Establishment of a controlled slow freezing-based approach for experimental clinical cryopreservation of human prepubertal testicular tissues

Kabiri, Doron; Safrai, Myriam; Gropp, Michal; Hidas, Guy; Mordechai-Daniel, Talya; Meir, Karen; Revel, Ariel; Imbar, Tal; Reubinoff, Benjamin

doi:10.1016/j.xfre.2021.11.001

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…FP poses a particular challenge in children and adolescents with cancer (Picton et al 2015 ). While adolescents are being offered long-established sperm and/or testicular tissue cryopreservation in our cryobank, FP in prepubertal patients is only available in experimental settings (Kabiri et al 2022 ). Immature testicular tissue cryopreservation in prepubertal boys is a promising technique (Kabiri et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…While adolescents are being offered long-established sperm and/or testicular tissue cryopreservation in our cryobank, FP in prepubertal patients is only available in experimental settings (Kabiri et al 2022 ). Immature testicular tissue cryopreservation in prepubertal boys is a promising technique (Kabiri et al 2022 ). We offer this procedure in collaboration with the Androprotect Study ( Universitätsklinik Münster, Germany ).…”

Section: Discussionmentioning

confidence: 99%

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Sperm and testicular tissue cryopreservation and assisted reproductive technology outcomes in male cancer patients: a 15-year experience

Fernandez-González

Radauer-Plank

Stelzer

et al. 2022

J Cancer Res Clin Oncol

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Objective To explore the characteristics of cancer patients who cryopreserved sperm/testicular tissue samples in the Cryobank of Charité-Universitätsmedizin Berlin between 2004 and 2019, and the ART utilization rate with associated outcomes. Methods Retrospective data were available for 506 cancer patients, of which 46 (9.1%) had used their samples for artificial reproductive technologies (ART). Corresponding cycle information was collected from external fertility centers. Results Our cohort included 53/506 (10.5%) patients aged < 18 years at diagnosis. While adolescents and adults mainly banked sperm, adolescents showed higher rates of testicular tissue cryopreservation before (11.8%, 6/51 vs. 6.4%, 26/406) and after treatment (16.7%, 4/24 vs. 7.8%, 13/167). At study conduction, storage had been ended for 44.8% (269/601) of samples. The majority of samples used for ART were requested within the first 3 years after cryopreservation (71.5%, 28/39, range = 0–12 years). Pregnancy rate was 51.4% (19/37 cycles), resulting in 11 singleton births, 3 twin pairs, and 4 miscarriages. Conclusion With the new advantage of public health insurance coverage of fertility preservation (FP) in Germany, an increased utilization has already been noticed in our center, emphasizing the necessity of further knowledge for individual counseling. Adolescent cancer patients need to be addressed specifically, as these patients show especially low cryopreservation rates.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sperm and testicular tissue cryopreservation and assisted reproductive technology outcomes in male cancer patients: a 15-year experience

Fernandez-González

Radauer-Plank

Stelzer

et al. 2022

J Cancer Res Clin Oncol

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“…The majority of centres nowadays perform histological or immunohistochemical analyses of testicular tissues prior to cryopreservation in order to assess the presence and quantity of germ cells, with a particular focus on spermatogonia. Moreover, individual centres have established these analyses also for frozen/thawed testicular tissues, for quality assurance purposes, and have published the results of these assessments ( Keros et al , 2005 , 2007 ; Kvist et al , 2006 ; Gille et al , 2021 ; Kabiri et al , 2022 ; Wang et al , 2022 ). Semi-quantitative analytical techniques have been proposed as a means of standardized quality assessment of freezing techniques and integrity of frozen tissue ( Rives-Feraille et al , 2022 ).…”

Section: Discussionmentioning

confidence: 99%

A 20-year overview of fertility preservation in boys: new insights gained through a comprehensive international survey

Duffin,

Neuhaus,

Andersen

et al. 2024

Human Reproduction Open

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STUDY QUESTION Twenty years after the inception of the first fertility preservation programme for pre-pubertal boys, what are the current international practices with regards to cryopreservation of immature testicular tissue? SUMMARY ANSWER Worldwide, testicular tissue has been cryopreserved from over 3000 boys under the age of 18 years for a variety of malignant and non-malignant indications; there is variability in practices related to eligibility, clinical assessment, storage, and funding. WHAT IS KNOWN ALREADY For male patients receiving gonadotoxic treatment prior to puberty, testicular tissue cryopreservation may provide a method of fertility preservation. While this technique remains experimental, an increasing number of centres worldwide are cryopreserving immature testicular tissue and are approaching clinical application of methods to use this stored tissue to restore fertility. As such, standards for quality assurance and clinical care in preserving immature testicular tissue should be established. STUDY DESIGN, SIZE, DURATION A detailed survey was sent to 17 centres within the ORCHID-NET consortium, which offer testicular tissue cryopreservation to patients under the age of 18 years. The study encompassed 60 questions and remained open from 1st July to 1st November 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS Of the 17 invited centres, 16 completed the survey, with representation from Europe, Australia, and the USA Collectively, these centres have cryopreserved testicular tissue from patients under the age of 18 years. Data are presented using descriptive analysis. MAIN RESULTS AND THE ROLE OF CHANCE Since the establishment of the first formal fertility preservation programme for pre-pubertal males in 2002, these 16 centres have cryopreserved tissue from 3118 patients under the age of 18 years, with both malignant (60.4%) and non-malignant (39.6%) diagnoses. All centres perform unilateral biopsies, while 6/16 sometimes perform bilateral biopsies. When cryopreserving tissue, 9/16 centres preserve fragments sized ≤5 mm3 with the remainder preserving fragments sized 6-20 mm3. Dimethylsulphoxide is commonly used as a cryoprotectant, with medium supplements varying across centres. There are variations in funding source, storage duration, and follow-up practice. Research, with consent, is conducted on stored tissue in 13/16 centres. LIMITATIONS, REASONS FOR CAUTION While this is a multi-national study, it will not encompass every centre worldwide that is cryopreserving testicular tissue from males under 18 years of age. As such, it is likely that the actual number of patients is even higher than we report. Whilst the study is likely to reflect global practice overall, it will not provide a complete picture of practices in every centre. WIDER IMPLICATIONS OF THE FINDINGS Given the research advances, it is reasonable to suggest that cryopreserved immature testicular tissue will in the future be used clinically to restore fertility. The growing number of patients undergoing this procedure necessitates collaboration between centres to better harmonize clinical and research protocols evaluating tissue function and clinical outcomes in these patients. STUDY FUNDING/COMPETING INTEREST(S) KD is supported by a CRUK grant (C157/A25193). RTM is supported by a UK Research and Innovation (UKRI) Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health at the University of Edinburgh is supported by MRC (MR/N022556/1). CLM is funded by Kika86 and ZonMW TAS 116003002. AvP is supported by ZonMW TAS 116003002. EG was supported by the Research Program of the Research Foundation—Flanders (G.0109.18N), Kom op tegen Kanker, the Strategic Research Program (VUB_SRP89) and the Scientific Fund Willy Gepts. JBS is supported by the Swedish Childhood Cancer Foundation (TJ2020-0026). The work of NORDFERTIL is supported by the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115), the Swedish Research Council (2018-03094; 2021-02107), and the Birgitta and Carl-Axel Rydbeck’s Research Grant for Paediatric Research (2020-00348; 2021-00073; 2022-00317; 2023-00353). CEA is supported by the Health Department of the Basque Government (Grant 2019111068 and 2022111067) and Inocente Inocente Foundation (FII22/001). MPR is funded by a Medical Research Council Centre for Reproductive Health Grant No: MR/N022556/1. AF and NR received support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. KEO is funded by the University of Pittsburgh Medical Center and the US National Institutes of Health HD100197. EG, NN, SS, CLM, AvP, CE, RTM, KD, MPR are members of COST Action CA20119 (ANDRONET) supported by COST (European Cooperation in Science and Technology). The Danish Child Cancer Foundation is also thanked for financial support (CYA). The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A

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“…To date, the methods that exist for TTC are the controlled and uncontrolled SF (CSF and USF, respectively). Last, the vitrification option is currently applied in animals but is still in an experimental phase in humans ( 187 – 189 ). As far as TTC is concerned, the SF method (particularly the CSF) is considered to be the golden standard, in terms of optimal tissue preservation and prevention of ice crystal formation ( 134 , 189 ).…”

Section: Not Routinely Applied Assisted Reproductive Technologies For...mentioning

confidence: 99%

“…Last, the vitrification option is currently applied in animals but is still in an experimental phase in humans ( 187 – 189 ). As far as TTC is concerned, the SF method (particularly the CSF) is considered to be the golden standard, in terms of optimal tissue preservation and prevention of ice crystal formation ( 134 , 189 ). Data regarding the TTC method showed significant differences between the DMSO-based medium for immature TTC and the G-base medium for mature TTC ( 190 , 191 ).…”

Section: Not Routinely Applied Assisted Reproductive Technologies For...mentioning

confidence: 99%

A comprehensive review and update on human fertility cryopreservation methods and tools

et al. 2023

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The broad conceptualization of fertility preservation and restoration has become already a major concern in the modern western world since a large number of individuals often face it in the everyday life. Driven by different health conditions and/or social reasons, a variety of patients currently rely on routinely and non-routinely applied assisted reproductive technologies, and mostly on the possibility to cryopreserve gametes and/or gonadal tissues for expanding their reproductive lifespan. This review embraces the data present in human-focused literature regarding the up-to-date methodologies and tools contemporarily applied in IVF laboratories' clinical setting of the oocyte, sperm, and embryo cryopreservation and explores the latest news and issues related to the optimization of methods used in ovarian and testicular tissue cryopreservation.

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Establishment of a controlled slow freezing-based approach for experimental clinical cryopreservation of human prepubertal testicular tissues

Cited by 9 publications

References 33 publications

Sperm and testicular tissue cryopreservation and assisted reproductive technology outcomes in male cancer patients: a 15-year experience

Sperm and testicular tissue cryopreservation and assisted reproductive technology outcomes in male cancer patients: a 15-year experience

A 20-year overview of fertility preservation in boys: new insights gained through a comprehensive international survey

A comprehensive review and update on human fertility cryopreservation methods and tools

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