Open versus closed systems for vitrification of human oocytes and blastocysts

      Vitrification has resulted in a watershed in human embryology during the past decade. This approach enabled safe and efficient cryopreservation of human oocytes and blastocysts allowing efficient application of ART procedures such as elective single blastocyst transfer (eSET) and preimplantation genetic screening (PGS), and opening new possibilities for patients including preservation of fertility for both medical and nonmedical reasons, and resolving many logistic problems during oocyte donation. However, the path was not smooth, and continuous concerns are risen re. Safety issues including long term consequences, potentially toxic cryoprotectant components, and first of all, dangers of disease transmission mediated by liquid nitrogen. Vitrification methods are commonly divided in two categories: open systems allow and closed systems eliminate direct contact with liquid nitrogen – consequently open systems are safe, and closed systems are unsafe.


      The situation, however, is much more complicated. From disease transmission point of view, there are at least four categories including
- 1. Fully open systems as the first versions of OPS, Cryotop, Cryolock, Cryoleaf etc.
- 2. Open cooling and closed storage systems eliminating the major possible source of infection during storage in dewars by using heat-sealed container straws for storage. This method was first described for the OPS in 1998 and used recently for Cryotop and other systems, as well.
- 3. Semi-closed cooling systems exposing samples to the vapor of liquid nitrogen, another potential source of infection (Cryohook, Rapid I) with open or closed storage
- 4. Thin-walled narrow capillaries, where no entirely safe procedure for aseptic expelling of the sample was described yet (Cryotip, Cryopette), and delayed expelling may also result in increased exposure to cryoprotectants.
- 5. Fully closed systems including Vitrisafe where the carrier tool is sealed into a container during cooling and storage. With this approach, the high cooling rates are sacrificed for biosafety with possible consequences on efficiency when sensitive samples are cryopreserved.
      It has to be stated clearly that the danger of disease transmission is theoretical, and if exists, it should be extremely low. The estimated >500,000 transfers after vitrification with fully open (Group 1) systems did not result in a single infection, accordingly the probability seems to be less than 0.0002%, qualifying open vitrification as one of the safest medical interventions.
      Obviously, even the theoretical danger should be considered and attempts should be made to eliminate it. However, there are other points, as well.
      It is very hard to determine the proportion of clinics using open cooling – open or closed storage systems (Group 1 or 2), but according to the publications and personal experience of authors, the percentage should be around 80% of all IVF units, and considerably higher among those focusing on oocyte vitrification. None of these laboratories use opens systems to deliberately or inadvertently expose samples and patients to potential harm. They use these systems because they are unable to find an appropriate alternative for the given purpose.
      One may refer the "primum nil nocere" principle. In fact, the duty of health care provider is not to refuse any intervention with potential negative effects (do we have any intervention free of possible complications?), but to make the right decision between the possible benefits and chances of harm. This is not just a moral duty, but a legal responsibility. According to the definition of medical malpractice or negligence, it occurs when a healthcare provider fails to provide adequate treatment for his or her patient. The consequences in ART may be serious: loss of the possibility of having children.
      Thorough analysis of existing techniques has revealed that only a fraction of the so-called closed methods is really free of any possible sources of contamination. Overwhelming evidence shows that open cooling systems allowing direct contact between liquid nitrogen and the sample (Group 1 and 2) are efficient for both blastocyst and oocyte vitrification. On the other hand, relevant data on closed systems are sporadic, especially in the case of human oocytes, and far from convincing yet. A pragmatic approach in both legislation and scientific evaluation is suggested; in other words, consider the facts instead of theories, and acknowledge the value of methods that are used in thousands of clinics and have helped many infertile couples.