I have to do map: what is it?

Many couples, unable to have a child naturally, take the path of assisted fertilization.

Let's see what it consists of, the diagnostic tests and for whom it is recommended. ● When to use it ● Diagnostic tests ● Procedure ○ Ovarian stimulation and monitoring ○ Oocyte retrieval or pick-up ○ Fertilization in the laboratory ○ Embryo transfer ● After the transfer ● Results Assisted fertilization was born in practice in 1978 by Robert Edwards (Nobel Prize for Medicine in 2010) who did birth of the first baby in the world conceived in a test tube with a technique called IVF (In Vitro Fertilization and Embryo Transfer).

Since then it has been possible to achieve pregnancy even in couples suffering from tubal infertility that cannot be treated surgically and in many other infertility conditions.

Edwards spoke at various conferences we organized.

An innovative consequence of in vitro fertilization was ICSI (Intracytoplasmic Sperm Injection) with which by inserting a single sperm into the oocyte it was possible to resolve almost all cases of male infertility.

We were among the first to use it in Italy.

The two main assisted fertilization techniques are: ● IVF (In Vitro Fertilization and Embryo Transfer) ● ICSI (Intracytoplasmic Sperm Injection) IVF is a ART technique in which the oocytes are fertilized by sperm outside the uterus in a natural way.

ICSI is an innovative consequence of IVF with which by inserting a single sperm into the oocyte it is possible to resolve almost all cases of male infertility.

When to use it In vitro fertilization is recommended in the presence of: ● Obstruction of the fallopian tubes ● Medium and severe andrological infertility not suitable for intrauterine insemination ● Repeated failures of intrauterine insemination ● Long period of infertility ● Advanced age of the woman ● Low ovarian reserve ● Endometriosis ● Diseases hereditary in which pre-implantation diagnosis is necessary ● Unexplained infertility Diagnostic tests ● Hormonal analyzes to be performed on certain days of the cycle, to evaluate the ovarian reserve. ● Spermiogram sometimes also sperm culture to check the quantity and quality of the sperm. ● Pelvic ultrasound to count antral follicles and exclude ovarian and uterine pathologies. ● Genetic tests such as karyotyping and cystic fibrosis for the prevention of certain diseases or anomalies of the embryo. ● Infectious disease tests for the prevention of transmissible infectious diseases.

Procedure Ovarian stimulation and monitoring In order to proceed with the treatment, the first step for the woman is to undergo ovarian stimulation, which begins with the cycle and lasts approximately 10 days.

The patient will be administered hormonal drugs through a daily injection.

The objective of ovarian stimulation is to obtain a sufficiently large number of oocytes and, above all, of the highest possible quality.

For this reason, after having best understood the ovarian reserve and the endocrine situation of the woman, it is necessary to choose the most suitable protocol and carry out extremely personalized monitoring, through periodic ultrasound scans and blood tests.

Therefore, sufficiently frequent ultrasound monitoring (at least 3 or 4 times) and hormonal monitoring will indicate the dose and type of gonadotropins and other drugs to use day by day (in particular by measuring estradiol).

It is therefore necessary to prevent anomalous situations such as an excessive increase in Estradiol, especially in the case of polycystic ovaries; this is in order to avoid the onset of hyperstimulation syndrome.

For this reason it will sometimes be appropriate to measure this hormone daily to best adapt the doses of the drugs.

It will also be useful to measure other hormones such as progesterone.

In fact, during stimulation, anomalous elevations of progesterone can occur which make the endometrium less receptive to the embryos after transfer, as has been demonstrated for some time and confirmed in a recent case series of over 10,000 PMA cycles (Huang et al, 2015).

The more progesterone rises during stimulation, the fewer pregnancies are established, especially above certain values.

Monitoring, however, becomes critical especially towards the end of the stimulation where the diameters of the various follicles, the thickness of the endometrium and the trend of all the hormones will decide the most suitable moment to end this phase with the administration of chorionic gonadotropin.

Therefore, having a center available 7 days a week allows maximum personalization of the stimulation.

We can ultimately say that the maximum number of oocytes, their optimal maturity and quality, the best endometrial receptivity require a daily commitment from the team both for monitoring and for the day of egg collection.

In fact, each patient can have a different duration of stimulation.

Therefore a monitoring or a pick up on a public holiday cannot discourage the team which makes customization its strong point.

Oocyte retrieval or pick-up Once the stimulation is finished, because a certain number of follicles are large enough, the oocytes inside them must be removed.

This is done approximately 36-38 hours after the end of the stimulation through a puncture of these follicles using ultrasound guidance with which the liquid inside them is aspirated.

This is a short procedure (usually a few minutes) that can be done on an outpatient basis even under local anesthesia.

After a few hours it is possible to return home.

Some women have some fears about this phase but if the team is reassuring with an expert and fast operator the sensations are reduced to some menstrual pain that passes quickly, thus avoiding complete anesthesia.

Theoretically, as many oocytes should be collected as follicles are aspirated but this does not always happen for various reasons.

However, from the publication of a recent international consensus among important scholars and biologists in the field, it emerges that the best centers collect between 80 and 95% of oocytes from aspirated follicles (ESHRE, ALPHA, 2017), at least in women aged <40 years.

Fertilization in the laboratory The follicular fluid collected in the test tubes is immediately brought to the laboratory at the required temperature, the biologist looks for the oocytes and one by one places them in the suitable culture medium waiting to be inseminated.

The seminal fluid also arrives in the laboratory after the partner's collection and will be treated appropriately to select the best and most suitable spermatozoa to fertilize the oocytes.

Depending on the number and quality of the oocytes found, the number of oocytes to be inseminated, the number of embryos to be formed and transferred and the incubation times for their development outside the body will be decided.

The gametes (oocytes and spermatozoa) are then appropriately prepared for the actual fertilization process.

The embryos that form will usually be kept in culture for 2-3 days before being transferred to the uterus.

Furthermore, if a large number of oocytes are obtained, it is possible to cryopreserve some of them, through a technique called vitrification which thus avoids the process of stimulation, collection and culture to be used for possible failures and/or possibly for subsequent pregnancies.

This is a very delicate phase that requires a lot of experience and skill on the part of the biologist to treat the oocytes, choose the right spermatozoa and carry out insemination without trauma.

The laboratory techniques used for fertilization are: conventional IVF (In Vitro Fertilization and Embryo Transfer), the collected eggs are then placed on the culture plate with the spermatozoa, in order to fertilize them naturally.

ICSI is intracytoplasmic microinjection, the sperm is injected through a small cannula directly into the oocyte.

ICSI is currently the most used technique for the fertilization of oocytes, especially in the case of previous fertilization failures.

Here too, personalization can play a decisive role because oocytes, sperm and embryos are not all the same and sometimes require very different treatments.

In the laboratory phase, the skill, patience, experience and wisdom of the embryologist are fundamental to obtain the best results.

The oocytes, spermatozoa and embryos must be maintained in conditions closest to those of the body, trying to imitate as much as possible the natural reproductive environment, i.e. the tubes and the uterus.

It is known that the percentage of fertilization and the grade of the embryos obtained depends greatly on the quality of the PMA laboratory.

Here are some important things to know in my opinion about the biological aspects of the Embryo Transfer procedure. Once a certain number of embryos have been formed in the laboratory, they will have to be transferred to the uterus.

This is generally a quick and painless procedure for the woman.

The embryologist inserts the embryos into the appropriate catheter and immediately hands it to the gynecologist who transfers them into the uterus.

This is a very delicate moment because the correct execution of this phase is important for the success of the entire procedure.

To be on the safe side, it is performed under ultrasound control but we even do a simulation of the transfer the previous cycle to prevent possible problems, choosing the best catheter and measuring the uterus.

After the transfer After the transfer, most of the studies available today suggest continuing a regular life according to each person's habits because no advantages have emerged in terms of results by remaining at rest; There are particular techniques that can be used in the PMA laboratory which are performed or requested and which we believe should be treated with a critical sense in light of the scientific literature and the most up-to-date opinions of the medical-scientific community.

Results The results of PMA techniques are linked to many factors and in particular to the age of the woman because this factor greatly influences the quality of the oocytes.

On average in Italy the percentage of pregnancies resulting in the birth of children through transfer is: < 10% for IUI, 17.7% for IVF or ICSI attempts (average data from the Italian centers for 2018 from the ART Registry at the ISS for women aged 36.7 years) and 4.7% for women aged > 40 years. The personalization of our therapies allows us to offer average results. higher than those described above: 26.8% of transfer deliveries in patients with an average age of 37.3 years and 11.1% for patients aged > 40 years.

Unfortunately, our patients often come from numerous attempts that have previously failed elsewhere. However, the results can be very variable between 10% and 40% both depending on the age of the woman and the quality of the center you rely on, as demonstrated by the data from American centers where it is possible to verify the results center by center.

In particular, the personalization of treatments is very important. In cases of older age and low ovarian reserve we have special programs.