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Assisted Reproduction Technology (ART)
Assisted Reproduction Technology (ART)
Q1. Look at the names of assisted reproductive technologies (ART) in Box 1, and tick the
ones you have heard of before. In this chapter most but not all of these techniques will
be introduced and discussed.
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_ Ultrasound scanning
_ Egg and embryo donation; posthumous gamete donation
_ Flow cytometry
_ Surrogacy
_ Cloning technology
Male-Factor Infertility
In this section some factors that affect male fertility are discussed.
(i) Standard Semen Parameters
A variety of factors (parameters = a factor we can measure) can indicate poor
quality semen that reduces male fertility. These are sperm count (number), sperm
motility (movement), sperm morphology (shape) and sperm fertilizability (joining of
sperm with the egg). Sperm counts are easy to perform, so it is often used to assess
fertility. Sperm morphology is one of the best indicators of fertility; however,
examination with the light microscope can provide only limited information on their
internal structure.
The most common group of conditions affecting fertility is characterized by
insufficient or poor-quality sperm in the man’s semen (see Chapter 8 for lifestyle/social
factors). The usual rule of thumb is that a man is likely to be subfertile if there are
fewer than 20 million sperm per milliliter of semen or if the fraction of the sperm that
has normal motility is less than 50%.
Q2. Do you know where in your city there are frozen sperm collections?
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If the male partner is completely sterile or the couple does not want to use his
sperm as, for example, when he carries a gene for a serious genetic disease, women can
use artificial insemination by donor or AID. Donor insemination (DI) is also
employed for single women who want to become pregnant, or for women who are
partnered by other women.
Internationally recognized insemination centers restrict donor recruitment to
men who are healthy, free from transmissible genetic disorders and sexually-transmitted
disease and have semen with a high fertilization potential. Information about potential
donors’ physical appearance, profession and other interests is usually available to
potential recipients.
Donor insemination is more successful than partner insemination, does not carry
an increased risk of spontaneous abortion or congenital anomalies, and has advantages
over adoption in that the child is genetically related to the mother and the couple can
experience conception, pregnancy and delivery. It is, therefore, one of the major
treatments for male infertility (see also the section on ‘Sperm, Egg and Embryo
Donation).
Q3. Do you think there should be restrictions on who can use donor insemination?
What sorts of restrictions?
(iii) Intracytoplasmic sperm injection (ICSI)
Intracytoplasmic sperm injection or ICSI, in conjunction with IVF technology,
has given hope to men with severe infertility problems. This technique involves the
injection, via a micropipette, of a single sperm directly into the cytoplasm of the oocyte
(egg) and can be used for non-motile or otherwise damaged sperm. Even a man who
produces no mature sperm at all may be able to father a child. Immature spermatids
(sperm precursor cells) can be harvested by needle aspiration of the man’s testis and
used to fertilize the egg.
Soon after the development of the ICSI technology it became the standard
treatment for severe male-factor infertility but there remain unanswered questions
relating to unidentified risks in the children conceived by this procedure. Debate is also
continuing as to its use when the male has normal semen parameters. In the presence of
normal semen parameters, fertilization by ICSI does not show an advantage over
conventional IVF treatment, however, some centers use ICSI for all cases of IVF in
order to protect against the possibility of fertilization failure.
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Female-Factor Infertility
About 20% of female infertility is caused by abnormalities of the reproductive
tract with the commonest being abnormal fallopian tubes. They can become scarred,
obstructed, or denuded of cilia as a consequence of pelvic inflammatory disease – a
general term for infections of the uterus or oviducts, usually caused by sexually
transmitted organisms such as chlamydia or gonorrhea. Another condition that can
interfere with fertility is endometriosis, a condition where endometrial (uterine) tissue
grows at unusual locations such as on the ovaries or oviducts. Although surgery can
sometimes restore fertility in such conditions, it often fails to do so. In such cases it is
possible to bypass the fallopian tubes by performing IVF and placing the resulting
embryos directly into the uterus.
Another 20% or so of infertility cases are caused by failure to ovulate. These
conditions can be caused by a variety of physical and psychological stresses (see
Chapter 8 on Fertility). Menstrual irregularity may be caused by, for example, excessive
weight loss, strenuous athletic training, anxiety, grief, depression and certain drugs.
Q4. Do you think the government should fund ways to help people have children if their
infertility was the result of their unhealthy lifestyle during their younger days?
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Q5. How many times would you try IVF in order to have a child?
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wish regarding the fate of surplus IVF embryos, should there be any. Spare embryos
may be discarded, stored frozen for later use, donated to infertile couples or donated to
research.
If a woman’s oocytes cannot be used, oocytes can also be obtained from donors.
Obtaining oocytes from female donors is more complex and expensive than sperm
donation because the donor must undergo hormone treatment followed by oocyte
aspiration (see IVF section). There are certain risks for the donor, including the risk of
injury or infection associated with the procedure itself, the risk of unwanted pregnancy
(because the donor cannot use oral contraceptives during the period before the
donation), the risk of psychological trauma, and a small chance of negative effect on
future fertility. Still many women altruistically become donors.
Q6. If you were born from donated eggs or sperm, or were an adopted baby, do you
think your parents should tell you who your genetic parents are?
Surrogacy
Surrogacy is when someone does something in place of another person. Some
women get pregnant for another woman. Gay male couples who wish to have children
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may also ask a surrogate mother since they cannot get pregnant. In genetic or partial
surrogacy the surrogate mother agrees to be artificially inseminated using the sperm
from the partner of the woman, and she then carries any resulting fetus or fetuses to
term. If the woman who cannot sustain a pregnancy can nevertheless produce healthy
oocytes, those oocytes can be fertilized with the partner’s sperm by IVF and then
implanted into the surrogate’s uterus. This procedure is called gestational or total
surrogacy. Either way, when the child is born, the surrogate gives it up for adoption by
the couple.
Modern surrogacy challenges traditional assumptions about parenthood because
assisted reproduction procedures make it possible to separate out the various phases of
the reproductive process. It is now possible for a child to be subject to multiple
parenting with two men (genetic and adoptee) fulfilling the functions of ‘father’ and up
to three women (genetic, gestational and adoptee) fulfilling the differing functions of
‘mother’. The birth of such children also holds wider kin implications for grandparents
or other relatives.
Q8. Would you like to have a girl or a boy? If you already had 3 boys would you like to
have the next child be a girl?
Some people would prefer their child to be of one particular sex. Sometimes
their preference has specific medical reasons; for example, in instances of sex-linked
genetic disorders the couple may want a child of the other sex. This usually means a girl,
because most sex-linked disorders affect boys. Another reason why couples would prefer
a child of a particular sex is for specific social or even religious reasons.
Most individuals who donate gametes (eggs or sperm) are motivated principally
by the desire to help infertile couples and do it for free or a modest fee. However, the
question arises whether the ARTs should be available to all to try to improve selected
qualities in their children which are unrelated to health.
Athletic achievement, beauty, brains, social skills come immediately to mind. It
is a fact that some wealthy couples, in the hope of having gifted or attractive children,
are willing to pay large sums of money to donors they feel produce gametes of
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outstanding genetic quality. This demand has led, particularly in the US, to the
development of competitive markets for superior sperm and oocytes dubbed “über-eggs”
raising disconcerting echoes of eugenics (selective breeding programs) and related fears.
The commercialization of oocyte donation, for instance, may coerce women to ignore
the possible risks of IVF procedures or to conceal undesirable aspects of their and their
family’s medical history (payment for organ donations is widely prohibited for this
reason). An additional concern is whether extraordinary payments for gametes converts
the child into a mere commodity.
Q9. Would you like to choose gametes from famous persons? From clever persons?
From strong persons? Or just from the person you love?
Summary
The main difficulty in evaluating new technology for effectiveness is that we
have no good way of seeing how they all work together with each other. It would be
wrong to look upon assisted reproduction as the panacea for all causes of childlessness.
Instead the technologies are assessed one by one, as if they exist in isolation
when what is needed is to assess the impact of ART innovation as a whole. Thus, when
forced to choose among several ART possibilities, the logical clinical protocol is to
integrate the best available evidence from the literature with clinical expertise and tailor
it to the individual situation. Certainly there is also the responsibility for researchers to
assess the risks posed by assisted reproduction. This requires epidemiological follow-up
studies to determine whether the ART created children bear any cellular or molecular
abnormalities beyond the expected in the population at large. Some recent studies have
started to raise doubts about the safety of IVF, but for most children born they are
merely grateful for the means for their creation.
For the sake of future generations of assisted reproduction children, research on
human embryos should be encouraged. Finally, taking into consideration new scientific
insights, we may be able to retain what is biologically relevant and adaptive, and modify
what is not.
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Teacher's Notes
Chapters 9 and 8 are linked to each other in discussing fertility and assisted
reproductive technologies. There are many issues that could be discussed, so the
chapters are long and you may want to split them into more class times, or selectively
use specific sections. There are also photographs in the CD or on the website that can be
downloaded.
Chapters 8 and 9 have four specific aims:
1. To fully discuss the divide between fertility and infertility.
2. To outline the influences of lifestyle, environment and social development on
personal empowerment and reproductive health.
3. To describe the assisted reproductive technologies.
4. To highlight major bioscience-bioethical concerns.
The following notes could provide extra material to teach chapter 9.
Photos illustrating sperm forms, ICSI and cross-cultural family members are
available.
Male Infertility
Sperm fertilizability tests investigate sperm fertilizing capacity and have
become a valuable adjunct to the classical semen analysis. Sperm function tests may
indicate whether conventional methods of assisted reproduction should first be applied
or whether the couple should immediately be included into a micro-manipulation
program such as ICSI (see section on ICSI).
Various steps can be taken to achieve pregnancy in patients with poor sperm
quality. Intrauterine insemination is often successful because placing the prepared
semen high up in the uterus, allows sperm to bypass the cervix and its mucus that can
contain anti-sperm antibodies. Partner insemination is usually called artificial
insemination by the husband (AIH) and has been useful in cases of paraplegia (sperm is
collected by electroejaculation), obstructed vas deferens or epididymis (sperm is
aspirated from the epididymis) and forced separation of couples (prisoners on long-term
sentences).
Donor insemination may also be used in combination with other ART
technologies, including sperm separation for sex preselection and for other ‘designer’
characteristics. The latter application raises serious concerns from the ethical, legal and
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Female infertility
A woman may stop menstruating (called secondary amenorrhea) or menstruate
irregularly (called oligomenorrhea) or just fail to ovulate but menstruate normally.
Many fertility problems can be reversed by lifestyle changes, psychotherapy (if
the cause is depression or an eating disorder, for example), or failing the above, by drug
treatment such as clomiphene or its generic versions. Clomiphene is an estrogen
antagonist which by several feedback mechanisms promotes the maturation of ovarian
follicles restoring fertility; sometimes too effectively as 5-10% of clomiphene-induced
pregnancies are twins (compared with about 1% of normal pregnancies).
IVF
In IVF only a small number of sperm are needed because no long-distance
migration is involved. Various IVF adaptions are discussed below. You may want to use
these for class if students are competent enough.
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Adoption
Adoption is a low-tech but often very successful way for infertile couples, or
couples who have chosen against reproduction, to have children. A major problem with
adoption from the perspective of would-be parents living in societies such as the United
States of America or Australia, is the acute shortage of suitable adoptees; that is, healthy
infants of the same ethnicity as themselves. Older or ‘special-needs’ children; that is,
children with disabilities or other medical or psychological problems, are much more
readily available and so are sets of siblings who want to be adopted together. For this
reason and for a variety of other personal preferences, many couples nowadays choose to
adopt infants from abroad even though this involves 1-3 years waiting periods and
considerable expense. Cross-cultural family relationships have revealed them to be
especially rewarding in that they generate wider understanding and respect for difference
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Surrogacy
If a woman cannot sustain pregnancy at all because, for example, her uterus is
malformed or absent, or because her general medical condition makes pregnancy
inadvisable, or she is unwilling to reproduce naturally because of inheritable genetic
disease, an option is to use a surrogate mother. In a further twist of gestational
surrogacy, the oocytes used for IVF may be taken from neither the woman nor the
surrogate, but from a third woman whose genes are considered preferable to those of the
surrogate.
Sex selection
For example, they may have one or more children of one sex and now want to
balance the family with a child of the other sex, or perhaps think that it’s good for a
brother to have a sister, or vice versa. More troubling, however, is the general social
preference for boys seen in a variety of Asian and African cultures. Boys are preferred
because traditionally they help with the farm work, bring money into the family and
their children will carry on the family name. Girls are less favored because marrying
them off requires heavy bridal payments and they leave their birth family after marriage.
A particular abhorrent practice of the past was infanticide or abandoning newborn
children of the unwanted sex. Nowadays, with amniocentesis and chorionic villus
sampling it is possible to determine the sex of a fetus before birth. The introduction of
obstetric ultrasonography has made it also possible to visualize a fetus’s genitals and to
determine its sex. This can be done with reasonable accuracy by 12-14 weeks post-
conception. As a consequence, sex-selective abortion is now a realistic option. Studies
have exposed that the practice of aborting female fetuses is prevalent in India and China
where the sex ratio of newborn children has become noticeably skewed toward males. In
China, for example, about 119 male births are registered for every 100 female births, and
in some parts of India the ratio is 126:100. The natural sex ratio at birth is about
105:100, at least for Western populations. Might not the present be an opportune time to
reconsider abandoning gender discriminatory practices and return to women their due
value and proper recognition?
Considerable high-tech research has gone into developing techniques for
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selecting a child’s sex before fertilization. Because the fetus’s sex is determined by
whether the oocyte is fertilized by an X-bearing or a Y-bearing sperm, researches have
developed sperm separation techniques by focusing on the sperm’s total DNA content
(X-bearing sperm contain about 2.9% more DNA that Y-bearing sperm). This difference
is detected by a technique called flow cytometry. X- or Y-enriched fractions of sperm
may then be selected to inseminate women who desire a girl or a boy, respectively. The
researchers claim over 90% success with girls; results with boys are only slightly better
than chance.
A more complex, but more reliable method of selecting a child’s sex is by
preimplantation genetic screening where only embryos of the preferred sex are
transferred for implantation. Although this technique is mostly done to avoid sex-linked
disease, some fertility clinics are said to offer this service for the purpose of family
planning.
Designer children
A market for ‘superior’ sperm has long existed but the demand seems to be
geared to donors with high intellectual attainment. For example, the Repository for
Germinal Choice in Escondido, California, is a nonprofit organization founded in 1980
by Robert Graham. It distributed sperm from Nobel Prize winners, and other high
achievers. The Repository has since gone out of business, but another organization
Heredity Choice continues to offer semen from prominent scientists and others.
Counseling
Most of us understand counseling to be a therapeutic technique providing advice
and guidance to a patient and significant others. Therefore, counseling is an important
part of any fertility treatment and applies both to the doctor, who maybe motivated by a
too enthusiastic desire to help the infertile couple, and the couple who maybe blinded to
consider valid alternatives by their desperate desire for a child. When it comes to
infertility treatment protocols, all known potential risks must be carefully explained and
received. Accredited IVF clinics require couples to sign a general consent form
acknowledging that they have understood and accepted the information provided. This
information typically clarifies the various assisted reproductive technologies planned,
includes a warning that there may be associated short, medium and long term health
risks, that there is no guarantee of a successful pregnancy and that they have been given
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fair opportunities to become better informed. The advantages of this practice to the
couple are immeasurable from the point of view of increased understanding and in
establishing mutual respect for each other and their unborn children.
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reproductive success?
2. A man was found to have around 12 million sperm per milliliter of semen. In
all probability will he be able to father children in the normal way?
3. During hysterectomy a woman has her uterus removed. What effect will this
have on her producing eggs?
4. If the technique of reproductive cloning were perfected and adopted, would that
affect people’s ethical views about reproductive behavior?
5. Compare and contrast what in your opinion is right or wrong in the reproduction
domain.
6. Explain how your views have changed following this bioethics module.
7. For both sperm and oocyte donations, there is a market for donors who are
perceived to be genetically superior, and higher fees may be paid in such cases
especially for oocytes. Discuss the bioethical ramifications of this.
8. What in your mind are the ‘correctness’ issues raised in the case of a rich couple
using a poor woman’s body to surrogate their child?
9. Discuss the pros and cons of paying high prices for ‘genetically favored’
gametes. Will the couple love their child as much or will they be resentful if their
dream of a ‘superior’ child does not come true?
10. Scientific discoveries build on previous scientific discoveries and the outcome of
scientific experiments cannot be known in advance. Discuss
11. What are the perceived, including culturally-specific, barriers to seeking and
utilizing ART assistance and other reproductive care services?
12. How can we, as potential parents, best benefit from the insights gained by
scientists since the birth of the first IVF baby in 1978?
13. Discover culturally-dependent fertility beliefs and practices.
Bibliography
Macer, Darryl (editor) ‘UNESCO/IUBS/EUBIOS Living Dictionary of Bioethics’.
http://www.biol.tsukuba.ac.jp/~macer/biodict.htm
Pollard, Irina (2002). ‘Life, Love and Children: A Practical Introduction to Bioscience
Ethics and Bioethics’. Kluwer Academic, Boston.
Pollard, Irina (1994). ‘A Guide to Reproduction Social Issues and Human Concerns’.
Cambridge University Press, Cambridge.
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