✓ All medically assisted procreation techniques

Medically assisted procreation techniques

According to the Del Paesene guidelines on MAP, we talk about infertility (male, female or couple) when a woman is unable to get pregnant after 12-24 months of unprotected intercourse. This problem is more widespread than expected, so much so that according to the World Health Organization it concerns about the 15% of couples of childbearing age living in Western countries. Fortunately, today there are numerous medically assisted procreation techniques that allow even those who have now lost hope of being able to become parents. In fact, after more than 40 years from the birth of Louise Joy Brown, the first child born into the world thanks to in vitro fertilization, science continues to make progress thus allowing many couples to be able to hold in their arms the child they have so desired. .

Medically assisted procreation techniques are divided into several levels:

1st level: characterized by a relative simplicity of execution, the first level techniques do not involve any or only minimal manipulation of the gametes (spermatozoa). Fertilization takes place inside the woman's body, as in natural procreation;
2st level: they are instead more complex, because they involve manipulation of the female and male gametes, and because they involve in vitro fertilization, that is, in a test tube, and the subsequent transfer of the embryo into the uterus. The main one is called Fivet, an acronym which means in Vitro Fertilization and Embrio-Transfer;
3st level: they are less used because they involve more invasive procedures, but above all they are used for severe forms of male infertility or when the second level techniques have proved ineffective.

The first step to take, before embarking on an MAP, is to carry out all the investigations of the case. In fact, as Prof. Nappi points out, "it is not that all couples who are unable to procreate after one or two years will necessarily have to resort to MAP techniques to become parents. It is necessary to contact a specialized center to understand what the causes are. that do not allow the couple to have a baby, always trying to remain calm and to do not put off counseling for too long with a specialist in MAP. "Also because the age factor greatly influences the time needed to search for a pregnancy.

rea Borini, clinical manager of the national network 9PuntoBaby, talks about medically assisted procreation of the first and second level.

The causes of infertility

Before starting a process of MAP, the causes of infertility / sterility must be carefully researched, identifying all the relevant factors. The causes, grouped into categories, can coexist with each other and the most common are:

endometriosis: a disease of which there is still too little talk and for which women sometimes wait many years before being diagnosed;
tubariche/pelviche: in the event that there is obstruction or closure of the fallopian tubes, or there are pelvic adhesions;
ovulatory / hormonal: when ovulation is missing or occurs irregularly, but also in case of hyperprolactinemia, irregular menstrual cycle, micropolicistic ovarian syndrome and reduced or absent ovarian reserve;
cervical: if due to infections, estrogen deficiency or previous surgical procedures that have compromised the cervical glands, the mucus present in the woman's cervix "obstructs" the passage of spermatozoa;
male: when the partner does not produce an adequate number of spermatozoa or if they have characteristics (shape, mobility) that make fertilization difficult;
uterine: caused by malformations of the uterus, myomas, or by adhesions present inside the uterine cavity;
genetic: linked to alterations of the female or male chromosomes;
unknown (idiopathic infertility): when the tests have not highlighted one or more causes that explain the infertility.

The causes of infertility can therefore be traced back to the woman, the man or both, but it is always good in any case to talk about couple infertility. An accurate medical history and a correct physical examination represent the first step in being able to direct PMA specialists towards clinical and instrumental investigations and laboratory tests. Once the diagnostic process has been completed, it will be possible to start one of the therapeutic paths available.

Read also: Naturally pregnant after 5 attempts at APM

First level medically assisted procreation techniques

The Del Paesene guidelines (law 40/2004) envisage the use in the first instance of the simplest therapeutic options, starting with first-level MAP techniques. "It's about simple methods and not very invasive, characterized by the fact that fertilization takes place inside the female genital system - explains Prof.ssa - are intracorporeal techniques where the physiology of reproduction is respected ".

Here you go.

Ovulation monitoring

Ovulation monitoring is used for:

check whether a woman ovulates correctly or not;
direct a couple towards the best days (fertile period) in which to have sexual intercourse, thus increasing the likelihood of conception.

Ovulation monitoring consists in following, through a series of ultrasound scans, the growth of the follicle, that is the small chest in the ovaries inside which theegg to be fertilized. The patient then undergoes a series of ultrasound scans, performed a few days after each other, with the aim of identifying the dominant follicle, that is, the one that will grow and give ovulation. In order to better follow the development of the follicle, in addition to ultrasound scans, hormonal dosages are also performed through a blood sample.

With ultrasound scans the follicle is measured and based on its size it is predicted when the woman ovulates. In this way, the MAP specialist can direct the couple towards the best days to try to conceive a child.

Ovulation monitoring can also be accompanied by ovulation induction.

The induction of ovulation

The induction of ovulation is one of the most used practices in the treatment of infertility, in particular when the woman has periods without ovulation (anovulatory cycles) or irregular. Thanks to the administration of some drugs, used at particular moments in a woman's cycle, it is possible to stimulate the growth of more than one follicle in order to obtain more oocytes and thus increase the chances of getting pregnant.

This practice can only be considered if there are no problems related to tubal closure and in the absence of important factors of male infertility. The induction of ovulation allows the follicles to mature and ovulate regularly.

How is it done?

To induce ovulation they are administered to the patient drugs such as Clomiphene citrate or Gonadotropins which stimulate the activity of the ovaries and the production of follicles. The effect of the drugs is checked both through a series of ultrasound scans performed a few days apart, and with hormonal dosages (estradiol).

It is important that the specialist doses the medications correctly because if the doses are too low there is a risk of not having any follicles, while if they are too high there is a risk of multiple pregnancies. "We always try to make a stimulation as close as possible to what normally happens inside the body. Then this technique must be combined with targeted sexual intercourse or intrauterine insemination that is induced with a specific trigger ", explains Dr. Nappi

Intrauterine insemination - IUI

Intrauterine insemination is performed by introducing the partner's seminal fluid into the uterine cavity, thus facilitating the meeting between the spermatozoa and the oocyte. According to the guidelines of the Ministry of Health, this practice is indicated in cases of:

bad ovulation (endocrinological infertility);
unexplained infertility;
repeated pregnancy induction failures with stimulation of ovulation and targeted intercourse;
mild endometriosis, that is, when the disease has not affected the tubes;
problems during the passage of spermatozoa in the cervical mucus;
prevention of the risk of transmission of infectious diseases (HIV) in serodiscordant couples;
mild cases oligoasthenospermia (quantity, motility or shape of the spermatozoa below the norm) because before insemination the seminal fluid is treated in such a way as to improve its quality.

How is it done?

To perform intrauterine insemination, the woman's spontaneous ovulation can be exploited or ovulation is induced through the use of drugs such as Clomiphene citrate or injectable gonadotropins. Their effect on follicular growth, as we have seen before, must be monitored through a series of ultrasounds and with hormonal dosages.

The patient's partner, a few hours before insemination, must provide a semen sample which will be collected in a sterile container and analyzed to ensure that there is an adequate number of motile spermatozoa among which to select the best ones. The seminal fluid can be treated in the laboratory with the aim of "improving" it. "At this point, with the help of a small catheter that is inserted inside the uterus, we introduce, thanks to a syringe, the seminal fluid of the partner or a donor" explains the gynecologist.

After insemination

After intrauterine insemination the woman can resume her normal daily activities. They could occur:

leucorrhea, i.e. loss of vaginal secretions due to the thinning of the cervical mucus;
abdominal cramps;
spotting or minor bleeding.

In the days following the insemination, a woman may be prescribed hormone therapy to help implant the embryo and two weeks after intrauterine insemination, a pregnancy test must be performed.

Le complications related to this practice are rare, but cannot be completely excluded and among these we find:

upper genital tract infection;
ectopic pregnancy;
ovarian hyperstimulation syndrome (in the case of pharmacological induction of ovulation);
multiple gestation.

The chances of pregnancy for each cycle performed are just over 10% in insemination. The guidelines suggest a maximum of 3/6 intrauterine insemination cycles after which it will be necessary to consider a second level medically assisted procreation technique.

Read also: IUI intrauterine insemination: what it is and how it works

Second level medically assisted procreation techniques

"The second level techniques are the real ART techniques - explains the gynecologist - and essentially we can say that IVF was invented for women and ICSI for men".

IVF - in vitro fertilization with embryo transfer

In vitro fertilization with embryo transfer is one of the most widespread medical practices of assisted reproduction. The procedure involves joining the gametes (oocytes and sperm) outside the woman's body and, subsequently, the transfer of the embryo into the uterus.

IVF is particularly indicated in case of:

failure of previous attempts at intrauterine insemination;
advanced endometriosis;
women with severe fallopian tube injuries;
major infections leading to pelvic inflammatory disease.

Thanks to this technique, Louise Joy Brown was born in 1978, the first "test tube" baby.

How to do it

"First of all, women are stimulated with drugs in order to grow as many oocytes as possible, but in number, if possible, always less than 20 in order not to incur an exaggerated stimulation that causes inflammation" explains Prof. Nappi. "Then, through a series of ultrasound scans it is checked development of oocytes until you do the "pick-up" procedure where, after a mild sedation of the patient, the oocytes are taken from the ovaries.

Once collected, the oocytes are placed on a culture plate and surrounded by the spermatozoa, in order to fertilize them with the partner's seminal fluid. If you are having problems with your partner's sperm quality, IVF can be done with the sperm of a DONORS.

The embryos obtained are analyzed in the laboratory and classified according to their morphology and cleavage capacity and only those of the best quality will be transferred to the uterus of the woman. It is a quick and absolutely painless process. Unused embryos can be frozen for a subsequent IVF cycle.

Read also: Artificial insemination. I would do it all again, it was worth it

ICSI - intra-cytoplasmic sperm injection

"Intracytoplasmic sperm injection is a practice indicated in cases where human spermatozoa are present in very small numbers, or have motility problems," says Nappi. It is a technique that it is part of in vitro fertilization and in fact the first steps (stimulation of ovulation and egg retrieval) are exactly the same as those performed for IVF too. Unlike the latter, however, in ICSI the biologist specializing in MAP select the best sperm and therefore natural selection cannot take place. The sperm is injected directly into the egg with a small cannula. If there are more oocytes, more spermatozoa are selected.

Again, the embryos are classified and subsequently transferred to the uterus with a catheter. To be precise, ultrasound vision is used to deposit the embryos in the bottom of the uterus.

If there are other good quality embryos that have not been used, they can be cryopreserved.

Read also: The story I will tell to my son born with assisted fertilization

After in vitro fertilization

About two weeks after the embryo transfer (both for IVF and ICSI), a pregnancy test can be performed to find out if the procedure has been successful. The probability of pregnancy for the second level techniques they are about 30%. A very important factor that can change this data is the maternal age, which is why it is advisable not to wait too long before going to a medically assisted procreation center.

Read also: Icsi, intracytoplasmic sperm injection

Third level medically assisted procreation techniques

"Finally, there are also third-level techniques - explains Prof. Nappi - which, however, are not applied in all MAP centers because they require the presence of an andrologist who knows collect spermatozoa directly from the testicle or epididymis, that is, the canal that carries the sperm. "This practice is used in case of azoospermia, a condition in which there are no sperm in the man's semen. For patients with sperm-free seminal fluid, some techniques have been invented (TESE, TESA, MESA, PESA) which allow the recovery of spermatozoa directly from the testicles and epididymis. Then you can proceed with an ICSI.

Thanks to these techniques, many patients avoid resorting to heterologous fertilization.

Heterologous fertilization, what does it mean?

In some cases the gametes of one of the two partners or of both cannot be used and therefore heterologous fertilization is used. The techniques used are the same as we have presented, but the oocytes and / or spermatozoa of a donor and a donor are used.

The donation of gametes is a voluntary, free and anonymous gesture that can help many couples who wish to become parents. In Del Paese, heterologous fertilization is allowed from 2022 after the Constitutional Court overturned the ban provided for by law 40 of 2004.

Read also: Heterologous fertilization: the first two children born in Del Paese are twins

Cryopreservation of gametes and embryos

The Del Paesena law on assisted procreation now also allows the cryopreservation of gametes and embryos. For example, when a large number of oocytes are collected from a patient who has to perform an in vitro fertilization, she is given the opportunity to cryopreserve the oocytes that "move forward". Initially this technique was introduced for women who had to undergo treatments such as chemotherapy in order to preserve the possibility of conceiving in the future, but it was then extended to all other women as well.

The cryopreservation of oocytes, but also that of seminal fluid, is offered to couples who are following a path of MAP, to never waste a so precious biological material and also to avoid the woman having to undergo again, in the event of a negative result, the induction of ovulation and the retrieval of oocytes.

Furthermore, since 2009, with the sentence of the Constitutional Court, the cryopreservation of embryos, avoiding having to necessarily introduce all the embryos produced into the woman, as required by law, and thus reducing the risk related to multiple pregnancies. In this way, if embryos "advance" after in vitro fertilization, the couple can agree to cryopreserve them for later use.

Read also: Cryopreservation of oocytes: everything you need to know

What else does the Del Paesena law say about MAP techniques

In addition to the indications we have seen so far, the Del Paesena law on MAP provides that:

access to MAP techniques is allowed only to couples made up of adults, heterosexuals, married or cohabiting, of childbearing age;
medically assisted procreation techniques can be used only if infertility cannot be resolved in other ways;
couples carrying transmissible genetic diseases can access the preimplantation diagnosis;
access to the techniques is also allowed to serodiscordant pairs, that is, in which one of the two partners is a carrier of sexually transmitted viral diseases such as HIV;
children born thanks to MAP are legitimate children of the couple.

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