Spermatogenesis, when haploid spermatozoa develop from germ cells, requires a number of factors to work in perfect synchronicity. Sperm production is controlled by the hypothalamo-pituitary-gonadal axis. Gonadotropin-releasing hormone is secreted by the hypothalamus and stimulates the anterior pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH stimulate Leydig cells and the germinal epithelium to produce testosterone and sperm, respectively. Testosterone is required for the completion of the meiotic division and spermatid development and thus plays an important role in the initiation and maintenance of spermatogenesis. FSH also stimulates Sertoli cells, which produce inhibin B. LH and FSH are under negative feedback control by testosterone and inhibin B, respectively ^[4,5].

Patients with pre-testicular and testicular azoospermia have been found to have abnormal levels of ^{[5,6,7,8,9,10,11]}:

• Luteinizing hormone (LH).
• Follicle-stimulating hormones (FSH).
• Serum testosterone.
• Intratesticular testosterone (ITT).
• Inhibin B.

How Our Products Can Treat Non-Obstructive Azoospermia

We use products derived from the umbilical cord tissues of human babies in all our therapy programs - Wharton's Jelly MSCs (wjMSCs). In both animal and human studies, MSCs of differing sources have been found to be able to:

• regulate follicle stimulating hormones (FSH) levels ^[12,13].
• regulate inhibin B levels ^[13].
• regulate testosterone levels ^[12,14,15].
• increase testicular size ^[12,16].
• differentiate into germ-like cells ^{[17,18,19,20,21,22,23,24,25,26,27]}.
• initiate spermatogenesis ^{[16,28,29,30,31,32,33,34]}.
• migrate to sites of injury (chemotaxis) ^[35,36,37].
• communicate with and alter nearby cells (paracrine effect) ^[38,39,40].
• encourage your cells to self-repair (autocrine effect) ^{[38, 41, 42]}.
• prevent rejection by regulating the immune system (immunomodulation) ^{[36, 37,43,44,45,46,47,48]}.
• incapable of forming tumours ^{[36,46,49,50,51]}.

Treating Non-Obstructive Azoospermia

There are currently numerous animal and human clinical trials exploring the use of wjMSCs in the treatment of Non-Obstructive Azoospermia. These have been registered but results and findings have yet to be posted ^{[52,53,54,55,56,57]}.

In 2014, researchers at Al-Azhar University and Cairo University, Egypt, treated 60 non-obstructive azoospermic patients (including those who developed the condition as a consequence of chemotherapy or radiotherapy) with the patients’ own (autologous) bone marrow-derived MSCs (bmMSCs). 60ml of bone marrow was aspirated from each patient’s pelvic bone to produce the final volume of 5ml of bmMSCs (containing 20 million bmMSCs) that was injected into the rete testis. 12 months post-transplantation, all patients’ hormonal profile (serum testosterone, FSH, LH, inhibin B and prolactin), testicular size and semen analysis results were re-evaluated.

60% of the patients showed an increase in testicular size, the elevation of testosterone levels and reduction of FSH levels. 3 patients (5%) showed the appearance of sperm in their ejaculate, 12 patients (20%) showed sperm in needle aspiration, 8 patients (13.4%) showed sperm in testicular biopsy samples, 15 patients (25%) showed round/elongated spermatids in their ejaculate while 22 patients (36.6%) experienced no improvement of their condition at the time of reporting ^[12].

Between 2015 to 2016, researchers at the Institut Modern Medical Technologies, Ukraine, treated 6 patients diagnosed with non-obstructive azoospermia with autologous MSCs. At the beginning of the trial, each patient was tested and found to have more than 25mlU/ml (31 +/- 4.5) of FSH and less than 16 (9.8 +/- 3.8) of inhibitin B. These 6 men had also received negative results from Micro-TESE. bmMSCs derived from the patients were injected into only 1 testicle. Hormone levels were monitored at 3, 6 and 9 months post-therapy.

All patients reacted positively to therapy with improvements in hormone levels. FSH levels decreased to 16.3+/- 5.6 while inhibitin B levels increased to 14.5 +/- 2.4. 3 patients went on to try Intracytoplasmic Sperm Injection (ICSI)-assisted in vitro fertilisation (IVF) using germ cells produced after treatment. All 3 couples registered pregnancies ^[13].

In 2016, the Bio ART Fertility Center in Rosebank, South Africa treated a 36-year-old male with idiopathic non-obstructive azoospermia (characterized by eugonadism, primary infertility, low testicular volume, and high follicle-stimulating hormone values). His condition was confirmed by multiple semen analyses and, at least, two testicular biopsies; both with histological Johnsen scores of 5. It is of note that having received a course of gonadotrophin therapy prior to the second biopsy did not alter his Johnsen score of 5. Chromosomal analysis revealed a normal male karyotype, and investigations for cystic fibrosis and bilharzia were normal. Prior to treatment, his most recent serum FSH and LH levels were 7.7U/L and 8.9U/L, respectively, and his free testosterone level was 298.1 pmol/L. Both he and his wife agreed to each undergo 4 sessions of therapy using autologous adipose MSCs (adMSCs). The initial 3 sessions consisted of 1 intravenous (I.V.) infusion every 14 days. The final session was done 1 month after the last session and consisted of injections directly into both testicles. Gonadotrophin therapy was started 2 days later.

Simple semen analysis was done 4 months post-therapy and the presence of sperm was noted in the ejaculate. The sample was cryopreserved and the couple went on to have an IVF cycle. 3 good grade embryos were successfully cultured and trans-cervically transferred into the endometrial cavity.  Unfortunately, the embryos failed to implant and no pregnancy occurred ^[58].

Cyrona’s Program

Achieving high standards in our work is of paramount importance to us. Depending on a patient’s needs, we combine our premium grade Passage 2 wjMSCs with physiotherapy, occupational therapy, speech and language therapy and/or rehabilitative medicine. 

Learn more about our Products and Programs.

Why Choose Cyrona?

• Latest cellular research and technology.
• Unique, tailored therapy outlines.
• Products that meet international standards.
• Microbiology & clinical team with extensive experience in advanced medicine.
• Board-certified physicians geared toward patient safety.
• Fact-based information from clinical studies and trials.
• No outlandish promises of a one-stop-cure or false improvement rates.

Therapy Packages

All our therapy packages come inclusive of:

INTERNATIONAL PATIENTS

• Premium grade Passage 2 wjMSCs.
• Treatment by qualified specialist(s).
• Certificate of Analysis (CoA).
• Airport transfer.
• Transportation to & from therapy session(s).
• Accommodation.
• Hospital room for therapy.

LOCAL PATIENTS

• Premium grade Passage 2 wjMSCs.
• Treatment by qualified specialist(s).
• Certificate of Analysis (CoA).
• Transportation to & from therapy session(s).
• Hospital room for therapy.

How Do We Proceed

All our therapies are charged based on the number of wjMSCs and supplementary infusions required for the patient’s specific condition. As no two people are alike, our specialists review each patient’s medical reports before tailoring a therapy catered to addressing his or her individual needs.

You may chat with one of our Customer Care Representatives or send an e-mail detailing the patient’s condition to one of our Liaison Officers. It would expedite the process if you can provide us with:

• Imaging results (MRI scan / CT scan / X-Ray).
• Haematology reports (blood test).
• Doctor’s assessment reports.
• Pictures or videos of the patient (if relevant).

Upon getting in touch with us, a Liaison Officer evaluates and assigns the case to the specialist best equipped to treat the condition. A therapy, unique only to the patient, is drawn up and a price quoted accordingly.

Should you decide to proceed with therapy, our specialists require that all patients have Cancer Marker Screening performed in their country of residence before travelling to us for therapy. If the patient has had Cancer Marker Screening within the last 3 months, you may e-mail those results to us. In the event that the patient’s Cancer Marker Screening results are not satisfactory, our specialists will refuse to proceed with therapy. It is for this reason that we request that patients have Cancer Marker Screening performed in their country of residence prior to travelling to us.

One week prior to arrival, a deposit payment is required in order to arrange accommodation and transportation.

Full payment is required to be made one-day prior to therapy commencement.

Post-treatment, our specialist will provide the patient with a post-treatment protocol as well as what to expect on his or her journey towards a better, and hopefully, healthier new life.