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In vitro fertilization (IVF) is a technique in
which egg cells are fertilized outside the woman's body. IVF is a major
treatment in infertility where other methods of achieving conception have
failed.
The process involves hormonally controlling the ovulatory process, removing
ova (eggs) from the woman's ovaries and letting sperm fertilize them in a
fluid medium. The fertilized egg (zygote) is then transferred to the
patient's uterus with the intent to establish a successful pregnancy. "In
vitro" is Latin for "in glass", referring to the test tubes; however neither
glass nor test tubes are used, and the term is used generically for
laboratory procedures. Babies that are the result of IVF have been called "test
tube babies". |
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Indications |
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Initially IVF was developed to overcome infertility due to
problems of the fallopian tube, but it turned out that it was successful in
most other infertility situations as well. The introduction of
intracytoplasmic sperm injection addresses the problem of male infertility
to a large extent.
Thus, for IVF to be successful it may be easier to say that it requires
healthy ova, sperm that can fertilize, and a uterus that can maintain a
pregnancy. Cost considerations generally place IVF as a treatment when other
less expensive options have failed.
This means that IVF can be used for females already gone through pregnancy.
The donated oocyte can be fertilized in a crucible. If the fertilization is
successful, the fertilized egg will be implanted into the uterus, within
which it will develop into an embryo. |
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Method |
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Ovarian stimulation
Treatment cycles are typically started on the third day of menstruation and
consist of a regimen of fertility medications to stimulate the development
of multiple follicles of the ovaries. In most patients injectable
gonadotropins (usually FSH analogues) are used under close monitoring. Such
monitoring frequently checks the estradiol level and, by means of
gynaecologic ultrasonography, follicular growth. Typically approximately 10
days of injections will be necessary. Endogenous ovulation is blocked by the
use of GnRH agonists or GnRH antagonists.
Oocyte retrieval
When follicular maturation is judged to be adequate, human chorionic
gonadotropin (β-hCG) is given. This agent, which acts as an analogue of
luteinising hormone, would cause ovulation about 36 hours after injection,
but a retrieval procedure takes place just prior to that, in order to
recover the egg cells from the ovary. The eggs are retrieved from the
patient using a transvaginal technique 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 handed to the IVF
laboratory to identify ova. The retrieval procedure takes about 20 minutes
and is usually done under conscious sedation or general anaesthesia.
IVF laboratory
In the laboratory, the identified eggs are stripped of surrounding cells and
prepared for fertilization. In the meantime, semen provided by the male
partner is prepared for fertilization by removing inactive cells and seminal
fluid. The sperm and the egg are incubated together (at a ratio of about
75,000:1) in the culture media for about 18 hours. By that time
fertilization should have taken place and the fertilized egg would show two
pronuclei. In situations where the sperm count is low a single sperm is
injected directly into the egg using intracytoplasmic sperm injection (ICSI).
The fertilized egg is passed to a special growth medium and left for about
48 hours until the egg has reached the 6-8 cell stage.
8-cell embryo for transfer
Enlarge
8-cell embryo for transfer
Laboratories have developed grading methods to judge oocyte and embryo
quality. Typically, embryos that have reached the 6-8 cell stage are
transferred three days after retrieval. In many programmes, however, embryos
are placed into an extended culture system with a transfer done at the
blastocyst stage, especially if many good-quality day-3 embryos are
available. Blastocysts may give higher pregnancy rates if embryo quality is
in doubt. However, many studies have shown no difference in pregnancy rates
between day-3 and day-5 transfers.
Embryo transfer
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.
Often, several embryos are passed into the uterus to improve chances of
implantation and pregnancy.
Post-transfer
The patient has to wait two weeks before she returns to the clinic for the
pregnancy test. During this time she may receive progesterone—a hormone that
keeps the uterus lining thickened and suitable for implantation. Many IVF
programmes provide additional medications as part of their protocol.
Acupuncture
According to the latest reports published in Fertility and Sterility, if
done correctly, Acupuncture significantly improves IVF success rate.
Acupuncture is integrated into the treatment protocols by many progressive
fertility clinics in the United States. |
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Pregnancy |
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The chance of a successful pregnancy is approximately
20-30% for each IVF cycle, although selected clinics are now able to quote
rates up to 50% per cycle. [2] There are many factors that determine success
rates including the age of the patient, the quality of the eggs and sperm,
the duration of the infertility, the health of the uterus, and the medical
expertise. It is a common practice for IVF programmes to boost the pregnancy
rate by placing multiple embryos during embryo transfer. A flip side of this
practice is a higher risk of multiple pregnancy, itself associated with
obstetric complications.
IVF programmes generally publish their pregnancy rates, however comparisons
between clinics are difficult as many variables determine outcome.
Furthermore, these statistics depend strongly on the type of patients
selected.
There are many reasons why pregnancy may not occur following IVF and embryo
transfer, including
• The timing of ovulation may be misjudged, or ovulation may not be able to
be predicted or may not occur
• Attempts to obtain eggs that develop during the monitored cycle may be
unsuccessful
• The eggs obtained may be abnormal or may have been damaged during the
retrieval process
• A semen specimen may not be able to be provided
• Fertilization of eggs to form embryos may not occur
• Cleavage or cell division of the fertilized eggs may not take place
• The embryo may not develop normally
• Implantation may not occur
• Equipment failure, infection and/or human error or other unforeseen and
uncontrollable factors, which may result in the loss of or damage to the
eggs, the semen sample and/or the embryos[4] |
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Complications |
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The major complication of IVF is the risk of multiple
births.[3] This is directly related to the practice of transferring multiple
embryos at embryo transfer. Multiple births are related to increased risk of
pregnancy loss, obstetrical complications, prematurity, and neonatal
morbidity with the potential for long term damage. Strict limits on the
number of embryos that may be transferred have been enacted in some
countries (e.g., England) to reduce the risk of high-order multiples
(triplets or more), but are not universally followed or accepted.
Spontaneous splitting of embryos in the womb after transfer does occur, but
is rare (<1%) and would lead to identical twins. Recent evidence suggest
that singleton offspring after IVF is at higher risk for lower birth weight
for unknown reasons.
Another risk of ovarian stimulation is the development of ovarian
hyperstimulation syndrome.
If the underlying infertility is related to abnormalities in
spermatogenesis, it is plausible, but too early to examine that male
offspring is at higher risk for sperm abnormalities.
Birth defects
The issue of birth defects remains a controversial topic in IVF. A majority
of studies do not show a significant increase after use of IVF. Some studies
suggest higher rates for ICSI , while others do not support this finding.[5]
Major birth defect include chromosomal abnormalities, genetic imprinting
defects, and multiple organ abnormalities. Hansen et al conducted a
systematic review of published studies (including ICSI) and found a 30-40%
increase risk of birth defects associated with assisted reproductive
technology when compared to children born after spontaneous conception.[6]
Possible explanations offered were the underlying cause of the infertility,
factors associated with IVF/ICSI, culture conditions, and medications,
however, the actual cause is not known. |
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