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OCR for page 15
C=PIER 1
IN Vet ~:L:[Z~ON AND EME~O MANS'
AND SOCCAL OONCE3~
lee scientific Alvarez that today permit clinicians arm
veteri~~ariar~ o 11~ SUM pi as dmg therapy, laser surgery,
artificial initiation, in vitro fertilization, arm embryo transfer to
cx~t human infertility or improve the primitive capabilities of
valuable animals are the results of the work of generations of
investigators. Sometimes Muse achievements came ~ because of
r~ a; at resolving Specific Prague; ream ~ human inferLili~r
or Card enabling livened atoners to improve the reman on their
invesbrents. Ire often, hover, sci~cific add rat frmn ~
inquiries of scientists investigating fatal biological per ~ a=== In
Me he of Specific applications. mus, ~ work of investigators
areas such as physiology, morphology, endocrinology, molecular biology,
develcpmental biology, and biochemistry have contributed to improvements
in the treatment of infertility and to progress in assisted conception in
humans and other animals.
Just ~.c the findings of scientists Ruin answers to—tic science
questions often oc~ntribute in ~t~ ways, the work of t:h~ pushing
the frontiers; of musically ~~=is~ corrosion has applications beyond the
limited Her of maples with infertility problerrE; do can benefit
directly. mere are e ~ tations that, in the future, the work being done
to improve the practice of in vitro fertilization and embryo transfer
(IVFET) will enable practitioners to identify genetic defects in embryos
without damaging them, and to quickly determine the sex of embryos so that
those with sex-linked genetic diseases can be identified at a very early
stage. me stress of abortion later in a pregnancy could be avoided.
this chapter briefly airlines sad major areas ~ which adders
research In Chic reproductive biology and IVAN wand make large
contributions.
Infertility
Infertility Is defined in mark ways. most often the word is 11~ to
denote the inability of a An to chive after scare months (12 to 24)
of inters without contraception, or the inability to carry a
pregnancy to term. Am)rdi~ to a Try by the National Center for
Health Statistics (Nat;), sane 8.2 Perot of An of dhildbearir~ age
(4.4 million) suffered fan "impaired f~n~dity" In 1982- the latest delta
available. -this category include curer 800, 000 An who said Cat it was
impassible for them to have a baby because of accidents or our
unexplained reasons. Also ir~cl~d are 2.9 million wan defined as
OCR for page 16
"subfecund" who said that it was physically difficult for them to conceive
or deliver a baby, and 650,000 sexually active women who reported that
they did nct use contraception and did not hQfnme pregnant within 36
months. Defining as infertile couples those who were continucusly
married, had not used contraception, and had not conceived during the
pry 12 months, ICE; Dory that 2.3 million warren were infertile
~ 1982. This represents a Kline fraa 11 percent of an In 1965 to 8
percent In 1982. Hoer, primly of infertility are not diminish for
all sections of the probation. me overall decline masks an Case In
infertility ardors women urger 30 year:; of age, arm an insane face
a~r~x~nat=ly 700,000 to nearly me million infertile cables with no
children (National Cents for Health Statistics, 1985~.
Alth - ah these figures give a rough approximation of the feamdity of
an ~ 1982, they do not indicate the mob of men and women who want a
child and are experiencir~ difficulty conceiving. Mbre than half of ye
aver 4.2 million wan who have been surgically sterilizer] for
r~on-contrac~ptive reasons, and half of the 4.4 million who have impaired
fecundity, say they would like to become pregnant (Fuchs and Perreault,
1986~.
The magnitude of the problem of human infertility is further
reflected ~ data on ceding care for infertility. Although not all
infertile individuals seek treatment, by one estimate $1 billion was spent
in 1980 on medical serving for infertility treatment (Office of
Technology Assessment, 1988b). In 1982, 1 ~ llion women between the ages
of 15 and 44 who were or had been married reported at least one
infertility visit during the past year (FUChs and Perreault, 1986~. A
similar estimate is prc~uced by a survey of primary care and reprc~uctive
care specialists in 1987 whit indicated that they treated approximately
1.2 mi11ion patients for infertility (Office of Technology Assessment
1988a).
Infertility is not confined to problems experienced by women. By one
estimate, about half of infertility problems are due in whole or In part
to problems of the male (FuChs and Perreault, 1986~. Indeed, over 80
percent of the wan seeking artificial sedition did so because of the
infertility of their male partner, arm approxi~ly 65,000 children were
conceived by artificial insertion during a 12-~nth period ~ 1986-1987
(Office of Technology Ant, 1988a).
Although the emotions toll of infertility carrot be appreciated Luau
these data, in recent years the communications Iota have begun to portray
saw of the distress of childlessness, arx] groups such as Twelve, begun
~ 1973, have r~r~ed ~ the emotional suborn newer by child
couples. Equally telling are we laths to With individuals will go in
attesting to conceive. The many ads Spent ur~ergoing diagr=;tic
pa ~ rue can be followed by additional efforts of dn ~ therapy, surgery,
and finally the physical, financial, and psychological stress of IVFET.
- 16 -
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IVEEr ~ a Ex~;sible solution to infertility for only a Snow
of copies. py one estimate, as ~ as 10 ~ 15 percent of infertile
copies who cold not be stressfully treated by other owns Scold be
offer Acre throw IV=r or by a related technology, gamete
~ntrafallqpian tea nsfer (Gate) (Office of T ~ nology As ~ s ~ nt, 1988b).
Indications for Face of [VFET are quite specific and include tube Ice
that has not responded to other t ~ ins, endometriosis, oligFEperm~a,
oervir~l mucus abnormalities and unexplained infertility. Indications for
GIFT are more limited becalms= it can only be used when fallopian Ethic are
normal. As knowledge expands, ~-C=isbed conception of all sorts ~
Item to became applicable to a wider parse of indications. Iv~r can
be applied r~ar~-~= of whether fallopian tubes are present, therefore it
is possible that Iv~r will fine a major therapy relative to the lard
nuder of individuals with infertility prowls (Jorge, 1989~. Ever,
Heat that a*var~es the practice of IV=r will at the same time promote
under starship of human rep ~ :ioa1 and has the potential of advancing
cipher forms of infertility treatment as well as providing better meth 0=
of contraception. As noted by a recent comprehensive study of
infertility, "Even as infertility treatments become more sophisticated and
complex, basic knowledge of the male and female reproductive process
remains lacking. Further research stands as a prerequisite in order for
dramatic improvements in infertility treatment to occur" (Office of
Technology Assessment, 1988b).
Treatments for Infertility
Infertility can be treated in a variety of ways, including ensuring
that the infertile couple know how to pinpoint the time of ovulation,
eliminating causes of infertility such as infectious diseases or
endometriosis, evaluating sperm seminal fluid, using fertility drugs to
induce ovulation, performing surging repair procedures in the male or
female, and emptying artificial ir~oination. Before Hiss
Suction t~rK>logies are att~ a seaward Suction is cord
which includes hormonal evaluation, ~ometrial biopsy,
hyst~alpingcgram, diagnostic Apart. Alternate therapy sub as
micro Logical corrections of tube d ~ ase or endometriosis might be
attempted. At least two noncoital reproductive technologies have been
intrc~uced In the last ten years. The major technologies are in vitro
fertilization and embryo transfer (IVFET) and gamete intrafallqpian
transfer (GIFT). mese technologies for establishing a pregnancy are
reviewed In detail in a variety of recent publications (Office of
Technology Assessment, 1988b; Seibel, 1988). TO facilitate the
~3i~ of the reward agenda pried in this report, a brief
review of He sips Citizen curing IVETT, Giver and sane other Lathes of
assisted conception foliate.
OCR for page 18
In Vitro Fertilization and Embryo Transfer
[VFET can be used to overcome infertility caused by numerous
conditions including tubal disease, endometrios ~ and olig ~ ia. A
first step in IVFET is to prepare the woman for removal of eggs
(oocybes) Two methods are And to accomplish this. Sometimes oocybes
can be obtained during a natural cycle of a woman by determining the time
of the marked increase In the Ju~inizir~ harn~ne level in the blood,
which precedes ovulation by abaft 1 l/2 days. Using a natural cycle,
hover, frequent blood samples nest be analyzed to exactly pinpoirrt the
ir~:e in this honoree fired. Curly one mature egg is usually Staid
by this method. Alternatively, fo1li~lar go ~ h are mat ration, which
leads to ovulation, can be induced by the use of various fertility drugs
such as human mencpau=~1 ganadakrephin. The subsequent development of
ovarian follicles can be monitored by ultrasound and by measuring blood
estrogen levels. By this method, which is most commonly used today, more
than one ooc~ Is stimulated to develpE? arm can be hairy for
fertilization.
Just before the timed ovulation ~d char, Locates am Caved fen
the ovary either la~r~ or by rile aspiration guided bar
ultrasorx~ra~hy. me eggs, with their adherent reverse cells, are places in
a petri dish so that their state of maturation can be as ~ s ~ using the
state of dispersion of the attached Otis as a marker. Fertilization of
the mature egg is accomplished by incubation for approximately 24 hours
the petri dish with washed sperm that have been treater to ensure
capacitation. Fertilization is defined by the visible presence of two
pronuclei in the newly formed zygote.
m e first cleavage of the zygote occurs approximately 1 1/2 days
after insemination. A catheter is used to transfer the dividing embryo
into the lumen of the uterus at somewhere between the 2- and 16-cell
stage. TO supplement the natural lutes phase, hormones such as
progesterone are sometimes administered after transfer of the embryo, (or
embryos if Are Can one oocyte has been fertilized) to the uterus.
Ear is established Hen the developing embryo implants itself irrto
the wall of the uterus. Implantation can be documented by a measure
impose In blood levels of human dhorion~c gonadotrophin.
Sc~netimes, a greater ~ of mature eggs are hat than can
usefully be implanted. ~ reasingly, these ego=== ~ gs are fertilized art
preserved by cryc preservation for subsequent use.
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Ganete l~trafall~ian Transfer
In 1985, Ash et al. (1985) reported on gamete int~fall~pian
transfer (G]P'1') as a new treatment for infertility. In 1987, he At
Aced that Girl had bed readily aged In to clinic practice (text,
1987). GIIT involves the transfer of eggs and Sperm into patent fallopian
he so that fertilization may take place in viva. Folliallar Growth of
Axles and retrieval are performed In a mare similar to that ~~ for
IV=r. grin Is c~llec~d and placed In a catheter with the 6~, which
are then transferred to the fallopian tubes. In 1987, GIFT was achieving
a higher sub= rate than IVEET. Al~cha~h this might have bun due to
the better conditions of In viva fertilization, ~ r ~ to In vitro, it
may also have been due to patient selection. G1P '11 requires that at 1-ass
ane fallopian tube be patent and that a sufficient number of normal sperm
can be obtained (Lancet, 1987~. By 1987 there was a report of ~Kx~=fu
use of GIFT ~ th donated oocytes (Craft et al. 1987~. Gift can be used
when infertility is caused by such factors as endometrios~s, premature
Ovarian failure, oligospermia, and unexplained infertility (Office of
Technology Assessment, 1988b).
Donated Gametes or Conoepti
Sometimes the donation of spermatozoa, eggs, or in some Rae===
fertilized zygotes, are necessary. Excess eggs collected from one female
donor patient undergoing IVFET can be fertilized and implant ~ in a
recipient uterus which has been synchronized with the donor's cycle.
Artificial insemination using donor spermatozoa is a common technique.
The results of one survey indicate that each year about 30~000 babies are
born from artificial insemination using donor spermatoza (Office of
Technology Assessment, 1988a).
Two leas frequently TYPO methods of treatment for infertility that
also involve the manipulation of eggs or embryos are tubal ovum transfer
and embryo ravage and transfer. Egg stimulation and harvesting are
undertaken as in [VFET and GIFT. The egg is then reins orbed below
fallopian tube blockage or cipher damage and fertilization takes place in
viva (Office of Technology Assessment, 1988b).
In embryo lav age and transfer fertilized eggs are flushed out and
removed by a special catheter. m ey are then transferred to a recipient
whose cycle has been synchronized to be reedy for the introduced egg.
This technique is gig 1~= fray USA, partly because of fears
abaft transmission of virus arm be risk of Cocaine embryos rating In
pr~nar~y In the Torpor.
— 19 —
OCR for page 20
~ntra~ion
h3v~s ~ Me basic science ~t ~d improve the clinics
practice of ~.mcis~ corrosion, sum as improve<] ur~sb~i~ of ~
Panics of ~ implantation, ~161 be likely, at the same time, to help
in Me sears for bear c~rac~ive ~nologics.
Contraceptive reshows range from rhythm mess, the oontra~ive
sense, birth control pills, arm intrauterine device to surgical
sterilization arx] barrier ~:hods, incises I;, ~rmici~C,
cervical cam, and cliaphra~n~. Mare than half of Africa Karen aged 15
44 year; use saw form of Oration, at a ~ of $2.4 bionics
1982 (Fuchs arx] ~rreault, 1986~. Indite this widespread use of
oc)ntrac~ption, there ~ma~n unsolved prnblmE; of safety, efficacy, and
a~bility for each type of Curative.
~ seat for improved form of contraception ~ Purred net only }fly
the desire of ir~ivi*uals for Iron over their r~pr~uctive live;, but
also by the social cats of unwanted pregnancies art the pr ~ of
fast-growing populations in countries whose Amiss are unable to
provide an adequate standard of living for their present population.
Countries have several options of how to cut their rate of population
growth, according to a study by the Office of Technology Assessment
(1988c), but the only solution that is both morally tenable and forcible
Is to lower fertility rates. Contraceptive use Is by far the most
important weans of attaining that goal.
Agriculture
In 1890, Walter Hoe wrote the first paper on transfer of a
fertilized egg, stating, "In this preli~ note I with merely to ~rd
an experiment by which it is The n that it is possible to ~ ke BURP of the
uterus of one variety of rabbit as a medium for the growth and obsolete
fetal development of fertilized ova of another variety of rabbit." (Heape
cited in Adams, 1982~. It was not until 1932 that a su-~-n-==cful transfer
in a larger animal, a goat, was reported. Only after the second World War
was the potential for application of the techniques for livestock
improvement end production realized (Adams, 1982~. In1981, it was
reared ~ Science that a '~timillion collar icy centered on
~very, in vitro An are, and trar~;fer of bovine curios has evolved
aver the last diode." This fast groins activity had developed in lo
than a decade into a $20 million a year iffy (Seidel, 1981). By 1985,
a.c-=isted Option was the rearm in dairy axes, with 70 percent fertilized
by artificial Action; 100,000 embryo transfers vow performed In the
United Staff In 1984, and 200,000worldwide, of Airs 25 parent were
with frozen Embryos. Artificial insertion resulted In genetic
- 20 -
OCR for page 21
invest in dairy cattle to an extent bat milk production, per on
dall31ed in 30 years (First, Critter, arm R~1, 1985~. Ibe major once of
embryo transfer technology in the f~-pr~ir~ industry is to increase
rate of Orion of valuable cons. the nines of
~ regulation, recovery of embryos, storage in vitro, and transfer to a
recipient cow enable some cows to be the egg donors for 50 calves in a
year. [VFET can also be used to enable infertile but genetically sound
cows to reproduce. The new technologies.make the export of cattle
breeding stock more econom~1 because it is cheaper to transport embryos
(frozen or unfrozen) than mature animals. Mbreover, the resulting calves
have inanity to local paths; (received via We fir n~ther's
ool~trurn), With imported animals lack (Seidel 1981~. In 1988 We
poss~ili~ se of further inverts In the reproductive efficierx~y
of focxi-pr~cing anions; We Granada Corporation chains that Anises
for cloning animals were n~rir~ commercial abdication (Schneider, 1988~.
me devel~nt of pro for the control of reproduction In
d~ic animus has core fmn universities, nonprofit relearn ~
institutions,- art Dial organizations. Arch of commercial intent
has been Ant ~ rapid. In 1986, Are than 115 cx~rcial Denies
art 100 veterinary practicer offers embryo transfer services. Scare of
these Hernial organizations also oontri ~ e to the ~ an ~ effort by
establi ~ research laboratories (Dresser and Leibo, 1986~.
The ado pLion of the new reprc~uctive technologies to enhance the
production of food-producing animals has potential for lowering the cost
of food and for increasing the speed with which animals genetically suited
to difficult climatic can be created. The impact of artificial
insemination on the productivity of cows has already been seen. There is
reason to expect that further advances in reproductive technologies could
improve production of other food animal s.
Biodiversi~y
Advances in reproductive technologies are potentially important in
sustaining biodiversity by improving the reproductive efficiency of
endangered species. The new reproductive technologies are being storied
by zoo researchers interested in conservation of species. These
researchers see IVFET and artificial insemination as a way of improving
the reproductive processes of endangered species. Breeding of animals is
a new role for zoos, which have in the past regarded Themselves mainly as
a place to display animals. However, as z006 become the last repository
for some endangered species, and as genetic diversity is lost begat of
inbreeding, maintaining diversity has borage an important goal. Thus, the
development of reproductive technologies that can be used for endangered
exotic Species tales on a new urgency as it is irx~asingly realized that
captive breeding prc~rans can prevent extinction (lesser, 1988).
OCR for page 22
Primate for Rearm
me armoire battle between life preservationists arm scientists
who use primates for Irk purism is a final illustration of the far
reaching implications of develc~nts in reproductive teleologies.
me U.S. Fish are Wildlife service has been at to put Inn;
on me er~a~ered Species list. Scare of muse making this retest—1 isle
that the t~=- of ~inp~z~ in biar~ir=1 r~r~ is ore c- of their
er~anger~nt. Is assertion is did by officials at the National
Institutes of Health. If the ~i~nzee is declare dangers, new
prohibitions ~ cadre, transport, are use of this specie will be
it. me question mains whether, with such restrictions, the 950
~i~nz~- in gcnrer~rent facilities at the present time are etch to
Nat the reds of bianedim=l r~, espy tally in light of their
important role in AIDS Heard (Science, 1988~.
It is here that the Essential of new repr~uc:tive teleologies might
play a role. With a limited mmiber of available animals it will become
ir~ingly important to maximize the repr~x3uctive capabilities of the
350 ~anzees that have been set aside for breeding in go~rer~nt
facilities.
— 22
-
OCR for page 23
~RENOF~
Adams, Cyril E. 1982. Mammalian Egg Transfer. Boca Raton, Florida: CRC
Passe ~
Arch, R.H. et al. 1985. Gamete intra-fallopian transfer (GIFT): A new
treatment for infertility. International Jcurnal of Fertility.
30: 41-45.
Biggers, John D. 1988. Human Generation: Fact, Foible and Fable.
Plenary Lecture to the American Association for the Advancement of
-& fence. RnRton, Mass. February 2.
Braude, Peter. 1988. Gene Expression in Folly Embryonic Development Paper
Presented at the Institute of Medicine, Board on Agriculture,
Works p on the Chic Science Formations of Medically Assist
Conception, Irvine, =1 ifornia, it.
craft, Ian. et al. 1987. Sulfur Births After Ovum Donation. fetter.
beret. April 18. p. 916-917.
lesser, Betsy L. 1988. Biodiversity. E.O. Wilson ed. C:rycbiola3y,
Embryo Transfer and Artificial Pagination In Ex Situ Arrival
Conservation tram. Wash;~t=, D.C.: National Scaler mess.
Dresser, Betsy L. and Leibo, S.P. 1986. Technologies to Maintain Animal
Germplasm in Domestic and Win ~ Species. In Evaluation of
Technologies to Maintain Biological Diversity. Vol.l, Contract
Papers, Part B. Animal Technologies. Washington, D.C.: Office of
Technology Assessment.
First, N.L., Critser, E.S., and Rcbl, J.M. 1985. Bovine Embryo: Deve-
lop meet, Cloning/ Sexing and Transfer of Genes for Immunology of
P~ction art Oo~aception, P. balsas, ed. Elsevier, 1985
Fuchs, Victor, R. arm Per~ault, T-clie. 1986. E~iturm; for Pepr~
~tion-Rela~ Health Am. Journal of the American MA
Asscx~iation, Vol. 225, No. 1, Jan 3, EN 76-81.
Jones, HE E. Jr., 1989. Ed arx] Georgeanra Jones, Institute for
P~pr~uctive medicine. Person Fornication. February 23.
fit. 1987. Clinical Slates of IVF, GIN and Related Piques.
Imp. (itch 26, Ed. 945~947.
OCR for page 24
National Center for Health Statistic;. ,985. F~xtity arm Infertility
In the Unity Stab, 1965-82. data, No. 104. Fib. 11,
Wait, D.C.: U.S. fib of Health arm Stan Serbia,
Public Health Savior.
Office of Technology Ass_~t. l98sa. Artificial ~eminatioa~ Practice
In the Uhited States. Ctm BA BP 48. August. Walton, D.C.:
Office of Technology Ass~nh.
Office of l~ol~y Ass_~t. 1988b. Infertility:
C0i~. ad BA 358. May. Shit, D.C.:
As~t.
Dimes ~ did
Office of Ideology
Office of ]~logy ~C~=rner~t. 1988c. World Predation art Fertility
P1~ Technologies: ~ N~t 20 Years. Summary. ~ Et 158.
February. Wait, D.C.: Office of Penology Aunt.
Sc~ider, Keith. 1988. Better Form Anli~s Duplicate by Cloning.
New York Times, Action D, Page 1, Fib 16.
Libel, Madhelle M. 1988. A New Era In P—reductive Technology. In Vitro
Fertilization, Gamed Intrnfall~ian Transfer, and Donald Gaelic
arm Embryos. New E=1arx] Journal of Medicine. 318~130~: 828-834.
Seidel, George E., Jr. 1981. ~rovulation arm Embryo Transfer
in Cattle. Scienoe. 211 (4479): 251-357.
Science. 1988. aliens arm ~rd~:
Science 241: 777-778 .
— 24 —
Erx3angE~d? New art dent.
Representative terms from entire chapter:
vitro fertilization
