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The Journal of Reproductive Medicine for the Obstetrician and Gynecologist
Volume 11, Number 5, November 1973
In Vitro Fertilization of Human Ova and Blastocyst Transfer
An Invitational Symposium
Coordinator
Gebhard F. B. Schumacher, M.D.
Department of Obstetrics and Gynecology
The University of Chicago
Correspondents
B.G. Brackett, D.V.M., Ph.D.
Department of Obstetrics and Gynecology
University of Pennsylvania
Joseph Fletcher, B.D., S.T.D.
Department of Ethics
School of Medicine
University of Virginia
J.J. Marik, M.D.
The Tyler Clinic
Los Angeles, California
In vitro fertilization of human-ova and subsequent transfer of the human
blastocyst into the uterus of a woman, either the egg donor or a foster
mother, has not yet been reported to be a successful measure to grow an
embryo to term. However, it is conceivable that such a procedure may become
clinical routine sometime in the future after a variety of unsolved problems
have been overcome. It is a controversial issue at present whether one
should attempt to produce new human beings in this way. There is serious
concern about the ethics o f such an attempt, considering the apparent
insufficiency o f information on the possible damage to the fetus as well
as the moral and legal aspects which are, in essence, similar to the aspects
of donor insemination and abortion.
It is the feeling of the Editors of this journal that their readers should
have an opportunity to inform themselves about the present status of the
technology, its clinical consequences and the other problems involved
in such an approach. A discussion of this topic seems particularly indicated
since reports in the lay press are often dictated by sensationalism which
may create too much hope for couples plagued with childlessness and too
much fear of a totally uninhibited use of discoveries by irresponsible
scientists.
Several prominent investigators and scientists in the field o f reproductive
biology and medicine have been in
vited to participate in a symposium by correspondence. The following five
questions have been asked:
I. What is the potential clinical significance o f in vitro fertilization
of human ova and blastocyst transfer for infertility problems?
2. What are the technical problems in in vitro fertilization and in culturing
the fertilized egg, and what are the prerequisites for a successful egg
transfer from the test tube into the uterus of the mother-to-be?
3. What are the possibilities and dangers in manipulating the human conceptus
in early developmental stages?
4. Does the present status of technology allow us to project a possible
clinical application in the future?
5. Are there serious objections to in vitro fertilization and blastocyst
transfer in humans, on ethical grounds?
The contributions are presented in alphabetical order by authors' names,
as answers to each of the five questions. One group preferred to present
an article on the "Current Status of in vitro fertilization and Embryo
Transplantation", which is considered part of this symposium and
appears, therefore, after the Question and Answer section. G. F. B. S.
Question I. What is the potential clinical significance of in vitro
fertilization of human ova and blastocyst transfer for infertility problems?
Dr. Brackett:
The most obvious direct application of a procedure for in vitro fertilization
of human ova would be as a treatment of patients with infertility secondary
to tubal disease. By obtaining an ovum from a patient. s ovarv. fertilizing
it, culturing it through early- cleavage. and transferring it from the
culture dish into her uterus. a means for circumventing infertility resulting
from blocked oviducts should be possible. In addition to this important
clinical application in human medicine, other important applications can
be foreseen in the realm of veterinary medicine. Development of clinical
procedures for in vitro fertilization should make possible the combination
of gametes from animals with desirable traits and transfer of resulting
embryos into less valuable surrogate dams, thereby making possible rapid
upgrading of the world's livestock. Another example of clinical application
of in vitro fertilization in veterinary medicine might be in testing bull
sperm for its ability to fertilize ova before arid after frozen storage
of the sperm. Early elimination of bulls that yield semen that cannot
be stored would be of tremendous economic importance.
Dr. Mastroianni:
At this point in time, in vitro fertilization of the human ovum must be
looked upon solely as a biological experiment. The potential clinical
importance of this procedure will have its roots in knowledge derived
from study of the basic processes of human fertilization. The sequence
of events which result in the completion of the fertilization process
is still poorly understood in laboratory species. let alone in man. When
we have more complete information. we will be in a better position to
control human fertilization, and such knowledge could eventually lead
to new systems of contraception at the oviductal level. Once the vagaries
of in vitro human fertilization and early development have been worked
out. there is the obvious possibility that one could obviate the necessity
for the fallopian tube. Thus, in patients with absent or severely damaged
tubes one might some day recover an oocyte at laparoscopy, fertilize it
in vitro, culture it for three days and then transfer it to the uterus
of the donor. This approach would certainly require elaborate safeguards
in order to insure a healthy- product.
Dr. Shettles:
Bypassing blocked uterine tubes is the major potential clinical application
of in vitro fertilization. Corollary to this might be the identification
of functionally obstructive
uterine tubes or tubes that act too fast in egb transport. These latter,
which are speculative, must await more refined studies on tubal physiology
arid pathophysiology. Of some clinical importance would be the bypassing
of congenital anomalies of the tube or cornua, or the spatial problem
sometimes found in women with either developmental or surgically induced
contralateral single ovary and single tube. In numbers, this potential
might have the greatest impact in the reversal of the effects of voluntary
sterilization by tribal interruption, which is increasingly the method
of choice for "permanent" fertility control in the human female.
Question II. What are the technical problems in in, vitro fertilization
and culturing the fertilized egg and what are the prerequisites for successful
egg transfer from the test tube into the uterus of the mother-to-be?
Dr. Bracket:
Although procedures are described that enable human fertilization to occur
in vitro, the conditions for ovum recovery and sperm capacitation (assuming
a conditioning of the sperm cells to be necessary for rapid penetration
of ova) have not been adequately defined. An adequate definition of physical
and chemical conditions; and of physiological conditions of the gametes
themselves. which allow fertilization of human ova in vitro must be forthcoming
before useful applications of this procedure can be realized. One of the
major technical problems in\ olv es the recovery of an ovum that either
is already competent. or that can attain competency for fertilization
and continued development during a culture interval in vitro. Media used
for culture of ova and spermatozoa and for development of the recently
penetrated ovum must be composed of the necessary factors for normal development.
In experiments with rabbits, there was a suggestion that a defined medium
which supported in vitro fertilization and cleavage of ova which were
originally obtained from ovarian follicles was inadequate for development
following embryo transfer [26]. This is not surprising, since oviductal
fluid in which many of these events normally occur has been shown by many
investigators to change in composition as the beginnings of life progress
under its influence (for review, see [3]). Another imposin- technical
problem is that of conditioning the sperm cells for the role which they
play in the fertilization process.
Once a procedure is perfected for fertilization and early development
of human ova, the surgical transfer of the embryo into the uterus of the
mother-to-be should not present a formidable obstacle. The culture interval
required before embryo transfer may indeed be less than anticipated. There
is some evidence to suggest that a human ovum that has reached the eight-cell
stage by the third day after the time of ovulation may be advanced enough
to survive in a suitably receptive uterus [34]. Additional evidence obtained
in- studies of rhesus monkeys supports this idea [25].
Prerequisites for direct clinical application of human in vitro fertilization
procedures should include more animal experimentation. Answers to questions
concerning the risks involved along with the anticipated incidence of
success must first come from animal experimentation. The most successful
experiments along these lines have been accomplished with rabbits [4]
and with mice [27]. From these studies, only about 10 per cent probability
can presently be predicted for successfullv obtaining an ovum from an
ovarian follicle. carrying-out in vitro fertilization, and obtaining a
live offspring after surgical transfer of the resulting embryo into the
female reproductive tract of a surrogate dam. Additional experiments have
been conducted in rabbits to support the potential for future clinical
application of this procedure [26]. These experiments confirm the low
probability of success for any single ovum. whether recovered from an
ovarian follicle or following ovulation from the ovarian surface. Also,
these experiments support previous conclusions regarding embryo transfers.
i.e. the surviving offspring are apparently normal. In the opinion of
this writer, more animal experiments of this sort are a necessary prerequisite
for clinical development of such procedures for use in man.
ripe" ovum; nor is there any guarantee that there will not be excessive
aging of the egg in vitro before actual fertilization. Ova which are too
old are fertilizable but often exhibit abnormal development after activation.
In addition, there is no way to be sure that in vitro conditions are sufficiently
controlled such that ovum development does not occur faster or slower
than it would occur in vi The he timing of transfer into the uterus would
have to be carefully worked out to allow normal implantation. A discrepancy
between the age of the egg and the level of development of the endometrium
would result in a high rate of implantation failure. The endocrinologic
events that surround the removal of the oocyte from its follicle (man-made
ovulation) are still not adequately documented. In all, these drawbacks
would necessitate repeated attempts at transfer involving repeated gonadotropin
treatment and laparoscopy. At best one can predict a very low success
rate with a prognosis which would be considerably worse than that presently
obtained with tuboplasty procedures on severely damaged tubes - not a
happy prospect.
Dr. Shettles:
In order to achieve in vitro fertilization, freshness of the ovum is essential.
It is preferable that the ovum be not more than 12 hours old. The presence
of the first polar body is the sign that the egg is mature and ready for
fertilization (Figure 1). By culturing oocytes. the number of mature ova
to work with is greater, and con
Dr. Mastroianni:
There are a number of technical problems associated with in vitro fertilization
studies in the human. Not the least of these is the proper timing of the
experiment. AIthough oocytes recovered at various times in the menstrual
cycle can be cultured through metaphase of the second maturation division
and polar body release, such oocytes are not uniformly fertilizable. Work
in our laboratory has demonstrated that rabbit follicular oocytes could
not be fertilized in vitro unless the animal had been pretreated with
gonadotropins. Human oocytes which have been fertilized in vitro have
been recovered in the immediately preovulatory phase of the menstrual
cycle or have been obtained from patients who were pretreated with exogenous
gonadotropins. The relative inaccessibility of the human ovum has posed
a problem which has been solved recently by development of techniques
for o\ vum recovery via the Iaparoscope. A more efficient. and less demanding.
system for recover v of eggs is needed. however. Another technical problem
concerns the timing of ovum recovery. Present methods for scheduling ovum
recovery do not insure against the recovery of an "over
sequently the incidence of those fertilized is increased. Appropriate
hormonal treatment prior to laparoscopy is in order to enhance the harvest
of ova. To culture the fertilized egg to the blastocyst stage so that
it is ready for placement in utero, the conditions existing in the normal
site of fertilization in vivo (i.e. the distal third of the fallopian
tube) must be duplicated. The egg with the first polar body is discernible
by means of phase contrast microscopy through the halo of some 3000-4000
corona radiata and granulosa cells. Once this stage has been observed,
follicular fluid, tribal mucosa and spermatozoa in a state of readiness
for fertilization are introduced; controlled O2 tension is supplied to
the chamber, normal body temperature is regulated and pH controlled. The
addition of human placental serum to this medium has proven to be very
successful.
The prerequisites for a successful egg transfer from the test tube (culture
dish) into the uterus of the mother-tobe are illustrated by the following:
A nearly mature egg was aspirated from its follicle in the ovary of a
woman undergoing an operation to correct a defect in one of the fallopian
tubes. The egg was matured in vitro, i.e. until the first polar body appeared,
fertilized with spermatozoa from the woman's husband, grown in culture
for five
days to the blastocyst stage (Figure 21 and then transferred by means
of pipette and a segment of caudal catheter via the cervix into the uterus
of a second individual scheduled for surgery. The menstrual cycles of
the two women were synchronized hormonally (shown histologically by endometrial
biopsies) which afforded a hospitable environment of the transplanted
blastocyst. Informed consent was obtained to ascertain whether implantation
could normally occur.
Two days after the transplant; the previously scheduled hysterectomy was
performed on the recipient. The implanting blastocyst was then located,
with the dissecting microscope, on the upper, posterior lining of the
excised uterus. Examination and comparison with implanting blastocysts
following fertilization in vivo [36, 37] showed that it was nidating properly.
It consisted of several hundred cells at this point and no contraindications
for continued development were discernible.
Question III. What are the possibilities and dangers in manipulating the
human conceptus in early developmental stages?
Dr. Brackett:
Dangers inherent in such a procedure as clinical application of in vitro
fertilization and embryo transfer for human patients, at this point, comprise
an area for speculation. Although effects of such an experiment on human
beings is completely unknown, extrapolation from animal experiments that
have been done to date might lend encouragement. It is presently thought
that any significant damage that is done to the ovum, sperm cell, or developing
embryo leads to embryonic death rather than to abnormalities of offspring
that are delivered. More definitive statements regarding dangers involved
in these procedures can only come from further experimentation with lower
species. If such studies provide no contraindications, similar procedures
might be ready for human application.
Dr. Mastroianni:
Manipulation of the human ovum in an artificial environment might easily
produce a defective product. Such an embryo would likely be aborted early
in pregnancy, but there is no guarantee that this would happen. Chromosome
analysis of amniotic cells later in pregnancy would be helpful as a screening
measure, but a normal idiogram would not automatically guarantee normal
offspring.
Dr. Shettles:
With fertilization in vivo, the zona pellucida (Figures 3, 4) remains
intact until the dividing egg passes in utero and until the blastocyst
commences to send the protoplasmic extensions out which traverse the zona
pellucida and start nidation. For the developing egg to traverse the interstitial
part of the fallopian tube, it must pass through the very narrow portion
of the tube. To skillfully handle the egg, aspirate and transfer it under
direct vision, it would not be subjected to anything like the pressure
encountered in passing through the interstitial portion of the tube. The
zona pellucida possesses great elasticity [50. 51, 52] and the ovum is
protected in the perivitelline fluid similar to the infant in the amniotic
fluid. Great teasing, stretching must be carried out in order to disrupt
the zona pellucida. Consequently, in the proper culture medium there is
little likelihood of damaging the human conceptus at this stage when all
is still within the zona pellucida. I would say from 20 years work with
the human ovum, that the possibilities are nil. It stands to reason that
if even one of the blastomere cells were damaged, this could lead to developmental
anomalies. The indiscriminate giving of medications in patients in the
earliest stages of in vivo fertilization present infinitely greater chances
of injury to the conceptus.
Question IV. Does the present status of technology allow us to project
a possible clinical application in the future?
Dr. Brackett:
Yes. Clinical application may be expected within a few years. Rapid advancements
have been made in this area during the last two decades. Rabbit ova were
first fertilized in vitro with capacitated sperm during the early 1950-s
[66]. Ten years later, hamster ova were fertilized in vitro [74]. Five
years after this, mouse ova were fertilized in vitro [71] and during the
last five years ova of the cat [22], human being [17, 42], guinea pig
[73], Mongolian gerbil [29] and rat [69] have been added to the list of
mammalian species in which fertilization can occur in vitro.
Efforts directed toward obtaining human ova which have the ability to
undergo fertilization are becoming more successful; especially following
the use of hormonal therapy [65]. Advancements in recovery of preovulatory
human oocytes following priming of patients with gonadotropins has been
practiced by 5teptoe and Edwards for several years now [64].
Assuming fertilizable ova can be obtained, the major remaining obstacle,
then, is to reach an understanding of sperm capacitation. Capacitation
of sperm can occur spontaneously- in vitro in defined media, as in the
mouse [68. 69], or in fluids from the female reproductive tract, as in
the rabbit [5], and rapid progress is being made in understanding the
mechanism of sperm capacitation in mammalian species. A new simple immunological
approach for detecting removal of seminal plasma components from the rabbit
sperm surface during the sperm capacitation process [30] has led to the
development of a sort of radioimmuno-assay for sperm capacitation [31].
This assay enables one to follow in a more quantitative way the removal
of antigenic seminal plasma components that normally coat the surface
of ejaculated sperm. It is likely that these seminal plasma components
are related to decapacitation factor (DF) [2. 10. 72] of seminal plasma
and that their removal comprises a major part of the capacitation process.
At the time of this writing. it is possible to effect capacitation under
defined in vitro conditions for epididymal sperm of two mammalian species
- the hamster [74] and the mouse [68. 69]. Sperm of different species
seem to require various degrees of conditioning as reflected by the varying
g time intervals which they must reside in the respective female reproductive
tracts before gaining the ability- to penetrate ova. However, it seems
likely that the basic mechanism of sperm capacitation is the same in all
mammals. An understanding of this mechanism is on the horizon and it should
soon be possible by similar means to achieve in vitro capacitation under
defined conditions for sperm from any mammalian species.
With the advent of these advances. clinical application of procedures
for in vitro fertilization can be predicted in human and veterinary medicine.
However, a continuation of basic research in the important area of mammalian
fertilization should receive even greater impetus
with the development of this procedure. From basic. studies of in vitro
fertilization clues leading to development of better means of contraception
and new ways of enhancing gamete union can be anticipated.
Dr. Mastroianni:
Present technology does not allow one to project a clinical application
in the near future. Optimistic predictions for future success only serve
to victimize patients who have read about such procedures and have been
led to believe that a solution to their infertility problem is close at
hand. Clinicians treating infertility patients realize that often their
patients are willing to subject themselves to extreme approaches. We should
be mindful of this always and temper our enthusiasm for new and untried
approaches with an extreme degree of caution.
Dr. Shettles:
A review of the publications [15. 17, 20, 22. 35-37,40-62] would allow
us to project a possible clinical application now, not necessarily in
the future. Also, other mammalian work would pave the way.
Question V. Are there serious objections to in vitro fertilization and
blastocyst transfer in humans, on ethical grounds?
Dr. Brackett:
In this author's opinion, no serious objections on ethical grounds should
be anticipated for application of a procedure for in- vitro fertilization
with subsequent embryo transfer when using a patient's ovum and her husband's
sperm in an effort to circumvent the consequences of the woman's nonfunctional
oviducts. Perhaps other applications of this procedure might meet with
disapproval by some on ethical (,rounds. as artificial insemination genetic
counseling. and abortion are clinical procedures that are not universally
accepted.
Dr. Fletcher:
The first four questions call for a knowledge of reproductive medicine
be yond my competence and I will therefore restrict my response to the
last one, the ethical question. I have -in view egg transfers from third
party donors (ETD) as well as transfers of a wife's own egg (ETW).
A primary and basic ethical proposition is that the entire procedure (the
egg's extraction. its laboratory fertilization, and its implantation in
utero) is morally licit. unless the consequences should rule it out as
a violation of the classical principle of proportionate good.
Put another way, any clinical means of overcoming, childlessness and protecting
the patient's or prospective child's health is justified by the end sought:
therefore if it could ever be morally objectionable it would be because
the foreseeable evil consequences outweigh the foreseeable good. Looked
at this way, medical practices are never intrinsically wrong: if they
are wrong sometimes it will be because of extrinsic factors. This ethical
relativity y or flexibility is the very essence of clinical ethics. y
Biomedical morality is humanistic. Its highest good or first-order value
is human health and wllbeing. Legitimate ends or purposes of in, vitro
fertilization and blastocyst transfer (ET) are. for example. to bypass
tubal blocks from infection or a salpingectomy, or to avoid passing g
on a woman's genetic defects by substituting a donor's egg for implant.
In short, it may be done for reasons of either pathology or quality of
-life. The procedure is more complicated and onerous than artificial insemination,
whether from husband or donor. but ethically regarded they are much the
same thing: ET and AI are both forms of assisted reproduction. the only
difference between them being the sexual one. -
What then are the objections? They appear to be of two kinds. One is metaphisical,
and in its moral thrust it is inimical to the humanism of medical care.
The other is more empirical, more subject to proof or disproof. The first
is a religious or belief assertion that ET is immoral because in the case
of a wife's egg it is un-natural and in the case of a donor's egg it is
adultery in addition to unnatural - i.e., it uses a generative factor
from outside the
spouses' own resources. The second objection is that the procedure risks
harm to the prospective child; even if it is presumably- safe for the
patient.
The first objection, the religious one, is a matter of belief or personal
opinion. It is neither verifiable nor falsifiable. Without mentioning
names we can take note that two or three vigorous, not to say strident,
discussions have been published taking this line. The argument stems from
an a priori assertion or syllogistic "major premise" that to
be moral human reproduction must be. coital (the "natural" mode).
It is sometimes reinforced by claiming that artificial technologies undermine
both individuals and the family, but this pseudo-consequential reasoning
---- the tail to the a priori dog. Such rhetoric uses putdown language
like "guinea pigs" and "test tube babies." At bottom
this posture ignores the fact that artificial modalities of conception
such as ET and A1 (cloning or nuclear transplants would fall into this
bracket) are as fully biological or "natural" as coitus. The
v may be less desirable but they are acceptable. To subordinate human
need in this way to a doctrinaire negative prohibition is, of course.
alien to humanistic medicine. And the superficial notion that "the
natural is better" cannot survive a critical scrutiny ethically or
biologically.
The second objection to ET is of a kind which makes more sense and poses
more substantial reasons for pause and for a conscientious examination
of the practice. Perhaps the A.M.A.'s editorial appeal for a moritorium
is too typical of rnedical politicians who will not allow any issue to
be decided on its own merits, but it is after all a part of the picture
[l3]. This policy of "benign neglect" has been endorsed by those
who demand more animal tests before we approve of any clinical use of
ET in human reproduction [22]. This posture is based on the opinion that
we cannot avoid damaging all or at least some of the conceptuses. and
possibly the patients too. As an appeal to consequentialist calculation
it is a more meaningful objection, and some of those who raise this objection
appear to do so in a quite consequentialist way, without tying it to the
first objection - at least not openly and admittedly.
Appeals to Primum, non nocere are naive if the principle is used as an
absolute prohibition or if the "harm" alleged is in fact not
harmful. If the patient is harmed invariably or even only frequently in
ET it would be a very rare clinical situation in which it could be justified.
But this. I gather is not the case.
The real bone of contention, therefore. is the conceptus and its fate.
Some of the anti-ET people regard prenatal life at any stage as being
human in the sense of a person. a "human being" or a "nascent"
human being. with a "right to life" - and on this basis to damage
a blastocyst in an in vitro fertilization and implantation is practically
killing an innocent human being (murder). This is the doctrine or dogma
which the U. S. Supreme Court rejected in January, 1973, for legal reasons
which coincide with medical and biological reasoning. To imply that experimental
embryologists or fetologists (in selective abortion) are mass murderers
is next thing to mumbojumbo. Others among them, less radically, assign
personal status only to a nidated conceptus, an embryo.
Even if our monitoring were wholly accurate, so that we could terminate
all damaged as well as defective conceptuses, the first group would not
be mollified because of their condemnation of abortion; the second less
radical group, if their thinking is objective and logical, would raise
no further objection. Nature, not being as indiscrimatingly "pro-life"
as some people are, takes care of most such aberrations by spontaneous
abortion, at or about nidation - as medicine should and will when it is
able. But just how successfully and generally such damage could be detected
clinically, I do not know.
Assuming that monitoring for damage and defects is not yet reliable in
ET but that an implant has succeeded, and assuming further that the watchful
eye of amniocentesis and other hopefully earlier check tests would still
let a certain number of damaged or defective fetuses reach birth undetected
and unforestalled, is the range of error of sufficient magnitude to rule
out ET, as such, always? Morally, can we take the chance, run the risk?
We need more hard data than we now have to figure out good trade-off or
cost-benefit estimates. This is the main "word to the wise"
from ethicists to the scientists and clinicians, at this point in medical
history. As Joshua Lederberg once remarked, ignorance is not a good reason
for staying ignorant because there is a foreseeable margin of error. "How
can the ignorant know what they should not know [24]?" On my own
account I would add that dangerous ignorance is far more dangerous than
dangerous knowledge. Egg transfer cannot ever cope with its decision-making
problems until it has had enough experience to provide an empirical base,
i.e., until it has done enough actual transfers as investigative or exploratory
medicine. We have to run some risk in ETs, as in everything else, to know
what we are doing. The refusal to run risk is sheer stasis, moral hardening
of the arteries.
Prudence, an ancient "cardinal" virtue, asks us. to face the
calculation of legitimate risks, saying, "Make sure you don't pay
too much, that you don't lose too much to get what you want." This
is very different from the so-called wedge argument, which forbids dangerous
or chancey actions on the ground that they would become a slippery slope
to the loss of everything - so that, for example. even one ET done as
an act of investigative medicine would be immoral. One debator has actually
joined this tactic of opposition to ET to the claim that ET is a sur
gical intervention and that two persons are involved, the potential child
as well as the patient, and that since consent cannot be forthcoming from
the "nascent" party to the procedure it would be unethical to
do it even though the patient wanted it.
It is hard to take this contentiousness as a serious discussion, yet it
was developed at length in a well known medical survey journal [32, 33].
Looking at our problem of right-wrong, good-evil, desirable-undesirable
in terms of relative values and the uncertainties of decision making in
a finite world of so many problematic options, what are we to say to physicians
in reproductive medicine as they stand on this new frontier opened up
by artificial enovulation - following up artificial insemination?
If we believe (we cannot know) that conceptuses or embryos are human beings
or that somehow they have an "unalienable right" to go on developing
towards human status without medical interference, we will logically oppose
all laboratory sacrifices or fetal terminations. (There still remains
the ethical question whether and under what conditions this necessarily
private belief would ever justify obstructing research and investigative
treatment, or justify refusing abortions to those who do not hold the
same belief or doctrine.) The more we learn about the biology and sociology
of human reproduction the less tenable this particular doctrine is pragmatically
- which means morally when our first-order value is human health and wellbeing.
My own conclusion is that given the unknown quantities already noted,
the most humane thing to do (i.e., the best thing morally) is to explain
things as they are in ET to patients and let them choose or reject the
treatment, as we do in all surgical care. Medicine's forward movement
is due fundamentally to investigative or experimental treatment. To deny
patients their initiative and choice in the matter is to impose on them
one's own subjective theory of prenatal life and to deny them control
of their lives reproductively.
This is a Promethean way of looking at it, perhaps, but we need to remember
that, as Gerald Feinberg says, Prometheus' name comes not from arrogance
(hubris) or trying to play God but from the Greek for forethought [15].
Pro and mathein, to think ahead to emerging needs and options, is what
raises human stature.
Dr. Mastroianni:
In my judgment, ethical considerations of in vitro fertilization and blastocyst
transfer include the moral issue surrounding the uncertainty that the
product being transferred will develop normally. At present, we cannot
say whether we will ever be confident enough of such techniques as to
allow such human experimentation. Attitudes toward these procedures in
Homo sapiens are
naturally influenced by attitudes in general toward the recently fertilized
developing human embryo, with all of the concomitant philosophical implications.
Dr. Sh.ettles:
In vitro fertilizations and blastocyst transfers in humans have invoked
criticisms similar to those launched at work with artificial insemination
[39] and clinical use of frozen semen [8, 38]. The critics of in vitro
fertilization have directed their attack toward those who are trying to
enable infertile couples to have the child they want so much. It is the
opinion of this writer that childless couples' rights to utilize whatever
methods and techniques
are available to produce wanted offspring far exceeds and surpasses the
rights and privileges of the critics who would condemn and suppress scientific
work directed toward helping them to accomplish this aim.
We have invested considerable energies in striving to help the infertile
couple conceive. Why not continue this mission by constantly advancing
our knowledge and skills? Through in vitro fertilization and blastocyst
transfers we can begin to help the woman whose tubes have been blocked
for one reason or another but who still wants to have a child. Just because
the bridge may be out or blocked should not prevent the use of the helicopter.
The Editors of this journal would like to express their appreciation
to the authors for their willingness to contribute to this symposium by
correspondence on a controversial issue.
In vitro fertilization and blastocyst transfer may be a way in the future
to overcome childlessness due to impairment o f the Fallopian tubes. The
vagaries o f collect ing o f oocytes, o f in vitro fertilization, o f
blastocyst culturing, and of artificial implantation in a hormonally synchronized
uterus must be worked out. The possible hazards to the fetus as well as
to the mother must be determined to be minimal. The risk-benefit analysis
will be an important factor in future research considerations as well
as in each individual case where, such an approach may be attempted.
The scientific community should observe carefully and objectively the
developments in this field. We have to be concerned with overpopulation
as physicians and as inhabitants of this world. We also have to be concerned
with the individual patient seeking the help of a physician with respect
to family size and child spacing as well as her suffering from childlessness.
The infertile patient is entitled to the best possible treatment like
any other patient.
1 f the present technology is not sufficiently developed and if there
is still a lack of information on the possible hazards o f in vitro fertilization
and blastocyst transfer, the application to human medicine should probably
be postponed. This, however, should not prevent research in these aspects
of reproductive biology. All possible efforts must be undertaken to provide
more basic information for future applications in patients with tubular
occlusion. We look forward to their benefit one day from the progress
that has been made in reproductive medicine.
Comments and discussion remarks by readers of the Journal. will be welcome.
G. F. B. Schumacher, M.D.
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