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CRYOPRESERVATION AS A MEANS TO PRESERVE FERTILITY

Human reproduction has benefited from the possibilities offered by cryopreservation as much as any other discipline, in particular with the latest use of vitrification as opposed to slow freezing techniques (1). The increased efficiency of different techniques has progressively led to a “freeze-all” strategy within the last years, which supports an improvement in clinical outcomes.

Current social trends imply a significant delay in the age of motherhood. There are a variety of factors to explain such shifts in demographic charts. However, not only social freezing has popularised the use of vitrification for female gametes; the reality is that research on oocytes, donor banks, or fertility preservation treatments in cases of cancer are possible thanks to cryopreservation.

Considering the efficiency of vitrification over slow-rate freezing methods when applied to embryos and oocytes (1), it is understandable how technology and research combined succeed in providing new and improved techniques. A good example of this is the development of devices for automated vitrification like GaviTM (2).

AUTOMATED OOCYTE VITRIFICATION

The basics of vitrification are the combination of an ultra-rapid drop of temperature and the use of high concentrations of cryoprotectants, with the aim of achieving the total elimination of ice crystal formation, both in the inside and the outside of the cell. The volume of the medium in which the oocyte is immersed also needs to be minimized in order to favour the fastest temperature drop. Closed systems (in which the oocyte is not in direct contact with liquid nitrogen) need to make up for the recipient and its volume to avoid further interference in this vein.

Prior to the ultra-fast cooling, the oocyte is exposed to different solutions that need to be adequately incorporated (and removed) to safely “equilibrate” the cell while avoiding toxic effects and osmotic shock (1, 3). To date, multiple open and closed systems to cryopreserve oocytes (and embryos) have been designed (4, 5), but all of them require strict control of incubation times, steady hands and high expertise from the embryologist. However, automated systems allow treating every single cell in the exact same way, thus removing any external variable that may introduce artefactual variation between oocytes, and guaranteeing a consistent vitrification method. Potentially, procedures like this may represent a more efficient approach.

EVIDENCE FOR A MORE EFFICIENT VITRIFICATION: AUTOMATED SYSTEMS

Recently, the group of Dr. Montserrat Boada from Dexeus Mujer (Barcelona, Spain) has presented original results from an on-going investigation on the fertility potential of automated vitrified oocytes. According to the authors, there is strong evidence to support that the use of automated systems may result in higher quality oocytes than by performing the manual procedures currently standardized in clinics (6).

Improved data may be explained by the elimination of inter-oocyte variation, achieved by treating every single cell in exactly the same way; oocytes are first loaded in batches onto specific pods in the device, which automatically adds and removes the cryoprotectant and equilibration solutions. Additionally, the specific design guarantees minimization of the volume, any possible interference with the oocytes is eliminated, and pods are sealed to protect from direct contact with liquid nitrogen (7, 8). These and other features of the system represent a great advance as a whole, given the results achieved by the investigators (2, 6).

Oocytes that were automatically vitrified showed a slightly higher survival rate. This correlates with higher quality, even though the authors state that “(…) results were not significant due to the small number of oocytes utilized up to date (…)” (6). Nevertheless, fertilization rates were in fact notably higher than for manually vitrified oocytes when the experimental group was subsequently subjected to ICSI (6). Moreover, specific defects on oocytes were less frequent in those from automated vitrification (Table 1). Altogether, results shown are actually promising and may point to the right path in the laboratory for future applications.

Table 1. Original results from (6).

The study has been presented at the recent Congress of the American Society for Reproductive Medicine, held in San Antonio, Texas (US), and at the IX Congress of the ASEBIR in Barcelona (Spain), in which Dr. Miquel Solé, the first author of the published study, was awarded the Best Cryobiology Communication Prize. Nonetheless, news got even better; the work of this group has resulted in the first baby in the world born from a (semi-)automatically vitrified oocyte. The achievement took place last September in Italy, thanks to the work done at Dexeus Mujer in Barcelona [click here to read the press release from Dexeus Mujer (in Spanish)]. The baby was born through natural labour and was perfectly healthy.

With these data and the proven clinical success, it seems reasonable to think that automation of vitrification arises as significant progress in assisted reproduction. Nevertheless, further clinical and technological research is needed to keep improving this type of approach, and only time will tell how much automated procedures can serve assisted reproduction.

This article has been selected for publication in the Scientists in Reproductive Technologies (SIRT) Newsletter of The Fertility Society of Australia: DE LA FUENTE, R. (2017) Automated vitrification systems: the future of embryo/oocyte vitrification? Fertility Society of Australia – SIRT Newsletter 4(20): 23-24.

 

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REFERENCES

  1. Edgar DH, Gook DA. A critical appraisal of cryopreservation (slow cooling versus vitrification) of human oocytes and embryos. Hum Reprod Update. 2012;18(5):536-54.
  2. Roy TK, Brandi S, Tappe NM, Bradley CK, Vom E, Henderson C, et al. Embryo vitrification using a novel semi-automated closed system yields in vitro outcomes equivalent to the manual Cryotop method. Hum Reprod. 2014;29(11):2431-8.
  3. De Munck N, Vajta G. Safety and efficiency of oocyte vitrification. Cryobiology. 2017. 10.1016/j.cryobiol.2017.07.009.
  4. Vajta G, Rienzi L, Ubaldi FM. Open versus closed systems for vitrification of human oocytes and embryos. Reprod Biomed Online. 2015;30:325-33.
  5. Momozawa K, Matsuzawa A, Tokunaga Y, Abe S, Koyanagi Y, Kurita M, et al. Efficient vitrification of mouse embryos using the Kitasato Vitrification System as a novel vitrification device. Reprod Biol Endocrinol. 2017;15(1):29.
  6. Sole M, Polyzos N, Gonzalez Llagostera C, Carrasco B, Coroleu B, Veiga A, et al. Automatic vs manual vitrification of human oocytes. Preliminary results of the first randomised controlled trial using sibling oocytes. Fertil Steril. 2017;108(3 Supplement):e57.
  7. https://www.professionalsinfertility.com/en/our-fertility-technology/gavi.html