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One
of the most frustrating aspects of assisted reproductive
technology for patients and fertilityprofessionals
alike is having to deal with failure. This is especially
true in couples who have attempted assisted reproductive
procedures many times, and also in those whose time
isrunning out because of their age. Assisted hatching
is offering hope to couples who fall into these categories.
Assisted
hatching was developed from the observation that
embryos which had a thin zona pellucida (shell) had
a higher rate of implantation during in vitro fertilization.
It was postulated that creating a minor defect in the
zona might result in a greater chance of the embryo
"hatching," or shedding its shell, allowing
for a better chance of implantation in the endometrium.
Initial
controlled trials at New York-Cornell Medical College
showed an increase in implantation in all women studied
and particularly in those over age 38 or with an elevated
FSH level on Day 3 of the menstrual cycle. Couples with
multiple failed IVF cycles also appear to benefit from
assisted hatching. AH may be helpful in these infertile
couples because their embryos lack sufficient energy
to complete the "hatching" process. It is
thought that some women may fail multiple cycles of
IVF because their eggs have a thicker shell; therefore
they have a better prognosis with assisted hatching.
In addition, hatched embryos implant one day early,
which may allow a greater opportunity for implantation
to occur, particularly if the endometrium is advanced
by the ovarian stimulation.
The
addition of assisted
hatching to the standard IVF protocol does add extra
laboratory manipulation, and therefore added costs.
There is a small risk of damage to the embryo during
the micromanipulation process or at the time of transfer,
and there may be a slight increase in identical twinning
compared with regular IVF. We have not observed a higher
rate of identical twins than with routine IVF. This
may relate to whether a large enough opening is made
in the zona to prevent pinching of the embryo during
the hatching process.
The
IVF cycle is conducted in the routine manner until the
evening of the day of retrieval, when the patient is
started on four days of a steroid, methylprednisolone,
and an antibiotic, tetracycline, to protect the embryo
from inflammatory cells. The fertilized embryos are
allowed to develop until the third day following the
retrieval, since the more advanced embryo is more resistant
to the effects of inflammatory cells.
The
assisted hatching procedure, like ICSI, is carried out
by a technique known as micromanipulation. In small
dishes the embryos, which now contain an average of
six to eight cells, are stabilized by a holding pipette,
while on the opposite side a small pipette containing
acidified Tyrode's solution creates a small defect in
the zona. The size of the defect is critical; if it
is too small it may pinch off the embryo during hatching
and either reduce the chance of implantation or cause
identical twinning. The embryos are then rinsed to remove
any excess acid solution and returned to the incubator
for a few hours before transfer into the uterus.
This relatively small variation in the IVF procedure
has yielded dramatic results. First, we discovered that
there is a learning curve for this procedure that requires
a certain amount of experience with the technique before
patients can reap maximum benefits. Our second conclusion
was that assisted hatching improved the success rate
in women between 35 and 40 so much that it began exceeding
the results of our women under 35. Since the initial
results with AH reported at Cornell showed an improved
outcome at all ages, we have therefore also done this
procedure in the younger women.
Our
third observation is that assisted hatching is most
effective through age 42. We feel that patients over
age 42 will be better served by egg
donation if they are willing to accept the concept.
This
technique seems so promising that it is surprising that
it is not a standard technique in all centers. The results
in the literature have been mixed, but the overall bulk
of evidence shows improved outcomes. AH is highly technique
dependents, which may explain why not all IVF programs
have seen the same improved success we have experienced.
This was clear in one study reporting no benefit in
which there were multiple obvious deficiencies in technique.
In addition, not all centers employed the entire regimen,
including antibiotics and steroids around the time of
transfer.
The
bottom line for couples who fall into the poor-prognosis
category because of age, previously failed cycles, or
elevated FSH levels on the third day of their menstrual
cycle is that they should consider adding assisted hatching
to the regular regimen of in vitro fertilization. It
is important to be sure that the center they choose
has enough experience with the technique to assure they
have passed the early part of the learning curve and
are achieving an enhanced success rate.
Adapted
from "Conceptions & Misconceptions: The Informed
Consumer's Guide through the Maze of In Vitro Fertilization
& Other Assisted Reproduction Techniques" by
Arthur L. Wisot M. D., FACOG and David R. Meldrum M.D.,
FACOG, Hartley & Marks Publishers, Point Roberts,
WA (published Spring 2004)
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