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The
roller coaster ride of fertility treatment is emotionally
and physically exhausting. Couples typically begin
treatment with simple and relatively inexpensive interventions
such as ovulation induction and intrauterine insemination
(IUI), and when treatment has failed, progress to
injectable medications and finally in vitro fertilization
(IVF). Each treatment protocol may last up to one
month and several cycles of the same method are often
repeated to maximize chances for success.
The
same is true for the most time consuming and expensive
treatment protocols involving IVF. The IVF process
begins, in most cases, with a downregulation period
whereby natural secretion of endogenous hormones,
luteinizing hormone (LH) and follicle stimulating
hormone (FSH), is suppressed (down regulated) prior
to initiation of injections of fertility medications.
This is often achieved using daily injections of a
medication called Lupron®.
Once
down regulation is confirmed, by a blood test and
an ultrasound examination, daily injections of fertility
medications (Repronex®, Gonal-F®, or Follistim®)
is begun, often lasting eight to nine days. The purpose
of administering such medications is to stimulate
the ovaries to produce multiple follicles (in a natural
cycle a single follicle is commonly selected for growth
and ovulation), so that multiple eggs harbored in
such follicles can be harvested.The ultrasound examinations
are performed regularly along with blood tests, every
two to three days during the stimulation period, to
follow the development of follicles within the ovaries.
Once
several of the follicles have reached a mature size,
ovulation is induced with yet another injection, human
chorionic gonadotropin (hCG). Next, eggs are recovered
from the ovaries 36 hours later in a minor surgical
procedure called transvaginal ultrasound-guided follicle
aspiration. Mature eggs are mixed or injected with
sperm (intracytoplasmic sperm injection, ICSI) in
a small dish in the laboratory and fertilization of
eggs is assessed the next morning.
If fertilization had occurred (successful approximately
80% of the time), the development of the now growing
embryo (early fetus) is followed daily until the third
day of the embryo's life (three days after egg retrieval).
Meanwhile, the patient injects herself daily with
progesterone shots in preparation for the embryo transfer
procedure. Next, three day old embryos of the highest
quality are transferred into the patient's uterus
using a special catheter inserted through the patient's
cervix. A pregnancy test is performed 9 to 11 days
later.
Now,
imagine failing this process one time. Imagine failing
this process two times. Imagine failing this entire
process three times or more. Devastating? Absolutely!
Couples who have failed IVF multiple times are often
depressed, angry, disappointed, discouraged, and in
general emotionally, physically, and financially drained.
If IVF, the procedure with the highest success rate
for achieving pregnancy, has failed, what other hope
is there?
When
standard IVF and trans-cervical embryo transfer have
failed multiple times, common practice among fertility
specialists has been to offer couples a procedure
in which gametes (eggs and sperm) or zygotes (day-one
embryos) are transferred into the fallopian tubes
instead: gamete intra-fallopian transfer (GIFT), or
zygote intra-fallopian transfer (ZIFT).
Several
studies have shown significantly higher success rates
with GIFT or ZIFT as compared to standard IVF. In
GIFT and ZIFT, all steps from downregulation to ovarian
stimulation to egg retrieval, are identical to standard
IVF. However, several important differences exist.
In
a GIFT procedure, retrieved eggs and sperm are mixed
together and transferred into one or both fallopian
tubes (where natural fertilization normally occurs).
In a ZIFT procedure, on the other hand, fertilization
is allowed to take place in the laboratory just like
in standard IVF, however when day-one embryos are
formed, they are transferred into the fallopian tube(s)
instead of the usual transfer of day-three embryos
into the uterus through the cervix, as in standard
IVF. The transfer of gametes, or early embryos, into
the fallopian tubes requires a surgical procedure
called a laparoscopy.
Several
limitations exist with either a GIFT or ZIFT procedure.
First, tubal embryo transfer is not suitable for patients
with tubal factor infertility, as at least one normal
tube has to be present. Second, not all fertility
programs can offer this procedure since it requires
surgical intervention at the time of, or one day following,
the egg retrieval procedure.
This
requires that a laboratory equipped to handle gametes
and embryos be in close proximity to an operating
room. Third, success rates, although reported to be
higher than standard IVF when prior IVF cycles have
failed, are only modestly higher and are individualized
to different IVF clinics. In our program, for example,
we found that with prior failed IVF cycles, a GIFT
or ZIFT procedure achieved similar pregnancy success
rates to standard IVF, however were more expensive
and potentially risky.
So
what is next? Recently, yet another technique had
been described offering the infertile couple who had
exhausted all other standard treatment modalities
(IVF, GIFT, ZIFT) true hope: combination GIFT/IVF
or ZIFT/IVF.
In
these procedures, all known technologies are combined
to maximize success rates. After transfer of gametes
or day-one embryos into the fallopian tube(s) via
laparoscopic surgery (a GIFT or ZIFT procedure), remaining
embryos that had been left to develop in the laboratory
are transferred into the uterus through the cervix
two or three days later, when the embryo is three
days old. The advantage of combined treatment is only
one: highest pregnancy success rates in couples who
have failed multiple prior cycles of standard IVF.
In
a recent review of over 100 of our own cycles of combined
GIFT/IVF and ZIFT/IVF procedures, couples that had
failed on the average at least 2 prior IVF cycles
had a clinical pregnancy rate of 60% across all age
groups, the oldest patient conceiving at age 44 (data
soon to be published). Twin and triplet pregnancy
rates were found to be identical to standard IVF,
reassuring that transfer of more gametes or embryos
in the combined procedure did not result in any significant
increase in the multiple gestation rates, compared
to IVF.
Inability
to conceive can be a devastating phenomenon to a couple.
Often times, the road of fertility treatment may be
torturous and full of disappointment. Thanks to medical
advances in the field of Reproductive Endocrinology
and Infertility, couples that had met previous failure
can now be offered new procedures that may significantly
enhance success rates and offer renewed hope.
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