| One of the most frustrating
problems in infertility today is IVF failure - also called
implantation failure. This refers to infertile patients
who have undergone many IVF cycles and produced beautiful
embryos - but the embryos have consistently failed to
implant for unexplained reasons.
Our pregnancy rates in patients who have failed IVF
cycles elsewhere is very high, because we can transfer
more embryos in difficult patients ( unlike clinics
in UK and Australia, where the number of embryos which
can be transferred is limited by law). While transferring
more embryos does increase the risk of high-order multiple
pregnancies, this risk is negligible in difficult patients
( for example, the older women or women with previous
failed IVF cycles). In our clinic, we customise the
number of embryos we transfer for each patient we treat,
rather than just blindly follow a guideline ( which
has been laid down for the general population, without
considering each individual's specific problem).
The other common reason for a failed IVF cycle is a
poor ovarian response, which means patients get few
eggs and few embryos. For these patients, we offer the
option of aggressive superovulation, with high doses
of HMG, in order to help them grow more eggs, so we
have more embryos to transfer.
For patients with a poor ovarian response, we also
offer the option of GIFT - gamete intrafallopian transfer,
in which we transfer the eggs and sperm directly into
the fallopian tubes by performing a laparoscopy. This
has a better pregnancy rate than IVF, because we put
the eggs and sperm back where they belong - in the fallopian
tubes, rather than in our incubator.
Sometimes the reason for IVF failure is because the
embryo transfer was technically difficult, because of
cervical stenosis. This means that the transfer is often
traumatic, and is associated with bleeding. For these
patients, if their fallopian tubes are open, we prefer
doing a fallopian tube transfer ( ZIFT ( ZIFT Video
) , zygote intrafallopian transfer) so that we can bypass
the cervix and place the embryos directly in the fallopian
tubes. This ensures a very high pregnancy rate.
Another group of patients who often do poorly in other
IVF clinics are those who have PCOD. Because many doctors
are so worried about the danger of OHSS ( ovarian hyperstimulation)
in these patients, they often end up superovulating
these patients badly, and retrieve few poor quality
eggs, compromising the pregnancy rate. In our clinic,
we prevent OHSS by carefully aspirating each and every
follicle at the time of egg retrieval , and flushing
it repeatedly with a double-lumen needle, until it collapses
completely. By removing the follicular cells which are
responsible for producing VEGF and causing OHSS, we
have been able to prevent OHSS in PCOD patients very
successfully in our clinic by using this novel technique.
Successful embryo implantation depends upon the health
of the embryo, and one of the reasons embryos may fail
to implant is that they may be chromosomally abnormal
(even though they look normal). Research has shown that
the incidence of chromosomal abnormalities even in good
looking embryos is as high as 50% !
We can also offer the following advanced technique
to help patients who have failed multiple cycles of
IVF .
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After fertilisation in vitro, which is performed in
the normal fashion, we perform an embryo biopsy on Day
3, using a laser, and study the genetic composition
of each embryo. This allows to select only the chromosomally
normal embryos. The normal embryos are then transferred
into the uterus on Day 5, when they are blastocysts.
This combined technique offers many advantages, especially
for older women, who are more likely to produce abnormal
embryos.
1. It allows us to select
the chromosomally normal embryos. Not only does this
increase the chances of embryo implantation, it also
means the risk of a genetically abnormal baby is reduced.
2. We drill the zona with
a laser. This allows us to facilitate embryo hatching
, thus increasing the chances of embryo implantation.
3. Since we are transferring
blastcysts on Day 5, the synchronisation between embryo
and the endomterium is increased, thus enhancing implantation.
4. Since we can transfer
fewer embryos ( each embryo now has a higher chance
of becoming a baby ), the risk of multiple pregnancies
is also reduced.
Since this technique is very labour-intensive and technologically
demanding, the cost is more than that of a regular IVF
cycle. However, for patients who have failed 2 IVF cycles,
and are not happy about the idea of repeating another
similar IVF cycle again; and for older patients, this
advanced option can be very cost-effective.
We are often asked what we feel about immune testing
for patients with repeated IVF failures . Patients who
have had failed IVF cycles even though apparently perfect
embryos were transferred, are understandably upset,
frustrated and distressed. They are looking for answers
as to why they are not getting pregnant, and a plausible
reason is that their body is “rejecting”
their embryos. This is why immune testing for patients
with reproductive failure has become very fashionable
recently. There is a long list of expensive tests which
many labs now perform – and these include: DQ
Alpha, Leukocyte Antibody Detection, Reproductive Immunophenotype,
ANA (Antinuclear Antibody), Anti-DNA/Histone Antibodies,
APA (Antiphospholipid Antibodies), Natural Killer Cell
Assay and TJ6 Protein. This mind –boggling range
of catchy acronyms conceals the fact that no one knows
whether the immune system is really responsible for
the failure of the embryos to implant in these women.
Many labs use different protocols to carry out these
tests, which are still poorly standardized. This means
that results for the same test from different labs vary
widely, making interpretation very difficult. Also,
intelligently interpreting these tests in individual
patients is virtually impossible, because of the considerable
overlap in the results in normal fertile women and those
who are infertile, since many fertile women will also
have abnormal results when subjected to these tests.
Sadly, most labs do not bother to standardize their
test results by doing them on normal fertile women.
This means that if a woman who has had an IVF failure
is subjected to these tests and has an abnormal result,
her doctor happily jumps to the erroneous conclusion
that he has now “diagnosed “ the reason
for the IVF failure, little realizing that the abnormal
result could just be a “red herring”, since
“abnormal “ results are often found in “normal
“ fertile women as well.
( These are called “ false positives “ -
test results which are abnormal ('positive'), even though
the patient has no disease. ) Unfortunately, most infertility
specialists do not really understand much about the
immune system, or what these test results mean, and
are so happy to be able to offer any treatment at all
to these desperate patients, that they often do so mindlessly.
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What about those patients who have had multiple IVF
failures, and then do finally have a healthy baby after
immune therapy ? While these patients ( and their doctors)
are happy to credit the immune therapy with their success,
the fact remains that there is no evidence to suggest
that it was in fact the immune therapy which resulted
in the successful pregnancy. This common post hoc ergo
propter hoc (after this , therefore because of this)
logical fallacy is based upon the mistaken notion that
simply because one thing happens after another, the
first event was a cause of the second event. All IVF
clinics have had many patients who have finally conceived
after multiple IVF attempts, even though there was no
change in the treatment protocol whatsoever. Sometimes,
it just needs a bit of luck , patience and perseverance
!
This is why we do not suggest that patients with repeated
IVF failures do any of these immune tests. The results
do not really influence the treatment plan - and why
do a test if it's not going to change your treatment
?
For more information, watch this video !
When IVF
fails
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Reference
Hum Reprod 2000 Sep;15(9):2003-7.
Kahraman S, Bahce M, Samli H, Imirzalioglu N, Yakisn
K, Cengiz G, Donmez E.
Healthy births and ongoing pregnancies obtained by preimplantation
genetic diagnosis in patients with advanced maternal
age and recurrent implantation failure.
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