University years

Can we fight female infertility?

Since after one week of holidays back in my hometown in the South of Italy I kind of stabilised myself and recovered a little bit from the PhD stress, this Sunday I can eventually move on from the sad topics of depression and anxiety during PhD studies and I can finally write about my bachelor thesis in Molecular Biotechnology. As I have already mentioned a couple of posts ago, I decided to apply to the Developmental and Stem Cells laboratory for my thesis and eventually they accepted my request.

Unfortunately, I was not aware of the new regulations on bachelor thesis that the University of Pavia approved, that involved the rule of having only literature reviews on a topic in the lab of choice. Therefore, when I first met the researchers and doctoral students there, I was offered only with some main topics that I had to eventually develop in order to talk about the state of art and the advantages/disadvantages of that technique/topic. It was a bit sad and upsetting not being able to put my hands on the lab bench to actually create some data, but I did not actually have any choice and I had to stick with the rules. However, even if at that moment I was a bit unmotivated by writing a thesis just by reading papers, I eventually learnt how to properly do a literary search on a topic and it taught me to critically read papers and find gaps in research that I could and would eventually fill in.

Therefore today I will write about the state of art of the in vitro maturation (IVM) of murine follicles in alginate matrix, a topic that in the end I found out was very much related to my life, since my mother had to use an in vitro fertilisation (IVF) in order to be able to get pregnant and eventually have me. But let’s start from the beginning and let’s talk about the main problem that required the development of such techniques: infertility.

Infertility is a pathology of the feminine and masculine reproductive system, that affects more and more couples around the world, and it is defined as the inability to conceive from women in reproductive age (15-49 years). Over the years many techniques have been developed to treat infertility and among these the most used ones involve the IVF, like the intrauterine insemination (IUI) that involves injection of washed sperm into the uterus with a catheter, the in vitro fertilization with consequent embryo transfer in utero or the intracytoplasmatic injection of the spermatozoon and  transfer in utero. Even if the survival of the embryos and the success of pregnancies are high, a disadvantage of this techniques is the hormonal treatments that women have to do before having a controlled ovulation: this can be threating to the women’s health, since there might be the risk of developing polycystic ovary syndrome (PCOS) or hyperstimulation ovarian syndrome (OHSS).

An alternative method, used when it is not possible to apply the IVF techniques, is the IVM of immature ovarian follicles, that allows women to skip the hormonal treatments. However, to this date there is no standard protocol able to allow good yields comparable to the ones where the oocytes have completed the maturation in vivo. Currently, the IVM protocol with the best yields in terms of meiosis recovery and competency to the embryonic development involves the use of a two-dimensional culture system. However, the knowledge of the maturation process of the follicles (a complex structure composed of the oocyte, the cell that will then be fertilised, and the follicular cells, that support and direct its growth) emphasises how the maintenance of the follicle spherical morphology and the contacts between the oocyte and the follicular cells are essential for a proper completion of the maturation process of the feminine gamete (see picture below).

“Schematic of the various stages of follicles in the human ovary”. Highlighted in red is the stage where the follicles are retrieved from women for the IVM. From

Consequently, it emerged the need of developing protocols able to sustain the growth and the three-dimensional development of the follicle outside the ovarian compartment. To date, researchers developed mechanical approaches (like moving cultures) or cultures that involve the use of biomaterials that incapsulate the follicle in their inside, in order to prevent the flattening of the follicle and its adhesion to the supporting culture. During my literature review for my Biotechnology Bachelor thesis, I focused on the technique that involve the culture of preantral murine follicles on alginate matrix, a natural bio polymer produced by brown algae that, thanks to its chemical-physical characteristics, gave promising results on human follicles as well.

Indeed, the high biocompatibility, the high affinity for water and its manageability made alginate one of the principal biomaterials used in the cellular micro-encapsulation, and its ability to form hydrogels in the presence of calcium, its biochemical characteristics and its structure make it a good candidate to support the in vitro culture of complex three-dimensions structures like the ovarian follicles. However, even if almost 6 years already passed since I wrote this literature review, research in this field is going slow and the promising data obtained are still not conclusive. Therefore, I believe that more effort should be put in this field, in order to allow women with infertility to be able to conceive babies without the risks of hormonal treatments.

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