Transcript Schenker - children preservation polandx

Fertility Preservation
in Children
Joseph G. Schenker
MD. FRCOG. FACOG.FIAHR.FIAPM
President of International Academy of Human Reproduction
Hebrew University –Hadassah Medical Centre
Jerusalem ,Israel
Presently Medical Professionals must Focused on
Treating Cancers in Children to Extend their Lives with
Concern over Preserving their Fertility.
Fertility Preservation in
PREPUBERTAL CHILDREN is a particularly Complicated
Arena.
The Medical ,Ethical and Legal Issues will be Discussed
Childhood Cancer Rate
National Cancer Institute 2012
UP TO 80% SURVIVE THE PRIMARY CANCER
Survival rate Leukemia
Cancer Therapy
Ovarian Failure Rate - Disease Oriented
100
% 90
80
70
60
50
40
30
20
10
0
15
32
44
50
Ovarian Failure
Normal Ovarian Function
Leukemia
Leukemia
NHL
AML
Lymphoma
Lymphoma
Hodgkin’s
NHL
Breast
Lymphoma
Cancer
Hodgkin's
AML
Breast Ca.
Ovarian Failure by Drug
Age Adjusted Odds Ratio
Exposed- vs.- Unexposed
4
3
2.5
2
1.5
1
Plant
Alkaloids
Anti
Metabolites
Antibiotics
0
Platine
0.5
Alkylating
agents
Odds Ratio
3.5
The Risk of Ovarian Failure
Dependent on
Treatment
Patient Age.
Fertility %
100
80
60
CHEMO
TBI
40
20
CHEMO +TBI
AGE
0
10
20
30
40
Effect of Chemotherapy
On Reproduction
Is determined by the Patient's
Sex
Age
Drug used
Dose administered
Cancer Treatments
by Risk of Gonadotoxicity
Low Risk (‹ 20%)
High Risk (+ 80%)
Whole-body irradiation •
Localised radiotherapy:
pelvic or testicular •
Chemotherapy conditioning
•
for bone marrow
transplantation
Hodgkin’s disease:
Treatment with alkylating drugs
Soft-tissue sarcoma: stage IV
Ewing’s sarcoma: metastatic
G Ryan
•
Acute lymphoblastic leukemia
Wilms’ tumor
Soft-tissue sarcoma: stage I
Germ cell tumors
Retinoblastoma
Brain tumor:
surgery only
cranial irradiation ‹ 24 Gy
In: Ethical Dilemma in ART Ed. JG Schenker
Gender-Tailored Therapy
Males are more Susceptible to the Damage of Chemotherapy,
Treated with Lower Doses of Chemotherapy
Females , high risk of Radiation-Induced Secondary Malignancies
Less prone to Chemotherapy-Induced Gonadal Damage
Treated with More Intensive Chemotherapy
without Radiation when Feasible.
Bhatia S, et al.. Journal of Clinical Oncology. 2003; 21,4386
Effect of Radiation
on Uterus
Radiation Therapy in Girls may Cause Uterine Damage
That leads to Pregnancy Complications such as:
Miscarriage,
Preterm Labor,
Low Birth Weight
Gonadoprotective Measures
Limiting radiation exposure by shielding
or removing the testes from the radiation
field should be implemented whenever
possible
No Effective Gonadoprotective
Drugs are so far Available for use
in Humans.
Endocrine Status
Prepubertal Age
Pubertal Girls
Aspiration
In- vitro
Fertilization
Mature Oocyte
Cryopreservation
Fertility Preservation
in Children
Cryopreservation of Embryos
Most Eficient Technology
Unmarried
Vitrification of Mature Oocytes
Both Methods Require
Hormonal Stimulation
Delay Urgent Treatment
Premenarchal - Females
Aspiration of any Follicles Present
Maturation in vitro
Cryopreservation
Ovarian Tissue Cryopreservation
Experimental
1997
Ovarian Tissue Slow Freezing
Ovarian cortex is separated from the medulla
Permeation of cryoprotective agents into the cells ;
to protect from freezing injuries
Cryoprotective solution:
dimethyl sulfoxide
-1,2propanediol
sucrose and human serum albumin
.
Gradually Cooled
Temperature reaches 140°−C
Plunged into liquid nitrogen at 196°−C for storage
Rapid Freezing - Vitrification
Ovarian cortical Fragments
Immersed
in a Highly Concentrated
Cryoprotective Solution.
Ovarian TIssue
Plunged directly into
Liquid Nitrogen
For Storage
Efficacy of Ovarian Tissue
Cryopreservation
Histological examination revealed a higher
percentage of degenerated follicles after
cryopreservation and thawing.
Conclusions
Ovarian tissue cryopreservation and
thawing impairs the viability of ovarian
tissue in oncological patients opting for
fertility preservation
Journal of Assisted Reproduction and Genetics
2014:31,1003-1012
Ovarian Tissue Preservation
Denmark's registry, 18% of patients
younger than 14 years of age ( 2011)
Belgium - 59 girls under 16 years of age
(2011)
Hadassah , Jerusalem 15% under 15 years
of age (2012)
Transplantation of Ovarian Tissue
in Girls
Orthotopic Location
OVARY
Transplantation can be performed
Laparoscopy
Laparotomy
Heterotopic Location.
Successful transplantation of ovarian tissue
In girls has not yet been REPORTED
Fertility Preservation in Boys
Malignant Conditions
Leukemia
Hodgkin's disease
Non-Hodgkin's lymphoma
Myelodysplastic syndromes
Solid tumors
Fertility Preservation in Prepubertal
Boys
• Hematological disorders:
thalassemia major, sickle cell disease, aplastic anemia,
Fanconi anemia
• Primary Immuno-deficiencies
• Severe Autoimmune DIseases
Unresponsive to immunosuppressive therapy:
Juvenile idiopathic arthritis, juvenile systemic lupus
erythematosus, systemic sclerosis, immune cytopenias
• Enzyme Deficiency Disease: Hurler's
syndrome
*Risk of testicular degeneration
• Klinefelter syndrome
.
Postpubertal Boys,
Cryopreservation of mature spermatozoa
is an ideal option.
Semen may be obtained through:
Masturbation
Assistance of Penile or Rectal Stimulation
Testicular Sperm Extraction
Epididymal Aspiration
Normal Mature Spermatozoa
Survive Cryopreservation and Thawing very Well
May be used in the future for
Intrauterine Insemination
In vitro Insemination.
Spermatogenesis
Fertility Preservation in Prepubertal
Boys
Animal data
Healthy offsprings have been obtained
after
Transplantation of Frozen Testicular Cell
Suspensions or Tissue Pieces.
In Humans
None of the fertility restoration options of
Frozen Tissue
Cell suspension Transplantation,
Tissue grafting
IVM
Have proved Efficient and safe
in humans as yet.
Spermatogenesis
The Prepubertal Testis does not Complete
Spermatogenesis
Cytotoxic Treatment Given to Prepubertal Boys
Afects Fertility,
Fertility Preservation in Prepubertal
Boys
Animal data
Healthy ofsprings have been
obtained
after
Transplantation of Frozen
Testicular Cell Suspensions
or
Tissue Pieces.
Fertility Preservation in Prepubertal
Boys
In Humans
None of the fertility restoration
options
of
Transplantation, :
Frozen
Testicular Tissue
Cell suspension
Have Proved Efficient and Safe
in Humans as Yet.
Prepubertal Boys
Testicular-Tissue Harvesting and
Cryo-preservation.
An experimental process
Its success relies not only
on
The Survival of the Tissue
but also on its ability to graft
After Reimplantation
To restart the
Cellular Processes Needed to Generate
Mature Spermatogonia.
Fertility Preservation in Prepubertal
Boys
Fertility in Adult Life may be Severely Impaired
by Gonadotoxic Therapies.
For Young Boys who do not Yet Produce
Spermatozoa,
Cryopreservation of Immature Testicular Tissue
(ITT) is an Option to Preserve their Fertility,
Still Experimental
The ethics and legalities of medical treatment of children
have always been an area of active discussion
Due to ongoing
Cognitive
Physical
Development in childhood
Family well-being,
.
Primary Physician Duty is to Provide Counseling to
Children and their Families
Regarding :
The Risks of their Cancer
Treatment of their Cancer
Treatment Regarding Future Fertility
Options for Fertility Preservation.
Counseling to Children of all Ages,
Should be done in a manner appropriate
to both Age and Sexual Maturity
Ethical Issues
of Fertility-Preservation Options
Must be Considered on an Individual Basis
Cancer diagnosis
Recommended Treatment
Prognosis
Gonadotoxicity of Treatment,
Length of Delay Fertility Preservation,
Benefit
Harm
The Age and Desires of the Child
Input of the Child’s Family.
Ethical Issues
The Weighing of Harms and Benefits
Is Extremely Difficult
Because there are Inadequate Data on
which
to base an Individual Case
Ethical Issues
Harms
Delay of Treatment
Hormonal Manipulations
that Worsen Cancer Outcomes
Reintroduction of Cancer
Cells with Gonadal-tissue Following
Reimplantation
Risks of Surgical Interventions,
Providing False Hope.
Ethical Issues
Concerns about the Procreation of Cancer
Survivals
Decreased Life Expectancy
Risk of Early Death in Adulthood
Risk of Chronic Diseases
ETHICALY ?
Fertility Preservation
in Children
Up to 20% of Children will be not cured
of their Primary Cancers
Part of 80% of Survivors
Premature Death
Ongoing Chronic Disease
Precludes Future Use
of any
Cryopreserved Tissues or Gametes
Posthumous Reproduction
Fertility Preservation
in Children
Conceiving a Child
or
implanting an Embryo Shortly Before
or anytime
After the Death
of
One or More of Its Parents
Bethany Spielman, In Ethical Dilemmas in ART – ED.J Schenker
Ben-Shoshan A and J.Schenker Hum Reprod. 1998 May;13(5):1407-10
Posthumous Reproduction
Parents may have the Legal Authority
to Decide on the Disposition
of
Cryopreserved
Tissue or Gametes
To Assuage their Grief over their Loss
To Experience Grandparenthood
ART Practice
Two-Step Consent
ISRAEL
Cryopreservation
Implantation
Warsaw-