One of the most frustrating aspects of assisted reproductive technology
for patients and fertility professionals 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 is running out because
of their age. Now, a recently developed technique, assisted hatching, is
offering new 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 a marked increase in
implantation in women over age 35 and particularly over 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. Assisted
hatching 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. 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. |