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Sertoli Cell–Only Syndrome
Introduction
About 15% of all couples have some degree of infertility, with the male partner solely responsible about 30% of the time. Geographically, West Africa and East Asia have the highest incidence of infertility cases. In infertile men, about 10% to 15% will demonstrate azoospermia or the complete absence of any sperm in the semen.[1]
Azoospermia is generally categorized as either obstructive (due to scarring or surgery of the vas or epididymis) or non-obstructive. Non-obstructive azoospermia can be from Sertoli cell-only syndrome, early or late maturation arrest, or hypospermatogenesis.[2] Sertoli cell-only syndrome is the most common of these, closely followed by maturation arrest.[3]
Sertoli cell-only syndrome 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 play a critical role in spermatogenesis and sperm production. The cells respond to follicle-stimulating hormone (FSH) produced by the anterior pituitary as a response to stimulation by the pulsatile release of GnRH by the hypothalamus.[4] Patients with Sertoli cell-only syndrome are typically males between the ages of 20 to 40 years.
In Sertoli cell-only syndrome, only Sertoli cells line the seminiferous tubules of the testis, and the patients have extremely low or absent spermatogenesis. Some patients may only have focal disease, which would leave some areas of the testis capable of normal spermatogenesis.[1][5][6] These patients are typically normal on physical examination as this condition presents with infertility without sexual abnormality. The definitive diagnosis is usually only made based on testicular biopsy findings. Most cases are multifactorial and idiopathic. Many patients can still reproduce with assisted reproductive techniques.[7]
Etiology
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Etiology
Sertoli cell-only syndrome does not have a specific, exact, identified etiology, but various causes have been proposed. These include microdeletions on the Y-chromosome (particularly in the azoospermia factor (AZF) region), chemical or toxin exposure, radiation therapy, or severe testicular trauma. Recent data suggests a Y-chromosomal CDY1 deletion in Sertoli cell-only syndrome, and analysis of DAZ and CDY1 genes by reverse transcription-polymerase chain reaction (RT-PCR) testing may ultimately help predict this condition and evaluate the potential for finding any mature spermatozoa for assisted reproduction.[8] Microdeletions within the AZF region are most closely associated with Sertoli cell-only syndrome and germ cell maturational arrest.
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, which leads to the regression of the Mullerian ducts in a male fetus.[9] Anti-Mullerian hormone prevents the development of any internal female reproductive organs during the early stages of embryogenesis in a male fetus.[9]
Sertoli cells also secrete inhibin-B, which provides the down-regulatory effect of follicle-stimulating hormone secretion on the hypothalamus.[4]
Activin is another product secreted by Sertoli cells. It provides positive feedback on the hypothalamus for spermatogenesis and leads to a higher FSH level.[4]
The exact cause of most cases of Sertoli cell-only syndrome is unknown, but various etiologies have been proposed. These include microdeletions on the Y-chromosome (particularly in the azoospermia factor (AZF) region), chemical or toxin exposure, radiation therapy, or severe testicular trauma. Recent data suggests a Y-chromosomal CDY1 deletion in Sertoli cell-only syndrome and that an analysis of DAZ and CDY1 genes by reverse transcription-polymerase chain reaction (RT-PCR) may ultimately help predict this condition and the potential for finding any mature spermatozoa for assisted reproduction.[8] Microdeletions within the AZF region are most closely associated with Sertoli cell-only syndrome and germ cell maturational arrest.
Sertoli cells in Sertoli cell-only syndrome express different microRNA than these cells in obstructive azoospermia, suggesting they may play some role in the syndrome's pathogenesis.[10]
Ovol1 and Ovol2 are zinc-finger transcription factors found in spermatogenesis at the third stage of meiosis in male germ cells. Using RT-PCR techniques, researchers have found that these factors were not detectable in the testes of patients with Sertoli cell-only syndrome but were found in other men capable of spermatogenesis.[11] This finding opens the door to a possible future therapy for this condition.
Klinefelters syndrome is classically associated histologically with Sertoli cell-only syndrome and Leydig cell hyperplasia.[12]
A case of Sertoli cell-only syndrome associated with a varicocele has also been reported.[13]
Epidemiology
While there are no exact figures for the prevalence of this condition, it is estimated that about 5% to 10% or less of all infertile men may have Sertoli cell-only syndrome.[14] The only presenting symptom is male infertility, specifically azoospermia.
While there is no racial predilection, it appears to be slightly more common in Caucasian males. The most commonly affected age group involves adults 20 to 40 years of age.
Pathophysiology
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 of 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 on the long arm of the Y chromosome is also known as the azoospermia factor region (AZF region). Microdeletions in the Yq11 area of the Y chromosome, especially in the AZFc region, have been found in patients with Sertoli cell-only syndrome. In infertile men with AZFc microdeletions, Sertoli cell-only syndrome will be found histologically in 46%, maturation arrest will be seen in 38.2%, and hypospermatogenesis will be present in 15.7%.[3]
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.[15][16][17][18]
The patients present with normal levels of luteinizing hormone (LH) and testosterone. A low level of inhibin-B may lead to a higher than normal level of follicle-stimulating hormone (FSH).
A study by Stouffs et al. showed that in White-race males with Sertoli cell-only syndrome, karyotype abnormalities (such as Klinefelter syndrome) were the most common genetic disorders.[12]
The pathophysiology of the disease can be summarized as follows:
- Mostly idiopathic
- Genetic due to Y chromosomal microdeletions primarily in the AZF region
- Toxin exposure that leads to lower spermatogenesis
- Radiation exposure to the testicular region
- History of trauma leading to decreased sperm cell production
- Viral infection
Histopathology
Histological examination of a testis biopsy is the definitive method of diagnosis.
In Sertoli cell-only syndrome, all seminiferous tubules are lined exclusively with Sertoli cells. No germ cells are present, although there may be focal areas of normal, preserved spermatogenesis somewhere in the testis.[6] Compared to obstructive azoospermia, patients with Sertoli cell-only syndrome have thicker basement membranes with narrower lumens.[19] Extracellular matrix (laminin) is also increased, possibly due to inhibited spermatogenesis.[19] There is also a significant decrease of seminal laminin in Sertoli cell-only syndrome, which has been suggested as a possible screening test.[19]
There are two histological types of Sertoli cell-only syndrome; primary and secondary.[1][20][21]
Primary or pure Sertoli cell-only syndrome is generally thought to arise from a disorder of gonocyte migration that fails to reach the gonads. This causes uniform or primary Sertoli cell-only syndrome with no focal spermatogenesis.[1][6][20][22] Seminiferous tubular lumen size is smaller than normal, but the walls are not thickened. Only small amounts of Sertoli cell cytoplasmic lipids are seen.[6]
Secondary Sertoli cell-only syndrome is thought to occur following some insult to otherwise healthy testes, which may not affect all of the seminiferous tissue sparing some focal areas.[6][22] While the tubular lumen is small, the walls are markedly thickened with hyalinization, peritubular fibrosis, and irregular widening of the inner collagen layer. Reabsorption of degenerated germ cells causes increased lipid granules in the cytoplasm of the Sertoli cells, and some tubules may show germ cells.[1][6][20][22] The thickened seminiferous tubular wall may impair the normal Sertoli cell effect on tubular interstitial tissue and hormonal permeability that could affect inhibin B and FSH levels.[21]
Four different types of Sertoli cells have been described.[22] Sertoli cell-specific maturation markers can be used for cellular differentiation, but light and electron microscopy are used more frequently.[22][23][24]
Histological differentiation of Sertoli cells can generally be done according to these criteria:
- Normal mature cells which typically demonstrate a vaguely triangular shape and a prominent nucleolus
- Immature cells with round nuclei but immature cytoplasm
- Dysgenetic cells with immature nuclei
- Involuted cells with irregular nuclei[22]
History and Physical
The patients are typically young males aged 20 to 40 who present for an infertility evaluation. The testes can be normal or slightly smaller in size and have a normal consistency and shape, although some patients have been reported to show some testicular atrophy. There may be a history of male infertility.
On physical examination, no gynecomastia is seen, and patients present with normal virilization. Secondary sexual characteristics are normal, as is the time of puberty and hair pattern. No other physical abnormalities are usually reported.
Evaluation
Most patients who ultimately are found to have Sertoli cell-only syndrome are initially evaluated by conducting two separate semen analyses. Azoospermia, which refers to the complete absence of sperm in the semen, is often seen in such patients. A small percentage of patients may still have a low detectable level of sperm (severe hypospermatogenesis and oligospermia).
Most patients with Sertoli cell-only syndrome (up to 90%) will have elevated FSH levels, usually two to three times normal. (Such high readings typically indicate a severe failure of spermatogenesis.) Testosterone levels are usually normal.
The definitive test for non-obstructive azoospermia and diagnosing Sertoli cell-only syndrome is the testis biopsy.
FSH levels are routinely checked in infertile men. A study of 125 men with abnormal spermatogenesis and spermatogenic dysfunction suggested that these findings can be reliably predicted (89%) by finding elevated FSH levels over 7.6 IU/L and small testicles with a long axis of no more than 4.6 cm.[25] Higher FSH levels (22.9 IU/L vs. 13.3IU/L) and smaller testicular volumes (13.3 cc vs. 10.4 cc) have sometimes been associated with more severe spermatogenic dysfunction.[26] Favorable readings in this study were associated with an overall 91.7% successful sperm retrieval rate, while unfavorable measurements had only 56% success.[26]
However, the predictive value of FSH levels is highly controversial, with several studies indicating that FSH is not a reliable predictor, while others suggest that high FSH levels were more likely to be associated with sperm retrieval failure. The consensus suggests that higher FSH levels overall tend to be associated with slightly higher sperm retrieval rates, but the data is too conflicting and inconsistent to make any conclusive recommendations.[1] Therefore, at this time, the role of FSH in predicting successful sperm retrieval rates with microscopic testicular sperm extraction (micro-TESE) remains unclear.[1][27][28]
Routine genetic testing yields a diagnosis in about 20% of cases.[29]
Recently, testicular volume apparent diffusion coefficient (ADC) histogram analysis has been used to help predict the presence of spermatozoa in patients with non-obstructive azoospermia prior to sperm extraction procedures. It was found that the median ADC was the most significant parameter predicting the presence of viable spermatozoa.[30]
A Y chromosomal defect in a man is transmissible to his male offspring if assisted reproductive technologies (ART) using his sperm are successful. Thus, genetic counseling should be offered to all men with non-obstructive azoospermia or sperm concentrations with <5 million/mL before expensive assisted reproductive technologies, such as intracytoplasmic sperm injection (ICSI), are performed.[31] A meta-analysis from 2019 determined that genetic testing for Y chromosomal microdeletions is reasonable and cost-effective only for men with <1 million sperm/mL, as such defects are rarely found in men with >1 million sperm/mL.[32]
Male infertility patients with azoospermia and Sertoli cell-only syndrome who are considering micro-TESE and intracytoplasmic sperm injection (ICSI) should have karyotyping, genetic testing, a Y-chromosome microdeletion assay, and genetic counseling before proceeding with advanced assisted reproductive treatment.
Treatment / Management
Currently, there is no specific cure or treatment for Sertoli cell-only syndrome or male maturation arrest. However, in some cases, patients with very low sperm counts or even no sperm in the semen can still be considered for assisted reproductive procedures. Microscopic testicular sperm extraction (micro-TESE) allows for the microsurgical extraction of sperm directly from the patient's testes. It has a much higher success rate of sperm retrieval than testicular sperm aspiration (TESA), which is done with a simple needle stick but does not require a skilled microscopic surgeon.[33][34][35] These sperm can be used to fertilize an egg via intracytoplasmic sperm injection (ICSI).[36] Some studies have shown that sperm recovery is better with higher FSH levels in the blood, but this remains controversial.[37][38](A1)
The rate of successfully retrieving sperm from men with Sertoli cell-only syndrome varies substantially. Multiple factors, such as the presence of even small numbers of sperm cells and the surgeon's experience, can substantially influence the outcome of TESE/TESA, micro-TESE, and ICSI.
Just using an operating microscope can still miss up to an estimated third of infertile men who still have some limited spermatogenesis.[39] A planned, detailed, and comprehensive microdissection, possibly involving both testes, by an experienced microscopic infertility surgeon is necessary for optimal results.[39] Both testes may need to be explored microscopically as 8% of cases will only find viable sperm in one testis.[39] (B2)
In general, the rate of successful fertilization and pregnancy from ICSI is significantly lower in men (48% vs. 60%) with non-obstructive azoospermia compared to men with obstructive disease.[40](B2)
In one study, the sperm retrieval rate in patients with Sertoli-cell-only pathology was 30.35%, hypospermatogenesis was 89.74%, and maturation arrest was 32.43%.[41] However, different studies show highly variable success rates in sperm retrieval.
In multiple reports, including a meta-analysis of 32 studies, the mean overall sperm retrieval success rate in Sertoli cell-only syndrome was only about 50% (47%), while ICSI by itself only enjoys about an average 40% to 50% pregnancy rate (although 24% to 80% rates are reported).[3][25][42][43][44][45] Some studies have suggested that only 13% of patients with Sertoli cell-only syndrome actually managed to ultimately have a biological child via these procedures.[46] The overall chances of a successful pregnancy in Sertoli cell-only syndrome are only about 25% or less, depending on sperm retrieval rates, female factors, surgical experience, and many other variables. Before starting expensive fertility treatments, this information should be communicated to the infertile couple.(B2)
In one study of 125 non-obstructive azoospermic men where no sperm were found on their first micro-TESE, there was an 18.4% chance of a repeat procedure successfully retrieving viable spermatozoa.[47]
Klinefelter patients have a reported successful sperm retrieval rate with micro-TESE as high as 50% to 72% in some studies.[48][49][50] Slightly improved rates of successful sperm extraction have been noted in Klinefelter patients over 30 years of age, with poorer results if TESE is attempted prior to 16 years.[51] A comprehensive meta-analysis of 37 trials of Klinefelters patients showed an overall sperm retrieval success rate of 38% to 52%, with an ICSI pregnancy rate of 43%.[52] Out of 1,248 infertile men with Klinefelters, there were a total of 218 pregnancies for an overall pregnancy success rate of only about 17.5%.[52] These numbers are very similar to the results with Sertoli cell-only syndrome.(A1)
Couples are advised to undergo genetic testing to confirm if their biological children could also be at risk of the same condition. This is because Y chromosomal defects are transmissible to biological male offspring if TESE and ICSI are ultimately successful. Therefore, genetic testing and counseling should be given to men with Sertoli cell-only syndrome and similar severe genetically transmissible fertility disorders prior to starting assisted reproductive techniques. It has been suggested that this applies to all men with non-obstructive azoospermia or severe oligospermia (<5 million sperm/mL).[31]
Maturation arrest is a separate and distinct entity but is often confused with Sertoli cell-only syndrome as they both present similarly with non-obstructive azoospermia. Maturation arrest in men is defined as the extensive and uniform interruption of spermatogenesis in both testes without any apparent impairment of the Leydig or Sertoli cells.[53] It has been linked to at least 13 separate genes and is thought to be caused by intrinsic germ cell defects and/or extrinsic factors.[29][54][55] Like Sertoli cell-only syndrome, it is considered inherently irreversible, but treatment is possible with assisted reproductive techniques. Like Sertoli cell-only syndrome, the diagnosis is generally made only by a histological examination of a testis biopsy.(B3)
Maturation arrest may be early or late. Early maturation arrest has spermatogenesis halted at the primary spermatocyte stage and constitutes 69% of the total.[53] Patients tend to have higher FSH levels and lower testosterone titers than men with the late type of the disorder. Early maturation arrest is considered the more severe form with a reduced chance of finding mature sperm, but if found, the pregnancy rate is about the same as with other male infertility problems treated with ICSI.[56] Late maturation arrest generally has spermatogenesis halted at a more advanced stage, usually early spermatids.[53] The sperm retrieval rate in early maturation arrest is reportedly only 40% compared to 78% in late disease, which enjoys an overall sperm retrieval success rate of 52%.[53] Late maturation arrest is considered less severe and more amenable to successful sperm retrieval with FSH therapy and micro-TESE.[53] (B2)
Like Sertoli cell-only syndrome, maturation arrest can be primary or diffuse with total involvement of all seminiferous tubules (24%) or just focal (76%).[53] Sperm retrieval rates with diffuse maturation arrest are significantly lower (35%) compared with focal disease (57%).[53] Favorable indicators for successful micro-TESE sperm retrieval in the disorder include late maturation arrest, focal disease, and possibly higher FSH levels.[53]
in one study, twenty-six patients with late-stage non-diffuse maturation arrest who had failed initial micro-TESE were treated with recombinant FSH for 12 months. Mature sperm were found in the ejaculate of 5 (19%) patients, but only two resulted in a successful pregnancy for an overall success rate of only about 8%.[57] This and similar case reports suggest that FSH therapy can be used successfully in selected patients with late, non-diffuse maturation arrest even if initial micro-TESE fails.[57][58] However, the FSH therapy takes considerable time (9 to 12 months), and the overall pregnancy success rate is not very high at <10%.[57](B2)
Sertoli cell-only syndrome and early maturation arrest tend to have poorer overall results with assisted reproduction techniques than hypospermatogenesis or late maturation arrest.
The American Society of Reproductive Medicine has recommended that all men with non-obstructive azoospermia (which includes Sertoli cell-only syndrome and maturation arrest) or severe oligozoospermia be offered a karyotype chromosomal examination before undergoing assisted reproductive procedures.[44]
Whole-exome sequencing is potentially useful in predicting successful testicular sperm extraction (TESE), especially after a failed first attempt in men with maturational arrest. However, further data and studies are needed before this technology can be useful clinically.[59]
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 from other causes
- Cystic fibrosis
- Leydig cell hyperplasia
- Klinefelter syndrome
- Maturational arrest
- Post bilateral vasectomy
- End-stage testis failure
- Sexual dysfunction
- Severe oligospermia
- Hypospermatogenesis
- Varicocele
- Improper specimen collection or handling
Prognosis
The prognosis of the patients in terms of fertility varies greatly. In many cases, assisted reproductive techniques can help with biological reproduction, but these therapies can be expensive and take time with no guarantee of a successful pregnancy in the end. For this reason, a careful and frank discussion should be held with the patient and his family about the time, costs, and reasonable expectations for a successful pregnancy. Karyotype analysis and genetic counseling should be offered to all men with azoospermia or severe oligospermia.[44] While variable, the overall success rate of sperm retrieval with Sertoli cell-only syndrome or maturational arrest is only about 50%, with no guarantee of a successful pregnancy carried to term even if sperm are extracted.
If micro-TESE fails to retrieve any viable sperm, further attempts at assisted reproduction are unlikely to be successful, although there is a small chance of finding viable sperm with a second attempt. Men who have complete deletions of the AZFa, AZFb, or AZFc regions will have virtually no chance of successful sperm retrieval.[1]
Neither hormonal concentrations, histological diagnosis, testicular volume, age, testosterone, LH, nor FSH levels are sufficiently reliable enough to predict the presence of sperm on micro-TESE although there is a slight overall suggestion that higher FSH levels might indicate a somewhat better successful retrieval rate.[1][60]
There is no specific marker in serum or seminal fluid that has so far proven useful in reliably predicting the presence of sperm in non-obstructive azoospermic men with either Sertoli cell-only syndrome or maturational arrest.[1]
It may be possible at some future time to use somatic cells (in patients who have no germ cells) and induce changes that make them pluripotent stem cells.[61] But such a day is still far in the future.
Experimentally, testis-specific mRNA transcripts from seminal fluid may ultimately be a better way of classifying non-obstructive azoospermia than standard histopathology, which can be obtained non-invasively.[62] Another promising experimental approach involves the artificial maturation of spermatogonial stem cells extracted from patients with Sertoli cell-only syndrome who have no sperm available for micro-TESE.[63] These are still investigational techniques and are a long way from clinical use in practice.
Azoospermia has been associated as a risk factor for the development of future cancers.[44][64] There is an estimated 10.5% risk of testicular cancer development in men with Sertoli cell-only syndrome and a 26% risk of testicular nodules.[65]
Complications
There are generally only minimal direct male complications related to Sertoli cell-only syndrome or maturational arrest other than infertility and the possibility of passing on heritable male factor infertility genes to any potential male offspring. Obtaining a testis biopsy has a small risk of infection, bleeding, or a testis rupture, but these are relatively rare and easily managed. The biggest complication may be emotional and psychological to the individuals and couples affected by a devastating infertility diagnosis with a relatively low success rate even with optimal assisted reproductive technology.
Consultations
Patients should have proper follow-ups with their physicians. It is also strongly recommended that patients avoid radiation therapy, unnecessary medications, and gonadotoxins, such as chemotherapy, to preserve any remaining fertility.
Deterrence and Patient Education
Sertoli cell-only syndrome is most often a multifactorial, idiopathic condition that leads to germ cell aplasia and azoospermia. Like maturation arrest, patients are sexually normal but have significantly impaired spermatogenesis.
- There is an infertility problem as 15% of all couples encounter some degree of infertility, with the male being responsible about 50% of the time.
- In general, small testes associated with azoospermia are highly likely to have poor outcomes.
- Overall, sperm retrieval rates with Sertoli cell-only syndrome or maturation arrest are likely achievable <50% of the time, even with modern assisted reproductive technologies.
- Successful pregnancies are even more uncommon, with an average overall success rate of <25%.
- If no sperm can be retrieved by micro-TESE, then there is no chance.
- Families should also understand that there is a likelihood of passing on genetic infertility factors, particularly to any male offspring. This has to be considered and discussed.
- Alternatives such as adoption, donor insemination, and donated sperm for ICSI should be carefully considered before patients spend their time, money, and resources on increasingly expensive fertility treatments, which are not generally covered by insurance and have such limited reported overall success rates.
Pearls and Other Issues
- A semen analysis will usually show azoospermia in about 10% to 15% of male patients seeking help for infertility.
- There are generally two types of azoospermia: obstructive and non-obstructive.
- All male patients with azoospermia or severe oligospermia are recommended to undergo karyotype evaluations.
- Klinefelters syndrome is a common cause of non-obstructive azoospermia. The diagnosis is made by a karyotype examination.
- Genetic abnormalities are common in men with non-obstructive azoospermia.
- The specific diagnosis for non-obstructive azoospermia is typically made by histological appearance and generally requires a testis biopsy.
- Non-obstructive azoospermia is generally composed of Sertoli cell-only syndrome, maturation arrest, or severe hypospermatogenesis.
- The presence of any sperm in any semen analysis increases the chances of successful micro-TESE.
- Favorable indicators are younger age, normal-sized testes, no fertility issues in the female partner, focal disease, and the presence of any visible sperm on histological examination of the testis biopsy.
- In maturation arrest, the late stage is more advantageous than the early stage.
- Patients who are considering micro-TESE and ICSI should have karyotyping, genetic testing, a Y-chromosome microdeletion assay, and genetic counseling.
- Micro-TESE is much more successful than TESA but requires surgery by a skilled microscopic-trained surgeon.
- Surgeons should try to find a dilated and opaque seminiferous tubule.
- Various techniques are available to help patients who have some level of sperm reproduce. The success rate, however, varies.
Enhancing Healthcare Team Outcomes
Sertoli cell-only syndrome and maturational arrest are best managed by an experienced interprofessional team, including OB-GYN, infertility specialists, urologists, primary care, genetic counseling, psychologists, and nurses. While the diagnosis is not difficult, the treatment can be lengthy, costly, and often unsatisfactory for couples who want to conceive, as the overall success rate for bringing a pregnancy to term is only about 10%. All team members must document their observations on the case so that other team members can access the same data and contribute from their area of expertise appropriately. Open communication between team members is essential to drive the patient outcomes to their optimal endpoint. [Level 5]
Currently, there is no specific treatment or cure for Sertoli cell-only syndrome or maturation arrest. However, in many cases, patients with very low sperm counts can still be considered for testicular sperm extraction (TESE) techniques and ICSI. TESE allows the removal of sperm from the patient's testes. The sperm can then be used to fertilize an egg via intracytoplasmic sperm injection (ICSI). Some studies have shown that recovery may be better with higher FSH levels in the blood, but this is not considered a reliable finding. Karyotype analysis, genetic testing, and counseling are important components of patient care. Patients also need to be informed that these procedures can be prohibitively expensive, are not covered by insurance, and do not guarantee fertility or a successful outcome.
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