Matt Tomlinson, NUH Life Fertility Services, Nottingham
Approximately 950 delegates registered for cryogovernance webinar on the 12th October 2021, which was organised by i3 and the international IVF initiative https://ivfmeeting.com/. I was invited along with Dr Kim Pomeroy to act as moderator for the event. Kim is Head of the World egg bank and director of two IVF units.
Cryopreservation: no room for complacency
My talk was based on a relatively recent publication (Semin Reprod Med 2018; 36: 289-298), describing an overall approach to risk management (RM) within a cryo-facility, a discussion of some of the high profile catastrophic incidents that have occurred (in the UK, USA and Canada), what can be learnt from them and how we might avoid the same sort of horrendous headlines they generated
Publicity we don’t want
I also briefly discussed the basis for legal action in one such example and how defining loss from the patients’ perspective was initially difficult to define. The RM process was summarised in terms of the entire fabric of the facility and its equipment, the staff (training) and procedures and demonstrated that failing to adequately incorporate the prior knowledge from high profile incidents could leave centres vulnerable. Earlier incidents from the late 90s/early noughties where sperm bank dewars failed and the more recent ones in the USA involving significant losses of oocytes/embryos have given us all sufficient fair warning that these things can still happen and there is no longer any excuse for failing to control for them. The Bristol case at Southmead Hospital (Yearworth vs North Bristol) in 2003 became something of a test case, since although the trust (sperm bank) were found at fault for failing to monitor a faulty CBS bulk refrigerator, when it came to awarding damages, the judge dismissed the first 6 claims, stating that the losses could not be defined as ‘personal property’ or ‘personal injury and therefore there could be no claim for mental injury/distress. After many years of delay and legal wrangling the claimants eventually won on appeal, with the judge defining the claim under ‘gratuitous bailment’, legal speak for the ‘transfer of possession but not ownership’ (just as you do when you give money to the bank for safe keeping) with the clinic being found negligent by not having appropriate alarms and emergency procedures in place and were therefore failing in their ‘duty of care’. This had knock-on effects in settling similar cases in the English speaking world i.e. the ones we are more aware of in Edinburgh, Canada and more recently in Chicago. In fact the latter case where 42 sperm banking patients were affected finally awarded damages last year to its first claimant with a $1 million dollar payout.
The significant negative publicity related to such incidents and at least 3 deaths (that we know of) due to nitrogen asphyxiation associated with ART means that the industry would have few excuses for not being prepared or at least trying to control for similar catastrophic events. The damage done to reputation and ultimately the entire business will be more severe if found to be negligent. Centres must now learn from this ‘prior knowledge,’ and incorporate into their risk assessments contingency planning and training.
An increasingly rare cryo-training event
Technical Advances in Cryostorage
The second talk was an industry-sponsored lecture by Dr Mitch Schiewe who works in California (Newport Beach and Los Angeles). Mitch has also recently published on risk assessment in cryopreservation and produced some useful guidance from a technical perspective (Schiewe et al 2019, JARG 36(1) 5-14). The talk was entitled ‘Applying the KISS Principle to CryoStorage Quality Management’, and was sponsored by Boreas, a cryo-safety company who seem to be working closely with Mitch on developing a novel real-time dewar/tank monitoring systems (see image below). Mitch started by re-iterating some of the issues I had mentioned but more from an American perspective on the need to be more aware of the potential pitfalls and legal and financial burdens associated with cryogenic storage. The two catastrophic events in Cleveland and San Franciso had certainly made the US cryobanking and IVF industries more sensitive and Mitch has been at the forefront in developing process and equipment aimed at reducing the risk of anything similar occurring. He demonstrated a dewar monitoring system based on real-time vessel weight which utilises a device integrated into the dewar’s roller base (see below). Mitch explained that the advantages are simple, in that not only can alarms be generated when weight reaches a critical pre-defined level but the software package demonstrated how all vessels can be continuously monitored and then replaced if they begin to perform poorly.
Boreas dewar monitoring system
He then went onto discussing some novel equipment developments and advances in dewar design that are likely to be introduced into the modern cryo-facility in the near future, with some hopefully replacing the more hazardous roles that reproductive scientists currently perform, such as placing/retrieving material from storage, and physical tank audit. He talked briefly about the recent developments combining robotic and RFID technology (see www.tmrw.org) which can provide automated vitrification, placement in permanent storage as well as automated retrieval. Real-time monitoring and knowing the precise location of RFID tagged material at all times, could and should do away with the need for routine physical audit, which represents a risk to both operator and samples. It all seemed very futuristic and on a path to something akin to an ‘ATM for sperm, oocytes and embryos’ but as it was described later, we need to bring cryogenics out of the dark ages from its agricultural industry beginnings and take it forward into modern medicine.
Tomorrow’s technology – automated cooling, storage and retrieval
Lastly, Mitch talked about some other novel high capacity freezer designs, aimed at those labs who’s cryoroom might be full of dewars and need extra capacity but are either concerned or don’t have the space for very large high capacity vapour phase storage systems. The new nitrogen efficient ‘low boy’ had the capacity for 1200 canes, a flat working surface and low ergonomic design, which was WiFi enabled to a ‘cloud-based’ monitoring and alarm system.
The scary legal stuff
The final talk of the session was by the legal expert, Colleen Quinn. Colleen is a prize-winning US lawyer who has recently been involved in the legal actions arising from the high profile cryo-disasters in San Franciso California and Cleveland Ohio in 2018. Approximately 7500 oocytes and embryos were lost as a result of a failure of equipment/process/systems at both clinics and the first resulting legal actions have now reached the courts. Colleen’s talk ‘When Systems Fail: Liability for Lost & Mishandled Gametes & Embryos’ initially described in detail exactly how the legal profession had arrived at defining loss within a class action lawsuit and how they started to calculate the level of damages. As with the North Bristol case mentioned previously, to award damages, there first has to be an assessment of the legal basis of the award and to define in law how exactly patients have been wronged. Colleen used a number of legal descriptors which may or may not be applied to similar cases involving the loss of, or damage to patient material (gametes and embryos) and these included; malpractice, breach of contract, bailment, negligent or intentional infliction of emotional distress, wrongful death, negligence (general and physical injury), loss of property, detinue (wrongful taking of property), wrongful life and even fraud.
There was also a description of how clinics may attempt to limit their damages (known as liquidated damages) by asking patients to agree to a local contract or agreement which sets out terms even in the event of something going wrong. Colleen described how these can be used but most courts will not enforce them if they are not a reasonable estimate of actual damages and therefore open to challenge. In one example, liquidated damages were estimated by the clinic as being the total storage charge plus $400 per embryo lost. However, although the eventual figures could not be disclosed calculations were far higher than those previously outlined in the initial storage agreement, which may have implications for a number of other centres. Moreover, this is a common practice used by specialist couriers, who transport sperm and embryos around and attempt to ‘limit’ their liability using contracts and internal disclaimers. Clearly, these are not going to stand up to scrutiny if the patient decided to go to court.
specialist couriers…transport sperm and embryos around and attempt to ‘limit’ their liability using contracts and internal disclaimers. Clearly, these are not going to stand up to scrutiny if the patient decided to go to court.
Lastly, Colleen turned to the most recent high profile incidents at Pacific Fertility and Cleveland Ohio. Colleen was involved in assessing damages which was clearly very difficult. Although costs can be calculated for replacement of IVF treatments, storage costs, and compensation for time/travel etc, there are many intangible costs that cannot be calculated, such as oocyte/embryo quality, what was the prospect of pregnancy? In all cases however, decisions were made in court in relation to emotional distress which would have huge implications for the awarding of damages. The initial economic evaluations appeared relatively modest with losses somewhere in the region of $25,000. However in the first class action to be awarded so far, three women losing oocytes and 1 couple losing embryos were awarded a share of $15 million. Bearing in mind the number of lost embryos/oocytes is estimated at 3500, estimated liabilities could be as high as half a billion dollars, a sum that neither the clinics nor manufacturers of the affected freezer would or could be insured for.
Headlines to avoid
Round table discussion
Attendees were asked to post questions during and after the sessions and a lively discussion followed. Many delegates asked similar if not the same type of very valid technical questions including:
- What is the shelf life of dewars?
- Are liquid storage dewars safer than bulk storage freezers?
- Can we over-audit and over-handle material?
Some quick imperfect (part consensus, part opinion) answers to some of these
- There probably is no recommended ‘shelf life’ for dewars. They were not intended as being classed as ‘medical devices’ when first produced and I’m sure this issue has caused manufacturers some difficulty. They may warranty the dewar vacuum for say 3 to 5 years but the vessels can perform perfectly well for 20 or more years. Although some labs will undoubtedly take a rather cautious approach and replace vessels after say 10 years, this is both expensive and probably unnecessary since dewars have no moving parts and will work fine providing the fabric and integrity remains undamaged. In fact an acute vacuum loss is probably just as likely to occur in a relatively new vessel. A more sensible approach would be to take the approach suggested by Mitch Schiewe and monitor their performance in real-time, only replacing those that begin to require more nitrogen to keep them cool.
- The consensus was that liquid phase storage in small dewars was most definitely less risky than bulk vapour storage and really based on the fact that the majority of high profile incidents mentioned by al three speakers including those in Bristol, Cleveland and San Francisco involved failures of autofill systems in bulk refrigerators. Conversely, there are very few reports of Dewar-vacuum failure and should it occur the smaller size of the vessel means that the any losses will be proportionately lower.
- Can we over-audit and over-handle material? The answer was a resounding ‘yes’ and an issue that regulators and inspectorates must be aware of. There is no evidence-base to support annual reconciliation of material versus records over any other time-frame and the exercise has to be offset against the risks posed by repeated retrieval, identification and replacement of material in terms of both staff and sample safety.
The fact that many delegates were asking the same questions suggests that, as an industry many of us are having the same thoughts, yet there remains a lack of national/international standards and guidance to give us a steer.
Transporting frozen samples – Indemnity issues
Delegates were not surprisingly slightly stunned by the sums involved in the recent court cases and a number of questions were therefore directed towards clinic insurance and indemnity of individual practitioners. One or two raised the issue of transport shippers, highlighting that losses of material in transit is occurring on a daily basis, yet what regulations are couriers/shipping companies working to? And where do the liabilities lie should material become lost in transit? In the UK, this is a thorny issue, since the HFEA license applies to either the despatching or receiving centres and not the courier who requires no license, no documented competency and no training in order to be temporarily responsible for the safe-keeping for a patient’ gametes or embryos. Given the sums potentially involved if these are then lost in transit, this grey area in the transfer of liability needs more scrutiny. Colleagues in the USA have got to be thinking that insurers are unlikely to want to be involved in IVF, considering the sums potentially involved in their recent legal cases. The knock on effect for the UK is slightly unknown as both the healthcare and legal frameworks are clearly different. The majority of sperm banks will fall under the NHS umbrella and therefore covered by ‘crown indemnity’, and the sums involved in any UK legal actions are unlikely to reach the dizzy heights of those seen in the US, especially since damages in the UK are not awarded by jury. However, NHS and private clinics alike must take stock of current practices and re-appraise the true cost of having to provide this service, given the potential liabilities. Moreover, learning lessons from the two most recent events we should continually review practice, facilities and training and ensure that we limit those liabilities. Moreover, learning lessons from the two most recent events we should continually review practice, facilities and training and ensure that we limit those liabilities as far as possible.