/'Jl:

Ethics Advisory Board

Depeirtment of Hecdth,
Education, eind Welfare

Report and Coidusions:

HEW Support of
Research Involving Human
In Vitro Fertilization and
Embryo Transfer

May 4, 1979 qmss^t^

tjEPOSlTORY
 Ethics Advisory Board

Department of Hecilth,
Education, and Welfare

Report and Conclusions:

HEW Support of
Research Involving Human
In Vitro Fertilization and
Embryo Transfer

May 4, 1979

For sale
3l^>^
by the Superintendent ol Documents, U.S. Govemment Printing Office, Washington, D.C. 20402
 ETHICS ADVISORY BOARD

CHAIRMAN: James C. Gaither, J.D.

VICE CHAIRIWJ: David A. Hamburg, M.D.

Sissela Bok, Ph.D. Maurice Lazarus

Lecturer in Medical Ethics Chairman, Finance Committee
Harvard University Federated Department Stores, Inc,
Boston, Massachusetts

Jack T. Conway Richard A. McCormick, S.T.D.

Senior Vice President Professor of Christian Ethics
United Way of America Kennedy Institute for the Study
Washington, D.C. of Reproduction and Bioethics
Georgetown University

Henry W. Foster, M.D. Robert F. Murray, M.D.

Professor and Chairman Chief, Division of
Department of Obstetrics Medical Genetics
and Gynecology College of Medicine
Meharry Medical College Howard University

James C. Gaither, J.D. Mitchell W. Spellman, M.D.

Cooley, Godward, Castro Dean for Medical Services
Huddleson and latum and Professor of Surgery
San Francisco, California Harvard Medical School

Daniel C. Tosteson, M.D.

David A. Hamburg, M.D. Dean, Medical School
President, Institute of Medicine Harvard University
National Academy of Sciences
Washington, D.C. Agnes N. Williams, LL.B.
Potomac, Maryland

Donald A. Henderson, M.D.

Dean, School of Hygiene Eugene M. Zweiback, M.D.
and Public Health Surgeon in Private Practice
Johns Hopkins University Omaha, Nebraska
 ETHICS ADVISORY BOARD STAF

PROFESSIONAL STAFF SUPPORT STAFF

Charles R. McCarthy, Ph.D. Roberta Garfinkle

Staff Director Committee Assistant

Barbara Mishkin, M.A. Erma L. Pender

Deputy Staff Director

Coral M. Sweeney
F. William Dommel, Jr., J.D.
Special Assistant to the
Staff Director Eleanor S. Yago

Roy Branson, Ph.D.

Ethics

SPECIAL CONSULTANTS STUDENT ASSISTANTS

Philip Halpern, J.D. Jose Pertierra, M.A.

Legal Consultant to the
Chairman
Ray Moseley, M.A.

LeRoy Walters, Ph.D.

Director, Center for Bioethics
Kennedy Institute
Georgetown University
 TABLE OF CONTENTS

I. Background 1

A. The Normal Human Reproductive Process 1

B. Previous Research with and Application of

In Vitro Fertilization and/or Embryo Transfer 2
C. The First Phase of the Ethical Debate 11
D. The Evolution of HEW Involvement 13

II. Laboratory Research Involving Human In Vitro

Fertilization and/or the Culture of Early Human
Embryos: Technical and Ethical Issues 21

A. The Goals and Potential Benefits of the Research 22

B. The Design of the Research 25
C. The Consent of Sperm and Ovum Donors. 26
D. The Status of the Early Human Embryo 27
E. Potential Adverse Consequences of the Research 30

III. Clinical Applications of In Vitro Fertilization

and/or Embryo Transfer: Technical and Ethical Issues 37

A. The Need for and Potential Benefits of In Vitro

Fertilization and Embryo Transfer 37
B. The Need for and Adequacy of Prior Laboratory
and Animal Research 39
C. Risks of Procedures 45
D. The Consent of Sperm and Ovum Donors 47
E. The Status of the Early Human Embryo 48
F. Potential Adverse Consequences of Clinical
Applications 50
G. Questions of Allocation 52

IV. Legal Issues Surrounding Human In Vitro Fertilization,

Embryo Culture, and Embryo Transfer 60

A. Existing Federal and State Law Applicable to

Human In Vitro Fertilization and/or Embryo Transfer ... 60
B. Constitutional Issues 63
C. Liability for Injuries 71
D. Criminal Law 75

V. Review of Public Attitudes 81

A. Responses Received by the EAB 81

B. Public Opinion Surveys 88
C. List of Public Witnesses 90

VI. Summary and Conclusions 100

 .

PREFACE

Current regulations of the Department of Health, Education, and

Welfare (HEW) prohibit the support of research involving the ferti-

lization of a woman's egg (ovum) outside her body (in vitro fertil i-

zation) until the Ethics Advisory Board has advised the Secretary as to

its ethical acceptability. In 1977, the Department received an application

for support of such research and, after it had been approved from a

scientific point of view, forwarded it to the Board. At its meeting in

May 1978, the Board agreed to review the research proposal.

Over the summer, the announcement of the birth of a baby following

in vitro fertilization in England aroused great public interest; it

appears that a number of couples are ready and eager to avail themselves

of such procedures in order to overcome infertility. Therefore, in

September, Secretary Califano asked the Board to broaden its consideration

of the pending application to include the scientific, ethical, legal and

social issues surrounding human in vitro fertilization and embryo transfer

in general

This report is the result of over a half a year of study during

which the Board asked scholars and experts in the fields of reproductive

science, ethics, theology, law and the social sciences, to prepare

reports and discuss the issues with Board members in public meetings. In

addition, the Board held a series of eleven public hearings throughout

the country in which private individuals, professional societies and

public interest groups had an opportunity to present their views. The

Board also received over 2,000 pieces of correspondence including letters,

postcards and formal testimony, all of which were copied and distributed

to each of the members.

 Chapter I of the Report provides background information about the

human reproductive process and research involving in vitro fertilization

and embryo transfer. Chapter II explores the technical and ethical

issues surrounding such research in humans and Chapter III addresses the

technical and ethical issues surrounding the use of the procedures in

clinical practice. Chapter IV presents a review of the legal issues,

and Chapter V summarizes public attitudes as presented to the board and

as determined by recent public opinion polls. The Board's conclusions

are set forth in Chapter VI.

The Board hopes that its deliberations and conclusions will be

useful to the Secretary and staff of the Department in making decisions

regarding the support and conduct of research involving hum.an in vitro

fertilization and embryo transfer.

An appendix containing papers prepared for the Board by scholars in

the fields of reproductive science, ethics, theology, law, statistics, and

social policy will be available through the U.S. Government Printing Office.

Ordering information may be obtained from the Ethics Advisory Board, Westwood

Building, Room 125, 5333 Westbard Avenue, Bethesda, Maryland 20016,

telephone: (301) 496-7776.

 CHAPTER I: BACKGROUND

A. The Normal Human Reproductive Process

Through long years of painstaking study reproductive biologists

have been able to acquire significant information concerning the human

reproductive process. The gathering of data on this process has presented

formidable obstacles, since fertilization and the earliest days of

embryonic development occur within the woman's body where, for both

technical and ethical reasons, they are not readily accessible for

scientific study.

According to the best available evidence, for the average couple

the performance of the human reproductive system is only partially

"efficient." That is, not every meeting of sperm and ovum results in

the production of a viable embryo. One study estimates that in 16% of

the cases where human ova are exposed to sperm, fertilization fails to

occur. When fertilization does occur, the rate of embryonic loss during

the first week is estimated to be 18% and in the second week an addi-

tional 32%. According to this study, only 37% of human zygotes survive

to be delivered subsequently as live infants,' Statistical surveys of

the length of time generally required to establish a pregnancy seem to

9
lend support to these estimates."^

These relatively high rates of embryonic loss are due in part to

external environmental factors which impede continued embryonic develop-

ment and in part to chromosomal or genetic abnormalities in the embryo

itself. The exact proportion of embryonic loss due to each of these

factors is unknown. However, one study estimates that perhaps 50% of

the embryonic loss subsequent to successful fertilization is due to

3
chromosomal aberrations. Thus, natural selection against most embryos

with serious chromosomal abnormalities seems to occur during pregnancy,

particularly during the first eight weeks following fertilization.

B. Previous Research with and Application of In Vitro Fertilization

and/or Embryo Transfer

1 . General

In previous research with humans and other species three major

techniques have been employed: (a) in vitro fertilization without

subsequent transfer of the embryo to the uterus of a female; (b) in

vitro fertilization followed by embryo transfer; and (c) embryo transfer

following fertilization by mating or artificial insemination. Only the

first and second techniques have been employed with human beings.

For in vitro fertilization (in either the first or second cases

listed above) a method must be found for harvesting ova from the female

and for bringing the ova into contact with sperm from the male in the

laboratory setting. In human beings ova are usually secured from the

female by means of a surgical procedure called laparoscopy. A needle is

passed through the woman's navel and brought into proximity to one or

both of her ovaries. Through visual sighting follicles containing mature

ova are located, and the ova are removed from the follicles by means of

the needle. Human females normally produce only one mature ovum per

menstrual cycle; however, if certain hormones are administered early in

a given menstrual cycle, multiple ova are produced which can then be

harvested during a single laparoscopic procedure.

 Following the successful harvesting of ova, the ova and sperm from

a male are placed in a laboratory medium where ova and sperm complete

maturation and fertilization occurs. The early embryo is then trans-

ferred to a different laboratory medium for subsequent growth. In the

first case noted above the embryo is retained in culture in the labora-

tory setting. In the second case the embryo is transferred to the

uterus of a female -- either the female donor of the ova or another

female whose hormonal cycle is at approximately the same stage as the

cycle of the donor female. If the transfer is successful, implantation

and subsequent development of the embryo occur in the uterus of the

recipient female.

In the third case fertilization occurs in vivo in the animal,

either through mating or through artificial insemination. The ova may

be either those of the inseminated female or those of a donor. Follow-

ing fertilization but prior to implantation, the resulting embryo or

embryos are removed from the reproductive tract of the female and are

transferred to the reproductive tract(s) of one or more recipient females.

If the transfer is successful, implantation and subsequent embryonic

development occur in the recipient female(s).

In summary, the following combinations of in vitro fertilization

and/or embryo transfer are possible:

i. In vitro fertilization without embryo transfer

ii. In vitro fertilization and subsequent embryo transfer

a. Transfer to the uterus of the donor

b. Transfer to the uterus of one or more other
females
 iii. In vivo fertilization and subsequent embryo transfer

a. Fertilization by means of mating

b. Fertilization by means of artificial insemination
c. Ova of the mated or inseminated female
d. Donor ova introduced into the female prior to
fertlization

2. Research and Applications with Animal Species

a. Nonprimate Laboratory Animals. Successful laboratory ex-

periments with embryo transfer of early rabbit embryos predated by

almost 70 years the first successful experiment with in vitro fertilization.

In 1890 Walter Heape -- working in Cambridge, England -- succeeded in

transferring two embryos from an Angora doe rabbit which had been mated

with an Angora buck into the oviduct of a Belgian hare doe which had

itself mated several hours before. Six offspring were born to the
4
Belgian hare doe, of which two were clearly Angoras. A similar technique

was applied to cultured mouse blastocysts in 1958 by Anne McClaren and

John D. Biggers. Some of the offspring grew to adulthood and reproduced

5
naturally to yield a second generation.

Between 1930 and 1959 many investigators sought to imitate the

process of embryonic development in the laboratory setting by means of

in vitro fertilization. However, the researchers failed to devise

sufficiently stringent criteria to demonstrate that early embryonic

development was indeed the result of fertilization of ova by sperm

rather than the effect of laboratory manipulation of the unfertilized

ovum. (Severe trauma to the ovum, e.g. , puncture or electric shock, can

in some cases induce cell division without fertilization). In 1959,

however, M.C. Chang of the Worcester Foundation in Massachusetts succeeded

in documenting in vitro fertilization in the rabbit by taking sperm from

male rabbits with specific traits not present in the female ovum donor.

The presence of the male traits in the offspring (following embryo

transfer and subsequent development) provided unequivocal proof that the

sperm had indeed transmitted genetic information to the offspring.

Since 1933 there have been 5 published studies of embryo transfer

following in vivo fertilization in rabbits, 3 in rats, and 1 in mice.

From 1959 to the present, 13 papers (including Chang's initial paper) on

in vitro fertilization followed by embryo transfer in rabbits have been

published, 8 papers on the same procedure in mice, and 1 in rats. In 3

of those studies, 1 on rats and 2 on rabbits, abnormal offspring were

Q
reported; however, the causes of the abnormalities are unknown.

Many studies in experimental embryology do not include embryo

transfer as a component; rather, they involve various types of laboratory

investigation of the early embryo -- whether produced by in vivo or in

vitro fertilization. These non-transfer studies examine such topics as

mechanisms of normal and abnormal fertilization; the earliest stages of

embryonic development; causes of abnormality in early embryos; and the

effect of various environmental factors, e.g. , radiation, freezing, and

g
various chemicals, on fertilization and early development. Research

techniques employed in the study of these topics include fertilization

in vitro ; in vitro culture of early embryos to and beyond the blastocyst

stage; the fusion of embryonic cells with other cells; the infection of

embryonic cells with viruses; the introduction of various changes (chemical

or temperature changes, for example) into the embryonic environment;

biochemical studies of embryonic cells; and microscopic analysis of

embryonic cells.
 6

The technique of superovulation -- that is, the administration of a

hormone which induces the female to produce a larger than usual number

of ova -- has sometimes been employed in conjunction with J_n vitro

fertilization. Superovulation has been studied rather extensively in

rabbits. In one controlled comparison of normally ovulated and superovulated

oocytes (total number = 538) 60.1% of embryos obtained following superovulation

and 54.6% of those obtained following normal ovulation developed into

normal young. In contrast, several other studies in rabbits, as well

as in mice, ndve concluded that an increase in the incidence of chromosomal

12
aberrations occurs following superovulation.

The effects of freezing mammalian embryos have also been studied in

considerable detail. The most studied species is the mouse. In one

study mouse embryos stored at -195° C for 369 days were cultured and

transferred after having been frozen and thawed. The freezing process

caused some cellular damage, as evidenced by the fact that a smaller

percentage of frozen embryos survived than did unfrozen controls.

However, previously frozen offspring were normal and grew and reproduced

at the same rate as control animals. The second-generation progeny of

13
the frozen embryos were also normal.

b. Farm Animals. In research with farm animals -- particularly,

cows, horses, sheep, goats, and pigs -- the primary emphasis has been on

application rather than on the development of basic knowledge. For this

reason, more work has been done on embryo transfer following in vivo

fertilization than on in vitro fertilization itself. Research both with

in vitro fertlization and with embryo transfer is dwarfed by the use of

artificial insemination for commercial breeding purposes: with the aid of

artificial insemination no fewer than 100,000,000 cattle have been
14
produced in the United States alone.

Relatively little laboratory research with in vitro fertilization

or with in vivo fertilization using donated ova has been performed in

farm animals. Five successful studies in cattle, three in sheep, and

1 5
one in pigs have been reported.

In contrast, embryo transfer following in vivo fertilization of the

female's own ova has been widely employed, primarily in cattle, during

the past five years. Indeed, thousands of progeny have been produced by

this method. Techniques for recovering early embryos from the female

following fertilization include both surgical and nonsurgical means.

Offspring from embryo transfer appear to be normal, although no carefully

controlled study of the outcome of pregnancy has been undertaken.

Two additional techniques which can be employed in conjunction with

in vitro fertilization and/or embryo transfer have been studied in farm

animals. In two studies efforts were made to evaluate the overall

quality of early cattle embryos by examining them for compactness,

symmetry, and density. These subjective qualitative assessments were

successful in predicting differential rates of subsequent pregnancy.

A second technique which has been employed experimentally with cattle

embryos is the determination of sex through removing cells from the

trophoblastic layer of the early embryo. However, many embryos are

1 Q
damaged in the process of sex determination.

c. Non-Human Primates. Relatively little research on in

vitro fertilization and/or embryo transfer has been performed with non-

human primates. Three studies beginning with that of Gould and associates
 8

in 1973 and continuing with the work of Dukelow and Kuehl have

demonstrated fertilization in vitro with the squirrel monkey. In vitro

fertilization studies with the Olive baboon and the rhesus monkey have

not yet provided definitive proof that fertilization has in fact occurred.

However, in 1976 D.C. Kraemer and associates reported the successful

transfer of an embryo from an Olive babboon to a synchronized female

?1
following in vivo fertilization. Similarly, in 1977 J.H. Marston and

associates reported a successful embryo transfer from one oviduct to the

22
other in a female rhesus monkey after in vivo fertilization.

The meager data from primate research may reflect technical and

funding limitatons on the one hand, or a lack of interest or incentive

on the other. Gould has noted that primate research is expensive and

that the competition for research funds is a limiting factor. He further

observes that investigators may be confronting "as yet unidentified

problems regarding the culture requirements for successful maintenance

23
on nonhuman primate gametes in vitro ." By contrast, Sackett and Smith

have expressed confidence that there would be no problem in obtaining a

sufficient number of primates to undertake research in this area; further,

they report that reliable normative data regarding fertilization, pregnancy,

and early development exist against which to measure deviations from the
24
norm resulting from in vitro fertilization and embryo transfer.

3. Research and Applications in Humans

Most successful human research has been concentrated on achieving

in vitro fertilization and on culturing early human embryos in the

laboratory. Efforts at clinical application of in vitro fertilization

and embryo transfer to overcome infertility were notably unsuccessful

until the latter half of 1978 and early 1979 when the delivery of three

apparently healthy infants following these procedures was announced.

The first well documented achievement of in vitro fertilization

with human gametes was reported in 1970 by R.G. Edwards, P.C. Steptoe,

and J.M. Purdy. Since 1970 there have been seven additional scientific

reports of successful in vitro fertilization -- four by R.G. Edwards and

?fi 27
his colleagues, two by A. Lopata and associates in Australia, and
?8
one by Soupart and Strong in the United States. No details concerning

the apparently successful in vitro fertilization in Calcutta, India,

have been published.

Embryo transfer in humans has been attempted only following in

vitro fertilization. A total of three reports of such efforts have

appeared in the scientific literature, one by the Australian group (in

1973),^^ and two by Edwards and Steptoe (in 1976 and 1978).^° The first

attempt led to raised levels of human chorionic gonadotropin in the

maternal blood, but implantation was not documented. The second resulted

in an ectopic pregnancy in one of the woman's Fallopian tubes. As is

well known, the third reported attempt culminated in the birth of a

female infant. In oral presentations to scientific meetings, Edwards

and Steptoe have reported the birth of a second healthy child, a male,

as well as the occurrence of spontaneous abortions in two additional

pregnancies initiated by means of in vitro fertilization and embryo

transfer. The four pregnancies reported by Edwards and Steptoe followed

31
32 attempts at embryo transfer. In addition, the birth of a female

child in India following in vitro fertilization and embryo tranfer has

32
been reported in the press.
 10

The potential risks of several aspects of human in vitro fertilization

and embryo transfer have received some discussion in the scientific

literature. The technique of superovulation is frequently (though not

necessarily) employed in efforts to recover multiple oocytes for in

vitro fertilization. One report indicates that the technique of superovulation

may be associated with higher rates of a chromosomal abnormality (trisomy)

33
in humans. Similarly, evidence from research with mice suggests that

too-high a concentration of sperm around the ovum in vitro may result in

its fertilization by multiple sperm and thus lead to another type of

34
abnormality (triploidy) in the embryo.

In vitro fertilization techniques may also bypass a natural screening

process to which sperm are subjected in human reproduction in vivo .

There is some evidence to indicate that the female reproductive tract

selectively eliminates many abnormal sperm. In one study of the human

Fallopian tube, for example, it was demonstrated that few morphologically

35
abnormal sperm reach the site of fertilization. Similar observations

have been made in studies of mice. The extent of this risk, as well

as tne two lypes of risks noted in the preceding paragraph, is unknown.

Two other theoretical sources of risk to human embryos have not

been documented in research performed to date: the risk of inducing

37
point mutation or teratogenic effects in the early embryo. The mammalian

embryo is highly resistant to environmental insults. Massive insults

generally kill rather than merely damage the preimplantation embryo.

These five types of potential risks in humans are, at present,

either theoretical or hypothesized on the basis of rather limited data.

In addition, even if superovulation or in vitro fertilization were to

 11

produce a chromosomally or genetically abnormal embryo, there is only a

low probability that such an embryo would develop to term. The natural

process by which most abnormal early embryos are lost during the early

weeks of pregnancy would presumably be operative following in vitro

fertilization, as well.

C. The First Phase of the Ethical Debate

Within the American context, the public debate concerning ethical

aspects of in vitro fertilization was initiated by biologist James

Watson. In an extended statement presented in January 1971 to the Panel

on Science and Technology of the House Committee on Science and Astronautics,

Watson expressed concern that research advances in human j_n vrtro^ fertiliza-

tion and the cloning of frogs could in the future lead to attempts to
38
clone human beings. Watson's views were given wide circulation through
39
being excerpted in the May 1971 issue of Atlantic magazine.

An essay defending in vitro fertilization appeared in Nature in May

1971 -- the same month that Watson's comments were published in the

Atlantic . The Nature essay, written by British biologist R.G. Edwards

and American lawyer David Sharpe, indicated potential benefits of in

vitro fertilization research and advocated interdisciplinary consulta-

40
tion as the best method for social monitoring of the research.

In late 1971 and the first half of 1972, ethical critiques of in

vitro fertilization were eloquently presented by biologist-philosopher

Leon Kass and theologian Paul Ramsey. The essays of Ramsey and Kass,

published in leading medical and public-policy journals, questioned the

means being employed in in vitro fertilization research and voiced

 12

41 ' 42
concern about the potential future applications of the research.

In announcing that it would publish the Ramsey essay, the Journal of

the American Medical Association editorially called for a moratorium on

43
human in vitro fertilization research.

From mid-1972 to early 1974 relatively little ethical analysis of

in vitro fertilization was published. A Ciba Foundation symposium on

44
"The Law and Ethics of AID and Embryo Transfer" was held in 1972. In

an invitational symposium published in the November 1973 issue of the

Journal of Reproductive Medicine , several authors -- including veterin-

arian Benjamin Brackett, ethicist Joseph Fletcher, and physicians Luigi

45
Mastroianni and Landrum Shettles -- presented sharply divergent viewpoints.

In addition, the Committee on the Life Sciences and Social Policy of the

National Research Council, whose executive secretary was Leon Kass,

completed a detailed technology assessment of in vitro fertilization in

46
1973. Publication of the report was delayed until 1975.

In 1974 the ethical discussion of in vitro fertilization seemed to

revive. Biologist R.G. Edwards published an extensive survey of medical,

ethical, and legal questions surrounding the technique. Edwards devoted

particular attention to answering the ethical objections which had

47
previously been raised by Kass and Ramsey. During the same year

Joseph Fletcher published The Ethics of Genetic Control . In this work

Fletcher affirmed the value, indeed the superiority, of numerous genetic

and reproductive technologies, including in vitro fertilization, as

48
compared with the conventional method of human reproduction.
 13

Between the publication of the National Research Council's technology

assessment in 1975 and the middle of 1978 little new ethical literature

on in vitro fertilization appeared. The first phase in the ethical

debate on in vitro fertilization thus concluded with a pause. Not until

the birth of a child conceived with the aid of the technique did the

pause end and the second phase of the ethical debate begin.

D. The Evolution of HEW Involvement

HEW involvement in setting guidelines for research involving in

vitro fertilization and/or embryo transfer has resulted in the publica-

tion of three documents: a "draft working document of proposed policy"

;^'^
(November 16, 1973);^^ a set of proposed regulations (August 23, 1974)
51
and final regulations (August 8, 1975). It is perhaps worthy of note

that the questions of fetal research, research with pregnant women, and

research involving children received substantially greater attention in

the three HEW documents than did the issue of in vitro fertilization.

This differential allocation of attention accurately reflected the

public-policy setting of 1973, when fetal research, in particular, was a

matter of significant public controversy. The relative de-emphasis of

in vitro fertilization in the HEW guidelines also reflected the view

that successful embryo transfer in humans was not likely to be technically

feasible in the near future.

The successive versions of HEW guidelines and rules published

between 1973 and 1975 tended toward less detail in their stipulations

and toward a greater emphasis on a review procedure for proposed research

with human in vitro fertilization and/or embryo transfer. The 1973

draft policy stipulated that:

 14

1. "Care must be taken not to bring human ova fertilized

"
in vitro to viability

2. "All proposals for research involving human in vitro

fertilization must be reviewed by the Ethical Review
Board."

3. "No research involving the implantation of human ova

fertilized in the laboratory into recipient women
should be supported until the appropriate scientific
review boards are satisfied that there has been suf-
ficient work in animals (including sub-human primates)
to demonstrate the safety of the technique. It is
recommended that this determination of safety include
studies of natural born offspring of the products of
in vitro fertilization."

4. "No implantation of human ova fertilized in the laboratory

should be attempted until guidelines are developed govern-
ing the responsibilities of the donor and recipient no
'parents' and of research institutions and personnel."

In August 1974, subsequent to the passage of legislation establishing

the National Commission for the Protection of Human Subjects but prior

to the Commission's first meeting, HEW published proposed rule-making on

research with several specific groups of human subjects. This document

responded to comments on the November 16, 1973 preliminary draft regarding

in vitro fertilization research, clarified the definition of a fetus,

and suggested issues to be considered by the Ethical Advisory Board in

its review of any proposed HEW supported research involving human in

vitro fertilization or embryo transfer. In this 1974 document "fetus"

was defined to include "both the product of in vivo conception and the

product of in vitro fertilization which is subsequently implanted in the

53
donor of the ovum." With respect to unimplanted human embryos, the

1974 rules proposed no specific guidelines.

 15

However, the 1974 HEW document recommended that the Ethical Advisory

Board take into account certain issues in reviewing research proposals

involving in vitro fertilization and/or embryo transfer:

With respect to the fertilization of human ova in vitro ,

it is expected that the Board will consider the extent to

which current technology permits the continued development
of such ova, as well as the legal and ethical issues sur-
rounding the initiation and disposition of the products of
such research.

With respect to implantation of fertilized human ova, it

is expected that the Board will consider such factors as the
safety of the technique (with respect to offspring) as
demonstrated in animal studies, and clarification of the
legal responsibilities of the donor.and recipient parent(s)
as well as the research personnel.

In August 1975, HEW responded to the National Commission's report

and recommendations concerning fetal research. Since the Commission had

not specifically addressed the issue of research involving in vitro

fertilization and/or embryo transfer, HEW chose not to promulgate substantive

regulations governing such research. It did, however, clearly reiterate

a procedural requirement:

(e) No application or proposal involving human in vitro

fertilization may be funded by the Department or any com-
ponent thereof until the application or proposal has been
reviewed by the Ethical Advisory Board and the Board has
rendered advice as to its acceptability from an ethical
standpoint.

The effect of this review requirement between August 1975 and September

1977, when the Ethics Advisory Board was appointed by HEW Secretary

Califano, was to place a de facto moratorium on all HEW supported human

research involving in vitro fertilization and/or embryo transfer.

 16

FOOTNOTES

1. Biggers, John D., In Vitro Fertilization, Embryo Culture and Embryo

Transfer in the Human, a paper prepared for the Ethics Advisory
Board, 1978, Table 2, p. 10, citing Leridon, H., Demographie des
Echers de la Reproduction, in: Boue, A. and Thibault, C, eds.,
Les Accidents Chromosomiques de la Reproduction Paris, Centre ,

International de I'Enfance, 1973, pp. 13-27.

2. Biggers, op. cit. p. 11, citing Roberts, C.J. and Lowe, C.R.,
,

Where Have all the Conceptions Gone?, Lancet vol. i, pp. 498-499,
,

1975.

3. Biggers, op. cit. , p. 13, citing Boue, J.G. and Boue, A., Chromosomal
Anomalies in Early Spontaneous Abortion, Current Topics in Pathology ,

vol. 62, 1976, pp. 193-208.

4. Biggers, op. cit. p. 19, citing Heape, W.

, Preliminary Note on the
,

Transplantation and Growth of Mammalian Ova with a Uterine Foster-

mother, Proceedings of the Royal Society vol. 48, 1890, pp. 457-458.
,

5. Biggers, op. cit. p. 19, citing McLaren, A. and Biggers, J.D.,

,

Successful Development and Birth of Mice Cultivated In Vitro as

Early Embryos, Nature vol. 182, 1959, pp. 877-878.
,

6. Biggers, op. cit. p. 20, citing Chang, M.C., Fertilization of

,

Rabbit Ova In Vitro Nature, vol. 184, 1959, pp. 466-467.

,

7. Rice, Catherine, Supplement to: In Vitro Fertilization, Embryo

Culture and Embryo Transfer in the Human by John D. Biggers, 1978,
Table 1 pp ,1-6.

8. Biggers, op. cit. , Table 7, p. 40.

9. Ibid. Table 3, p. 22; see also Walters, LeRoy, Ethical Issues in

,

Human In Vitro Fertilization and Research Involving Early Human

Embryos, a paper prepared for the Ethics Advisory Board, 1978,
p. 32, citing Fowler, Ruth E. and Edwards R.G., The Genetics
of Early Human Development, in: Steinberg, Arthur G. and Beam,
Alexander G., eds.. Progress in Medical Genetics Vol. IX, New ,

York, Grune and Stratton, 1973, pp. 92-95; Karp, L.E. and Donahue,
R.P., Preimplantational Ectogenesis -- Science and Speculation
Concerning In Vitro Fertilization and Related Procedures (Medical
Progress), Western Journal of Medicine vol. 124, p. 296, April
,

1976; National Research Council, Assembly of Behavioral and Social

Sciences, Committee on the Life Sciences and Social Policy, Assessing
Biomedical Technologies An Inquiry Into the Nature of the Process
: ,

Washington, D.C., National Academy of Sciences, 1975, p. 27.

 17

10. Culture of human embryos beyond the blastocyst stage has not yet
been reported in the scientific literature. Walters, op. cit.,

p. 32. The use of several of these techniques in research with

non-human embryos is described by Edwards, R.G., Fertilization
of Human Eggs In Vitro Morals, Ethics, and the Law, Quarterly
:

Review of Biology , vol. 49, March, 1974, pp. 3-6.

11. Foote, Robert H., In Vitro Fertil ization in Perspective, Relative

to the Science and Art of Domestic Animal Reproduction, a paper
prepared for the Ethics Advisory Board, 1978, p. 6, citing
Maurer, R.R., Hunt, W.L., Van Vleck, L.D., and Foote, R.H.,
Developmental Potential of Superovulated Rabbit Ova, Journal
of Reproduction and Fertility , vol. 15, 1968, pp. 171-175.

12. Biggers, op. cit. p. 33, citing Fujimoto, S., Pahlaven, N. and
,

Dukelow, W.R. Chromosome Abnormalities in Rabbit Preimplantation

,

Blastocysts Induced by Superovulation, Journal of Reproduction

and Fertility vol. 40, 1974, pp. 177-181; Fujimoto, S., Passantino,
,

T.J., and Koenczoel I., A Preliminary Note on Chromosome Abnormal-

,

ities in Intratubal Rabbit Embryos, Proceedings of the Japanese

Academy vol. 51, 1975, pp. 51-55; Takagi, N., and Sasaki, M.,
,

Digynic Triploidy After Superovulation in Mice, Nature vol. 264,

,

1976, pp. 278-281; Maudlin, I., and Eraser, I.R., The Effect of
PMSG Dose on the Incidence of Chromosomal Anomalies in Mouse
Embryos Fertlized In Vitro Journal of Reproduction and Fertility
, ,

vol. 50, 1977, pp. 275-280.

13. Foote, op. cit. p. 16, citing Maurer, R.R., Bank, H., and Staples
R.E., Pre- and Postnatal Development of Mouse Embryos After
Storage for Different Periods at Cryogenic Temperatures, Biology
of Reproduction , vol. 16, 1977, pp. 139-146.

14. Foote, op. cit. , p. 5.

15. Ibid ., pp. 10-14.

16. Ibid. p. 17, citing Betteridge, K.J., ed.. Embryo Transfer in

,

Farm Animals Ottawa, Ontario, Canada Department of Agriculture,

,

Monograph, vol. 16, 1977.

17. Foote, op. cit. , p. 18, citing Shea, B.F., Hines, D.J., Lightfoot,
D.E., Ollis, G.W., and Olson, S.M., The Transfer of Bovine Embryos,
in: Rowson, L.E.A., ed.. Egg Transfer in Cattle , Luxembourg, Com-
mission of European Communities, EUR 5491, 1976, pp. 145-152;
Elsden, R.P., Nelson, L.D., and Seidel, G.E., Jr., Superovulation
of Cows with Follicle Stimulating Hormone and Pregnant Mare's
Serum Gonadotropin, Theriogenology , vol. 9, 1978, pp. 17-26.
 18

18. Foote, op. cit. p. 19, citing Hare, W.C.D. and Betteridge, K.H.,
,

Relationship of Embryo Sexing to Other Methods of Prenatal Sex

Determination in Farm Animals: A Review, Theriogenology vol. 9,
,

1978, pp. 27-43.

19. Gould, K.G., Fertilization In Vitro of Nonhuman Primate Ova:

Present Status and Rationale for Further Development of the
Technique, a paper prepared for the Ethics Advisory Board, 1978,
p. 9, citing Gould, Cline, E.M. and Williams, W.L., Observation
on the Introduction of Ovulation and Fertilization In Vitro in
the Squirrel Monkey (Saimiri Sciureus), Fertility and Sterility ,

vol. 24, 1973, pp. 260-268.

20. Gould, op. cit. , p. 9, citing Kuehl , T.J. and Dukelow, W.R.,
Ovulation Induction During the Anovulatory Season in Saimiri
Sciureus, Journal of Medical Primatology , vol. 4, 1975, pp.
209-216; Dukelow, W.R. and Kuehl, T.J., in: Thibault, C, ed..
La Fecondation , Paris, Masson, 1975, pp. 67-80.

21. Gould, op. cit. pp. 8-9, citing Kraemer, D.C., Moore, G.T.,
,

and Kramen, M.A., Babboon Infant Produced by Embryo Transfer,

Science , vol. 192, 1976, pp. 1246-1247.

22. Gould, op. cit. , pp. 7-8, citing Marston, J.H., Penn, R., and
Sivelle, P.C, Successful Autotransfer of Tubal Eggs in the
Rhesus Monkey (Macaca Mulatta), Journal of Reproduction and
Fertility , vol. 49, 1977, pp. 175-176.

23. Gould, op. cit. , p. 13.

24. Sackett, G.P., A Nonhuman Primate Research Model of Developmental

Risk Following In Vitro Fertilization and Embryo Transfer, a paper
prepared for the Ethics Advisory Board, 1979.

25. Biggers, op. cit. , p. 27, citing Edwards, R.G., Steptoe, P.C,
and Purdy, J.M., Fertilization and Cleavage In Vitro of Preovular
Human Oocytes, Nature , vol. 227, 1970, pp. 1307-1309.

26. Biggers, op. cit. , pp. 27-28, citing Steptoe, P.C, Edwards,
R.G., and Purdy, J.M., Human Blastocysts Grown in Culture,
Nature, vol. 119, 1971, pp. 132-133; Steptoe, P.C, and
Edwards, R.G., Preimplantation of a Human Embryo with Subse-
quent Tubal Pregnancy, Lancet vol. i, 1976, pp. 880-882;
,

Steptoe, P.C, and Edwards, R.G., Birth after the Reimplanta-

tion of a Human Embryo, Lancet, vol. ii, 1978, p. 336.

27. Biggers, op. cit. pp. 2, 29 citing DeKretzer, D., Dennis,

,

P., Hudson, B., Leeton, J. Lopata, A., Outch, K. , Talbot,

J., and Wood, C, Transfer of a Human Zygote, Lancet , vol. ii,
1973, pp. 728-729; Lopata, A., McMaster, R., McBain, J.C,
and Johnston, W.I.H., In Vitro Fertilization of Preovulatory
Human Eggs, Journal of Reproduction and Fertility , vol. 52, 1978,
pp. 339-342.
 .

19

28. Biggers, op. cit. pp. 30-31, citing Soupart, P. and Strong, P. A.,
,

Ultrastructural Observations on Human Oocytes Fertilized In Vitro ,

Fertility and Sterility vol. 25, 1974, pp. 11-44.

,

29. Biggers, op. cit. pp. 30-31, citing DeKretzer, et al

, Transfer
,

of a Human Zygote, Lancet , vol. ii, 1973, pp. 728-729.

30. Biggers, op. cit. , p. 29, citing Steptoe, P.C., and Edwards, R.G.,
Reimplantation of a Human Embryo with Subsequent Tubal Pregnancy,
Lancet vol. i, 1976, pp. 880-882; Steptoe, P.C, and Edwards,
,

R.G., Birth after the Reimplantation of a Human Embryo, Lancet ,

vol. ii, 1978, p. 366.

31. Short, R.V., Summary of the Presentation of Dr. P.C. Steptoe and
Dr. R.G. Edwards at the Royal College of Obstetricians on Friday,
January 26th, 1979, written report presented to the Ethics
Advisory Board, February 2, 1979.

32. Test Tube Baby, World's Second, Born in India, Washington Post ,
October 6, 1978.

33. Biggers, op. cit. p. 32, citing Boue, J.G., and Boue, A., Increased
,

Frequency of Chromosomal Anomalies in Abortions After Induced

Ovulation, Lancet , vol. i, 1973, p. 679.

34. Biggers, op. cit. p. 33, citing Eraser, L.R., Zenellotti, H.M.,
,

Paton, G.R., and Drury, L.M., Increased Incidence of Triploidy

in Embryos Derived from Mouse Eggs Fertilized In Vitro Nature ,
,

vol. 260, 1976, pp. 39-40; Eraser, L.R., and Maudlin, I.,
Relationship Between Sperm Concentration and the Incidence of
Polyspermy in Mouse Embryos Fertilized In Vitro Journal of
,

Reproduction and Fertility , vol. 52, 1978, pp. 103-106.

35. Biggers, op. cit. , p. 33, citing Ahlgren, M., Sperm Transport
to and Survival in the Human Fallopian Tube, Gynecologic Investigation ,

vol. 6, 1975, pp. 200-214.

36. Biggers, op. cit. , citing Krzanowska, H., The Passage of Abnormal
Spermatozoa Through the Uterotubal Junction of the Mouse, Journal
of Reproduction and Fertility vol. 38, 1974, pp. 81-90,
,

37. Biggers, op. cit. , pp. 33-35.

38. Watson, James D., Statement at the twelfth meeting of the Panel
on Science and Technology, in International Science Policy ,

(Proceedings before the Committee on Science and Astronautics,

U.S. House of Representatives, 92nd Congress, 1st Session,
January 26,27, and 28, 1971), Washington, D.C., U.S. Government
Printing Office, 1971, pp. 336-344.
 .

20

39. Watson, James D., Moving Toward Clonal Man: Is This What we Want?
Alantic vol 227, 1971, pp. 50-53.
.

40. Edwards, Robert G., and Sharke, David J., Social Values and
Research in Human Embryology, Nature vol. 231, 1971, pp. 87-91.
,

41. Kass, Leon R., Babies by Means of In Vitro Fertilization: Unethical

Experiments on the Unborn?, New England Journal of Medicine vol. 285, ,

1971, pp. 1174-1179; Kass Leon R. , Making Babies The New Biology —
and the "old" Morality, Public Interest vol. 26, 1972, pp. 18-56.
,

42. Ramsey, Paul, Shall We 'Reproduce'?, Journal of the American Medical

Association vol. 220, 1972, pp. 1346-1350, 1480-1485.
,

43. Genetic Engineering in Man: Ethical Considerations (editorial),

Journal of the American Medical Association , vol. 220, 1972, p. 721.

44. Law and Ethics of A.I.D. and Embryo Transfer , New York, American
Elsevier, 1973.

45. Schumacher, Gebhard, P., et al , In Vitro Fertilization of Human

Ova and Blastocyst Transfer: An Invitational Symposium, Journal
of Reproductive Medicine , vol. 11, 1973, pp. 192-200.

46. National Research Council, Assembly of Behavioral and Social

Sciences, Committee on the Life Sciences and Social Policy,
Assessing Biomedical Technologies: An Inquiry into the
Nature of the Process Washington, D.C., National Academy of
,

Sciences, 1975, pp. 13-31.

47. Edwards, R.G., Fertilization of Human Eggs In Vitro Morals, :

Ethics and the Law, Quarterly Review of Biology vol. 49, ,

1974, pp. 3-26.

48. Fletcher, Joseph, The Ethics of Genetic Control : Ending Reproduc-

tive Roulette New York, Doubleday, 1974.
,

49. Federal Register , vol. 38, November 16, 1973, p. 31743.

50. Federal Register , vol. 39, August 23, 1974, p. 30650.

51. Federal Register , vol. 40, August 8, 1975, p. 33527.

52. Federal Register , vol. 38, November 16, 1973, p. 31743.

53. Federal Register , vol. 39, August 23, 1974, p. 30650.

54. Ibid .

55. Federal Register , vol. 40, August 8, 1975, p. 33529.

 21

CHAPTER II: LABORATORY RESEARCH INVOLVING HUMAN IN VITRO

FERTILIZATION AND/OR THE CULTURE OF EARLY
HUMAN EMBRYOS: TECHNICAL AND ETHICAL ISSUES

The technical and ethical issues surrounding in vitro fertilization

using human gametes depend, to some extent, on whether or not the procedure

is performed with the intent of transferring the resulting embryos to

women for further development. The discussion in this chapter relates

to in vitro fertilization of human ova when there is no intention of

transferring the product to establish a pregnancy. Chapter III deals

with human in vitro fertilization performed with the specific intent of

initiating a pregnancy.

These two chapters focus primary attention on technical and ethical

issues as presented to the Ethics Advisory Board in papers prepared by

its consultants. Thus, they do not summarize the primary scientific and

ethical publications concerning in vitro fertilization and/or embryo

transfer.

In one of the papers prepared at the request of the Board, LeRoy

Walters surveyed the ethical literature on in vitro fertilization published

through August 1978. This survey noted that most of the ethical discussion

on in vitro fertilization has concentrated on clinical applications of

the technique (the topic of Chapter III) rather than on laboratory

research with early human embryos (the topic of the present chapter).

Central issues in the ethical literature on basic research with human

embryos included the moral status of the early embryo, the need for such

research, and the potential long-term consequences of the research.

According to the same survey, comnentators on ethical issues in the

 22

application of in vitro fertilization and/or embryo transfer discussed,

among other topics, the need for in vitro fertilization as a method for

overcoming infertility, the adequacy of prior laboratory and animal

research, the risks of in vitro fertilization and embryo transfer to the

ovum donor as well as to potential offspring, and the appropriateness of

allocating scarce health care resources to the clinical application of

such techniques. Many of these issues recurred in the papers presented

to the Board, which are systematically reviewed in this and the following

chapter.

A. The Goals and Potential Benefits of the Research

As noted in the preceding chapter many studies in experimental

embryology do not include embryo transfer as a component. Several

possible goals of laboratory research with human embryos have been

identified:
2
1. Developing or testing more adequate contraceptives;
3
2. Determining causes of infertility;

3. Investigating the circumstances leading to the

development of hyatidiform moles and their -

potential transformation into malignant tumors;

4. Evaluating the effect of noxious agents or tera-

togens on the early embryo by means of an u[ vitro
screening system;

5. Studying the mechanisms by which chromosomal

abnormalities are produced; and

6. Investigating the totipotential cells of very

early embryos to increase understanding of
normal and abnormal cell growth and differen-
tiation.
 23

One additional potential goal of human in vitro fertilization and

embryo culture is more controversial and therefore merits more detailed

comment. R.V. Short suggests that a kind of in vitro assessment (or

"toxicology testing") study might be performed to determine whether J_n

vitro fertilization produces a higher incidence of embryonic abnor-

malities than the conventional in vivo method of human reproduction. In

Short's view, if in vitro fertilization techniques do in fact lead to an

excess of embryonic abnormalities, it would be preferable to discover

that excess in the laboratory rather than at the time of amniocentesis

or birth. Short argues that such a controlled in vitro study would also

provide information concerning the probable success rate of in vitro

o
fertil ization.

Several objections can be raised to such a proposal, as Short

himself observes. First, there would be little basis for comparison

following such a laboratory study since data concerning the incidence of

abnormalities, particularly chromosomal abnormalities, in early human

embryos following in vivo fertil ization are quite limited. In fact, the

totality of in vivo information relating to human preimplantation ova

and embryos is "confined to 15 specimens, 9 recovered from the oviduct

Q
and 6 from the uterus." At least two replies to this objection can be

made. First, James Schlesselman notes that one can extrapolate statistically

from three major studies of the incidence of chromosomal abnormalities

following in vivo fertilization that the natural incidence of such

abnormalities in humans is between 396 per 1,000 and 477 per 1,000 at

the time of implantation; prior to implantation the incidence of such

abnormalities is presumably somewhat higher. Schlesselman concludes

 24

that a 40-50% chromosomal abnormality rate in human embryos following in

vivo fertilization is a reasonable baseline against which to compare the

results of in vitro fertilization. A second reply is proposed by Short

himself, who suggests that one could perform a controlled study of the

actual incidence of embryonic defects following in vivo fertilization by

flushing early embryos from the reproductive tracts of consenting volunteer

research subjects. Short concedes that this aspect of the proposed

risk-assessment study would present both medical and ethical difficulties

of its own.

A second possible objection to Short's proposal for a laboratory

risk-assessment study is that it is unnecessary. This objection can

take one of two forms. Schlesselman notes that for every 1,000 chromosomal

abnormalities which are present in implanted blastocysts, only 5 to 7

survive to the point of live birth. Thus, 99.3% to 99.5% of chromosomally

abnormal fetuses are eliminated in vivo through spontaneous abortion or

fetal death. It follows, therefore, that even a doubling in the inci-

dence of chromosomal abnormalities following in vitro fertilization --

assuming that the technique or ancillary medical treatment did not

facilitate the survival of abnormal embryos -- would yield only an

additional 6 to 7 chromosomally abnormal fetuses, which could, in

Schlesselman's view, be detected by means of prenatal diagnosis and

13
selectively aborted.

An alternative argument against the necessity of Short's proposed

risk-assessment study can be based on the essays of Biggers, who asserts

that for the investigation of most questions concerning human reproduction

 25

a suitable animal model can be found. In his view, women should not be

subjected to research risks and valuable human ova and embryos should

not be used in research unless there is no reasonable alternative to a

study in humans.

Biggers' position suggests a final issue to be considered under the

rubric of goals and potential benefits of the research: How stringent a

standard should be set with respect to the need for laboratory research

on human in vitro fertilization and embryo transfer? There are three

possible answers to this question. The least stringent standard would

be that benefits can be expected from the human research. A somewhat

more stringent standard would be that human research should hold out the

prospect of more significant or more reliable benefits than research

1 5
employing animal models. The most stringent standard would require

that the promised benefits of human research be achievable only through

research using human gametes and early human embryos.

B. The Design of the Research

Biggers emphasizes that research on human in vitro fertilization

and embryo culture, since it involves human volunteers, "should only be

undertaken if efficiently designed experiments of adequate size are

possible." In his view, this stipulation may require that collabora-

tive trials be conducted. Schlesselman's discussion of appropriate

sample size for answering specific questions regarding human in vitro

fertilization illustrates both the complexity of the design issue and

the essential role of the biostatistician in helping to plan laboratory

research with human gametes and embryos.

 8

26

C. The Consent of Sperm and Ovum Donors

Most discussion of the consent question for laboratory studies of

in vitro fertilization has focused on the ovum donor. In most cases ova

are harvested from women with intact ovaries by means of laparoscopy.

The donation of ova may be associated with receiving hormones to induce

superovulation and/or to mature the ova in vivo prior to harvest. In

some cases ova are harvested at the same time that a tubal ligation is

performed. There is unanimous agreement that the informed consent of

ovum donors must be secured in advance of their participation as research

1
subjects. In addition, the particular vulnerability of infertility

patients, who are dependent on the health professions for assistance in

achieving pregnancy and who nonetheless may be asked to serve as ovum

19
donors, has been noted in the literature on the consent question.

Less thoroughly discussed are the issues of consent by semen donors

and the use of ova excised from ovarian tissue removed for clinical

reasons. Consent by semen donors might be particularly difficult to

secure if semen were secured from a sperm bank rather than from a pros-

pectively recruited donor. The view expressed in one published assess-

ment of in vitro fertilization is that prior consent should be secured

20
from all males whose sperm are to be used for in vitro fertilization.

The harvesting of ova from excised ovarian tissue may prove to be

inefficient from a purely practical standpoint unless hormone treatments

are administered in advance of surgery. Prior consent to such hormone

treatment would presumably be secured. However, even if ova were harvested

 27

from such tissue, without the previous administration of hormone to the

female patient, gradually evolving general standards with respect to the

21
use of human tissues for research purposes would seem to suggest the

necessity for securing the patient's consent to the use of her ova in

laboratory research.

D. The Status of the Early Human Embryo

Two primary objections to laboratory research with human in vitro

fertilization and embryo culture have been raised. The first is that

such research is incompatible with the respect that is due to early

human embryos. The second is that the potential adverse consequences of

the research outweigh the potential benefits. These two objections will

be discussed in the present and the succeeding section of this chapter.

The shape of the embryonic status question differs somewhat in the

laboratory research context and the clinical context. As Leon Kass

points out, many human embryos which would be studied in the laboratory

would have been created solely for research purposes. The major

alternative would be to perform laboratory studies on untransferred

embryos remaining after the fertilization of multiple ova and the transfer

of only one to the uterus. However, from a research design standpoint,

total reliance on the use of untransferred embryos would seem to exclude

research on the fertilization process and on the earliest stages of

embryonic development.

At least three distinguishable answers to the embryonic-status

question in the research context have been proposed. Kass himself,

impressed by the continuities in embryonic and fetal development and by

 28

the potential viability of the early human embryo if it is transferred

at the proper time, argues (1) that embryos ought not be deliberately
23
created for research purposes and (2) that no invasive or manipulative
24
research should be performed on already-existing human embryos. Any

other policy would, according to Kass, symbolize the belief that early
25
human embryos are "things or mere stuff.

A second position on the embryonic-status issue is presented by

Charles Curran, who argues that:

From my ethical perspective truly human life is present

two to three weeks after conception or shortly after the
implantation of the embryo. Hence experimentation after
that time and attempts to culture embryos in vitrg gbeyond
this stage raise insurmountable ethical problems.

However, even for research involving the earliest stages of embryonic

life Curran asserts that "[t]he nature of the matter involved in the
„27
research calls for respect and economy avoiding unnecessary waste.

A similar position is articulated by Clifford Grobstein who sug-

gests that "human cells, tissues and organs that have no reasonable

prospect of possessing or developing sentient awareness" are "human

materials rather than human beings or persons." Grobstein notes that

"there are established practices for dealing with and disposing of human

materials, practices that take into account the special status they
OQ
have, having originated as human." Grobstein's position is charac-

terized as being similar rather than identical to Curran's for two

reasons. First, it is not clear that Curran would extend his principle

of respect to include non-embryonic human organs, tissues, or cells.

Second, the criterion of possessing a potential for sentience seems not

 29

to be a part of Curran's position on embryonic status. Indeed, one

could construe this criterion broadly to include all preimplantation

embryos since, as Kass notes, they could be transferred, implanted, and

develop to maturity; or one could interpret the criterion narrowly to

exclude all preimplantation embryos since it is infeasible, given the

current state of medical technology, to culture human embryos in vitro

beyond the blastocyst stage.

A third position on embryonic status, represented by Samuel Gorovitz,

adopts sentience (rather than the potential for sentience) as the primary

criterion for determining the moral status of the human embryo or fetus.

In Gorovitz's view:

The status of the embryo is not equivalent to that of

a person, a child, an infant, or a fetus -- at least a
fetus from the point of development of the capacity for
even primitive sentience.

If by "primitive sentience" Gorovitz means the capacity to respond to

sensory stimuli, then the transition from embyronic to fetal status (at

the eighth week of gestation) or, at the latest, the tenth gestational

week of fetal development would seem to mark the transition from non-
30
protected to protected status. In fact, however, Gorovitz notes that

he would draw the line of acceptability somewhat conservatively, that

is, "rather close to the point where cell differentiation begins, rather
31
far from the capacity for independent survival."

A possible reason for the multiplicity of viewpoints on the status

of the human embryo is suggested by Gorovitz. In his view, questions

like embryonic status or the appropriate criteria of death are not

matters of fact which can be clarified through appropriate research

 30

programs. Rather, these questions provide the occasion for individuals

32
to make decisions and for societies to establish policies. In contrast,

while Kass does not directly address the fact/decision distinction, he

clearly regards the discontinuity of fertilization and the continuity of

the embryonic development which follows as factual considerations which

33
lead ineluctably to certain moral conclusions.

E. Potential Adverse Consequences of the Research

Concerns about adverse consequences of laboratory research with

human in vitro fertilization and embryo culture have been focused in

three areas: (1) the same types of research procedures that have been

performed with nonhuman mammalian embryos may be performed with human

embryos; (2) certain undesirable technological or clinical appl ications

may arise from such research; and (3) the research may have a desensi-

tizing or dehumanizing effect on investigators.

Kass outlines some of the scientific procedures which in his view

are likely to be applied in the future to human embryos:

1. Culture beyond the blastocyst stage;

2. Formation of hybrids or chimeras (intra-

specific and inter-specific);

3. Gene, chromosome, and plasmid insertion,

excision, or alteration;

4. Nuclear transplantation or cloning; and

34
5. The freezing of embryos.

Kass ventures this prediction because, in his view, the same arguments

which can be advanced to justify, for example, the simpler and earlier

procedures proposed by Pierre Soupart can without logical contradiction

 31

be extended to the more ambitious and later procedures outlined above.

Among these justifying principles are the following:

1. "It is desirable to learn as much as possible about

the process of fertilization, growth, implantation,
and differentiation of human embryos and about human
gene expression and its control.

2. "It would be desirable to acquire improved techniques

for enchancing conception and implantation, for
preventing conception and implantation, for the
treatment of genetic and chromosomal abnormalities,
etc.

3. "Finally, only research using human embryos can answer

these questions and provide these techniques.

4. "There should be no censorship or limitation of scien-

tific inquiry or research."

Without specifically advocating the types of experiments which Kass

regards as undesirable, Gorovitz adopts a general position which could

in principle allow him to approve such experiments. If one extrapolates

from Gorovitz's views on embryonic status, one concludes that he would

approve any type of research procedure on the human embryo, provided

only that the research terminated prior to the onset of embryonic or

fetal sentience and that other canons of research ethics (consent of

36
gamete donors, appropriate research design, etc.) were carefully followed.

Gorovitz explicitly accepts Kass's formal point that the justifying

arguments for such research should be carefully formulated, in order to

37
avoid the "slippery slope." However, his material principle of drawing

the dividing line at the point of sentience rather than fertilization or

implantation seems, at least, to lead Gorovitz to approve as potentially

beneficial the experiments which Kass regards as negative consequences

of laboratory research with preimplantation embryos.

 32

A specific research technique, interspecies fertilization using

human sperm or ova, has provoked considerable discussion and therefore

merits brief further comment. Cross-fertilization raises both conceptual

and ethical questions. Conceptually, is fertilization research involving

the use of only human sperm or human ova and the culture of the resultant

hybrid embryo human research ? Ethically, Kass regards such research as

an adverse consequence of intraspecific in vitro fertilization. On the

other hand, Short, while acknowledging that interspecific fertilization

carries with it undertones of a novel type of genetic manipulation,

argues that technical and ethical hedges could be constructed to prevent

what he regards as the major potential adverse consequence of such

research -- namely, any effort to transfer the hybrid embryo into the

uterus of a human or animal female for further development.

A second type of potential adverse consequence identified by some

critics of human in vitro fertilization and embryo culture concerns

possible applications of the research rather than the research procedures

themselves. Kass suggests that the research might lead to the banking

39
of human ova or embryos for commercial purposes. In the literature on

this topic several other potential adverse consequences are noted: the

cloning of human beings, the creation of human/animal hybrids, and the

development of devices which would allow for the extracorporeal gestation,

40
or ectogenesis, of human embryos and fetuses. Without commenting

specifically on these potential developments, Gorovitz expresses reser-

vations about the wedge argument in its predictive (as distinguished

from its logical) form. He also expresses confidence in the collective

capacity of human beings to exercise good judgment, citing as examples

 33

public policy on abortion, appropriate treatment of newborn infants, the

treatment of irretrievably comatose patients, and the setting of limits

41
on the freedom of scientific inquiry.

In an earlier essay on in vitro fertilization and cloning Leon Kass

identified a third general type of potential adverse consequence which

might result from laboratory research involving human embryos. According

to Kass, one should "be concerned about the effects on the attitude

toward and respect for human life engendered in persons who are engaged
42
in such practices. No other author has commented on the possibly

dehumanizing effects on the researcher of human in vitro fertilization

and embryo culture. It is probable that authors like Curran and Gorovitz

would link the dehumanization question to the issue of embryonic or

fetal status, arguing that only research on embryos which have developed

beyond the two-to-three-week stage (Curran) or to the point of sentience

(Gorovitz) would show disrespect for the human embryo or fetus and that

only research which manifested such disrespect would be likely to desensitize

the researcher.
 34

FOOTNOTES

1. Short, R.V,, Human In Vitro Fertilization and Embryo Transfer,

a paper prepared for the Ethics Advisory Board, 1978, pp. 2-3;
Mastroianni, Luigi, Jr., In Vitro Fertilization and Embryo
Transfer, a paper prepared for the Ethics Advisory Board, 1978,
p. 5.

2. Short, op. cit. , pp. 3-5; Mastroianni, op. cit. , p. 5.

3. Short, op. cit. , pp. 5-6.

4. Mastroianni, op. cit. , p. 5.

5. Ibid.

6. Ibid.

7. Short, op. cit. , pp. 5-7.

8. Ibid ., pp. 8-10.

9. Schlesselman, James J., How Does One Assess the Risk of Abnormalities
From Human In Vitro Fertilization?, a paper prepared for the Ethics
Advisory Board, 1979, p. 17; cf. Biggers, John D., In Vitro Ferti-
lization, Embryo Culture and Embryo Transfer in the Human, a paper
prepared for the Ethics Advisory Board, 1978, p. 6 and Appendix I,
Table 3.

10. Schlesselman, op. cit. pp. 7-8, citing, Boue, J.G. and Boue, A.,
,

Chromosomal Anomalies in Early Spontaneous Abortion, Current

Topics in Pathology vol. 62, 1976, pp. 193-208; Creasy, M.R.,
,

Crolla, J. A., and Alberman, E.D., A Cytogenetic Study of Human

Spontaneous Abortions Using Banding Techniques, Humangenetik ,

vol. 31, 1976, pp. 177-196; Alberman, E.D. and Creasy, M.R.,
Frequency of Chromosomal Abnormalities in Miscarriages and
Perinatal Deaths, Journal of Medical Genetics vol. 14, 1977, ,

pp. 313-315.

11. Schlesselman, op. cit. , p. 19.

12. Short, op. cit. , p. 10; cf. Schlesselman, op. cit. ,

pp. 24-25.

13. Schlesselman, op. cit. , p. 30.

14. Biggers, op. cit. p. 412; cf.

, Kass, Leon R., Ethical
Issues in Human In Vitro Fertilization, Embryo Culture and
Research, and Embryo Transfer, a paper prepared for the Ethics
Advisory Board, 1978, p. 27.
 35

15. Walters, LeRoy, Ethical Issues in Human In Vitro Fertilization and

Research Involving Early Human Embryos, a paper prepared for the
Ethics Advisory Board, 1978, fn. 178, citing Mastroianni, Luigi,
Jr., In Vitro Fertilization, in: Reich, Warren, ed.. Encyclopedia
of Bioethics (vol. 4), New York, Free Press-Macmillan, 1978,
,

pp. 1448-1451.

16. Biggers, op. cit. , p. 41a.

17. Schlesselman, op. cit. , pp. 20-27.

18. Short, op. cit. , p. 9; cf. Walters, op. cit. , pp. 37-38.

19. Walters, op. cit. fn. 182, citing National Research Council,
,

Assembly of Behavioral and Social Sciences, Committee on the Life

Sciences and Social Policy, Assessing Biomedical Technologies: An
Inquiry into the Nature of the Process Washington, D.C., National
,

Academy of Sciences, 1975, p. 27.

20. Ibid .

21. Holder, Angela R. and Levine, Robert J., Informed Consent for
Research on Specimens Obtained at Autopsy or Surgery: A Case Study
in the Overprotection of Human Subjects, Clinical Research vol. ,

24, 1976, pp. 68-77.

22. Kass, op. cit. , fn. 14, p. 28.

23. Ibid ., p. 5.

24. Ibid ., pp. 10-11.

25. Ibid ., p. 11.

26. Curran, Charles E., In Vitro Fertilization and Embryo Transfer:

From a Perspective of Moral Theology, a paper prepared for the
Ethics Advisory Board, 1978, p. 22.

27. Ibid ., p. 26.

28. Grobstein, Clifford, Statement to the Ethics Advisory Board, Transcript

of Meeting III, September 15, 1978, National Technical Information
Service , PB-288 764, p. 229.

29. Gorovitz, Samuel, In Vitro Fertilization: Sense and Nonsense, a

paper prepared for The Ethics Advisory Board, 1979, p. 28.

30. Williams, John W,, Williams Obstetrics , Pritchard, Jack A. and

MacDonald, Paul C, eds., 14th ed., New York, Appleton-Century-
Crofts, 1971, p. 223.
 36

31. Gorovitz, op. cit ., p. 28.

32. Ibid ., pp. 1-4.

33. Kass, op. cit. , pp. 5-7.

34. Ibid ., pp. 18-19.

35. Ibid ., p. 20.

36. Gorovitz, op. cit. , pp. 27-28.

37. Ibid ., p. 15.

38. Short, op. cit. , p. 7.

39. Kass, op. cit. , p. 19.

40. Walters, op. cit. , pp. 39-40.

41. Gorovitz, op. cit. , p. 14.

42. Kass, Leon, Making Babies -- the New Biology and the 'Old' Morality,
Public Interest, vol. 26, 1972, p. 33.
 37

CHAPTER III: CLINICAL APPLICATIONS OF IN VITRO FERTILIZATION

AND/OR EMBRYO TRANSFER: TECHNICAL AND ETHICAL
ISSUES

A. The Need for and Potential Benefits of In Vitro Fertilization and

Embryo Transfer

The major potential benefit to be derived from clinical applications

of in vitro fertilization and embryo transfer is that it may enable some

otherwise-infertile women to conceive and bear children. Most commenta-

tors on the clinical use of in vitro fertilization and embryo transfer

view the alleviation of infertility, particularly in the context of

heterosexual marriage, as a desirable goal J In opposition to this

majority position, however, Stanley Hauerwas argues that even within

marriage, resort to in vitro fertilization as a method to overcome

infertility reflects an undue emphasis on the importance of biological

parentage.

There are at least two senses in which the need for this potential

benefit has been discussed. First, how many women who wish to bear

children are infertile because of blocked Fallopian tubes? Second, of

these infertile women, how many need in vitro fertilization and embryo

transfer in the sense that they have no alternative means for producing

children of their own?

Precise data on the extent of need in these two senses are unavail-

able. Rough estimates of the upper limits of need in the United States

are provided by Biggers:

There are 60 million women reproductively active in

the USAi seven percent of couples are infertile, and
a third of these Are infertile because of sterility
of the wife. Thus, there are 1,400,000 sterile women
in the population. Pathology of the oviduct accounts
for 40 percent of the cases so that there are about
560,000 women with diseased oviducts.-^
 38

The major alternative to in vitro fertilization and embryo transfer

for women is one of several surgical procedures available for repairing

blocked oviducts: salpingolysis, resection and reanastomosis, fimbrio-

plasty, and tubal implantation. According to a recent survey, the rates

of term pregnancy following the first three of these procedures are 40-

50%, 25-40%, and 10-25% respectively.^ Thus, at least 280,000 U.S.

women with tubal obstruction are not likely to achieve pregnancy by

surgicaV methods alone. Of these women, an unknown number may also

suffer from ovarian and/or uterine dysfunction and thus may be incapable

"•of producing offspring even with the aid of in vitro fertilization and

embryo transfer.^ An additional adjustment in the estimate of the "need"

for in vitro fertilization would be required if one were to consider

women who had previously elected sterilization by tubal ligation but who

later desire to become pregnant.

While the alleviation of infertility among couples is generally re-

garded as the major potential benefit of clinical in vitro fertilization

and embryo transfer, some witnesses and some commentators in the litera-

ture have identified what they regard as additional benefits. Sid

Leiman regards the surrogate-motherhood role as closely analogous to

that of a wet nurse and therefore sees no ethical objection to extra-

marital 'involvement in gestation in cases in which intramarital repro-

duction is physically impossible. ^ In his writings on this topic R.G.

Edwards mentions sex preselection as an additional potential benefit of

clinical in vitro fertil ization and embryo transfer.'' Other potential

 39

benefits cited by various authors are pre-transfer screening for abnor-

8 Q
malities, re-transfer repair of defects,^ and extracorporeal gesta-

tion.^^ The potential consequences enumerated in this paragraph are not

universally judged to be beneficial, however, as Section F below illustrates.

B. The Need for and Adequacy of Prior Laboratory and Animal Research

Three major types of studies have been proposed as precursors to

clinical applications of in vitro fertilization and embryo transfer: (1)

laboratory research on human sperm, ova, and embryos without embryo

transfer, as described in Chapter 2, Section A above; (2) feasibility

and safety studies in non-primate species; and (3) feasibility and

safety studies in primates. Reservations have been expressed by some

witnesses about each of these types of preliminary research.

Laboratory research with human sperm, ova, and embryos has been

advocated most vigorously by R.V. Short. Short presents four arguments

for a risk-assessment program based on such laboratory studies:

1. It would be better to discover an increased incidence, of

abnormal embryos and/or low success rate "in the test tube
rather than in the long-suffering female patient."

2. Laboratory tests could establish whether fertilization errors

leading to potentially malignant trophoblastic tumors occur
with in vitro fertilization.

3. Although chromosomally abnormal fetuses could be detected by

amniocentesis, the discovery of such an affected fetus would
confront an infertile couple with an agonizing decision;
perhaps the decision would be viewed as a choice between
having a handicapped child and no child at all.

4. Laboratory tests could establish whether the lack of the

natural screen against defective sperm which is provided by
the female reproductive tract leads to an increase in the
number of abnormal embryos produced in vitro .^^
 1

40

Four possible lines of objection to the type of risk-assessment

study proposed by Short are suggested by the testimony of other wit-

nesses. Diggers notes that large numbers of human ova would need to be

collected and used in such studies in order to attain statistical signif-

cance and that the research would therefore involve a substantial number

of women acting as donors.'^ Second, even if risk-assessment studies

with human sperm, ova, and embryos were considered a necessary preliminary

step, it can be argued that such studies would not be sufficient, since

they would not detect the subtle types of mental or developmental deficits
1
which might be discovered in a carefully conducted study of primates.

(As will be noted below. Short regards primate studies as too time-

consuming.''^) Third, in Biggers' view, there is already sufficient

evidence from laboratory studies with rats, mice, and rabbits and from

the use of embryo transfer in farm animals to justify the conclusion

that in vitro fertilization and embryo transfer do not produce a significant

increase in the number of abnormal offspring. On this view, the conduct

of laboratory studies as proposed by Short is unnecessary. ^^ A final

type of objection to risk-assessment studies with human gametes and

embryos can be derived from Schlesselman's essay -- namely, that the

efficiency of the human female reproductive system in screening against

chromosomally abnormal embryos is so high (99.3% to 99.5%) that proceeding

directly to embryo transfer in humans would probably not lead to a

significantly higher number of abnormal fetuses (presumably detected by

amniocentesis) or handicapped offspring. According to Schlesselman,

 41

the primary result of an increase in the number of embryonic chromosomal

abnormalities would be an increased rate of spontaneous abortion J6

A second proposal is to perform feasibility and safety studies in

non-primate species of laboratory animals, e.g. , the mouse and the rab-

bit. Mastroianni, a proponent of prior studies in both primate and non-

primate species, asserts that:

... Extensive work in the laboratory animal should be a

necessary prerequisite before proceeding with clinical
trials. Statistically valid proof in animals that pre-
sent techniques predictably produce normal offspring
has not as yet been presented. Successful uterine
transfer of in vitro fertil ized ova has been accomplished
in only two laboratory species.^'

Short's position is in part similar to that of Mastroianni. In his

view, the results of research with laboratory animals "although somewhat

inadequate, are on the whole encouraging. The high abnormality rate in

the rat experiment [conducted by Toyoda and Chang^S] ^as probably not

due to the in vitro procedure at all (Chang, personal communication) but

nevertheless the experiment should be repeated. "^^

Kass indicates his agreement with the "cautious" position of Luigi

Mastroianni, Benjamin Brackett, and R.V. Short that:

... The risks for humans have not been sufficiently

assessed, in large part because the risks in animals
have been so poorly assessed (due to the small number
of such births and to the absence of any prospective
study to identify and evaluate deviations from the
norm) .^^

Two objections have been raised regarding studies with non-primate

laboratory animals. First, Barton Childs observes that most animal

species are so inbred that it would be invalid to extrapolate from the

results of in vitro fertilization studies, even in large numbers of

 42

laboratory animals, to the probable result of clinical applications in

humans, who are outbred.21 Second, in Biggers' view the results of

studies with various laboratory animals and of the use of the procedures

in farm animals already provide sufficient evidence of safety. ^^

A third possible objection to further studies with non-primate

animals is implicit in the Sackett proposal: subtle mental deficits

caused by in vitro fertilization might not be detected in non-primate

animals, 23 Fourth and finally, Schlesselman's calculations concerning

the low probability of producing abnormal human offspring following in

vitro fertilization and embryo transfer^^ can be viewed as an argument

against performing further risk-assessment studies with laboratory

animals.

A third proposal for preliminary risk-assessment studies is advanced

by Sackett. He recommends the conduct of a two-year trial in the pigtail

monkey which would include (1) in vitro fertilization with some embryos

transferred back to the donors of the ova and some transferred to other

females, (2) a study of the incidence of abnormalities in products of in

vitro fertilization, and (3) an assessment of learning abilities and

development in the offspring of in vitro fertil ization.^^ Gould advocates

the use of another primate model, the squirrel monkey, for risk-assessment

studies.

Several objections have been or can be lodged against the proposal

to perform primate risk-assessment studies. Short comments on the time-

investment required:

Whilst it would be helpful to have primate data, the

constraints inherent in studying this problem in primates
mean that it would be several years before adequate infor-
mation would be forthcoming, and it would seem wrong to hold
up progress until the information was available. 27
 .

43

Childs echoes this objection. ° Second, as noted above, Childs argues

that all non-human species are relatively or strictly inbred, so that

the range of genetic variability present in humans cannot be duplicated

in non-human species. 29 Two other general objections are also applicable

to proposed primate research: (1) the studies already performed in

several non-primate species provide sufficient evidence concerning risks

(Biggers^O), and (2) abnormal human embryos resulting from in vitro

techniques are likely to be spontaneously aborted (Schlesselman-^^ )

In summary, there is a clear division of opinion within the scien-

tific and ethical communities concerning the need for and adequacy of

prior laboratory and animal research. The extent of the disagreement is

unclear because not all of the expert witnesses have discussed the three

alternative risk-assessment strategies outlined above. In particular,

few experts have had the opportunity to comment specifically on the

Short and Sackett proposals.

The following positions, however, have been stated with clarity.

Biggers regards further risk-assessment studies of any kind as unnecessary.

Childs, while acknowledging the reassurance that further animal studies

might provide, argues that such studies could never provide conclusive

evidence. Short, Mastroianni, Kass, Sackett, and Gould agree that

further risk-assessment studies should be performed but disagree on

what kind of studies would be most feasible and appropriate. Short

advocates the performance of in vitro studies with human sperm and ova

and the replication of a single rat study; he opposes primate studies on

grounds of infeasibility and the amount of time required. Mastroianni

and Kass support the performance of additional studies in animals,

 44

presumably in both primates and non-primates. Sackett and Gould regard

non-primate risk-assessment studies as insufficient for drawing conclu-

sions concerning primates and therefore recommend the conduct of primate

research. In a word, there is majority support among the expert witnesses

for some type of additional risk-assessment study but only minority

support for any particular kind of study.

In addition, the data and calculations presented by Schlesselman

may be relevant to the entire risk-assessment question. Schlesselman's

thesis, which has not been commented on by proponents of risk-assessment

studies, is that the probability of producing chromosomally-abnormal

infants by means of clinical applications of in vitro fertilization and

embryo transfer is quite low because of the human female's highly-

efficient natural screen against chromosomally-abnormal embryos.

A little-discussed aspect of the risk-assessment debate is the kind

of model (regarding proof of safety) which the protagonists have in

mind. This model, in turn, can have important implications for the

burden of proof issue. If one accepts the drug-testing model, as Short

does, then the burden of proof is on investigators to demonstrate that

the techniques of in vitro fertilization and embryo transfer are safe.-^^

(It should be noted that, in a published essay, R.G. Edwards accepts the

drug-testing model but argues that the results to date in several species

of non-primate laboratory animals constitute sufficient proof of safety. ^•^)

On the other hand, if one adopts a surgery model, as Gorovitz does, than

one can argue that the clinician is free to adopt new techniques unless

opponents can demonstrate that prohibition of the techniques is justified.-^'*

 45

C. Risks of Procedures

1. Risks to Potential Offspring

The major sources of potential risk to offspring from in vitro

fertilization and embryo transfer have been briefly outlined in Chapter

1, Section B.35 ip general, the surgical procedure of embryo transfer

seems to occasion the least concern, in part perhaps because of the

widespread use of embryo transfer following natural fertilization in

farm animals.^" The conditions under which the early embryo is cultured

are also not a matter of primary concern, since the early mammalian

embryo is known to be highly resistant to damage from environmental

insults. -^^ The major potential sources of damage to the early embryo

are related to either the development of ova, the selection of sperm,

the fertilization process, or the freezing of gametes or embryos. Spe-

cifically, potential sources of damage are the following:

a. Superovulation, sometimes employed prior to in vitro

fertilization, may be correlated with an increase in
the incidence of a chromosomal abnormality (trisomy)
in embryos. 38

b. The quality of sperm reaching and fertilizing the

ovum in vitro may differ from the quality of sperm
fertilizing the ovum in the Fallopian tube, since
the female reproductive tract selects against some
types of abnormal sperm. ^^

c. The quantity of sperm reaching the ovum simultaneously

in vitro may break down the usual block to fertilization
by multiple sperm; a polyploid embryo may result. ^^

d. The use of freezing techniques to preserve gametes or

embryos may produce mutations.^'

The precise extent to which each of these theoretical sources of

risk is likely to be realized in human clinical applications of in vitro

 46

fertilization and embryo transfer cannot be estimated with certainty.

The data and calculations of Schlesselman suggest that even if an excess

of chromosomal ly abnormal embryos were produced by in vitro techniques,

only a small proportion (less than 10%) would develop to term because of

the natural process by which most such embryos are lost early in gestation.

Whether the ancillary medical treatment associated with in vitro fertili-

zation and embryo transfer would enhance the survivability of chromosomally

abnormal embryos is unknown, as Schlesselman acknowledges.^^ Similarly,

if subtler genetic (as distinguished from chromosomal) abnormalities

were to result from in vitro techniques, the abnormal embryos might not

be affected by the natural screening process described by Schlesselman.

Judgments about the acceptabil ity of various levels of risk to

offspring diverge. Kass would require that such risks be equivalent to

or less than those of natural reproduction.^^ Curran adopts a similar

(although perhaps slightly less stringent) position, arguing that the

risks of the in vitro fertilization and transfer procedures to the

offspring ought to be "about the same as in the normal process. "^^ On

the other hand. Bigger notes that there is an estimated three percent

additional risk of abnormality in offspring suggested by animal studies,

and suggests that such an added risk would be acceptable, particularly

in light of the fact that some couples who receive genetic counseling

are not deterred from procreation by a twenty-five percent risk of

genetical ly-abnormal offspring. ^^

 47

Schlesselman explicitly raises the question: to what are the risks

of human in vitro fertilization being compared? His answer is that the

women and embryos being lised for comparison should have the same medical

history relevant to their infertility as those undergoing in vitro

fertilization and embryo transfer.

2. Risks to donors

Most discussion of risks to donors has focused on risks to the

women donating ova. The following sources of risk have been identified:

a. Hormonal treatment of the women, sometimes employed to

induce superovulation; this treatment can lead to ovarian
hyperstimulation or ovarian cysts. ^^

b. Laparoscopy, a surgical procedure generally performed under

general anesthesia; this procedure may have to be repeated. ^^

c. Ectopic pregnancy, a potential danger if the embryo fails

to implant in the uterus. ^8

d. uarerui monitoring or
Careful of any resulting uterine pregnancy, often
including amniocentesis. ^9

e. The possibility of a higher-than-average rate of embryo loss

or spontaneous abortion. ^0

These risks are considered to be comparable to the risks faced by female

infertility patients, in general, and by women who undergo surgery for

the correction of blocked Fallopian tubes, in particular. ^^

D. The Consent of Sperm and Ovum Donors

The issue of informed consent by sperm and oocyte donors was not

addressed by the expert witnesses who testified before the Board. In

the literature, however, there is unanimous agreement that the informed

consent of the would-be mother and presumably of both parents must be

secured. Several specific items of information have been identified by

various commentators as being material to the decision of the couple and

therefore requiring disclosure:

 48

a. The availability of potentially effective alternative thera-

pies, e.g. , surgical reconstruction of the Fallopian tubes. 52

b. The anticipated need for repeated laparoscopies.

c. The low probability of success.

d. The likelihood that the primary beneficiaries of the

research will be other couples rather than the research
participants themselves. 53

The sources of the gametes to be used in the attempted

in vitro fertilization (i.e. , a guarantee that only
the sperm and ova of the couple will be employed). ^4

f. The disposition to be made of sperm, ova, and embryos

not used in the transfer attempt. 55

In the literature on informed consent, several commentators have

remarked that infertility patients may be strongly influenced by their

desperate desire to have children. 56 On the other hand, R.G. Edwards

notes that many candidates for in vitro fertilization and embryo transfer

are professional persons or their wives. Edwards expresses confidence

that the patients seeking this therapy are fully capable of understanding

and consenting to its procedures. 57

E. The Status of the Early Human Embryo

The question of embryonic status in the clinical context differs to

some extent from the same question in the laboratory-research context.

Perhaps the most obvious difference is that in the clinical context

there is at least a possibility that each embryo "created" will be

transferred to the uterus, will implant, and will develop to the point

of viability. Because of this difference in probabilities, as well as

the directly-therapeutic intention present in the clinical context, most

expert witnesses on ethical issues surrounding in vitro fertilization

and embryo transfer viewed the status of the early embryo as less problematic

in the clinical situation.

 49

For persons who regard the embryo as deserving of respect or pro-

tection from the time of fertilization there are two major concerns: (1)

loss of embryos following transfer, and (2) the disposition of untransferred

embryos. Kass argues that there is no qualitative difference between

embryonic loss following natural reproduction and that which follows in

vitro fertilization. ° The second issue is somewhat more complex,

however, since, as Kass notes, the "surplus" embryos can be transferred

to women other than the donor, used for laboratory research purposes, or

allowed to die.^^ A fourth possibility, not mentioned by Kass, would be

to freeze the untransferred embryos, perhaps for later transfer to the

same donor. Among the first three possibilities, Kass expresses a clear

preference for allowing untransferred embryos to die. In his view, this

choice is most compatible with concerns about lineage (which would argue

against transfer to other women) and about the respect which is owed to

early human embryos. 60 Curran's position on the discard of embryos is

similar to that of Kass, although Curran adds the note that discards and

losses should be minimized insofar as possible. ^1

A potential method for reducing the number of untransferred embryos

is suggested by both Kass and Leiman^^. ova could be fertilized one at

a time, and any additional ova could be stored, perhaps by freezing, for

future attempts at in vitro fertilization and embryo transfer. A

possible objection to this one-at-a-time procedure is that if fertiliz-

ation failed to occur, embryo transfer might be delayed until the next

menstrual cycle.
 50

An issue not discussed by the expert witnesses and only hinted at

in the literature on in vitro fertilization is the disposition of grossly

abnormal embryos. Some have argued that to decide that such embryos

should not be transferred is the first step toward deciding which fetuses

(or persons) are not worthy to live.

Finally, some witnesses such as Gorovitz and Short do not explicitly

consider the issue of embryonic status in the clinical context. However,

if one extrapolates from their views on embryonic status in general or

on laboratory research with early embryos, one can conclude with some

confidence that they would regard the embryonic loss following embryo

transfer and the discard of untransferred embryos as ethically acceptable.

F. Potential Adverse Consequences of Clinical Applications

Two types of potential adverse consequences of in vitro fertiliza-

tion and embryo transfer have been identified: (1) adverse consequences

for the family; and (2) other adverse consequences. Kass notes that

even if the initial aim of clinical applications is to assist married

couples to bear children of their own, the techniques employed provide

"the immediate possibility" of egg donation (egg from donor, sperm from

husband), embryo donation (egg and sperm both from outside the marriage),

and foster pregnancy (another woman carrying the pregnancy to term).^^

In Kass's view, there will be a strong demand for such extramarital uses

of the clinical procedures -- a demand which, if fulfilled, will further

compromise "the virtues of family, lineage, and heterosexual ity" or

weaken "the taboos against adultery and even incest. "^^

 51

Responses to the thesis that clinical uses of in vitro fertilization

and embryo transfer will weaken the family have taken two forms. The

first, represented by Gorovitz, is to argue that the demand for labora-

tory-assisted methods of reproduction in general will be limited and

that other technological innovations (e.g. , modern contraceptive techniques]

will have a much more significant adverse impact on the family."^ A

second kind of response, briefly developed by Leiman, is to deny that

surrogate motherhood is necessarily detrimental to the family, if this

novel method of becoming a parent is resorted to for good reasons (e.g. ,

if a couple would otherwise be unable to have a child).""

Other potential consequences considered adverse by some expert

witnesses and commentators include:

a. The development of commercial ovum and embryo banks. ^^

b. The genetic selection or manipulation of early embryos. ^^

c. The transfer of nuclei from adult individuals to early

embryos, or cloning.^^

d. Extracorporeal gestation, or bringing an embryo all the

way to viability in the laboratory. ''O

As noted above in Section A of the present chapter, the second and

fourth consequences in this list are regarded by some commentators as

potential benefits of clinical in vitro fertilization and embryo transfer.

Few have advocated that commercial ovum and embryo banks be created or

that human beings be cloned. Some commentators (for example, Gorovitz)

have advanced the procedural suggestion that each potential consequence

of in vitro fertilization and embryo transfer be carefully evaluated

from the standpoint of both likelihood and probable impact. 71

 52

G. Questions of Allocation

Three general positions on the allocation issue can be distinguished.

The first, represented by Biggers, is that applied laboratory research

directed toward improving techniques for testing infertility by means of

in vitro fertilization and embryo transfer should receive high pri-

ority — or, at least, that it should receive a higher priority than

basic laboratory research involving human gametes and embryos. The pri-

mary rationale for this position is Biggers' view that the supply of

human ova available for research purposes is extremely limited and

should be devoted either to directly clinical purposes or to answering

questions that cannot be satisfactorily resolved by studying laboratory

.'7?
animal

A second position, represented by Leiman^S and Curran^^, is that

the federal government should support the clinical application of in

vitro fertilization and embryo transfer. Leiman regards involuntary

infertility as an extremely serious problem.

The rabbis put it this way, some fifteen centuries ago.

Four are considered as if they were dead; the poor, the
diseased, the blind, and the childless.'^

In his view, the public funding of medical means for overcoming infertility

(for example, through Medicaid) is entirely appropriate. Indeed, Leiman

argues that:

It would be a sad commentary on the American ethos if

federal funds could be used for the taking of human life,
that is, therapeutic abortion, but not the creation of
human life, that is, therapeutic conception.''^
 53

Although Kass disagrees with this second position, he presents an additional

argument which some have used to support it:

... As he who pays the piper calls the tune, Federal

support would make easy the Federal regulation and
supervision of this research.''

In contrast, a third position on allocation is that federal funds

should not be spent for in vitro fertilization and embryo transfer in

clinical practice. Hauerwas, Gorovitz, and Kass all take this position,

although for somewhat different reasons. In Hauerwas' view, the impor-

tance of being pregnant or of bearing a child that is genetically "one's

own" has been overstated. Therefore the substantial investment of

public funds to develop these anti -infertility techniques, particularly

in light of other "immense needs of our society," (for example, the

provision of an effective clotting factor for hemophiliacs) is inappro-

priate. ^^ While he may not share Hauerwas' views on parenthood, Gorovitz

agrees with his sense of priorities.

In the competition for support, the burden of making

a convincing case should rest with the proponent of a
given line of work. With forty million Americans having
no adequate access to decent health care, with thousands
of children born annually without prospect of a family
to nurture them, with venereal disease -- a major cause
of infertility -- on the rise, it is implausible that
research into making IVF more readily and reliably
available should be a project of high priority concern.
It isn't so much the harm or risk it involves as the
plainly greater importance of addressing more fundamen-
tal and widespread problems of health and the delivery
of health care. 79

Kass presents three arguments for assigning a low priority to

clinical applications of in vitro fertilization and embryo transfer.

First, in agreement with Hauerwas and Gorovitz, he asserts that other

 54

health-related needs are more pressing. Kass goes on to argue that even

within the sphere of infertility research, other approaches will be more

cost-effective:

... With money for research as limited as it is, research

funds targeted for the relief of infertility should certainly
go first to epidemiological and preventive measure —
especially where the costs of success in the high-technology
cure are likely to be great ^Q
.

Second, according to Kass, the non-financial costs of developing these

technologies — that is, their potential adverse consequences -- also

militate against assigning their development a high priority.^' Finally,

Kass notes that a substantial number of American citizens are opposed on

moral grounds to research on, or application of, in vitro fertilization

in humans. In his view, these citizens would strenuously — and legiti-

mately -- object to any use of their taxes to promote human in vitro

fertilization and embryo transfer. ^^

 .

55

FOOTNOTES

1. Kass, Leon R., Ethical Issues in Human In Vitro Fertilization, Embryo

Culture and Research, and Embryo Transfer, a paper prepared for the
Ethics Advisory Board, 1978, pp. 13-14; Leiman, Sid Z., Statement
to the Ethics Advisory Board, Transcript of Meeting V, November 10,
1978, National Technical Information Service , PB-288 405, p. 130.

2. Hauerwas, Stanley, Theological Reflections on In Vitro Fertilization,

a paper prepared for the Ethics Advisory Board, 1978, pp. 6-12.

3. Biggers, John D., In Vitro Fertilization, Embryo Culture and Embryo

Transfer in the Human, a paper prepared for the Ethics Advisory
Board, 1978, p. 35.

4. Biggers, op. cit. p. 36 and Table 4, p. 37, citing Shane, J.M.,

,

Schiff, I., and Wilson, E.A., The Infertile Couple, Clinical

Symposia vol. 28, 1976, pp. 1-40.
,

5. Biggers, op. cit. , p. 35; Kass, op. cit. , pp. 36-37.

6. Leiman, op. cit. . pp. 126-130.

7. Walters, LeRoy, Ethical Issues in Human In Vitro Fertilization and

Research Involving Early Human Embryos, a paper prepared for the
Ethics Advisory Board, 1978, fn. 112, citing Edwards, R.G.,
Fertilization of Human Eggs In Vitro Morals, Ethics, and the
:

Law, Quarterly Review of Biology vol. 49, 1974, p. 12.

,

8. Walters, op. cit. fn. 113, citing Karp, Laurence E. and Donahue, Roger
, P,
Preimplantational Ectogenesis: Science and Speculation Concerning
In Vitro Fertilization and Related Procedures, Western Journal of
Medicine vol. 124, 1976, p. 295.
,

9. Walters, op. cit. fn. 115, citing Sinshiemer, Robert L., Prospects
,

for Future Scientific Developments: Ambush or Opportunity, in:

Hilton, Bruce et al eds.. Ethical Issues in Human Genetics:
, Genetic
Counseling and the Use of Genetic Knowledge New York, Plenum Press,
,

1973, pp. 346-348.

10. Walters, op. cit. , fn. 118, citing Fletcher, Joseph, The Ethics
of Genetic Control: Ending Reproductive Roulette Garden City, ,

N.Y., Anchor Press/Doubleday, 1974, pp. 163-165.

11. Short, R.V., Human In Vitro Fertilization and Embryo Transfer, a

paper prepared for the Ethics Advisory Board, 1978, p. 9.

12. Biggers, John D. Statement to the Ethics Advisory Board, Transcript

,

of Meeting III, September 16, 1978, National Technical Information

Service PB-288 764, pp. 235-239.
 .

56

13. Sackett, Gene P., A Nonhuman Primate Model of Developmental Risk

Following In Vitro Fertilization and Embryo Transfer, a paper
prepared for the Ethics Advisory Board, 1979, pp. 26-28.

14. Short, op. cit. , p. 8.

15. Biggers, Statement to the Ethics Advisory Board, op. cit. ,

pp. 257, 260-261.

16. Schlesselman, James J., How Does One Assess the Risk of Abnormalities
from Human In Vitro Fertilization?, a paper prepared for the Ethics
Advisory Board, 1979, pp. 29-31.

17. Mastroianni, Luigi, Jr., In Vitro Fertilization and Embryo Transfer,

a paper prepared for the Ethics Advisory Board, 1978, p. 6.

18. Toyoda, Y. and Chang, M.C., Fertilization of Rat Eggs In Vitro by

Epididymal Sperm and the Development of Eggs Following Transfer,
Journal of Reproduction and Fertility vol. 36, 1976, pp. 9-22. ,

19. Short, op. cit. , p. 8.

20. Kass, op. cit. , 1978, pp. 12-13.

21. Childs, Barton, Statement to the Ethics Advisory Board, Transcript

of Meeting III, September 16, 1978, National Technical Information
Service, PB-288 764, pp. 252-253.

22. Biggers, Statement to the Ethics Advisory Board, op. cit. , pp. 257,
260-261

23. Sackett, op. cit. , pp. 26-28.

24. Schlesselman, op. cit. , pp. 29-31.

25. Sackett, op. cit. , pp. 31-32.

26. Gould, Kenneth G., Fertilization In Vitro of Nonhuman Primate Ova:

Present Status and Rationale for Further Development of the Technique,
a paper prepared for the Ethics Advisory Board, 1978, pp. 21-23.

27. Short, op. cit. , p. 8.

28. Childs, op. cit. , p. 232a.

29. Ibid .

30. Biggers, Statement to the Ethics Advisory Board, op. cit. ,

pp. 257, 260-261.

 57

31. Schlesselman, op. cit. , pp. 29-31.

32. Short, op. cit. , pp. 8-10.

33. Walters, op. cit. fn. 50, citing Edwards, R.G., Fertilization of
,

Human Eggs In Vitro Morals, Ethics and the Law, Quarterly Review
:

of Biology vol. 49, 1974, pp. 8-9.

,

34. Gorovitz, Samuel, In Vitro Fertilization: Sense and Nonsense,

a paper prepared for the Ethics Advisory Board, 1979, p. 24.

35. See Chapter I of this report, pp. 9-10.

36. Short, op. cit. p. 8; Foote, R.H., In Vitro Fertilization in

,

Perspective, Relative to the Science and Art of Domestic Animal

Reproduction, a paper prepared for the Ethics Advisory Board,
1978, p. 17.

37. Biggers, op. cit. , p. 34.

38. Biggers, op. cit. , p. 34, citing Boue, J.G. and Boue, A., Increased
Frequency of Chromosomal Anomalies in Abortions After Induced
Ovulation, Lancet vol. i, 1973, p. 679.
,

39. Biggers, op. cit. p. 33, citing Ahlgren, M., Sperm Transport to
,

and Survival in the Human Fallopian Tube, Gynecologic Investigation ,

vol. 6, 1975, pp. 206-214.

40. Biggers, op. cit. p. 33, citing Eraser, L.R., Zenellotti, H.M.,
,

Paton, G.R. and Drury, L.M., Increased Incidence of Triploidy in

Embryos Derived from Mouse Eggs Fertilized In Vitro Nature
, ,

vol. 260, 1976, pp. 39-40; Eraser, L.R., and Maudlin, I.,
Relationship Between Sperm Concentration and the Incidence of
Polyspermy in Mouse Embryos Fertilized In Vitro , Journal of
Reproduction and Fertility vol. 52, 1978, pp. 103-106.
,

41. Biggers, op. cit. , p. 34.

42. Schlesselman, op. cit. , pp. 29-31.

43. Kass, op. cit. , 1978, p. 12.

44. Curran, Charles E., In Vitro Fertilization and Embryo Transfer:

From a Perspective of Moral Theology, a paper prepared for the
Ethics Advisory Board, 1978, p. 19.

45. Biggers, Statement to the Ethics Advisory Board, op. cit. ,

pp. 261-263; see also Shulman, Joseph, Testimony for the

Ethics Advisory Board, 1978, p. 3.
 . .

58

46. Gould, op. cit. , p. 17; Mastroianni, op. cit. , p. 3.

47. Gould, op. cit. , pp. 17-18.

48. Ibid ., pp. 18-19.

49 Ibid . , p . 19.

50. Schlesselman, op. cit. , pp. 29-31.

51. Gould, op. cit. p. 17; Edwards, op. cit.

, p. 8; Mastroianni, ,

Luigi, Jr., In Vitro Fertilization, in: Reich, Warren, ed..

Encyclopedia of Bioethics , vol. 4, New York, Free Press-Macmillan,
1978, pp. 1448-1451.

52. Kass, Leon, Making Babies -- the New Biology and the 'Old' Morality,
Public Interest vol. 26, 1972, p. 31,
,

53. Items (b) through (d) are enumerated in: National Research Council,
Assembly of Behavioral and Social Sciences, Committee on the Life
Sciences and Social Policy, Assessing Biomedical Technologies:
An Inquiry into the Nature of the Process, Washington, D.C.,
National Academy of Sciences, 1975, p. 21.

54. British Medical Association, Board of Science and Education Panel,

Professional Standards London, British Medical Association, 1972,
,

p. 10.

55. National Research Council, op. cit. , pp. 21, 27.

56. Mastroianni, Luigi, Jr., In Vitro Fertilization of Human Ova and

Blastocyst Transfer: An Invitational Symposium, in: Schumacher,
Gebhard, F., et a1 Journal of Reproductive Medicine vol. 11,
, ,

1973, p. 197; National Research Council, op. cit. 1975, p. 21, ,

57. Edwards, op, cit, , p, 11,

58. Kass, op. cit. , pp. 9-10,

59. Ibid ., p. 10.

60. Ibid ., pp. 9-11.

61. Curran, op. cit. , pp. 17, 26.

62. Kass, op, cit, , 1972, p. 34; Leiman, op, cit, , p, 126.

63. Kass, op, cit, , 1978, p, 15.

 59

64. Ibid .

65. Gorovitz, op. cit. , pp. 20-21.

66. Leiman, op. cit. , pp. 128-129.

67. Kass, op. cit. , 1978, p. 19.

68. Walters, op. cit. , fn. 113 (see fn. 9 above).

69. Ibid .

70. Ibid , fn. 118 (see fn. 10 above).

71. Gorovitz, op. cit. , pp. 14-15.

72. Biggers, Statement to the Ethics Advisory Board, op. cit. ,

pp. 236-237.

73. Leiman, op. cit. , pp. 130-131.

74. Curran, op. cit. . p. 28.

75. Leiman, op. cit. , p. 131.

76. Ibid .

77. Kass, op. cit. , 1978, p. 22.

78. Hauerwas, op. cit. , p. 18.

79. Gorovitz, op. cit. , p. 26.

80. Kass, op. cit. , 1978, p. 25.

81. Ibid .

82. Ibid ., pp. 28-29.

 60

CHAPTER IV: LEGAL ISSUES SURROUNDING HUMAN IN VITRO FERTILIZATION,

EMBRYO CULTURE, AND EMBRYO TRANSFER

Two papers written for the Board examined the legal issues sur-

rounding human in vitro fertilization; one was prepared by Dennis Flannery

and his colleagues at the Washington law firm of Wilmer, Cutler and

Pickering, the other was written by Barbara Katz, Office of Legal

Affairs, University of Colorado Medical Center. The discussion which

follows reflects the legal analysis and conclusions presented by the two

papers; in any areas where they differed, the differences are noted.

Four main topics are addressed: (A) existing law that might be applicable

to human in vitro fertilization and embryo transfer; (B) Constitutional

questions raised either by the use, or by restrictions imposed on the

use, of the techniques; (C) possible implications for tort liability;

and (D) criminal law.

A. Existing Federal and State Law Applicable to Human

In Vitro Fertilization and/or Embryo Transfer

1 . Federal Law

The only existing federal control of human in vitro fertilization

is a regulation of the Department of Health, Education, and Welfare:

No application or proposal involving human in vitro ferti-

lization may be funded by the Department or any component
thereof until the application or proposal has been reviewed
by the Ethical Advisory Board and the Board has rendered
advice as to its acceptability from an ethical standpoint.^

In its notice of proposed rulemaking entitled "Protection of Human

Subjects: Proposed Policy" issued August 23, 1974, the Department

indicated the kind of issues it expected the Ethics Advisory Board to

consider:
 5 ^

61

With respect to the fertilization of human ova in vitro ,

it is expected that the Board will consider the extent to

which current technology permits the continued develop-
ment of such ova, as well as the legal and ethical issues
surrounding the initiation and disposition of such pro-
ducts of research.

With respect to implantation of fertilized human ova, it

is expected that the Board will consider such factors as
the safety of the technique (with respect to offspring)
as demonstrated in animal studies and clarification of
the legal responsibilities of the donor and recipient
parent(s) as well as the research personnel.

Two other general requirements of HEW regulations are presumably

applicable to research involving human in vitro fertilization, as well.

All such research conducted or supported by the Department must be

reviewed by a local Institutional Review Board (IRB)-^; in addition,

studies involving human in vitro fertilization should not be conducted

or supported by HEW unless "appropriate studies on animals and nonpregnant

individuals have been completed."^

Moreover, the Department interprets the National Research Act as

authorizing (if not requiring) IRB review of human research not funded

by HEW at any institution which receives a grant or contract involving

human subjects under the Public Health Service Act.

The Secretary shall by regulation require that each

entity which applies for a grant or contract under
this Act for any project or program which involves
the conduct of biomedical or behavioral research
involving human subjects submit in or with its
application for such grant or contract assurances
satisfactory to the Secretary that it has established
(in accordance with regulations which the Secretary
shall prescribe) a board (to be known as an 'Insti-
tutional Review Board') to review biomedical and
behavioral research involving human subjects con-
ducted at or sponsored by such entity in order to
protect the rights of the human subjects of such
research.
 62

However, the standards to be employed by the local Institutional Review

Board in reviewing non-federal ly funded human research are not specified

by the statute.

2. State Law

No state has enacted legislation or promulgated regulations directly

governing human in vitro fertilization and/or embryo transfer. Such

laws or regulations could affect the conduct of research involving in

vitro fertilization within particular jurisdictions, especially since

the federal regulations governing such research specifically do not

preempt state or local law in this sphere:

Nothing in this subpart shall be construed as indicating

that compliance with the procedures set forth herein
will in any way render inapplicable pertinent State
or local laws bearing upon activities covered by this
subpart.^

The types of existing law which provide the closest analogies to human

in vitro fertilization and/or embryo transfer are state statutes or

court decisions concerning (a) artificial insemination and (b) research

involving human fetuses.

Within the context of family law, the issue of artificial insemin-

ation, especially artificial insemination with donor sperm (AID), has

received legislative or judicial attention in approximately one-third of

the states. Case law concerning AID has focused primary attention on

whether AID is equivalent to adultery and thus, whether children conceived

as a result of AID are legitimate. (Legitimacy has implications both

for inheritance rights and for claims to paternal support.) The general

trend of recent case law, particularly in California and New York, has
 9

63

been toward the view that AID does not constitute adultery and that

children conceived as a result of AID are legitimate. Nineteen states

have enacted legislation regarding one or more aspects of artificial

insemination; many of the statutes include a requirement for prior

written consent by both husband and wife. However, in the remaining

states, the legal status of children conceived following AID is left in

doubt.

A second area of state legislative interest -- research with live

human fetuses -- is also at least partially analogous to research involving

human in vitro fertilization. Approximately sixteen states have enacted

statutes governing fetal research. The primary focus of all such statutes

is the permissibility of research on the fetus (1) following implantation

and (2) before, during, or after induced abortion. However, the language

of at least one state statute on fetal research may be sufficiently

broad to encompass, as well, research involving unimplanted early human

embryos.

B. Constitutional Issues

1 . Preliminary Distinctions

Federal or state action may be found unconstitutional if it infringes

upon a fundamental right of United States citizens and the government

cannot demonstrate (1) that the law is necessary to protect a "compelling

state interest" and (2) that it does not go beyond what is necessary to

protect those interests.'^ If, on the other hand, a governmental action

restricts individual activities in ways that do not infringe a fundamental

right, then the government need only show that its action is rationally

related to a constitutionally permissible purpose. ^^ Thus, a critical

 64

question regarding human in vitro fertil ization -- whether in the labora-

tory or the clinical context -- will be whether individuals proposing to

employ, or seeking access to, the technique can be said to be asserting

a fundamental legal right. This, in turn, determines whether the government

will be required to justify its regulation of human in vitro fertilization

by demonstrating a compelling state interest that it seeks to protect or

only by demonstrating a rational basis for its action.

A second distinction is also important: the distinction between a

governmental restriction of an activity, on the one hand, and a govern-

mental decision not to fund the activity, on the other. In 1977, in a

case challenging the constitutionality of restrictions on the use of

Medicaid funds for abortions, the United States Supreme Court held that

a governmental restriction of the use of public funds to support the

exercise of a fundamental right does not, by itself, constitute impermissible

1p
"^
interference with the exercise of that right. The Court concluded

that the existence of a fundamental right "implies no limitation on the

authority of a state to make a value judgment [to discourage the exercise

of that right] and to implement that judgment by the allocation of

public funds. "^^ As applied to the question of in vitro fertilization,

that langauge suggests that a governmental decision to restrict either

laboratory research or clinical applications of the technique would need

stronger justification than would a decision not to provide funds for

such activities.

2. Clinical Applications of In Vitro Fertilization and Embryo

Transfer

Constitutional principles affecting reproductive activity are more

fully articulated than those relating to basic laboratory research.

 65

Therefore, it is useful to examine the rights pertaining to reproductive^

choices before attempting to analyze what rights might be implicated in

government regulation of basic laboratory research.

The argument for a constitutional right to reproduce by means of in

vitro fertilization would rest on the right to privacy as related to

procreation, the marital relationship, and contraception. In 1942, in a

decision striking down Oklahoma's compulsory sterilization law, the

Supreme Court held that individuals have a right to be free from unwar-

ranted governmental interference with procreative capabilities. (Skinner

v. Oklahoma )^^ This might be termed "the right to procreation. "^5 /\

second constitutionally protected area is the privacy of the marital

relationship. This was recognized in a 1965 decision (Griswold v. Connecticut )

invalidating a Connecticut statute forbidding the use of contraceptives

by married couples. There, the Court said:

The entire fabric of the Constitution and the purposes

that clearly underlie its specific guarantees demonstrate
that the rights to marital privacy and to marry and raise
a family are of similar order and magnitude as the funda-
mental rights specifically protected ..The fact that
. .

no particular provision of the Constitution explicitly

forbids the State from disrupting the traditional rela-
tion of the family -- a relation as old and as fundamental
as our entire civilization -- surely does not show that
the Government was meant to have the power to do so.'°

The privacy interests recognized in Griswold were expanded in later

cases to include "the right of the individual, married or single, to be

free from governmental intrusion into matters so fundamentally affecting

a person as the decision whether to bear or beget children."''

 66

The extent to which any individual's access to in vitro fertilization

will be viewed as involving a fundamental right will depend upon how

closely analogous it is to the rights already recognized by the Supreme

Court. Thus, for example, a married couple with no alternative means

for having a child of their own could claim that restriction of access

to in vitro fertilization is interference with the fundamental right of

marital privacy and with their right to choose whether, and in what

manner, to achieve procreation. Since these rights are reasonably analo-

gous to those recognized by the Court in Skinner , Griswold , and Eisenstadt ,

the argument might well be persuasive. If the Court agreed with the

view that the rights in this instance are fundamental, the government

would have to demonstrate a compelling state interest to justify inter-

fering with the exercise of those rights.

On the other hand, an unmarried woman who wished to utilize in

vitro fertilization followed by embryo transfer to another (surrogate)

mother, in order to have a genetic child of her own without the expense

and inconvenience of pregnancy, would have a much weaker case. There

would be neither marital privacy nor a procreative capacity, in the

normal sense, to protect. Thus, courts might well find the right asserted

to be less than fundamental, and the government would have to show only

a rational basis for restricting the exercise of that "right".

Several grounds for prohibiting or limiting access to clinical

applications of in vitro fertilization could be advanced. First, a

state or the federal government might argue that this reproductive

technique inevitably involves the loss of human embryos. Accordingly,

 67

a government might enact legislation to protect early human embryos.

Such a law might pass the rational basis test but might not withstand

constitutional challenge by individuals who could assert a fundamental

right to access to in vitro fertilization.

A second possible basis for state intervention in the clinical

applications of in vitro fertilization would be the government's interest

in fostering marriage and discouraging illegitimacy. This rationale

might be proffered, for example, in support of a law restricting publicly

'^
funded in vitro fertilization and embryo transfer to married couples.

There is little room for doubt that such a funding limitation would be

found constitutionally permissible; it is not clear, however, whether

courts would uphold an outright prohibition on the access of single

20
persons to in vitro fertilization and embryo transfer.

Third, a government might prohibit or limit access to clinical

applications of in vitro fertilization in order to preclude institutional

or individual genetic planning or manipulation. It has been suggested

that the potential social impact of a large-scale genetic program might

justify governmental regulation, but that interference with the genetic

planning of individual families would have to be justified by a compelling

state interest. 21

Fourth, a state or the federal government might conclude that the

use of surrogate or host mothers in connection with clinical in vitro

fertilization would create insuperable legal problems that would

 68

justify a prohibition of such activities -- perhaps on the ground that

service as a surrogate mother is an unacceptable form of employment. ^^

In the opinion of Flannery and associates such a prohibition would

probably withstand legal challenge on both "rational basis" and "com-

pelling state interest" grounds. ^-^

Finally, if clinical applications of in vitro fertilization should

appear to present health risks to mother or offspring which are substan-

tially greater than those usually associated with conception and child-

birth, then a state or the federal government might well decide to

prohibit or limit access to this reproductive technique. Whether such a

state intervention would withstand constitutional challenge would depend

in part on the probability and magnitude of the risks involved. 24

In addition to making basic decisions regarding the regulation of

access to clinical applications of in vitro fertilization, the states

and the federal government may wish to establish policies on such related

matters as the legal status of children who are produced by means of in

vitro fertilization and embryo transfer, the role of attending physicians

in decisions regarding implantation and abortion, and record-keeping re-

quirements. ^^

3. Laboratory Research Involving In Vitro Fertilization and/or

Embryo Culture

a. Constitutional bases for asserting a right to perform or

participate in laboratory research involving in vitro fertilization

and/or embryo culture. Two major constitutional arguments could be

advanced in support of basic laboratory research involving human in

vitro fertilization. The first is freedom of inquiry, or the right

 69

of scientists to perform their research without governmental interference.

This argument can be asserted most vigorously in defense of research

conducted without the assistance of government funding. The second is

the right of individuals to dispose of their genetic material as they

see fit.

In a recent report, the National Commission for the Protection of

Human Subjects of Biomedical and Behavioral Research expressed the view

that although the Supreme Court might recognize a First Amendment right

to seek new ideas or knowledge (i.e. , a "right to research" )26, that

must be distinguished from a right to be free from regulations governing

the manner in which research may be conducted. ^^

... [T]he state may not interfere with the researcher's

choice of the end or topic of research, but it may regulate
only the methods used in the research, in order to protect
interests in health, order and safety with which unrestricted
research might conflict. Such restrictions are valid if they
are reasonably related to protection of non-speech interests
and are not so vague and over broad that they chill the
exercise of protected speech. 28

Accepting the National Commission's distinction between the goal and the

manner of research as valid, then the applicability of this putative

right to basic research involving human in vitro fertilization is proble-

matic, since it is the manner of achieving the knowledge -- that is,

through the creation and study of human embryos -- that is most likely

to be the target of governmental regulation. 29

A second constitutional argument in support of laboratory research

involving human in vitro fertilization focuses attention on the rights

of potential gamete donors to dispose of their reproductive cells in

 70

whatever manner they see fit. According to this view, donors have a

"constitutionally protected fundamental privacy right to control the use

and manipulation of their own genetic materials. "^^ Such a privacy

right is clearer, however, in cases involving contraception or abortion

than in the case of genetic materials donated for basic laboratory

research. Once the materials are outside the body of the donor, any

personal rights of privacy regarding their use become attenuated.-^'

b. Constitutional bases for governments' prohibiting or refusing

to fund laboratory research involving human in vitro fertilization . If

the analysis of the preceding section is accepted, then it would appear

that no fundamental constitutional right to perform or participate in

basic research involving in vitro fertilization is likely to be found.

In the absence of such a right, the government could, if it wished,

prohibit in vitro fertilization research if it had a rational basis for

doing so. A prohibition would most probably be based on the view that

the creation, study, and destruction of early human embryos is inconsis-

tent with the dignity which should be accorded to forms of potential

human life. Even if a fundamental right to conduct or participate in

such research did exist, the government could still decline to support

it with public funds. Such a refusal could be based on an administrative

determination that other areas of research would be more useful to the

government. -^^

If research with early human embryos were to involve embryo transfer

and subsequent implantation, the current HEW regulations governing fetal

research would apply, since the "fetus" is defined as the embryo "from

the time of implantation. "33 State statutes regarding fetal research

might or might not apply, depending on their formulation.

 71

In addition to deciding whether to prohibit or to support laboratory

research involving human in vitro fertilization, states or the federal

government might wish to formulate standards governing the conduct of

such research, if the research is permitted. For example, regulations

to protect the health of ovum donors or to set standards for protecting

the dignity of potential human life might be adopted. Moreover, a

government might require that gamete donors consent in advance to the

use of their reproductive cells in research involving in vitro fertili-

zation. These procedural regulations, designed to achieve a rational

governmental purpose, should be constitutionally permissible."^^

C. Liability for Injuries

The federal government might be liable for injuries arising from in

vitro fertilization in research programs conducted or supported by HEW.

This section explores three questions: (1) whether such suits would be

barred by the doctrine of sovereign iirimunity; (2) what causes of action

might be considered valid; and (3) whether a program could be established

to provide compensation for such injuries.

1. Sovereign immunity . Under the Federal Tort Claims Act, the

United States is liable for the "negligent or wrongful" acts or omissions

of its employees while they are acting within the scope of their employ-
35
ment. Exceptions to such liability include acts or omissions that are

within an agency or officer's "discretionary duty" (as, for example, a

decision to initiate a particular research program). 36 Whether the

doctrine of sovereign immunity would bar a suit for damages arising

within an HEW-conducted or supported research program involving in vitro

fertilization would depend upon:

 72

1. Whether the investigator is considered a federal "employee."

(Does this category include, for example, grantees or
contractors in HEW-funded research programs?)

2. Whether the alledged wrong occurred because of the employee's

exercise of protected "discretionary functions" at the
policy level or through a failure to exercise due care in
a particular program at the operational level.

3. Whether the employee's act fell within an exception to

liability under the Federal Tort Claims Act.

The Board's legal consultants suggest that the United States, but not

individual investigators, would probably be liable for any negligence of

subordinate HEW officers or employees who design or conduct a particular

research program involving in vitro fertilization. If the conduct

violated existing HEW regulations, even the discretionary exception

would not prevent liability. 37

2. Possible causes of action

a. Actions on behalf of the child . Two kinds of suits might

be brought on behalf of a child born alive with handicaps following in

vitro fertilization and embryo transfer. First, a suit might be brought

on the basis of prenatal or even preconception injuries sustained by the

child. (Preconception injuries might be claimed if, for example, labora-

tory procedures involving the gametes were thought to have given rise to

the damage.) The plaintiff in such a suit would face the difficult task

of demonstrating a causal connection between the procedures of j_n vitro

fertilization or embryo transfer and the child's injuries.-^^

 73

Alternatively, a "wrongful life" suit might be brought on behalf of

a child born alive but handicapped following in vitro fertilization and

embryo transfer. Such a suit would claim that it would be better for a

child not to be born at all than to be born in a damaged condition. With

one exception, -^^ the courts have refused to recognize "wrongful life" as

a valid ground for recovery of damages. This refusal appears to stem

from a reluctance or inability to assign a monetary value to either

impaired existence or nonexistence as a basis for recovery. ^0 Even if

"wrongful life" were accepted as a valid cause of action in principle,

the plaintiff would still face the challenge of showing a causal connection

between the procedures employed and the child's injuries. ^^

b. Actions to compensate the parents . Two distinct types of

suit might be brought under this general heading. First, it might be

claimed that negligently-caused damage to a child conceived by means of

in vitro fertilization had caused the parents economic loss and/or

emotional distress. Courts have held that the following "wrongful

birth" suits stated a valid cause of action:

1. The mother of a severely deformed child brought suit

against her physician for his failure to diagnose rubella
during pregnancy. ^2

2. Parents brought suit against a physician for failing to

diagnose a pregnancy in time to allow the woman to secure
an abortion. ^-^

3. A pharmacist was sued for mistakenly filling a prescription

for the contraceptive Norinyl with a different drug,
Nardil, when the woman subsequently became pregnant. ^^
 74

4. A couple brought suit against a physician whose sterili-

zation of the husband failed to prevent the wife's con-
ception of a subsequent child. 45

If a "wrongful birth" suit were brought because of the birth of a handi-

capped child following in vitro fertilization, the plaintiff would face

the difficulties of demonstrating causation which have been alluded to

nr
in the preceding paragraphs.

A second possible cause of action which might be brought by would-

be parents on their own behalf is an action for the "wrongful death" of

a hoped-for child. All states currently allow actions for wrongful

death caused by prenatal injuries if the death occurs following live

birth. In addition, many states allow recovery for the prenatal death

of a viable fetus. 47 The question raised by in vitro fertilization and

embryo transfer is whether the theory of "wrongful death" would be

extended by the courts to cover preimplantation human embryos.

Under a somewhat different legal theory -- one which focused on the

destruction of the would-be parents' property rather than on the "wrongful

death" of an early embryo -- a New York jury recently awarded $50,000

for emotional distress following the intentional destruction of a culture

containing gametes from the husband and wife.'^^ In the opinion of

Flannery and associates, it is unlikely that the courts will ultimately

extend the concept of "wrongful death" to include the intentional destruction

of a preimplantation embryo. ^^ According to Katz, suits charging physician

negligence in the unintentional death of an embryo or fetus conceived

with the aid of in vitro fertilization are also unlikely to succeed

because of the experimental character of the procedure and because of

the absence of a clear standard of due care.^"^

 75

3. Compensation for Injury . In part because traditional tort

concepts seem inapplicable to research involving in vitro fertilization

and/or embryo transfer, Katz proposes the establishment of a federal

compensation fund to provide monetary redress in the event of injury

associated with such research. ^1 In her view, the rationale for creation

of such a fund is that society has a substantial interest in establishing

a program of human in vitro fertilization research and therefore has an

obligation to the human subjects who may be injured as a result of their

participation in such a program. Any injury which is not clearly unrelated

to participation in the in vitro fertilization program would be compensable.

The amount of compensation would be determined by calculating the monetary

requirements for making the situation of a damaged child or mother equal

to that of a normal person, insofar as such calculation is possible. The

compensation fund would be financed through premiums paid by researchers

or their institutions, by adding a surcharge to hospital bills, or by

allocating general revenues to this purpose. The plan would include

financial incentives to encourage the exercise of due care by investigators

and institutions.

D. Criminal Law

The primary question of criminal law that might arise is whether

the act of allowing preimplantation human embryos to die or killing them

would constitute the crime of feticide, a species of homicide. After

surveying developments in English and American jurisprudence, Katz

concludes that the destruction of preimplantation human embryos is not

likely to fall within either homicide or feticide statutes. ^^

 76

As noted above, however, state statutes enacted to regulate research

involving human fetuses may be broad enough to include research involving

preimplantation human embryos. For example, one state statute defines

the "human conceptus" as "any human organism, conceived either in the

human body or produced in an aritificial environment other than the

53
human body, from fertilization through the first 265 days thereafter."

The statute continues:

Whoever uses or permits the use of a living human

conceptus for any type of scientific, laboratory
research or other experimentation except to protect
the life or health of the conceptus, or except as
herein ppvided, shall be guilty of a gross misde
meanor.

In summary, aside from HEW regulations governing research supported

by the Department, and a very few broadly written state statutes prohibiting

research on the human fetus, no state or federal laws apply to human in

vitro fertilization. However, Supreme Court decisions recognizing a

fundamental right to privacy in marital relations and reproductive

activity suggest that married couples might successfully assert a right

of access to in vitro fertilization and embryo transfer as a means of

bearing their own children. The government would have to demonstrate a

compelling state interest (e.g. , protecting the health and safety of

mothers and offspring) to justify restricting such access. The government

need not, however, provide federal support for such procedures. In the

research context, the government may regulate the manner in which research

is conducted, especially if the research is supported by funds and it

involves human subjects. Questions about legal responsibility for the

care of the offspring cannot be answered with clarity. Analogous statutory

and case law in the field of artificial insemination suggests that the
 77

law in this area is confused, at best. Similarly, questions about

liability and compensation for injuries to the mothers and offspring

need to be addressed.
 78

FOOTNOTES

NOTE: The two papers prepared for the Board and cited often throughout
are: Dennis M. Flannery, et aj_. , "Legal Issues Concerning In Vitro
Fertilization" (hereinafter cited as, Flannery et^ al_. ) and Barbara F.
Katz, "Legal Implications of In Vitro Fertilization and Its Regulation"
(hereinafter cited as Katz).

1. 45 CFR §46. 204(d).

2. 39 Federal Register 30650, August 23, 1974.

3. 45 CFR §46.205.

4. 45 CFR §46. 202(a)(1).

5. Public Law 93-348, 88 Stat. 348, July 12, 1974.

6. 45 CFR §46. 201(b).

7. Katz, pp. 6-10; cf. Flannery et aj[. , pp. 48-49.

8. Katz, pp. 6-10; cf. Flannery et al_. , pp. 48-49.

9. Flannery et aj_, , pp. 5-6; Katz, pp. 42-44.

10. Flannery et^ al_. , p. 35.

11. Maher v. Roe, 432 U.S. 464, 478 (1977).

12. Flannery et^ al_. , p. 35.

13. Maher v. Roe, 432 U.S. 464, 474 (1977).

14. Skinner v. Oklahoma, 316 U.S. 535 (1942).

15. Flannery et al^. , p. 10.

16. Griswold v. Connecticut, 381 U.S. 479 (1965).

17. Eisenstadt v. Baird, 405 U.S. 438, 453 (1972); see also , Carey v.
Population Services International 431 U.S. 678 "(T977).

18. Flannery e^ al_., pp. 38-40; Katz, p. 49.

19. Flannery et al_. , p. 40.

20. Id. at 41-42.

 )

79

21. 16^. at 42-44.

22. Id. at 45, n. 68.

23. U. at 45-46.

24. ld_. at 45-47; Katz, p. 49.

25. Flannery e^ aj_. , pp. 47-54.

26. National Commission for the Protection of Human Subjects of Biomedical

and Behavioral Research. Institutional Review Boards: Report and
Recommendations , DHEW Publication No. (OS) 78-0008, U.S. Government
Printing Office, Washington, D.C., 1978, p. 78. (Discussed in
Flannery et a]_. , p. 58 et seq .

27. ld_. at 79.

28. Id_.

29. Flannery et al., p. 60; Katz, pp. 45-46,

30. Flannery et^ al_. , p. 61.

31. Id., pp. 61-63; Katz, p. 49.

32. Flannery ejt a]_. . pp. 63-65.

33. 45 CFR §46. 203(d).

34. Flannery etal., pp. 70-72.

35. 28 U.S.C. §1346(b); Flannery et al_^, pp. 73-74.

36. 28 U.S.C. §2680(a).

37. Flannery et al_. , pp. 76-82.

38. Katz, p. 15; Flannery et al_. , pp. 85-86.

39. Park v. Chessin, 60 App.Div.2d 80, 400 N.Y.S.2d 110 (1978).

40. Katz, p. 18; Flannery et al. , p. 87.

41. Katz, p. 18.

42. Jacobs v. Theimer, 519 S.W.2d 846 (Texas 1975); cited by Katz,
pp. 18-19.

43. Ziemoa v. Sternberg, 400 N.Y.2d 110 (1977); cited by Katz, p. 19.

44. Troppi v. Scarf, 187 N.W.2d 511 (Mich. 1971); cited by Katz, p. 19.
and Flannery et al., p. 88.
 ,

80

45. Doerr v. Villate, 220 N.E.2d 767 (111. 1966); cited by Katz, p. 19.

46. Katz, pp. 19-20; Flannery et al_. , pp. 88-89.

47. Flannery etal., p. 88; Katz, pp. 29-30.

48. Del Zio v. Presbyterian Hospital, 1974 Civ. 3588 (S.D.N.Y. 1978).

49. Flannery et a]_. , p. 88.

50. Katz, p. 27.

51. Katz, pp. 32-37.

52. Katz, pp. 21-25.

53. Minn. Stat. Ann. §145.521, section 2 (West 1977); cited by Flannery
et al,, n. 19.

54. Minn. Stat. Ann. §145.522 (West 1977); cited by Flannery et al .

n. 19.
 81

CHAPTER V: REVIEW OF PUBLIC ATTITUDES

A. Responses Received by the EAB

Between September 15 and December 15, 1978, the Ethics Advisory

Board held eleven public hearings on the question of federal support of

research involving human in vitro fertil ization (IVF) in order to afford

an opportunity for members of the public to present their views. In

all, several thousand hearing notices were sent to professional organ-

izations, public interest groups, universities, clergy, and individuals.

Everyone who requested to appear was heard; 179 individuals presented

testimony in hearings in Bethesda (Maryland), Boston, Seattle, San

Francisco, Atlanta, Kansas City, Detroit, Philadelphia, Denver, Dallas

and New York City. Eighteen people preferred to submit formal written

testimony in lieu of oral presentation. In addition, the Board received

over 2000 letters and postcards, some of which were forwarded from

President Carter and Secretary Califano.

Transcripts of all formal presentations (both oral and written)

have been distributed to members of the Board and are available to the

general public from the National Technical Information Service (NTIS).

All of the correspondence received by the Board has been duplicated and

distributed to members; copies are on file at the office of the EAB and

are available for public inspection.

In the arguments and presentations made to the Board, it was

evident that many people did not distinguish between basic research

involving laboratory fertilization of human ova (IVF) on the one hand,

and the subsequent transfer of the resulting embryos to establish

 82

a pregnancy, on the other. Thus, some of the arguments both for and

against "1n vitro fertilization" referred only to one or another of the

procedures under consideration by the Board. At the public hearings, it

was often possible to elicit clarification by asking whether a person's

statement was intended to apply to both the basic research and the

clinical application; this was not the case with respect to written

communications. Summaries of the arguments are presented below.

1. Arguments in Favor of Federal Funding. Although there were, of

course, many variations on the theme, most of the arguments in favor of

federal support of IVF focused on either the risks and benefits of IVF

or the rights of investigators and infertile couples: (a) the scientific

benefits to be gained; (b) the need for federal regulation; (c) the

necessity to evaluate and to reduce the risks inherent in the procedure

and the reliance of such research on federal support; (d) freedom of

inquiry for scientists; (e) freedom of reproductive choice for infertile

couples; and (f) the rights of infertile couples to some return on their

taxes paid for general health and welfare.

The majority of individuals who favor federal funding for research

involving human IVF stressed the benefits it would produce for the

general welfare ( e.g . , understanding and correcting infertility, pre-

venting birth defects, understanding certain hereditary diseases,

furthering the search for a cure for cancer, improving our knowledge of

early fetal development, and developing better methods of contracep-

tion). A number of witnesses stated that there are many scientific

 83

procedures that can be used for either the benefit or the detriment of

mankind; but the possibility for abuse does not in and of itself make

their development morally wrong. Many responded to the concern regard-

ing "discards" by noting that fertilized eggs are often lost in the

natural process of reproduction. Some stated that it is morally

irrelevant whether embryo loss occurs naturally or in a laboratory.

Other individuals pointed out that zygote wastage may eventually be

eliminated. For example, it may be possible to extract only one ovum at

a time, as suggested by Dr. Steptoe (on Meet the Press), once the tech-

niques of fertilization and embryo transfer are improved. Moreover,

some public witnesses stated that once the technique of freezing the

embryos is perfected, fertilized eggs that are not transferred immediately

may be preserved for later attempts at implantation.

Numerous witnesses expressed concern about the possible risks of

embryo transfer procedures already being performed in the private sec-

tor. A few stressed the need to hold investigators accountable for

their actions; others urged federal support of the activities in order

to apply regulations to assure that they will be conducted in a res-

ponsible manner. They thought that if the government were to fund

research and adopt regulations governing the experimentation, investi-

gators receiving non-government money would follow the government regu-

lations.

Some stressed the need for government support to assure greater

exploration of animal models and to encourage basic research in human

IVF so that the safety and efficacy of the procedure can be evaluated

before clinical application of embryo transfer is permitted. A related

 84

argument was that if research is permitted, scientists may be expected

to improve the technique of in vitro fertilization and embryo transfer

so that risks to mother and offspring will be substantially reduced.

Several individuals stressed the responsibility of the government

to assure freedom of inquiry. Others urged the government to educate

the public about the significance of new scientific discoveries to the

public. They were concerned that the development of federal policy with

such profound implications might be influenced by a public unnecessarily

alarmed by inaccuracies and misinterpretations.

The last set of arguments in favor of federal funding related

to the rights of infertile couples as taxpayers and the corresponding

duties of the government. A number of individuals felt that since

childless couples have paid taxes that subsidize the costs of contra-

ception and childbearing, as well as education and welfare, for other

people's children, the government has an obligation to assist them by

supporting research and services relevant to their reproductive needs.

Some argued that it is the government's responsibility to ensure freedom

of choice for women by making both alternatives -- raising a family or

remaining childless -- available to all couples.

It was stated that at the present time, adoption is not a viable

alternative for childless couples. The waiting list for infants is very

long and the cost for international adoption is exhorbitant and limited.

There was additional testimony, however, that even if adoption procedures

could be improved, problems would remain; adoption does not satisfy the

very strong desire to bear one's own child. Some even suggested that
 85

the unfulfilled desire to bear children threatens the mental health of

women and the stability of marriages. They argued that infertility is

a disorder requiring medical intervention, and that the government has a

responsibility to make such health care available to all citizens. Since

the government funds therapeutic abortions when bearing a child would

threaten the life or health of the mother, they noted, the government

ought to fund "therapeutic conception" as well. Some elaborated on this

argument, stating that government funding is necessary to assure that

the option of having a child through in vitro fertilization is available

to poor women as well as to those who are able to purchase the option in

the private sector.

2. Arguments Opposed to Federal Funding. In general, the argu-

ments against federal support of IVF and embryo transfer stemmed from

five major concerns: (a) the moral status of the embryo; (b) questions

of safety; (c) funding priorities; (d) decreasing ability to limit more

objectionable procedures; and (e) detrimental social and psychological

effects on offspring, family and physicians.

The most frequently articulated argument against federal funding of

IVF was based on the moral status of the fertilized egg and embryo.

Proponents of this argument believed that human life should be respected

from the moment of fertilization. They argued that deliberately to

create human life merely for experimental purposes with no intent or

expectation of sustaining such life is immoral.

Since many fertilized eggs are discarded in the normal process of

procreation some proponents of this position said that they might not
 86

oppose in vitro fertilization research if a technique could be perfected

that would allow the investigators to extract and fertilize only one

egg, or freeze for later transfer the embryos which could not be

implanted immediately. Others stated that even if such a technique were

perfected, it would still be unethical to fund in vitro fertilization

research because of the immorality of interfering with the natural

process of human reproduction.

Many individuals expressed concern about proceeding with embryo

transfer in humans without further data concerning its safety. They

believed that more should be known about the probability of producing

defective embryos. They also thought it important to gain more infor-

mation concerning level of risk to the women undergoing the procedures.

Among opponents of federal funding on the grounds of safety were those

who thought that people have a right to take risks by volunteering for

research conducted in the private sector, but that it is unethical for

the government to approve and support IVF and embryo transfer in humans

before the risks and benefits have been more fully evaluated.

A large number of persons opposed government funding of IVF and

embryo transfer because they believe it is not an important national

priority. Various other needs were suggested as having greater claims

upon government funds. A favorite alternative was research to develop

methods of preventing and treating disorders (such as pelvic infectious

diseases) that result in the tubal occlusion giving rise to demands for

IVF. Others indicated that funds would be better spent in improving

fertility control and in learning to prevent or treat birth defects

 87

and genetic abnormalities. Still others stressed society's responsi-

bility toward those children already in existence who have been abused

or abandoned. Programs encouraging adoption should have higher priority

than IVF. There were also those who believed it inappropriate to fund

IVF when the majority, they were certain, opposed such research on

deeply-felt ethical or religious grounds. The government should not

spend public money for experiments so clearly in conflict with the basic

commitments of many of the citizens.

Some expressed a fear that approving policies that permit researchers

consciously to intend human life to die in vitro could lead to an inability

to draw barriers to policies that allowed more obviously objectionable

occasions for humans to end the life of other humans. Some proponents

of this argument believed that the selective destruction of undesirable

fertilized eggs might contribute to the creation of a eugenic program

controlled by some officially condoned elite. There was even the fear

that barriers would fall to the creation of half-animal, half-human

hybrids or chimeras.

A variety of harmful consequences to the psychological and social

wellbeing of those involved in IVF were cited as reasons for not funding

such research. Fears were expressed that children born through in vitro

fertilization would initially be subject to considerable noteriety and

be unable to escape a continuing stigma. There was concern that IVF

might endanger the family by reducing the human act of reproduction to

an artificial or mechanical laboratory procedure. An even greater

threat to the family would be the possible use of surrogate mothers

and extra-marital donors of genetic material. This set of reasons for

opposing government funding of IVF included the dehumanizing of scientists

and doctors involved in the research who must dispose of the human embryos,

Another possible consequence cited as a reason for opposing funding was

the possible exploitation of uneducated, poor and minority women.

B. Public Opinion Surveys

Since the birth of Louise Brown on July 25, 1979, both the Gallup

and Harris survey organizations have conducted polls providing the

clearest indication available of United States public opinion concerning

IVF. The Gallup survey included reactions of both men and women. The

Harris survey, conducted August, 1978 for Parents magazine, polled 1501

representatively selected American women. Both polls revealed that

majority opinion favors IVF. However, most women in the Harris survey

wanted IVF prohibited until further testing had established its safety,

and they opposed federal funding of research on IVF.

Gallup reported that 60% of both men and women "favored" the opera-

tion. Of persons who could fully explain the procedure, lb% approved,

indicating that more knowledge of IVF led to greater acceptance. Approval

was even higher among the women in the Harris poll. Eighty-five percent

said that the procedure should be an option for couples otherwise unable

to have children.

As to whether Americans would be willing to avail themselves of the

operation, the two polls reported that a majority would do so. Gallup

found 53% of Americans generally would undergo the procedure. Harris

reported that 58% of women of childbearing age would consider using IVF.
 89

More specifically defined groups among childbearing women produced even

more favorable attitudes: 61% of younger women, age 18-39, approved of

IVF, as did 66% of the women actually planning to have children.

While most women in the Harris survey approved of IVF as a legitimate

option, when they were asked if they couldn't have children would they

prefer adoption or IVF, more than twice as many chose adoption (57%) as

IVF (21%). Furthermore, a healthy majority (63%) wanted IVF to be banned

as standard medical practice until further research had determined

whether the operation increased the likelihood of birth defects. (Only

24% wanted IVF available immediately.) Interestingly, although most

women wanted further testing of IVF, half (50%) opposed federal funding

of such research.
 90

PUBLIC WITNESSES

ATLANTA, GEORGIA Martha Robb

Science for the People
Cambridge, Massachusetts
Catherine S. Amos, O.D.
Private Citizen Joseph Stanton, M.D.
Birmingham, Alabama Associate Clinical Professor
of Medicine
Mrs. Barbara Holmes Tufts University School
Adoption Consultant of Medicine
Department of Human Resources Boston, Massachusetts
State of Georgia
College Park, Georgia Joyce T. Tuomy
Member, Town Meeting
Joseph P. Williams, M.D. Framingham, Massachusetts
Private Citizen
Athens, Georgia Rabbi Dr. Samuel J. Fox
President,
Massachusetts Council of Rabbis
BETHESDA, MARYLAND Lynn, Massachusetts

Barbara Manning
Mr. and Mrs. Dennis R. Grills Private Citizen
Private Citizens Belmont, Massachusetts
Hendersonville, Tennessee
Charles Leavitt Sullivan, M.D.
William F. Colliton, Jr., M.D. Private Citizen
National Right to Life West Newton, Massachusetts
Washington, D.C.
Reverend Paul J. Murphy, S.J.
Ted Howard Professor of Theology (retired)
Co-Director, People's Boston College
Business Commission Newton, Massachusetts
Washington, D.C.
Honorable William X. Wall
John Gorby Senator
Right to Life and Right to Die 2nd Essex and Middlesex District
Committee of the American Boston, Massachusetts
Bar Association
A. Bruce MacDonald, Ph.D.
Professor and Head,
BOSTON, MASSACHUSETTS Department of Microbiology
University of Massachusetts
Amherst, Massachusetts
Tabitha Powledge, M.S.
Hastings Institute of Society,
Ethics, and the Life Sciences
Hastings-on-Hudson, New York
 91

BOSTON (CONT.) DALLAS, TEXAS

Joan Ghio Frank E. Ladwig

Private Citizen Associate Professor & Director,
Burlington, Massachusetts Social Work Program
College of Santa Fe
Tina and Peter Golden Dallas, Texas
Private Citizens
Roslindale, Massachusetts John McDonald
Private Citizen
Anthony Sbarra, Ph.D. Houston, Texas
Director of Clinical Laboratories
and Research Ms. Ann Ford
St. Margaret's Hospital for Women Private Citizen
Boston, Massachusetts Dallas, Texas

Debra and Kevin Canniff L.C. Powell, M.D.

Private Citizens Professor of Obstetrics &
Belmont, Massachusetts Gynecology
University of Texas
William A, Lynch, M.D. Medical Branch
Massachusetts Catholic Conference, Galveston, Texas
National Federation of Catholic
Physicians Guild Ms. Brenda Marshall
Milton, Massachusetts Private Citizen
Dallas, Texas
Jonathan King, Ph.D.
Coalition for Responsible Genetic Ms. Isabel Shavers
Research Private Citizen
Cambridge, Massachusetts Dallas, Texas

Joseph A. Zdonczyk Mrs. Jim Welsh, R.N.

Private Citizen Private' Citizen
Wolcott, Connecticut Dallas, Texas

Rosemary and Charles Hersey Mrs. Leon (Ann) Lesniak

Private Citizens Private Citizen
Belmont, Massachusetts Dallas, Texas

Ruth Hubbard, Ph.D. Desiree Inget

Professor of Biology Private Citizen
Harvard University Austin, Texas
Cambridge, Massachusetts
Reverend Joseph T. Leonard, S.J,
Randolph W. Seed, M.D. Catholic Diocese of Dallas
Richard G. Seed, Ph.D. Irving, Texas
Reproduction and Fertility
Clinic, Inc.
Elgin, Illinois
 92

DALLAS (CONT.) T.I. Ballinger, M.D.

Private Citizen
Fort Worth, Texas
Dr. Michael M. Donovan
Chief Surgeon, Shriners Hospital John Crosby
for Crippled Children and Philosophy Department
Clinical Professor at University University of Dallas
of Texas Medical School at Houston Irving, Texas
Houston, Texas
Josef Seifert, Ph.D.
Dr. Joseph Graham Associate Professor of Philosophy
Professor of Philosophy and Director of Graduate
University of St. Thomas Philosophy Program
Houston, Texas University of Dallas
Irving, Texas
John McDonald
Private Citizen J. Patrick McCarty, M.D.
Houston, Texas University of Texas
Southwestern Medical School
Reverend Steve Shiffman Dallas, Texas
Private Citizen
Atlanta, Georgia L. Russell Malinak, M.D.
Baylor College of Medicine
Mrs. Sharon Johns Houston, Texas
Private Citizen
Garland, Texas Mr. Louis A. Shone III
Private Citizen
La Neil Wright Dallas, Texas
Governor's Commission on the
Status of Women
Dallas, Texas DENVER, COLORADO

Roy J. Heyne, Jr. M.D.

,

Assistant Professor of Pediatrics Vicar James Cotter

University of Texas -- Health Science Bethlehem Lutheran Church
Center, Southwestern Medical School Lakewood, Colorado
Irving, Texas
Virgil Dechant
Lewis E. Berry, Jr. Supreme Knight, Knights of
Attorney Columbus
Houston, Texas Aurora, Colorado
(Testimony presented by William
Reverend Ed Robinson Small)
Biology Department
Bishop Lynch High School Caroline Reutter, M.D.
Dallas, Texas Women's Medical Association
 93

DENVER (CONT.) Richard P. Francis, Ph.D.

Professor of Ethics
University of Colorado
Frank Morriss Colorado Springs, Colorado
ContributitiQ Editor
The Wanderer A.D. Lodwick
St. Paul, Minnesota Private Citizen
Denver, Colorado
Angeline D. Heaton, M.D.
President, American Medical Father Nicholas Persech
Women's Association Dean of Theology School at
Colorado Commission on Women St. Thomas Seminary
Denver, Colorado Denver, Colorado

George Betz, M.D. Ruth Dolan

School of Medicine President, Denver Metro
Professor of Obstetrics & Chapter of Colorado
Gynecology Right to Life Committee
Denver, Colorado Denver, Colorado

Earl F. Dodge Barbara Zibbideo

President, Colorado Right to Private Citizen
Life Committee Greeley, Colorado
Denver, Colorado
Carol Lees
Father Gerald Sullivan Private Citizen
Catholic Social Services Denver, Colorado
Casper, Wyoming
Jerry Durnford
Dr. Thomas C. Washburn Private Citizen
University of Colorado Medical Denver, Colorado
Center
Denver, Colorado Mary Rita Urbish
Colorado Right to Life
Joseph D. Mclnerney Denver, Colorado
Center for Education in Human
and Medical Genetics Janet Foster
Boulder, Colorado Private Citizen
Denver, Colorado
Reverend Alex Lukens, Jr.
Episcopal Priest and Hospital
Chaplain DETROIT, MICHIGAN

Rand L. Kannenberg
Private Citizen Diane Fagelman
Colorado Springs, Colorado Private Citizen
Pontiac, Michigan
Andrew D. Keller
Private Citizen Father Walter A. Markowicz
Longmont, Colorado Archdiocese of Detroit
Detroit, Michigan
 94

David Favre Mr. Kevin Conley

Professor of Law Private Citizen
Detroit College of Law Kansas City, Kansas
Detroit, Michigan
Mrs. Ginger Drybread
Sister Betty Gaiss Private Citizen
Office of Health Affairs Olathe, Kansas
Diocese of Lansing
Lansing, Michigan Right Reverend Jerome Hanus
Abbot, Order of St. Benedict
Dr. Hans A. Schieser Conception Abbey
Associate Professor of Education Conception, Missouri
DePaul University
Chicago, Illinois Carolyn Harris
Diocesan Council of Catholic
David Thompson Women
Private Citizen Kansas City, Missouri
Detroit, Michigan
Linda J. Borman
Judy Jones Private Citizen
Private Citizen Council Bluffs, Iowa
Farmington Hills, Michigan
Mr. Norman Bettis
Frank Teskey PRO-Family Forum
Regional Director Kansas City, Missouri
Catholics United for Faith
Royal Oak, Michigan Ann O'Donnel, R.N.
Missouri Citizen for Life
Patricia Nixon St. Louis, Missouri
President, Educational Center
for Life Values Reverend Alberts S. Morzczewski
Birmingham, Michigan O.P., Ph.D.
President, Pope John XXIII
Tom Evans, M.D. Medical -Moral Research and
Chairman, Department of Education Center
Obstetrics and Gynecology St. Louis, Missouri
Wayne State University
Detroit, Michigan Fred Bolton
Pro-Life and Life Advocates
of Wyandotte County
KANSAS CITY, Missouri Kansas City, Kansas

Shirley Woods
Helen Froesman Saint Peters Pro-Life Group
Archdiocese of Kansas City Kansas City, Kansas
Kansas City, Kansas
Sister Aerab Pottinger
Mrs. Jane Clark Embryologist
Private Citizen St. Mary's Hospital
Overland Park, Kansas Kansas City, Missouri
 95

Mary Miller Mrs. Adelaide Bracalenti

Chairperson, Eastern Kansas Private Citizen
Right to Life Woodlyn, Pennsylvania

Mr. Terry Richards Ms. Donna Draus

Private Citizen Private Citizen
Kansas City, Kansas Philadelphia, Pennsylvania

Emanuel Heigelman, D.O.

PHILADELPHIA, PENNSYLVANIA Private Citizen
Philadelphia, Pennsylvania

Councilman James J. Tayoun Mr. Ronald Zukin

Philadelphia, Pennsylvania Private Citizen
Westchester, Pennsylvania
Dr. Will iam Mellman
Professor and Chairman, Department Mrs. Ann Schecter
of Human Genetics Private Citizen
University of Pennsylvania Bala Cynwyd, Pennsylvania
Philadelphia, Pennsylvania
Joseph Gambescia, M.D.
Edward Wortham, Ph.D. St. Agnes Hospital
Assistant Professor of Philadelphia, Pennsylvania
Biological Sciences
Old Dominion University Carl Stark, M.D.
Norfolk, Virginia Mayor
Wytheville, Virginia
Brother Patrick Ell is
President Mrs. Eileen Meyers
LaSalle College Co-Chairman, Stop ERA in
Philadelphia, Pennsylvania Pennsylvania
Cornwells Heights, Pennsylvania
Edward Stemmler, M.D.
Dean, School of Medicine Ms. Malana Petite
University of Pennsylvania Women Ad Hoc Health Commission
Philadelphia, Pennsylvania Philadelphia, Pennsylvania

Mrs. Peter Hoffman David E. Price, M.D.

Private Citizen Special Assistant to Provost
Wallingford, Pennsylvania and Director of Research
Programs
Mr. Sam A. Banks Johns Hopkins School of Medicine
President, Dickinson College Baltimore, Maryland
Carlisle, Pennsylvania
Reverend James J. McCartney
Mrs. Patricia Provost (on behalf of)
Private Citizen Warren T. Reich, Ph.D.
Bryn Mawr, Pennsylvania Georgetown University School of
Medicine
Washington, D.C.
 96

Deborah DeBardeleben Gino Pappola, M.D.

President, L.I.F.E. America President, International
Quanyville, Pennsylvania Federation of Catholic
Medical Associations
Mr. J. P.Stanton Philadelphia, Pennsylvania
Director, Pennsylvania Right to Life
Jenkintown, Pennsylvania Ms. Katherine Gil let
Private Citizen
Mr. Harold W. Luebs Philadelphia, Pennsylvania
Administrator, Children's Hospital
of Pittsburgh Reverend Francis Meehan
Pittsburgh, Pennsylvania Archdiocese of Philadelphia
Philadelphia, Pennsylvania
George Isajiw, M.D.
Private Citizen Allen Enders, Ph.D.
Upper Darby, Pennsylvania Researcher
University of California
Mr. Robert Korsan Davis, California
Private Citizen
Philadelphia, Pennsylvania Raymond Dennehy, Ph.D.
Department of Philosophy
Jay W. MacMoran, M.D. University of San Francisco
Chairman, Commission of Medicine, San Francisco, California
Religion and Bioethics
Pennsylvania Medical Society Donna Daentl, M.D.
Lemoyne, Pennsylvania University of California
San Francisco, California
Dr. Donald Self
Bioethicist & Director Ann K. Brothers, Ph.D.
of Human Values in Medicine Assistant Professor
Eastern Virginia Medical School Department of Zoology
Norfolk, Virginia University of California
Berkeley, California
P. Apostolidis, M.D.
Clinical Associate Professor of Mary Anne Schwab
Gynecology at Jefferson Medical Legislative Information
College Chairman
Philadelphia, Pennsylvania National Council of Catholic
Women
John M. Levinson, M.D. San Francisco, California
President-Elect of the Delaware
Obstetrical Society Diane Coleman
Wilmington, Delaware Private Citizen
San Francisco, California
Mr. Gizzi
Private Citizen David Schaeffer
Mawhaw, New Jersey Private Citizen
San Francisco, California
 97

Edward E. Wallach, M.D. Mrs. Norge Humeniuk

Director, Obstetrics and Gynecology Private Citizen
Pennsylvania Hospital & Professor Mills Valley, Cal ifornia
Obstetrics and Gynecology,
University of Pennsylvania School Evelyn Eaton, Ph.D.
of Medicine Sociology (Free-lance)
Philadelphia, Pennsylvania
Mrs. Arlene Kessler
Francis Felice Private Citizen
Professor of Biology Oakland, California
University of San Francisco
Deacon, Archdiocese of San Francisco David Galvin
San Francisco, California Private Citizen
Oakland, California
Phil ip Martin
Private Citizen Mr. Robert Kessler
San Francisco, California Private Citizen
Oakland, California
Deborah Streeter
Private Citizen Ms. Lois Bogarot
Berkeley, California Private Citizen
Redwood City, California
Mr. Paul Herbert
Private Citizen Bruce Hilton, Ph.D.
San Francisco, California National Center for Bioethics
Berkeley, California
Judy Johnson
Private Citizen Lynn Szwabinsky
San Francisco, California Private Citizen
Concord, California
Leonie Watson, M.D.
National Doctors for Life George Maloff, M.D.
San Francisco, California Pro-Life Medical Association
of California
Mitchell S. Golbus, M.D. San Francisco, California
University of California
San Francisco, California
SEATTLE. WASHINGTON
Roger A. Pedersen, Ph.D.
Professor of Radiobiology
University of California Dr. Lawrence Karp
Medical Center Associate Professor of Obstetrics
San Francisco, California and Gynecology
University of Washington
Robert Glass, Ph.D. Seattle, Washington
University of California
Berkeley, California Lois Lundquist
Private Citizen
Ms. Nancy Fund Issaquah, Washington
Research Associate, Health Services
Research, Stanford University
 98

Joan Ramos
Private Citizen
Seattle, Washington

Reverend Stanley Stefancic

East Shore Unitarian Church
Bellevue, Washington

Janice Rowe
Private Citizen
Seattle, Washington

Robert E. Mcintosh, M.D.

Private Citizen
Seattle, Washington

Margaret K. Ose
Private Citizen
Mercer, Island, Washington

Dale Beasley
Department of Science
St. Philomena School
Des Moines, Washington

Mrs. Cynthia Bortz

Program Assistant
Department of Obstetrics &
Gynecology
University Hospital
Seattle, Washington

Connie Miller
Private Citizen
Seattle, Washington

Lex Mottl, M.D.

Virginia Mason Hospital
Seattle, Washington

Donald E. Moore, M.D.

Assistant Professor and Director
Division of Reproductive Endocrinology
and Infertility
University Hospital
Seattle, Washington

Dr. Richard M. Soderstrom

Past President of the American
Association of Laparoscopy
Seattle, Washington
 Individuals Who Submitted Written Testimony
99
in lieu of Oral Presentation

Rev. Joseph C. Frisch, Ph.D., S.T.D. John Hoaglund

Philosophy Department Private Citizen
College of Saint Teresa Newport News, Virginia
Winona, Minnesota

Maureen E. Webb
Nancy J. Schmitt Assistant Professor in Biological
Adoption Research Council Science
Potomac, Maryland Holy Name College
Oakland, California

Michael A. Goheen
Private Citizen Walter Funk
Kalamazoo, Michigan Chairman, Department of Health
West Chester State College
West Chester, Pennsylvania
Perry Stearns, M.D.
Wayne County Department of Health
Eloise, Michigan Laurence B. McCullough, Ph.D.
Assistant Professor
College of Medicine
Susan L. Heine & John D. Heine Texas A & M University
Private Citizens College Station, Texas
Annandale, Virginia

Dr. William R. Cunnick

Dona B. Morris President, American Social Health
Private Citizen Association
Arlington, Virginia Palo Alto, California

Rev. Charles McConnell Mary Stirl ing

Salem Bible Fellowship Church Private Citizen
Allentown, Pennsylvania Mountaintop, Pennsylvania

Connie Brewer Paul Ramsey

Private Citizen Professor of Religion
La Mirada, California Princeton University
Princeton, New Jersey

Amitai Etzioni
Director, Center for Policy Research Dolores R. Lear
Professor of Sociology Private Citizen
Columbia University Kansas City, Missouri
New York, New York

James H. Sammons, M.D.

Executive Vice-President
American Medical Association
Chicago, Illinois
 100

CHAPTER VI: SUMMARY AND CONCLUSIONS

It is now technically possible to fertilize a human egg outside the

body of a woman and then transfer the fertilized egg (sometimes called a

blastocyst or preimplantation embryo) back into the woman to establish a

pregnancy. For some women, in vitro fertilization may be the only way

to bear children of their own. It does not appear, however, that the

procedure for achieving pregnancy by this means is yet very effective;

the best available data indicate that a number of attempts have been

necessary before a pregnancy in a particular woman can be established,

if at all. In addition, many questions remain as to the safety of the

procedure for the offspring. Nevertheless, there is reason to believe

that clinics may soon be established, both in this country and abroad,

where in vitro fertilization and embryo transfer will be offered as

"therapy" for infertile couples.

The Board is required by HEW regulations to review research pro-

posals involving human in vitro fertilization and advise the Secretary

as to their "acceptability from an ethical standpoint."* This phrase is

broad enough to include at least two interpretations: (1) "clearly

ethically right" or (2) "ethically defensible but still legitimately

controverted." In finding that research involving human in vitro

fertilization is "acceptable from an ethical standpoint" the Board is

using the phrase in the second sense; the Board wishes to emphasize that

it is not finding that the ethical considerations against such research

are insubstantial. Indeed, concerns regarding the moral status of the

embryo and the potential long-range consequences of this research were

among the most difficult that confronted the Board.

^45 CFR 46.204(d;

 101

In its deliberations on human in vitro fertilization, the Board

confronted many ethical, scientific and legal issues. Among the more

difficult were the following: (A) the moral status of the embryo; (B)

the safety and efficacy* of the procedure; (C) the potential long-range

adverse effects of such research; and (D) the appropriateness of Depart-

mental support.

A. After much analysis and discussion regarding both scientific

data and the moral status of the embryo, the Board is in agreement that

the human embryo is entitled to profound respect; but this respect does

not necessarily encompass the full legal and moral rights attributed to

persons. In addition, the Board noted the high rate of embryo loss that

occurs in the natural process of reproduction. It concluded that some

embryo loss associated with attempts to assist otherwise infertile

couples to bear children of their own through in vitro fertilization may

be regarded as acceptable from an ethical standpoint, under certain

conditions, as more fully described below.

B. The Board is concerned about still unanswered questions of

safety for both mother and offspring of in vitro fertilization and

embryo transfer; it is concerned, as well, about the physical and mental

health of the children born following such a procedure and about their

legal status. Many women have told the Board that in order to bear a

child of their own they will submit to whatever risks are involved. The

Board believes that while the Department should not interfere with such

*By "efficacy" the Board means not only whether the procedure can be
done but also how efficient it is, e.g. the number of procedures
,

required to achieve the desire result.

 102

reproductive decisions, it has a legitimate interest in developing and

disseminating information regarding safety and health so that fully

informed choices about reproduction can be made.

C. A number of fears have been expressed with regard to adverse

effects of technological intervention in the reproductive process: fears

that such intervention might lead to genetic manipulation or encourage

casual experimentation with human embryos, or bring with it the use of

surrogate mothers, cloning, or the creation of genetic hybrids. Some

•have suggested that such research might also have a dehumanizing effect

on investigators, the families involved, and society generally. (See

Chapter III of this report.)

Although the Board recognizes that there is an opportunity for

abuse in the application of this technology as other technologies, it

concluded that a broad prohibition of research involving human in vitro

fertilization is neither justified nor wise. Among the developments

warned against by some who testified before the Board, a few ( e.g. , the

cloning of human beings and the creation of animal/human hybrids) are of

uncertain or remote risk. Other possible developments, such as the use

of surrogate mothers, may be contained by regulation or legislation.

Other abuses may be avoided by the use of good judgment based upon

accurate information of the type collected by the Board and now being

disseminated in this report. Finally, where reproductive decisions are

concerned, it is important to guard against unwarranted governmental

intrusion into personal and marital privacy.

D. The question of Federal support of research involving human in

vitro fertilization and embryo transfer was troublesome for the Board in
 103

view of the uncertain risks, the dangers of abuse and because funding

the procedure is morally objectionable to many. In weighing these

considerations, the Board noted that the procedures may soon be in use

in the private sector and that Departmental involvement might help to

resolve questions of risk and avoid abuse by encouraging wel -designed

1

research by qualified scientists. Such involvement might also help to

shape the use of the procedures through regulation and by example. The

Board concluded that it should not advise the Department on the level of

Federal support, if any, of such research; but it concluded that Federal

support, if decided upon after due consideration of all that is at

issue, would be acceptable from an ethical standpoint.

Evidence presented to the Board indicates that human in vitro

fertilization and embryo transfer techniques may, in the near future, be

employed throughout the world in both research and clinical practice

settings. The Board believes that data from these activities as well as

related types of animal research should be collected, analyzed and, when

appropriate, given wide public dissemination. Accordingly, the Board

recommends in conclusion #4 below, that the Department take the primary

initiative in carrying out these functions.

Having carefully weighed diverse ethical points of view and a broad

base of scientific considerations regarding human in vitro fertilization

and embryo transfer, the Board has concluded that: (1) the Department

should consider support of more animal research in order to assess the

risks to both mother and offspring associated with the procedures; (2)

the conduct of research involving human in vitro fertilization designed

to establish the safety and effectiveness of the procedures is ethically

acceptable under certain conditions; (3) Departmental support of such

 104

research would be acceptable from an ethical standpoint, although the

Board did not address the question of the level of funding, if any,

which such research might be given; (4) the Department should take the

initiative in collecting, analyzing and disseminating data from both

research and clinical practice involving in vitro fertilization throughout

the world; and (5) model or uniform laws should be developed to define

the rights and responsibilities of all parties involved in such activities.

Finally, the Board is aware of the possibility of research that

involves the collection and culture of early human embryos in the

laboratory which have been fertilized naturally rather than in vitro .

The ethical aspects of such research, which appears to bear a close

resemblance to research involving in vitro fertilization, have not been

examined by the Board. Therefore it has not reached a conclusion con-

cerning the ethical acceptability of these procedures. However, the

Board intends to consider in the near future the need for setting

standards for such research.

CONCLUSION (1) THE DEPARTMENT SHOULD CONSIDER SUPPORT OF CAREFULLY

DESIGNED RESEARCH INVOLVING IN VITRO FERTILIZATION AND EMBRYO TRANSFER

IN ANIMALS, INCLUDING NONHUMAN PRIMATES, IN ORDER TO OBTAIN A BETTER

UNDERSTANDING OF THE PROCESS OF FERTILIZATION, IMPLANTATION AND EMBRYO

DEVELOPMENT, TO ASSESS THE RISKS TO BOTH MOTHER AND OFFSPRING ASSOCIATED

WITH SUCH PROCEDURES, AND TO IMPROVE THE EFFICACY OF THE PROCEDURE.

Discussion : As indicated in Chapter III of the Board's report,

available scientific data do not indicate clearly either the relative

safety or the efficacy of procedures of in vitro fertilization and

 105

embryo transfer. Some scientists have suggested that in vitro fertilization

may result in a higher incidence of abnormal embryos than is associated

with the normal reproductive process, although there are no animal data

that clearly demonstrate such an effect. Neither are there data that

demonstrate an absence of increased abnormality in embryos following in

vitro fertil ization. The Board feels that additional data should be

gathered that might indicate whether abnormal embryos are more likely to

result and, if so, whether there is a significant increase in the risk

of abnormal offspring actually being born following such procedures.

Experts appearing before the Board agreed that there has been

insufficient controlled animal research designed to determine the long-

range effects of in vitro fertilization and embryo transfer. The lack

of primate work is particularly noteworthy in view of the opportunity

provided by primate models for assessing subtle neurological, cognitive

and developmental effects of such procedures. The Board has been advised

that controlled studies of embryo transfer following in vitro fertiliza-

tion in animals, designed to include developmental assessments, may be

feasible and may permit more confident estimates of the risk to human

offspring associated with such procedures.

Information regarding the effectiveness of the procedures for in

vitro fertilization and embryo transfer is also lacking. It does not

appear possible to predict with reliability the number of laparoscopies

and embryo transfers that might be required, or the likelihood of success

of the procedure for any couple, given the fact that, to date, only

three successes have been reported in humans, and that very limited

information is available concerning this work. Such data as are available

 106

suggest that any woman hoping to bear a child through in vitro fertilization

is likely to face numerous unsuccessful procedures and delays with no

assurance of achieving her goal.

Careful research with animal models might provide a more accurate

estimate of the chances of achieving a successful pregnancy. It might

also reduce the inconvenience and risk to women of undergoing multiple

procedures to establish a pregnancy by improving techniques for recovering

ova, identifying embryonic abnormalities and achieving implantation. It

is often the case in medicine that, even after therapies are already

being applied to humans, investigations continue in animals in order to

test further or to improve their safety and effectiveness. The Board

believes that the Department should consider support of well-designed

animal studies whether or not human research or clinical trials are also

in progress.

CONCLUSION (2) THE ETHICS ADVISORY BOARD FINDS THAT IT IS ACCEPTABLE

FROM AN ETHICAL STANDPOINT TO UNDERTAKE RESEARCH INVOLVING HUMAN IH

VITRO FERTILIZATION AND EMBRYO TRANSFER PROVIDED THAT:

A. IF THE RESEARCH INVOLVES HUMAN IN VITRO FERTILIZATION WITHOUT

EMBRYO TRANSFER, THE FOLLOWING CONDITIONS ARE SATISFIED:

1. THE RESEARCH COMPLIES WITH ALL APPROPRIATE PROVISIONS

OF THE REGULATIONS GOVERNING RESEARCH WITH HUMAN

SUBJECTS (45 CFR 46);

2. THE RESEARCH IS DESIGNED PRIMARILY: (A) TO ESTABLISH

THE SAFETY AND EFFICACY OF EMBRYO TRANSFER AND (B) TO

OBTAIN IMPORTANT SCIENTIFIC INFORMATION TOWARD THAT END

NOT REASONABLY ATTAINABLE BY OTHER MEANS;

 107

3. HUMAN GAMETES USED IN SUCH RESEARCH WILL BE OBTAINED

EXCLUSIVELY FROM PERSONS WHO HAVE BEEN INFORMED OF

THE NATURE AND PURPOSE OF THE RESEARCH IN WHICH

SUCH MATERIALS WILL BE USED AND HAVE SPECIFICALLY

CONSENTED TO SUCH USE;

4. NO EMBRYOS WILL BE SUSTAINED IN VITRO BEYOND THE

STAGE NORMALLY ASSOCIATED WITH THE COMPLETION OF

IMPLANTATION (14 DAYS AFTER FERTILIZATION); AND

5. ALL INTERESTED PARTIES AND THE GENERAL PUBLIC WILL

BE ADVISED IF EVIDENCE BEGINS TO SHOW THAT THE PRO-

CEDURE ENTAILS RISKS OF ABNORMAL OFFSPRING HIGHER

THAN THOSE ASSOCIATED WITH NATURAL HUMAN REPRODUC-

TION.

B. IN ADDITION, IF THE RESEARCH INVOLVES EMBRYO TRANSFER

FOLLOWING HUMAN IN VITRO FERTILIZATION, EMBRYO TRANSFER WILL

BE ATTEMPTED ONLY WITH GAMETES OBTAINED FROM LAWFULLY MARRIED

COUPLES.

Discussion : This conclusion relates to the ethics of conducting

research involving in vitro fertilization in general; it does not address

the question of Departmental support of such research. The purpose of

this more general conclusion is to provide guidance to Institutional

Review Boards and other groups who are asked to review research that

will not be supported by HEW.* Whether or not the Department decides

* Federal law requires all institutions receiving research funds from

HEW to establish an Institutional Review Board (IRB) to review biomedical
and behavioral research involving human subjects. (Public Law 93-348).
The Department, in implementing that law, requires all such research
conducted at an institution to be reviewed by the IRB, whether or not
the research is supported by HEW.
 108

to provide funds for such research, the Board wishes to express its

views regarding the conduct of human in vitro fertilization and embryo

transfer, so that review groups may benefit from the deliberations of

the Board as they conduct their own review of specific research proposals.

As emphasized above, the Board believes that much remains to be

learned about the safety and effectiveness of these procedures before

they can be considered standard, accepted medical practice. Research

designed to provide reliable data regarding safety and efficacy is

acceptable from an ethical standpoint if conducted within the constraints

indicated above. In the case of research involving embryo transfer, the

Board intends not only that the gametes be obtained from lawfully married

couples but also that the embryo be transferred back to the wife whose

ova were used for fertilization.

The Board also discussed research designed primarily to establish

safety and efficacy but which may, in addition, obtain information of

scientific importance unrelated to in vitro fertilization and embryo

transfer. The Board believes that such research, if performed as a

corollary to research designed primarily to establish safety and efficacy

of in vitro fertilization and embryo transfer, would also be acceptable

from an ethical standpoint.

CONCLUSION (3) THE BOARD FINDS IT ACCEPTABLE FROM AN ETHICAL

STANDPOINT FOR THE DEPARTMENT TO SUPPORT OR CONDUCT RESEARCH INVOLVING

HUMAN IN VITRO FERTILIZATION AND EMBRYO TRANSFER, PROVIDED THAT THE

APPLICABLE CONDITIONS SET FORTH IN CONCLUSION (2) ARE MET. HOWEVER, THE

BOARD HAS DECIDED NOT TO ADDRESS THE QUESTION OF THE LEVEL OF FUNDING,

IF ANY, WHICH SUCH RESEARCH MIGHT BE GIVEN.

 109

Discussion :

1 . Departmental support . The Board consciously adopted the

language "acceptable from an ethical standpoint" to

indicate the limits of its inquiry. Even though the

members are aware that ethical considerations pervade

decisions regarding the level, if any, of Departmental

support of human in vitro fertilization, the Board has

concluded that it lacks the resources needed to render

meaningful advice with respect to such decisions. The

Board, therefore, defers to established political, scien-

tific and administrative procedures for allocating public

research funds.

The Board wishes to note that such decisions have

significant ethical dimensions. For example, some believe

that research involving human in vitro fertilization

should have a relatively low priority at a time when

other health needs, arguably more basic in character and

long-term in nature, are unmet. Others find such research

objectionable either on grounds related to the moral

status of the embryo or because it may lead to undesirable

genetic interventions or have a long-range adverse effect.

(See Chapter III of this report.) Still others believe

that research on human in vitro fertilization and embryo

transfer should have a high priority because it might

help parents overcome physical obstacles to having their

own children and ensure the mothers' safety and the

normality of offspring.
 110

The Board has found that these and other ethical

arguments for and against public funding of research

involving human in vitro fertilization, by themselves,

are not conclusive. Instead, the Board believes that the

questions of whether to fund and at what level should be

made in the larger context where all relevant data and

arguments -- scientific, political, economic, legal and

ethical -- can be considered. In that context questions

such as health and safety, availability of funds, and

alternative research proposals, must be considered along

with the very difficult type of ethical isssues described

above which arise in allocation of resources.

Research without embryo transfer . As previously noted

the risks of producing abnormal offspring are still

undetermined; therefore, an important goal would be to

gain as much information as possible from well -designed

research on in vitro fertilization not involving embryo

transfer in humans. The Department should conduct a

careful scientific evaluation of the possibility, sup-

ported by some expert testimony before the Board, that

animal research and studies involving human in vitro

fertilization without embryo transfer, over a relatively

short period, might substantially increase our knowledge

concerning the possible risk of abnormal offspring as

well as lead to the development of safe and more effective

techniques.
 m
3. Research involving embryo transfer . While initial research

efforts designed to gain as much information as possible

from animal studies and human research not involving

embryo transfer may be desirable, the Board does not wish

to discourage planning and preparation that may lead to

clinical trials or other forms of research involving

embryo transfer. The Department's participation in, or

support of, clinical trials is often an effective method

to evaluate the safety and efficacy of innovative medical

procedures, particularly as the use of the procedures

increases.

4. Research for other purposes . Potentially valuable infor-

mation about reproductive biology, the etiology of birth

defects, and other subjects may be revealed through re-

search involving human in vitro fertilization, without

embryo transfer, and unrelated to the safety and efficacy

of procedures for overcoming infertility. The Board

makes no judgment at this time regarding the ethical

acceptability of such research nor does it speculate

about what research might be sufficiently compelling to

justify the use of human embryos. Instead, it notes that

applications for support of such research should be

submitted to the Board for ethical review in accordance

with 45 CFR 46.204(d).

 112

5. Pending Research Application . Given the criteria specified

in Conclusion (2) and incorporated in Conclusion (3) for

evaluatiiig research involving human in vitro fertilization,

and the Board's views about Departmental support of such

research, the Board recommends that the Secretary refer

the pending application of Vanderbilt University back to

the National Institutes of Health for a determination as

to whether the proposal meets those criteria and for

further review in light of the considerations set forth

in this report.

CONCLUSION (4) THE NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN

DEVELOPMENT (NICHD) AND OTHER APPROPRIATE AGENCIES SHOULD WORK WITH

PROFESSIONAL SOCIETIES, FOREIGN GOVERNMENTS AND INTERNATIONAL ORGAN-

IZATIONS TO COLLECT, ANALYZE AND DISSEMINATE INFORMATION DERIVED FROM

RESEARCH (IN BOTH ANIMALS AND HUMANS) AND CLINICAL EXPERIENCE THROUGHOUT

THE WORLD INVOLVING IN VITRO FERTILIZATION AND EMBRYO TRANSFER.

Discussion : The Board is aware that the most valuable information

regarding in vitro fertilization and embryo transfer is likely to come

from well -control led clinical trials. But it is expected that in vitro

fertilization and embryo transfer will soon be performed in clinics

throughout the world, sometimes without benefit of research design or

experimental controls. It would be unfortunate not to have access to

the information that might be gained from such clinical experience,

notwithstanding the fact that well-designed investigations would be

preferable. With that in mind, the Board recommends that every effort
 113

be made to collect whatever information may be elicited from practi-

tioners in this country and abroad. NICHD should also consider sug-

gesting to practitioners a basic protocol for collecting vital infor-

mation, to which each would be encouraged to add their own observations.

The data from such clinical experience and from research conducted

throughout the world should be analyzed along with that derived from

animal studies so that individuals contemplating in vitro fertilization

and embryo transfer will have access to the best information available

regarding risks to both mother and offspring. Timely dissemination of

the information would increase the opportunity for investigators,

clinicians and propsective patients to be fully informed.

CONCLUSION (5) THE SECRETARY SHOULD ENCOURAGE THE DEVELOPMENT OF A

UNIFORM OR MODEL LAW TO CLARIFY THE LEGAL STATUS OF CHILDREN BORN AS A

RESULT OF IN VITRO FERTILIZATION AND EMBRYO TRANSFER. TO THE EXTENT

THAT FUNDS MAY BE NECESSARY TO DEVELOP SUCH LEGISLATION, THE DEPARTMENT

SHOULD CONSIDER PROVIDING APPROPRIATE SUPPORT.

Discussion : The Board is concerned about the ambiguity regarding

the legal status of children born following artificial insemination and

a similar ambiguity that may surround the legal status of children born

following in vitro fertilization and embryo transfer. The Board is also

concerned about lack of clarity regarding the legal responsibilities of

those who utilize, support, or permit use of such procedures. Because

of the complexity of the legal problems involved in new techniques for

human reproduction, the Board recommends that a model or uniform law be

 114

drafted that would establish with clarity the rights and responsibilities

of donor and recipient "parents", of offspring, and of those who participate

in the process of reproduction through new technologies.

The Board urges that such a uniform or model law be drafted by the

National Conference of Commissioners on Uniform State Laws, the American

Law Institute, or some other qualified body. Because of the complex

nature of the subject matter, however, the Board is aware that the task

may be a major undertaking and suggests that the Department consider pro-

viding funds for drafting the legislation. Since the purpose is to safe-

guard the health and welfare of children and their families, it appears

to be an appropriate project for Departmental support.

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