Definition &

Meaning

Assisted reproductive technology (ART) a general term referring to methods

used to achieve pregnancy by artificial or partially artificial means. It is reproductive
technology used primarily in infertility treatments. Some forms of ART are also used in fertile
couples for genetic reasons. ART is also used in couples who are discordant for certain

communicable diseases, e.g. AIDS, to reduce the risk of infection when a pregnancy is
desired. Examples of ART include in vitro fertilisation, intra-cytoplasmic sperm injection
(ICSI), cryopreservation, and intrauterine insemination (IUI). There is yet no strict definition
of the term. Usage of the ART mainly belongs in the field of reproductive endocrinology and
infertility.

Definition:
The Centres for Disease Control and Prevention (CDC)which is required as a
result of the 1992 Fertility Clinic Success Rate and Certification Act to publish the annual
ART success rates at U.S. fertility clinicsdefines ART to include "all fertility treatments in
which both eggs and sperm are handled. In general, ART procedures involve surgically
removing eggs from a woman's ovaries, combining them with sperm in the laboratory, and
returning them to the woman's body or donating them to another woman." According to CDC,
"they do not include treatments in which only sperm are handled (i.e., intrauterineor
artificialinsemination) or procedures in which a woman takes medicine only to stimulate
egg production without the intention of having eggs retrieved."

Brief Discussion
ART has been used in the United States since 1981 to help women become pregnant, most
commonly through the transfer of fertilized human eggs into a womans uterus (in vitro
fertilization). However, deciding whether to undergo this expensive and time

consuming treatment can be difficult.

According to CDCs 2010 ART Success Rates, 147,260* ART cycles were performed at 443
reporting clinics in the United States during 2010, resulting in 47,090 live births (deliveries
of one or more living infants) and 61,564 infants. Although the use of ART is still relatively
rare as compared to the potential demand, its use has doubled over the past decade. Today,
over 1% of all infants born in the U.S. every year are conceived using ART.
*Excludes cycles in which a new treatment procedure was being evaluated.

The National Institute of Child Health and Human Development held

a
workshop on September 12-13, 2005, to summarize the risks for adverse pregnancy outcomes
after assisted reproductive technology (ART), develop an approach to counseling couples
regarding these risks, and establish a research agenda. Although the majority of ART children
are normal, there are concerns about the increased risk for adverse pregnancy outcomes.
More than 30% of ART pregnancies are twins or higher-order multiple gestations (triplets or
greater) and more than one half of all ART neonates are the products of multifetal gestations,
with an attendant increase in prematurity complications. Assisted reproductive technology
singleton pregnancies also demonstrate increased rates of perinatal complications-small for
gestational age infants, preterm delivery, and perinatal mortality-as well as maternal
complications, such as preeclampsia, gestational diabetes, placenta previa, placental
abruption, and cesarean delivery. Although it is not possible to separate ART-related risks
from those secondary to the underlying reproductive pathology, the overall increased
frequency of obstetric complications, including preterm birth and small for gestational age
neonates, should be discussed with the couple. Significant gaps in knowledge were identified,
and the basic science and clinical and epidemiologic research required to address these gaps
is outlined.

Examples

Artificial

Embryonic

Insemination
splitting

Cryopreservation

of

or

Cloning

cleavage

sperms,

oocytes

or

embryos Embryo transfer Fertility

medication Hormone treatment In-vitro
fertilization
injection

Intra-cytoplasmic

sperm

Artificial
Insemination

Artificial insemination (AI) is the deliberate introduction of semen into a female for the
purpose of fertilisation, by means other than ejaculation directly into the vagina or oviduct.
Artificial insemination is a fertility treatment for humans, and is a common practice in the
breeding of dairy cattle and pigs. Artificial insemination may employ assisted reproductive
technology, donated sperm, and/or animal husbandry techniques.

In Humans
Artificial insemination is a means for a woman to conceive when she does not have a male
partner, when she does not want a male partner, or when a male partner's sexual inhibition or
physical limitation impedes his ability to impregnate her by sexual intercourse. Women who
have issues with the cervix such as cervical scarring, cervical blockage from endometriosis,
or thick cervical mucus also benefit from AI since the sperm must pass through the cervix to
result in fertilization.

Cloning

Human cloning is the creation of a genetically identical copy of a human. It does not refer to
monozygotic multiple births or the reproduction of humans/animals cells or tissue. The ethics
of cloning is an extremely controversial issue. The term is generally used to refer to artificial
human cloning; human clones in the form of identical twins are commonplace, with their
cloning occurring during the natural process of reproduction.

There are two commonly discussed types of human cloning: therapeutic cloning and
reproductive cloning. Therapeutic cloning involves cloning cells from an adult for use in
medicine and transplants, and is an active area of research. Reproductive cloning would
involve making cloned humans, for couples wanting to have a child, but cannot naturally.

Embryonic

splitting

or

cleavage

In embryology, cleavage is the division of cells in the early embryo. The zygotes of many
species undergo rapid cell cycles with no significant growth, producing a cluster of cells the
same size as the original zygote. The different cells derived from cleavage are called
blastomeres and form a compact mass called the morula. Cleavage ends with the formation of
the blastula.
Depending mostly on the amount of yolk in the egg, the cleavage can be holoblastic (total or
entire cleavage) or meroblastic (partial cleavage). The pole of the egg with the highest
concentration of yolk is referred to as the vegetal pole while the opposite is referred to as the
animal pole.
Cleavage differs from other forms of cell division in that it increases the number of cells
without increasing the mass. This means that with each successive subdivision, the ratio of
nuclear to cytoplasmic material increases.

Cryopreservation

of

sperms,

or

oocytes

embryos

Cryopreservation is a process where sperms, oocytes and embryos are preserved by cooling
to sub-zero temperatures, typically 77 K (= 196 C, the boiling point of liquid nitrogen). At
these cold temperatures, any biological activity, including the biochemical reactions that
would cause cell death, is effectively stopped. However, if cryoprotectant solutions are not
used, the cells being preserved are likely to be damaged due to freezing during the cooling or
thawing process.

Embryo Transfer

Embryo transfer refers to a step in the process of assisted reproduction in which embryos
are placed into the uterus of a female with the intent to establish a pregnancy. This technique
(which is often used in connection with in vitro fertilization (IVF)), may be used in humans
or in animals, in which situations the goals may vary.

Fertility Medication

Fertility medication are drugs which enhance reproductive fertility. For women, fertility
medication is used to stimulate follicle development of the ovary. There are currently very
few fertility medication options available for men.

Hormone Treatment

Hormone treatment or hormonal therapy is the use of hormones in medical

treatment. Treatment with hormone antagonists may also referred to as hormonal therapy.

In-vitro
fertilization

In vitro fertilization (IVF) is the technique of letting fertilization of the male and female
gametes (sperm and egg) occur outside the female body.
Techniques usually used in in vitro fertilization include:

Transvaginal ovum retrieval (OCR) is the process whereby a small needle is inserted through
the back of the vagina and guided via ultrasound into the ovarian follicles to collect the fluid
that contains the eggs.
Embryo transfer is the step in the process whereby one or several embryos are placed into the
uterus of the female with the intent to establish a pregnancy.

Intra-cytoplasmic sperm
injection

Intracytoplasmic sperm injection (ICSI) is a procedure in which a single sperm is injected

directly into an egg.
This procedure is most commonly used to overcome male infertility problems, although it
may also be used where eggs cannot easily be penetrated by sperm, and occasionally in
addition tosperm donation.
It can be used in teratozoospermia, because once the egg is fertilized, abnormal sperm
morphology does not appear to influence blastocyst development or blastocyst morphology.[3]
Even with severe teratozoospermia, microscopy can still detect the few sperm cells that have
a "normal" morphology, allowing for optimal success rate.

Detailed study of Invitro

fertilization
In vitro fertilisation (IVF) is a process by which an egg is fertilised by sperm outside the
body: in vitro. IVF is a major treatment for infertility when other methods of assisted
reproductive technology have failed. The process involves monitoring a woman's ovulatory
process, removing ovum or ova(egg or eggs) from the woman's ovaries and letting sperm
fertilize them in a fluid medium in a laboratory. When a woman's natural cycle is monitored
to collect a naturally selected ovum (egg) for fertilisation, it is known as natural cycle IVF.
The fertilised egg (zygote) is then transferred to the patient'suterus with the intention of
establishing a successful pregnancy. The first successful birth of a "test tube baby", Louise
Brown, occurred in 1978. Louise Brown was born as a result of natural cycle IVF. Robert G.
Edwards, the physiologist who developed the treatment, was awarded the Nobel Prize in
Physiology or Medicine in 2010.

The term in vitro, from the Latin meaning in glass, is used, because early biological
experiments involving cultivation of tissues outside the living organism from which they
came, were carried out in glass containers such as beakers, test tubes, or petri dishes. Today,
the term in vitro is used to refer to any biological procedure that is performed outside the
organism it would normally be occurring in, to distinguish it from an in vivo procedure,
where the tissue remains inside the living organism within which it is normally found. A
colloquial term for babies conceived as the result of IVF, "test tube babies", refers to the
tube-shaped containers of glass or plastic resin, called test tubes, that are commonly used in
chemistry labs and biology labs. However, in vitro fertilisation is usually performed in the
shallower containers called Petri dishes. One IVF method, Autologous Endometrial
Coculture, is actually performed on organic material, but is still considered in vitro.

IVF may be used to overcome female infertility in the woman due to problems of the
fallopian tube, making fertilisation in vivo difficult. It may also assist in male infertility,
where there is a defect in sperm quality, and in such cases intracytoplasmic sperm injection
(ICSI) may be used, where a sperm cell is injected directly into the egg cell. This is used
when sperm have difficulty penetrating the egg, and in these cases the partner's or a donor's
sperm may be used. ICSI is also used when sperm numbers are very low. ICSI results in
success rates equal to those of IVF.
For IVF to be successful it typically requires healthy ova, sperm that can fertilise, and a
uterus that can maintain a pregnancy. Due to the costs of the procedure, IVF is generally
attempted only after less expensive options have failed.
IVF can also be used with egg donation or surrogacy where the woman providing the egg
isn't the same who will carry the pregnancy to term. This means that IVF can be used for
females who have already gone through menopause. The donated oocyte can be fertilised in a
crucible. If the fertilisation is successful, the embryo will be transferred into the uterus,
within which it may implant.
IVF can also be combined with preimplantation genetic diagnosis (PGD) to rule out presence
of genetic
been

disorders.

similar

but

more general

developed called Preimplantation Genetic Haplotyping

test

has

Method
Theoretically, in vitro fertilisation could be performed by collecting the contents from a
woman's fallopian tubes or uterus after natural ovulation, mixing it with semen, and
reinserting into the uterus. However, without additional techniques, the chances of pregnancy
would be extremely small. Such additional techniques that are routinely used in IVF include
ovarian hyper stimulation to retrieve multiple eggs, ultrasound-guided transvaginal oocyte
retrieval directly from the ovaries, egg and sperm preparation, as well as culture and selection
of resultant embryos before embryo transfer back into the uterus.

Egg

&

Sperm

Preparation

In the laboratory, the identified eggs are stripped of surrounding cells and prepared for
fertilisation. An oocyte selection may be performed prior to fertilisation to select eggs with
optimal chances of successful pregnancy. In the meantime, semen is prepared for fertilisation
by removing inactive cells and seminal fluid in a process called sperm washing. If semen is
being provided by a sperm donor, it will usually have been prepared for treatment before
being frozen and quarantined, and it will be thawed ready for use.

Fertilization
The sperm and the egg are incubated together at a ratio of about 75,000:1 in the culture media
for about 18 hours. In most cases, the egg will be fertilised by that time and the fertilised egg
will show two pronuclei. In certain situations, such as low sperm count or motility, a single
sperm may be injected directly into the egg using intracytoplasmic sperm injection (ICSI).

The fertilised egg is passed to a special growth medium and left for about 48 hours until the
egg consists of six to eight cells.
In gamete intrafallopian transfer, eggs are removed from the woman and placed in one of the
fallopian tubes, along with the man's sperm. This allows fertilisation to take place inside the
woman's body. Therefore, this variation is actually an in vivo fertilisation, not an in vitro
fertilisation.

Embryo Culture

Typically, embryos are cultured until having reached the 68 cell stage three days after
retrieval. In many Canadian, American and Australian programmes , however, embryos are
placed into an extended culture system with a transfer done at the blastocyst stage at around
five days after retrieval, especially if many good-quality embryos are still available on day 3.
Blastocyst stage transfers have been shown to result in higher pregnancy rates. [9] In Europe,
transfers after 2 days are common.
Culture of embryos can either be performed in an artificial culture medium or in an
autologous endometrial coculture (on top of a layer of cells from the woman's own uterine
lining). With artificial culture medium, there can either be the same culture medium
throughout the period, or a sequential system can be used, in which the embryo is
sequentially placed in different media. For example, when culturing to the blastocyst stage,
one medium may be used for culture to day 3, and a second medium is used for culture
thereafter. Single or sequential medium are equally effective for the culture of human
embryos to the blastocyst stage. Artificial embryo culture media basically contain glucose,
pyruvate, and energy-providing components, but the addition of amino acids, nucleotides,
vitamins, and cholesterol improve the performance of embryonic growth and development.
Methods to permit dynamic embryo culture with fluid flow and embryo movement are also
available. A new method in development uses the uterus as an incubator and the naturally
occurring intrauterine fluids as culture medium by encapsulating the embryos in permeable
intrauterine vessel.

Embryo
transfer

Selection

&

Laboratories have developed grading methods to judge oocyte and embryo quality. In order to
optimise pregnancy rates, there is significant evidence that a morphological scoring system is
the best strategy for the selection of embryos. However, presence of soluble HLA-G might be
considered as a second parameter if a choice has to be made between embryos of
morphologically equal quality. Also, two-pronuclear zygotes (2PN) transitioning through
1PN or 3PN states tend to develop into poorer-quality embryos than those that constantly
remain 2PN.

Embryos are failed by the embryologist based on the amount of cells, evenness of growth
and degree of fragmentation. The number to be transferred depends on the number available,
the age of the woman and other health and diagnostic factors. In countries such as Canada,
the UK, Australia and New Zealand, a maximum of two embryos are transferred except in
unusual circumstances. In the UK and according to HFEA regulations, a woman over 40 may
have up to three embryos transferred, whereas in the USA, younger women may have many
embryos transferred based on individual fertility diagnosis. Most clinics and country
regulatory bodies seek to minimise the risk of pregnancies carrying multiples, as it is not
uncommon for more implantations to take than desired. The embryos judged to be the "best"
are transferred to the patient's uterus through a thin, plastic catheter, which goes through her
vagina and cervix. Several embryos may be passed into the uterus to improve chances of
implantation and pregnancy.

Success Rates
IVF success rates are the percentage of all IVF procedures which result in a favorable
outcome. Depending on the type of calculation used, this outcome may represent the number
of confirmed pregnancies, called the pregnancy rate or number of live births, called the live
birth rate.
Due to advancement in reproductive technology, the IVF success rates are substantially better
today than they were just a few years ago. The most current data available in the United
States a 2009 summary complied by the Society for Reproductive Medicine which reports the
average national IVF success rates per age group using non-donor eggs.

Expansions of
IVF
In zygote intrafallopian transfer (ZIFT), egg cells are removed from the woman's ovaries and
fertilized in the laboratory; the resulting zygote is then placed into the fallopian tube. The
following are techniques generally requires methods of in vitro fertilisation. In vitro fertilization,
however, usually does not require these techniques.

Assisted zona hatching (AZH) is performed shortly before the embryo is transferred to the uterus. A
small opening is made in the outer layer surrounding the egg in order to help the embryo hatch out
and aid in the implantation process of the growing embryo.

Intracytoplasmic sperm injection (ICSI) is beneficial in the case of male factor infertility
where sperm counts are very low or failed fertilization occurred with previous IVF
attempt(s). The ICSI procedure involves a single sperm carefully injected into the center of
an egg using a microneedle. This method is also sometimes employed when donor sperm is
used.

Autologous endometrial coculture is a possible treatment for patients who have failed previous IVF
attempts or who have poor embryo quality. The patient's fertilized eggs are placed on top of a layer of
cells from the patient's own uterine lining, creating a more natural environment for embryo
development.

Cytoplasmic transfer is the technique in which the contents of a fertile egg from a donor are injected
into the infertile egg of the patient along with the sperm.

Egg donors are resources for women with no eggs due to surgery, chemotherapy, or genetic causes; or
with poor egg quality, previously unsuccessful IVF cycles or advanced maternal age. In the egg donor
process, eggs are retrieved from a donor's ovaries, fertilized in the laboratory with the sperm from the
recipient's partner, and the resulting healthy embryos are returned to the recipient's uterus.

Sperm donation may provide the source for the sperm used in IVF procedures where the male partner
produces no sperm or has an inheritable disease, or where the woman being treated has no male
partner.

A gestational carrier is an option when a patient's medical condition prevents a safe

pregnancy, when a patient has ovaries but no uterus due to congenital absence or previous
surgical removal, and where a patient has no ovaries and is also unable to carry a pregnancy
to full term.

Preimplantation genetic diagnosis (PGD) involves the use of genetic screening mechanisms
such as Fluorescent In Situ Hybridization (FISH) or Comparative Genomic Hybridization
(CGH) to help identify genetically abnormal embryos and improve healthy outcomes.

Embryo splitting can be used for twinning to increase the number of available embryos.

Risks
The risk of birth defects in infants born following assisted reproductive technology (ART)
treatment is a controversial question. Most publications examining the prevalence of birth
defects in ICSI and IVF infants compared to spontaneously conceived infants have serious
methodological limitations; despite this, most researchers have concluded that there is no
increased risk. METHODS: We carried out a systematic review to identify all papers published
by March 2003 with data relating to the prevalence of birth defects in infants conceived
following IVF and/or ICSI compared with spontaneously conceived infants. Independent expert
reviewers used criteria defined a priori to determine whether studies were suitable for inclusion
in a meta-analysis. Fixed effects meta-analysis was performed for all studies and reviewerselected studies. RESULTS: Twenty-five studies were identified for review. Two-thirds of these
showed a 25% or greater increased risk of birth defects in ART infants. The results of metaanalyses of the seven reviewer-selected studies and of all 25 studies suggest a statistically
significant 3040% increased risk of birth defects associated with ART.
CONCLUSIONS: Pooled results from all suitable published studies suggest that children born
following ART are at increased risk of birth defects compared with spontaneous conceptions.
This information should be made available to couples seeking ART treatment.

Bibliography

www.google.com
www.wikipedia.com
Various magazines and
newspapers