Download In Vitro Fertilization Overview Manual

In Vitro Fertilization
Overview Manual
Welcome to the Center for Reproductive Health
In Vitro Fertilization Program
On behalf of the physicians, embryologists, nurses and administrative staff, we would
like to welcome you to Kaiser Permanente’s In Vitro Fertilization (IVF) program. We are
honored to be working with you and your partner in your desire to have a child. In an
effort to help you, we have prepared this handout as a guide to understanding the IVF
process. After reviewing the material, please feel free to ask questions at any time
during your cycle. Our goal is to provide you with the tools you need to help make your
IVF experience a positive one.
IVF is one of the most effective techniques available for improving your chances for a
pregnancy. In order to reach this potential, your participation and that of your
reproductive endocrinologist, nurses, and laboratory staff, requires close coordination.
Precise timing of medications is critical and close monitoring with blood tests and
ultrasounds is required.
Pharmacy Partners in Your Care
We have partnered with highly experienced mail order specialty pharmacies to provide
you with your medications while undergoing treatment. Please contact our clinic to
obtain a list of current preferred pharmacies. Please feel free to contact the pharmacies
directly if you have any questions regarding pricing or how to arrange for delivery of
your medication. Medication prescriptions required for your cycle will be faxed directly to
the pharmacy of your choice. If you do not have a preference, we will send to one of
our partners on your behalf.
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ASSISTED REPRODUCTIVE TECHNOLOGIES (ART)
IVF (In Vitro Fertilization)
In Vitro Fertilization, also known as IVF is the process of combining a woman’s eggs
with a man’s sperm outside the body, in a laboratory. Any combination can be used
including the patient’s own eggs and your partner’s sperm, as well as donor eggs and
donor sperm.
IVF is used for patients experiencing infertility, and may be a treatment option if:
 You have blocked or missing tubes
 You have endometriosis
 Your husband/partner has a low sperm count, or motility
 You have had artificial insemination cycles that have not been successful
 You have unexplained infertility
In this technique, oocytes (eggs) are retrieved for the ovary and placed in a Petri dish
with active, motile sperm. Fertilization occurs in the Petri dish, thus the name “In Vitro”
meaning “in glass”. The eggs and sperm are maintained in a special culture media
(nutrient fluid) within a controlled environment (incubator) for approximately three to five
days.
During this incubation period, the fertilized eggs develop into early dividing embryos,
usually consisting of four to eight cells (three days after fertilization). If allowed to
continue, the embryos continue to mature and form a blastocyst two days later (five
days after fertilization).
Embryo’s (Day 3) or blastocyst (Day 5), are transferred via a thin catheter, through the
cervix, directly into the uterus using ultrasound guidance.
INTRACYTOPLASMIC SPERM INJECTION (ICSI)
In the early 1990’s a technique became available for the treatment of infertility due to a
severe male factor (low count or poor motility). Following standard IVF egg retrieval, a
single sperm is injected directly into the cytoplasm of the egg using a device called a
micromanipulator. Using this technique, fertilization, and pregnancy rates are
comparable with those found using standard IVF procedures. This technique can also
be used for males with a prior vasectomy or congenital absence of the vas deference
who require sperm aspiration directly for the epididymis or testes by an urologist. ICSI is
used routinely in cases of low sperm count, high percentage of abnormal sperm, low
sperm motility and low yield of eggs on the day of egg retrieval.
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Assisted Hatching
The morning of embryo transfer the embryologist will be assessing the quality of each
individual embryo. Each embryo is unique and develops independent of each other.
The embryologist will grade each of the embryos based on subjective criteria which will
describe the “look “of the embryo.
Assisted hatching is a technique used by embryologists to weaken the outer wall of the
embryo to aid with the implantation process. During the late 80’s and early 90’s a weak
acid solution was used to dissolve the outer coating (zona). Today, with the
advancement of technology, embryologists use a laser to create a precise incision to
the zona, thereby, creating a weakening.
Will all embryos undergo assisted hatching?
No. The embryologist uses strict criteria to assess each individual embryo. Only
embryos which they feel need it, will have assisted hatching.
There are cases where assisted hatching is a standard application, these include:
 Advanced maternal age (38 years and greater)
 Thick zona on morning of day three transfer
 Past history of repeated failed IVF cycles
 High degree of fragmentation (poor quality embryos)
 Frozen Embryo Cycle
How many embryos will be transferred?
Deciding on the number of embryos to transfer is a collective decision between your
physician, embryology lab and patient. We want to give you the best chance of getting
pregnant, without putting you at risk for multiple gestations. The recommendations for
number of embryos to transfer, are based on Day 3 vs. Day 5 transfer:
Day 3 Transfer
Day 5 Transfer
Favorable
Others
1-2
2
35-37
2
38-40
Favorable
Other
<35
1
2
3
35-37
2
2
3
4
38-40
2
3
>=41
5
5
>=41
3
3
OD
2*
OD
1
<35
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Can we freeze any embryos that are not transferred?
Yes. If we have good quality embryos that are not used during the fresh embryo
transfer, we will freeze them for future use. You will then be able to do a frozen embryo
transfer cycle.
Guide to In Vitro Fertilization
I. Contacting Financial personnel and IVF Case Manager
Once your reproductive endocrinologist has discussed the recommendations for moving
forward with IVF, a meeting or telephone call can be arranged with our financial
coordinator and case mangers. You will learn about costs related to IVF, tentative
stimulation start date, and the next steps. The case manager will be your liaison with
the physicians and embryology laboratory personnel as you move forward with your
cycle.
II. Preliminary Testing*
These include:
 Semen Analysis (with morphology)
 Infectious disease blood work (patient and partner)
o HIV
o HTLV
o Hepatitis B (surface antigen)
o Hepatitis C (antibody)
o RPR or T. Pallidum
o Rubella (Female partner only)
It may also include (patient only):
 Saline Sonogram or/ Hysteroscopy and /or HSG
 Antral follicle count and trial transfer
 Day 3 FSH, and Estradiol
 LH
 ABO Rh
 Thyroid
 Prolactin
 AMH (Anti-Mullarian hormone)
 Cystic Fibrosis (may include partner)
 Genetic testing (may include partner)
* If there was recent testing, repeat testing may not be required.
III. Your IVF Cycle
Once all pre-testing is completed, you will receive a schedule specific to the protocol
your physician has chosen for you, detailing ultrasound appointments, medication start
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dates and potential retrieval date, you will be given access to the secure patient portal
and asked to view the online IVF 101 class.
Your IVF cycle has been divided into three distinct phases:

Phase 1: Initial IVF evaluation, ultrasound monitoring, and blood work will
be done at each of the regional clinics

Phase 2: Egg retrieval and transfer will be done at the IVF center in
Fremont

Phase 3: Post transfer care and obstetrical ultrasounds will be done at
each of the regional clinics
PHASE I

Birth Control Pills (BCP’s)*:
Phase one begins with the onset of oral contraceptives. You will be requested to
call in with cycle day one the month prior to your IVF cycle. The case manager
will instruct you when to begin the oral contraceptives.
*Please note: Birth Control Pill use will be determined by your physician on a
case by case basis.

Injection Class:
You and your partner will be scheduled for hands on injection class with your
IVF case manager. Prior to your class please view the IVF 101 orientation
available through the secure patient portal. Please print off the attestation
following the video presentation and bring with you to the injection class along
with your consents.

Pre- Lupron Ultrasound:
While you are on the birth control pills and prior to beginning Lupron, you will
have a transvaginal ultrasound to determine if everything is appropriate for
staring Lupron (only applicable for patients on a Long Luteal Protocol).

Baseline Ultrasound:
A baseline ultrasounds is performed once oral contraceptives have stopped.
This ultrasound is done to ensure you are ready to proceed with the start of
stimulation. Occasionally you may have an ovarian cyst; it often disappears with
continued Lupron use. In the rare instance that it does not begin to reduce in
size, your doctor may recommend a cyst aspiration (removal of fluid) to help it
collapse faster.

Estradiol Level:
In addition to ultrasound monitoring, estrodial blood work will be performed to
interpret follicular development. During phase 1, blood work is drawn to
determine adequate suppression of the ovary prior to the initiation of fertility
medications and to monitor your progress as you proceed with medication.
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
Back-Up Semen Sample:
In certain cases, a back up semen sample is obtained from the male partner,
frozen, and stored as a “back-up” sample for the day of retrieval. Please check
with your case manager if this is an option for you.

Beginning Stimulation:
You will be assigned a stimulation start date, also called “STIM DAY 1”. This
date reflects the beginning of your IVF cycle. You will be asked to begin the
administration of fertility medication which will be taken every evening by self
administered injections. We will be monitoring you with transvaginal
ultrasounds and blood work to track the development of follicles. Follicles are
fluid filled sacs found within the ovary. There are thousands of follicles in each
ovary, but only a few grow large enough to be tracked by ultrasound. Oocytes
(eggs) develop within the follicle and are approximately a tenth of a millimeter in
diameter. The follicle is about one hundred times bigger that the egg, therefore,
during monitoring your physician will be monitoring the growth of each individual
follicle. Each follicle contains an egg approximately 70% of the time.
The medication you will be injecting causes your body to produce several
follicles. The response to medication will vary from person to person. On
average, 12-14 follicles are typical; however, factors such as your age and FSH
will impact your response to the medication.
Your specific protocol will be determined by your physician after assessing all
preliminary test results, age, antral follicle count, and any pertinent prior history.
The follicle stimulating hormones have three main risks which are discussed in
detail in the medication manual and your consent forms.
These risks may include:
o Ovarian Hyperstimulation Syndrome
o Multiple births
o Possibility of increased risk of ovarian cancer (please speak with your IVF
provider for additional information)

Timing of HCG:
When the ultrasound and estrogen levels suggest that the follicles are large
enough (usually about 18mm in diameter), you will be instructed to stop
Lupron/Cetrotide/Ganirelix Acetate (whichever applies to your cycle) and
stimulation medication. You will take a one time dose of Human Chorionic
Gonadotropin (HCG).
The timing of HCG is critical to the successful outcome of your retrieval.
The IVF case manager will instruct you when and how to take this last injection.
This injection is very important.
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PHASE II

Oocyte Retrieval:
Approximately 35 to 36 hours after the HCG injection, the egg retrieval will be
performed using IV sedation. Your partner will need to bring you to this
appointment as you need to be driven home following anesthesia. Also, your
partner will be asked to provide a semen sample on this day which will be used
to fertilize the eggs that have been retrieved.
You will be instructed to not eat or drink after midnight the night before the
retrieval. Please notify your physician or nurse if you are on any other
medication to discuss options for the morning of the procedure.
Once you are sedated, the vagina will be cleansed with a salt water solution. A
needle pierces through the vaginal wall and is introduced into the ovary under
ultrasound guidance. The follicular fluid from the ovary is then collected in test
tubes and passed to the IVF lab. The egg retrieval takes approximately 20-45
minutes and discomfort is minimal. After the procedure, you will be transferred to
the recovery room where you will spend approximately 45 minutes.
Recovery after anesthesia is quite rapid. You will be in the recovery room for
approximately one hour. You may feel some pelvic heaviness, soreness, and
cramping following the procedure. Often there is a small amount of spotting, this
is normal. If this should increase to a menstrual period, please contact the IVF
Center.
You will need to take the day of retrieval off from work and other activities. You
are not to drive home on your own following the procedure. Your partner, a
friend, or family member is required to be here on the day of your retrieval.
 Semen Sample:
Your partner will be asked to provide a semen sample the morning of the
retrieval. On rare occasions, a second sample will be required. For optimal
sample quality, abstinence for 2 to 5 days prior to the day of retrieval is
recommended. Please do not abstain from ejaculation longer than 5 days as the
sperm will begin to lose motility.

Laboratory Aspects of In Vitro Fertilization:
Once the eggs are retrieved and placed in a temperature regulated incubator,
they mature for several hours before the sperm is added. The addition of sperm
to the culture media is called insemination, and is followed by fertilization, once
the sperm enters the egg.
The stages that follow are very important to the future embryo. After fertilization,
the sperm loses its tail and its head enlarges. At this stage, the egg looks like a
cell with two separate cells known as pronuclei. The 2 pro nuclei will eventually
fuse together to create a single true nucleus.
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The day after your retrieval is very critical. The embryologists will be looking
for the presence of pronuclei which indicates successful fertilization. The
procedure nurse will notify you of how many embryos have reached the 2PN
stage.
Once fusion of the pro-nuclei takes place, the embryo can begin cleaving
(dividing). Cleavage to four cells generally takes 36-48 hours or more after the
day of egg retrieval. Embryo transfer usually occurs at the 6-8 cell stage with a
day three transfer, and blastocyst stage with a day five transfer.

Embryo Transfer:
Multiple gestations are a risk when several embryos are transferred. During
retrieval, all the follicles will be aspirated. If multiple embryos are transferred into
the uterus, twins, triplets, or more are possible. However, high order multiples
are rare. In IVF, the risk of a multiple pregnancy depends on the number and
quality of the embryos transferred back into the uterus. The physician and
embryologist will discuss the risks, specific to your case prior to your transfer.
You can then make an informed decision regarding the amount of risk you and
your partner are willing to take. Please note: We follow the ASRM
recommended guidelines for embryo transfer; the decision to transfer outside the
recommendations is only done after careful consultation with your physician and
embryologist. Please see chart above for detailed breakdown of ASRM
guidelines.
Good quality embryos that are not transferred during the fresh cycle can be
frozen for future use. Please note: Not all remaining embryos will be frozen.
The embryologist has selection criteria to determine which embryos have the
best odds for survival and continued development once thawed.
You will be scheduled for transfer on either the third day following retrieval or on
the fifth day following retrieval. The transfer day depends on the quality and total
number of embryos. You will receive an update from the IVF procedure room
nurses following notification from the embryology laboratory personnel which will
detail embryo quality based on an embryo grading system.
The embryo transfer is performed by placing a small soft catheter (tube)
containing the embryos into your uterus along with a very small amount of fluid.
No anesthesia is required; however, you may be prescribed a valium for
relaxation to be taken following the embryology /physician consult just prior to the
embryo transfer procedure (optional).
You may have a sensation or a slight cramp as the catheter is passed through
your cervix. The transfer takes approximately 30-60 seconds; however, the
whole procedure will take about 10-20 minutes. It is very important to realize that
once the embryos are transferred into the uterus, they will not fall out! If
possible, please take the day after transfer off from work and other activities to
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relax at home; this is the perfect time to get caught up on the latest DVD
releases. Bed rest is not needed!
PHASE III
During phase III you will return to your regional clinic to continue care. You will
be asked to have someone at home administer intramuscular progesterone
injections on a daily schedule. Progesterone is vital to early implantation and
continued embryo development until there is independent placental functioning at
approximately 10-12 weeks of gestation.
The 14 days following retrieval will feel like an eternity. Cramping and slight
spotting are very normal. If you should develop a full menstrual cycle following
the transfer, please contact your case manager.
A date for your pregnancy test will be given to you following the transfer. Please
have the test regardless of what you may think the results are. Doing a home
pregnancy test is not recommended and may not provide the same results as the
blood pregnancy test we will direct you to have.
If the pregnancy test is positive, progesterone will continue until placental
functioning is established at approximately 10 weeks of gestation. You will have
additional blood testing to ensure early levels are rising appropriately.
An ultrasound will be scheduled at 6 and 8 weeks of gestation.
If the pregnancy test is negative, you will be asked to stop all medication and
follow up with your case manager on cycle day one of your next menstrual
period. A follow up visit will be scheduled with your physician.
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Please contact the IVF Center with any questions:
Fremont: (510) 248-6900, option #3 to speak with an IVF RN
San Ramon:
If you have an urgent issue after hours, weekends and holidays, please call (510) 2486900, option #3 for the afterhours answering serivce.
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