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The Human Body Background notes 19
19. The reproductive system: case study – In Vitro Fertilisation (IVF)
The world’s first IVF baby was born in England in 1978 amongst much hype and controversy. IVF involves
the union of egg and sperm in a laboratory test-tube or dish.
IVF research began in Melbourne in 1971 as a joint venture between The Queen Victoria Medical Centre
(Monash University) and The Royal Women’s Hospital (University of Melbourne). Melbourne scientists have
played a leading role in developing in vitro fertilisation (IVF) techniques, which are used around the world.
Candice Reed, Australia’s first IVF baby, was born in 1980 at the Royal Women’s Hospital through the efforts
of teams from Monash and Melbourne universities. Melbourne scientists have since devised techniques that
have greatly improved pregnancy rates by IVF procedures.
Monash university researchers developed freezing techniques that allow embryos to be thawed and
transferred at the optimum time of the mother’s cycle. This minimises embryo wastage because additional
embryos can be frozen for future transfer. As a consequence of this technique, Zoe Leyland, the world’s first
frozen embryo baby, was born in 1984.
In 1999, Monash IVF celebrated its 21st birthday and its 5000th IVF baby. During this time, 15 per cent of
couples who enrolled in an IVF program achieved parenthood. The rate of pregnancy success continues to
improve every year. About 30 000 IVF Australians were born between 1980 and 1999. One percent of
Australian births are now the result of assisted reproductive technologies. This figure is predicted to double
by 2020. Research in assisted reproductive technologies continues to advance through alliances between
specialist doctors, scientists and patients. The Monash IVF program now operates in many countries
including the UK, India, and the USA.
Infertility in males and females
Today more than one in ten couples are infertile. Some couples can benefit from assisted reproductive
technologies. Infertility occurs equally in men and women. There are many reasons for infertility including
both genetic and environmental conditions. Infertility in men often involves low sperm count, abnormally
shaped sperm, and poor swimming ability of sperm. In women, infertility is often associated with blocked
fallopian tubes, problems with egg release, and cervical and uterine conditions.
(Left to right) : Acrosome-intact sperm; Sperm with a defective nucleus; Round-headed sperm with no acrosome.
Source: National University Hospital of Singapore.
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The Human Body Background notes 19
Collecting sperm and eggs for IVF
The egg is the largest human cell, about the size of a grain of sand, while the sperm is the smallest, visible
only through a microscope. For IVF to take place, these cells are collected, analysed and stored until they
are brought together.
Sperm from the males
Semen is collected from the intended father into specimen jars. On average, a man produces about a
teaspoonful of semen containing 300 to 500 million sperm during ejaculation.
The sperm is analysed using a sperm counter. This sperm counter is used to record the number and shape
of sperm viewed in a microscope. The operator uses gridlines on the haemocytometer (glass plate) to count
the number and observe the shape of the sperm. Today sperm analysis is often carried out using computers.
(Left to right) : Photo of sperm in a Neubauer haemocytometer; computerised sperm counter.
Eggs from the females
Drugs are taken to suppress the woman’s natural cycle. A series of hormone injections stimulates the
ovaries to produce, ripen and release a number of eggs that are then harvested. Having several mature eggs
available for fertilisation and transfer increases the likelihood that at least one will result in a pregnancy.
In the 1970s a laproscopy was the surgical procedure used to view pelvic structures and to extract mature
eggs. A laparoscope, a fibre-optic tube attached to a camera, was inserted through the navel to view the
ovary. Additional instruments were passed through the abdomen to hold the ovary and collect eggs.
Laparoscopy is still used today for some assisted reproductive procedures.
Today, mature eggs are collected by aspiration via a fine needle and catheter, which is guided through the
vaginal wall with the aid of ultrasound.
Laparoscopic egg pick-up technique.
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The Human Body Background notes 19
Storing the egg and sperm
Sperm and embryos (fertilised eggs) can be stored by a deep-freezing process called cryo-preservation.
Straws containing sperm or embryos are suspended in a container of liquid nitrogen at –196°C. Frozen
embryos can be thawed and then implanted at the optimum time in a woman’s menstrual cycle. Human
embryos stored for up to 11 years in liquid nitrogen have produced healthy babies.
In vitro fertilization
In vitro’ fertilisation literally means fertilisation ‘in glass’. Egg and sperm are mixed in a sterile laboratory testtube or petri dish.
For fertilisation to be successful a single sperm must successfully penetrate an egg. Conception occurs
when the genetic material from the egg and sperm fuse. In 30 hours the cell divides into 2 cells. In 42 hours
there are 4 cells. In 52 hours there are 8 cells. By eight days the cluster of cells has formed a blastocyst, a
multicellular ball of embryonic stem cells that have the potential to differentiate into any cell within the body.
In the early days of IVF several embryos were transferred to increase the chance of pregnancy. Multiple
births also increased, so now the number of embryos transferred is usually limited to two.
Recently there has been much discussion and ethical debate around the subject of using blastocyst derived
embryonic stem cells for research purposes. ES cells have been identified as useful potential tools for the
cloning of therapeutic tissue and organs. The use of donor sperm, eggs and embryos has also challenged
traditional notions of parentage.
The process of in vitro fertilisation (IVF)
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The Human Body Background notes 20
20. The reproductive system: case study - cloning, ES cells and
biotechnology
Cloning happens naturally
Clones are produced when two or more genetically identical organisms, or cells, originate from a single
organism or cell. Microorganisms, plants, and some animals, such as worms, starfish and some lizards, are
able to naturally reproduce, without sexual fertilisation, to produce genetically identical clones. This cloning
process, or reproduction without the exchange of genetic material, is called asexual reproduction, and it
accelerates the multiplication of individuals outside of the normal breeding cycle.
Sometimes humans, and other animals, give birth naturally to identical offspring that are clones. This occurs
when the early embryo (cluster of cells) splits and new each cluster develops into a separate new embryo.
The twins, triplets or quadruplets that develop are biological clones of each other because they originate
from a single embryonic cell and have an identical genetic make-up. They are not clones of either of their
parents.
Today, there is broad potential for cloning with modern biotechnology that raises many issues and ethical
questions
Cloning means different things.
Gene Cloning: Genes are duplicated in a host bacterium. This
technique is used in almost all genetic research, gene therapy,
development of drugs, vaccines and genetic diseases
Cellular cloning: Cells are copied into ‘cell lines’ of identical
cells for medical research.
Embryo splitting or embryo twinning: This event, which
sometimes occurs spontaneously in nature, occurs when an
embryo is split in half resulting in twins. Twins are genetically
identical to each other but not to either of the parents. Embryo
splitting is a common practice in cattle breeding programs. In
some countries it has been approved during human IVF
procedures, although this practice has provoked medical and
ethical controversy.
Somatic cell cloning (nuclear transfer): The nucleus, or the
whole cell, of one individual is placed in an enucleated egg cell
(nucleus and chromosomes removed) of another individual. The
offspring in this case is a genetic twin of the parent that donates
the DNA.
Nuclear transfer cloning
Biotechnology and cloning today
In 1997, research into genetically modified mammals led to one of the most unexpected steps in science –
the cloning of Dolly, the sheep. Dolly was not the first mammal to be cloned − earlier successful laboratory
efforts were able to clone mammals using embryo splitting techniques. Somatic cell cloning differs from
embryo splitting because it results in offspring that are genetically identical to the ‘parent’ cell. Potentially,
this means that any animal – adult or embryo − with desired characteristics can now be cloned.
Dolly proved that adult cells that have already differentiated and specialised can be reprogrammed or
reverted back into a cell that resemble the original ‘Toti-potent’ stem cells can then differentiate and divide
into all of the cells required to make a new individual. The cloned individual is a genetic replica of the adult
cell it was derived from. Cell differentiation is therefore a reversible process. Somatic cell cloning has paved
the way for the study of important biological issues such as: ageing, cancer susceptibility of clones, and
fertility.
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The Human Body Background notes 20
Cloning replacement cells and tissues
Embryos contain versatile all-purpose cells, called embryonic stem cells (ES cells), that are not yet
specialised. Stem cells, such as these, or perhaps even clonal stem cells reverted from adult cells, could be
used as self-compatible replacement cells for tissue and organ repair or replacement in the future. Although
researchers have been growing mouse ES cells in the laboratory for nearly 20 years, human ES cells were
not isolated until 1998. During this experiment human ES cells were removed from the inner cell mass of a
one-week old embryo, called a blastocyst. They were grown in a laboratory on a nutrient rich medium. By
changing the conditions in which the cells grew, researchers were able to prompt the cells to differentiate into
many different specialised cells, including cells of lung and gut tissue, nerve cells, muscle cells, bone and
cartilage. Researchers hope to eventually produce every type of cell this way.
There is now great interest in cloning ES cells as donor cells
for tissue and organ repair. Currently, only one human
organ, skin, can be grown in the laboratory for its use to
provide self-compatible skin grafts for burns victims. Cloning
other cells and tissue, such as nerve cells for patients with
spinal injuries or cardiac muscle cells for heart attack
victims, is now a very real prospect. ES cells have the
potential to be used as a source for any tissue in the body.
If they could be cloned by somatic nuclear replacement, with
an individual’s DNA into an enucleated egg cell, they could
overcome the problems of rejection of replacement tissues
and organs. If ES cells could be cloned on demand, new
tissue could be grown for people’s individual needs or for
storage banks. Although the potential is great, therapeutic
Cloning ES cells as donor cells for tissue and organ
cloning will probably take some time to become reality.
repair
Currently, ES cells are extracted from week-old blastocysts. There are ethical issues raised about the use of
embryonic stem cells for therapeutic cloning because they are extracted from week-old human blastocyst.
Researchers are hoping to learn enough about reprogramming cells to be able to create ES cells without
going through the embryo stage. Future technologies may include isolating and culturing dispersed stem
cells known to exist in adult animals; fully or partially reversing differentiated adult cells; and culturing ES cell
lines that may be coaxed into becoming specialised cells, such as, muscle cells, nerve cells, glandular cells,
blood and immune cells.
Reproductive cloning of humans
The ability to clone adult mammals by nuclear transfer is one of the most recent challenges to human
identity. When the Edinburgh researchers announced the existence of Dolly the cloned sheep, the scenario
of human cloning moved from science fiction into the world of possibility. It sparked vigorous debate in both
public and scientific circles. The process of nuclear transfer cloning, used to produce Dolly, showed that cells
from adult mammals can be ‘reprogrammed’ to start over again and develop from a single cell into a
complete adult. Until then, the differentiation of a stem cell into a specialised cell was thought to be
irreversible. Questions were raised immediately. Is it also possible to reprogram human adult cells to revert
to earlier stages of development? If human cells were reprogrammed this way could they be used to grow
new human beings?
Since Dolly, many of the public debates have focused on prospects of reproductive cloning of humans.
Would it be possible for an individual incapable of having children by other reproductive methods, to have a
cloned child? What if couples with a high risk of passing on a genetic condition could avoid it by cloning?
Would a cloned child simply be a genetic twin of the individual that donated the DNA for the original cell? Is
cloning really any different to identical twins that are born naturally? Would some people choose to have a
child cloned to conveniently provide compatible tissue or organs for an adult or previous child suffering from
life-threatening illnesses? Some people also imagine a future that uses reproductive cloning of humans to
provide the ultimate human replacement body parts for individuals or perhaps even replacement clones, of
lost loved ones. What ever its justification, the direct transfer of reproductive cloning technologies to humans
is generally found unacceptable by most people, in both the scientific and non-scientific community. The
arguments, that cloning denies a person his or her genetic individuality or that human cloning could
eventually lead to unacceptable eugenic practices.
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