IVF

IVF or in-vitro fertilization literally translates to fertilization

outside the body, IVF is a first line therapy for a variety of
problems such as endometriosis, tubo-peritoneal
disturbances, pelvic adhesions, PCOD and cases of
unexplained infertility. Also, patients who have had repeated
failures of IUI or simple treatment methods in the past qualify
for IVF
n vitro fertilization (IVF) is an assisted reproductive
technology (ART) initially introduced by Patrick
Steptoe and Robert Edwards in the 1970s to treat
female infertility caused by damaged or blocked
fallopian tubes. This major breakthrough in embryo
research has provided large numbers of women the
possibility of becoming pregnant, and subsequent
advances have dramatically increased their chances.
IVF is a laboratory procedure in which sperm and egg
are fertilized outside the body; the term in vitro is
Latin for in glass.
Although the procedure was not successfully
established until the last quarter of the twentieth
century, the history behind the development of IVF
dates back much further. The first attempt at IVF on
mammalian eggs was performed by Viennese
embryologist Samuel Leopold Schenk in 1878.
Working with rabbit and guinea pig ova, Schenk noted
that cell division occurred in cultures after sperm were
added to ova. In 1934 Gregory Pincus and Ernst
Vinzenz Enzmann also attempted in vitro fertilization
with rabbits. They claimed to have produced the first
successful pregnancy using IVF, but later analysis of
their study suggests that their fertilization technically
occurred in vivo, or in the body, rather than in vitro,
in glass. They implanted the eggs into the rabbits
uterus after only twelve hours, before the eggs had
fully matured, and fertilization actually occurred inside

the body.
The next milestone was in 1951, when two scientists
working independently, Colin Russell Austin in
Australia and Min Chueh Chang in the United Sates,
demonstrated that spermatozoa need to mature
through certain stages before they develop the
capacity to fertilize. By 1959 Chang was able to
successfully use IVF to impregnate a rabbit. Significant
progress in developing a successful IVF technique with
human embryos, however, would have to wait until
the 1970s.
Patrick Steptoe, a practicing gynecologist at Oldam
General Hospital who pioneered the use of
laparoscopy in gynecology, teamed up with Edwards,
a professor of human reproduction at Cambridge
University, to try to achieve a successful pregnancy in
humans using IVF. Their collaboration started in 1968
when Edwards attended a lecture Steptoe gave on
laparoscopy at the Royal Society of Medicine in
London. They initially achieved successful fertilization
and cell division of eggs in vitro (in a petri dish) with
freshly extracted semen, but were unable to
successfully implant the fertilized egg into the female
uterus until 1978. They manipulated hormone levels in
the female until the eggs were fully mature and then
extracted several eggs from the ovaries through
laparoscopy, an invasive technique requiring entry
through the navel. The doctors fertilized the eggs in
vitro, and waited until the fertilized eggs divided into
eight cells before implanting them into the female
uterus (up until the mid-1970s, they had waited until
the fertilized egg divided into 100 cells before
implantation).
In 1976 Edwards and Steptoe began working with an
infertile couple, Lesley and John Brown. In the
successful attempt, Edward and Steptoe transferred a
fertilized egg at midnight, the time at which the egg

was matureaccidental timing that they later

discovered was critical when they realized that diurnal
cycles of hormonal levels are crucial to the success of
the egg implanting in the wall of the uterus. On 25 July
1978, Leslie gave birth to Louise Brown, the first test
tube baby.
Since the birth of Louise Brown, over three million
babies have been born as a result of IVF and other
assisted reproductive technologies, and the technique
has improved as well. Laparoscopy is no longer used
to extract eggs from the ovaries. Instead, physicians
use transvaginal oocyte retrieval; that is, with a
sonogram to visualize what they are doing, they guide
a needle through the vaginal wall, and enter the
ovaries to extract the eggs. By using this method, the
risks associated with the anesthesia required for
laparoscopy as well as the costs of the procedure are
considerably reduced.
Physicians now begin giving women hormone therapy
two weeks prior to retrieving the eggs to increase the
chance of recovering several healthy, mature eggs.
Hormone therapies are usually administered through
oral medications such as clomiphene citrate, also
known as Clomid. Ultrasounds and blood tests are
used to determine the optimal time for egg retrieval
(when the eggs are almost ready for fertilization).
Once physicians obtain the eggs, they then place
them in a petri dish with sperm for fertilization.
Usually about seven to nine eggs are fertilized. If a
male fertility problem exists such as sperm immotility
or a low sperm count, intracytoplasmic sperm injection
(ICSI) is commonly used to combat the problem. With
ICSI, the physician manually injects a sperm into an
egg with a needle to fertilize it.
The number of fertilized eggs physicians place in the
uterus in hopes that at least one will implant varies
with the physician conducting the procedure.

Physicians consider different factors with each couple,

such as the number of trials the couple can afford to
attempt. The remaining embryos are preserved
through cryopreservation, frozen for future use in case
the first few embryos fail to implant in the uterus wall
on the initial attempt. Once the fertilized eggs each
divide into eight cells, they are placed in a catheter
and inserted through the cervix into the uterus (this
usually occurs from two to three days after retrieving
the eggs and follows the same timeline as if the eggs
were fertilized naturally).
When Edwards and Steptoe successfully helped the
Browns give birth to Louise, the first test tube baby,
many ethical debates arose. Many of these issues still
surround embryo research today, and they include
who essentially owns the embryos as well as
whether scientists should be allowed to perform
experiments for stem cell research with the extra
cryopreserved embryos that are not implanted. Many
religious groups, the Roman Catholic Church being the
most prominent, are strongly against IVF because it is
not considered natural conception.
IVF has greatly advanced embryo research as well as
helped many infertile couples conceive when adoption
was once their only option for children. Though there
are other similar assisted reproductive technologies
(ART) such as gamete intrafallopian transfer (GIFT)
and zygote intrafallopian transfer (ZIFT), IVF is
currently the most popular. The development of
intracytoplasmic sperm injection (ICSI) has improved
success rates.

Specific steps of an in vitro fertilization (IVF) cycle carry risks,

including:
Multiple births. IVF increases the risk of multiple births if
more than one embryo is implanted in your uterus. A
pregnancy with multiple fetuses carries a higher risk of early

labor and low birth weight than pregnancy with a single fetus
does.
Premature delivery and low birth weight. Research
suggests that use of IVF slightly increases the risk that a baby
will be born early or with a low birth weight.
Ovarian hyperstimulation syndrome. Use of injectable
fertility drugs, such as human chorionic gonadotropin (HCG),
to induce ovulation can cause ovarian hyperstimulation
syndrome, in which your ovaries become swollen and painful.
Signs and symptoms typically last a week and include mild
abdominal pain, bloating, nausea, vomiting and diarrhea. If
you become pregnant, however, your symptoms might last
several weeks. Rarely, it's possible to develop a more-severe
form of ovarian hyperstimulation syndrome that can also
cause rapid weight gain and shortness of breath.
Miscarriage. The rate of miscarriage for women who
conceive using IVF with fresh embryos is similar to that of
women who conceive naturally about 15 to 25 percent
but the rate increases with maternal age. Use of frozen
embryos during IVF, however, may slightly increase the risk of
miscarriage.
Egg-retrieval procedure complications. Use of an
aspirating needle to collect eggs could possibly cause
bleeding, infection or damage to the bowel, bladder or a blood
vessel. Risks are also associated with general anesthesia, if
used.
Ectopic pregnancy. About 2 to 5 percent of women who use
IVF will have an ectopic pregnancy when the fertilized egg
implants outside the uterus, usually in a fallopian tube. The
fertilized egg can't survive outside the uterus, and there's no
way to continue the pregnancy.
Birth defects. The age of the mother is the primary risk factor
in the development of birth defects, no matter how the child is
conceived. More research is needed to determine whether
babies conceived using IVF might be at increased risk of
certain birth defects. Some experts believe that the use of IVF
does not increase the risk of having a baby with birth defects.

Ovarian cancer. Although some early studies suggested

there may be a link between certain medications used to
stimulate egg growth and the development of a specific type
of ovarian tumor, more recent studies do not support these
findings.
Stress. Use of IVF can be financially, physically and
emotionally draining. Support from counselors, family and
friends can help you and your partner through the ups and
downs of infertility treatment.
Your clinic will discuss the risks of in vitro fertilisation (IVF)
with you before you begin treatment. It is very important that
you are fully aware of all the potential problems involved.

Drug reaction
A mild reaction to fertility drugs may involve hot flushes,
feeling down or irritable, headaches and restlessness.
Symptoms usually disappear after a short time but if they do
not, you should see a doctor as soon as possible.
Fertility drugs

"

Ovarian hyper-stimulation syndrome (OHSS)

OHSS can be a dangerous over-reaction to fertility drugs used
to stimulate egg production. It can cause symptoms such as a
swollen stomach, stomach pains, nausea and vomiting.
If you start to experience any of these symptoms you must
contact your doctor immediately.
Risks of fertility treatment - OHSS

"

Miscarriage
Although the risk of a miscarriage after IVF is no higher than
after a natural conception, nor is the risk lower.
Your clinic will arrange an early pregnancy ultrasound scan if
you conceive after IVF. This is to check that the pregnancy is
not likely to miscarry. The scan is usually done about two
weeks after the positive pregnancy test.
Miscarriage association website

"

Ectopic pregnancy
When an embryo develops in your fallopian tube rather than
your womb, the pregnancy is said to be ectopic.
An ectopic pregnancy can still occur after IVF. Ectopic
pregnancy can cause vaginal bleeding, low pregnancy
hormone levels and miscarriage.
Hormone tests and scans are used to detect ectopic
pregnancies and you should tell your doctor about any vaginal
bleeding or stomach pain.
The Ectopic Pregnancy Trust website
Multiple births
Having a multiple birth (twins, triplets or more) is the single
greatest health risk associated with fertility treatment.
Your clinic should discuss this risk with you when deciding
how many embryos to transfer in your treatment.

IVF - chance of success

A womans ability to conceive a child reduces with age. If you
are using your own eggs, on average, the younger you are the
higher your chances of success.
In 2010 (the year for which the most recent data is
available) women having in vitro fertilisation (IVF) using fresh
embryos created with their own fresh eggs, the percentage of
cycles started that resulted in a live birth (national averages)
was:
32.2% for women aged under 35
27.7% for women aged between 3537
20.8% for women aged between 3839
13.6% for women aged between 4042
5.0% for women aged between 4344

1.9% for women aged 45 and over

Please note that IVF and intra-cytoplasmic sperm injection
(ICSI) success are very similar and as such are no longer
presented seperately. The above results are for both IVF and
ICSI together.
IVF treatment options
It is worth exploring the various in vitro fertilisation (IVF)
treatment options to ensure that you understand what is
available:
Natural cycle IVF
Natural cycle IVF involves collecting and fertilising the one
egg that you release during your normal monthly cycle. No
fertility drugs are used in this treatment.
Mild stimulation IVF
With mild stimulation IVF, the woman is either given a lower
dose of fertility drugs or is given them over a shorter period
than with conventional IVF.
In vitro maturation (IVM)
In the IVM process, eggs are removed from the ovaries and
are collected when they are still immature. They are then
matured in the laboratory before being fertilised.
Embryo transfer
Embryo transfer takes place after eggs have been collected
and fertilised in the laboratory. Depending on your situation
between one and three of the best quality embryos are
selected and then transferred to the womans womb.
Blastocyst transfer
With blastocyst transfer, embryos are cultured in the
laboratory incubator to the blastocyst stage before they are
transferred to the womb.

Assisted hatching
It has been suggested that making a hole in or thinning this
outer layer may help embryos to hatch, increasing the
chances of the woman becoming pregnant in some cases.

CASE STUDY