Assisted fertilization

The results of map in women aged 40 and over with the selection of eggs an important scientific work by prof.

Manna, director of the PMA Biofertility center, was published in one of the most quoted medical journals: Journal of Clinical Medicine.

It demonstrates good results in terms of births for PMA cycles performed in the most difficult group of patients: age from 40 years onwards, low ovarian reserve and numerous previous failures.

Furthermore, these results were obtained by selecting the oocytes to be inseminated and not the embryos (therefore without cryopreserving any of them) and the transfers were performed after 2 days of embryo culture (or after just one).

This technique was chosen to not excessively stress the already fragile embryos in these couples and therefore give them more chances of implantation, to reduce obstetric problems which have been shown to be greater with in vitro cultures that are too long (5 or more days), and to avoid accumulating frozen embryos with an uncertain fate.

The results were in fact: 95.7% fertilization rate (the international average of the centers is 65%) 10% of births per ART cycle (the average of the Italian centers according to the ISS in 2019 was 4.7% for ages 40 and over.

But it is also interesting to note that in the case studies of all ages the Italian centers had recorded 11.2% of births) 16.7% of twin pregnancies (2 twins, none with 3; in Europe the % of twin pregnancies was 16.9%) Pregnancies and births were also obtained in 44 year old women (transfer the day after the pick up) This protocol has therefore given good results and, above all, aims to reduce the risks obstetric and neonatal which a growing number of scientific studies instead associate with long embryonic cultures (blastocysts) and pre-implantation diagnosis techniques (PGT-A).

First of all, it must be considered that a non-negligible number of embryos do not even reach the blastocyst stage (for this reason at least 18.8% of women did not perform the transfer in a large study of patients of normal age but many more failed transfers were recorded in women over 40 years of age). It has been demonstrated by numerous studies that pregnancies following blastocyst transfer (5-6 days) presented more pre-term births, placenta previa and placental abruption, fetuses that are too small or too large for the gestational age compared to those recorded after the transfer of embryos at earlier stages of in vitro development (2-3 days).

Furthermore, it has been demonstrated mainly on the embryos of various animal species that the in vitro culture environment, when it is too prolonged, negatively affects the expression of the embryo's genes and even at birth, therefore pathological characteristics could manifest due to this previous exposure (epigenetic problems).

In conclusion, our study shows that even in the most difficult cases it is possible to obtain good results with PMA by choosing the best oocytes to inseminate with extensive and personalized work in the laboratory (instead of selecting the embryos and cryopreserving them) and by transferring the embryos into the uterus early.

This organ still represents the most perfected incubator after millions of years of evolution of animal species including the human one.

In fact, even the most advanced incubators that are available on the market today (and that we use anyway) cannot maintain vital parameters such as Temperature, pH, Osmolarity with the same efficiency and, above all, they do not contain in the culture media the myriad of elements, hormones and growth factors present in the reproductive system in such sensitive phases.

We therefore believe that we are practicing techniques that respect the highest ethical principles in such a delicate sector of medicine.

Research is currently underway in our center which will have to improve the ability to increasingly identify the true quality of oocytes with artificial intelligence techniques to which we have been dedicating ourselves since 2003.

The aim is to select the oocytes through their images as we have underlined in the present study, inseminate only the best ones and transfer them to the uterus.

Furthermore, in this way we would better understand the stimulation protocols and the best drugs capable of providing good oocytes both for the purpose of insemination and cryopreservation.

In fact, there are studies that demonstrate that only 5% of all the oocytes collected in the pick-ups are capable of generating a child (Lemmon et al, J Assist Reprod Genet 33.7, 2016): 1148 first IVF or ICSI cycles, all the transfers done with their cryopreserved embryos, in total 9529 oocytes and 2507 embryos, in short, a good number of elements that made us understand where did that 5% come from in this Danish study.