Dia 1 - Bundeskanzleramt

Ethical aspects
of modern
reproductive
medicine and
research
Petra De Sutter, MD PhD
Dept Reproductive Medicine
Ethics Committee
University Hospital
Ghent
Reproductive medicine and research
•
Assisted reproductive technologies:
–
Intrauterine insemination
–
In vitro fertilization / intracytoplasmic sperm injection
–
Gamete and embryo donation
–
Cryopreservation of gametes, gonads and embryos
–
Preimplantation genetic diagnosis / screening
–
Designer babies, sex selection
–
Surrogacy
–
Multiple pregnancies
•
Reproductive medicine research
–
(embryonic) stem cell research (artificial gametes)
–
Artificial oocyte activation / parthenogenesis
–
Somatic cell nuclear transfer (cloning)
Age limits for treatment ?
Own oocytes
Donor oocytes
Pregnancy after IVF and IUI
as a function of female age
40
35
30
Pregnancy 25
rate per 20
cycle
15
IVF
IUI
10
5
0
< 30
30 - 35 36 - 38 39 - 40 41 - 42
Age
> 42
Pregnancy and miscarriage after
IVF/ICSI as a function of female age
40
35
30
Pregnancy 25
rate per 20
cycle
15
10
Pregnancy
Miscarriage
5
0
< 30 30 - 35 36 - 38 39 - 40 41 - 42 > 42
Female age
Clinicians autonomy
Patient autonomy
Societal interests
Multiple pregnancies following
ART:
blessing or curse?
Twins and Triplets: England and Wales
and France 1970-1998
Twins
Triplets
Blondel & Kaminski 2002. Semin Perinatol 26:239-49.
Multiple Pregnancy and Prematurity
UK (Scotland)
UK (Northern Ireland)
Sweden
Netherlands
Italy
Singleton births
Multiple births
Ireland
Germany (9 Bundeslander)
France (Perinatal survey)
Finland
Denmark
Belgium (Flanders)
Austria
0
10
20
30
40
50
60
Percent < 37 Weeks
Blondel et al 2006. BJOG 113:528-35.
70
80
Maternal Morbidity
Multiple (n=44,674) vs singleton pregnancy (n=165,188)
RR (95% CI)
Pre-eclampsia
2.8 (2.7-2.9)
Gestational diabetes
1.1 (1.9-1.2)
Myocardial infarction
3.7 (2.3-5.8)
Heart failure
12.9 (2.7-62.3)
Venous thromboembolism
2.7 (2.0-3.5)
Pulmonary oedema
7.1 (4.5-11.3)
Post partum haemorrhage
1.9 (1.8-1.9)
Caesarean delivery
2.2 (2.1-2.2)
Hysterectomy
2.3 (1.7-3.2)
Walker et al, BJOG, 2004
Single embryo transfer
Introduction of eSET
50
3,0
Proof of
concept
45
40
Funding
2,5
34,4
2,0
30
1,4
25
1,5
20
1,0
15
8,9
10
0,5
5
0
0,0
1995
1996
1997
1998
Multiple PR
1999
2000
OPR/transfer
2001
2002
2003
embryos/transfer
2004
embryos/transfer
percentage
35
BELGIAN FUNDING REGULATION
•Six IVF/ICSI cycles (= oocyte harvests) funded in a life-time
•1187€ per cycle for laboratory costs ( gamete procurement and handling )
•Including cryocycles
•Up to the age of 43 years
Linked to a rational transfer strategy
≤ 36 years
1st trial ever or 1st trial after
previous IVF/ICSI-delivery:
always one fresh embryo;
2nd trial: one embryo if of
sufficient quality; two if of
insufficient quality;
≥3rd trial: maximum 2 embryos.
>36 - ≤39 years
> 39 years
1st and 2nd trial:
maximum 2 embryos;
No maximum number
of embryos to
transfer is dictated
≥3rd trials: maximum
3 embryos.
CRYOCYCLES: 1 or 2 embryos
● Unmarried persons and gays and lesbians have interests in
having and rearing children.
● There is no persuasive evidence that children raised by
single parents or by gays and lesbians are harmed or
disadvantaged by that fact alone.
● Programs should treat all requests for assisted reproduction
equally without regard to marital status or sexual
orientation.
The instrumentalisation / commercialism
of reproductive medicine …
• "Donation" of eggs generate between $2,000 and
$50,000 per donation, as ironic as that may seem. Men
"donate" sperm for an average of $200 per transaction.
Since no governmental or medical regulation covers
these "donations" there are no hard facts as to the total
outlay for eggs and sperm. Researchers estimate that
the figure is nearly $18 billion, citing that one researcher
paid $1.5 million for eggs in one year.
• The IRS reports that doctors of fertility medicine average
adjusted income (after deducting expenses) of $9 million
per year, with a gross income of over $20 million each.
1. Financial compensation of women donating oocytes for infertility therapy or for research is
justified on ethical grounds.
2. Compensation should be structured to acknowledge the time, inconvenience, and discomfort
associated with screening, ovarian stimulation, and oocyte retrieval. Compensation should not
vary according to the planned use of the oocytes, the number or quality of oocytes retrieved, the
number or outcome of prior donation cycles, or the donor’s
ethnic or other personal characteristics.
3. Total payments to donors in excess of $5,000 require justification and sums above $10,000
are not appropriate.
4. To discourage inappropriate decisions to donate oocytes, programs should adopt effective
information disclosure and counseling processes. Donors independently recruited by
prospective oocyte recipients or agencies should undergo the same disclosure and counseling
process as donors recruited by the program.
5. Oocyte-sharing programs should formulate and disclose clear policies on the eligibility criteria
for participants and on how oocytes will be allocated, especially if a low number of oocytes or
oocytes of varying quality are produced.
6. Treating physicians owe the same duties to oocyte donors as to any other patients. Programs
should ensure equitable and fair provision of services to donors.
7. Programs should adopt and disclose policies regarding coverage of an oocyte donor’s
medical costs should she experience complications from the procedure.
Preimplantation genetic diagnosis
Preimplantation genetic diagnosis
SCNT
(therapeutical
cloning) and
stem cel
technology
Ethical concerns regarding cloning
Cloning / stem cell research
•
Ethical concerns are often clouded by subjectivity, emotion, and perspective
•
In animals?
– Cloning members of an endangered species is generally regarded as positive,
whereas attempting to clone an extinct mammoth from preserved tissue is regarded
as negative (interferes with nature).
– Cloning pets might be seen as unethical (knowing that strays crowd shelters)
•
In the human?
– Ethical objections to cloning < this is not a normal way to have a baby, exact
duplicates?.
– the U.S. House of Representatives voted on July 31, 2001 to outlaw human cloning for
any reason (impeding other types of medical research, thus introducing a different
bioethical dilemma).
•
“Reproductive cloning" (to create a baby) versus "therapeutic cloning" (to create embryonic
stem cells that are genetically identical to the individual who donated the nucleus).
– Does therapeutic cloning violate the rights of early-stage embryos ?
– Does banning this research violate the rights of people who might benefit from
embryonic stem cell therapy?
As far as reproductive cloning is concerned, many motives have been proposed, from
the frankly selfish (the elderly millionaire vainly seeking immortality) to the apparently
acceptable (the couple seeking a replacement for a dead child, or a fully compatible
donor for a dying child, or the attempt to perpetuate some extraordinary artistic or
intellectual talent). Considerations of instrumentalization and eugenics render any such
acts ethically unacceptable. In addition, since these techniques entail increased
potential risks, safety considerations constitute another ethical objection. In the light of
these considerations, any attempt to produce a genetically identical human individual by
nuclear substitution from a human adult or child cell (“reproductive cloning”) should be
prohibited.
The ethical objections against cloning also rule out any attempt to make genetically
identical embryos for clinical use in assisted reproduction, either by embryo splitting or
by nuclear transfer from an existing embryo, however understandable.
Multiple cloning is a fortiori unacceptable. In any case, its demands on egg donors and
surrogate mothers would be outwith the realms of practicality at the present time.
ART law in Belgium 2007
•
FORBIDDEN: sexing, reproductive cloning, commercial
donation
•
Separate law on research on embryos (11-05-2003) –
federal commission
•
Not regulated:
–
surrogacy,
–
ethically controversial situations ( single women, homosexual
couples )
–
vulnerable psychosocial situations,
–
male age
–
In all of these cases: -> psychosocial evaluation -> ethical
commissions
“Embryo law”
Federal Commission for
Medical and Scientific
Research on
Embryos In Vitro
Act relating to research on embryos in vitro
(11 May 2003)
• The Commission is composed of:
–
–
–
–
4
4
2
4
MDs
PhDs
Legal experts
Experts in ethical questions
and social sciences
• and their substitutes (# 14)
• Centralise all information
related to
research projects on
embryos in vitro
• To licence research
projects on embryos in vitro
• Recommendations to the
Parliament and Senate
• Inform application of law to
local ethical committees
www.health.fgov.be/embryo
www.embryos.be
Research on embryos in vitro is allowed when
• Therapeutic objective
• Based on the most recent scientific knowledge
• Performed in an accredited laboratory from
- a University Centre for Reproductive Medicine
- a Centre for Medical Genetics
• Directed by MD or PhD
• During the first 14 days of embryo development
• No alternative method as effective to obtain
the information
It is not allowed
• To implant human embryos into animals
• To create chimaeras or hybrids
• To replace human embryos subjected to reseach
except …
• To use embryos, gametes and embryonic stem
cells for commercial purposes
• To do ‘eugenetic’ research
• To do sex selection except to prevent sex-linked
genetic diseases
• Reproductive cloning
Comments
• Some pathological conditions can only be diagnosed by
injecting human sperm in oocytes of another species
(because human oocytes are not readily available):
– Hamster ovum penetration assay
– Hamster zona binding assay
– Mouse oocyte activation test
• Reproductive cloning
– May be an option for many azoospermic men to have
genetically own offspring
– Sperm donation in Islam unacceptable: reproductive cloning
unofficially accepted option as soon a technically possible
Belgian Advisory Committee on Bioethics and
cloning
Consensus
The analysis of these arguments led all the members of the Committee
to the conclusion that, regardless of any other consideration, it is out
of the question at present to contemplate reproductive human
cloning.
In effect, in view of the scientific, technical and ethical uncertainties
surrounding the technique of reproductive human cloning, an outright
ban on any attempt to carry out cloning of this type in the near future
is to be recommended.
All the members of the Committee would like the psychological,
philosophical, medical and ethical studies on this subject to be
developed in greater depth, in order to help citizens form an
enlightened opinion of the phenomenon of cloning.
All the members of the Committee also agree that if a human clone was
to be born - even if it was due to an illegal act - he would still be a
full human being and none of the arguments put forward could
challenge his dignity as a human.
Belgian Advisory Committee on Bioethics and
cloning
POSITION A : consider the above-mentioned prohibition to be a
moratorium
-> Knowledge as regards the possibilities and implications of reproductive human
cloning from the biological, psychological, social and ethical points of view is
so limited at present that no sound argument in favour of the definitive
prohibition of any form of reproductive human cloning can be put forward.
-> concepts such as "human dignity", "uniqueness", "identity", "determinism" and
"instrumentalization" were used without an in-depth analysis and without a
comparison with their application in other spheres of human behaviour.
POSITION B: prohibit cloning < with the current state of knowledge,
representations and social relations and in view of:
-
-
the problems raised concerning construction of the clone's identity;
the disruption of the relationship between genetic identity and phenotypic
identity, especially through the identity of appearance that reproductive
human cloning would introduce
the problems of intergenerational relationships to which it could give rise
the problem of the social and, conversely, the self-perception of the clone
the instrumentalization logic to be found in the hypotheses in which the use of
this technique is envisaged, it would be wise to prohibit cloning.
POSITION C: prohibit and penalize as a crime
TNX