Test Tube Babies - IVF & GIFT
from the book How to Have a Baby:
by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.
table of contents
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Embryo transfer is most often done on an outpatient basis. No anesthesia is
used, although some women may wish to have a mild sedative. The patient lies on
a table or bed, usually with her feet in stirrups.. Using a vaginal speculum,
the doctor exposes the cervix. One or more embryos suspended in a drop of
culture medium are drawn into a transfer catheter, a long, thin sterile tube
with a syringe on one end. Gently, the doctor guides the tip of the loaded
catheter through the cervix and deposits the fluid containing the embryos into
the uterine cavity. The procedure should be done with great care and usually
takes between 10 and 20 minutes. Some doctors perform the transfer under
ultrasound guidance, to ensure proper placement of the embryos in the uterine
cavity. Most doctors advise a few hours of bed rest after the transfer.
Fig 5. Schematic of the embryo transfer procedure
Most clinics today transfer 2-3 good quality embryos on Day 2 or Day 3.
Embryos are graded according to their appearance and rate of cell-division and
good quality embryos are those which have 4-8 cells, of equal size, with clear
cytoplasm, and with few fragments. You should ask the doctor to show you your
embryos under the microscope. Some times, only embryos of poor quality are
available for transfer. While the chance of getting pregnant when only poor
quality embryos are transferred, you can be reassured that if a pregnancy
results, the children will be normal !
How many embryos to transfer is one of the most difficult decisions facing an
IVF patient today. The more the embryos transferred, the greater the chances of
getting pregnant. Since the purpose of an IVF cycle is to achieve a pregnancy,
then why not transfer as many as possible ? However, the price you pay for
transferring more embryos is that the risk of a multiple pregnancy increases as
well. In some countries, such as the UK, doctors are allowed to replace a
maximum of only 3 embryos, to reduce the risk of high-order multiple births.
Some clinics in Scandinavia have now started transferring only one embryo in
young women, in order to reduce the risk of a multiple pregnancy. In USA and
India, there are no laws, and some clinics will transfer 4 embryos for young
patients, and upto 6 for older women – and this number is quite arbitrary.
Doctors have tried to develop an embryo score ( based on the number of embryos
and embryo quality ) in order to predict the chances of a pregnancy after embryo
transfer, but this is still not precise. Since there is no easy answer as to how
many embryos to transfer, many clinics will allow patients to decide for
themselves. This is always a difficult decision, and you need to carefully weigh
the pros and cons before making up your mind. There is no right or wrong number
– and you need to take the path of least regret. Transferring more embryos
increases the chances of getting pregnant, and also increases the risk of a
multiple pregnancy. However, a high-order pregnancy is a complication for which
the doctor can perform a selective fetal reduction , in order to reduce this to
twins. Not getting pregnant may be a worse outcome for some patients ! If embryo
freezing facilities are available, then supernumerary embryos can be stored, and
this needs to be factored in as well.
The embryo transfer completes the medical treatment in the IVF cycle and most
clinics provide "luteal phase support" after the transfer , usually
with estrogen tablets and progesterone suppositories, to increase the chances of
implantation. However, this period is often the hardest part of an IVF cycle for
the patient, because of the agony and suspense of waiting to find out if a
pregnancy has occurred. This can be determined by a blood test , which measures
the level of the hormone, HCG ( human chorionic gonadotropin) only 10 to 14 days
after the transfer. For many patients, these 14 days are often the longest days
of their life !
It is normal to blame yourself for something you may or may not have done
during this time if you do not conceive. Therefore, try not to do anything for
which you will blame yourself if you do not get pregnant. In general the
following guidelines are offered:
- No tub baths or swimming for 48 hours after replacement
- No douching or tampons
- No intercourse or orgasms until the fetal heartbeat is seen on ultrasound, or
the pregnancy test is negative
- Do not undertake excessive physical activity such as jogging, aerobics, or
- Do not taken any non-prescription medications or other prescribed medications
without the approval of the IVF team
- No heavy lifting
- You may return to "work" after 24 hours of bed rest (getting up for
bathroom and meals only) and one to two days of light activity.
You may have some vaginal spotting or bleeding prior to your blood test.
However, you must have the blood test done, even if you think your period has
started. There are no symptoms or signs which will be able to tell you whether
or not you are pregnant.
Many doctors used to advise "strict bed rest" after an embryo
transfer. However, remember that your physical activity does not affect your
chances of getting pregnant. Resting when you are well can be very emotionally
taxing, and we encourage patients to lead as normal a life as possible. Many
patients are worried that if they cough or sneeze , the embryo will "fall
out". However, remember that this is physically impossible, and that if the
embryo is going to implant, it will, no matter how much you exert.
Thus, there are numerous stages to every IVF treatment cycle, each of which
must be reached and completed before moving on to the next stage:
- more than one should egg develop
- eggs should mature
- ovulation should not occur before the eggs can be collected
- eggs must be retrieved during the "pick-up"
- sperm must fertilize at least one egg
- fertilized eggs must divide and grow healthily,... and all this so that...
- the embryos might get implanted in the uterus
Think of it as a series of hurdles, all of which have to be cleared , in
order to win the race !
The enigma of embryo implantation – why doesn’t every embryo become a
While modern technology is very good at making embryos in the laboratory, we
still cannot control the implantation process. We do not know which embryo will
become a baby – and this can be very frustrating, for both patients and
doctors ! Many patients who do not get pregnant after an embryo transfer start
believing that their bodies are defective, and that they have
"rejected" the embryo. They feel that if they failed to become
pregnant even after the doctor transferred 3-4 good quality embryos, that they
are flawed. However, you need to remember that embryo implantation is a very
complex process, which consists of a series of phases in which the embryo has to
appose and attach itself to the maternal endometrium and invade into it.
the embryo has to undergo further development, till it reaches the blastocyst
stage, when it hatches from its shell, known as the zona. The hatched blastocyst
then needs to implant in the endometrium, and the three phases of implantation
are known as apposition, adhesion and invasion, and occur during the period of
time known as the implantation window. Apposition, or orientation of the embryo
(which is at the blastocyst stage at this time ) within the cavity of the
uterus, starts when the cavity has become minimal due to the suction of
endometrial fluid by pynopods (small protrusions found on the surface membrane
of the cells lining the uterus). Adhesion of the blastocyst is a progressive
phenomenon that ties the embryo to the endometrium and is the primary event
initiating invasion. Many molecules, such as cytokines, growth factors and cell
adhesion proteins called integrins play an important role in this complex
process during which the blastocyst and maternal endometrium must undergo an
exquisite dialogue. Invasion is a self-controlled proteolytic process that
allows the embryonic trophoblast to penetrate deep into the maternal decidua and
to invade the endometrial spiral arteries by producing chemicals called
proteinases. How implantation is regulated and brought about remains an enigma,
but we need to remember that the implantation process is surprisingly
inefficient in humans – Nature is not always very competent! After IVF, it’s
only about 10%, which means that only 10% of embryos implant successfully to
become a baby.
The responsibility for this low efficiency has to be shared
between the embryo as well as a defective embryo-endometrium dialogue. We still
cannot successfully predict which patient will get pregnant after embryo
transfer . We now know that one of the major reasons for failure of the embryo
to implant is a genetically abnormal embryo. Basic research on implantation is
of great interest today, because embryonic implantation is the major factor
limiting in allowing pregnancy after ART, but we still need to learn a lot about
this "black hole" in our knowledge, before we can learn to control it
Many patients blame themselves when they don’t get pregnant after an embryo
transfer. They feel that the fact that the embryo did not implant means either
that their body is defective; or that it "rejected" the embryo; or
that they did not rest enough. However, please do remember that embryo
implantation is a complex process, which you cannot influence by your diet or
physical activity – so there is no need for you to blame yourself if the
embryos do not implant.
Maximizing Chances For Success
- Avoid all medications other than Tylenol. If you are taking other
prescription medications check with us prior to beginning your treatment cycle.
- No smoking or alcohol use. Studies show both can result in lower pregnancy
rates and a greater risk of miscarriage. Why put yourself through this if you
are not doing everything YOU can to insure your success.
- No more than two caffeinated beverages per day.
- Avoid change in diet or weight loss or fad diets during IVF cycle. A healthy
well balanced diet works best.
- Refrain from intercourse three to four days prior to egg retrieval and
following embryo replacement until pregnancy determination is made.
- Normal exercise may continue unless enlargement of your ovaries produces
- Avoid hot tubs or saunas.
- Fever greater than 100.4o one to two months prior to IVF treatment may
adversely effect sperm quality. Be sure to let us know. If you are sick, please
take your temperature and report any febrile illnesses.
- Sitting in hot tubs and saunas is not recommended. Even a single episode in
the hot tub can adversely effect sperm function. Please refrain from this for at
least three months prior to treatment.
- Drugs, alcohol, and cigarette smoking should be avoided for three months
prior to treatment and at all times during the ongoing IVF treatment cycle to
get the best results.
- Abstain from intercourse for at least three days, but not more than seven
days prior to collection of semen for egg collection and during treatment.
The Cost of IVF
The cost of a single IVF treatment cycle varies widely from approximately Rs
30,000 to more than Rs 75,000 depending on the program and the items included in
the fee. It is important to get an itemized listing from the selected program of
what costs are included in the treatment cycle. Try to find your
"total" medical cost - how much you will have to spend out of your own
pocket for the entire treatment. Many clinics do not include the cost of certain
procedures ( such as ultrasound scans) and these can then add up to quite a bit
! Other expenses to be aware of include time missed from work and travel and
lodging expenses. The number of treatment cycles needed to achieve pregnancy
will, of course, determine the final cost.
A reduction in cost may be obtained by using "Natural Cycle IVF."
This procedure does not employ ovulation enhancement; therefore the additional
expense on the injections used for superovulation is eliminated. However, only
one mature egg is usually obtained, and the pregnancy rate per cycle is
therefore less for this method. A newer technique called "in vitro
maturation" allows doctors to collect many immature eggs, and them mature
them in the laboratory.
[continued on next page]
by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.
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