Autologous Adipose-Derived Adult Stromal Vascular Cell Administration for Male Patients With Infertility

Study Overview
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Brief Summary
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Severe Oligospermia (oligozoospermia) refer to semen with a low concentration of sperm and is a common finding in male infertility. Often semen with a decreased sperm concentration may also show significant abnormalities in sperm morphology and motility that affect Male fertility. The purpose of this study is to assess the ability of Autologous Adipose-Derived Adult Stromal Vascular Fraction (SVF) cells to stimulate Sertoli and spermatogonia cells and affect male fertility.

Detailed Description
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This is an open-label study to evaluate efficiency of administration of Autologous Adipose-Derived Adult Stromal Vascular Fraction (SVF) in the testis in patients with oligospermia and azoospermia. Forty men with several form oligozoospermia and azoospermia will be recruited for the study. 20 patients with same diagnosis served as a control with standard medications.Other patients -10 with oligospermia and 10 with azoospermia will receive standard medication and SVF injections. The diagnosis of Azoospermia (Oligospermia) will be established on the basis of two and more semen analysis evaluations done at separate occasions and detailed history taking, physical examination and investigations (blood tests include hormon levels as testosteron. follicle stimulating hormone (FSH), luteinizing hormone (LH). karyotyping and testosterone levels, and may include testicular biopsy or transrectal ultrasound if indicated. This study affect only Pretesticular and Testicular forms, without chromosomal aberration. SVF can produce a lot of cytokines ( as EGF, FGF, NGF, PDGF, VEGF, IGF, GMCSF, GCSF, TGF, Erythropoetin, TPO, BMP, HGF, GDF, Neurotrophins, MSF, SGF, GDF and growth factors) moreover the microvesicles and exosomes released by this cells can prevent cells from apoptosis and stimulate regenerative process of surrounding tissues and cells. SVF will be transplanted by an andrological surgeon through a standard surgical approach. Subjects will be monitored frequently for a total of one year after cell injection.

Official Title
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Efficiency Evaluation of Adipose-Derived Adult Stromal Vascular Cells in Patients With Spermatogenesis Disorders.

Conditions
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Azoospermia, Oligozoospermia

Intervention / Treatment
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* Biological: Lipoaspiration and SVF introduction.
* Drug: Standard therapy.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: idiopathic oligozoospermia (spermatozoid number <2x10^6/mL) - 10 patients cryptozoospermia/azoospermia - 10 patients Exclusion Criteria: age before 18 or after 60 years old heart insufficiency. stroke (during 1 year) anemia blood disease pelvis bone trauma chronic diseases in decompensation stage skin diseases tuberculosis hyperprolactinaemia hyper or hypothyreosis obstructive zoospermia sperm stimulating hormone therapy Men with previous surgery in testis Men with infectious genital diseases and anatomical abnormalities of the genital tract Those with major medical problems such as malignancy, hepatitis B . C, etc. HIV Chromosomal aberration (e.g. Y microdeletion, trisomy….)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study consist 40 patients in 4 groups. Two working groups and two control groups. Each group consist 10 Males.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lipoaspiration and SVF introduction I.<br>Patients with azoospermia that introduce with standard treatment and Lipoaspiration and SVF introduction. | Biological: Lipoaspiration and SVF introduction.<br>* Lipoaspiration, isolation of SVF and introduction into testis Interstitium.<br>Drug: Standard therapy.<br>* Standard therapy include to give up bad habits, to establish a healthy diet, to eliminate excessive physical exertion. eliminate. In the case of endocrine disorders, hormone therapy is prescribed.<br>* Other names: healthy diet, physical exertion eliminate. hormone therapy.;|
| Active Comparator: Standard therapy I.<br>Patients with azoospermia that introduce with Standard therapy only. | Drug: Standard therapy.<br>* Standard therapy include to give up bad habits, to establish a healthy diet, to eliminate excessive physical exertion. eliminate. In the case of endocrine disorders, hormone therapy is prescribed.<br>* Other names: healthy diet, physical exertion eliminate. hormone therapy.;|
| Experimental: Lipoaspiration and SVF introduction II<br>Patients with oligospermia that introduce with standard treatment and Lipoaspiration and SVF introduction. | Biological: Lipoaspiration and SVF introduction.<br>* Lipoaspiration, isolation of SVF and introduction into testis Interstitium.<br>Drug: Standard therapy.<br>* Standard therapy include to give up bad habits, to establish a healthy diet, to eliminate excessive physical exertion. eliminate. In the case of endocrine disorders, hormone therapy is prescribed.<br>* Other names: healthy diet, physical exertion eliminate. hormone therapy.;|
| Active Comparator: Standard therapy II.<br>Patients with oligospermia that introduce with Standard therapy only. | Drug: Standard therapy.<br>* Standard therapy include to give up bad habits, to establish a healthy diet, to eliminate excessive physical exertion. eliminate. In the case of endocrine disorders, hormone therapy is prescribed.<br>* Other names: healthy diet, physical exertion eliminate. hormone therapy.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sperm concentration in ejaculate | Sperm quantity and quality will be evaluated with automatic sperm cout analyzer a month, two and three after injection of SVF. Total measures - 3. | 1, 2, 3 month | 
| Spermatozoa in testicular biopsy | Testicular sperm aspiration (TESA) will be performed after 3 month after SVF injection. | 3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Testosterone | Testosterone will be measured a three month after injection of SVF. | 3 month | 
| Inhibin-B | Inhibin-B will be measured a three month after injection of SVF. | 3 month | 
| Follicle stimulating hormone (FSH) | Follicle stimulating hormone will be measured a three month after injection of SVF. | 3 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous Stem Cell, Male infertility, Adipose-Derived stem cell, Azoospermia, Oligospermia