columbia-Presbyterian Medical Center, Columbia University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; J Stuart Wolf, Jr, MD, FACS, David A Bloom Professor of Urology, Director, Division of Minimally Invasive Urology, Department of Urology, University of Michigan Medical Center; Stephen W Leslie, MD, FACS, Founder and Medical Director of the Lorain Kidney Stone Research Center, Clinical Assistant Professor, Department of Urology, Medical College of Ohio
Author and Editor Disclosure
Synonyms and related keywords:
Sertoli-cell-only syndrome, germinal cell aplasia, SCO, infertility, azoospermatism, azoospermic, Klinefelter syndrome, azoospermia, spermatogenic failure, spermatogenic obstruction
Background
Sertoli-cell-only (SCO) syndrome, also called germ cell aplasia, describes a condition of the testes in which only Sertoli cells line the seminiferous tubules. Typically, these men present between age 20-40 years for evaluation of infertility and are found to be azoospermic, a term describing the absence of sperm in the ejaculate. Physical examination is often unremarkable, and the diagnosis is made based on testicular biopsy findings. While investigation to identify a cause of SCO syndrome is ongoing, the etiology and mechanism of this process are currently unknown. No known effective treatment exists.
Pathophysiology
SCO syndrome is a condition of the testes. Involvement of other organ systems is rare but is secondary to the underlying condition causing SCO syndrome. As an example, Klinefelter syndrome is characterized by SCO and Leydig cell hyperplasia.
Frequency
United States
The prevalence of SCO syndrome in the overall population is extremely low. Approximately 10% of US couples are affected by infertility. Of these couples, approximately 30% have a pure male factor as the underlying cause, and another 20% have a combined male and female factor. Although precise figures are difficult to obtain, less than 5-10% of these infertile men have SCO syndrome.
Mortality/Morbidity
SCO syndrome presents during the evaluation of azoospermia in couples having difficulty in initiating a pregnancy. These men typically present with infertility as the only symptom.
Race
No known racial predilection for SCO exists; however, SCO presents more frequently in white men. In most series, most couples who present for evaluation of male infertility are white.
Sex
SCO syndrome affects only phenotypic men.
Age
The most common age of presentation is from 20-40 years. These age groups represent men who are trying to initiate a pregnancy.
History
- The most common presentation is a young man seeking evaluation for infertility.
- His semen analysis has demonstrated azoospermia, the absence of sperm.
- Azoospermia may be due to spermatogenic failure or obstruction. Examples of causes of spermatogenic failure include genetic, hormonal, idiopathic, toxin exposure, history of radiation therapy, and history of severe trauma. These conditions may be associated with Sertoli-cell-only (SCO) syndrome. Obstruction would not be associated with SCO.
- Less commonly, these men may have severely decreased sperm densities of less than 1 million sperm per mL. In this latter situation, the testes have foci of SCO and hypospermatogenesis.
- SCO is diagnosed with testicular biopsy.
- Sperm production may be patchy and heterogenous within and between the testes.
- In its purest sense, SCO must present as azoospermia; however, a minority of men may have foci of spermatogenesis in a testis that is predominantly SCO.
Physical
- The testes are usually small to normal in size, with a normal shape and consistency.
- The testes also may present with more marked atrophy.
- Patients exhibit normal virilization without gynecomastia.
- The remainder of the physical examination findings are typically unrevealing.
Causes
- Most causes are idiopathic. A congenital absence of germ cells due to failure of migration of gonocytes is theoretically possible.
- In the future, genetic causes likely will be identified. Y chromosome microdeletions are occasionally identified as a cause of SCO.
- Exposure to chemicals and toxins may cause SCO; however, direct cause-and-effect relationships in humans have been difficult to document.
- Klinefelter syndrome, 47 XXY, has a characteristic biopsy appearance of SCO and Leydig cell hyperplasia.
- Attempting to distinguish between primary (congenital) and secondary (acquired) SCO syndrome is of no prognostic significance.
Other Problems to be Considered
Leydig cell hyperplasia
Azoospermia
Klinefelter syndrome
End-stage testis failure
Hypospermatogenesis
Maturation arrest
Lab Studies
- Men undergoing evaluation for infertility typically undergo hormonal evaluation with follicle-stimulating hormone (FSH) and testosterone. Luteinizing hormone (LH) and prolactin testing are not routinely necessary. In addition, routine testing for male infertility includes several semen analyses.
- Plasma testosterone levels are typically normal.
- Azoospermia and an elevated serum FSH level (>2-3 times reference range) indicate spermatogenic failure.
- Azoospermia and a serum FSH level within the reference range suggest possible spermatogenic failure or an obstruction.
- The serum FSH level is typically (90%) elevated. Elevations of greater than 2.5-3 0 times the reference range are diagnostic for spermatogenic failure.
- Findings on testicular biopsy may include severe hypospermatogenesis, maturation arrest-spermatid stage, maturation arrest-spermatocyte stage, or Sertoli-cell-only (SCO) syndrome.
- If a couple is considering intracytoplasmic sperm injection (ICSI), a micromanipulation technique in which a single sperm is injected into an oocyte, they should be offered genetic testing with a Y chromosome microdeletion assay and karyotyping.
Imaging Studies
- Imaging studies are not indicated.
Other Tests
- Azoospermia should be documented with a semen pellet analysis. The semen pellet is performed by centrifuging a grossly azoospermic semen specimen for 10 minutes at 1500-2000 rpm. This pellet is considered standard for the diagnosis of azoospermia. The pellet at the bottom of the conical tube is examined under a microscope at a magnification of 400. If sperm are identified, then patchy spermatogenesis within the testes is present.
Procedures
- The testis biopsy is the criterion standard for diagnosis of SCO. Most urologists are familiar with the open biopsy technique.
- This technique may be performed with a local cord block for most men.
- Alternatively, a general anesthetic may be used.
- A small biopsy sample is taken from the surface of the testis and placed in Bouin's fixative.
- Men may be offered a testis biopsy to define whether an obstruction or spermatogenic failure is present. If the serum FSH level is greater than 2.5-3 times the reference range and intracytoplasmic sperm injection (ICSI) is not a consideration, the biopsy findings would not change the management plan. If the couple is considering ICSI, a diagnostic biopsy may be helpful to provide counseling regarding the possibility of finding sperm at the time of ICSI. If spermatogenic failure is predominant and rare sperm are identified, testicular extraction of sperm with ICSI may be possible at a later time. At the time of testis biopsy, a specimen may be cryopreserved for potential use of any sperm at a later time.
- Some investigators discuss the use of fine-needle aspiration cytology (FNAC) prior to biopsy as a less invasive means of establishing a diagnosis. In addition, this technique can offer prognostic information regarding the likelihood of successful testicular sperm extraction (TESE).
Histologic Findings
Germinal cell aplasia (SCO syndrome) is histologically characterized by seminiferous tubules that contain only Sertoli cells, with a complete absence of all germ cells. In most cases, the tunica propria and basement membranes are not thickened appreciably, and the tubules are normal or slightly decreased in diameter. The interstitium contains normal numbers of Leydig cells. One may observe a patient with an otherwise classic example of germinal cell aplasia who has an occasional tubule with some degree of spermatogenesis. Levin has classified this as germinal cell aplasia and focal spermatogenesis.
Medical Care
No effective medical therapy exists.
Surgical Care
- Testicular sperm extraction (TESE) may be offered to the couple considering in vitro fertilization (IVF)/ICSI.
- At specialty centers, as many as 20-40% of men with Sertoli-cell-only (SCO) may have isolated foci of spermatogenesis within the testis; however, the option of using donor sperm must be discussed with the couple. At most centers, sperm recovery rates are much lower.
- TESE is a testis biopsy performed with the intent of finding mature sperm within the seminiferous tubules. Multiple and extensive biopsies are typically required when SCO is present. Because spermatogenesis may be patchy within the testis, occasional pockets of isolated sperm production may be identified, even when the predominant histopathology is SCO syndrome.
- Microsurgical TESE may be performed at some specialty centers, offering improved chances of successful sperm extraction with decreased risk and morbidity.
- In patients with SCO syndrome with pockets of sperm production, repair of a concurrent varicocele can increase the chances of subsequent successful surgical retrieval of sperm.
Consultations
If the couple is considering IVF/ICSI, consultation with a reproductive endocrinologist is necessary.
No known effective medical therapies exist.
Deterrence/Prevention
- Avoidance of known gonadotoxins, such as chemotherapy and radiation therapy, is recommended for men with known fertility.
Prognosis
- Sertoli-cell-only (SCO) syndrome remains a stable condition with no appreciable improvement in prognosis or sperm production.
- Investigations that have been recently completed suggest that the prevalence of testicular nodules and cancer in patients with SCO syndrome is greater than that of the baseline. Initial reports show a 26% risk of nodules and a 10.5% risk of malignancy in testicles of men with pure SCO syndrome. Further studies would be helpful to support this initial report.
Patient Education
Couples who wish to raise children and are faced with a diagnosis of SCO have the following options: - Adoption: Adoption is an effective option; however, couples must understand that adoption can be a lengthy and costly process.
- Use of donor sperm with intrauterine insemination: Donor sperm may be used for intrauterine insemination. Donor sperm may be obtained locally or nationally through sperm banks.
- Attempt at TESE with IVF/ICSI: Although sperm may be successfully extracted from small pockets of spermatogenesis in up to 20-40% of men with a diagnosis of SCO syndrome, the use of these sperm for IVF/ICSI is successful in only a small percentage of patients and thus should not be offered as a standard of care.
Medical/Legal Pitfalls
- Failure to diagnose Sertoli-cell-only SCO syndrome
| Media file 1:
This hematoxylin and eosin section of a testis biopsy (400X) demonstrates an individual tubule lined only with Sertoli cells (Sertoli-cell-only [SCO] syndrome). The Sertoli cells line the seminiferous tubule. |
 |  View Full Size Image | |
Media type: Image
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Sertoli-Cell-Only Syndrome excerpt Article Last Updated: Feb 1, 2007
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