Background and Rationale:
Testicular and ovarian failure, often called 'gonadal failure,' occurs when the testes or
ovaries lose their ability to produce gametes. Both lead to reduced fertility and
hormonal deficiencies, significantly impacting an individual's health and quality of
life. Conventional treatments such as hormone replacement therapy (HRT) help alleviate
symptoms but do not restore fertility.
Surgical options (testicular sperm retrieval, ultrasound-guided egg retrieval) are found
to be helpful for some. However, they are not uniformly successful 11. Surgeries
(testicular biopsies) always carry risks such as risk of bleeding or infection and lack
of guaranteed success 12. Clinicians are exploring less invasive alternatives like stem
cell-based therapies, including adipose-derived stem cells (ADSCs) and exosomes. Stem
cells or stem cell-derived exosome therapy offers a promising regenerative approach for
restoring gonadal function by enhancing tissue repair, stimulating folliculogenesis or
spermatogenesis, modulating hormonal balance, and improving overall reproductive
potential in individuals with testicular or ovarian failure.
This study assesses the safety and efficacy of intra-gonadal (testicular or ovarian) stem
cells or stem cell-derived exosome injection for patients with testicular and ovarian
failure who have not responded to conventional treatments. ADSC therapy has been studied
in humans for related conditions like ovarian insufficiency and POF (Premature ovarian
failure)6. It has shown encouraging results in repairing damaged tissues and improving
hormonal function, showing early successes that provide hope for its potential. This
research assumes even greater importance in the UAE, where donor sperm and eggs are not
permitted due to religious and legal restrictions 13. Testing the safety and long-term
efficacy of ADSC therapy for gonadal failure in the UAE could provide a groundbreaking,
culturally appropriate solution for individuals facing reproductive challenges, giving
them new opportunities for treatment and a renewed sense of hope.
The Bioscience Institute, a DHA-approved facility, will provide the stem cells or stem
cell-derived exosomes under an existing Memorandum of Understanding (MOU) with the First
IVF Clinic and Day Surgery Center. The stem cells or stem cell-derived exosomes will be
extracted and produced in an off-site laboratory (Bioscience Institute) and undergo
sterility, cell count, and viability check before being prepared for administration back
into the patient. The manufacturing process follows CGTP. The cells will be injected
directly into the testes and ovaries under anesthesia.
Study Objectives
Primary Objective:
- To evaluate the safety and efficacy of intraovarian or intratesticular
injections of stem cells or stem cell-derived exosomes in restoring gonadal
function, as measured by hormonal changes (testosterone, estradiol, FSH, AMH)
and reproductive capacity from baseline to post-treatment.
Secondary Objectives:
Assess gonadal tissue regeneration using imaging techniques.
Monitor long-term treatment effects at follow-up points
Document any adverse events or complications related to stem cell or exosome
therapy, such as fibrosis, infection, or immune reactions.
Evaluate functional outcomes such as spermatogenesis in men (via semen
analysis) and ovarian follicular activity in women (via antral follicle count
and menstrual cycle regularity).
Compare the effects of stem cells vs. stem cell-derived exosomes in improving
gonadal function and hormone levels.
Study Design and Objectives This open-label, single-arm, pilot observational study will
serve as a preliminary investigation into the use of adipose-derived stem cells (ADSCs)
or stem cell-derived exosomes for treating gonadal failure in both men and women. The
study's primary focus will be on assessing safety and feasibility, while also gathering
initial efficacy data to support future large-scale trials.
Study Population The study will enroll 60 adults (30 males, 30 females) aged 20 to 50
years diagnosed with gonadal failure, including testicular failure, hypogonadism, ovarian
insufficiency, or premature ovarian failure (POF). Participants must have failed or
experienced suboptimal responses to conventional treatments, such as hormone replacement
therapy (HRT), testosterone replacement therapy (TRT), or assisted reproductive
technologies (ART).
Recruitment will take place at First IVF Clinic, Dubai, where participants are actively
receiving evaluation and treatment for gonadal failure. The inclusion and exclusion
criteria will ensure that the study targets individuals most likely to benefit from
therapy while prioritizing patient safety.
Sample Size Rationale A sample size of 60 participants was selected based on the
exploratory nature of the study. The primary objective is to assess the feasibility,
safety, and preliminary efficacy of stem cell or exosome therapy while providing
sufficient data to inform the design of future, larger trials. Given the clinic's patient
population, recruiting 60 participants over the planned two-year study period is
considered achievable.
Study Procedures
Informed Consent Participants will receive detailed information about the study,
including its risks and potential benefits, and will provide written consent prior
to enrollment.
Baseline Assessments
Before treatment, participants will undergo comprehensive baseline testing,
including:
Hormonal blood tests (Testosterone, Estradiol, FSH, AMH)
Ultrasound imaging (AFC for ovaries, testicular volume for testes)
Semen analysis (for male participants, if applicable)
Medical history review and general health evaluation
Therapeutic Administration
For ADSCs:
ADSCs will be harvested via minimally invasive liposuction from the participant's
own adipose tissue.
The cells will be processed, purified, and prepared for injection into the ovaries
(females) or testes (males).
For Exosomes:
Exosomes will be derived from stem cells, isolated, and purified before
administration.
The injections will follow the same procedure as stem cell therapy, ensuring
targeted delivery into the gonads.
Injection Procedure:
Ovarian injections: Administered via direct intraovarian injection. Testicular
injections: Administered via direct intratesticular injection in rete testis.
Follow-Up Monitoring
Participants will be monitored immediately post-injection for any adverse reactions and
will return for regular follow-ups at 3, 6, 9, and 12 months to assess:
Data Collection and Analysis Collected data will be analyzed to evaluate primary and
secondary outcomes.
Primary Outcome:
Hormonal level changes from baseline to 12 months post-treatment.
Secondary Outcomes:
Changes in gonadal tissue structure (AFC, testicular volume). Functional improvements
(spermatogenesis, menstrual cycle regulation). Incidence of adverse events (infection,
fibrosis, immune response). Surgical sperm retrieval and Egg retrieval success
Ethical Considerations This study will adhere to strict ethical standards for clinical
research.
Ethics Committee Review: The protocol will be reviewed and approved by an independent
ethics board.
Informed Consent: Participants will have full autonomy to decide on participation and may
withdraw at any time without affecting their standard medical care.
Confidentiality: All patient data will be anonymized and stored securely to ensure
privacy.
Expected Outcomes
This study aims to provide early evidence on the safety and potential efficacy of stem
cell or exosome therapy for gonadal failure. If successful, participants are expected to
show:
Improvements in hormone levels and reproductive function. Gonadal tissue regeneration,
restoring follicular activity or spermatogenesis. Minimal adverse effects, confirming
safety and feasibility. The findings from this study will help guide future, larger-scale
trials and contribute to the development of regenerative therapies for gonadal failure,
offering a novel and culturally appropriate solution for fertility preservation in the
UAE.