Failed IVF Pregnancy – What Next?

 

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) , 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 fertilization 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.

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 ?

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