Reproduction and Responsibility:
The Regulation of New Biotechnologies
The President's Council on Bioethics
In each of the next five chapters—beginning
with this one—we will discuss in detail a separate, discrete
area of our larger domain of inquiry. Each of these chapters
will be structured as follows. First, the chapter will review
the relevant techniques and practices; next, it will address
the ethical considerations; and finally, it will consider
the existing regulatory activities.
For reasons discussed above, we will take the practice
of assisted reproduction as our fundamental point of departure.
Although readers are no doubt familiar with the main features
of assisted reproduction techniques and practices, we will
give a detailed account of them in order to clarify which
aspects might give rise to a need for monitoring, oversight,
I. Techniques and Practices
Most methods of assisted reproduction involve five discrete
phases: (1) collection and preparation of gametes; (2) fertilization;
(3) transfer of an embryo or multiple embryos to a woman’s
uterus; (4) pregnancy; and (5) delivery and birth. We will
discuss each phase separately. Additional issues connected
with recruitment, intake, and possible payment of gamete
donors will be discussed extensively in Chapter 6 (on commerce).
A. Collection and Preparation of Gametes
The precursors of human life are the gametes: sperm and
ova. Parents seeking to conceive through assisted reproduction
usually provide their own gametes. In the United States
in the year 2001, 75.2 percent of the ART cycles undertaken
used never-frozen, nondonor ova or embryos and another 13.7
percent used frozen nondonor ova or embryos. Of the remaining
11.1 percent of cycles using donor embryos, the breakdown
is as follows: 3.2 percent of the embryos were previously
cryopreserved, and 8 percent were not.i
Sperm are typically acquired directly from the male prospective
parent. The minority of men who cannot ejaculate, or who
have a blocked reproductive tube, may undergo assisted sperm
retrieval (ASR). Alternatively, sperm precursor cells obtained
by testicular biopsy may be used for purposes of insemination
(though this yields a lower pregnancy rate).
Acquiring ova for use in artificial reproduction is significantly
more onerous, painful, and risky than acquiring sperm (though
its risks are still low in absolute terms). In the normal
course of ovulation, one mature oocyte is produced per menstrual
cycle. However in assisted reproduction—to increase the
probability of success—many more ova are typically retrieved
and fertilized. Thus, the ova source (who is usually also
the gestational mother) undergoes a drug-induced process
intended to stimulate her ovaries to produce many mature
oocytes in a single cycle. This procedure, commonly referred
to as “superovulation,” requires the daily injection of
a synthetic gonadatropin analog, accompanied by frequent
monitoring using blood tests and ultrasound examinations.
This treatment begins midway through the previous menstrual
cycle and continues until just before ova retrieval. The
synthetic gonadatropin analogs give the clinician greater
control over ovarian stimulation and prevent premature release
of the ova.
A very small percentage of women using assisted reproduction
(in 2001, fewer than 1 percent of assisted reproduction
patients) opted not to undergo ovarian stimulation prior
to ova retrieval.2
In such “unstimulated” procedures, the clinician monitors
the development of an ovarian follicle (via ultrasound)
and uses daily blood sampling to predict the moment of ovulation.
Only one follicle develops and the timing of maturation
and release is not controlled. Because there are fewer embryos
for transfer, this process yields a lower success rate than
does in vitro fertilization (IVF) following ovarian stimulation.
When blood testing and ultrasound monitoring suggest that
the ova are sufficiently mature, the clinician attempts
to harvest them. This is typically achieved by ultrasound-guided
transvaginal aspiration. In this procedure, a needle guided
by ultrasound is inserted through the vaginal wall and into
the mature ovarian follicles. An ovum is withdrawn (along
with some fluid) from each follicle. This is an outpatient
procedure. Risks and complications are low, but may include
accidental puncture of nearby organs such as the bowel,
ureter, bladder, or blood vessels, as well as the typical
risks accompanying outpatient surgery (for example, risks
related to administration of anesthesia, infection, etc.).
Once sperm and ova have been collected, they are cultured
and treated to maximize the probability of success. Ova
are transferred into a culture medium containing the intended
mother’s blood serum. The seminal fluid is removed from
sperm and replaced with an artificial medium. For infertile
men, the clinician removes excess material and concentrates
the motile sperm.ii
Once the ova and sperm have been properly prepared, the
clinician attempts to induce fertilization—the union of
sperm and ovum culminating in the fusion of their separate
pronuclei and the initiation of a new, integrated, self-directing
organism. It is common practice to attempt to fertilize
all available ova.iii
Fertilization can be achieved through a number of means
including (1) “classical” IVF, (2) gamete intrafallopian
(3) intracytoplasmic sperm injection (ICSI), and (4) various
other methods of zona pellucida manipulation.v
IVF is the most common method of artificial fertilization.
In 2001, it was used by 99 percent of ART patients.3
As noted previously, both sperm and ovum are cultured to
maximize the probability of fertilization. The ova are examined
and rated for maturity in an effort to calculate the optimal
time for fertilization. They are usually placed in a tissue
culture medium and left undisturbed for two to twenty-four
hours. The sperm are prepared as described above. Once the
gametes are adequately prepared, thousands of tiny droplets
of sperm are placed in the culture medium containing a single
ovum. After 24 hours, each of the oocytes is examined to
determine whether fertilization has occurred.
GIFT was introduced in 1984 as an alternative to standard
IVF. Today, attempts at fertilization via GIFT are rare.
In 2001, they accounted for less than 1 percent of all attempts
at fertilization used by ART patients.4
As the name suggests, fertilization using GIFT occurs within
the woman’s body. Ovarian stimulation and retrieval are
performed in the same manner as in IVF. In a single procedure,
ova are retrieved, combined with the sperm outside the body,
and then transferred back into the fallopian tube where
it is hoped that fertilization itself will occur. Typically,
two or more ova are retrieved and transferred. GIFT requires
only one functional fallopian tube to succeed. Because fertilization
takes place inside the woman’s body, substantially less
lab work is required and there is no need for embryo culturing.
For the same reason, however, if several ova are transferred,
GIFT exposes the patient to a higher-than-normal risk of
multiple gestations. Moreover, when GIFT does not succeed
practitioners frequently cannot determine why it failed,
for example, whether the ovum was not fertilized or the
embryo did not implant.
A new and increasingly popular technique for fertilization
is intracytoplasmic sperm injection. As the name implies,
with ICSI, ovum-sperm fusion is accomplished not by chance,
but by injecting a single sperm directly into an oocyte.
The oocyte is treated with an enzyme that removes certain
cells that surround it (“nurse cells”). The sperm are placed
in a viscous solution that greatly slows their motility.
A single sperm is selected and drawn into a thin pipette
from which it is injected into the cytoplasm of the ovum
ICSI is indicated in cases of severe male-factor infertility,
in which male patients have either malformed sperm or an
abnormally low sperm count. ICSI is also ideal for patients
whose sperm would not otherwise penetrate the exterior of
ICSI was used in 49.2 percent of all ART cycles in 2001.5
However, 42.2 percent of those ICSI cycles were undertaken
by couples without male-factor infertility.6
The growing popularity of this technique most likely has
to do with the wish to increase the control over, and success
rates for, fertilization: ICSI, unlike standard IVF, guarantees
the entrance of a single sperm directly into a single egg.vii
Clinicians can also attempt to induce fertilization artificially
through manipulation of the zona pellucida, the thick extra-cellular
covering that surrounds the ovum. To assist the sperm’s
penetration of the ovum, clinicians perforate the zona pellucida
using an acidic solution (“zona drilling”) or a needle or
pipette (“partial zona dissection”). Alternatively, clinicians
inject sperm underneath the zona pellucida, but not directly
into the ovum’s cytoplasm (“subzonal insemination”). Zona
drilling results in few pregnancies and has been linked
to inhibition of early embryo growth, perhaps due to the
acidic solution entering the ovum itself.7
Few embryos conceived through partial zona dissection have
a normal appearance, but it is not definitively known why
this is so or whether the difference is significant in any
way to the health of the developing child. Subzonal insemination
can be effective in the hands of a skilled practitioner,
but frequently results in unfertilized oocytes or fertilization
by multiple sperm, rendering the embryo unusable.8
The safety risks associated with these procedures are discussed
A recently developed adjunct to IVF is ooplasm transfer.
This procedure has been used for women whose fertilized
ova do not develop normally owing to a deficiency in their
mitochondria. To remedy this problem at the time of fertilization,
the oocyte is injected with donor cytoplasm that contains
healthy mitochondria. Because the new cytoplasm contains
the donor’s mitochondrial DNA, the resulting child will
have inherited DNA from three individuals: the father, the
mother, and mitochondrial DNA from the ooplasm donor. Moreover,
the donor mitochondria could be passed on to future generations
through the resulting child. To date, there have been thirty
children born worldwide as a result of this procedure.9
However, for reasons discussed elsewhere in this document,
this technique is not currently approved for use in clinical
practice in the United States.viii
Once fertilization has occurred, the new embryos remain
in the culture medium. Nutrients are added to the medium.
Some commercially produced preparations exist but, typically,
ART clinics make their own on-site. Some clinics co-culture
developing embryos: that is, they culture the embryos in
a medium containing other cells that enhance the growth
of the embryos and remove toxins. Various types of cells
have been used for such co-culture, including cells extracted
from the uterus or fallopian tubes of patients or donors,
rat liver cells, monkey kidney cells, cow uterine cells,
and human ovarian cancer cells. The embryos remain in culture
and are warmed in an incubator until they are either transferred
into the recipient’s uterus or cryopreserved.
Because in many cases not all embryos are transferred
in each cycle, cryopreservation of embryos has become an
integral part of ART.ix
The American Society for Reproductive Medicine (ASRM) has
deemed cryopreservation “essential” to the practice of assisted
reproduction and provides extensive guidance to technicians
as to the maintenance of cryopreservation facilities. Cryopreservation
is a complicated process that requires embryo preparation,
sophisticated freezing technology, reliable storage, and
meticulous record keeping. To guard against the formation
of ice crystals that could destroy the embryo, the clinician
introduces a cryoprotectant solution into the early-stage
embryo’s interior. The prepared embryos are then placed
in a straw-like structure that is gradually frozen. Once
frozen, these structures are stored in canisters at very
low temperature (typically around minus 196 degrees centigrade).
Some researchers suggest that it may be possible to cryopreserve
embryos safely for fifty years or longer.10
A recently reported study by the Society for Assisted Reproductive
Technology and RAND estimates that 400,000 embryos are in
cryostorage in the United States.11
Most ART patients do not receive cryopreserved embryos.
In 2001, only 14 percent of all ART cycles involved transfer
of frozen embryos.12
The rate of live births for cycles using cryopreserved embryos
is significantly lower than it is for never-frozen embryos
(23.4 percent versus 33.4 percent).13Experts
estimate that only 65 percent of frozen embryos survive
the thawing process.14
There are, however, incentives for couples to use cryopreserved
embryos; doing so eliminates the cost and effort of further
oocyte retrieval. This can decrease the cost of a future
cycle by roughly $6,000.15
Transfer of cryopreserved embryos might be preferable also
for recipients who are suffering from ovarian hyperstimulation
syndrome (discussed below). Because pregnancy aggravates
this disorder, delayed transfer can be helpful, and cryopreservation
allows such delay. The additional control over the timing
of transfer conferred by cryopreservation is also helpful
to women whose uterine lining is not fully prepared to receive
an embryo at the time of its creation. Cryopreservation
also reduces pressure to implant all embryos at once, thus
reducing the risk of high-order multiple pregnancies.
Following the creation of a human embryo by IVF, the next
discrete phase in the assisted reproduction process is transfer
of the embryo into the uterus of the mother (or gestational
Typically, the embryos are transferred on the second or
third day after fertilization, at the four- to eight-cell
stage. To maximize the probability of implantation, some
clinicians cultivate embryos until the blastocyst stage
(five days after fertilization) before transferring them
to the uterus.16
Prior to transfer, the clinician evaluates the embryos’
shape and appearance. There is believed to be some correlation
between the external appearance of an embryo and its likelihood
of implantation and successful development, but appearances
can also be misleading. Some unhealthy-looking embryos implant
and develop into healthy fetuses and children, and some
healthy-looking embryos fail to implant or experience developmental
Other methods of evaluation include analysis of chemicals
produced by the embryos in culture and pre-evaluation of
the quality of sperm and ovum.
A more recently developed method of embryo analysis is
preimplantation genetic diagnosis. In PGD, one or more cells
are extracted from the eight- to sixteen-cell embryo by
means of biopsy. The clinician tests the sample cell(s)
for chromosomal or genetic characteristics, including the
sex of the embryo, with special attention to any genetic
disorder for which the relevant mutation has been identified
in the parents or an earlier child. (PGD will be discussed
further in Chapter 3.)
Prior to transfer, some clinicians attempt to facilitate
implantation by means of a process called assisted hatching.
Several days after fertilization, an embryo must break out
of the zona pellucida so that it can implant into the uterine
wall. In some instances, the zona pellucida proves to be
too hard to break and implantation fails as a result. To
aid in hatching, clinicians use chemicals, lasers, or mechanical
manipulation of the zona pellucida.18
Once the embryos have been selected and prepared, they
are transferred into the uterus. The total number of embryos
transferred per cycle varies, usually according to the age
of the recipient. For women under 35, the average number
of never-frozen embryos transplanted per transfer procedure
was 2.8. For women 35 to 37, 38 to 40, and 41 to 42, the
average numbers of never-frozen embryos transplanted per
transfer procedure were, respectively, 3.1, 3.4, and 3.7.19
The Centers for Disease Control (CDC) report notes that
in 32 percent of ART cycles using never-frozen, nondonor
ova or embryos in 2001, 4 or more embryos were transferred.20
Typically embryos are transferred into the uterus using
a catheter. The catheter is inserted through the woman’s
cervix and the embryos are injected into her uterus (along
with some amount of the culture fluid). This procedure does
not require anesthesia. Following injection, the patient
must lie still for at least one hour. While the transfer
procedure is regarded as simple, different practitioners
tend to achieve different outcomes.21
An alternative method of embryo transfer is zygote intrafallopian
transfer (ZIFT). In ZIFT, the embryo is placed (via laparoscopy)
directly into the fallopian tube, rather than into the uterus.
In this way, it is similar to the transfer of gametes in
GIFT. Some individuals opt for ZIFT on the theory that it
enhances the likelihood of implantation, given that the
embryo matures en route to the uterus, presumably as it
would in natural conception and implantation. Additionally,
many patients prefer ZIFT to GIFT because the process of
fertilization and early development of the embryo may be
However, ZIFT remains a rare choice, accounting for 0.8
percent of all ART cycles in 2001.23
Successful implantation of an embryo in the uterine lining
marks the beginning of pregnancy. In 2001, 32.8 percent
of the ART cycles undertaken resulted in clinical pregnancy.xi
This number varied according to patient age.25
After the inception of pregnancy, patients are carefully
monitored and treated by an obstetrician. Pregnancies resulting
from assisted reproduction are sometimes treated as high
Clinicians recommend prenatal diagnosis and testing for
many pregnancies resulting from assisted reproduction.
There are a number of medications and procedures that
may be indicated during a pregnancy facilitated by assisted
reproduction. It is typical for a patient to receive progesterone
injections to support key functions necessary to pregnancy.
Multiple gestations are common among pregnancies facilitated
by assisted reproductive technologies. The rate of multiple-fetus
pregnancies from ART cycles using never-frozen, nondonor
ova or embryos in 2001 was 36.7 percent.xii
For the same time period, the multiple infant birth rate
in the United States was 3 percent. The extraordinarily
high rate of multiple pregnancies resulting from assisted
reproduction is almost entirely attributable to the transfer
of multiple embryos per cycle.xiii
In an effort to reduce the risks of multiple pregnancy,
practitioners sometimes employ a procedure termed “fetal
reduction,” the reduction in the number of fetuses in utero
by selective abortion. Fetuses are selected for destruction
based on size, position, and viability (in the clinician’s
The clinician, using ultrasound for guidance, inserts a
needle through the mother’s abdomen (transabdominal multifetal
reduction) through the uterine wall. The clinician then
administers a lethal injection to the heart of the selected
fetus—typically potassium chloride. The dead fetus’s body
decomposes and is resorbed. To be effective, transabdominal
multifetal reduction must be performed at ten to twelve
weeks’ gestation. In an alternative procedure, transvaginal
multifetal reduction, a needle is inserted through the vagina.
Transvaginal multifetal reduction must be performed between
six and eight weeks gestation (eight weeks is recommended).
In 2001, for never-frozen nondonor ova or embryos, the
overall rate of live births per cyclexiv
was 27 percent (33.4 percent live births per transfer).xv
28 Among these
pregnancies, 82.2 percent resulted in live births.29
Of these resulting 21,813 live births, 35.8 percent were
multiple infant births (32 percent twins and 3.8 percent
triplets or more).xvi
One 1993 Canadian study showed that nearly 25 percent of
all births facilitated by ART are premature, and 30 percent
of the resulting infants had low birthweight.xvii
While this low birthweight may be attributable to the high
rate of multiple pregnancies, one 1987-89 French study reported
that even for singleton births facilitated by ART, the rate
of prematurity and low birthweight was twice that of children
conceived by natural means.32
Another study suggests that women using ART are more likely
to induce labor and undergo elective caesarian section delivery.33
F. Disposition of Unused Embryos
As mentioned above, in many cases of ART there are in
vitro embryos that remain untransferred following a successful
cycle. There are five possible outcomes for such an embryo:
(1) it may remain in cryostorage until transferred into
the mother’s uterus in a future ART cycle; (2) it may be
donated to another person or couple seeking to initiate
a pregnancy; (3) it may be donated for purposes of research;
(4) it may remain in cryostorage indefinitely; or (5) it
may be thawed and destroyed.
G. Projected Techniques/Recent
There is a range of research in the reproductive technology
area that is now experimental and in some cases speculative,
but still worth noting. One such area of research is “nuclear
transfer,” which involves transplanting the nucleus from
a fertilized human egg into an enucleated fertilized human
The process is similar to somatic cell nuclear transfer
(or human cloning), except that the nucleus inserted into
the egg comes from another fertilized egg rather than from
a somatic cell of a living child or adult. The resulting
child could conceivably carry genetic material from three
(perhaps four) people: the male and female progenitors of
the original fertilized human egg and at least the mitochondrial
DNA from the donor of the egg into which the embryo’s nucleus
is inserted. In experiments in China in 2003, researchers
reported achieving a triplet pregnancy with such embryos,
though none of the fetuses survived to birth (a result they
attribute to substandard obstetrical care).34
Researchers have also begun investigating whether ovarian
tissues from aborted fetuses may be developed in the lab
in hopes of one day providing mature eggs suitable for IVF.xix
In July 2003, researchers announced that they obtained ovarian
follicles from aborted fetuses aged between twenty-two and
thirty-three weeks gestation, and were able to develop the
follicles in culture to a secondary stage. The researchers
are working to improve the culture media and prolong the
culture period to completely develop the follicles as a
source for human eggs.35
In their quest for alternative sources of gametes, researchers
are working to develop human eggs and sperm from embryonic
stem cells. There has already been some success coaxing
embryonic stem cells from mice to develop into sperm and
eggs, and some researchers project that this technology
will succeed with human embryonic stem cells in “about ten
This would make possible the novel prospects of producing
male-derived eggs or female-derived sperm, and of producing
children whose biological progenitors were embryos that
were disaggregated for their stem cells. There has also
been an experiment that fused blastomeres from two separate
embryos to produce a single (in this case, hybrid male-female)
Most speculative is research aimed at engineering uterine
lining tissue outside the body, for use as a diagnostic
tool to study implantation. Researchers have transferred
human embryos to an artificial endometrium, to which these
embryos attached and began to develop. The implanted, developing
embryos were grown for six days, but researchers did not
attempt to cultivate them further.37
It is not possible now to predict just how much further
in vitro human embryos may someday be developed with such
“uterine-like” substitutes. Another area of highly speculative
research involves uterus transplants, contemplated as a
means to enable women with damaged or absent uteri to bear
There has also been speculation about the prospect of implanting
human embryos into specially prepared non-human animal uteruses
in order to study their development, but there are as yet
no reports of such experiments having taken place with any
II. Ethical Considerations
The development and practice of assisted reproductive
technologies have yielded great goods. They have relieved
the suffering of many who are afflicted with infertility,
helping them to conceive biologically related children.
Yet these activities also raise a variety of ethical issues.
Some concern the well-being of the participants in assisted
reproduction: gamete donors, prospective parents, and their
resulting children. Other issues arise from the expansion
of control over reproduction, including current and projected
possibilities for altering the biological relationships
central to human procreation. Still other issues concern
the use and disposition of human embryos that are incident
to these new capacities and techniques.
The intersection of two key factors—patient vulnerability
and novel (in some cases untested) technology—defines much
of the arena of concern. First, assisted reproduction is
generally practiced on patients who are experiencing great
emotional strain. When it succeeds it can be a source of
great joy—as it has been for tens of thousands of parents
each year. But success is far from universal, especially
for older patients; and even when it happens, the process
and the circumstances surrounding it can be difficult to
bear. Those suffering from infertility often come to practitioners
of assisted reproduction after prolonged periods of failure
and dismay. This vulnerability may lead some individuals
to take undue risks (such as to insist on transferring an
unduly large number of embryos). The occasional irresponsible
clinician may even pressure patients to take such risks,
for the sake of improving his reportable success rates.
Second, some assisted reproductive technologies have been
used in clinical practice without prior rigorous testing
in primates or studies of long-term outcomes. IVF itself
was performed on at least 1,200 women before it was reported
to have been performed on chimps, although it had been extensively
investigated in rabbits, hamsters, and mice.39
The same is true for ICSI. The reproductive use of ICSI
was first introduced by Belgian researchers in 1992.40
Two years later, relying on a two-study review of safety
and efficacy, ASRM declared ICSI to be a “clinical” rather
than “experimental” procedure. Yet the first non-human primate
conceived by ICSI was born only in 1997 and the first successful
ICSI procedure in mice was reported in 1995. 41
Absent long-term studies of the children conceived using
ICSI or other novel procedures, it is unclear to what extent
these alterations in the ART process affect the health and
development of the children so conceived.42
Below, we survey the ethical concerns raised by ART in
four specific areas: (1) the well-being of children born
with the aid of ART; (2) the well-being of women in the
ART process; (3) the meaning of enhanced control over procreation;
and (4) the use and destruction of embryonic human life.
As we proceed, two points are worth noting. First, we raise
these areas of concern solely to enable us to diagnose whether
the current regulatory system is adequately protecting the
human goods at stake. In no way have we lost sight of the
human goods made possible by ART—most notably, the
treatment of infertility and the creation of biologically
related children for couples who desire and could not otherwise
have them. Second, we shall be raising three different kinds
of questions: First, questions of fact, such
as whether a certain assisted reproduction technique is
safe. Second, questions of principle, such
as the moral significance of embryo destruction incident
to fertility treatment or the significance of using fetal
gametes for reproductive purposes. Third, questions of judgment,
such as what degree of risk to the carrying mother or child
conceived with assisted reproduction is justified in cases
where bearing such risks is the only way for individuals
or couples to have a biologically related child. Connected
to this last question is the issue of who should make such
judgments—individuals, doctors, or society as a whole acting
through public institutions. For each of these questions—questions
of fact, questions of principle, and questions of judgment—both
better data and more public discussion are crucial.
A. Well-Being of the Child
The central figure in the process of assisted reproduction,
directly affected by every action taken but incapable of
consenting to such actions, is the child born with the aid
of ART. Each intervention or stage in the ART process might
affect this child’s health and well-being: gamete retrieval
and preparation, fertilization, embryo culture, embryo transfer,
pregnancy, and of course birth.43
The health of the child born through ART may be affected by
actions taken as early as gamete retrieval and preparation. Some
studies show that superovulation decreases embryo and fetal viability
(compared with those in unstimulated cycles).44
One study of embryos created during stimulated cycles revealed
a high level of “developmental arrest, embryonic aneu- ploidy,
mosaicism, apoptosis and failure of cytokinesis.”45
It is possible that lesser abnormalities, compatible with birth,
make their way into the children born alive.
There have been very few comprehensive or long-term studies
of the health and well-being of children born using ART,
although more than 170,000 such children have been born
in the United States.46
The fact that no major investigation or public study has
yet been called for in this area might suggest that there
is no discernible health crisis in assisted reproduction,
as does the fact that demand for ART has grown substantially
and continuously since its inception. At the same time,
however, our ability to know this with certainty is limited,
both because of the absence of major longitudinal studies
of the well-being of children born using different assisted
reproduction techniques, and because the oldest person conceived
through ART is only in her mid-twenties.
Some recent studies have associated various birth defects
and developmental difficulties with the uses of various
technologies and practices of assisted reproduction. None
of these studies provide a causal link between ART and the
dysfunctions observed, and some commentators have taken
issue with some of the methodologies used. Nevertheless,
these findings have raised some concerns. One such study
concluded that children conceived by assisted reproduction
are twice as likely to suffer major birth defects as children
conceived without such assistance.xxii
Other recent studies have reached similar conclusions.48
Additional studies have associated the use of assisted reproduction
technologies with a higher incidence of diseases and malformations,
including Beckwith-Wiedemann syndrome (BWS),xxii
rare urological defects, retinoblastoma,49
neural tube defects,50
and Angelman syndrome.51
While many are concerned about the increased risk to children
suggested by these studies, the overall incidence of such
harms is low enough that infertile couples have not been
deterred in their efforts to conceive using IVF or ICSI.
Indeed, ART clinicians (and in some cases the authors of
advise their patients that such data should not dissuade
them from pursuing infertility treatment.
ICSI has raised concerns among some observers largely
for the very reasons that it has proven so successful as
a means of fertilization: ICSI circumvents the ovum’s natural
barrier against sperm otherwise incapable of insemination.
Some suspect that removing this barrier may permit a damaged
sperm (for example, aneuploid or with damaged DNA) to fertilize
an ovum, resulting in spontaneous abortion or harm to the
resulting child. Some male ART patients have a gene mutation
or a chromosomal deletion that renders them infertile. Yet,
if a sperm can be retrieved from these patients, they may
be able to conceive a child via ICSI, possibly passing along
the genetic abnormality to the resulting child. For example,
two-thirds of men with congenital bilateral absence of the
vas deferens (rendering them unable to ejaculate) carry
certain cystic fibrosis mutations.53
ICSI may permit these men to overcome their infertility,
but the resulting child will (in 50 percent of the cases)
bear this genetic mutation. Similarly, another form of male
factor infertility characterized by a very low sperm count
is associated with a particular Y-chromosome deletion. The
use of ICSI in such cases risks transferring this chromosome
deletion to the resulting child, rendering any male child
infertile, and, according to some studies, at risk for sex-chromosome
Additional studies have associated the use of ICSI with
an increased incidence in novel chromosomal abnormalities
and mental developmental delays.55
It is a matter of concern that there have been few longitudinal
studies analyzing the long-term effects of ICSI on the children
born with its aid. The Belgian group that pioneered ICSI
has collected a database that details neonatal outcome and
congenital malformations in children conceived through ICSI.56
But there do not seem to be any ongoing or published studies
of this kind investigating the long-term effects of ICSI
beyond the neonatal stage.
Many adjuncts to the fertilization and transfer process
raise concerns for the health and well-being of the children
born as a result.xxiii
Some have speculated that factors such as culture conditions
and length of time an embryo spends in culture may affect
the development of the children later born.57
Some authorities claim that differences in salt or amino
acid concentrations in the culture media can affect gene
Additionally, one researcher notes that the process of extended
culture in mice (for example, permitting extended embryo
development prior to transfer) can cause imprinting problems
leading to abnormal development.59
Still other adjuncts to fertilization and transfer may
not be risk-free. Cryopreservation might affect gene expression
or lead to other molecular effects such as “telomere shortening
and replicative senescence, damage to plasma and nuclear
membranes, and inappropriate chromatin condensation.”60
Similarly, ooplasm transfer has been linked to an unusually
high rate of Turner syndrome.61
Finally, assisted hatching (or any technique that results
in manipulation of the zona pellucida) has been associated
with a higher incidence of monozygotic twinning and an increased
risk of twins carried in the same amniotic sac, which can
lead to malformation, disparities in growth, and pregnancy
Multiple gestations, far more common in the context of
assisted reproduction than in natural conception,xxiv
have a higher incidence of adverse impacts on the health
of the children born.64
Such pregnancies greatly increase the risk of prenatal death.65
Multiple pregnancies are also more likely to lead to premature
birth; and prematurity is associated with myriad health
problems including serious infection, respiratory distress
syndrome, and heart defects.66
One in ten children born following high-order pregnancies
dies before one year of age.67
Children born following a multiple pregnancy are at greater
risk for such disabilities as blindness, respiratory dysfunction,
and brain damage.68
Moreover, infants born following such a pregnancy tend to
have an extremely low birthweight, which is itself associated
with a number of health problems, including some that manifest
themselves only later in life, such as hypertension, cardiac
disease, stroke, and osteoporosis in middle age.69
Interestingly, the higher incidence of low birth-weight
may not be limited to infants born from multiple pregnancies.
According to recent studies, singletons born with the aid
of ART tend to have an abnormally high incidence of prematurity
and low birthweight.70
So-called “fetal reduction” aims to reduce the problems
associated with multiple pregnancy. But fetal reduction
is itself potentially associated with a number of adverse
effects on the children who remain following the procedure.
One study shows that following transabdominal multifetal
reduction there is a miscarriage rate of 16.2 percent, and
16.5 percent of the remaining pregnancies end in premature
The alternative method, transvaginal multifetal reduction,
carries a higher risk of infection and has been associated
with a higher risk of infant mortality than its counterpart.72
It has been observed that children born following fetal
reduction (by either method) tend to be premature, thus
exposing them to the complications described above.73
One study has suggested that children born following fetal
reduction are more vulnerable to periventricular leukomalacia,
which is characterized by brain dysfunction and developmental
Taken together, the significance of these various studies
is uncertain. They raise a broad range of concerns, but
the scale of the research has been limited. In many cases,
there are observed correlations between ART and a higher
incidence of certain health problems in the resulting children.
But in most studies, there is no demonstrable causal relationship
between a particular facet of ART and the undesirable health
effect. Infertile individuals seeking assisted reproduction
may be disproportionately afflicted with heritable disorders,
and these may in part account for the higher incidence of
birth and developmental abnormalities in ART children compared
to those conceived in vivo. The results are therefore still
preliminary. The need seems clear for more data to determine
what risks, if any, different assisted reproduction techniques
present to the well-being of the future child. Moreover,
in cases where ART is the only available means for individuals
or couples to conceive a biologically related child, it
is an important ethical and social question what level of
increased risk can be privately justified by patients and
doctors, and what level of increased risk should be publicly
justified by society as a whole, especially should the society
bear the costs of caring for any resulting health problems.
B. Well-Being of Women in the ART Process
Another concern is for the well-being of the women who
participate directly in the process of assisted reproduction.
Aside from the discomforts and burdens of ovarian stimulation
and monitoring, there are also some risks attached to hormonal
stimulation. One such risk is “ovarian hyperstimulation
syndrome,” characterized by dramatic enlargement of the
ovaries and fluid imbalances that can be (in extreme cases)
Complications can include rupture of the ovaries, cysts,
and cancers. The reported incidence of severe ovarian hyperstimulation
syndrome is between 0.5 and 5.0 percent.75
Additionally, adverse side effects of the hormones administered
during superovulation have included memory loss, nerological
dysfunction, cardiac disorders, and even sudden death.76
There do not appear to be any studies on the incidence of
such side effects.77
Some women who become pregnant with the aid of assisted
reproduction are treated as “high-risk” patients and experience
a higher incidence of complications than do women with natural
pregnancies. Some commentators have suggested that this
is due to the age of the patients (who tend to be older
than most childbearing women) and the high rate of multiple
Multiple pregnancies are far more common following ART,
owing especially to the practice of transferring multiple
embryos but also to the higher incidence of spontaneous
twinning with any single embryo. Multiple pregnancies pose
greater risks to mothers than do singleton pregnancies.
A woman carrying multiple fetuses has a greater chance of
suffering from high blood pressure, anemia, or pre-eclampsia.79
Because multiple-gestation pregnancies are generally more
taxing on the mother’s body, they are likelier to aggravate
pre-existing medical conditions.80
Moreover, such pregnancies expose the woman to higher risks
of uterine rupture, placenta previa, or abruption.81
One commentator noted in 1995 that the added expense growing
out of complications from multiple-gestation pregnancies
is one of the primary reasons private health insurance generally
does not cover assisted reproduction.82
Both professional societies and advocates for infertile
patients argue that mandating insurance coverage could reduce
multiple- gestation pregnancies because it would reduce
financial pressure to succeed in the first attempt.xxvi
C. Meaning of Enhanced Control over Procreation
The ability to initiate fertilization artificially may
also profoundly affect the character of human reproduction
and our attitudes toward it, as well as the relationships
between parents and children and across generations. Three
potential hazards or concerns seem especially worthy of
note. First, ART raises novel possibilities for altering
the biological relationships that are central to normal
sexual reproduction, and thus for confounding the human
relationships that follow from it. Through ART, it is now
possible for a surrogate (or an adoptive parent) to carry
and give birth to another couple’s biological child; it
is possible for a woman to become pregnant with an anonymous
donor’s sperm; it is possible for a deceased male to become
a biological father after death; and it is possible to produce
a child with genetic material from three progenitors. Moreover,
current research might one day make it possible to use gametes
from aborted fetuses, and thus make such fetuses into biological
parents, and to produce eggs from male-derived embryonic
stem cells or sperm from female-derived embryonic stem cells,
which would in theory allow for the creation of a child
with two male or two female embryonic progenitors.
Second, ART raises the possibility of moving human procreation
in the direction of manufacture, by introducing technical
approaches or attitudes into the activity of human reproduction.
And finally, ART might affect our general understanding
of or attitudes about parenthood and childhood, by making
sexual reproduction simply one option among many, with no
special significance for how we understand the coming-to-be
of the next generation.
Particular techniques raise certain specific concerns
in this regard. Cryopreservation, ooplasm transfer, and
the possible use of fetal oocytes directly raise concerns
about the definition and identity of “father” and “mother.”
Cryopreservation of sperm and embryos makes posthumous parentage
possible. For instance, some American soldiers have been
reported to store up sperm on the eve of shipping out to
a battle zone. And instances have been reported in which
women have requested that their newly deceased husband’s
sperm be harvested via assisted sperm retrieval from the
corpse and used for artificial insemination. If techniques
for cryopreservation of ova are ever perfected, or if ova
can be derived from adult stem cells, new opportunities
for posthumous conception involving deceased women will
Ooplasm transfer raises a slightly different issue. Because
donated ooplasm contains mitochondrial DNA from the donor,
the resulting child receives a small genetic contribution
from a third person. Moreover, because mitochondrial DNA
is maternally inherited, if the resulting child is female,
she will pass on to her own offspring the genetic contribution
of both her mother and the female ooplasm donor.
A projected technique that raises new ethical concerns
is the harvesting and use of fetal oocytes. Some researchers
have posited that oocytes (or their precursors) might be
harvested from aborted fetuses and used as donated ova (once
they have matured in vitro) for patients who have impaired
The aborted fetuses would be the genetic mothers of any
resulting children. If recent studies in which mouse oocytes
have been derived from mouse embryonic stem cells83
can be replicated in humans, a five-day-old embryo (the
age of the mouse embryo when cells were retrieved) could
also become the biological progenitor of new children.84
These procedures, and others like them, raise the possibility
that children conceived through ART might be connected to
their biological parents in fundamentally different ways
than children conceived and born without artificial intervention.
In some cases, children conceived with these technologies
might be denied the biparental origins that human beings
have always taken for granted and that have always been
the foundation of familial relations and generational connections.
ART techniques do not have to disrupt such relations, but
they might be used in ways that confound parentage, involve
more or fewer than two biological parents, or otherwise
depart from the biologically grounded parent-child relation.
Fetal reduction raises its own distinct set of concerns.
In this procedure, parents effectively choose to have some
developing fetuses (each of which was conceived in the hope
that it would be developed to term) live and some not, and
they use surgical procedures to reduce the number of living
fetuses in utero.
D. Use and Destruction of Human Embryos
Assisted reproduction usually entails the loss of human
embryos, especially when superovulation is used and many
ova are fertilized at once. Large numbers of embryos die
at all stages of assisted reproduction (in vitro and in
An unknown number of additional embryos are discarded when
it is determined that they are no longer needed or desired.
Still others are donated to researchers, who use them in
biomedical or scientific experiments that involve or lead
to their destruction. Thousands of embryos are cryopreserved
for indefinite periods of time. As previously noted, an
estimated 400,000 embryos were in cryostorage in the United
States as of April 2002.
Actions that result in the end of embryonic life are morally
significant and require careful consideration and attention.
We consider the ethical significance and current regulation
of human embryo research in Chapter 5.
III. Current Regulation
The following discussion provides an overview of the current
state of regulation of the biotechnologies and practices
discussed above. The discussion will be broadly divided
into sections treating the governmental (federal and state)
and nongovernmental regulation of assisted reproduction,
both direct and indirect. Each source of regulation will
be described in terms of its aims, animating values, jurisdictional
scope and requirements, mechanisms of regulation, and efficacy.
A. Direct Governmental Regulation of Assisted
1. Federal Oversight.
a. Consumer protection and embryo laboratory standards.
There is only one federal statute that aims at the regulation
of assisted reproduction: the Fertility Clinic Success Rate
and Certification Act of 1992 (“the Act”).85
The purposes of the statute and its related regulations
are twofold: (1) to provide consumers with reliable and
useful information about the efficacy of ART services offered
by fertility clinics, and (2) to provide states with a model
certification process for embryo laboratories.
(i) Success rates: Under the implementing regulations
of the Act, each ART program or clinic in the United States
is required to report annually to the CDC data relating
to its rates of success.86
The Act defines ART as “all treatments or procedures which
include the handling of human oocytes or embryos, including
in vitro fertilization, gamete intrafallopian transfer,
zygote intrafallopian transfer, and such other specific
technologies as the Secretary [of Health and Human Services]
may include in this definition . . .”87
An “ART program or clinic” is defined as a legal entity
practicing under state law, recognizable to the consumer,
that provides ART services to couples who have experienced
infertility or are undergoing ART for other reasons.88
Each ART program is required to collect and report data
for each cycle of treatment initiated. For these purposes,
an “ART cycle” is initiated when a woman begins taking
fertility drugs or starts ovarian monitoring with the
intent of creating embryos for transfer. The data that
must be collected include: patient demographics; medical
history and infertility diagnosis; clinical information
pertaining to the ART cycle; and information on resulting
pregnancies and births.
Information is presented in terms of pregnancies per
cycle, live births per cycle, and live births per transfer
(including never-frozen and frozen embryos from both patients
and donors). The statistics are also organized according
to age (younger than 35, 35 to 39, and older than 39).
Programs are also required to report information on cancelled
cycles, number of embryos transferred per cycle, multiple
birth rates per transfer, percentage of patients with
particular diagnoses, and types and frequency of ARTs
used (for example, the frequency with which ICSI is used).
The outcome information that ART clinics must report includes
the maximum number of fetal hearts observed in ultrasound,
whether there was a medically induced fetal reduction,
and birth defects diagnosed for each live-born and still-born
The data, reported by the Society for Assisted Reproductive
Technology (SART, with whom CDC has contracted to implement
the Act) are subject to external validation through an
performed by SART’s Validation Committee in conjunction
with the CDC. This committee is composed of fourteen members
assembled from both SART and non-SART member programs.
Inspection teams of two Validation Committee members visit
ten percent of the reporting clinics for each annual report.
The clinics visited are randomly selected by the CDC.
All live births reported by each visited clinic are validated.
Additionally, twenty other variables are validated from
fifty randomly selected cycles. The data collected during
the on-site inspections are compiled and jointly reviewed
by the Validation Committee and the CDC.
Any ART program can satisfy the federal
reporting requirements by reporting its data to SART. If
a clinic or program fails to comply with the requirements
of the act, it is listed as “nonreporting” in the annual
CDC publication that collects and analyzes the data reported.
There are no other penalties for failure to report.
CDC publishes much (but not all) of the information it
collects in an annual report of ART success rates. Each
annual report includes three sections: (1) a national
report that compiles information from all ART programs
to provide an in-depth national picture of ART; (2) fertility
clinic reports that provide ART success rates for each
ART program that reports and verifies its data; and (3)
an appendix containing a glossary of terms, an explanation
of how the success rates (according to age group) were
calculated, the names and addresses of reporting programs,
and a list of programs not reporting data, including those
who refuse to participate in the validation process discussed
The annual report does not include some of the information
that ART clinics are required to report, such as the number
of oocytes retrieved, embryos transferred, or cryopreserved;
maximum number of fetal hearts observed in ultrasound;
the number of fetal reductions performed; and adverse
outcomes (including information relating to birth defects
or low birthweight).
Have the reporting requirements of the
Act been an effective means of informing and protecting
consumers? Critics assert that because there are no serious
penalties for noncompliance, the law is merely hortatory.
Supporters of the Act respond that the stigma of being listed
as “nonreporting” creates sufficient market pressure to
compel the vast majority of ART programs to report the required
data. Indeed, in 2000, 384 of the nation’s 421 ART programs
were deemed in compliance with the Act’s reporting requirements.
Some critics argue that the reporting requirements could
be greatly improved to provide more information for prospective
patients. For example, Pamela Madsen, Executive Director
of the American Infertility Association (an advocacy organization
for infertile persons) has called for “improving informed
consent, augmenting reporting from clinics, and delineating
Moreover, some have observed that focusing on pregnancy
success rates (per cycle) may create an incentive to transfer
too many embryos per cycle, resulting in multiple pregnancies
that can be extremely risky for both mother and children.
One clinician has noted: “We’re under pressure to have
high pregnancy rates . . . the problem is we’ve never
had any way of knowing what was the right number of embryos
Finally, some have argued that “success rates” are not
a reliable measure, given the ease with which they can
be manipulated; clinics can artificially inflate these
rates by accepting only those patients with promising
prognoses, reclassifying or canceling failed cycles rather
than reporting them, or transferring many embryos per
(ii) Model certification program: The
second function of the Act is to provide states with a
model certification program for embryo laboratories. An
“embryo laboratory” is defined as “a facility in which
human oocytes are subject to assisted reproductive technology
treatment or procedures based on manipulation of oocytes
or embryos which are subject to implantation.”92
Unlike the reporting system, adoption of the model program
is entirely voluntary. The model certification program
is intended to provide a resource for states wishing to
develop their own programs or for professional organizations
seeking to develop guidelines or standards for embryo
labs. States can apply to the Secretary of Health and
Human Services to adopt the program and qualifying states
will be required to administer the program as provided
by the regulations. To date, no state has done so.
The overarching purpose of the model program is to help
states to assure consistent quality control, record keeping,
performance of procedures, and quality of personnel. The
specific standards applied were developed in conjunction
with the College of American Pathologists and ASRM, borrowing
generously from the guidelines used in the voluntary certification
program (discussed further below).
The final version of the program, incorporating comments
received by the CDC, was published in the Federal Register
on July 21, 1999.93
Under the program, embryo laboratories may apply
to their respective states for certification. Those laboratories
that choose to do so are inspected and certified by states
or approved accreditation organizations. Certification
is valid for a two-year period. The Secretary, through
the CDC, has authority to inspect any laboratory that
has been certified by a state to ensure compliance with
the standards. The penalty for noncompliance under the
model program is revocation of certification. A key limitation
of the program is that neither the Secretary nor the states
may establish “any regulation, standard or requirement
which has the effect of exercising supervision or control
over the practice of medicine in assisted reproductive
Even if a state were to adopt the program, there is no
requirement that laboratories apply for certification;
it is entirely voluntary.
2. State Oversight.
There are a variety of state laws that bear directly on
the clinical practice of assisted reproduction. The vast
majority of state statutes directly concerned with assisted
reproduction, however, are concerned mostly with the question
of access to such services. These states have legislative
directives as to whether and to what extent assisted reproduction
services will be covered as insurance benefits. Other state
statutes regarding assisted reproduction aim to prevent
the malfeasance of rogue practitioners (for example, California
criminalizes unauthorized use of sperm, ova, and embryos).
Still others focus on the regulation of gamete and embryo
donation (for example, California sets forth screening requirements
for donated sperm). There are a host of states whose laws
dictate parental rights and obligations in the context of
A few jurisdictions (such as New Hampshire and Pennsylvania)
have statutes that provide for fairly comprehensive regulation
of the practitioners and participants in ART. Many jurisdictions
have statutes that bear generally on the treatment and disposition
of embryos, but only a subset of these jurisdictions explicitly
speaks to the treatment of embryos in the context of assisted
reproduction (including Louisiana, New Mexico, and South
New Hampshire has an “In Vitro Fertilization and Pre-embryo
Transfer” statutory scheme that provides that “IVF will
be performed in accordance with the rules adopted by the
[state] department of Health and Human Services.”96
The state additionally specifies who may receive IVF treatment,
namely, a woman who is at least twenty-one years of age,
who has been medically evaluated for her “acceptability”
to undergo the treatment (it is unclear what this means),
and who has undergone requisite counseling.97
New Hampshire likewise extends the medical and counseling
requirement to the woman’s husband.98
Pennsylvania also regulates ART as such, but focuses its
efforts on record keeping and standards for maintenance
of clinical facilities.99
All IVF practitioners are required to submit reports and
be available for inspection. The reports must include the
names of the practitioners, their locations, the number
of ova fertilized, the number of embryos destroyed or discarded,
and the number of women “implanted with a fertilized egg.”
Louisiana, New Mexico, and South Dakota, as noted, have
embryo experimentation statutes that directly speak to assisted
The New Mexico statute prohibits any “clinical research
activit[ies] involving fetuses, live-born infants or pregnant
Clinical research “includes research involving human in
vitro fertilization, but . . . shall not include
human in vitro fertilization performed to treat infertility;
provided that this procedure shall include provisions to
insure that each living fertilized ovum, zygote or embryo
is implanted in a human female recipient . . .”102There
have been no court opinions interpreting this language,
but some commentators suggest that this effectively proscribes
the practice of IVF except in cases in which all embryos
are transferred to the mother.103
South Dakota, like New Mexico, prohibits “non-therapeutic
research” on embryos. In contrast to New Mexico, however,
it explicitly exempts from this definition “IVF and transfer,
or diagnostic tests which may assist in the future care
of a child subjected to this test.” Again, there are no
cases interpreting this language, but it seems that this
statute would not require the transfer to a uterus of all
embryos created in the process of IVF.
Louisiana’s regulation of ART provides the highest level
of protection to human embryos of any U.S. jurisdiction.
It defines the in vitro embryo as a “juridical person” with
nearly all of the attendant rights and protections of infants.xxxi
It stipulates that the use of an in vitro embryo must be
solely for “the support and contribution of the complete
development of human in utero implantation.” The production,
culture, or use of human embryos for any other purpose is
proscribed. An in vitro embryo is not considered the property
of the clinician or the gamete donors. If the ART patients
identify themselves as the embryo’s progenitors, they are
deemed parents according to the Louisiana Civil Code. If
the ART patients do not identify themselves, the “physician
shall be deemed to be the temporary guardian . . .
until adoptive implantation can occur.” The physician who
creates the embryo through IVF is directly responsible for
its safekeeping. The gamete donors owe the embryo “a high
duty of care and prudent administration.” They may, however,
renounce their parental rights through a formal proceeding,
after which the embryo shall be available for adoptive implantation.
Donors may convey their parental rights to another married
couple, but only if “the other couple is willing and able
to receive” the embryo. Under Louisiana law, the judicial
standard governing any disputes involving the embryo is
“the best interests of the embryo.” Thus, there can be no
intentional destruction of a viable embryo.
Louisiana has also set standards for who may perform IVF
and where IVF may be performed: It may be practiced only
by a licensed physician in medical facilities that meet
“the standards of [ASRM] and the American College of Obstetricians
Some states have enacted statutes that preclude “experimentation”
on human embryos. Given the experimental nature of certain
ART procedures (such as preimplantation genetic diagnosis),
these statutes might be construed broadly to reach such
practices. Some individuals have challenged such statutes
on constitutional grounds, arguing that the operative terms
are so vague as to violate the constitutional guarantee
of due process.xxxii
Practitioners have argued that they have not been adequately
informed about which procedures could expose them to criminal
liability. Courts in three jurisdictions have invalidated
such statutes on these grounds.104
One court among these three struck down the statute on the
additional ground that it impermissibly infringed the plaintiff’s
right to choose a particular means of reproduction, noting:
“It takes no great leap of logic to see that within the
cluster of constitutionally protected choices that includes
access to contraceptives, there must be included within
that cluster the right to submit to a medical procedure
that may bring about, rather than prevent, pregnancy.”105
In short, there are very few state laws that bear directly
on assisted reproduction. Most of these laws relate to the
provision of insurance coverage for infertility treatment.
A few state laws directly relating to ART focus on health
and safety concerns; a handful of states provide modest
consumer protections. Some state laws regulating embryo
research may indirectly affect the practice of assisted
reproduction, though the decisional law in this area is
unsettled. In the main, however, assisted reproduction is
regulated at the state level by the same mechanisms that
apply to the practice of medicine more generally, namely,
through the licensure and certification of practitioners.
B. Indirect Governmental Regulation of Assisted
There are a number of state and federal governmental authorities
that do not explicitly aim at the regulation of ART, but
indirectly and incidentally provide some measure of oversight
1. Federal Oversight.
a. Safety and efficacy of products and public health.
The U.S. Food and Drug Administration (FDA) is the federal
agency that regulates some of the articles used
in assisted reproduction, but it does not, as a general
matter, oversee the practice of assisted reproduction.
FDA regulates drugs, devices, and biologics that are
or will be marketed for use in the United States. Its
principal purpose is to ensure the safety and efficacy
of products according to their approved use.106
The FDA is also broadly authorized to adopt regulations
to prevent the spread of communicable disease.107
Additionally, it exercises regulatory
authority over clinical trials of unapproved medical products
subject to its regulations. The FDA does not, however,
have the authority to regulate “the practice of medicine”
(which is the province of the states). Thus physicians
may, in the course of administering medical treatment
according to acceptable standards of care, employ FDA-approved
articles in a manner that is outside the scope of their
approved use. This is sometimes called “off-label” use.
The FDA’s jurisdiction is a product of congressional
authority under the interstate commerce clause of the
United States Constitution. FDA’s principal powers derive
from the authority conferred by the Food, Drug, and Cosmetic
Act (FDCA) and the Public Health Services Act (PHSA) to
regulate the introduction of certain products (and their
components) into interstate commerce. Given the Supreme
Court’s expansive interpretation of what constitutes “interstate
activity” for purposes of deciding cases involving the
commerce clause, this has not proven to be a significant
limitation on the FDA’s authority. Nevertheless, it is
conceivable that one might mount a credible constitutional
challenge to FDA regulation of an activity that is wholly
FDA regulatory mechanisms are driven by the statutory
definitions provided by the FDCA and PHSA. If FDA determines
that a given article falls within the broad statutory
definitions of “drug,” “device,” or “biologic,” it could
exercise jurisdiction, provided the interstate nexus is
satisfied. Thus, to describe the breadth and depth of
FDA’s authority, particularly as it relates to assisted
reproduction, it is necessary to explain in some detail
how these statutory definitions and related provisions
function in practice.
“Drug” is defined by the FDCA in an extremely expansive
way, encompassing any officially recognized article that
is either (1) intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease in man,
or (2) (excepting foods) intended to affect the structure
or any function of the body of man. The definition also
extends to anything intended for use as a component of
the foregoing articles.108
It is unlawful to introduce a “new drug”—a legal category
that encompasses nearly every prescription and many non-prescription
drugs—into interstate commerce without an FDA-approved
New Drug Application (NDA).109
The NDA process is onerous and expensive, requiring the
sponsor to provide large amounts of information to the
FDA including details regarding the composition of the
drug, “the chemistry of the formulation for delivering
the active ingredient, methods of manufacture and packaging,
proposed labeling, and, most critically, the results of
clinical studies that will support a conclusion that the
drug product is safe and effective.”110
As Professor Richard Merrill points out, the FDA’s proscription
on distribution of unapproved drugs, combined with its
demand for clinical trials as a pre-requisite to new drug
approval, seems to create a paradox.111
For how can a “new drug” be tested for safety and efficacy
if it cannot move in interstate commerce? Congress enabled
the FDA to resolve this tension by creating a limited
exemption for distribution of an “Investigational New
is, a limited approval solely for purposes of a clinical
trial. Upon receipt of an IND application, FDA imposes
a thirty-day waiting period during which it reviews the
proposed protocols. FDA can deny or suspend an IND (called
a “clinical hold”) and effectively prevent clinical trials
for a new drug if it finds that (1) human subjects would
be exposed to unreasonable and significant risk of illness
or injury or (2) the IND does not contain sufficient information
required to assess the risks to subjects of the
Pursuant to Section 351 of the PHSA, the FDA has the
authority to regulate “biological products,” defined as
“any virus, therapeutic serum, toxin, anti-toxin, vaccine,
blood, blood component or derivative, allergenic product
or analogous product, applicable to the prevention, treatment
or cure of diseases or injuries to humans.”113
This is, on its face, a very broad definition, particularly
in light of the somewhat ambiguous phrase “analogous product.”
Under Section 351, it is unlawful to introduce any biological
product into interstate commerce without an approved biologics
license application (BLA).114
The BLA process is much akin to the NDA process in that
applicants are required to demonstrate that the biological
product is “safe, pure, and potent,” and manufactured
in a facility meeting certain specifications.115
The data in support of the application must be developed
through clinical and nonclinical studies. The same regulations
governing preclinical testing and clinical testing of
new drugs in the IND context116
govern these activities in the BLA process as well. Indeed,
the definition of “biological product” falls within the
statutory definition of “drug” in the FDCA. However, if
a biologic is licensed under Section 351, it need not
be approved under the parallel FDCA provisions.117
Pursuant to its authority to regulate biological products,
FDA’s Center for Biologics Evaluation and Research (CBER)
has also undertaken regulation of cellular and gene-therapy
products. Researchers developing gene-therapy products
must receive an IND before studying gene-therapy products
in humans and must meet FDA requirements for safety and
efficacy before such products can be approved for marketing.
The regulation of such activities is discussed extensively
in Chapter 5.
Section 361 of the PHSA empowers the FDA to issue regulations
to prevent the spread of communicable diseases.118
Under this authority, CBER has issued or proposed regulations
for Human Cellular and Tissue-Based Products (HCT/Ps),
which include a variety of medical products derived from
the human body and used for replacement, reproductive,
or therapeutic purposes, such as semen, ova, and embryos
used for reproductive purposes.xxxiii
Sperm, ova, and embryos were originally exempted from
this definition, but were later added out of concern for
the transmission of disease. In 1997, the FDA released
a general plan for the comprehensive regulation of HCT/Ps.
In 1998, the FDA published three proposed rules that would
require: (1) registration for facilities working with
reproductive tissue; (2) screening for communicable disease;
and (3) adherence to FDA good tissue practices for “minimally
processed or manipulated” tissues transplanted from one
person to another for their normal structural functions.120
The first rule is now final; the latter two are pending.xxxiv
Owners and operators of establishments or persons engaged
in the recovery, screening, testing, processing, storage,
or distribution of HCT/Ps must register with the FDA and
list those human cells, tissues, and cellular and tissue-based
products with CBER.xxxv
However, there are several important exceptions to these
registration requirements. Specifically, registration
is not required if (1) an establishment removes HCT/Ps
from an individual and implants such HCT/Ps into the same
individual during the same surgical procedure; (2) an
establishment does not recover, screen, test, process,
label, package, or distribute, but only receives or stores
HCT/Ps solely for implantation, transplantation, infusion,
or transfer within the facility; or (3) an establishment
only recovers reproductive cells or tissue and immediately
transfers them into a sexually intimate partner of the
cell or tissue donor.121
Like the statutory definition of “drug” and “biological
product” discussed above, “device” is defined in a similarly
expansive manner, covering any “instrument, apparatus,
implement, machine, contrivance, implant, in vitro reagent,
or other similar related article, including any component”
that is officially recognized, intended for the diagnosis,
treatment, cure, mitigation, or prevention of disease
in man, or intended to affect the structure and function
of the body of man, “and which does not achieve its primary
intended purpose through chemical action within or on
the body of man . . . and which is not dependent
upon being metabolized for achievement of its primary
Devices are categorized according to the risk of harm
associated with their use.123
Those devices that present a low safety risk are designated
as Class I or II. Devices that present the greatest risk,
such as those used to sustain or support life, or those
that are implanted in the human body, are designated as
Class III. All new devices are subject to a process known
as “premarket notification” (PMN), in which the FDA engages
in a preliminary evaluation of safety and efficacy, and
determines whether the proposed device is substantially
equivalent to a product that is already on the market.
Other devices (particularly those presenting a greater
safety risk) are subject to the more onerous “premarket
approval” (PMA) process, which is akin to the NDA procedure,
requiring a much more rigorous demonstration of safety
and efficacy. The timing and schedule of the PMA process
for new devices is highly complex, and beyond the scope
of the present inquiry.
FDA has a number of means at its disposal to enforce
the foregoing regulations under the PHSA and FDCA. FDA
has authority to conduct inspections to determine compliance
with these requirements.124
Approved BLAs or NDAs can be revoked (subject to an adversarial
License revocation is used to address concerns about the
marketability of a given product in general (perhaps based
on the FDA’s reassessment of the relative risks and benefits
of the given product). Additionally, the FDA has the power
to recall or seize previously approved products.xxxvi
Unlike license revocation, recall and seizure powers are
invoked to address concerns about a given subset
of marketed products (for example, a defective batch).
Finally, the FDA can pursue criminal prosecution as an
additional mechanism of enforcement.127
How do the above regulations of drugs,
devices, and biologics affect the practice of assisted reproduction?
First, to the extent that articles used in ART meet the
statutory definition of drug, device, or biologic, they
must satisfy the relevant FDA requirements for marketing.xxxvii
This is, however, principally a regulatory mechanism applicable
to the manufacturers of these articles—rather than the clinicians
who use them following their approval. Once an article is
approved, the FDA surrenders much of its regulatory control.
Clinicians treating infertile patients are regarded as engaged
in the practice of medicine, which has long been acknowledged
as beyond the regulatory reach of the FDA:
The physician may, as part of the practice
of medicine, lawfully prescribe a different dosage for
his patient, or may otherwise vary the conditions of use
from those approved in the package insert, without informing
or obtaining the approval of the Food and Drug Administration.
. . . [T]he Act does not require a physician to
file an investigational new drug plan before prescribing
an approved drug for unapproved use or submit . . .
data concerning the therapeutic results and adverse reactions.128
Further, federal courts have held that
a licensed physician, in treating a patient, can prescribe
a lawful drug for a non-FDA approved purpose.129
the FDA wants to control (or influence) off-label use of
approved products it would likely impose some new labeling
requirement warning users of the dangers animating its concern.
Again, any such action would influence the manufacturer
more than the clinician administering these articles in
the practice of medicine. Theoretically, if the FDA were
concerned that the risks of widespread off-label use utterly
outweighed the benefits of the approved use, it could withdraw
its approval. But this is not often done.
The FDA’s regulations for reproductive tissues, if and
when they are finalized (in the case of the screening
and good tissue practice provisions) and officially implemented,
may have some impact on assisted reproduction. The regulations
currently in effect require certain owners and operators
of facilities that work with reproductive tissues to register
and list such tissues with CBER. However, many fertility
clinics seem to be exempt from these requirements, as
In the main, the FDA has abstained from
regulating the field of assisted reproduction. This is understandable,
given that some of the activities in assisted reproduction
fall under the aegis of the practice of medicine, which
the FDA has not sought to regulate. Given that FDA’s authority
is largely driven by the statutory definitions of “articles”
under its purview, extension of this authority to the context
of assisted reproduction would require some strange re-categorization
of certain aspects of human procreation. For example, in
order to acquire jurisdiction under current law, it might
be necessary for the FDA to construe an embryo that might
be transferred into a uterus as a “drug,” “biological product,”
or “device.” What would safety and efficacy mean in such
a context? Finally, the FDA may have been historically hesitant
to assert jurisdiction over assisted reproduction because
of the nature of the regulatory mechanisms themselves. The
categorization and approval mechanisms through which FDA
exercises much of its authority are not graduated or flexible.
Thus, when FDA asserts jurisdiction over an article by defining
it as a “new drug” subject to the relevant approval requirements,
it becomes immediately unlawful to distribute it. FDA’s
unwillingness to regulate assisted reproduction under the
FDCA may be partly due to a concern that to do so would
effectively shut down the entire practice of assisted reproduction.
There are, however, some notable exceptions to the FDA’s
reluctance to step into the arena of assisted reproduction.
Already mentioned is the regulation, through HCT/P registration
requirements, of entities that collect, process, or distribute
sperm, ova, and embryos as reproductive tissue. A more
controversial example is the FDA’s recent pronouncements
on cloning for reproduction.xxxviii
Here, the FDA has invoked its authority by asserting that
the implantation of a cloned embryo into a woman’s uterus
is tantamount to the administration of an unapproved new
drug, requiring an IND.130
Because of safety concerns, FDA declared that it would
withhold approval of any such IND.xxxix
To date, no IND has been submitted. It bears noting that
the animating principles of FDA’s regulation in this context
are, as usual, safety and efficacy. A former head of CBER,
Katherine Zoon, told a congressional committee that if
concerns over safety were properly addressed, FDA would
not likely reject an IND for cloning for reproduction.131
Finally, the FDA has also ventured into
the field of assisted reproduction to halt the practice
of ooplasm transfer. In 2001, FDA asserted that clinicians
at St. Barnabas Hospital in Livingston, New Jersey, were
required to submit an IND before performing further procedures
involving ooplasm transfer, on the grounds that it is a
form of gene-transfer research, as the procedure results
in the transfer of mitochondrial DNA. This sent a shock
wave through the ART community, and most if not all practitioners
halted the procedure altogether rather than submit to the
These examples serve to illustrate the contours and limits
of FDA’s authority in the context of assisted reproduction.
First, it is clear that the FDA will act if it perceives
a sufficiently grave harm that can be formulated in terms
of FDA’s mandate—safety and efficacy, and the prevention
of communicable disease. However, to assert jurisdiction,
FDA must sometimes engage in definitional contortions.
By most lights, for example, human embryos are not “drugs.”
Finally, these examples suggest that the line between
clinical experimentation and the practice of medicine
is not always easy to draw. As a general rule, clinicians
can, without FDA oversight, employ novel and untested
interventions on patients in the course of treatment,
provided that the articles involved have been previously
approved for their originally intended purpose.
b. Quality assurance and control in
.Another federal authority that
indirectly affects assisted reproduction arises from the
Clinical Laboratory Improvement Amendments of 1988 (CLIA).132
This statute (and regulations issued thereunder by the Centers
for Medicare and Medicaid Services, or CMS) requires laboratories
engaged in the “examination of materials derived from the
human body for the purpose of providing information for
the diagnosis, prevention, or treatment of any disease or
impairment” to meet certain quality requirements. Specifically,
CLIA requires that such laboratories must satisfy requirements
relating to quality assurance, personnel qualifications
and responsibilities, record keeping, quality control, and
the like. Moreover, such labs must submit to inspections
(announced or unannounced). Failure to comply can result
in revocation of certification and inclusion in a published
list of sanctioned laboratories. States can opt out of CLIA
if they have their own certification program that is equally
or more rigorous.
CLIA does not apply to assisted reproduction laboratory
facilities as such. Rather, it applies to andrology and
endocrinology diagnostic tests (such as semen and blood-hormone
analysis) in such laboratories. These tests are not
covered by CLIA when undertaken as an adjunct to
the delivery of assisted reproduction services. This creates
what some consider to be a confusing regulatory atmosphere.
The American Board of Bioanalysis (ABB) (which advocates
on behalf of clinical laboratory directors) brought a
lawsuit in 1999 to compel Health and Human Services (HHS)
to apply CLIA to all ART embryo laboratories. The case
was dismissed on the grounds that the ABB lacked standing
to sue. The Court agreed with HHS’s contention that the
Department should be allotted more time to consider the
question of CLIA’s application.
c. Regulation of unfair trade practices. The Federal
Trade Commission (FTC) is charged with providing safeguards
against anti-competitive behavior and promoting truth in advertising
in interstate commerce. FTC thus has the authority to investigate
deceptive claims in advertising by health care providers,
including fertility clinics (for example, claims of pregnancy
a. Regulation of the practice of medicine. To describe
the current regulation of assisted reproduction fully
and fairly, it is necessary to treat in some detail the
regulation of the practice of medicine more generally.
The bulk of external governmental regulation of assisted
reproduction is entirely indirect, and is subsumed in
this more general context. The following requirements,
pertinent to the entire practice of medicine, apply also
to the practice of assisted reproduction. Despite the
fact that they are not specifically addressed to the practice
of reproductive medicine, these requirements are generally
cited by practitioners of ART in support of the proposition
that the field is subject to close regulatory scrutiny.
(i) Informed consent:One of the core principles
of ethical medical practice, supported also by legal standards,
is the requirement that patients provide their informed
consent to medical treatments and procedures. While informed
consent is necessary in all medical contexts, it is required
under the federal human-subject research regulations and,
in most states, is explicitly called for by the state’s
doctrine of informed consent has also been long recognized
in case law through recognition that treatment without
consent constitutes a battery. Even outside of the human-subject
research context, most hospitals require written informed
consent when complicated or risky procedures or treatments
are being administered (for example, chemotherapy treatments
or surgeries). This is also true when experimental procedures
are being utilized for treatment. Under such circumstances,
the informed consent form is commonly drafted in accordance
with the human-subject research requirements.
All physicians providing infertility treatment or working
in the field of assisted reproduction are bound by this
standard and must ensure that their patients give informed
consent to any intervention.
(ii) Licensure:The practice of medicine is
regulated under state licensing statutes. States regulate
the practice of medicine pursuant to their authority to
defend the health, safety, and general welfare of the
community (the so-called “police power”).Each state has
enacted a medical practice act governing the practice
of medicine. The model Medical Practice Act (set forth
by the Federation of State Medical Boards) defines the
practice of medicine quite broadly.xl
Persons practicing medicine must be licensed by the state
to do so and are subject to the state’s Medical Practice
Act and the regulations promulgated by the licensure board.
Licensure boards oversee the initial and continuing licensure
of physicians practicing in the state. These boards are
also responsible for disciplining physicians who render
incompetent or unprofessional care in violation of applicable
regulations and standards. The Federation of State Medical
Boards, in cooperation with the National Board of Medical
Examiners, creates and administers the required United
States Medical Licensing Examination (USMLE).
Physicians engaged in the field of reproductive medicine
must be licensed by their state as a condition of practicing.
This is the chief mechanism of regulation for the practice
of assisted reproduction.
(iii) Registration with DEA:All physicians,
including those working in the field of reproductive medicine,
are required by the Controlled Substances Act134to
register with the United States Drug Enforcement Agency
(DEA) if they will be prescribing or dispensing controlled
substances. The Controlled Substances Act is a federal
criminal statute. DEA registration permits physicians
to possess and dispense (prescribe) controlled substances
and certain listed chemicals to patients and research
subjects to the extent authorized by their registration
and in conformity with the Controlled Substances Act and
related regulations.There are state law counterparts to
the Controlled Substances Act that may impose additional
requirements on physicians beyond the federal law.
(iv) Hospital credentialing:Any practitioner
seeking to practice in the field of assisted reproduction
at a hospital is required to apply for medical staff privileges.
The process for obtaining privileges is often referred
to as “credentialing” because it is a method of ensuring
that a physician has the appropriate credentials prior
to granting permission to practice at a hospital. The
credentialing process is set forth in a hospital’s medical
staff bylaws. At a minimum, initial credentialing includes
a lengthy application process including proof and verification
of medical education, USMLE scores, residency training,
all past employment, criminal background checks, and professional
recommendations. The hospital’s governing board must approve
all credentialing appointments and reappointments (which
by Joint Commission on Accreditation of Healthcare Organizations
[JCAHO] accreditation standards must be every two years
at a minimum), as the hospital is generally considered
legally responsible for the acts of its medical staff.
(v) Board certification: In an effort to ensure
that a hospital has only physicians practicing good medicine
and providing the appropriate “standard of care,” many
hospitals now require Board certification in order for
a physician to obtain clinical privileges in a specialty
or to be granted privileges to perform certain procedures
(for example, to practice in the field of assisted reproduction).
A hospital’s medical staff bylaws establish this requirement,
which is enforced through the credentialing appointment
and reappointment process.
(vi) National Practitioners Data Bank:The
Health Care Quality and Improvement Act135
enacted in 1986, among other things, established the National
Practitioners Data Bank. This is a national, centralized
source of information on physician disciplinary actions
related to professional competence or conduct and medical
malpractice and settlements. State licensing boards and
all licensed hospitals are required to report disciplinary
actions to the Data Bank. Hospitals have a statutory duty
to request information from the Data Bank upon credentialing
a new physician for clinical privileges to practice at the
hospital and, at a minimum, every two years for every medical
staff member and privileged physician. The Data Bank is
not accessible to the public, and is accessible to plaintiff
attorneys in only very limited circumstances. This national
mechanism helps to prevent a physician found by one state
licensing board to be practicing below standard or violating
professional standards from continuing to practice medicine
legally by moving to another state.
(vii) Facility licensure:JCAHO is a
private accrediting body whose standards are voluntary
and do not have the force of law. However, the Medicare
regulations provide that a hospital’s compliance with
JCAHO standards is “deemed compliance” with Medicare’s
conditions of participation—a requirement for all hospitals
participating in the Medicare program (that is, receiving
any reimbursement from the government for the provision
of health care).136
As a result, virtually all hospitals in the United States
with more than twenty-five beds are JCAHO accredited.
These detailed standards cover hospital policy, procedures,
and operations with respect to several areas, including,
for example, clinical practice. Facilities delivering
health care are regulated by the state within which they
are located. Most states have specific standards applicable
to licensure of hospitals, clinics, free-standing surgical
centers, and other facilities where health care is provided.
Note, however, that most states do not require a doctor’s
office to be licensed as a health care facility.
(viii) Malpractice insurance coverage:As part
of the credentialing process, hospitals require physicians
to meet certain clinical standards in order to obtain
and maintain appropriate malpractice insurance. Carriers
are increasingly requiring hospitals through contract
to mandate specialty training and board certification
in order to maintain insurability for certain types of
procedures and treatments.Additionally, many states require
practicing physicians to maintain minimum levels of malpractice
insurance coverage as a condition of licensure.
(ix) Disciplinary proceedings by state
licensure board:In cases of suspected unprofessional
behavior or substandard care, the Board may investigate,
hold a hearing, and discipline physicians. Disciplinary
actions may include suspension or revocation of licensure.
Such actions are reported to the National Practitioners
In sum, practitioners in the field of assisted reproduction—like
all other physicians—must be: licensed by their states;
registered with the DEA (if they are prescribing or dispensing
controlled substances); appropriately credentialed (if they
are to practice in a hospital); Board certified (if their
hospitals require it); subject to the reporting requirements
of the National Practitioners Data Bank (if they are disciplined);
insured for malpractice (if their hospitals or states require
it); and subject to disciplinary proceedings by the state
licensure board (if appropriate). Also, like any other physicians,
those engaged in the practice of reproductive medicine must
ensure that their patients provide informed consent to all
medical treatments or interventions.
b. Litigation as regulation. Another crucial mechanism
for the regulation of the practice of medicine is litigation.
The most common litigation arising out of the context
of assisted reproduction relates to the custody or disposition
of untransferred embryos and the rights and obligations
of people standing in direct relation to these embryos.
Courts are currently struggling with how to handle such
cases, and they draw on concepts from family law, constitutional
law, and contract or informed consent law to resolve the
disputes. Several courts have encouraged clinics to assist
couples in planning and recording their preferences for
future embryo disposition if death, divorce, or other
unforeseen circumstances arise. Some courts have said
such documents should be enforced if the couple later
disagrees about embryo disposition.
In Davis v. Davis
the Tennessee Supreme Court took a slightly more nuanced
approach. The case involved a divorce-related custody dispute
over the disposition of a couple’s cryopreserved embryos.
The husband sought custody of the embryos so that he could
destroy them. The wife sought custody in order to convey
them to another couple seeking to become pregnant.xli
The Court began by noting that the embryos in question should
not be regarded legally as property or people, but rather
as occupying an interim category of “special respect.”138
It then provided an analytical framework for resolving such
[The Court should first look] to the preferences
of the progenitors [of the embryos]. If their wishes cannot
be ascertained, or if there is dispute, then their prior
agreement concerning disposition should be carried out.
If no prior agreement exists, then the relative interests
of the parties in using or not using the [embryos] must
be weighed. Ordinarily, the party wishing to avoid procreation
should prevail, assuming that the other party has a reasonable
probability of achieving parenthood by means other than
the use of the [embryos] in question. If no other reasonable
alternatives exist, then the argument in favor of using
the [embryos] to achieve pregnancy should be considered.
However, if the party seeking control of the [embryos]
intends merely to donate them to another couple, the objecting
party obviously has the greater interest and should prevail.
But the rule does not contemplate the creation of
an automatic veto, and . . . we would not wish to be
interpreted as so holding.139
Applying this rule to the facts presented,
the Court awarded custody to Mr. Davis, the husband.
Medical malpractice litigation is the primary tool available
to patients who have been harmed by a physician in the
delivery of medical services. To sustain a claim for medical
malpractice, an injured patient must demonstrate that
the defendant breached a duty owed to the patient and
that this breach resulted in harm. A physician breaches
his duty to a patient when he provides services that fall
below the recognized “standard of care.” Standard of care
is defined with respect to all applicable benchmarks,
including licensure standards, specialty protocols and
standards, and professional codes. The standard of care
has been formulated as “professional competence and care
customary in similar communities among physicians engaged
in the particular field of practice.” This duty attaches
once the physician-patient relationship is formed.
IVF is considered a specialty for purposes of the standard
of care. However, courts are sometimes reluctant to entertain
claims for harms in this context, to the extent that the
harms alleged are to persons not yet born. Moreover, it
is often difficult for claimants to demonstrate that the
actions of the clinician proximately caused the harm alleged.
For example, when an effort at assisted reproduction fails
it can be difficult to prove that the cause of such failure
was the result of the clinician’s negligence rather that
the underlying infertility.
Another tort theory on which injured parties might rely
in the context of assisted reproduction is wrongful conversion.
This theory has been invoked to sue individuals who have
destroyed in vitro embryos without the patients’ consent.
In one case, Del Zio v. Presbyterian Hospital,
a couple sued a hospital and its chief of obstetrics and
gynecology for $1.5 million for deliberately destroying
the couple’s in vitro embryos prior to implantation. In
addition to wrongful conversion, the couple alleged intentional
infliction of emotional distress. The jury awarded $50,000
to the wife for emotional distress, and the husband received
nominal damages. The jury rejected the couple’s claim
for wrongful conversion.140
Suits may also be filed for prenatal
and even preconception injuries to the unborn child. Many
states permit such suits only if the child is born alive.
Other states permit such suits only if the child was “viable”
at the time of injury. Suits on behalf of children born
through assisted reproduction can be brought as “wrongful
death” actions if the child is stillborn or born alive but
dies soon thereafter. A majority of states permit the administrator
of the estate of an unborn child to recover damages.
C. Nongovernmental Regulation
1. Safety, Efficacy, and Privacy.
The key sources of nongovernmental guidance and oversight
for the practice of assisted reproduction are the standards
propounded by ASRM, published in conjunction with its sister
organization, SART. SART clinics must agree to adhere to
these guidelines as a condition of membership. SART additionally
requires certification of its members’ embryo labs by the
College of American Pathologists, JCAHO, or the New York
State Tissue Bank program. Moreover, SART requires its members
to comply with the reporting provisions of the federal Fertility
Clinic Success Rate and Certification Act. According to
SART’s website, 95 percent of the nation’s assisted reproduction
clinics are SART members.
ASRM provides guidance by means of published statements,
opinions, and guidelines issued by its practice and ethics
committees. The chief values ASRM seeks to promote through
its opinions and guidelines are safety (of ART participants),
efficacy (of techniques and procedures), and privacy (of
ART patients). According to ASRM, these documents are framed
in a variety of ways:
Some, like the Practice Committee’s “Guidelines
for Gamete and Embryo Donation,” take the form of a list
of considerations to be made or steps to be followed, while
others take the form of a survey or review of research on
a particular medical topic, i.e., “Aging and Infertility
in Women.” Ethics Committee documents are usually framed
as a discussion of issues, sometimes leading to a particular
conclusion and other times recommending a number of approaches
based on different circumstances that can arise.141
The practice guidance documents provide direction
as to minimal standards for IVF (such as personnel requirements,
laboratory requirements, quality assurance, and control
standards). Specific examples of subjects covered by such
documents include guidelines for gamete and embryo donation,142
induction of ovarian follicle development and ovulation
with exogenous gonadatropins,145
number of embryos transferred,146
and preimplantation genetic diagnosis.147
Practice committees also evaluate novel procedures. These
committees review the existing literature on randomized
clinical trials. If two peer-reviewed published studies
show that the risk-benefit ratio is acceptable, the procedure
is elevated from “experimental” to “practice.” ICSI has
been elevated to practice status in this way, as have PGD
and blastocyst transfer.
The ethical guidelines published by ASRM address
a number of subjects including advertising,148
and disposition of abandoned embryos.150
Most are framed in terms of discussions that merely highlight
concerns rather than prescribe or proscribe specific courses
of conduct among members. However, as ASRM’s then-president,
Dr. Sandra Carson, pointed out in her presentation to the
President’s Council on Bioethics in March 2003, ASRM “actively
discourages” some procedures on ethical grounds. She gave
the examples of PGD for elective sex selection, oocyte donation
after natural menopause,xlii
posthumous reproduction in absence of advance directives,
and cloning for reproduction. Compliance of ART practitioners
with the ethical guidelines, as with the practice guidelines,
is entirely voluntary.
In conjunction with the College of American Pathologists,
ASRM has adopted a Reproductive Laboratory Accreditation
Program (RLAP). RLAP requires accredited laboratories working
with infertility programs to meet minimum standards, submit
to on-site inspections (every three years), and complete
proficiency testing surveys for evaluating performance.
The process is expensive and time consuming.
As mentioned above, in 2003 ASRM and RAND published a
study estimating the number of embryos in cryopreservation
at 400,000 in 2002. ASRM also collects information on congenital
abnormalities of IVF and ICSI births, but, according to
Dr. Carson, this process is non-rigorous and the data are
During her presentation, she noted that to undertake a comprehensive
and effective study on the association of ART with birth
defects would be extremely expensive. It would require neonatalogists,
epidemiologists, statisticians, and child development specialists.
ASRM has no current plans to undertake such a study.
ASRM committee opinions are advisory and are not formulated
as “commandments.” ASRM’s system of professional self-regulation
is voluntary and there appear to be no penalties for or
consequences of noncompliance. SART membership has a number
of requirements and conditions, but membership itself is
Recently ASRM, in conjunction with the Genetics and Public
Policy Center of Johns Hopkins University and the American
Academy of Pediatrics, has undertaken a comprehensive review
of all published materials relating to the health effects
of ART on children conceived with its aid. A report analyzing
this information is scheduled to be released in 2004. Additionally,
the American Infertility Association (a national patient’s
advocacy group for the infertile) recently announced that
it plans to collaborate with the RAND Corporation to study
the health and welfare of children conceived by IVF. The
study (which will be called “Footprints: The IVF Children’s
Health Study”) will collect general health information from
such children (on a voluntary basis) for their first three
years of life. Data to be collected will include information
relating to birthweight, multiple gestations, birth defects,
surgical procedures, and developmental milestones. The study
will include a control sample of children conceived with
the aid of intrauterine insemination (IUI). The study will
be supervised by a scientific advisory committee, including
representatives of the American Infertility Association
and RAND, reproductive endocrinologists, patient advocates,
mental health professionals, epidemiologists, pediatricians,
and the like.151
2. Safeguarding Professional Integrity and Promoting
the Ethical Practice of Medicine.
There are numerous professional medical associations
that have specific codes of practice or guidelines to which
its members agree to adhere. The most notable example
is the American Medical Association (AMA) Code of Ethics.
This code consists of the Principles of Medical Ethics,
which are adopted by the AMA’s House of Delegates, and the
Current Opinions of the Council on Ethical and Judicial
Affairs, which interpret the principles. The AMA’s Code
of Ethics is widely disseminated and has provided the most
commonly cited standard for courts, legislatures, administrative
agencies, medical boards, and other peer review entities.
Most medical societies, and virtually all state medical
societies, accept the code as the profession’s code.
The AMA has a specific code regarding assisted reproductive
which states four main principles: (1) The medical profession
should continue to develop technical and ethical guidelines
including educational materials on clinic-specific success
rates. (2) All fertility labs should participate in credible
professional accreditation and should voluntarily adhere
to ethical standards. Physicians should report unethical
behavior. (3) Patients should be fully informed of all aspects
of ART, and payment based on clinical outcome is unacceptable.
(4) Physicians practicing ART should, in any marketing materials,
accurately describe available services, success rates, fee
structures, and payment obligations.
The American Board of Obstetrics and Gynecology (ABOG)
certifies obstetricians and gynecologists in the United
States, and is one of twenty-four specialty boards recognized
by the American Board of Medical Specialties. New certificates
and maintenance of certification issued by the ABOG are
valid for six years.
ABOG has a Division of Reproductive Endocrinology and
Infertility. A reproductive endocrinologist is a sub-specialist
in obstetrics and gynecology trained to manage complex problems
relating to reproductive endocrinology and infertility.
The stated objectives of this Division are to promote health
care in this field, help maintain professional standards,
and establish standards and procedures for candidates for
The American Academy of Pediatrics (AAP) also has stated
positions that relate to the practice of assisted reproduction,
albeit in an attenuated way. AAP does not consider an in
vitro embryo a “person” or a pediatric patient. However,
one AAP statement entitled “Ethical considerations in Fetal
indicates that with recent advances in prenatal medicine,
the pregnant woman and her fetus are increasingly viewed
as two treatable patients.
How well do the current regulatory institutions and activities
address the various ethical concerns noted above? The current
regulatory landscape is a patchwork, with authority divided
among numerous sources of oversight. A first question might
be whether such a system of regulation, involving multiple
authorities, is well-suited to address the concerns. To
the extent that the harms are sufficiently grave and commonly
recognized, a uniform system might be preferable to this
patchwork one. On the other hand, to the extent that the
ethical concerns reflect matters of personal morality and
autonomy, a system of diverse or decentralized regulation
might be preferable.
The current system of regulation of assisted reproduction
is characterized not only by diverse authorities but also
by the diversity of the regulatory mechanisms brought to
bear on practitioners and participants. Such mechanisms
fall at every point on the regulatory spectrum, from criminal
enforcement by the federal government to hortatory and merely
aspirational statements of policy by professional organizations.
The objectives of current direct federal oversight of
ART are consumer protection and quality assurance for embryo
laboratories. While these are important goals, they do not
aim directly at most of the ethical concerns described above,
including the health and safety of women and children whose
lives are touched by ART. There is some federal record keeping
by the CDC regarding the practice of assisted reproduction,
focusing predominantly on pregnancy success rates at different
clinics. The CDC also collects some information regarding
the health effects of ART on women and children, but this
information has not, as yet, been publicly disseminated,
nor is the CDC legally required to publish it.
The objectives of analogous state regulation vary widely,
and include ensuring access to infertility services; policing
irresponsible clinicians; providing standards for donors
of human tissue; defining parental rights and obligations;
protecting embryonic human life; ensuring the quality of
ART practitioners; and protecting consumers of ART. Although
some of these state regulations do, in fact, aim at the
ethical concerns animating this inquiry, there is a lack
of uniformity among states, with many states providing little
regulation or none at all.
Indirect federal oversight of assisted reproduction aims
principally at the safety and efficacy of products for their
approved uses and the defense of the public against communicable
disease (FDA). However, the FDA mainly regulates manufacturers
and developers of products, and it does not reach off-label
uses in the practice of medicine. Moreover, because the
FDA’s authority is based largely on the definitions of the
articles it regulates, reaching ART seems to require some
questionable redefinition of aspects of human procreation
(for example, declaring the human embryo transferred to
a uterus to be a “drug” or “biological product”). Finally,
FDA lacks the mandate and institutional competence to make
decisions about moral and ethical concerns akin to those
at the heart of this inquiry; even securing the health and
well-being of the children born as a result of using ART
is not within FDA’s jurisdiction.
The application of CLIA, ensuring quality control in diagnostic
clinical laboratories, is minor in the context of ART labs—applying
only to andrological and endocrinological diagnostic activities
when performed for the sake of themselves; CLIA is inapplicable
when these tests are performed as an adjunct to the provision
of ART services. The FTC’s oversight of truth in advertising
and competition may promote better informed consent by ART
patients. But it does not go so far as to govern the sorts
of risks to which these individuals may be exposed.
The regulation of the practice of medicine by the states
aims at the safety of some ART participants, but seems to
neglect the health and well-being of the children produced
through ART, and it offers no guidance concerning the proper
treatment of embryonic human life. Another mechanism of
indirect regulation, namely, the tort system, is driven
by a concern for the rights and interests of injured parties.
The definitions of duty, breach, causation, and injury in
the context of assisted reproduction make this a problematic
source of regulation. While the tort system does regulate
assisted reproduction in ways that implicate the ethical
concerns raised above, an adversarial process that reduces
questions of procreation to theories of torts, contracts,
or even family law may not be adequate to or fitting for
the profound human goods at stake.
Nongovernmental regulation by ASRM is chiefly focused
on the safety, efficacy, and privacy of participants in
the ART process. ASRM provides practice guidelines and ethical
opinions to promote these values. The enforceability of
these guidelines, however, is weak. Indeed, one might argue
that the standards are merely hortatory and aspirational—evidenced
by the fact that one prominent member of SART openly
advertises a service that ASRM “actively discourages” on
ethical grounds (PGD for elective sex selection). As a substantive
matter, the guidelines provide very few direct, affirmative
protections for the well-being of the children who result
from ART, relying instead on their prospective parents to
safeguard their interests. This is certainly the norm in
most situations involving the delivery of medical care to
children. In such cases, however, the controlling criterion
is the best interests of the patient, namely, the sick child.
By contrast, in ART, the patient is the (often) infertile
individual or individuals and it is their interests that
are considered controlling. It is not necessarily the case
that the best interests of the ART patient and the resulting
children are co-extensive. Thus, using the interests of
the patient as a proxy for those of the children later born
is potentially problematic. The ASRM guidelines make no
allowance for any potential conflict of interest in this
ASRM’s animating ethical principles of safety, efficacy,
and privacy are neutral toward other relevant values. They
do not address other concerns occasioned by the growing
control over procreation conferred by the new capacities
discussed above. Nevertheless, ASRM’s ongoing effort to
review all existing literature on the health effects of
ART on children signals an increased concern and arguably
a new focus on this subject.
Finally, indirect regulation by professional medical associations
aims generally at the well-being of patients in the physician’s
care. Yet the AMA’s guidelines relating to ART do not seem
calculated to meet the ethical concerns raised above. The
same could be said of ABOG’s guidelines. The AAP guidelines
do seem to suggest that the child later born and the mother
may both be patients and thus entitled to all the attendant
duties and obligations of care. Such guidelines do not,
however, seem to reflect a concern for the use and destruction
of in vitro human embryos.
All of the foregoing professional society guidelines have
limited mechanisms of enforcement and rely primarily on
the good will of practitioners. For many of the ethical
matters of concern to this Council, beginning with the well-being
of children, existing procedures for monitoring, data collection,
or investigation are not adequate.
Due to rounding, the total does not equal 100 percent.1
There are a number of adjunct screening procedures that
may be performed at this stage of assisted reproduction
that are discussed extensively in Chapter 3.
The number of ova collected depends on a number of variables,
including the donor’s age, health, and other factors.
In some cases, ten or more ova are fertilized in a single
In GIFT, fertilization occurs in the fallopian tube, beyond
the clinician’s control.
ICSI and other forms of zona pellucida manipulation are
specialized techniques for inducing fertilization and
are adjuncts to conventional IVF.
ICSI is also indicated when sperm is acquired through
assisted sperm retrieval or in the course of a normal
IVF cycle for oocytes that have been mixed with sperm
but have not yet fertilized. Some ART clinics require
ICSI if patients desire to use preimplantation genetic
diagnosis, discussed further in Chapter 3.
Counterintuitively, the live birth rate for those cycles
using ICSI (for patients either with or without male factor
infertility) is lower than cycles in which such
patients used IVF without ICSI. See Centers for
Disease Control and Prevention (CDC), 2001 Assisted
Reproductive Technology Success Rates, National Summary
and Fertility Clinic Reports, Atlanta, GA: Government
Printing Office, 2003, pp. 40-41.
Research is currently underway on another procedure that
would help women with defective ova to conceive. The procedure,
called “ovarian nuclear transfer,” involves transplantation
of the nucleus of a fertilized ovum into an enucleated
donor fertilized ovum (including mitochondria).
There is not yet a reliable method of freezing unfertilized
ova. This is perhaps due to their large size and high
water content. Additionally, it seems that freezing an
ovum toughens the zona pellucida in a way that can inhibit
In the United States in 2001, gestational carriers were
used in 571 ART cycles.
This statistic is for never-frozen, nondonor ova or embryos—the
most common approach in 2001.
Specifically, 29.3 percent were twins, and 7.4 percent
were triplets or more. In 5.2 percent of ART pregnancies,
the pregnancy ended in miscarriage where the number of
fetuses was impossible to determine. (CDC Report, p.
20.) The rate of multiple-fetus pregnancies from ART cycles
using never-frozen donor ova was 43.6 percent. (CDC Report,
p. 50.) The rate of multiple- gestation pregnancies for
frozen nondonor embryos was 26.6 percent. (Id. at 46.)
It should be noted, however, that progress is being made
toward single- embryo transfer with retention and pregnancy
in about 34 percent of the transfers. See DeSutter,
P., et al., “Single Embryo Transfer and Multiple Pregnancy
Rate Reduction in IVF/ICSI: A Five Year Appraisal,” Reproductive
BioMedicine Online 6: 2003, http://www.rbmonline.com/Article/836
(accessed May 30, 2003).
A “cycle” is initiated when a woman begins the process
of superovulation and monitoring. (CDC Report, p. 4.)
Not all cycles result in successful ova collection, fertilization,
transfer, pregnancy, or birth.
There seems to be a negative association between cryopreservation
and implantation. For all pregnancies initiated using
frozen, nondonor embryos, the success rate was 20.3 percent
live births per transfer (19.5 percent per thaw). (CDC
Report, p. 44.) For cycles using never-frozen, donated
embryos, 43.4 percent of transfers resulted in live births.
(CDC Report, p. 49.) For frozen, donated embryos, the
success rate was 23.5 percent per transfer. (CDC Report,
Of the 3,075 live births using frozen, nondonor embryos,
26.8 percent resulted in multiple births (CDC Report,
p. 46). Of the 3,629 live births using never-frozen, donated
embryos, 41.7 percent resulted in multiple births. (CDC
Report, p. 50.) There are no such statistics for cycles
using frozen, donated embryos.
The U. S. national average for prematurity among children
born by natural means is approximately 12 percent. (March
of Dimes Survey, 2000.)
Here, we use the term “fertilized human egg” to denote
an egg that has been fertilized, but whose pronucleus
has not yet fused with that of the fertilizing sperm.
In the nucleus transfer procedure, both donor pronuclei
are transferred into the recipient egg and fuse thereafter.
Biron-Shental, T., et al., “Preliminary results of cultured
human ovaries from second and third trimester fetuses,”
presented at the 19th Annual Meeting of the
European Society of Human Reproduction and Embryology,
June 29 to July 2, 2003, Madrid, Spain (www.eshre.com).
“Stem cells can end infertility, say IVF pioneers,” NewScientist.com,
July 24, 2003, quoting Dr. Alan Trounson of the Monash
Institute of Reproduction and Development in Victoria,
Specifically, among the children in the study conceived
by IVF, 9 percent were diagnosed with a major birth defect
or defects by the age of one year. Among children conceived
using ICSI, the rate was 8.6 percent. The incidence of
such abnormalities among children in the study who were
conceived by natural means was 4.2 percent.
Researchers at Johns Hopkins University noted that among
the patients listed in the 1994 Beckwith-Wiedemann registry,
IVF conception was six times more common than in the general
population. That is, 4.6 percent of the patients in the
registry were conceived through IVF, as compared with
0.8 percent of the national population. Children with
BWS have symptoms that can include an abnormally large
tongue (which can cause respiratory difficulties), abdominal
wall defects (including umbilical hernia and protrusion
of intestine or other abdominal organs from the child’s
navel), low blood sugar, lethargy, poor feeding, seizures,
and enlargement of organs and some tissues. BWS sufferers
are predisposed to Wilms’ tumor, hepatoblastoma, neuroblastoma,
and other cancers. Despite their findings, JHU researchers
suggested that parents should not alter their plans to
use IVF. See, for example, DeBaun, M. R., et al., “Association
of in vitro fertilization with Beckwith-Wiedemann syndrome
and epigenetic alterations of LIT1 and H19,” American
Journal of Human Genetics 72: 156-160 (2003).
The discussion of one such adjunct, preimplantation genetic
diagnosis, will be deferred to Chapter 3.
This higher incidence of multiples is largely due to the
transfer of multiple embryos, rather than to the use of
IVF. But, as we have noted, IVF also produces a higher
incidence of identical twins (a result of embryo splitting),
perhaps the consequence of embryo manipulation.
Pregnancy itself increases the risks and aggravates the
duration and severity of the syndrome’s symptoms. Those
women who donate their ova to others are at much reduced
One published study concluded that in states where IVF
is covered by insurance, there are associated “decreases
in the number of embryos transferred per cycle, the percentages
of cycles resulting in pregnancy, and the percentage of
pregnancies with three or more fetuses.” Jain, T., et
al., “Insurance Coverage and Outcomes of In Vitro Fertilization,”
New England Journal of Medicine 347(9): 661 (August
It was announced in July 2003 that scientists had developed
in the laboratory ovarian tissues obtained from aborted
fetuses, which might one day provide mature female oocytes
suitable for in vitro fertilization. (Biron-Shental, T.,
et al., “Preliminary results of cultured human ovaries
from second and third trimester fetuses,” presented at
the 19th Annual Meeting of the European Society
of Human Reproduction and Embryology, June 29 to July
2, 2003, Madrid, Spain [www.eshre.com].)
In 2001, approximately 72 percent of all transfers failed
to result in birth. It bears noting, however, that there
is in the course of unassisted reproduction a very high
degree of embryo loss, much of it probably due to chromosomal
and genetic abnormalities. Because the causes of failure
in both natural and assisted reproduction are not fully
understood, it is difficult to compare the two phenomena
in a meaningful way.
Until recently, no federal money was budgeted for validation.
Instead, SART underwrote the costs of validation itself.
Macaluso, Maurizio, Division of Reproductive Health, National
Center for Chronic Disease Prevention and Health Promotion,
Centers for Disease Control and Prevention, written comments
to the President’s Council on Bioethics, May 12, 2003.
Note, however, that this provision attaches only to “fertilized
in vitro [ova].” La. Rev. Stat. Ann. § 9:129. Thus, embryos
created by means other than fertilization (for example,
embryos created by somatic cell nuclear transfer) would
not be deemed juridical persons by Louisiana law.
To prevail on a due process challenge for vagueness, the
plaintiffs must show that the statute at issue is “impermissibly
vague in all its applications” (Village of Hoffman
Estates v. Flipside, 455 U.S. 489, 497 ) and
that “men of common intelligence must necessarily guess
at its meaning and differ as to its applications” (Baggett
v. Bullitt, 377 U.S. 360, 367 ).
If HCT/Ps were “drugs,” requiring FDA approval, premarket
approval would be effectively required for all HCT/Ps
before any could be distributed to human beings (including
for clinical trials). This would effectively put all tissue
banks (including blood and sperm banks) and clinicians
working with the products of such banks out of business.
These tissues would not, however, be subject to the onerous
requirements for premarket approval. “Minimal manipulation”
was defined as “processing that does not alter the relevant
biological characteristics and, thus potentially, the
function or integrity of the cells or tissues.” (63 Fed.
Reg. 26,748 [May 14, 1998].) “More than minimally manipulated”
tissues and cells that are (1) combined with non-cellular
or non-tissue components, (2) labeled or promoted for
purposes other than their normal functions, or (3) have
systemic effect (except in cases of autologous use, transplantation
into a first-degree blood relative or reproductive use)
would require FDA’s more stringent premarket review and
approval described above.
As of February 2004 the effective date of these regulations
had been delayed.
Technically, the FDA has only the formal authority
to recall previously approved devices. Manufacturers and
distributors are likely in practice, however, to accede
to requests for voluntary recall of drugs and biological
products, so as to avoid forcible seizure of such articles
by the FDA.
Indeed, there are specific regulations governing devices
used in ART. See 21 C.F.R. § 884.6100 et seq.
Inclusion of this example is not meant to imply that practitioners
of assisted reproduction or their patients approve of
cloning to produce children.
The FDA has released no further statements on the subject
of cloning since 2001. It is not clear whether the agency
still subscribes to these jurisdictional and legal theories.
The Model Medical Practice Act defines “practice of medicine”
as: “advertising, holding out to the public or representing
in any manner that one is authorized to practice medicine
in the jurisdiction; offering or undertaking to prescribe,
order, give or administer any drug or medicine for the
use of any other person; offering or undertaking to prevent
or to diagnose, correct or treat in any manner or by any
means, methods, or devices any disease, illness, pain,
wound, fracture, infirmity, defect or abnormal physical
or mental condition of any person, including the management
of pregnancy and parturition; offering or undertaking
to perform any surgical operation upon any person; rendering
a written or otherwise documented medical opinion concerning
the diagnosis or treatment of a patient or the actual
rendering of treatment to a patient within a state by
a physician located outside the state as a result of transmission
of individual patient data by electronic or other means
from within a state to such physician or his or her agent;
rendering a determination of medical necessity or a decision
affecting the diagnosis or treatment of a patient; and
using the designation Doctor, Doctor of Medicine, Doctor
of Osteopathy, Physician, Surgeon, Physician and Surgeon,
Dr., M.D., D.O. or any combination thereof in the conduct
of any occupation or profession pertaining to the prevention,
diagnosis or treatment of human disease or condition unless
such a designation additionally contains the description
of another branch of the healing arts for which one holds
a valid license in the jurisdiction.”
Earlier in the divorce proceeding, the wife argued that
she wanted custody so that she could transfer the embryos
to her own uterus in an effort to become pregnant.
This guideline is currently being re-evaluated.
In her March 7, 2003, presentation to the President’s
Council on Bioethics, Dr. Carson said: “[SART, ASRM, and
CDC do] collect [data relating to] congenital anomalies
of IVF and ICSI births. However, it is a non-rigorous
collection. The data that we do collect we feel is inadequate
to come with a truly scientific evidence based review
of the birth defect risks. It’s a start, but it’s not
the best we can do.”
Centers for Disease Control and Prevention (CDC), 2001
Assisted Reproductive Technology Success Rates, National
Summary and Fertility Clinic Reports, Atlanta, Georgia:
Government Printing Office, 2003, p. 14.
Depypere, H., et al., “Intracellular pH Changes During Zona
Drilling,” Fertility and Sterility 61: 319 (1994).
Catt, J., et al., “Subzonal Insertion of Multiple Sperm
Is a Treatment for Male Factor Infertility,” Fertility
and Sterility 61: 123 (1994).
Barritt, J., et al., “Cytoplasmic Transfer in Assisted Reproduction,”
Human Reproduction Update 7: 428-435 (2001).
Edwards, R., et al., “Destruction of Cryopreserved Embryos:
UK Law Dictated the Destruction of 5000 Cryopreserved Human
Embryos,” Human Reproduction 12: 3 (1997).
Hoffman, D., et al., “Cryopreserved Embryos in the United
States and Their Availability for Research,” Fertility
and Sterility 79: 1063-1069 (2003).
CDC Report, op. cit., p. 45.
Hoffman, D., et al., op. cit.
Van Voorhis, B., et al., “The Efficacy and Cost Effectiveness
of Embryo Cryopreservation Compared with Other Assisted
Reproductive Techniques,” Fertility and Sterility
64: 647 (1995).
Gardner, D. K., et al., “Culture and Transfer of Human Blastocysts
Increases Implantation Rates and Reduces the Need for Multiple
Embryo Transfers,” Presentation at the October 1997 annual
meeting of the American Society for Reproductive Medicine,
Scott, R., et al., “Embryo Quality and Pregnancy Rates in
Patients Attempting Pregnancy Through In Vitro Fertilization,”
Fertility and Sterility 55: 426 (1991).
CDC Report, op. cit., p. 71.
See generally, CDC Report, op. cit., p.74
New York State Task Force on Life and the Law, Assisted
Reproductive Technologies: Analysis and Recommendations
for Public Policy, New York: New York, 1998, p. 63.
CDC Report, op. cit., p. 37.
NYSTF Report, op. cit., p. 69.
See, for example, NYSTF Report, op cit. p.
71 (citing R.L. Berkowitz, et al., “First-Trimester Transabdominal
Multifetal Pregnancy Reduction: A Report of Two Hundred
Completed Cases,” American Journal of Obstetrics and
Gynecology 169: 17, 18 ; R. Maymon, et al., “First
Trimester Embryo Reduction: A Medical Solution to an Iatrogenic
Problem,” Human Reproduction 10: 668 ).
CDC Report, op. cit., p. 17.
31. McElrath, T., et al., “Fertility Therapy and the Risk
of Very Low Birth Weight,” Obstetrics and Gynecology
90: 600 (1997); Mullen, M., “Medically Assisted Reproductive
Technologies: A Review,” Research Studies of the Royal
Commission on New Reproductive Technologies 9: 47 (1993).
32. Rufat, P., et al., “Task Force Report on the Outcome
of Pregnancies and Children Conceived by In Vitro Fertilization
(France: 1987 to 1989),” Fertility and Sterility
61: 324 (1994).
NYSTF Report, op. cit., p. 70.
Zhang, J., et al., “Pregnancy derived from human nuclear
transfer,” presented at the 59th annual meeting
of the American Society for Reproductive Medicine, October
11-15, 2003, San Antonio, Texas.
Biron-Shental, T., et al., “Preliminary Results of Cultured
Human Ovaries from Second and Third Trimester Fetuses,”
19th annual meeting of the European Society of
Human Reproduction and Embryology Final Program (June 30,
2003), p. 50.
Gleicher, N., “Blastomere Transplantation as a Possible
Treatment,” 19th annual meeting of the European
Society of Human Reproduction and Embryology Final Program
(July 1, 2003), p. 93.
See interview with Dr. Helen Liu at the 57th
annual meeting of ASRM, Orlando Florida, October 22-24,
2001 (available online at http://www.obgyn.net/displaytranscript.asp?page=/avtranscripts/asrm2001-liu);
see also, press release: “Highlights from the 57th
Annual Meeting of ASRM: Engineering Uterine Lining Tissue
Outside the Uterus” (October 22, 2001); see also,
Paula Moyer, “Engineered Endometrial Tissue May Provide
New Infertility Therapies,” Reuters Health Medical News,
October 24, 2001.
See Racho El-Akouri, R., “Normal Pregnancies Achieved
in Transplanted Murine Uteri after Long-Term Cold Preservation,”
19th annual meeting of the European Society of
Human Reproduction and Embryology Final Program (July 2,
2003), p. 120; see also, Rick Weiss, “Saudi Surgeons
Perform Human Uterus Transplant,” Washington Post,
March 7, 2002, Page A08.
See Edwards, R., et al., “Current Status of In-Vitro
Fertilisation and Implantation of Human Embryos,” Lancet
2: 1265-1269 (1983); and Gould, K., “Ovum Recovery and In
Vitro Fertilization in the Chimpanzee,” Fertility and
Sterility 40: 378-383 (1983).
Van Steirteghem, A., et al., “High Fertilization and Implantation
Rates After Intracytoplasmic Sperm Injection,” Human
Reproduction 8: 1061-1066 (1993).
Hewitson, L., et al., “Unique Checkpoints During the First
Cell Cycle of Fertilization After Intracytoplasmic Sperm
Injection in Rhesus Monkeys,” Nature Medicine 5:
431-433 (1999); Kimura, Y., et al., “Intracytoplasmic Sperm
Injection in the Mouse,” Biology of Reproduction
52: 709-720 (1995).
Schatten, G., “Safeguarding ART,” Nature Cell Biology
& Nature Medicine S19—S22 (2002).
Winston, R., et al., “Are We Ignoring Potential Dangers
of In Vitro Fertilization and Related Treatments?” Nature
Cell Biology & Nature Medicine S14-S18 (2002).
American Society for Reproductive Medicine press release,
“Highlights from ASRM 2002: The 58th Annual Meeting
of the American Society for Reproductive Medicine, October
12-17, 2002—Seattle, Washington; 170,000 Babies Born in
USA from ART since 1985: Success Rate More Than Doubled
in That Time,” October 14, 2002, http://www.asrm.org/Media/Press/170000babies.html
(June 1, 2003).
Hansen, M., et al., “The Risk of Major Birth Defects After
Intracytoplasmic Sperm Injection and In Vitro Fertilization,”
The New England Journal of Medicine 346: 725 (2002).
Bonduelle, M., et al., “Neonatal Data on a Cohort of 2889
Infants Born After ISCI (1991-1999) and of 2995 Infants
Born After IVF (1983-1999),” Human Reproduction 17:
671 (2002); see also Bergh, T., et al., “Deliveries
and Children Born After In-Vitro Fertilisation in Sweden
1982-1985,” Lancet 354: 1579-1585 (1999).
Moll, A., et al., “Incidence of Retinoblastoma in Children
Born After In-Vitro Fertilisation,” Lancet 361: 309-310
Bergh, T., et al., op. cit.
Mestel, R., “Some Studies See Ills for In Vitro Children:
Evidence of Increases in Eye Cancer and Mental Retardation
Needs to be Verified,” Los Angeles Times, January
24, 2003, Page A1.
Johns Hopkins Medical Institutions press release, “In Vitro
Fertilization May Be Linked to Bladder Defects,” March 18,
2003/March/030318A.htm (April 28, 2003), quoting the
study’s senior author, John P. Gearhart, M.D., “These defects
are extremely rare, and our preliminary findings should
not alone discourage couples from undergoing IVF.”
Josserand, R. N., et al., “Cystic Fibrosis phenotype evaluation
and paternity outcome in 50 males with congenital bilateral
absence of vas deferens,” Human Reproduction 16:
2093-2097 (2001); Robert F., et al., “Relation between the
anatomical genital phenotype and cystic fibrosis transmembrane
conductance regulator gene mutations in the absence of the
vas deferens,” Fertility and Sterility 77: 889-896
Oates, R. D., et al., “Clinical characterization of 42 oligospermic
or azoospermic men with microdeletion of the AZFc region
of the Y chromosome, and of 18 children conceived via ICSI,”
Human Reproduction 17: 2813-2824 (2002).
Hansen, M., et al., op. cit.; Bonduelle, M., et al.,
Winston, R. et al., op. cit.
Mestel, R., op. cit.; see also, Winston, R.
et al., “Are We Ignoring Potential Dangers of In Vitro Fertilization
and Related Treatments?” Nature Cell Biology
4 (S1), S14-S18 (2002), Nature Medicine 8 (S1), S14-S18
(2002) op. cit. (citing Kwong, W.Y., et al., Development
127, 4195-4202 ).
See Winston, R. et al., op. cit. (citing Ho,
Y., et al., Molecular Reproduction and Development
41(2): 232-238 ; Niemann, H., et al, Theriogenology
53: 21-34 ).
Winston, R., et al., op. cit. (citing Doherty, A.S.,
et al., Biological Reproduction 62: 1526-1535 (2000);
Khosla, S., et al., Human Reproduction Update 7:
Winston, R., et al., op. cit.
Schatten, G., “Safeguarding ART,” op. cit.
Slotnick, R., et al., “Monoamniotic Twinning and Zona Manipulation:
A Survey of U.S. IVF Centers Correlating Zona Manipulation
Procedures and High-Risk Twinning Frequency,” Journal
of Assisted Reproduction and Genetics 13: 381 (1996).
CDC Report, op. cit., p. 20; Wilcox, L., et al.,
“Assisted Reproductive Technologies: Estimates of Their
Contribution to Multiple Births and Newborn Hospital Days
in the United States,” Fertility and Sterility 65:
CDC Report, op. cit., p. 20.
Haning, R., et al., “Effects of Fetal Number and Multifetal
Reduction on Length of In Vitro Fertilization Pregnancies,”
Obstetrics and Gynecology 87: 964-966 (1996).
Martin, J., et al., “Triplet Births: Trends and Outcomes,
1971-1994,” Vital and Health Statistics. Series 21, Data
from the National Vital Statistics System 21: 1-20 (1997).
NYSTF Report, op. cit., p. 74.
Barker, D., “The Wellcome Foundation Lecture, 1994: The
Fetal Origins of Adult Disease,” Proceedings of the Royal
Society of London, Series B, Biological Sciences 262:
Helmerhorst, F., et al., “Perinatal Outcome of Singletons
and Twins after Assisted Conception: A Systematic Review
of Controlled Studies,” British Medical Journal,
doi:10.1136/bmj.37957.560278.EE (published January 23, 2004);
Schieve, L., et al., “Low and Very Low Birth Weight in Infants
Conceived with Use of Assisted Reproductive Technology,”
The New England Journal of Medicine 346: 731-737
Evans, M., et al., “Efficacy of Transabdominal Multifetal
Pregnancy Reduction: Collaborative Experience Among the
World’s Largest Centers,” Obstetrics and Gynecology
82: 61 (1993).
NYSTF Report, op. cit., p. 71.
Haning, R., et al., op. cit.; Lee, J., et al., “Obstetric
Outcomes of Twin Pregnancy after Multifetal Pregnancy Reduction
(MFPR) Are Affected by Initial Number of the Fetuses,” presentation
at the Annual Meeting of the American Society for Reproductive
Medicine, October 18-22, 1997, Cincinnati, Ohio.
Geva, E., et al., “Multifetal Pregnancy Reduction: A Possible
Risk Factor for Periventricular Leukomalacia in Premature
Newborn,” presentation at the annual meeting of the American
Society for Reproductive Medicine, October 18-22, 1997,
Delvigne, A., et al., “Systematic Review of Data Concerning
Etiopathology of Ovarian Hyperstimulation Syndrome,” International
Journal of Fertility and Women’s Medicine 47: 211-226
American Society for Reproductive Medicine, Practice Committee
Report, “Induction of Ovarian Follicle Development and Ovulation
with Exogenous Gonadotropins,” 1998,
2, 2003); Millican, L., testimony before the Senate Health,
Education, Labor, and Pensions Committee, April 24, 2002.
Verlaenen, H., et al., “Singleton Pregnancy After In Vitro
Fertilization: Expectations and Outcome,” Obstetrics
and Gynecology 86: 906 (1995).
NYSTF Report, op. cit., p. 70.
Collins, J., “A Couple with Infertility,” Journal of
the American Medical Association 274: 1159 (1995).
Hübner, K., et al., “Derivation of Oocytes from Mouse Embryonic
Stem Cells,” Science 300: 1251-1256 (2003).
Biron-Shental, T., et al., “Preliminary results of cultured
human ovaries from second and third trimester fetuses,”
presented at the 19th Annual Meeting of the European
Society of Human Reproduction and Embryology, June 29 to
July 2, 2003, Madrid, Spain (www.eshre.com).
Pub. L. No. 102-493, 106 Stat. 3146, codified at 42 U.S.C.
§ 263a-1 et seq.
42 U.S.C. § 263a-1(a).
42 U.S.C. § 263a-7(1).
65 Fed. Reg. 53,312 (September 1, 2000).
Madsen, P., American Infertility Association, letter to
the President’s Council on Bioethics, September 30, 2003;
see also Madsen’s public comments at the January
16, 2004, meeting of the President’s Council on Bioethics,
Washington, D.C., available at www.bioethics.gov.
Quoted in Shannon Brownlee, “Designer Babies,” Washington
Monthly, March 1, 2002.
See, Schulman, Joseph D., “What’s Your Success Rate?:
Understanding IVF Pregnancy Statistics: Part I,” published
by The Genetics and IVF Institute (available at http://www.givf.com/success.cfm).
42 U.S.C. § 263a-7(2).
64 Fed. Reg. 39,374-01 (July 21, 1999).
42 U.S.C. § 263a-2(i).
See, for example, Fla. Stat. Ann. § 742.11 et seq.;
La Rev. Stat. Ann. 9:126; Va. Code Ann. § 20-156 et seq.;
Wash. Rev. Code Ann. 26.26.700 et seq.
N.H. Rev. Stat. § 168-B:13.
18 Pa. Cons. Stat. Ann. § 3213(e).
N.M. Stat. Ann. § 24-9A-1 et seq.; La. Rev. Stat. Ann. 9:121
et seq.; S.D. Codified Laws § 34-14-17.
N.M. Stat. Ann. § 24-9A-5.
N.M. Stat. Ann. § 24-9A-1.
Reilly, C., “Constitutional Limits on New Mexico’s In Vitro
Fertilization Law,” New Mexico Law Review 24: 125-144
See generally, Lifchez v. Hartigan, 735 F.
Supp. 1361 (N.D. Il. 1990); Margaret S. v. Edwards,
794 F. 2d 994 (5th Cir. 1986); Jane L. v. Bangerter,
102 F. 3d 1112 (10th Cir. 1996).
Lifchez v. Hartigan, 735 F. Supp 1361, 1377 (N.D.
See generally, 21 U.S.C. § 301 et seq. (“Federal
Food, Drug and Cosmetic Act”); 42 U.S.C. § 201 et seq. (“Public
Health Services Act”).
42 U.S.C. § 264 (known as “Section 361” of the Public Health
21 U.S.C. § 321(g)(1).
Merrill, R., “Human Tissues and Reproductive Cloning: New
Technologies Challenge FDA,” Houston Journal Health Law
and Policy 3: 1-86 (2002), citing 21 U.S.C. § 355(b).
The specific FDA protections for human subjects involved
in clinical trials are discussed extensively in Chapter
42 U.S.C. § 262(a)(1)(A).
42 U.S.C. § 262(a)(C).
63 Fed. Reg. 26,744 (May 14, 1998).
21 C.F.R. § 1271.15.
42 U.S.C. § 262(a)(2)(A) and 21 U.S.C. § 355(f).
42 U.S.C. § 262(f) and 21 U.S.C. §§ 332, 333, and 334.
37 Fed. Reg. 16,503 (1972).
United States v. Evers, 643 F. 2d. 1043 (5th Cir.
1981). See also, United States v. Evers, 453
F. Supp. 1141 (M.D. Ala. 1978) (stating that Congress did
not intend for the FDA to interfere with the practice of
For an exhaustive analysis of the FDA’s exercise of jurisdiction
in the context of human cloning, see Merrill, R.,
Zoon, K., testimony before the Subcommittee on Oversight
and Investigations of the Committee on Energy and Commerce,
House of Representatives, March 28, 2001; see also,
Merrill, R., op. cit.
See, for example, Mass. Gen. Laws Ann. ch.111
21 U.S.C. § 801 et. seq.
42 U.S.C. §§ 11101-11152.
See 42 U.S.C. §§ 1395x(e), 1395bb.
842 S.W.2d 588 (Tenn. 1992).
Del Zio v. Presbyterian Hospital, 74 Civ. 3588 (S.D.N.Y.
April 12, 1978).
Rebar, R., American Society for Reproductive Medicine, written
comments to the President’s Council on Bioethics, April
See,for example, “2002 Guidelines for Gamete and
Embryo Donation: A Practice Committee Report,” Fertility
and Sterility, 77(6), Suppl. 5 (June 2002).
“Does Intracytoplasmic Sperm Injection (ICSI) Carry Inherent
Genetic Risks?” ASRM Practice Committee Report (November
“Elements to be Considered in Obtaining Informed Consent
for ART,” ASRM Practice Committee Report (1998).
“Induction of Ovarian Follicle Development and Ovulation
with Exogenous Gonadotropins,” ASRM Practice Committee
“Guidelines on Number of Embryos Transferred,” ASRM Practice
Committee Report (November 1999).
“Preimplantation Genetic Diagnosis,” ASRM Practice Committee
Report (April 2001).
“Guidelines for Advertising by ART Programs,” ASRM Practice
Committee Report (October 1999).
“Informed Consent and the Use of Gametes and Embryos for
Research,” ASRM Ethics Committee (1997).
“Disposition of Abandoned Embryos,” ASRM Ethics Committee
Report (July 1996).
March 2, 2004, letter from Pamela Madsen, Executive Director
of the American Infertility Association, to O. Carter Snead,
General Counsel, the President’s Council on Bioethics.
American Academy of Pediatrics, Fetal Therapy—Ethical
Considerations, May 1999, http://www.aap.org/policy/re9817.html
(accessed June 3, 2003).