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In vitro fertilization (IVF) literally means
"fertilization outside the human body" or, in broader
terms, in the laboratory. This term applies to any form
of assisted conception where fertilization takes place
outside the body.
The initial screening would cover hormone estimations
such as a serum FSH, LH, Prolactin and TSH. Also, a
Transvaginal ultrasound to diagnose any ovarian cysts,
submucous fibroids, endometrial polyps, chocolate cysts
and hydrosalpinges which would require a surgical correction
prior to IVF. Besides routine hematological investigations
such as CBC, Sugar, HIV, Hepatitis B & C, VDRL, a semen
analysis would help in selecting between IVF & ICSI
(the latter being preferred in the presence of low
sperm counts or poor sperm motility).
The next basic step after recruitment would be
selection of the ideal ovarian stimulation protocol.
Controlled ovarian stimulation
This involves a series of hormone injections to
encourage the ovaries to produce more eggs than usual.
You can have these injections either at our clinic if
you stay in the vicinity or from your general practitioner
or you could have a nurse or clinic assistant to come and
inject you at home or we could teach your husband how to
give the injections OR YOU COULD SELF INJECT.
The common drugs which would be
prescribed to you are as follows:
- GnRH-agonist (gonadotropin releasing hormone agonist) or a
GnRH-antagonist (e.g. Cetrotide / Ganirelix) to prevent release of the eggs before doctor can retrieve them
-
FSH (Follicle stimulating hormone) or hMG
(Human menopausal gonadotropin) to stimulate
development of multiple follicles and ensure a cohort of good quality and mature eggs
-
HCG (Human chorionic gonadotropin) to cause final
maturation of the eggs in the follicles.
The purpose of the GnRH-agonist (or antagonist) is to
suppress release of LH (luteinizing hormone) from the
woman's pituitary gland during the ovarian stimulation
process. LH surges would cause premature ovulation (release)
of the eggs before we can retrieve the eggs and are therefore
mandatory as part of the stimulation protocol.
The purpose of the FSH product is to stimulate development
of multiple follicles (structures that contain eggs) in the
ovaries.
Every month, as you approach ovulation, a
number of follicles begin to mature (exactly how many
varies, and depends on your age). Usually, the
follicle that is mature first is ovulated, and
all the other developing follicles shrink away
and are lost in a process call atresia. When you
are on the hormone treatment, most or all these
developing eggs are allowed to continue growing
until a number of them have reached maturity.
In this way, we can make use of eggs that would
have otherwise been wasted, without using up your
egg reserve any faster. Thus, there is no need to
fear early menopause because of these treatments.
Throughout the stimulation period, you will need to
visit us for ultrasound monitoring and sometimes blood
hormone levels. This will help us know when there are
enough follicles that are mature enough for us to go
ahead with the "egg pick-up".
Collecting the eggs
Usually, the egg pick-up is performed through the
wall of the vagina, guided by ultrasound. We
prefer a short acting propofol anesthesia to help
you recover immediately after the procedure.
The ovaries are scanned through the vagina,
in the same way that they were during your monitoring.
A needle is placed through the wall of the vagina and
into the ovary, where the follicles are emptied of
their fluids and their eggs. Post operative recovery
is usually quick and uneventful.
Simultaneously, an embryologist is present at the
time of the procedure in the embryo culture laboratory,
looking through the follicular fluid, finding the eggs,
and scoring them according to their maturity and quality.
Precautions are taken to maintain the eggs at body
temperature at all times.
Collecting the sperm
To ensure that we have an adequate quantity
of sperm for IVF, 3-7 days abstinence is required
before giving the semen sample. (We recommend that
you ejaculate on the day prior to the trigger injection.)
Sperm collection can be done in one of our special,
very private collection rooms. You may do this alone or
together with your wife, whichever you prefer.
If you anticipate that you will have any trouble
providing a sample on the day of the egg pick-up
procedure, we can arrange for you to collect ahead of
time and have the sperm frozen. We can also provide
special non-sperm-toxic condoms if you wish to collect at
home instead. If you choose this option though, you do
need to get the sample to us as quickly as possible
afterwards. In the laboratory, the sperm will be washed and
specially prepared for IVF.
Fertilization
Your eggs and sperm will be taken to our
embryology lab, which is adjoining the
operation theatre where you will have had
the procedure. Once in the lab, the eggs are
isolated from the fluid and other cells, and
prepared for IVF. The prepared sperm and eggs
are combined in a glass dish filled with a
nutritive medium. The eggs are then left in
an incubator overnight. The next day, the eggs
are checked for signs of fertilization. You can
tell the difference between a fertilized egg and
an unfertilized egg by two faint spheres visible
in an egg after fertilization.
These two spheres (pronuclei) hold the DNA
of the sperm and the egg, and will fuse to
form the nucleus of the embryo (called syngamy).
The fertilized eggs will be left to grow for
several days in the laboratory. The embryos grow
in the special mini-incubators (Ming, Cook, Australia)
that hold only 4 culture dishes, so that your embryos
are not disturbed every time someone else's embryos
are checked on, as they would be in the traditional
bigger incubators. The embryologist will record how
many eggs are successfully developing, and two or
three of the embryos will be chosen for the embryo
transfer. Any remaining good quality embryos can
be 'frozen' for future use if you wish.
By the time the embryo is transferred, it
consists of at least 2 to 8 cells, surrounded
by a soft "shell" (the zona pellucida). After the
transfer, the growing embryo will need to hatch out
of the zona pellucida to implant in the lining of
the uterus. On the day after the egg pick-up
procedure, please call us to find out if the eggs
have been fertilized. If at least one embryo is
available for transfer back to your uterus an appointment
will be made for the embryo transfer procedure.
Embryo transfer
The embryo transfer itself is a very simple
procedure, usually taking just a few minutes,
and requiring no anaesthesia or sedation. The
embryos are kept in the laboratory until you
are ready for the procedure. The embryos
are picked up with special two-part catheter
(a bit like a very thin syringe ). This is
carefully guided through the cervix, and a
thin soft tube that will not damage the lining
of the uterus is advanced out to reach the middle
of the uterus, and the embryos are deposited there.
The front and back of the uterus are normally
touching, and this holds the embryo in place -
so you can get up straight away.
After the transfer
To make sure the lining of your uterus
(the endometrium) is ready for the embryo to
implant, you will need to have daily injections
of progesterone in oil (Inj Gestone / Puregest / Susten).
This helps the endometrium swell up and envelop the
embryo so it has the best chance to implant. If you
find the injections too painful, you can request for
a vaginal gel or suppositories which have the same effect.
From this point, it is a matter of waiting
to see if an embryo implants successfully and
begins to develop. A pregnancy test can be
performed about 14 days after the embryo
transfer and the nurse co-ordinators will have the
results for you.
Blastocyst Transfer
A blastocyst transfer is the transfer of an
embryo from the laboratory to the uterus at
Day 5 of development, instead of Day 3. it is
one way of selecting the embryo or embryos most
likely to survive and implant, giving a better
chance of pregnancy. To appreciate the difference
two extra days can make to an embryo, first you
need to understand a little about early embryo development.
The first week…
After the sperm enters the ovum, the sperm head
\enlarges to form the male pronucleus. Within 24
hours, two small spheres, called the pronuclei,
can be seen in the cytoplasm of the egg. These contain
the genetic material from the mother and the father.
When the two pronuclei fuse, joining the DNA from both
parents together, fertilization is complete. As the
pre-embryo grows, it undergoes cleavage, where the
cell divides into smaller cells call blastomeres.
After 2 days, the embryo will consist of 4-8 blastomeres.
At this poing it is impossible to tell which embryos are
most likely to survive and develop normally. After about
3 days, when the embryo consists of 12-16 blastomeres,
the cells begin to compact, forming a morula. This is
the stage at which the embryo would normally enter the
uterus, where it floats for a day or two before attaching
to the lining of the uterus.
During those two days, huge changes in the embryo's
appearance can be seen, as the cells begin to differentiate
into those that will become the fetus, and those forming the
amniotic sac and placenta. These changes are characterized by
the formation of a cavity in the morula, to create a blastocyst.
After 4 or 5 days the embryo "hatches" out of the
outer shell of the egg, the zona pellucida, and
the blastocyst is able to attach to the endometrium.
By Day 7, the embryo has completely implanted in the
lining of the uterus.
Why have a blastocyst transfer?
By watching the embryo develop to the blastocyst
stage, the embryologists can have a better idea of
which embryos are most likely to be healthy and
continue to develop. One of the factors that decides
an embryo's fate is whether or not it has enough
energy for the first week of development, hatching and
implantation. Of course, there are still many stages
of development that the embryo must pass through to
create a successful pregnancy, but choosing the
healthiest 5-day-old embryos and transferring them
just before they would normally implant has given us
the best success rates yet. Ultimately, our goal is
to have such high success rates that only one blastocyst
will need to be transferred in each cycle for a good
chance at pregnancy.
We often recommend blastocyst transfers for couples
who have had a number of unsuccessful attempts at
routine IVF or in patients who are anxious about multiple pregnancy and would like to opt for just a single blastocyst transfer
Freezing Blastocysts
Normally "spare" embryos are frozen at the 4-8 cell
stage, and provide good results when transferred after
thawing. We are now able to successfully freeze and
thaw blastocysts.
Assisted Hatching: May be required if the egg has a very thick outer coat
How is assisted hatching performed?
- The embryo is held with a specialized holding pipette.
- A very delicate, hollow needle is used to expel an acidic solution against the outer "shell" (zona pellucida) of the embryo.
- A small hole is made in the shell by digesting it with the acidic solution.
- The embryo is then washed and put back in culture in the incubator.
- The embryo transfer procedure is done shortly after
the hatching procedure. Embryo transfer places the embryos
in the woman's uterus where they will hopefully implant
and develop to result in a live birth.
What about Bed rest?
Research has shown that extended bed rest has very few
benefits. In fact, some studies have shown that patients
who have 24 hours of bed rest as compared to patients who
have just 1 hour of bed rest have 7% lower pregnancy rate.
You can have light activities for 3 - 4 days
following which you can resume your daily chores as long
as they do not involve lifting heavy weights or strenuous
exercise.
What about sexual intercourse following embryo transfer?
At the current moment, we ask couples to abstain from sexual
intercourse for 15 days after embryo transfer. However,
in view of current research findings that seminal fluid
might also contain implantation factors besides
sperm, sexual intercourse might in fact prove to be
beneficial after embryo transfer. Further studies
are required before this becomes routine.
What should I expect from the IVF cycle?
Please remember that IVF success rates even in the best
centers in the world rarely exceed 30 - 40% per cycle.
Persistence and faith are important. It is important to
remember that the cumulative pregnancy rate after 3
cycles is close to 60 - 70%.
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