What is Sertoli Cell–Only Syndrome (Del Castillo syndrome )?
About one in seven couples struggle with some degree of infertility. In roughly one out of three of these cases, the issue lies with the male partner. Infertility issues are most common in West Africa and East Asia. In men experiencing fertility issues, about 10-15% show no sperm at all in their semen, a condition known as azoospermia.
Azoospermia can be broken down into two categories: obstructive and non-obstructive. Obstructive azoospermia could be due to scarring or surgery of the vas deferens or epididymis, the tubes that carry sperm. Non-obstructive azoospermia can be due to various conditions including Sertoli cell-only syndrome, maturation arrest, or reduced sperm production. Out of these, Sertoli cell-only syndrome is the most common, followed closely by maturation arrest.
Sertoli cell-only syndrome is also known as Del Castillo syndrome and germ cell aplasia. Sertoli cells are located in the coiled tubes of the testes, known as the seminiferous tubules, and they play a crucial role in the production of sperm. These cells react to a hormone called follicle-stimulating hormone (FSH) which is produced by the pituitary gland in response to signals from the hypothalamus. This condition typically affects men between 20 and 40 years of age.
In the case of Sertoli cell-only syndrome, only Sertoli cells are present in the seminiferous tubules, and very little or no sperm production occurs. However, some patients may have the condition only in certain areas, leaving other parts of the testes capable of normal sperm production. People with this condition usually appear normal upon physical examination because it causes infertility without affecting sexual function. The condition is usually diagnosed based on the results of a testicular biopsy. Most instances of the disease have multiple causes and are categorized as idiopathic, meaning the exact cause is unknown. Many men with this condition can still father children with the help of assisted reproductive technologies.
What Causes Sertoli Cell–Only Syndrome (Del Castillo syndrome )?
Sertoli cell-only syndrome doesn’t have a fully understood cause. However, it’s thought to potentially be a result of different possibilities, including small genetic deletions on the Y-chromosome, particularly in a region called the azoospermia factor (AZF), exposure to harmful chemicals or toxins, radiation therapy, or even severe trauma to the testicles. One recent idea suggests the deletion of a specific gene (CDY1) on the Y-chromosome. Further investigations and testing of this gene, along with another called DAZ, can possibly help predict this condition and assess the ability to find mature sperm for assisted reproduction in cases of this syndrome.
Sertoli cells, which are affected in this syndrome, have some very important jobs in male reproduction. Key aspects are to support and nourish the growth and development of cells which will later become sperm. They also produce a hormone (anti-Mullerian hormone) in male fetuses that stops the development of internal female reproductive organs.
In addition to the above, Sertoli cells also produce inhibin-B and activin, substances that regulate a hormone called follicle-stimulating hormone, to ensure the balance and proper function of sperm production.
Interestingly, the Sertoli cells in this particular syndrome have been found to express different microRNA (small molecules that control gene function) than in other conditions, like obstructive azoospermia. This hints that these different microRNA might be involved in this syndrome.
Also, important proteins linked to sperm production, called Ovol1 and Ovol2, are not found in the testes of patients with this syndrome, suggesting they play an essential role and their absence may be a potential area for future treatment options.
Finally, it’s worth noting that Sertoli cell-only syndrome is also often linked to other conditions like Klinefelter’s syndrome, and in some cases, it has even been found in association with varicoceles, swollen veins in the scrotum.
Risk Factors and Frequency for Sertoli Cell–Only Syndrome (Del Castillo syndrome )
Sertoli cell-only syndrome is a condition contributing to male infertility, affecting an estimated 5% to 10% of men who are infertile. The primary symptom of this syndrome is azoospermia, or the absence of sperm. Though it can affect men of any race, it seems to be a bit more common in Caucasian males. Usually, it impacts adults who are 20 to 40 years old.
- Sertoli cell-only syndrome affects around 5% to 10% of infertile men.
- The main symptom is azoospermia, meaning there’s no sperm in semen.
- Although it can affect all races, it tends to be slightly more common in Caucasian males.
- It most commonly affects adults between the ages of 20 and 40.
Signs and Symptoms of Sertoli Cell–Only Syndrome (Del Castillo syndrome )
Typically, men between 20 to 40 years old who are having fertility issues might experience this condition. Their testicles might be of regular size or notably smaller, and they might also experience normal shape and feel. In some cases though, shrinkage of the testes can occur. Other symptoms include a history of challenges with male fertility.
During a physical examination, the doctors typically don’t find any sign of gynecomastia (enlarged breast tissue in males), and patients have average male characteristics. Normal puberty timing and hair patterns are observed, and usually, no other physical abnormalities are noted.
Testing for Sertoli Cell–Only Syndrome (Del Castillo syndrome )
Sertoli cell-only syndrome is commonly tested with two separate semen analyses. This is because the condition often results in azoospermia – a medical term for having no sperm in semen. A few patients might still have very low levels of sperm.
Around 90% of patients with Sertoli cell-only syndrome have higher than normal levels of a hormone called follicle-stimulating hormone (FSH). High levels of FSH in the blood are usually a sign of severe failure of sperm production (spermatogenesis). However, testosterone levels are usually normal in these patients.
The definitive way to diagnose Sertoli cell-only syndrome is through a testis biopsy. This medical procedure involves removing a small piece of tissue from the testis for examination.
Doctors usually check FSH levels in men who are struggling to conceive. A study has suggested that if a man’s FSH level is over 7.6 IU/L and his testicles are no larger than 4.6 cm, he is very likely (around 89% probability) to have abnormal sperm production. However, the accuracy of FSH levels for predicting sperm production issues is a controversial topic. Some studies say that FSH is a reliable predictor, while others do not. The general consensus is that higher FSH levels could be associated with slightly higher sperm retrieval rates, but there is too much discrepancy in the findings to make any solid conclusions.
These days, genetic testing can confirm a diagnosis of Sertoli cell-only syndrome in about 20% of cases. Recently, a method that involves an analysis of testicular volume apparent diffusion coefficient (ADC) histogram has been used to predict the presence of viable sperm in patients with non-obstructive azoospermia before sperm extraction procedures.
A defect in the Y chromosome can be passed on to a man’s male children if assisted reproductive technologies using his sperm are successful. Therefore, genetic counseling should be offered to men with either non-obstructive azoospermia or extremely low sperm concentrations before they undertake costly assisted reproductive procedures.
Doctors usually recommend genetic testing for Y chromosomal microdeletions only for men with less than 1 million sperm/ml. This is because such defects are rarely found in men with over 1 million sperm/ml. Men considering advanced assisted reproductive treatments should have a range of tests, including karyotyping (a test that checks the number and structure of chromosomes), genetic testing, genetic counseling, and a Y-chromosome microdeletion assay (a test for small missing pieces in the Y chromosome).
Treatment Options for Sertoli Cell–Only Syndrome (Del Castillo syndrome )
Sertoli cell-only syndrome and male maturation arrest are conditions that affect a man’s ability to produce sperm, but currently, there’s no specific cure for these. However, treatments including assisted reproductive procedures can help men with severe sperm production issues achieve biological parenthood.
Microscopic testicular sperm extraction, or micro-TESE, is one such procedure. Micro-TESE involves the surgical removal of sperm directly from the testicles under a microscope for the highest success rates. The harvested sperm can then be used to fertilize an egg in a process called intracytoplasmic sperm injection (ICSI). While some studies suggest that high levels of the hormone FSH enhances sperm recovery, other studies argue otherwise.
It’s important to note that sperm retrieval rates in Sertoli cell-only syndrome can vary greatly depending on factors like the surgeon’s experience and whether there are any sperm cells existent. Despite using a microscope, a third of infertile men may still be missed, emphasizing the need for a meticulous and comprehensive exploration potentially on both testes by an experienced fertility surgeon.
The success rates of achieving pregnancy from ICSI are generally lower for men with conditions causing lack of or low sperm count compared with men who have blockages. For example, a study showed sperm recovery rates were about 30% for Sertoli cell-only condition, with other studies showing a wide range of success rates.
Couples should understand the procedure’s costs and success rates before starting treatment. In a study, about one in five men successfully retrieved sperm in a repeat microscopic testicular sperm extraction procedure after no sperm was found in the initial attempt.
Couples considering assisted reproduction should also get genetic testing as male children of sufferers of these conditions could inherit Y chromosome defects affecting fertility. Comprehensive genetic counseling should precede any fertility procedure in assisting those with severe genetically transmissible fertility disorders.
Maturation arrest is another condition with similarities to Sertoli cell-only syndrome where sperm production stops due to genetic or other factors. Depending on at what stage the sperm production halted and the procedure done, the chances of retrieving mature sperm can still be significant. Supplements of FSH hormone coupled with micro-TESE have also shown some success.
However, success of assisted reproduction techniques not as promising for Sertoli cell-only syndrome and early maturation arrest as they are for hypospermatogenesis or late maturation arrest. The American Society of Reproductive Medicine recommends men with severe sperm production issues undergo a chromosome exam before commencing any assisted reproductive procedure.
Finally, while whole-exome sequencing, a genetic testing method, can predict the success of surgical sperm retrieval, especially after an initial unsuccessful attempt, more research is needed before it can become standard practice.
What else can Sertoli Cell–Only Syndrome (Del Castillo syndrome ) be?
It’s important to correctly identify other health conditions that might be causing a low sperm count. Here are some possibilities:
- Azoospermia (no sperm in semen) due to other reasons
- Cystic fibrosis (a genetic disorder affecting the lungs and digestive system)
- Leydig cell hyperplasia (an increase in the number of Leydig cells, which produce testosterone)
- Klinefelter syndrome (a genetic condition in men caused by an extra X chromosome)
- Maturational arrest (where sperm cells don’t fully develop)
- Post bilateral vasectomy (a surgical procedure for male sterilization or permanent contraception)
- End-stage testis failure (when the testes can no longer function properly)
- Sexual dysfunction (problems during any stage of the sexual response cycle)
- Severe oligospermia (low sperm count)
- Hypospermatogenesis (reduced production of sperm)
- Varicocele (enlargement of the veins within the scrotum)
- Improper specimen collection or handling
What to expect with Sertoli Cell–Only Syndrome (Del Castillo syndrome )
The chances of a patient being able to conceive naturally can widely vary. There are medical treatments that can help with fertility, but these can be expensive, time-consuming, and do not always result in a successful pregnancy. Because of these factors, it’s essential for the patient and their family to fully understand what to expect in terms of time, cost, and the likelihood of a successful pregnancy. Men with azoospermia, which means having no sperm, or severe oligospermia, which means having a low sperm count, should consider genetic testing and counseling.
Unfortunately, the chances of successfully retrieving sperm in cases of conditions known as Sertoli cell-only syndrome or maturational arrest are only around 50%, and there’s no guarantee that a successful pregnancy will result even if sperm are extracted. If a surgical sperm retrieval technique, known as micro-TESE, isn’t successful, further attempts at fertility treatments may not be effective, though there could be a miniscule chance of discovering viable sperm in a second attempt.
For men with certain genetic deletions, namely AZFa, AZFb, or AZFc, the chances of successful sperm retrieval is approximately zero.
Existing methods of predicting the presence of sperm, such as hormone levels, the physical characteristics of the testes, or the levels of certain fertility hormones (LH and FSH), are not particularly reliable. Higher levels of FSH may suggest a slightly better chance of successful sperm retrieval, but there is no clear ‘marker’ in a man’s blood or semen that can accurately predict the presence of sperm in cases of non-obstructive azoospermia.
In the future, it might be possible to create sperm from other cell types in the body, but we’re not there yet. Ongoing scientific research is exploring new techniques, like using testis-specific mRNA transcripts to classify non-obstructive azoospermia, and even artificially maturing sperm cells. However, these are experimental methods and not yet available for clinical use.
Lastly, it’s important to note that azoospermia has been linked to an increased risk of developing cancers later in life. Specifically, men with Sertoli cell-only syndrome have a 10.5% risk of developing testicular cancer and a 26% risk of developing testicular nodules.
Possible Complications When Diagnosed with Sertoli Cell–Only Syndrome (Del Castillo syndrome )
Sertoli cell-only syndrome or maturational arrest causes very few physical complications in men, aside from infertility and the risk of passing on genes that can cause male infertility to their male children. Taking a sample from the testicles for testing does pose a small danger such as infection, bleeding, or testicle rupture. However, these situations are quite uncommon and can be easily handled.
The major complication lies in the emotional and psychological impact. Individuals and couples who receive a diagnosis of infertility often face significant emotional distress. This impact can be particularly intense given the relatively low success rate of fertility treatments, even when these treatments use the most advanced technology.
Common complications:
- Infertility
- Risk of infection during testicle biopsy
- Potential bleeding during testicle biopsy
- Possibility of testicle rupture during biopsy
- Emotional and psychological distress due to infertility diagnosis
- Low success rate of fertility treatments
Preventing Sertoli Cell–Only Syndrome (Del Castillo syndrome )
Sertoli Cell-Only Syndrome is a commonly complex and unexplained condition that can result in germ cell aplasia and azoospermia. In simpler terms, it means the patient can’t produce sperm normally. This condition can be compared to maturation arrest, another fertility condition, where affected individuals appear normal sexually but have serious problems with sperm production.
It’s important to note that fertility issues affect about 15% of all couples, and half of the time, it’s the male who has fertility problems. Generally, small testicles combined with azoospermia – complete absence of sperm – are a strong indicator of poor fertility outcomes.
Unfortunately, with Sertoli Cell-Only Syndrome or maturation arrest, the chances of retrieving sperm is likely below 50%, even when using state-of-the-art fertility methods. The chances of these treatment methods resulting in a successful pregnancy are even less common, with an average success rate that rarely exceeds 25%. If none of the sperm can be collected through a medical procedure known as micro-TESE, then it’s sadly not possible to conceive.
It’s essential for families to understand that these fertility problems could potentially be passed onto male children through genetic inheritance. This consideration is important and must be discussed. Alternatives like adoption, donor insemination, or receiving donated sperm for a procedure called Intra-Cytoplasmic Sperm Injection (ICSI) should be thought about carefully. Families need to weigh these options before committing their time, money, and effort towards often costly fertility treatments. These treatments usually aren’t covered by insurance and don’t guarantee a successful outcome.
