Fertilization (IVF) Program Summary
The following is a brief outline of the steps
involved in in vitro fertilization (TVF) and related procedures, also referred to as the Assisted Reproductive Technologies (ART). Due to individual needs, some steps may be changed for you, but the basic flow of steps remains
the same for most patients. Before discussing the process in detail, a few definitions of terms may be helpful:
Gametes: Eggs and Sperm
Zygote: Single cell embryo (fertilized
egg) before it begins to divide
IVF: In Vitro Fertilization or
fertilization of the egg outside the body (in the IVF laboratory); literally "fertilization in glass" after fertilization of the eggs, embryos are transferred into the uterus
GIFT: Gamete
Intrafallopian Transfer; just after the egg retrieval and prior to fertilization, eggsandsperm are placed into the fallopian tube (by laparoscopy)
ZIFT: Zygote Intrafallopian Transfer; zygotes are transferred into the fallopian tube (by laparoscopy)
ICSI: Intracytoplasmic Sperm Injection; a technique
used in conjunction with IVF that assists
fertilization by injecting one sperm directly into each egg
Indications for Treatment with ART
The following conditions can be successfully treated with
ART:
Tubal
Disease: Patients with tubal blockage or severe pelvic adhesions, or those who have not conceived after tubal
surgery are good candidates for IVF/ET. The other ART procedures (GIFT, ZIFT, TET)
are generally not appropriate for such patients.
Moderate to Severe Male Factor:
The ability to treat sperm in the rlab 'by'various techniques, along with the ability to concentrate large numbers of motile
sperm around eggs makes
IVF a good treatment for couples whose infertility is due to poor semen
quality. We feel that GIFT is less appropriate for such
couples, because the technique does not permit assessment of
fertilization. IVF whh ICSI may be indicated for some
of these couples depending on the severity of the problem.
Endometriosis andImmunologic Infertility: By bypassing the pelvic environment, IVF and ZIFT allow fertilization outside the body, away from the potentially destructive actions of pelvic fluids associated whh endometriosis and/or
anti-sperm antibodies or other immunologic substances.
Unexplained infertility
that has not responded to other types of therapy: All types of ART have successfully treated such couples. FVF or ZIFT can demonstrate the
ability of their sperm to fertilize eggs. Rarely,
unexplained infertility may be due to subtle defects in sperm or egg function.
Pre-Cvcle Evaluation
It may be necessary to schedule additional
tests in order to be optimally
prepared for the IVF cycle. Such investigations evaluate
several variables that are critical for the success of the procedure. The first
of these is the woman's ability
to respond to fertility drugs. While age affects this parameter,
measurement of the level
of follicle stimulating hormone (FSH) during the first
three days of the
menstrual cycle help us estimate a woman's ability to produce eggs in response to fertility drugs. In general, women with high FSH levels are more
resistant to ovarian stimulation. For selected patients, we recommend
a test known as the clomiphene citrate challenge test (C3T) hi which FSH and estradiol blood levels are assessed on cycle days 3 and 10. The patient is treated with a medication known as
clomiphene citrate on cycle days 5 through 9. In some situations, this test
gives us more information
than a single FSH level early hi the cycle.
The second factor we evaluate is the uterine environment. This is accomplished by looking at the uterine
lining just prior to ovulation by ultrasound (sonogram). Certain patterns of uterine lining development are associated
with poor pregnancy rates.
In addition, we recommend a procedure known as a hysteroscopy hi which a small telescope is inserted into the uterine cavhy through the cervical
opening. This is done to make sure there are no fibroids, polyps, or scar tissue
that could interfere with
implantation. Lastly, cervical cultures for ureaplasma, chlamydia, gonorrhea and other bacteria are taken before
beginning treatment and ensure that no significant infection is present.
The third factor we look at is the male
factor. This requires a semen analysis. Additionally, antibodies
to sperm are measured
in both partners. High levels of sperm antibodies can
interfere with fertilization and special techniques
are employed to correct this problem.
Couples contemplating
ART have the option of seeing a counselor. This licensed professional is
familiar with the emotional
impact of infertility and infertility treatments and can help
them deal with this important aspect of then- care.
Ovulation Induction and Monitoring
ART success rates
depend upon the number and quality of embryos available for transfer. The egg retrieval
must be carefully
timed so as to retrieve mature eggs. To accomplish these two goals, ovulation inducing medications and careful monitoring are employed. In most cases, the
female begins subcutaneous injections of Lupron one week before the onset of the next menses.
This hormone prevents
premature ovulation, which would result hi cancellation of the cycle. Nearly 20% of cycles are canceled when Lupron is not used.
Once menses occurs, a vaginal ultrasound examination is performed to
make sure there are no ovarian
cysts. As specified by the planned schedule of treatment, the woman then begins
injections of Menotropins (Fertinex, Pergonal, Humegon). Arbitrarily, we call the first day of Menotropin administration Cycle Day 2.
In order to monitor a patient's response to these drugs, daily ultrasound examinations and serum estradiol levels are performed beginning on Cycle Day 9. These help us determine when the eggs are ready for retrieval. (Most patients will also need to have a serum estradiol on Cycle
Day 7 prior to their first ultrasound.)
Once the follicles (containing the eggs) are deemed ready, the patient stops taking the Lupron and Menotropins. Thirty-six (36) hours prior to the egg retrieval, the patient takes an injection of human chorionic
gonadotropin (hCG). This hormone replaces the woman's
normal LH surge and is necessary for a final maturation of
the eggs so that they
can be fertilized.'
Egg Retrieval
In almost all cases, the egg retrieval is accomplished using a vaginal
ultrasound probe to guide a needle into the ovaries. This procedure does not require general anesthesia and is performed with intravenous sedation.administered
by an anesthesiologist. As a result, the experience is
not
painful and recovery is very brief
If the woman is to undergo
GIFT, a laparoscopy is performed immediately following the egg retrieval. Capacitated sperm (see below) and several eggs are injected into one of the fallopian tubes via a small catheter placed into the end of the tube. This procedure requires at least one normal fallopian tube.
Sperm Processing
Freshly ejaculated sperm
must undergo a biochemical and structural change called capachation = before they are able
to fertilize an
egg. In an TVF cycle, sperm are capacitated in the laboratory" prior to inseminating the eggs. This is accomplished by a process of centrifugation with isolation
of the population of motile sperm.
In Vitro Fertilization In-vitro fertilization literally means "fertilization in glass". The fluid obtained from the follicles is, carefully
examined in the IW laboratory and the eggs contained therein are isolated and placed in culture media inside an incubator. A few hours later, several thousand processed
sperm are placed around each egg. In some cases where •sperm counts ^are very low, the process of fertilization
must be assisted via the injection of individual sperm into each
egg (see ICSI below).
Eggs and sperm are left
to incubate together in the carefully controlled environment provided by i the IVF laboratory. Approximately 18 hours following insemination, the
eggs are inspected under the microscope to determine how many have been successfully fertilized.
These so-called "pronuclear" embryos or zygotes are still single cells at this stage.
Embryos
The embryos are examined daily and are graded
according to their quality. Three days following the
egg retrieval, the best embryos contain 6 to 10 cells
each. This is the stage at which many programs will perform the embryo transfer.
In selected patients,
embryos may be cultured for an additional two or three
days to a developmental stage known as the blastocyst stage. These embryos contain approximately 60 cells and represent the embryos with the highest
potential for establishing a pregnancy. As such, fewer
embryos may be transferred without lowering the chances for conception. Many programs, including
our own, have instituted this option for certain patients in
order to diminish the rate of multiple pregnancies.
Embryo Transfer
The embryos are loaded into a thin plastic catheter that is passed through the cervix and into the uterus.
They are then deposited in the upper part of the uterine cavity and the catheter is withdrawn. Very little discomfort is experienced with
this procedure.
Following the transfer of embryos, the patient remains immobile for approximately
one hour and then is sent home to rest for the following two -days. We feel this period
of limited activity is indicated, as hatching and implantation will occur during this time.
Micromanipulation
Intracytaplasmic Sperm Injection
Even with in vitro fertilization, men with very low concentrations of sperm and/or low motilrties may be at risk for impaired fertilization
of their partner's eggs. Fortunately, a procedure known as intracytoplasmic
sperm injection (ICSI) has all but eliminated this problem. This procedure involves the direct injection of a single sperm into each egg and requires a great deal of expertise as well as special instrumentation.
Assisted Hatching
Before an embryo implants itself into the uterine lining, it must first
hatch out of its shell (zona pellucida). In some cases, failure to concave may be due to a problem with
hatching and several procedures have been developed to assist
this process. The most common procedure utilizes a weak acid to "drill"
a hole in the zona
just before the embryo is
transferred. Several studies have shown this procedure
improves pregnancy rates in women who are 38 years or older. Other indications for assisted hatching may include thick zonas, priortunsuccessful TVFtreatment cycles, and fragmented embryos. This procedure is
usually performed on embryos to be transferred at the 72 hour stage. Assisted
hatching is probably of no benefit in blastocysts as
the zona pellucida is very thin at this stage.
Post-Transfer Management
During the follow-up phase, the female partner receives supplemental progesterone and estrogen to maintain
the integrity of the uterine lining. Progesterone may be
administered by a vaginal
gel preparation (Crinone),
by intramuscular injection, or by vaginal suppository.
Supplemental estrogen may be given by oral tablet, via
a skin patch, or by vaginal suppositories. At 8 and 10 days after the embryo transfer, blood pregnancy tests
are performed. Rising blood levels of the pregnancy hormone, hCG, indicate that implantation
has occurred. Approximately 10 days after the second
HCG level, a third hCG level is obtained to confirm normal progression of the gestation. Affirmation
of a clinical pregnancy is made by ultrasound examination four weeks following the transfer.
Cryopreservation
Freezing extra embryos gives couples an additional opportunity to conceive without going through another stimulation cycle and egg retrieval. The success rate with frozen/thawed embryos is
improved when the woman uses hormone replacement instead of her natural cycle. Approximately 7 days prior to an expected menses, therapy with Lupron
is initiated in the same manner as with a stimulation cycle. After the onset of
menses, the patient is treated with biweekly injections of estrogen and, several days prior to
the embryo transfer, daily injections of progesterone (or daily administration of Crinone) are initiated and the Lupron is discontinued. Prior to thawing the embryos, an ultrasound assessment of the uterine lining is performed to make sure
an adequate uterine environment is present.
In our
experience, approximately 60% of the frozen embryos survive the thawing process. Patients transferring 4 or more embryos will have the best
chances to conceive. We are currently experiencing a 30% pregnancy rate per frozen embryo
transfer procedure in patients under 40 years of age.
Success Rates
and Choice of Procedure
Nearly 35% of women
under the age of 40 (who have a normal uterus and a fertile male partner) undergoing
one cycle of IVF/ET can anticipate having a baby. Approximately 70% of such women could expect to give birth to
a healthy baby after three fresh embryo transfer procedures. The success rate
for women between the
ages of 40 and 42 is between 10 and 15% per embryo transfer procedure.
A frequently raised concern by many couples is that of bearing abnormal children as a result of these
procedures. Fortunately, a review of several thousand ART births has shown no higher
incidence of birth defects, or genetic abnormalities, when compared to the population at large. There has been recent evidence that certain men who require ICSI in order to fertilize their partner's eggs may produce offspring
(sons) with fertility problems similar to their own. Fortunately, this problem is not
a concern for the great majority
of patients being treated
with IVF with or without ICSI.
Some centers report higher success rates with GIFT. One of the problems
evaluating these claims is that the types of patients treated by IVF and GIFT are not always comparable. For
instance, couples with male factor infertility may be directed towards IVF, thus lowering the success rate with that approach. Since IVF
does not require surgery
and general anesthesia, most reproductive endocrinologists feel that even small improvements in success
rates with GIFT do not justify its use over IVF.
Participation as a Couple
We are well aware that infertility exacts
a very heavy toll. The emotional, financial, and physical burden is often overwhelming. It is for this reason that we encourage both partners to be supportive of one another and
participate in the treatment process together. Though not always possible, the male should make every effort to accompany
his partner with every visit.
If you have any further questions or concerns
regarding our program, please do not hesitate to call and speak to one of our qualified
team members.
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