Failure of ART (assisted reproduction): what it depends on and what we do

Unfortunately, failures of infertility treatments and in particular of assisted fertilization cycles are frequent.

I try to explain what these failures may depend on and what we do to identify the possible causes and consequently the remedies, especially after one or more failures of Assisted Reproduction (PMA).

First rule: don't think that because the first or second attempt at assisted reproduction (ICSI or IVF) was unsuccessful, it will always have to be like this! In fact, those who succeeded on the 3rd or 4th attempt today would not have the children they have if they had not tried again.

And how many have I seen! Second rule: try to understand why it went badly by analyzing all the details of the previous cycles.

Often apparently insignificant things come out that are actually important, even crucial for future success.

Third rule: see if all possible investigations have been carried out to highlight elements that influence fertility and correct them where they are found.

Proper preparation for PMA is important.

In a word, pay attention to the PERSONALIZATION of therapies.

Thus, from the previous stimulations it can be understood whether they were too light (few oocytes) or too strong (many poor quality oocytes with even hyperstimulation).

For this reason, an evaluation of the ovarian reserve with modern tools such as AMH (Anti-Müllerian Hormone) done in the laboratory using the automated technique and a well-done ultrasound count of the antral follicles (AFC) are important.

Therefore, in a subsequent stimulation the types and doses of drugs used can be changed.

However, be careful not to give too much importance to AMH which does not always express the ovarian reproductive potential alone.

This is what I explained to the Gynecology specialists (https://www.youtube.com/watch?v=e6d_I3dkqqI&t=27s) So follicular monitoring and above all hormonal monitoring are very important and should be done in the appropriate times and ways.

Dosing Progesterone can also tell us, for example, the right time to stop and proceed with the pick-up regardless of the follicles or estradiol.

In fact, it has been seen with studies carried out at an international level that too high a progesterone can affect the receptivity of the endometrium: this can happen even if the endometrium appears normal on ultrasound and, therefore, even if the embryos are truly normal they may not implant. (Huang et al, 2015) Normally, therefore, we measure Progesterone throughout the stimulation and we have developed techniques to prevent it from rising too much when we see a tendency to increase. Sometimes we also dose FSH during stimulation, which indicates how much of the administered drug (gonadotropins) actually circulates because some people absorb little and therefore it seems that they do not respond to the stimulation.

Instead, this sometimes depends on a difficulty in absorbing the drug itself.

In these cases we correct the situation with the right doses. Not all gonadotropins used for stimulation are the same and in order to personalize their use we should identify the type of gonadotropin most suitable for the individual patient.

These are just some examples of the things that need to be considered in the previous cycles to make a suitable attack plan: it is one of the aspects of our customization.

The quality of the oocytes chosen for fertilization can also be decisive.

In fact, the greatest influence on the quality of the embryos is given by the oocytes.

Today there are very advanced means to improve the quality of the oocytes that will be produced before stimulation thanks to latest generation supplements to be adapted to each individual to induce the formation of better oocytes.

But even the right doses and types of drugs during stimulation can be decisive for the quality of the oocytes.

The pick up must be done when the diameter of the follicles, the value of the various hormones and the thickness of the endometrium are the right ones.

Since each person reacts differently we must be ready any day of the week, even Saturday and Sunday.

You cannot delay until Monday if the follicles are ready on Sunday or bring it forward to Friday if they are not yet ripe.

Certainly this type of customization is very tiring for us but we do it willingly because we know that the results depend very much on compliance with the rules set out.

The presence of Polycystic Ovary requires particular attention, not only because of the risk of hyperstimulation which today can be adequately prevented.

In this situation, too many oocytes or the collection of immature oocytes can lead to the formation of poor quality embryos.

Even the endometrium in these cases may not be suitable for implantation.

We therefore pay particular attention to the type of stimulation and super personalized monitoring of the Polycystic Ovary which often requires daily checks up until the pick up.

Even after the transfer, it may be useful to check some hormones which could be correct if not adequate.

In fact, we believe that not everything ended with the transfer.

Psychological support is also useful in this delicate and stressful phase of waiting. Has the uterus been thoroughly investigated? Absolutely necessary question to ask yourself.

This is why hysteroscopy, for example, is very useful because it allows us to see things that ultrasound alone cannot demonstrate because the internal surface of this organ can only be seen with the optical fibers of the hysteroscope (e.g. inflammation, adhesions).

But you shouldn't do a generic hysteroscopy but rather an exam very dedicated to infertility looking for those slight anomalies of the endometrial mucosa that are often underestimated when you limit yourself to looking for septa, polyps or adhesions.

Diagnosing chronic endometritis, for example, indicates that there is a therapy to be carried out before making a new attempt which could otherwise fail even if we transfer the best embryos.

Finally, for the uterus we must see if there is an internal infection that can compromise the results and for this reason we sometimes practice an endometrial culture, (Cicinelli et al., 2015). Sometimes the embryo, even if it is really good, does not implant because it is not sufficiently coordinated with the endometrium, i.e. it does not fall into the so-called "IMPLANTATION WINDOW".

Finding out each person's planting window can be very helpful. this is done with specific tests such as "endometrial dating" carried out by histopathologists with great experience in the field. Furthermore, today we practice endometrial scratching which consists of mechanical stimulation of the endometrium which makes it more receptive to the transferred embryos.

Most studies show that this method can increase pregnancy rates (N.

E. van Hoogenhuijze et al, 2017) We analyze situations which, although not directly affecting the uterus or ovaries, can influence the results of PMA, for example the Thyroid.

For example, if this gland functions poorly, it can result in a lower implantation rate and a higher percentage of abortions.

For reproduction, hormonal values ​​are not those normally considered by laboratories as a normal range, especially when antibodies for thyroiditis are present.

Therefore, thyroid therapy must often be established and adapted before attempting PMA.

We also look for the presence of circulating antibodies or coagulation disorders that can jeopardize the attempt: preventive therapies can also be used in this case.

In fact, the sperm that fertilizes the oocyte must be of good quality to give an embryo that has maximum implantation potential.

This is especially true when the woman's age is no longer very young because the oocyte has less ability to correct sperm anomalies.

First of all, some specific tests are useful to identify deficits that may not be seen with a normal spermiogram.

Among these is the sperm DNA fragmentation test. In the event that these tests are altered it is advisable to carry out the right andrological therapies even if fertilization can be achieved with ICSI.

In fact, the oocyte can be fertilized by an imperfect sperm and then produce an abnormal embryo.

It is therefore important to improve the seminal fluid that will be used for PMA as much as possible.

This way it will be more likely to select healthy sperm to form the best embryos to transfer.

Naturally, the ability of the embryologist to choose the best sperm can be decisive and unfortunately not all embryologists have the same experience and ability.

However, it may be the choice of the right spermatozoon to insert well into the best oocyte that allows the embryo to develop suitable for implantation and continue growth for a normal pregnancy until childbirth! Even in the laboratory, therefore, extreme personalization is necessary in choosing the best sperm and oocytes, the right time to perform ICSI (even late in the evening or at night if necessary), and the way to treat the embryos.

All these considerations lead us to understand that many things influence the results of the techniques used and the quality of the centers that take them into consideration is decisive. https://www.youtube.com/watch?v=4esxRksG7vg&t=5s Finally, we cannot forget the stressful condition that our couples experience when they attempt PMA, and in particular the woman.

We cannot exclude that stress influences the success of the attempt and numerous studies suggest this (Frederiksen et al, 2015).

For this reason we pay particular attention to reducing stress thanks to the intervention of people specialized in this (couple tutor) and with the help of particular relaxation techniques.

We have discovered that the attitude of anxiety and fear of failure are very linked to results.

It would be useful to identify this level of stress and try to correct it before practicing the attempt in order to perform it with greater serenity to positively influence the results with some simple and quick but specific techniques. https://www.youtube.com/watch?v=HiOCqnYY8Tg These are just some examples of what we try to do to try assisted reproduction again.

The role of personalization is therefore decisive because each couple is different from another and the same therapies cannot always be repeated.

It's true that it takes courage to face the disappointment of failures.