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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 .
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.
- 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.
- We drill the zona with a laser. This allows us to
facilitate embryo hatching , thus increasing the chances of embryo
implantation.
- Since we are transferring blastcysts on Day 5,
the synchronisation between embryo and the endomterium is increased,
thus enhancing implantation.
- 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.
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 ?
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.
Want more information about IVF? Read the chapter on
IVF in our book, How to Have a Baby.
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