Azoospermia is a condition where there are no live or mature sperm cells in a man’s ejaculate. The ejaculate may contain semen with other cells, therefore, existence of a fluid ejaculate does not suggest existence of sperm cells. Azoospermia can be divided into two main categories:
Obstructive azoospermia: When there is an obstruction, sperm cells are not able to come out into the ejaculate even though there is active sperm production. Obstructive azoospermia can be caused by a number of reasons. The main cause of obstructive azoospermia today appears to be vasectomy, which would be something the patient would be aware of. However, there are other problems which can possibly block the sperm cells from entering into the ejaculate. These problems would include: Problems with the ductal system where the sperm cells need to travel to reach the urethra. Once sperm leaves the testes (testicles) (which is the point of production), it passes through several other structures. These structures are the epididymis, vas deferens (sometimes also referred to as the ductus deferens), ejaculatory duct and the urethra. Any problem involving the transport of sperm from one structure to the other, or even within these structures can block the sperm’s exit pathway. Figure on the right will help visualize these structures.
Problems with ejaculation where the emission process can be malfunctioning. The sperm cells are normally deposited into the urethra prior to ejaculation. This is known as emission. It can malfunction due to neurological damage or in some cases due to uncontrolled diabetes.
In cases of obstructive azoospermia, using surgical sperm extraction techniques often help obtain an acceptable number of sperm cells to be used during an IVF cycle.
Non-obstructive azoospermia treatment: When azoospermia is non-obstructive, there is a sperm production/maturation problem. In non-obstructive azoospermia, surgical sperm extraction methods are not likely to yield desired outcomes since the sperm cells are not being produced or being developed. The other two alternatives are: Stem cell therapy or IVF treatment using a sperm donor. If the patient is not yet ready to consider IVF treatment using donor sperm, an assessment can be made whether he qualifies for our stem cell therapy.
Stem cell therapy in the context of azoospermia can be carried out in two ways. One of these ways is a systemic infusion of stem cells via IV infusion and the other is injection of stem cells directly into the testes. While the prior method appears to have some success, the direct injection method has provided more favorable outcomes in existing literature as well as our own observations in our clinical practice.
At North Cyprus IVF Center, we use mesenchymal stem cells in our stem cell therapies. Mesenchymal stem cells are known as adult stem cells which are present in a person’s own adipose (fat) tissue. There are many different types of stem cells based on their lineage and place of origin. For instance, embryonic stem cells have the potential to grow and develop into any cell or tissue. However, they carry the potential for inducing carcinogenesis if they proliferate uncontrollably. For this reason, their use is considered both dangerous and unethical for obvious reasons. Mesenchymal stem cells, on the other hand, have been shown to have no carcinogenic properties in clinical studies and in fact have been proposed as therapy for certain cancers.
Stem cell therapy involves using the patient’s own adipose tissue for isolation of the cells. The adipose tissue is obtained via a liposuction procedure. This is a relatively short procedure since the aim is to obtain a small amount of tissue. Once the mesenchymal tissue is obtained, our lab isolates the mesenchymal stem cells while the patient is still sedated. At the same time, the patient’s own blood sample is obtained for isolation of platelet rich plasma. Combination of stem cells, PRP and exosomes are then mixed in a specific ratio. The combination cocktail is then injected into specific regions of both testes with the aim of re-initiating spermatogenesis.
Exosomes are tiny nanovesicles found in interstitial spaces as well as bodily fluids. Due to their sizes, exosomes have always been viewed as artifacts or cellular trash with no physiological function. However, with advancements in research in the field of medicine, they are now known to be a part of a meticulous intracellular communication system.
Exosomes are known for their involvement in all types of cellular communication. They provide local autocrinesignals between similar types of cells, local paracrine signals between different cell types as well as distant endocrine signals. Involvement in such extensive cellular signaling has gained them the name “signalosomes”. When exosomes are introduced in the body, they enhance communication via all channels, which helps with the overall health and function of cells.
Compared to adult stem cells, exosomes contain 300% more growth factors, which are essential for cellular growth, development and regeneration. Exosomes can be given via IV infusion or can be directed at a specific site by direct injection.
At North Cyprus IVF Center, the non-obstructive azoospermia treatment we offer is carried out with a cocktail of mesenchymal stem cells and platelet rich plasma. Stem cell isolation requires a minor surgical procedure and the PRP isolation is done after the patient’s blood sample is obtained. There are several tests to be performed prior to the stem cell therapy:
The first step is to obtain all the relevant test results which would involve:
1) Semen analysis and biopsy results
2) Blood tests including Alpha-fetoprotein (AFP), and beta human-chorionic gonadotropin (b-hCG)
The first one would relate to the diagnosis of non-obstructive azoospermia. The second test results would give us a green light to proceed once we have confirmed the non-existence of a neoplastic change in the testicles. The best part of using mesenchymal stem cells is that they do not initiate carcinogenesis. However, we want to be extra careful by making sure there are no neoplastic changes in the region which can proliferate using the stem cell infusion as their tech support. While many clinical studies have shown that mesenchymal stem cells are safe even when used in cancer patients and they even have cancer fighting capabilities, we do not take any risks in these patient groups for the time being before we have more concrete evidence.
Once the patient has been found fit for the stem cell therapy, the next step would be to obtain standard tests that are performed prior to any operation:
1) Complete blood count
2) Infectious disease screening
3) Patient’s vitals
4) Liver function tests
Majority of our patients travel to us from the UK or other parts of Europe. Due to commitments at home, travel time can be limited. This is why we ask for the preliminary tests to be performed locally prior to the patient’s arrival so that the length of stay in Cyprus can be minimized. You will be expected to stay in Cyprus for approximately 3 days for the stem cell therapy. This will give us enough time to run the necessary tests, obtain your blood sample, perform liposuction for the fat tissue and process all of them together for the injection. After injection with stem cells, there is a three month waiting period to observe the effect. Spermatogenesis (production and maturation of sperm cells) takes about 65 to 70 days. Therefore, anything that is likely to affect sperm cells will have an effect on the sperm sample after this period. If the semen analysis performed three months after the stem cell injection, an IVF treatment can be planned accordingly.
The cost of stem cell therapy for the treatment of non-obstructive azoospermia is 6,000 Euros. It includes the following:
– Liposuction procedure in order to obtain mesenchymal tissue
– Pre and post-operative testing and screening at our hospital (does not include local testing patients need to obtain prior to admission)
– Stem cell isolation, preparation and injection
– Hospital accommodation for one night after the procedure
Within a short period of time since introducing this treatment, we have achieved success with a large number of patients who previously had zero sperm count in their ejaculate and who had undergone surgical sperm extraction without success. However, we have also had patients who did not responded to therapy. Therefore, while, in theory, this treatment provides all the necessary elements for re-initiating spermatogenesis, more work is required to specifically research the which subgroups of patients are likely to benefit more than the others before this treatment becomes a bullet proof technique, at least for specific male populations.
While the number of patients treated, the amount of time elapsed after treatment and how long spermatogenesis can be sustained after the stem cell therapy are all important considerations for assessing how successful the treatment is, so far, the results are indicating about 56% success rate in generating new sperm cell production in patients with non-obstructive azoospermia. These are still preliminary results and actual statistics are to be published after we have offered this treatment to at least 500 patients and have observed their semen parameters for a follow-up period of at least 2 years. It is only then when we can properly assess the initial and ongoing success of this procedure.
Success with any type of fertility treatment will depend on several conditions and generalized success rates may not always apply equally to everyone. For a customized assessment, please contact our IVF specialists at North Cyprus IVF Center and request more information.
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