Minimal Infiltrative Disease Identification in Cryopreserved Ovarian Tissue of Girls with Cancer for Future Use: A Systematic Review

Grubliauskaite, Monika; van der Perk, M. E. Madeleine; Bos, Annelies M. E.; Meijer, Annelot J. M.; Gudleviciene, Zivile; van den Heuvel-Eibrink, Marry M.; Rascon, Jelena

doi:10.3390/cancers15174199

Cited by 5 publications

(2 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In their recent review, Grubliauskaite et al report the detection of malignant cells in ovarian tissue cryopreserved from 25 out of 115 female patients. In addition to histological and immunohistochemical techniques, these studies employed molecular approaches to assess for minimal residual disease ( Grubliauskaite et al , 2023 ). Ongoing consideration for the optimal technique(s) to assess testicular tissue is required.…”

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

View full text Add to dashboard Cite

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

show abstract

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

View full text Add to dashboard Cite

show abstract

“…While our primary emphasis lies in addressing the fertility concerns of women and young girls facing hematological malignancies, the broader impact of this approach extends to other high-risk patient groups. Specifically, young women and prepubertal girls at risk of ovarian metastasis from neuroblastoma and Ewing sarcoma ( Grubliauskaite et al , 2023 ), stand to benefit from our innovative methodology. Furthermore, patients undergoing gonadotoxic treatment due to autoimmune diseases ( Marder et al , 2012 ) could benefit from this fertility restoration approach.…”

Section: Discussionmentioning

confidence: 99%

Influence of ovarian stromal cells on human ovarian follicle growth in a 3D environment

Grubliauskaitė,

Vlieghe,

Moghassemi

et al. 2023

Human Reproduction Open

Self Cite

View full text Add to dashboard Cite

STUDY QUESTION Do ovarian stromal cells (OSCs) influence the viability and growth of human pre-antral follicles in vitro? SUMMARY ANSWER A feeder layer of oSCs promotes the growth and transition of low developmental stage follicles to the primary/secondary stage while maintaining a high proportion of viable follicles. WHAT IS KNOWN ALREADY In the ovary, follicles rely on the support of ovarian cells, which secrete essential factors for their survival and development. This phenomenon has also been demonstrated in vitro through the 3D culture of isolated mouse primary and secondary follicles on a feeder layer of ovarian stromal cells. This co-culture notably enhances follicle survival and growth. STUDY DESIGN, SIZE, DURATION Pre-antral follicles were isolated from human frozen-thawed ovarian tissue (OT) biopsies and then encapsulated in 1% alginate scaffolds. These embedded pre-antral follicles were either placed directly on the OSCs feeder layer or at the bottom of a culture dish for a 7-day in vitro culture (control). The study compared follicle viability, growth and hormone production between the different groups. PARTICIPANTS/MATERIALS, SETTING, METHODS Primordial/intermediate and primary follicles were isolated from frozen-thawed OT of cancer patients (n = 6). Ovarian stromal cells were then isolated from OT of post-menopausal women and cultured as a feeder layer. Follicle diameter was measured on days 0 and 7 using an inverted microscope to assess their development based on the increase in diameter. Viability was evaluated by staining a subset of follicles (n = 87) with calcein AM and ethidium homodimer-I, followed by classification into healthy/minimally damaged and damaged/dead follicles using confocal fluorescence microscopy. Additionally, estradiol levels were measured using ELISA. MAIN RESULTS AND THE ROLE OF CHANCE A total of 382 human preantral follicles (370 primordial/intermediate and 12 primary) with a mean diameter of 40.8 ± 9.9 µm (mean±SD) were isolated, embedded in 1% alginate hydrogel, and placed either on a monolayer of oSCs or directly on the plastic. By Day 7, the preantral follicles showed a significant size increase under both culture conditions (p < 0.0001 for D0 vs D7). The mean diameter of follicles (quiescent and growing) cultured on the feeder layer was 80.6 ± 11.0 μm compared to 67.3 ± 7.2 μm without it (p = 0.07). During the 7-day in vitro culture, the viability of the follicles significantly decreased only in the group without an OSCs monolayer compared to the D0 viability (p < 0.05). Additionally, more follicles transitioned to a higher developmental stage in the presence of OSCs (D0 primordial/intermediate: 184, primary: 7 vs D7 primordial/intermediate: 51, primary/secondary: 93) compared to those cultured without OSCs (D0 primordial/intermediate: 186, primary: 5 vs D7 primordial/intermediate: 84, primary/secondary: 65; p < 0.001). Specifically, 66 and 44 follicles reached the secondary stage (75 < x < 200 μm) in the presence and absence of OSCs, respectively. Moreover, the estradiol level was significantly higher (p = 0.006) in the alginate beads containing primordial and growing follicles cultured on the OSCs (54.1 ± 14.2 pg/ml) compared to those cultured without oSCs (29.9 ± 4.0 pg/ml). LARGE SCALE DATA N/A LIMITATIONS, REASONS FOR CAUTION This study was conducted using a short-term culture, and none of the primordial/intermediate/primary follicles reached the antral stage. Further in vitro studies are required to investigate follicular developmental capacity, physiology and steroidogenesis in alginate scaffolds with human ovarian stromal cells. WIDER IMPLICATIONS OF THE FINDINGS Activating and growing human primordial/intermediate follicles to a secondary stage in in vitro short-term culture has posed a longstanding challenge. However, co-culturing with human ovarian stromal cells has shown the potential to overcome this limitation. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR Convention grant number T.0004.20 awarded to C.A.A., Ph.D. scholarship awarded to H.V.), Fondation Louvain (awarded to C.A.A.; Ph.D. scholarship awarded to S.M., as part of a legacy from Mr Frans Heyes, and Ph.D. scholarship awarded to A.D. as part of a legacy from Mrs. Ilse Schirmer), Foundation Against Cancer (grant 2018-042 awarded to A.C.), and the European Community Structural Funds and Lithuanian Research Council (Agreement registration No. D-19-0874). The authors have no conflicts of interest to declare.

show abstract

Heterotopic ovarian transplantation instead hormonal replacement therapy after radical hysterectomy for cervical cancer: case report and review of literature

Courbiere,

Miquel,

Bottin

et al. 2024

J Assist Reprod Genet

View full text Add to dashboard Cite

Minimal Infiltrative Disease Identification in Cryopreserved Ovarian Tissue of Girls with Cancer for Future Use: A Systematic Review

Cited by 5 publications

References 110 publications

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

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

Influence of ovarian stromal cells on human ovarian follicle growth in a 3D environment

Heterotopic ovarian transplantation instead hormonal replacement therapy after radical hysterectomy for cervical cancer: case report and review of literature

Contact Info

Product

Resources

About