Management of Male Infertility What the future holds презентация

Содержание

Learning objectives At the completion of this presentation, participants will have an overview of: Sperm biomarkers as diagnostic and treatment tools Prospects of male fertility preservation Stem cells as new

Слайд 1Sandro Esteves, MD., PhD.
Medical & Scientific Director, ANDROFERT
Campinas, Brazil



Management of

Male Infertility
What the future holds

Reproductive Andrology Surgery Workshop II
Reproductive Medicine Unit - Jahra Hospital - Kuwait 2014


Слайд 2Learning objectives
At the completion of this presentation, participants will have an

overview of:
Sperm biomarkers as diagnostic and treatment tools
Prospects of male fertility preservation
Stem cells as new agents for the treatment of male infertility

Слайд 4Infertility Figures


Infertile couples worldwide
(50-80 million people)
10-15%




male factor infertility

Up to 50%



seek assistance for fertility issues

1 in 8 men


Слайд 5Irvin S, et al 1996, Auger J et al, 1995, Irvine

DS 1994, Jørgensen N et al 2001, Jørgensen N et al 2002, Swan SH 2003, Feki NC et al, 2009

Слайд 6Male reproductive relatively simple anatomy hides an overwhelmingly complex system


Слайд 7Spermatogenesis Process


Слайд 8Genetic and epigenetic- regulated process
~2,000 genes, but only 30 in the

Y chromosome

Hamada et al 2012


Слайд 9Extremely specialized cell type


Слайд 10Unexplained infertility affects up to 40% of infertile men
1 in 100

men have no sperm in ejaculate (azoospermia)
Up to 50% aspermatogenic (absolute sterility)

Слайд 11Limitations of current management

Conventional semen analysis

Conventional surgeries

Empirical medical treatments

ART overuse


Слайд 12Recent Advancements
Sperm Function Testing
Microsurgery
Genetic diagnosis
YCMD molecular diagnosis by PCR


Слайд 13
PROSPECTS IN
DIAGNOSIS





Слайд 14 Genomics
Transcriptomics
Proteomics
Metabolomics
The Era of Biomarkers


Слайд 15Researchers first to determine entire genetic sequence of individual sperm
We can

look at a particular individual, make some calls about what they would likely contribute genetically to an embryo and perhaps even diagnose or detect potential problems, and identify healthy sperm for use in IVF

Слайд 16DNA Micro-array Technology
Glass or silicon slides where thousands of features are

arrayed
Gene expression is measured hybridization process
Microarrays are read using laser-based fluorescence scanners
Determine which genes are active and at what levels
Compare with controls, etc.

Слайд 18 Potential Clinical Applications of Sperm Molecular Genetic Fingerprinting
Infertility diagnosis
Assessment of treatment

outcome (medical, surgical)
ART outcome (IUI, IVF, ICSI)
Sperm selection techniques



Слайд 19Seminal Fluid Molecular Genetic Fingerprinting


Слайд 21Proteins are also critical to understanding disease


Слайд 22Proteomics


Слайд 24Sperm & Seminal Plasma Proteomic Profiles


Слайд 25Sperm Proteomics


Слайд 26Camargo M et al. Hum. Reprod. 2013;28:33-46
Change in proteomic profiling in

seminal plasma of adult men before and after varicocelectomy

Слайд 27
PROSPECTS IN FERTILITY PRESERVATION






Слайд 32Spermatogonial stem cell preservation and transplantation
Boys facing gonadotropic treatment
Klinefelter syndrome patients
Cryopreservation

before SSC loss
Extraction: testicular biopsy
Freezing : slow-freezing and storage of testicular tissue or cell suspension in LN
Cryoprotectant: DMSO
Grafting: ectopic or homotopic (mouse)
When to graft: unknown
Fertilizing capacity in humans: unknown



Слайд 33

PROSPECT IN CREATING SPERM FROM IMMATURE AND SOMATIC CELLS




Слайд 34
Nonobstructive azoospermia irreversible condition
Esteves et al. Clinics 2011; 66: 691-700


Слайд 35Current method for identification of sperm production sites in nonobstructive azoospermia
Esteves

et al Int Braz J Urol 2013; 37: 570-83; Deruyver et al Andrology 2014; 2: 20-4

Слайд 36Morphometric Evaluation of Seminiferous Tubules
Verza Jr S, Esteves SC. Fertil Steril

2012; 98: S242

N=54; Tubule Diameter: KW-H (1;54) = 25.2; P<0.001


Слайд 37Novel methods for identification of sperm production sites in men with

nonobstructive azoospermia

Najari et al, J Urol 2012; Smith et al J Urol 2012; Ramasamy et al., J Pathol Inform 2012


Слайд 38No residual sperm production in up to 50% of men with

NOA

Слайд 39
In mice, transplanted stem cell-derived male gametes resulted in proper spermatogenesis


Слайд 40In mice, derived gametes generate viable offspring
Aponte et al, Clinics 2013


Слайд 41Biotechnological advancements in the treatment of aspermatogenic men


Слайд 42Conclusions
Novel genomic and proteomic biomarkers could add to work-up and clinical

treatment strategies

Advances in immature germ cells cryopreservation/transplantation will expand fertility options for oncological boys
Biotechnological approaches for generating male gametes last frontier to be accomplished


Слайд 43Why we should do all that …
Courtesy of E.N. & T.A.S.

with permission

Слайд 44

THANK YOU
شكرا
OBRIGADO




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