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Each month, usually only a single oocyte (egg) capable of
fertilization (uniting of egg and sperm) is produced. A higher
success rate with IVF-ET depends on use of medications to
stimulate the ovaries to produce more than a single oocyte.
The response of the ovary to these medications varies. Therefore,
the number of oocytes obtained at follicle aspiration varies
and often is difficult to predict. Attempt is made to collect
as many oocytes as possible at time of follicular aspiration.
A major test for oocyte quality is its capacity to be fertilized.
Since the quality of the oocyte may be difficult to determine
before fertilization, sperm is placed with all eggs. Therefore
in summary, to increase success of IVF-ET the ovary is stimulated
to produce more than one oocyte, all follicles possible are
aspirated, and an attempt at fertilization is made on all
oocytes. Oocytes are not frozen before fertilization because
of the very poor chance of pregnancy after thawing.
In some IVF-ET cycles, more than 2-3 normally developing embryos
are available for transfer. Since the number of embryos equals
the number of gestations “babies” possible (the
risk of identical twins is very small), the greater the number
of embryos transferred, the greater the risk of multiple pregnancy
(twin with two embryos, triplet with 3 embryos, quadruplet
with four etc.). Presently it is strongly suggested that no
more than 2 embryos be transferred in women under age 35.
In several countries it is a national law that no more than
two embryos are transferred. Because of the decreasing fertility
with age, the restrictions may be lifted somewhat to allow
3 embryos in women 36-40 and 4 at age 40 and above. Even in
these age groups their in no guarantee against multiple pregnancy
and for couples concerned about multiple pregnancy it is probably
better to transfer no more than two embryos at any age.
Therefore, the couple and their fertility clinic are sometimes
faced with more embryos thought to be capable of establishing
a pregnancy than should be transferred in any one cycle. The
ethical and economic solution is embryo cryopreservation.
After it has been determined that there will be an excess
of embryos available for transfer, a selection is made after
a consultation with the couple about the quality and number
of embryos to freeze. The freezing process involves placing
the embryos in a special protecting media to diminish to shock
of freezing and gradually lowering the temperature using liquid
in a especially designed device for this purpose. The embryos
are stored in liquid nitrogen -276 degrees Celsius in small
straws that have been individually labeled. Great care is
made to ensure that each straw is precisely labeled and the
storage position noted. The chance of a mix-up, while not
impossible, is very slim. The length of time that an embryo
may retain its viability is unknown.
The transfer should occur no later than the menses of the
cycle when the embryos are to be transferred. In some cases
cycle regulation or hormonal regulation may be necessary.
A variety of techniques including basal body temperature tracking,
ovulation detection kits, ultrasound and blood testing may
be used to better time the transfer to the most fertile period.
These interventions are typically significantly less than
in an IVF cycle.
Before a transfer, the embryos are thawed and each embryo
will be examined to determine whether it is medically appropriate
(a viable, normally developing embryo) to transfer. Only about
50% of frozen embryos, after microscopic analysis, are satisfactory
for transfer. It is thought that those that do not survive
the cryopreservation and thawing process may have been produced
from less viable oocytes or sperm.
The transfer process of frozen embryos is identical to that
of "fresh" embryos obtained in the IVF-ET cycle.
Cryopreservation has 2 major advantages: 1) It offers partial
protection against multiple gestations, 2) it allows storage
of embryos until they can be transferred in later cycles without
the need for drug therapy for ovarian stimulation or the procedure
of follicle aspiration to obtain oocytes.
The major disadvantage of cryopreservation is that success
rate of establishing a pregnancy using frozen/thawed embryos
is generally lower than in a “fresh cycle”. Success
rate varies among centers and generally range up to about
30%. Before the freezing of embryos, the couple should be
made aware of the present success rate and the expected chances
of pregnancy in a later cycle. A reasonable expectation is
about 50% of the Center’s stated success rate for the
initial cycle. In part this may be due to the fact that the
better embryos are transferred in the original IVF-ET cycle.
In part, this may be due to the detrimental effects of freezing
and thawing of the embryo. It is generally considered that
healthy embryos survive the freeze-thaw procedure well.
There is no exact test for embryo quality and the distinction
of a "good quality embryo" is a subjective assessment.
However, skilled embryologists are usually able to determine
which embryos appear to be suitable for freezing and later
initiating a pregnancy.
The transfer procedure itself is identical to that performed
in a routine IVF-ET cycle and has minimal, if any risk.
Although the first successful pregnancy after cryopreservation
was reported in 1983, the procedure of cryopreservation remains
relatively new and the long-term effects on the embryo and
subsequent offspring is unknown. To date with several thousand
births form cryopreserved embryos, there appears to be no
increase in genetic or birth defects. While IVF or cryopreservation
is not an indication for amniocentesis and is not recommended
unless otherwise indicated, the couple should be aware of
its availability and this issue discussed with your obstetrician.
Embryo cryopreservation requires medical support systems and
equipment failure, including: electrical, liquid, nitrogen,
and storage tank can occur. Unforeseen and unpreventable situations
could occur, which are beyond control. These problems might
lead to non-viability (death) of the embryos.
The alternatives to embryo cryopreservation are very simple,
the decision is very complex. The major alternatives to cryopreservation
are to 1) transfer all embryos with a higher chance of multiple
pregnancy, 2) not to transfer healthy embryos and allow them
to remain in culture until growth stops, usually several hours
to 4 days, or 3) limit the number of eggs fertilize which
may significantly lessen pregnancy chances. Because it is
virtually impossible to determine the number of eggs that
will fertilize, or the subsequent embryo quality, the third
alternative is considered a poor choice and may not be available.
A decision regarding disposition of the storage of cryopreserved
embryos must be made as soon as possible. It is assumed that
embryos are held for future transfer into the female partner
of the participating couple to initiate a pregnancy. Alternatives
to this transfer are: 1) release the embryos for anonymous
donation to other infertile couples; 2) release embryos for
one center for transfer to another facility; 3) elective thaw
embryos without transfer in a manner consistent with ethical
standards and applicable legal requirements, Embryos are destroyed
by removing the embryo from the controlled culture environment
which after several hours results in the dissolution of the
cells.
IVF and embryo cryopreservation are new areas in which legal
principles and requirements are not firmly established. Based
on currently accepted principles regarding legal ownership
of the human sperm and eggs, each embryo resulting from fertilization
of the female egg by male sperm should be considered equal
joint property of the each member of the participating couple.
As such, your joint consent will be required concerning the
use and disposition of any cryopreserved embryos unless an
agreement is made to alternative utilization or disposition
of the embryos, or the final decision of a court or other
governmental authority having jurisdiction over such decisions.
Although we do not like to consider the misfortunes of life,
it is a useful exercise to consider “worse case scenarios”
when considering embryo cryopreservation.
Infertility therapy is a time of great emotional pressure.
Embryo cryopreservation and disposition of the embryos is
an extremely important consideration that requires clear thinking.
Please make sure that you have had your questions answered.
Please make sure that you keep your infertility clinic always
knows how to reach you and that they are informed any change
in your intentions about the cryopreserved embryos
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