Assisted

reproductive
technology
Assisted reproductive technology

Intervention

Illustration depicting intracytoplasmic sperm injection (ICSI), an

example of assisted reproductive technology.

Assisted reproductive technology (ART) is the technology
used to achieve pregnancy in procedures such as fertility
medication, artificial insemination, in vitro
fertilization and surrogacy. It is reproductive
technology used primarily for infertilitytreatments, and
is also known as fertility treatment. It mainly belongs to
the field of reproductive endocrinology and infertility,
and may also include intracytoplasmic sperm
injection (ICSI) and cryopreservation. Some forms of ART
are also used with regard to fertile couples for genetic
reasons (preimplantation genetic diagnosis). ART is also
used for couples who are discordant for certain
communicable diseases; for example, HIV to reduce the
risk of infection when a pregnancy is desired.

PROCEDURE
With ART, the process of sexual intercourse is bypassed
either by artificial insemination or fertilization of
the oocytes in the laboratory environment (i.e., in vitro
fertilization). TheCenters 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 clinics—defines 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 donatin g them to another woman."
According to CDC, "they do not include treatments in
which only sperm are handled (i.e., intrauterine—or
artificial—insemination) or procedures in which a
woman takes medicine only to stimulate egg production
without the intention of having eggs retrieved."
Procedures are mainly fertility medication, as well as
ART techniques that use more substantial and forceful
interventions, of which in vitro fertilization (IVF) and
expansions of it (e.g. OCR, AZH, ICSI, ZIFT) are the most
prevalent. However, there are also other manual ART, not
necessarily dependent on IVF (e.g. PGD, GIFT, SSR).
Fertility medication
Most fertility medications are agents that stimulate the
development of follicles in the ovary. Examples are
gonadotropins and gonadotropin releasing hormone.

Usage
Assisted reproductive technology procedures performed
in the U.S. has more than doubled over the last 10 years,
with 140,000 procedures in 2006,[15] resulting in 55,000
births.[15]In Australia, 3.1% of births are a result of ART.
[16]In case of discontinuation of fertility treatment, the
most common reasons have been estimated to be:
postponement of treatment (39%), physical and
psychological burden (19%, psychological burden 14%,
physical burden 6.32%), relational and personal
problems (17%, personal reasons 9%, relational
problems 9%), treatment rejection (13%) and
organizational (12%) and clinic (8%) prob

ETHICS
Some couples find it difficult to stop treatment despite
very bad prognosis, resulting in futile therapies. This may
give ART providers a difficult decision of whether to
continue or refuse treatment
For treatment-specific ethical considerations, see entries
in individual subarticles, e.g. In vitro
fertilisation, Surrogacy and Sperm donation
Some assisted reproductive technologies can in fact be
harmful to both the mother and child. Posing a
psychological and a physical health risk, which may
impact the ongoing use of these treatments ,

In vitro fertilisation
In vitro fertilisation (or fertilization; IVF) is a process by
which an egg is fertilised by sperm outside the body: in
vitro ("in glass"). The process involves monitoring and
stimulating a woman's ovulatory process, removing
an ovum or ova (egg or eggs) from the
woman's ovaries and letting sperm fertilise them in a
liquid in a laboratory. The fertilised egg (zygote) is
cultured for 2–6 days in a growth medium and is then
transferred to the same or another woman's uterus, with
the intention of establishing a successful pregnancy.
IVF techniques can be used in different types of situations.
It is a technique of assisted reproductive technology for
treatment ofinfertility. IVF techniques are also employed
in gestational surrogacy, in which case the fertilised egg
is implanted into a surrogate's uterus, and the resulting
child is genetically unrelated to the surrogate. In some
situations, donated eggs or sperms may be used. Some
countries ban or otherwise regulate the availability of
IVF treatment, giving rise to fertility tourism. Restrictions
on availability of IVF include costs and age to carry a
healthy pregnancy to term. Due to the costs of the
procedure, IVF is mostly attempted only after less
expensive options have failed.
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 where no stimulation was
made.  With egg donation and IVF, women who are past
their reproductive years ormenopause can still become
pregnant. . After the IVF treatment many couples are able
to get pregnant without any fertility treatments. In 2012
it was estimated that five million children had been born
worldwide using IVF and other assisted reproduction
techniques

Medical uses
IVF may be used to overcome female
infertility where it is due to problems with
the fallopian tubes, making fertilisation in
vivo difficult. It can also assist in male
infertility, in those cases where there is a
defect in sperm quality; in such
situations intracytoplasmic sperm
injection (ICSI) may be used, where a
sperm cell is injected directly into the egg
cell. This is used when sperm has 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. When indicated, the use of ICSI
has been found to increase the success

rates of IVF.
According to the British NICE guidelines, IVF treatment is
appropriate in cases of unexplained infertility for women
that have not conceived after 2 years of regular
unprotected sexual intercourse.[4] This rule does not
apply to all countries. (See infertility.)

Complications
 Spread of infectious disease
By sperm washing, the risk that a chronic disease in
the male providing the sperm would infect the female
or offspring can be brought to negligible levels.In
males with hepatitis B, The Practice Committee of the
American Society for Reproductive Medicine advises
 that sperm washing is not necessary in IVF to prevent
transmission, unless the female partner has not been
effectively vaccinated.[29][30] In females with
hepatitis B, the risk of vertical transmission during IVF
is no different from the risk in spontaneous conception.
[30] However, there is not enough evidence to say
that ICSI procedures are safe in females with hepatitis
B in regard to vertical transmission to the offspring.
[30]

 Other risks to the egg provider/retriever

A risk of ovarian stimulation is the development
of ovarian hyperstimulation syndrome, particularly if
hCG is used for inducing final oocyte maturation. This
results in swollen, painful ovaries. It occurs in 30% of
patients. Mild cases can be treated with over the
counter medications and cases can be resolved in the
absence of pregnancy. In moderate cases, ovaries swell
and fluid accumulated in the abdominal cavities and
may have symptoms of heartburn, gas, nausea or loss
of appetite. In severe cases patients have sudden excess
abdominal pain, nausea, vomiting and will result in
hospitalisation.During egg retrieval, there’s a small
chance of bleeding, infection, and damage to
surrounding structures like bowel and bladder
(transvaginal ultrasound aspiration) as well as
difficulty in breathing, allergic reactions to
medication, or nerve damage (laproscopy).
Ectopic pregnancy may also occur if a fertilised egg
develops outside the uterus, usually in the fallopian tubes
and requires immediate destruction of the fetus.
IVF does not seem to be associated with an elevated risk
of cervical cancer, nor with ovarian
cancer or endometrial cancer when neutralising
the confounder of infertility itself.[32]Nor does it seem to
impart any increased risk for breast cancer.[33]
Regardless of pregnancy result, IVF treatment is usually
stressful for patients.[34] Neuroticism and the use
of escapist coping strategies are associated with a higher
degree of distress, while the presence social support has a
relieving effect.[34] A negative pregnancy test after IVF is
associated with an increased risk for depression in
women, but not with any increased risk of
developing anxiety disorders.[35] Pregnancy test results
do not seem to be a risk factor for depression or anxiety
among men.[35]
Other risks to the offspring
If the underlying infertility is related to abnormalities in
spermatogenesis, it is plausible, but too early to examine
that male offspring are at higher risk for sperm
abnormalities. [clarification needed]
IVF does not seem to confer any risks regarding cognitive
development, school performance, social functioning and
behaviour.[41] Also, IVF infants are known to be as
securely attached to their parents as those who were
naturally conceived, and IVF adolescents are as well-
adjusted as those who have been naturally conceived.[42]
Limited long-term follow-up data suggest that IVF may be
associated with an increased incidence
ofhypertension, impaired fasting glucose, increase in
total body fat composition, advancement of bone age,
subclinical thyroid disorder, early adulthood clinical
depression and binge drinking in the offspring.[41]
[43] It is not known, however, whether these potential
associations are caused by the IVF procedure in itself, by
adverse obstetric outcomes associated with IVF, by the
genetic origin of the children or by yet unknown IVF-
associated causes.[41][43] Increases in embryo
manipulation during IVF result in more deviant fetal
growth curves, but birth weight does not seem to be a
reliable marker of fetal stress.[44]
An IVF-associated incidence of cerebral
palsy and neurodevelopmental delay are believed to be
related to the confounders of prematurity and low
birthweight.[41] Similarly, an IVF-associated incidence
of autism andattention-deficit disorder are believed to
be related to confounders of maternal and obstetric
factors.[41]
Overall, IVF does not cause an increased risk of childhood
cancer.[46] Studies have shown a decrease in the risk of
certain cancers and an increased risks of certain others
including retinoblastoma[47] hepatoblastoma[46] and
rhabdomyosarcoma.[46]

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 sperm, and
reinserting the fertilised ova into the uterus. However,
without additional techniques, the chances of pregnancy
would be extremely small. The additional techniques that
are routinely used in IVF include ovarian
hyperstimulation to generate multiple eggs or
ultrasound-guided transvaginal oocyte retrieval directly
from the ovaries; after which the ova and sperm are
prepared, as well as culture and selection of resultant
embryos before embryo transfer into a uterus.
Natural IVF
There are several methods termed natural cycle IVF:
[49]IVF using no drugs for ovarian hyperstimulation,
while drugs for ovulation suppression may still be
used.IVF using ovarian hyperstimulation, including
gonadotropins, but with a GnRH antagonist protocol so
that the cycle initiates from natural mechanisms.Frozen
embryo transfer; IVF using ovarian hyperstimulation,
followed by embryo cryopreservation, followed
by embryo transfer in a later, natural, cycle.[50]
IVF using no drugs for ovarian hyperstimulation was the
method for the conception of Louise Brown. This method
can be successfully used when women want to avoid
taking ovarian stimulating drugs with its associated side-
effects. HFEA has estimated the live birth rate to be
approximately 1.3% per IVF cycle using no
hyperstimulation drugs for women aged between 40–42.
[51]
Final maturation
When the ovarian follicles have reached a certain degree
of development, induction of final oocyte maturation is
performed, generally by an injection of human chorionic
gonadotropin (hCG). Commonly, this is known as the
"trigger shot."[55] hCG acts as an analogue of luteinising
hormone, and ovulation would occur between 38 and 40
hours after a single HCG injection,[56] but the egg
retrieval is performed at a time usually between 34 and
36 hours after hCG injection, that is, just prior to when
the follicles would rupture. This avails for scheduling the
egg retrieval procedure at a time where the eggs are fully
mature. HCG injection confers a risk of ovarian
hyperstimulation syndrome. Using aGnRH
agonist instead of hCG eliminates the risk of ovarian
hyperstimulation syndrome, but with a delivery rate of
approximately 6% less than with hCG.

Eggs retrieval
The eggs are retrieved from the patient using a
transvaginal technique called transvaginal oocyte
retrieval, involving an ultrasound-guided needle piercing
the vaginal wall to reach the ovaries. Through this needle
follicles can be aspirated, and the follicular fluid is passed
to an embryologist to
identify ova. It is common to remove between ten and
thirty eggs. The retrieval procedure usually takes
between 20 and 40 minutes, depending on the number of
mature follicles, and is usually done under conscious
sedation orgeneral anaesthesia.
Egg and 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.
Co-incubation
The sperm and the egg are incubated together at a ratio
of about 75,000:1 in a culture media in order for the
actual fertilisation to take place. A review in 2013 came
to the result that a duration of this co-incubation of about
1 to 4 hours results in significantly higher pregnancy
rates 
than 16 to 24 hours.[58] In most cases, the egg will be
fertilised during co-incubation and 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.
Embryo culture[
The main durations of embryo culture are until cleavage
stage (day two to four after co-incubation) or
the blastocyst stage (day five or six after co-incubation).
[59] Embryo culture until the blastocyst stage confers a
significant increase in live birth rate per embryo
transfer, but also confers a decreased number of embryos
available for transfer and embryo cryopreservation
Embryo 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.[60] Since 2009 where the
first time-lapse microscopy system for IVF was approved
for clinical use,[61]morphokinetic scoring systems has
shown to improve to pregnancy rates further.
[62] However, when all different types of time-lapse
embryo imaging devices, with or without morphokinetic
scoring systems, are compared against conventional
embryo assessment for IVF, there is insufficient evidence
of a difference in live-birth, pregnancy, stillbirth or
miscarriage to choose between them. [63]

Embryo transfer
Embryos are graded 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.
Artificial insemination
Artificial insemination is the deliberately introduction of
sperms intofemale's uterus or cervix for the purpose of
achieving apregnancy through in vivo fertilization by
means other than sexual intercourse. It is a fertility
treatment for humans, and is a common practice
in animal breeding, including dairy cattle  (see Frozen
bovine semen) and pigs.
Artificial insemination may employ assisted reproductive
technology, sperm donation and animal
husbandry techniques. Artificial insemination techniques
available include intracervical
insemination and intrauterine insemination. The
primary beneficiaries of artificial insemination
are heterosexual couples suffering from male
infertility, lesbian couples and single women.
Intracervical insemination (ICI) is the easiest and most
common insemination technique and can be used in the
home for self-insemination without medical practitioner
assistance.[1] Compared to natural insemination (i.e.,
insemination by sexual intercourse), artificial
insemination can be more expensive and more invasive,
and may require professional assistance.
There are laws in some countries which restrict and
regulate who can donate sperms and who is able to
receive artificial insemination, and the consequences of
such insemination. Subject to any regulations restricting
who can obtain donor sperms, donor sperms are
available to all women who, for whatever reason, want or
need them. Some women living in a jurisdiction which
does not permit artificial insemination in the
circumstance in which she finds herself may travel to
another jurisdiction which permits it.
In humans
Before artificial insemination is turned to as the solution
to impregnate a woman, doctors will require an
examination of both the male and female involved in
order to remove any and all physical hindrances that are
preventing them from naturally achieving a pregnancy.
The couple is also given a fertility test to determine the
motility, number, and viability of the male's sperm and
the success of the female's ovulation. From these tests, the
doctor may or may not recommend a form of artificial

insemination.
The sperm used in artificial insemination may be
provided by either the woman's husband or partner
(partner sperm) or by a known or anonymous sperm
donation (donor sperm). Though there may be legal,
religious and cultural differences in these and other
characterizations, the manner in which the sperm is
actually used in AI would be the same, If the procedure is
successful, the woman will conceive and carry a baby to
term in the normal manner. A pregnancy resulting from
artificial insemination will be no different from a
pregnancy achieved by sexual intercourse. In all cases,
the woman would be the biological mother of any child
produced by AI, and the male whose sperm is used would
be the biological father.
There are a number of reasons why a woman would use
artificial insemination to achieve pregnancy. For
example, a woman's immune system may be rejecting her
partner's sperm as invading molecules.[2] Women who
have issues with the cervix, such as cervical scarring,
cervical blockage from endometriosis, or thick
cervical mucus may also benefit from artificial
insemination since the sperm must pass through the
cervix to result in fertilization.
Preparations
Timing is critical, as the window and opportunity for
fertilization is little more than twelve hours from the
release of the ovum. To increase the chance of success, the
woman's menstrual cycle is closely observed, often using
ovulation kits, ultrasounds or blood tests, such as basal
body temperature tests over, noting the color and texture
of the vaginal mucus, and the softness of the nose of her
cervix. To improve the success rate of AI, drugs to create
a stimulated cycle may be used, but the use of such drugs
also results in an increased chance of a multiple birth.
Sperm can be provided fresh or washed.[3] The washing
of sperm increases the chances of fertilization. Pre- and
post-concentration of motile sperm is counted. Sperm
from a sperm bank will be frozen and quarantined for a
period and the donor will be tested before and after
production of the sample to ensure that he does not carry
a transmissible disease. For fresh shipping, a semen
extender is used.
If sperm is provided by a private donor, either directly or
through a sperm agency, it is usually supplied fresh, not
frozen, and it will not be quarantined. Donor sperm
provided in this way may be given directly to the recipient
woman or her partner, or it may be transported in
specially insulated containers. Some donors have their
own freezing apparatus to freeze and store their sperm.
Techniques[edit]
The Human female reproductive system. The cervix is
part of the uterus. The cervical canal connects the
interiors of the uterus and vagina.
Semen used in insemination would be used either fresh,
raw or frozen. Where donor sperm is supplied by a sperm
bank, it will always be quarantined and frozen and will
need to be thawed before use. When an ovum is released,
semen is introduced into the
woman's vagina,uterus or cervix, depending on the
method being used.
Intrauterine insemination[edit]

Intrauterine insemination (IUI) involves injection of

washed sperm into the uterus with a catheter. If
unwashed semen is used, it may elicit uterine cramping,
expelling the semen and causing pain, due to content
of prostaglandins. (Prostaglandins are also the
compounds responsible for causing the myometrium to
contract and expel the menses from the uterus,
during menstruation.) Resting on the table for fifteen
minutes after an IUI is optimal for the woman to increase
the pregnancy rate.[4]
Unlike ICI, intrauterine insemination normally requires a
medical practitioner to perform the procedure. A female
under 30 years of age has optimal chances with IUI; for
the man, a TMS of more than 5 million per ml is optimal.
[5] In practice, donor sperm will satisfy these criteria. A
promising cycle is one that offers two follicles measuring
more than 16 mm, and estrogen of more than 500 pg/mL
on the day of hCG administration.[5] A short period of
ejaculatory abstinence before intrauterine insemination
is associated with higherpregnancy rates.
[6] However, GnRH agonist administration at the time of
implantation does not improve pregnancy outcome in
intrauterine insemination cycles according to
arandomized controlled trial.[7]
IUI is a more efficient method of artificial insemination.
Sperm is occasionally inserted twice within a 'treatment
cycle'. A double intrauterine insemination theoretically
increases pregnancy rates by decreasing the risk of
missing the fertile window during ovulation. However,
a randomized trial of insemination after ovarian
hyperstimulation found no difference in live birth rate
between single and double intrauterine insemination.[8]

Pregnancy rate[edit]
The pregnancy or success rates for artificial insemination
are 10 to 15% per menstrual cycle using ICI, and[13] and
15–20% per cycle for IUI.[13][unreliable source?] In IUI,
about 60 to 70% have achieved pregnancy after 6 cycles.
[14]However, these pregnancy rates may be very
misleading, since many factors, including the age and
health of the recipient, have to be included to give a
meaningful answer, e.g. definition of success and
calculation of the total population.[15] For couples
withunexplained infertility, unstimulated IUI is no more
effective than natural means of conception