A new paper published in Human Reproduction March 2019 helps to solve the question as to whether it is possible to eliminate metastasized cancer cells from ovarian cortex fragments prior to auto transplantation - without compromising the tissue or follicles. In ex vivo experiments pharmacological inhibition of YAP/TAZ enabled the team from Radboud University, The Netherlands, to eradicate from human ovarian tissue fragments induced small tumours. This research is important because auto transplantation of ovarian tissue fragments containing tumour cells could reintroduce malignancy to the recipient.
Human ovarian tissue was obtained after female-to-male sex reassignment surgery and human rhabdomyosarcoma, leukaemia, breast cancer and Ewing’s sarcoma cell lines were used to induce tumour foci. The tissue fragments were cultured to allow formation of metastasis-like structures followed by a 24 hours ex vivo treatment to eradicate cancer cells. Rhabdomyosarcoma and leukaemia cells were effectively purged from the cortex tissue but breast cancer and Ewing’s sarcoma did not respond. Ovarian tissue integrity seemed not affected by purging and no statistically significant difference was observed in the percentage of morphologically normal follicles, percentage of follicles with apoptotic cells, follicular viability or glucose uptake between the control treated ovarian cortex and Verteporfin treated ovarian cortex.
The results of the study, funded in part by Merck B.V., seems to show that ex-vivo tumour cell purging of ovarian cortex fragments for fertility preservation is feasible and helps the safety of ovarian cortex auto-transplantation, increasing the chances that this form of fertility restoration could become an option for patients with malignancies where ovarian cortex transplantation is currently considered unsafe. The team, led by Dr Callista Mulder, are unclear whether the results reflect the behaviour of malignant cells that have metastasized to the ovary during natural disease progression and suggest that the functionality of the ovarian tissue after ex vivo treatment requires further investigation in vivo.
For further information
Enhancing the safety of ovarian cortex autotransplantation: cancer cells are purged completely from human ovarian tissue fragments by pharmacological inhibition of YAP/TAZ oncoproteins
Callista L Mulder Lotte L Eijkenboom Catharina C M Beerendonk Didi D M Braat Ronald Peek
Human Reproduction, Volume 34, Issue 3, March 2019, Pages 506–518
Researchers at the University of Michigan working with mice report on a new approach to assist post cancer treatment girls; chemo and radio therapy for cancer are toxic to the follicles and normally leave patients sterile. Currently a young female patient’s route to pregnancy is to freeze ovarian tissue prior to treatment with the hope that follicle growth and maturation are a viable procedure.
In this case, the team, led by Lisa Green and Hong Zhou demonstrated they could improve the rate at which ovarian follicles developed mature eggs by surrounding the follicles with adipose derived adult stem cells in a 3D scaffold, mimicking the environment of the ovary. Historically, attempts to grow human follicles into eggs in two-dimensional petri dishes have failed. The new approach increased follicle survival from less than 5% to between 42% and 86%.
These 3D scaffolds allow a single follicle to grow in all directions within a polymer network - a hydrogel. By surrounding the follicle with the adult stem cells, the researchers created a delivery system for cytokines, growth stimulating substances that improved the chances for success.
If the process became a procedure, it would involve an ovary being removed and frozen prior to treatment and, after recovery and should pregnancy be sought, follicles would be isolated and grown in vitro using the adipose derived adult stem cells till the eggs matured. "Eventually translated to human application, the hope is ovarian follicles can be taken, grown in vitro, healthy eggs obtained and a normal IVF procedure followed,” said Associate Professor Ariella Shikanov, pictured here.
The 9th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2019) will be held on 2 – 5 May 2019 at the Hong Kong Convention and Exhibition Centre. This year, the annual congress is jointly organised by the Asia Pacific Initiative on Reproduction (ASPIRE) and the Hong Kong Society for Reproductive Medicine (HKSRM).
Over the four days, scientists, clinicians, nurses and embryologists will be coming together to share their expertise. In particular, the future of reproductive medicine will be discussed, dissected and presented during the pre-congress and main congress.
We are delighted to announce that Planer will be exhibiting at Aspire 2019. Do come and see us on Stand A44 to find out more about our CT37stax™ benchtop incubator, DATAssure™ laboratory wireless alarm and monitoring system and our range of slow freezers.
A combined team from Singapore's Sincere IVF and Gleneagles Hospital, report and describe successful ovarian freeze, transplant and ICSI fertilisation in the Journal of Reproductive Biotechnology and Fertility (Dr Jaffar Ali editor-in-chief). Ovarian tissue freezing is still a novel and complicated technique which can be used clinically for fertility preservation in female children, adolescents and adults with cancer.
The team, led by Professor SC NG, performed the auto-transplantation of cryopreserved ovarian tissue and reestablished a regular menstrual cycle, collecting one egg - and its successful fertilisation showed ovarian function had been restored. In the paper, published early 2019 the authors (from Embryonics International, ACS Clinic for Woman and Sincere IVF) tell that the patient, initially diagnosed with a serous borderline tumour for both ovaries, but with no definite stromal invasion, has, subsequent to the intervention and to date, been well with no evidence of relapse noted.
The 37-year old woman patient, whilst healthy, had twenty years absence of fertility due to her husband’s azoospermia; she was diagnosed with ovarian cancer and an oopherectomy was laparoscopically performed in 2016 at Gleneagles Hospital, Singapore. The subsequent investigation showed serous borderline tumour for both ovaries but with no stromal invasion.
Three slices of morphologically normal tissue from the right ovary were collected and immediately delivered to the laboratory where the medullary tissue was removed from the ovarian pieces, and a total of 10 pieces of ovarian cortex tissue approximately 5mm by 5mm and about 1mm in thickness were prepared for cryopreservation (see below). The slow freezing method (Andersen et al., 2008 https://www.ncbi.nlm.nih.gov/pubmed/18603535) was employed to freeze the prepared pieces of the ovarian tissue.
All ten pieces of ovarian tissue were equilibrated at 4 °C and were then placed into cryo-vials for computer controlled freezing with a Planer Kryo-360. The initial cooling rate was −2 °C/min to −9 °C with manual seeding performed and cooling was continued at different ramps to−140 °C, when the samples were plunged into liquid nitrogen at −196 °C, and transferred to a liquid nitrogen storage tank.
Neither chemotherapy nor radiotherapy was performed on the patient who ten months later underwent heterotopic transplantation of thawed ovarian tissue. Two cryo-vials containing four pieces of ovarian tissue were thawed for transplantation on 16 March 2017. The cryopreserved tissue was placed into a peritoneal pocket in the region of the broad ligament, below the fallopian tube. Menstruation commenced two months later after induction and follicle growth was monitored in the fifth menstruation cycle with one follicle observed in the peritoneal pocket.
The oocyte was successfully retrieved after the fifth cycle, six months after transplantation and fertilised via intracytoplasmic sperm injection (ICSI) using the husband’s frozen-thawed testicular sperm. One 7-cell cleavage stage embryo was then frozen but no embryo transfer has been performed to date.
Pictured here, Professor Soon-Chye Ng, one of the authors mentions "The results of our first ovarian tissue transplant confirmed previous reports and lent support to the objective that ovarian tissue freezing can preserve fertility for cancer patients. This success demonstrated that cryopreservation of ovarian tissue and subsequent transplantation is a viable option for preserving fertility."
Worldwide, it is estimated that several thousand women have had ovarian tissue cryopreserved, but the number of transplantations remains low although it is accepted in an increasing number of countries; to date, more than 100 children have been born from this procedure worldwide (Andersen et al., 2018 https://www.ncbi.nlm.nih.gov/pubmed/29718400).
The authors conclude that although cryopreserving of ovarian tissue for fertility restoration is still regarded as experimental, successful collection of oocytes and fertilisation from auto transplanted ovarian tissue, such as here, show that ovarian tissue freezing can preserve fertility for cancer patients. Goals for the future should include optimising the outcomes of transplantation, with improved tissue quality, reduced follicle loss, shorter transportation times, and longer periods of functionality in cryopreserved ovarian tissue. Such improvement in technique is important as survival rates for cancer patients in their early reproductive life continue to improve with advances in cancer treatment.
For further information
Read Paper http://www.ivf-hub.net/journal-archive-new/2019-2/
Planer Kryo 360: https://planer.com/products/cryo-freezers/small-crf/kryo-360.html
More from http://www.ivf-hub.net
The Bio-preservation Core Resource at the University of Minnesota is offering a new course on the emerging issues in preservation of cell therapies aligned with the fundamentals of cryo-preservation. The course includes cryo protocol development, the designing of a storage facility plus practical advice on cryo containers and equipment, reagents, regulatory issues along with clinical aspects of cryo-preservation and quality control.
The presentation will be given in person as a course on May 21st to 22nd, 2019 in Minneapolis with a simultaneous webcast of proceedings. The lecture topics will cover:-
The course material includes both fundamentals on preservation as well as emerging issues and approaches. The course is appropriate for managers of cell therapy laboratories, technicians who preserve cells as a part of their daily routine, scientists involved in the development of cell therapies, companies that produce products for the cell therapy space, repositories that store cells to be used therapeutically and related disciplines.
The class is offered in two different formats - via class attendance or via a simultaneous webcast of the class for those who cannot attend the in-class lecture. Lectures are recorded and attendees over the web have the opportunity to review the lectures at their convenience.
For women diagnosed with cancer, chemotherapy and radiotherapy treatment may cause irreversible ovarian damage. IVF prior to treatment is only available to women with a partner or those willing to use donor sperm and is contra indicated for those with hormone sensitive tumours and, additionally, may use up valuable time.
Ovarian tissue transplantation can overcome these problems and now a new freezing and transplantation service, the first in the UK to be fully funded by the NHS, will enable specialists in cancer and blood disorders to refer patients to the Royal Free London, ahead of their treatments, for ovarian tissue freezing down, cryostorage and subsequent implantation to hopefully restore fertility or prevent early menopause.
For pre-pubertal girls and some women with hormone sensitive tumours (for example some types of breast cancer), ovarian tissue freezing is the only way that they can preserve their fertility. Patients who are cured by their chemo/radiotherapy can have cryopreserved ovary tissue recovered, thawed and surgically placed onto the remaining ovary or into the lining of the abdominal cavity.
The treatment involves the patient undergoing keyhole surgery to remove one ovary which can then be processed in the hospital’s laboratory, carefully control rate frozen down and then stored at a liquid nitrogen temperature of -196 ℃. The controlled freezing facilitates a crucial ice nucleation step using a pre programmed series of cooling rates; once frozen safely the tissue is ready for cryo-storage. When needed the ovarian slices may be thawed and transplanted back to the patient post treatment - after months or years.
Around the world there have been well over a hundred successful births as a result of this treatment and many other women have benefitted from restoration of their menstrual cycle after tissue implantation.
Consultant Paul Hardiman (pictured here, above right) said: “We have modelled our protocols on how it is done at the Rigshospitalet, Copenhagen, one of the largest hospitals in Denmark, where they have been freezing human ovarian tissue since 1999. This is a well-established method in Europe, the US and Japan but the UK has lagged behind.”
Natalie Getreu (pictured left) is part of the team that has enabled this new service and she is also looking to increase the knowledge base and is researching methods previously used to reduce ischemia in other transplanted tissues, to the human ova
The Royal Free London has a unique mix of facilities and expertise in tissue freezing and cell therapy including the services of Professors Barry Fuller and Mark Lowdell, and is also a leading kidney and liver transplant centre and the principle UK centre for cell and tissue medicines. The new service will be offered to patients within the London but is planned to expand across the UK soon.
DATAssure™ combined temperature and level sensor released
Since its introduction in 2017 the DATAssure™ wireless and monitoring system has proven itself as the ‘go to’ monitoring system for laboratories around the world.
The easy to use and intuitive system provides a wide array of different sensors, many of which are designed by Planer for use within our customers’ specific applications, and has become a huge success.
One of the specialised probes that had previously been available on the DATAcentre system (the predecessor to DATAssure) was the combined temperature and level sensor for liquid nitrogen sample storage dewars - unique to the Planer system.
We are pleased to announce that the combined temperature and level sensor is now available for the DATAssure system, both 433MHz and 2.4GHz versions.
Part numbers for the new sensors can be found in the table below.
|Description||Part Number||Detailed Description|
|Temperature & Level
Dewar - up to 50 litres
|GDDA-TL-DEWAR-433||Premium combined temperature and level sensor for 433 MHZ DATAssure systems, formable to dewar shape to ensure no interference when entering or exiting samples|
|Temperature & Level
Dewar - up to 50 litres
|GDDA-TL-DEWAR-2400||Premium combined temperature and level sensor for 2.4GHz DATAssure systems, formable to dewar shape to ensure no interference when entering or exiting samples|
Range of "standard" sensors now available
Many of the premium sensor solutions, like the temperature level sensor, Planer has developed are bespoke sensors designed to provide the optimal solution to monitoring a specific parameter or a specific piece of equipment.
However we are frequently asked for more cost effective solutions. Therefore, we are also pleased to announce that as well as the premium sensor we already provide, we are adding a new range of standard sensors which will give more cost effective, although not optimal, solutions to monitoring requirements.
Details for all the new sensors can be found in the table below:
|Description||Part Number||Detailed Description|
|For 433 MHz Systems|
|Temperature - Benchtop Incubator - Standard||GDDA-T-BT-BAS433||Standard solution provides a flat ribbon cable sensor which can be stuck down inside the chamber and the cable ran out through the chamber seal. Requires one per chamber|
|Temperature - Dewar - Straight Sensor - Standard||GDDA-T-DEWSTR-BAS433||Standard solution incorporating stiff 370mm temperature sensor which can be inserted through the dewar lid to monitor the temperature inside the dewar chamber (requires hole to be drilled through dewar lid for installation)|
|Temperature - Dewar - Curved Sensor - Standard||GDDA-T-DEWCUR-BAS433||Standard solution incorporating flexible formable 1500mm temperature sensor which can be inserted through the dewar lid to monitor the temperature inside the dewar chamber (requires modification to dewar lid for installation)|
|Temperature - Fridge -45 to +45 - Standard||GDDA-TEMP-45-BAS433||Standard solution using NTC 5K sensor with round artic grade cable which will need to be inserted around the door seal. Will measure down to -45 °C.|
|Temperature - minus 40 Freezer - Standard||GDDA-TEMP-50-BAS433||Standard solution using NTC 5K sensor with round artic grade cable which will need to be inserted around the door seal. Will measure down to -50 °C.|
|Temperature - minus 80 Freezer - Standard||GDDA-TEMP-100-BAS433||Standard solution using PT1000 sensor with round artic grade cable which will need to be inserted around the door seal. Will measure down to -100 °C.|
|For 2.4 GHz Systems|
|Temperature - Benchtop Incubator - Standard||GDDA-T-BT-BAS2400||Standard solution provides a flat ribbon cable sensor which can be stuck down inside the chamber and the cable ran out through the chamber seal. Requires one per chamber.|
|Temperature - Dewar - Straight Sensor - Standard||GDDA-T-DEWSTR-BAS2400||Standard solution incorporating stiff 370mm temperature sensor which can be inserted through the dewar lid to monitor the temperature inside the dewar chamber (requires hole to be drilled through dewar lid for installation)|
|Temperature - Dewar - Curved Sensor - Standard||GDDA-T-DEWCUR-BAS2400||Standard solution incorporating flexible formable 1500mm temperature sensor which can be inserted through the dewar lid to monitor the temperature inside the dewar chamber (requires modification to dewar lid for installation)|
|Temperature - Fridge -45 to +45 - Standard||GDDA-TEMP-45-BAS2400||Standard solution using NTC 5K sensor with round artic grade cable which will need to be inserted around the door seal. Will measure down to -45 °C.|
|Temperature - minus 40 Freezer - Standard||GDDA-TEMP-50-BAS2400||Standard solution using NTC 5K sensor with round artic grade cable which will need to be inserted around the door seal. Will measure down to -50 °C.|
|Temperature - minus 80 Freezer - Standard||GDDA-TEMP-100-BAS2400||Standard solution using PT1000 sensor with round artic grade cable which will need to be inserted around the door seal. Will measure down to -100 °C.|
On the 29th March 2019 the UK is due to leave the European Union. At the current time negotiations on the new relationship between the UK and the rest of the EU are in a state of flux but a period of adjustment after that date seems likely.
However the unexpected can happen and so we, at Planer, have contingency plans in place for an unmanaged departure. In that event:
(1) Our interactions and transactions with the UK and countries outside the EU will remain unchanged.
(2) As we have exported to 85 countries since 1973 we are well versed in tariff and customs procedures so changes regarding shipments to and from the EU under any new rules should be routinely accommodated. We have a Customs Deferment facility under which we can import goods from around the world. Our products and components generally have low or no duties (import and export), being medical equipment.
(3) Some of our products are registered as medical devices across the world and will of course continue to comply with UK, US, Chinese, Russian, Asian and other areas as they currently do. When Britain leaves the EU we anticipate a period of equivalence with Europe.
(4) None of our staff will be impacted by any potential changes to immigration policy therefore we will be working as normal here at our Sunbury headquarters, ensuring product and services are available when required.
(5) Like many UK companies we have ordered extra stocks of parts that we import from any EU suppliers and we have sufficient to meet customer demand for quite a long period. We do not anticipate problems with components or products shipped into the UK. Extra staff will be available to minimise any impact and we are working with our freight partners to make sure goods can be shipped in the most efficient way.
We hope that a satisfactory agreement between the EU and UK will be achieved and that none of our contingency plans will be necessary. I would like to reassure all our customers in the UK, in the European Union and worldwide that the team here at Planer are confident products will be available globally just as they have been for the last 45 years.