Yardimla

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Yardimla üreme teknikleriSon Gelismeler

• Doç. Dr. Bülent DURAN
• C. Ü. Tip Fakültesi Kadin Hastaliklari ve Dogum
  AD.

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Tarihçe

• Louise Brown born July 25, 1978
• First IVF baby worldwide
• Pioneering work of Robert Edwards and Patrick
  Steptoe, England
• Elizabeth Carr born December 28, 1981
• First American IVF baby
• Drs. Howard and Georgeanna Jones, Norfolk

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Ilerlemeler

• Basari oranlarinin artmasi
• Çogul gebeliklerin azalmasi
• Yeni tedaviler
• Basit tedaviler

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Raporlandirma1985 1999

• Raporlandirma basladi. 1985
• Annual reports published by ASRM (American
  Society of Reproductive Medicine) and its SART
  (Society for Assisted Reproductive Technologies)
• Voluntary at first, now a requirement of
  membership and federally mandated
• Reported cycles
• 647, 208 treatment cycles
• 155,661 clinical pregnancies
• 177,745 babies

Fertil Steril 78943-50, 2002.
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Gebelik oranlari
Clinical Pregnancy / Transfer
Fertil Steril 78943-50, 2002.
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Daha az çogul gebelik
Triplet delivery rates
Quadruplet delivery rates
Fertil Steril 78943-50, 2002.
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Çogul gebelik
The major problem in ART pregnancies
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PREMATURITY n 57 / 247 (23.07 )
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Kadin yasinin güçlü etkisi
lt35 35-37 38-40 41-42 43

• Pregnancy rates within each age range continue
  to climb, but.
• Maternal age still a critical factor in overall
  success, i.e., success very limited when age gt 40
  years.

Fertil Steril 78943-50, 2002.
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MISCARRIAGE Kadin yasinin etkisi
per cent
40
33.33
33.33
35
30
25
20
15
10
1/3
2/6
5
0
20-24
25-29
30-34
35-39
40-44
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Yeni tedaviler

• Sperm problems ICSI (Intracytoplasmic sperm
  injection)
• Egg problems Donor Egg
• Uterine problems Gestational carrier
• Surplus embryos Cryopreservation
• Genetic problems PGD (Preimplantation genetic
  diagnosis)
• Clonings Stem
  cell

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Bioteknoloji nedir ?

• Biotechnology problemleri çözen ve ürünler
  gelistiren bir dizi bilimsel araçtir.
• Teknolojinin pek çok alanini kapsar
• Bazilari mantar hücrelerini yillardir kullanirken
  Genetik testler ise çok yenidir.
• Klonlama ve stem cell arastirmalari da
  bioteknolojinin diger dallaridir

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Giris

• Klonlama basitçe kopyalama demektir
• Insanlar bu konuyu düsündügünde insanin
  kopyalanmasi ya da klon koyun Dollyi
  animsamaktadirlar
• Fakat klonlama ile insan ve hayvanlarin tam
  kopyasi disinda da isler yapilmaktadir
• Bitki, hayvan ve insanlarin herbir hücresi hergün
  arastirma ve uygulama labaratuarlarinda
  kopyalanmaktadir.

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Klon nedir?

• Diger bir organizma ile ayni genetik bilgiyi
  tasiyan bir organizmadir.

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Niçin?

1. Istenen niteliklerdeki organizmalarin kitlesel
   üretimi
2. Tehlikesiz veya üstün türlerin çogaltilmasi
3. Insanlarda organ transplantasyonu için
   
4. En çok sevilenin yeniden yasatilmasi
5. Infertility kendilerinden fertil bir kopya
6. Yedek parça (Organs, blood, kidneys, etc.)
7. Vücut parçalarinin üretimi
8. Eugenics süper insan irkini yaratmak

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Eugenics

• Spesifik özellikleri seçerek digerlerini
  yoketmektir.
• Bilim adamlari tüm hastalik genlerini elimine
  ederek saglikli bir bebegi garanti edebilir.
• Ama bu etik midir?

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Embriyo yapmanin 3 yolu"

1. Sexual reproduction
2. Cloning or asexual reproduction
3. Parthenogenesis

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1. SEXUAL REPRODUCTION

• In sexual reproduction a child gets half its
  genes from the mother (in her egg) and half from
  its father (in his sperm)

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2. CLONING OR ASEXUAL REPRODUCTION

• Cloning üremenin aseksüel bir formudur.
• Çocugun tüm genleri tek bir bireyin bir vücut
  hücresinden gelir.

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2. CLONING OR ASEXUAL REPRODUCTION
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Who is the clonal child's genetic mother or
father?

• Anladigimiz gibi klonal bir çocugun genetik bir
  anne veya babasi olmayacaktir. Onun sadece tek
  bir nükleer donoru vardir.

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If a man cloned himself, would the child be that
man's son or his twin brother?

• Ikisi de degil, biolojik iliskide yeni bir
  kategori olacaktir onun klonu

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3. PARTHENOGENESIS
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Klonlamanin tarihçesi

• 5000 B.C.- Gelecek yilin tahili için tohumlarin
  yetistirilmesi
• 1952- Tarihte ilk kopyalanan hayvan bir kurbaga
  yavrusudur.
• 1976- Insan DNA si yeni fertilize bir siçan
  yumurtasina injekte edilerek kismen insan
  özellikleri tasiyan siçanlar üretildi.
• 1978- Dünyanin ilk tüp bebegi
• 1987- Embriyonik hücrelerden ilk memeliler
  kopyalandi.
• 1998- Dolly yöntemiyle Japonlar iki dana
  ürettiklerini bildirdiler.
• 1998- Hawaii Üniversitesi arastiricilari 50 den
  fazla siçan klonladiklarini bildirdiler.
• 2000- Ingiltere erken evre insan embriyolarin
  klonlanmasi patentini alan ilk ülke oldu. Geron
  enstitisü klon insanlar yaratma düsünceleri
  olmadigini açikladilar.
• 2000-Dolly i yaratan grup domuzlari da
  klonladiklarini ilan ettiler. Bilim adamlari
  genetik mühendislikle sekillendirilmis domuzlarin
  insan organlarinin üretilmesi için umutlu
  olduklarini açikladilar.

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3 tip klonlama vardir.

• 1) Molecular cloning
• 2) Cellular cloning
• 3) Cloning of animal

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Molecular cloning

• En basit seviyede moleküler biologlar DNA
  klonlari olustururlar. Genlerin moleküler
  temelini olustururlar
• DNA fragments containing genes are copied and
  amplified in a host cell, usually a bacterium.
• The process of molecular cloning allows the
  scientists to produce large quantities of
  identical DNA to be use in many scientific
  experiments.

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Cellular cloning

• At the cellular stage, cellular cloning copies
  are made of cells derived from the soma, or body,
  by growing these cells in a laboratory.
• The genetic makeup of the resulting cloned cells,
  called a cell line, is identical to that of the
  original cell.
• Since molecular and cellular cloning of this sort
  does not involve germ cells (eggs or sperm), the
  cloned cells are not capable of developing into a
  baby.

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Cloning of animal

• This type of cloning aims to reproduce
  genetically identical animals.
• This level of cloning can typically be divided
  into two distinct processes, 1. Blastomere
  separation and 2. Nuclear transplantation
  cloning.

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About Dolly

• On March 24 1999
• Dolly gave birth to 3 lambs ,2 boys and 1 girl
• Genetically she was 6 years -old when born.

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The potential benefits of human cloning

• Two major benefits to human health
• 1.Assisted Reproduction
• 2.Human Organ/Tissue Transplantation

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Potential Harms and Disadvantages

• Risks of physical harm to the child born through
  somatic cell nuclear transfer

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Risks of

1. hormonal manipulation in the egg donor
2. multiple miscarriages in the birth mother and
   possibly severe developmental abnormalities in
   any resulting child.
3.   The possibility of compromising
   individualities.
4.   Loss of genetic variation.
5.   A black market of fetuses may arise from
   desirable donors that will want to clone
   themselves, i.e., movie stars, athletes, etc.

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Risks of

• 6. Technology is not well developed.
•  It has a low fertility rate.
•  In cloning Dolly, 277 eggs were used, 30 started
  to divide, nine induced pregnancy, and only one
  survived to term (Nash).
• 7.  Clones may be treated as second-class
  citizens.
• 8.  Unknown psychosocial harms with impacts on
  the family and society.

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HUMAN GENETIC ENGINEERING

• Human genetic engineering means changing the
  genes in a living human cell.
• Suppose you had a lung disease caused by
  defective genes in your lung cells. If there was
  a way to fix those genes, you might be cured.
• Scientists change the genes in living cells by
  putting the desired "new" gene into a little
  virus-like organism which is allowed to get into
  your cells and which inserts the new gene into
  the cell along with the "old" genes

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HUMAN GENETIC ENGINEERING
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Designer Baby

• Called Designer Baby or the Child of your
  Dreams.
• This is done by picking up the correct type of
  genes you want the child to have.
• You can create the appearance of your child and
  design his or her intelligence level.
• Parents would be able to create a
  high-performance child.
• Selecting embryo with the right kind of gene to
  be implanted into the mothers womb would also
  enable the child to be free from inheritable
  diseases.

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PRE-IMPLANTATION GENETIC DIAGNOSIS AND SELECTION
(PDS)
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What are stem cells?

• Cells which have the ability to continuously
  divide and develop into various kinds of tissue.
• Stem cells are primordial cells capable of
  developing into a variety of types of cells.
• Some stem cells are found in the adult body.
• Others are found in very early embryos.
• These stem cells can be cultured in petri dishes
  and potentially used to generate "therapeutic
  tissues" or "spare organs"

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Cell Types

1. Somatic these are the normal cells in our body,
   except for our reproductive cells (egg and sperm)
2. Pluripotent these types of cells can give rise
   to most types of cells in the body, but cannot
   make a human embryo
3. Totipotent these types of cells have unlimited
   ability.
4. They can make a human embryo
5. They can specialize into any kind of cell in the
   body

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What totipotent cells can do?
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STEM CELLS
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STEM CELLS
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Potential medical benefits from stem cell research

• Stem cell technology is a new but rapidly
  expanding field.
• Researchers are hoping that stem cells can be
  used to repair diseased or damaged tissue in
  patients.

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Potential Benefits

1. Cancer research cancer cells display abnormal
   cell development. Stem cell research can help us
   understand why cancer cells begin to divide
   uncontrollably.
2. Birth defects some birth defects occur because
   of abnormal cell division or specialization.
3. Drug testing new medications could be tested
   using human cells instead of animal, evaluating
   their effectiveness earlier in the process.
4. Generation of new cells for a wide variety of uses

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The sources of stem cells

• Unused human embryos from in vitro fertilization.
• 2. Aborted human fetuses

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There is a third alternative for stem cells

• 3. Somatic Cell Nuclear Transfer which is the
  technique used in cloning

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Different kinds of stem cells

1. Embryonic stem cells come from embryos (lt6
   weeks).
2. Stem cells from blastocysts (2 weeks) are
   virtually immortal.
3. Fetal stem cells come from fetuses (gt 6 weeks)
4. Stem cells are present in some adult tissues,
   including brain, spinal cord, and bone marrow.

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Question to consider

• Is it acceptable to use stem cells from fetuses
  for medical research or treatment?

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Questions to consider

• Do we think it is acceptable to use early
  embryos to provide stem cells?
• Do early embryos have rights?
• Is it acceptable to create an embryo by cloning
  in order to provide stem cells to be used for
  medical research or treatment?

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Spare embryos

• There are many stored embryos in countries where
  infertility treatments are offered,
• If they are not used they are destroyed or
  allowed to perish.
• On the other hand, there is a shortage of
  unfertilized eggs available to infertility
  clinics.
• Researchers prefer using spare embryos.
• However, this method destroys one embryo to
  create another embryo, which is in turn destroyed
  by the removal of stem cells.

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Question to consider

• Is it acceptable to use early embryos remaining
  after fertility treatment, which would otherwise
  perish, to provide stem cells for research?

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Fetuses from pregnancy terminations

• Their ability to renew themselves is also more
  limited.
• If such cells could be multiplied in the
  laboratory, then less foetal tissue would needed
  for treating patients.
• However, animal studies have shown that it is
  more difficult to produce normal tissues from
  these cells.
• It is harder to collect stem cells from foetuses
  than from early embryos.

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Adults

• Even adults can provide some stem cells, which
  have limited powers of renewal and change.
• For example, bone marrow cells can produce all
  the different types of blood cells and recent
  research with animals indicates that they may
  also be able to rebuild damaged tissue.

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Question to consider

• Is it ethical to delay research using embryonic
  stem cells until it is known whether adult stem
  cells are as useful?

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Ethical and legal issues surrounding cloning and
stem cell research

• None of the therapies mentioned can be developed
  without a great deal of research and this depends
  on adequate supplies of stem cells.
• At present, early embryos are the best source of
  suitable cells.
• But creating and using early embryos as a source
  of stem cells raises ethical problems.

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The range of views people have about the status
of the human embryo

• On the one hand are people who see the early
  embryo as having the same rights to protection as
  they have.
• On the other hand are those who see the early
  embryo as simply a collection of cells with no
  special rights.
• There are many shades of opinion between these
  positions.

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Opposition to Stem cell Research

• Killing human embryos is unacceptable
• Embryonic stem cell therapies are not necessary
• Human embryonic stem cell research encourages
  abortions.
• The research will increase killing of human
  embryos
• Embryonic stem cells come from embryos that can
  become adults
• Embryonic stem cells come from embryos with
  recognizable body parts

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Current Situation

• Current laws do not regulate embryo production or
  use by private companies
• Most human embryonic stem lines belong to private
  companies.

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Türkiyede durum

• Üremeye Yardimci Tedavi Merkezleri Yönetmeliginde
  Degisiklik Yapilmasina Dair Yönetmelik Resmi
  Gazete Tarihi 08 Temmuz 2005 Resmi Gazete
  Sayisi 25869

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Türkiyede durum

• "Madde 17 Bu Yönetmelik ile gösterilen vasif ve
  sartlarda olmayarak izin belgesi veya ruhsatname
  alinmadan tabipler ve diger sahislar tarafindan
  ÜYTE uygulamak için özel yerler açilmasi veya
  oturduklari yerlerin bir bölümünün bu uygulamaya
  tahsis edilmesi kendilerine ÜYTE uygulanacak
  adaylardan alinan yumurta ve spermler ile elde
  edilen embriyolarin bir baska maksatla veya baska
  adaylarda, aday olmayanlardan alinanlarin da
  adaylarda kullanilmasi ve uygulanmasi ve bu
  Yönetmelikte belirtilenlerin disinda her ne
  maksatla olursa olsun bulundurulmasi,
  kullanilmasi, nakledilmesi, satilmasi yasaktir.
  Bu yasaga ve bu Yönetmelik hükümlerine uymadigi
  tespit edilenlerin faaliyetleri Bakanlikça
  durdurulur.

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Türkiyede durum

• Yardimci üreme tekniklerinin uygulandigi
  merkezlerde üçten fazla embriyo transfer
  edilmemesi esastir. Yas faktörü, embriyo kalitesi
  ve benzeri tibbî zorunluluk hallerinde üçten
  fazla embriyo transfer edilmesi durumunda
  uygulamayi yapan tabip gerekçesini belgelendirmek
  zorundadir. Üreme hücreleri ve gonad dokularinin
  saklanmasi yasaktir. Ancak tibbî zorunluluk
  hallerinde üreme hücreleri ve gonad dokulari
  saklanabilir. Saklanan üreme hücreleri ve gonad
  dokulari evlilik disinda ve baska sahislar için
  kullanilamaz. Dondurulan üreme hücreleri ve gonad
  dokulari alinan kisinin istegine göre imha
  edilebilir. Üreme hücreleri ve gonad dokularinin
  saklanmasini gerektiren tibbî zorunluluk
  hallerinin nelerden ibaret oldugu, üreme
  hücreleri ve gonad dokulari saklanmasina iliskin
  diger usül ve esaslar Bakanlikça yayimlanacak
  tebligle belirlenir.

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Türkiyede durum

• Adaylardan fazla embriyo alinmasi durumunda
  eslerden her ikisinin rizasi alinarak embriyolar
  dondurulmak suretiyle saklanabilir. Bes yili
  geçmemek sartiyla, merkez tarafindan tespit
  edilecek süre içinde her iki esin rizasi alinarak
  ayni adayda kullanilabilir. Bu süre sonunda veya
  eslerden birinin ölümü veya eslerin birlikte
  talebi veya bosanmanin hükmen sabit olmasi
  halinde, bu süreden önce saklanan embriyolar
  derhal imha edilir. Saklama, kullanma ve imha
  bilgileri Komisyon tarafindan belirlenen
  sürelerde Bakanliga bildirilir. Saklama ve imha
  islemlerinin yapilmasinda Ek 3deki Embriyo
  Saklama Bilgi Fisi ve Embriyo Imha Bilgi Fisi ile
  ÜYTE Uygulanacak Çiftlere Ait Izin Belgesi
  doldurulur."

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Türkiyede durum

• Türkiyede oosit donörlügü, sperm bagisi,
  tasiyici annelik yasaktir.
• Saglik bakanligi embriyonik kök hücre
  çalismalarini yasaklamistir.
• PGD sadece bazi merkezlerde yapilmaktadir.
• Saglik Bakanligi embriyo transferlerinde en çok 3
  yasagini getirmistir.

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Gelisme
Clinical Pregnancy / Transfer
X
Nuclear Transfer
X
Cytoplasmic Transfer
PGD
Hatching
ICSI
Subzonal Insertion
Partial Zona Dissection
X
Co-Culture
ZIFT
GIFT
Donor Egg
Cryopreservation
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ICSI Erkek faktörünün asilmasi
Fertil Steril 78943-50, 2002.
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Basit tedaviler

• Laparoscopic egg retrieval
• Now transvaginal ultrasound-guided
• Laparoscopic replacement of eggs / embryos
• Now transcervical embryo transfer
• Daily monitoring of response
• Now every few days during stimulation
• Intramuscular injections of hormones
• Now many given subcutaneously

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US ile Avrupanin karsilastirilmasiIVF, 1998
9.1
10.8
9.8
Fertil Steril 78943-50, 2002.
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Bildirilen sonuçlarin tarihçesi
Cycles Clinics
CDC system
Wyden law
Voluntary reporting
Fertil Steril 78943-50, 2002.
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FDA kurallari

• Advances to date developed without government
  funding, using traditional IRB / informed consent
  process
• In past year, FDA has asserted authority over ART
  procedures, and has prohibited
• Cytoplasmic Transfer
• Nuclear Transfer
• Embryo Co-Culture
• Consequences unpredictable, but now have serious
  federal regulations without serious (?any)
  federal support

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Ilerlemeler

• Improving success rates
• Lower rates of multiple
• pregnancies
• New therapies
• Simpler therapies
• Flexibility of American system
• Advantage compared to Europe
• Risk of impeded progress with regulation of
  therapy

Fertil Steril 78943-50, 2002.
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Tesekkür ederim.