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Why can a FIVET or ICSI attempt fail

letto 6397 volte | autore: Claudio Manna, ginecologo specialista in fecondazione assistita (vai al curriculum)


Failure of one or more attempts of Assisted reproduction represents a common enough experience for those who undergo this technique because attempts with good results are less numerous that failures.
Above all, from a psychological viewpoint it is a difficult experience, someone who has never tried it cannot understand, especially if this happens many times.  There is, however, no need to be discouraged because you might be able to find the reasons of failure and correct them.

Failed attempts, above all, often have economic implications.  In fact not everyone can  afford to spend money on interventions that are very costly; for this reason it is necessary to try and reduce the costs by keeping the therapy levels as high as possible.

Finally, the attempts involve a notable wastage of time (monitoring, therapy, rest after transfer)  For this reason all energy needs to be concentrated (for both the couple and the medical team) to the maximum for every single attempt.

Here we would like to explain to you why attempts can fail and what we do when this happens.  Naturally, this is a generic description and cannot substitute advice given in specific cases.

We, in fact, believe that the secret to success is the personalisation of the therapy, in all the phases of the cycle and particularly during stimulation.

Causes of failure
First of all, it is necessary to specify that the results  of  assisted reproductive cycles generally depend on 2 or 3 factors: the quality of the centre (there are centres that have less than 10% pregnancies and centres that have more than 50%), the age of the woman (the higher the age the lower the results especially after 50 years), ovarian response to stimulation (which is generally linked to the age of the woman).    Therefore, the principal causes of failure are because of:

  • Poor quality centre to which you resort
  • Advanced age of the woman
  • Poor  response to ovarian stimulation

The embryo
These factors negatively affect the quality of the embryo, on which the failure of the cycle principally depends.  In fact it is known that implantation is linked also to the uterus but to a much lower degree than the embryo.

The quality of the embryo depends principally on the quality of the ovum (to a much lower degree that of the spermatozoon).  Bad ova generally result from bad stimulation.  Good embryos have 4 to 6 cells that are equal, 48 hours after fertilisation.  Even a reduced number of  embryos transferred is often a cause of failure.  It is noted that especially in women of advanced age there is the need to transfer many embryos in order to have good chances.

Transfer: the transfer of embryos is a very delicate procedure, often difficult, in every instance it is critical because one wrong move that lasts a few seconds creates the risk of destroying all the work that was done before!  Wrong transfers are much more than you would believe.

Uterus: sometimes the uterus presents with myoma, polyps or other formations that can impede implantation of the  embryo and favour abortion.  This can happen if the uterus is not studied well before and these defects are not recognised and eliminated.

Immunological factors: numerous studies have identified the presence of circulating antibodies of different kinds that could impede implantation and favour abortion.  A study of these antibodies should be performed in the case of failure of Assisted reproduction.

Psychological factors: whether anxiety or other psychological factors can play a role in missed embryo engagement is often discussed.  It seems that excessive and un-coordinated contractions of the uterus can impede implantation.  Maybe adverse  psychological conditions can influence actual uterine contraction but this is not well documented.  Certainly, relaxed conditions are beneficial for
the normal progress of cycles of FIVET or ICSI.

What do we do in the case of FIVET or ICSI failure
The most important thing is to personalise every phase of the process to the maximum because every patient is different from the next and it is necessary to adapt all the phases of the Assisted Reproductive cycle to the organism on which it is being undertaken at that moment to maximise the results obtained.

This requires lots of effort from the team but we believe that it is worthwhile effort!
This way we can list our programme in the cases of previous failures.

Tests that precede the attempt
We perform a very profound hormonal test before we begin stimulation.  This allows us to apply the most ideal type of stimulation for the patient (type of drugs, quantity and the method of administration).  In the same test cycle we perform the so called “test of transfer” which allows for a simulation of real transfer in order to choose the type of catheter to use, know exactly where to position the embryos (because not everyone has the same size uterus), know in advance the exact path the catheter should follow  (especially in the uterus) before you reach one cm from the bottom.  If we find any big obstacles that make transfer difficult these are removed.  In fact real transfer should be a quick and painless manoeuvre.

A certain amount of ability and sensitivity is necessary in order to perform embryo transfer which is a very delicate and critical procedure. The trial of transfer is part of an accurate study of the uterus that includes a hysteroscopy.

Any polyps and submucal fibroids should be removed and any conditions of  endometriosis (inflammation of the emdometrium) that have been diagnosed with the hysteroscopy, that if present can impede embryo implantation  should be treated.  Serious investigation is undertaken to find antibodies and pathologies that could be an obstacle for the implantation of the embryo.  In the case that these antibodies are found appropriate therapy is performed.

What do we do during the execution of an ICSI or FIVET cycle
Stimulation includes the use of various drugs that need to be adapted to the “type of endocrine system” of the patient we have in our care. Special  attention is given to patients who tend to develop few follicles (“low responder”) using particular preparations that precede stimulation itself.

Even those who tend to respond with an excessive number of follicles are treated with a particular therapy protocol, not so much for the prevention of hyper-stimulation, but, mainly in order to improve the quality of the ovules that are harvested, which in this case are immature or dismature thus giving way to poor quality embryos.

The heart of stimulation, because this allows for maximum efficacy, is monitoring   is and undertaken with extreme care and attention. In fact the dosage of at least 3 hormones is measured and an ultrasound  is performed, in order to adapt and modify the types and the quality of the drugs used to obtain optimal stimulation of the follicles which give the highest possible quality of ovules.

This program allows us to better evaluate if something isn’t working and therefore interrupt stimulation without reaching the harvest of ova and transfer of embryos that would have little or no possibility of implantation.  The monitoring that we perform is also put under computerised analysis using particular programmes that help in the decisions that need to be taken regarding the  drugs to be used from day to day.

What do we do in the laboratory to improve
Above all we keep very tight control of the conditions of the cellular culture for both bacterial pollution and for substances which are potentially toxic for the  ova and the embryo and also use special filters for the ambiental air circulation.

To improve the quality of the embryos we can use a certain number of special techniques. Hatching which involves the making an incision in the outer shell of the ovum called the “Zona Pellucida” by means of particular substances and ideal micro-utensils.  This is done to improve the exit of the embryo when in it should implant in the endometrium.

Culture is a laboratory technique: it involves maintaining the embryo immerged in an ideal    liquid, not alone, but with other cells that perform the function of absorbing toxic substances produced by the embryo itself or from the environment and produce growth factors that help the embryo to develop well.  Since the quality of the ova represents the most critical element for the success of the ICSI or FIVET attempt if the ova produced are bad regardless of all the effort made with stimulation, the chances of obtaining good embryos are almost inexistent.

Since the cytoplasm of the ova, that is the part that surrounds the nucleus with the chromosomes is often, in most of these cases, defective many  vacuole  (dark spots) are evident the only possibility might be that of transferring a certain quantity of cytoplasm that comes from a good ovum into the cavity of the poor quality ovum; this involves the transfer of cytoplasm which is a complicated technique that can render good results in certain cases.

Since the genetic material of the chromosomes from other peoples ova is neither touched nor transferred, this procedure is bio-ethically valid: it regards giving nutritive substances that come from the ovule of another more fertile patient (generally younger).  It is possible to perform culture of the embryos for  5 days till the blastocyst stage, this way they have a better chance of implantation.  Notwithstanding, if the embryo  was of good quality to start of with, it transforms into blastocysts even in the uterus after transfer.  If , however, it was of poor quality from the beginning it will not transform to blastocysts be it in culture outside the body nor inside the body.

From transfer and thereafter
The number of embryos that are transferred into the uterus greatly influences the chances of pregnancy.  Undoubtedly  the increase of embryos transferred the probability of twin or triplet pregnancies is higher.  Nevertheless, when many attempts fail especially in advanced age, a higher than average number of embryos are transferred.

In fact we believe that you cannot set a limit to the number of  embryos (lets say 3) to transfer because after a certain age (from 40 on) the quality of the ovules is not very good, it is therefore necessary to transfer many embryos to have higher possibility that at least one implants.

Transfer is a very delicate moment and can also be difficult because it is a manoeuvre that is generally undertaken “blindly”.  In fact once the catheter enters the uterus nothing can be seen and everything is linked to sensation or an indirect point of reference.

To be sure that the catheter is effectively inside the uterus and in the right place we follow its progress using ultrasound.  It is even possible to see the drop of liquid that contains the embryo coming out of the catheter.  After transfer, apart from the progesterone that is prescribed, a variable pharmacological  therapy is undertaken in order to make the endometrium more receptive to the embryo.

Disclaimer: the information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her existing physician.

venerdì 21 marzo 2008

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