In Vitro Fertilization (IVF)
Cincinnati Institute for Reproductive Health
3805 Edward Road
Suite 450
Cincinnati, Ohio 45209
Tel: 513-924-5550
In vitro fertilization (IVF) and other "high
tech" procedures are now referred to as the
assisted reproductive technologies (ART). These
procedures all involve collecting the oocytes
(eggs) and placing them in direct contact with
sperm. Together they form an alphabet soup of
techniques including: IVF, GIFT, ZIFT, ICSI, and
FET.
In its simplest term, IVF is
simply the uniting of egg and sperm in vitro (in
the lab). Subsequently the embryos are
transferred into the uterus through the cervix
and pregnancy is allowed to begin. IVF was the
first of the ART techniques to be developed. The
first birth was in 1978 in England. The
procedure was pioneered by a Gynecologist and a
Ph.D. (Drs. Steptoe and Edwards). Next came
GIFT, which stands for gamete (egg and sperm)
intrafallopian transfer. This procedure requires
laparoscopy, which is a small incision surgery
and requires a general anesthetic. With existing
technology, pregnancy rates are similar with IVF
and GIFT. Since IVF does not require surgery, it
has supplanted GIFT.
ZIFT involves IVF and then a
laparoscopic surgical procedure to transfer the
embryos into the fallopian tube. Since
transferring embryos through the cervix with IVF
gives the same pregnancy rate as ZIFT, and is
nonsurgical, IVF has also supplanted GIFT.
As the years have passed, IVF
has become the dominant ART technology due to
its simplicity, efficacy and lack of
invasiveness. A typical IVF cycle begins with
shutting down the ovaries. This is done with a
medication known as a GnRH agonist. The most
common drug such used is Lupron. Lupron is given
for approximately two weeks after which the
ovaries are shut down temporarily. The next
phase involves stimulation of the ovaries with
potent ovulation medications such as Pergonal.
For a full description of these agents go to the
page on ovulation medication. These injections
are given for approximately 10 days. When the
eggs are ready for harvesting, a final step is
to give hCG to induce final maturation. The eggs
are then harvested by a process called
ultrasound guided vaginal retrieval. Under heavy
sedation, and with ultrasound guidance, a thin
needle is passed a short distance into the
ovaries and the eggs are suctioned from the
follicles. Typically 5-15 eggs are collected.
Typically the eggs are fertilized by adding
approximately 100,000 motile sperm to each egg.
If the sperm will not fertilize the eggs
naturally we can perform intracytoplasmic sperm
injection (ICSI). This procedure involves
puncturing the egg directly under a microscope
and injecting one sperm in the egg.
The day following retrieval, we
can document fertilization under the microscope.
We then observe the embryos for 3-6 days. The
current trend is to observe longer. Typically
3-4 embryos are then placed in a catheter and
transferred through the cervix into the uterus.
This is a simple procedure much like a Pap
smear. At the present time, embryos can be
transferred either 3 or six days following
retrieval. A 3-day embryo is usually at the
6-8-cell stage:
It is also possible now to
perform advanced stage or blastocyst embryo
transfers. These embryos are further along and
usually fewer of them need to be transferred:
Two weeks later a pregnancy test
can be obtained. Two weeks after the pregnancy
test, an ultrasound can be performed and the
fetal hear beat can be seen. If more embryos
were generated than can be replaced, freezing
(cryopreservation) can save these additional
embryos. Frozen embryos can be stored for future
replacement at much lower cost than the original
IVF cycle.
As the years have passed, IVF
has improved greatly. Today it is arguably the
most effective technique to treat infertility
when compared with others on a month by month
basis. IVF has created a lot of controversy
also. First, it is expensive. An IVF cycle can
cost $6,000 to $7,000. It may not work on the
first cycle. Multiple pregnancies can result.
The truth is that it is a powerful technology
and must be used carefully. Some patients may
have very high odds of success: 45 - 60% chance
per attempt. Others may due to their situation
have only a 20% chance of success.
The multiple pregnancy risk
varies with age. Younger patients need fewer
embryos to be replaced, and older patients need
more. The worst thing that has happened with IVF
is the various centers entering into a race to
see who can get "the best statistics". This has
encouraged centers to transfer high numbers of
embryos to get the statistics while accepting
too high a risk of multiple pregnancy.
Also in order to get the best
statistics, some patients will be refused care
in order to "protect the statistics".
f) cells, trigger a local or
widespread inflammatory response, and retain the
memory of the offending organism to repel it
again if it should ever return. Like any
finely-tuned machine, however, the system can
break down and leave us open to the threat of
infection, or, conversely, turn against our own
healthy tissues, as occurs in such diseases as
rheumatoid arthritis or lupus.
The immune system also plays an important role
in human reproduction. Inflammatory cells and
their secretory products are involved in the
processes of ovulation and preparation of the
endometrium for implantation of a fertilized
egg. Dysfunction of the immune system can
interfere with the normal reproductive processes
and result in infertility. It has been estimated
that an immune factor may be involved in up to
20% of couples with otherwise unexplained
infertility. Although many of these associations
with infertility remain unproven, there is solid
scientific evidence to implicate the formation
of antibodies against sperm as an important
infertility factor.
Antisperm
Antibodies: How common are they?
Sperm are relatively protected
from the immune system by a natural protective
mechanism called the blood-testes barrier. Tight
connections between the cells lining the male
reproductive tract keep immune cells from
gaining entry to the sperm within. If an injury
breaches this barrier, then the immune system
has access to sperm and antibodies are formed.
Antisperm antibodies have been reported in
approximately 10% of infertile men, compared to
less than 1% of fertile men. The prevalence of
antibodies jumps dramatically in men who have
had surgery on their reproductive tract: nearly
70% of men who have undergone a vasectomy
reversal will have antibodies present on their
sperm. Women have a much lower chance for
developing antibodies to sperm: less than 5% of
infertile women can be shown to have antisperm
antibodies, and it is unclear who is at risk for
their formation.
Who is at
risk for antisperm antibodies?
Anything that disrupts the
normal blood-testes barrier can result in the
formation of antisperm antibodies. This may
include any of the following conditions:
Vasectomy reversal
Varicocele (dilation of the veins surrounding
the spermatic cord)
Testicular torsion (twisting of the testicle)
Congenital absence of the vas deferens
Testicular biopsy
Cryptorchidism (failure of testicular descent)
Testicular cancer
Infection (orchitis, prostatitis)
Inguinal hernia repair prior to puberty
Fortunately, intrauterine insemination (the
placement of washed sperm into the uterine
cavity - a common fertility treatment) has not
been shown to cause antisperm antibody
formation.
Despite the long list of risk factors, most men
with antisperm antibodies have not had any of
the conditions listed above. Therefore all
infertile men are potentially at risk, and
consideration should be given to testing
infertile men for antisperm antibodies,
especially if no other reasons for the
infertility have been detected by the diagnostic
workup.
How do
antisperm antibodies cause infertility?
Antibodies that attach to the
sperm may impair motility and make it harder for
them to penetrate the cervical mucus and gain
entrance to the egg; they may also cause the
sperm to clump together, which is occasionally
noted on a routine semen analysis. Antibodies
may also interfere with the ability of the sperm
to fertilize the egg.
What is the
best way to detect antisperm antibodies?
Over the years, many tests have
been developed to detect antisperm antibodies.
In women, blood tests for antisperm antibodies
in women may be more practical than trying to
measure antibodies in the cervical mucus, which
is the primary site where her immune system
interacts with sperm. The postcoital test, which
has been a standard part of the infertility
evaluation, may suggest the presence of
antisperm antibodies. By examining the cervical
mucus following intercourse near the time of
ovulation, antisperm antibodies may result in
either a lack of sperm or in the presence of
sperm, which are shaking in place rather than
actively swimming through the mucus.
In men, a direct examination of their sperm for
attached antibodies is more reliable than
testing blood for the presence of antibodies.
Two commonly used tests are the immunobead assay
and the mixed agglutination reaction (MAR). Both
tests use antibodies bound to a small marker,
such as plastic beads or red blood cells, which
will attach to sperm that have antibodies on
their surface. The results are read as a
percentage of sperm bound by antibodies.
What
treatments are available for antisperm
antibodies?
Suppressing the immune system
with corticosteroids may decrease the production
of antibodies but can result in serious side
effects, including severe damage to the hipbone.
Intrauterine insemination, with or without the
use of fertility medications, has been used for
the treatment of antisperm antibodies. It is
believed to work by delivering the sperm
directly into the uterus and fallopian tubes,
thus bypassing the cervical mucus.
In vitro fertilization appears to be the most
effective treatment for antisperm antibodies,
especially when there are very high levels of
antibodies (near 100% of sperm are bound by
antibodies). There is no clear guidance on
whether intracytoplasmic sperm injection (ICSI),
the direct fertilization of an egg with a single
sperm, is required for the treatment of
antisperm antibodies, unless there had been a
complete absence of fertilization on a prior
attempt at in vitro fertilization
Are there other antibodies
that affect fertility?
For women with recurrent miscarriage, there are
a group of antibodies that appear to attack an
early developing pregnancy, resulting in either
a miscarriage or severe preeclampsia with risk
of intrauterine growth retardation or even fetal
death. Collectively these belong to a class of
antibodies known as antiphospholipid antibodies,
which include the lupus anticoagulant and the
anticardiolipin antibody. Testing for these
antibodies are an integral part of the workup
for recurrent pregnancy loss. However, it is
unclear whether these antibodies play any role
in the ability to conceive. Some physicians
believe that the presence of antiphospholipid
antibodies may decrease the chance for pregnancy
through in vitro fertilization. Although this is
a controversial subject, one of the largest
studies that looked for these antibodies in
women undergoing in vitro fertilization found
that these antibodies were no more likely to be
detected in those who did not become pregnant as
in women who did conceive. |
