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920 Frostwood Tower, Suite 680
Memorial City Hospital Campus
Houston, Texas (IH 10 and Gessner).
Assisted Hatching
The
inefficiency of human IVF is largely due to implantation
failure. Reasons for the low efficiency of IVF include
genetic abnormalities of embryos, sub optimal culture
conditions, and abnormalities of the zona pellucida
which may impair embryonic hatching. Assisted hatching
is a method directed at overcoming this impaired hatching
mechanism which may be induced by in vitro culture conditions.
Animal
experiments have shown in the mouse that hatching may
be impaired with in vitro culture and may be overcome
by creating a gap in the zona pellucida artificially.
Other experiments on "spare" human embryos
have also demonstrated enhanced blastocyst hatching
in vitro when a gap was created in the zona pellucida
artificially.
The
indications for assisted
hatching in the human include elevated maternal
age, elevated basal FSH, increased zona thickness, unexplained
implantation failure, and reduced cleavage rates or
excess embryonic fragmentation. The methods utilized
for assisted hatching have included partial zona dissection, zona drilling
with acid Tyrode's solution, and various laser technologies.
The size of the hole or gap created in the zona is critical
for success. A hole that is either too large or too
small will impair the ability of an embryo to implant.
Atraumatic transfer of the embryos is also a requirement
for success.
Numerous
clinical trial have verified the efficacy of assisted
hatching in poor prognosis IVF patients. The definitive
randomized control trial was reported by Cohen in 1992.
This study involved 330 IVF patients and demonstrated
an improvement in implantation rates with selective
assisted hatching, particularly in patients age 39 and
older and patients with elevated basal FSH levels.
Our center has reported two different trials utilizing
similar methods of assisted
hatching, and our results confirm the benefit of
this technology in poor prognosis patients. Several
other authors have reported on the benefit of assisted
hatching using acid Tyrode's solution, partial zona
dissection, and various laser methods.
Assisted
hatching has also been shown to improve the prognosis
of frozen thawed embryos. Recently enzymes have been
used to take the entire zona off the human embryo at
the blastocyst stage prior to transfer with success.
The potential adverse effects to assisted hatching include
a theoretical risk of increased identical twining, damage
to the embryo from the hatching procedure itself, and
damage to the embryo during transfer.
Assisted
hatching has been controversial since its inception
because not all authors can confirm its benefit. This
is most likely due to the difficulty of the technique
itself. As such, centers which create an improper hole
size, traumatize the embryo during the hatching procedure,
or fail to use absolute atraumatic transfer techniques
will find the procedure of no benefit or possibly detrimental.
In
the future, better techniques for assisted hatching
will hopefully ease the transfer of technology to other
centers and allow for a standardization of hole size,
thereby making the benefits of assisted hatching clear
to all. Ultimately, an improvement in culture conditions
may result in embryos which do not exhibit zona hardening,
slower cleavage rates, sub optimal cell numbers, or increased
rates of fragmentation. When such culture systems arrive,
the need for assisted hatching to "rescue"
sub optimal embryos may be eliminated.
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