scholarly journals Fertility preservation in boys: recent developments and new insights †

2020 ◽  
Vol 2020 (3) ◽  
Author(s):  
E Goossens ◽  
K Jahnukainen ◽  
RT Mitchell ◽  
AMM van Pelt ◽  
G Pennings ◽  
...  
Keyword(s):  
High Risk ◽  
Fertility Preservation ◽  
Patient Management ◽  
Experimental Methods ◽  
Testicular Tissue ◽  
Human Testis ◽  
Clinical Practices ◽  
Future Fertility ◽  
Prepubertal Boys ◽  
Tissue Cryopreservation

Abstract BACKGROUND Infertility is an important side effect of treatments used for cancer and other non-malignant conditions in males. This may be due to the loss of spermatogonial stem cells (SSCs) and/or altered functionality of testicular somatic cells (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation is the first-line procedure to preserve fertility in post-pubertal males, this option does not exist for prepubertal boys. For patients unable to produce sperm and at high risk of losing their fertility, testicular tissue freezing is now proposed as an alternative experimental option to safeguard their fertility. OBJECTIVE AND RATIONALE With this review, we aim to provide an update on clinical practices and experimental methods, as well as to describe patient management inclusion strategies used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss. SEARCH METHODS Based on the expertise of the participating centres and a literature search of the progress in clinical practices, patient management strategies and experimental methods used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss were identified. In addition, a survey was conducted amongst European and North American centres/networks that have published papers on their testicular tissue banking activity. OUTCOMES Since the first publication on murine SSC transplantation in 1994, remarkable progress has been made towards clinical application: cryopreservation protocols for testicular tissue have been developed in animal models and are now offered to patients in clinics as a still experimental procedure. Transplantation methods have been adapted for human testis, and the efficiency and safety of the technique are being evaluated in mouse and primate models. However, important practical, medical and ethical issues must be resolved before fertility restoration can be applied in the clinic.Since the previous survey conducted in 2012, the implementation of testicular tissue cryopreservation as a means to preserve the fertility of prepubertal boys has increased. Data have been collected from 24 co-ordinating centres worldwide, which are actively offering testis tissue cryobanking to safeguard the future fertility of boys. More than 1033 young patients (age range 3 months to 18 years) have already undergone testicular tissue retrieval and storage for fertility preservation. LIMITATIONS, REASONS FOR CAUTION The review does not include the data of all reproductive centres worldwide. Other centres might be offering testicular tissue cryopreservation. Therefore, the numbers might be not representative for the entire field in reproductive medicine and biology worldwide. The key ethical issue regarding fertility preservation in prepubertal boys remains the experimental nature of the intervention. WIDER IMPLICATIONS The revised procedures can be implemented by the multi-disciplinary teams offering and/or developing treatment strategies to preserve the fertility of prepubertal boys who have a high risk of fertility loss. STUDY FUNDING/COMPETING INTEREST(S) The work was funded by ESHRE. None of the authors has a conflict of interest.

Fertility Preservation

2018 ◽  
Author(s):  
Chantae S Sullivan-Pyke ◽  
Clarisa Gracia
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Testicular Tissue ◽  
Mature Oocyte ◽  
Gonadotropin Releasing Hormone ◽  
Oocyte Cryopreservation ◽  
Ovarian Tissue Cryopreservation ◽  
Embryo Cryopreservation ◽  
Gonadotropin Releasing Hormone Agonist ◽  
Tissue Cryopreservation

Fertility preservation has becoming increasingly important for patients at risk for gonadal failure, including those needing treatment for cancer or autoimmune conditions, genetic conditions that predispose to gonadal insufficiency, and age-related fertility decline. Embryo cryopreservation and mature oocyte cryopreservation are the standards for fertility preservation in postpubertal women. Ovarian tissue cryopreservation and gonadotropin-releasing hormone agonist use for ovarian suppression are experimental methods that may be offered to patients for whom embryo and/or mature oocyte cryopreservation are not applicable. The cryopreservation of spermatozoa is the standard for fertility preservation in postpubertal males, but testicular tissue cryopreservation may be offered to prepubertal males.   This review contains 10 figures, 6 tables and 53 references Key words: controlled ovarian stimulation, embryo cryopreservation, gonadotropin-releasing hormone agonist, in vitro maturation, oocyte cryopreservation, ovarian tissue cryopreservation, sperm extraction, testicular tissue cryopreservation  

38 Vitrification of prepubertal lamb spermatogonia using a novel vitrification system

2019 ◽  
Vol 31 (1) ◽  
pp. 145 ◽  
Author(s):  
S. Ledda ◽  
S. Pinna ◽  
S. Nieddu ◽  
D. Natan ◽  
A. Arav ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
In Vitro Culture ◽  
Dimethyl Sulfoxide ◽  
Fertility Preservation ◽  
Testicular Tissue ◽  
Gonadal Tissue ◽  
New Device ◽  
Vitrification Solution ◽  
Tissue Cryopreservation

Vitrification is a method extensively used for preserving oocytes and embryos and is also gaining acceptance for preserving gonadal tissue. Cryopreservation of spermatogonial stem cells is an applicable method for young males seeking fertility preservation before starting a treatment or can be a tool for genetic preservation of rare or high-value animals. The aim of this work was to evaluate the cryopreservation of testicular tissue from young lambs by vitrification using a new device named E.Vit (FertileSafe, Ness Ziona, Israel) that permits all cryopreservation procedures to be performed in straw. The new device consists of a 0.3-mL straw (Cryo Bio System, IMV, L’Aigle, France) with a capsule containing 50-µm pores inserted at one end. Testicular tissue extracts were prepared from testes of slaughtered lambs (n=10, 40 days old), opened by sagittal sectioning with a microblade and collecting small pieces of testicular tissue (1mm3) from the middle part of the rete testis. Three pieces of gonadal tissue were inserted into each E.Vit device. Each straw was sequentially loaded vertically in two 1.5-mL microtubes, which contained the following solutions: first, the equilibrating solution (7.5% dimethyl sulfoxide+7.5% ethylene glycol+20% FCS in TCM-199) for 6min, followed by 90min in the vitrification solution (18% dimethyl sulfoxide+18% ethylene glycol+0.5M Trehalose+BSA in TCM-199). After exposure to the equilibrating solution and vitrification solution, the solutions were removed and the straws were directly loaded into LN2. The warming procedure consisted of placing the straws directly into 5-mL tubes containing 100, 50, and 25% warming solution (1M sucrose in TCM-199+20% FCS) at 38.6°C for 5min each before arrival into the holding medium. Samples were recovered from the straws incubated at 38.6°C in 5% CO2 in air in TCM 199+5% FCS and evaluated at 0 and 2h post-warming for viability using trypan blue staining. Expression of a panel of specific genes (SOD2, HSP90b, BAX, POUF5/OCT4, TERT, CIRBP, KIF11, AR, FSHR) was analysed by real-time PCR in cryopreserved tissue in vitro cultured for 2h post-warming (2hV), in fresh controls immediately after tissue dissection (0hF), and after 2h of in vitro culture (2hF). The majority of cells survived after vitrification, although viability immediately after warming (0hV: 56%±1.45) or after 2h of in vitro culture (IVC) (2hV: 54±7%) was significantly lower compared with non-cryopreserved fresh controls (0hF: 89%±1.45; ANOVA P<0.05). Expression analysis showed specific patterns for the different genes. Notably, BAX transcript abundance was not affected by vitrification or IVC, indicating an acceptable level of stress for the cells. The genes HSP90b and CIRBP were down-regulated in 2hF but increased in 2hV, as expected. Expression of SOD1 and OCT4 was altered by vitrification but not by IVC. Conversely, expression of TERT, KIF11, and AR was affected by both IVC and cryopreservation (ANOVA P<0.05). This novel protocol for testicular tissue cryopreservation of prepubertal animals may be a promising strategy for fertility preservation and can contribute as a new approach in the development of large-scale biodiversity programs.

scholarly journals Setting Up a Cryopreservation Programme for Immature Testicular Tissue: Lessons Learned After More Than 15 Years of Experience

2019 ◽  
Vol 13 ◽  
pp. 117955811988634 ◽  
Author(s):  
Aude Braye ◽  
Herman Tournaye ◽  
Ellen Goossens
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Klinefelter Syndrome ◽  
Autologous Transplantation ◽  
Cell Loss ◽  
Testicular Tissue ◽  
Lessons Learned ◽  
Adult Age ◽  
Future Fertility

Young boys undergoing gonadotoxic treatments are at high risk of spermatogonial stem cell (SSC) loss and fertility problems later in life. Stem cell loss can also occur in specific genetic conditions, eg, Klinefelter syndrome (KS). Before puberty, these boys do not yet produce sperm. Hence, they cannot benefit from sperm banking. An emerging alternative is the freezing of testicular tissue aiming to preserve the SSCs for eventual autologous transplantation or in vitro maturation at adult age. Many fertility preservation programmes include cryopreservation of immature testicular tissue, although the restoration procedures are still under development. Until the end of 2018, the Universitair Ziekenhuis Brussel has frozen testicular tissues of 112 patients between 8 months and 18 years of age. Testicular tissue was removed in view of gonadotoxic cancer treatment (35%), gonadotoxic conditioning therapy for bone marrow transplantation (35%) or in boys diagnosed with KS (30%). So far, none of these boys had their testicular tissue transplanted back. This article summarizes our experience with cryopreservation of immature testicular tissue over the past 16 years (2002-2018) and describes the key issues for setting up a cryopreservation programme for immature testicular tissue as a means to safeguard the future fertility of boys at high risk of SSC loss.

Current State of Fertility Preservation in Cancer Patients—What is Established and What is Still Controversial?

2016 ◽  
Vol 12 (01) ◽  
pp. 33
Author(s):  
Kutluk Oktay ◽  
Giuliano Bedoschi ◽  
◽  
◽  
◽  
...  
Keyword(s):  
Cancer Patients ◽  
Fertility Preservation ◽  
Cancer Care ◽  
Testicular Tissue ◽  
Semen Cryopreservation ◽  
Young Females ◽  
Current State ◽  
Preservation Method ◽  
Prepubertal Boys ◽  
Straightforward Approach

Fertility Preservation is an essential part of cancer care when treating young females and men. While semen cryopreservation is a straightforward approach for postpubertal men and there is the option of experimental testicular tissue freezing for prepubertal boys, the options for females are more tumultuous. The last 17 years brought us established approaches such the embryo and oocyte cryopreservation and the ovarian cryopreservation is ready to join the list. However, there still is no proven medical fertility preservation method and the controversy around the utility of GnRHa continues.

scholarly journals Effects of different cryoprotectants on the cryopreservation of cattle testicular tissue

2015 ◽  
Vol 58 (2) ◽  
pp. 433-439 ◽  
Author(s):  
S. Hu ◽  
Q.-C. Zhu ◽  
C. Han ◽  
X.-G. Zhang ◽  
B. Y. Song ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Cell Viability ◽  
Dimethyl Sulfoxide ◽  
Fertility Preservation ◽  
Testicular Tissue ◽  
Optimal Concentration ◽  
Effective Protection ◽  
Testosterone Production ◽  
Significant Difference ◽  
Tissue Cryopreservation

Abstract. Cryopreservation of testicular tissue is a new option in fertility preservation for prepubertal male animals. The purpose of this study was to explore the effects of different cryoprotectant agents (CPAs) at various concentrations on testes after the cryopreservation of calf testicular tissue. These experiments selected dimethyl sulfoxide (DMSO), glycerol, propylene glycol (PrOH), and sucrose as CPAs in varying doses (2.5, 5, 7.5, 10, 12.5, 15, 17.5, and 20 %; v/v) in 8-month-old calf testicular tissue that was frozen and preserved. Then, cell viability, testosterone production, malondialdehyde (MDA) level, and superoxide dismutase (SOD) level were detected and analyzed following cryopreservation. The results showed that the optimal concentrations of DMSO, PrOH, glycerol, and sucrose were 10, 10, 7.5, and 10 %, respectively. Compared to the optimal concentrations of CPAs, cell viability and testosterone production decreased significantly at a lower and higher CPA concentration (P < 0.05). At the optimal concentrations of CPAs, the DMSO group showed higher cell viability and testosterone production than other CPA groups (P < 0.05). Compared to the optimal concentration of CPAs, the MDA level increased and the SOD level decreased at a lower or higher concentration of CPAs, but there was no significant difference (P > 0.05). Cell viability was significantly positively correlated with testosterone production (P < 0.05). In conclusion, DMSO provided the most effective protection for calf testicular tissue cryopreservation and the optimal concentration was 10 %.

Infrastructure of Fertility Preservation Services for Pediatric Cancer Patients: A Report From the Children's Oncology Group

2021 ◽  
Author(s):  
Natasha N. Frederick ◽  
James L. Klosky ◽  
Lillian R. Meacham ◽  
Gwendolyn P. Quinn ◽  
Joanne Frankel Kelvin ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Testicular Tissue ◽  
Ovarian Tissue Cryopreservation ◽  
Embryo Cryopreservation ◽  
Oncology Group ◽  
Modifiable Factors ◽  
Pediatric Cancer Patients ◽  
Tissue Cryopreservation

PURPOSE Fertility preservation (FP) services are part of comprehensive care for those newly diagnosed with cancer. The capacity to offer these services to children and adolescents with cancer is unknown. METHODS A cross-sectional survey was sent to 220 Children's Oncology Group member institutions regarding institutional characteristics, structure and organization of FP services, and barriers to FP. Standard descriptive statistics were computed for all variables. The association between site-specific factors and selected outcomes was examined using multivariable logistic regression. RESULTS One hundred forty-four programs (65.5%) returned surveys. Fifty-three (36.8%) reported a designated FP individual or team. Sperm banking was offered at 135 (97.8%) institutions, and testicular tissue cryopreservation at 37 (27.0%). Oocyte and embryo cryopreservation were offered at 91 (67.9%) and 62 (46.6%) institutions, respectively; ovarian tissue cryopreservation was offered at 64 (47.8%) institutions. The presence of dedicated FP personnel was independently associated with the ability to offer oocyte or embryo cryopreservation (odds ratio [OR], 4.7; 95% CI, 1.7 to 13.5), ovarian tissue cryopreservation (OR, 2.7; 95% CI, 1.2 to 6.0), and testicular tissue cryopreservation (OR, 3.3; 95% CI, 1.4 to 97.8). Only 26 (18.1%) participating institutions offered all current nonexperimental FP interventions. Barriers included cost (70.9%), inadequate knowledge or training (60.7%), difficulty characterizing fertility risk (50.4%), inadequate staffing (45.5%), and logistics with reproductive specialties (38%-39%). CONCLUSION This study provides the most comprehensive view of the current landscape of FP infrastructure for children and adolescents with cancer and demonstrates that existing infrastructure is inadequate to offer comprehensive services to patients. We discuss modifiable factors to improve patient access to FP.

scholarly journals Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Melissa D. Tharmalingam ◽  
Gabriele Matilionyte ◽  
William H. B. Wallace ◽  
Jan-Bernd Stukenborg ◽  
Kirsi Jahnukainen ◽  
...  
Keyword(s):  
Germ Cell ◽  
Childhood Cancer ◽  
Cell Loss ◽  
Testicular Tissue ◽  
Cell Number ◽  
Human Testis ◽  
Cell Populations ◽  
Similar Degree ◽  
Future Fertility ◽  
The Impact

Abstract Background Clinical studies indicate chemotherapy agents used in childhood cancer treatment regimens may impact future fertility. However, effects of individual agents on prepubertal human testis, necessary to identify later risk, have not been determined. The study aimed to investigate the impact of cisplatin, commonly used in childhood cancer, on immature (foetal and prepubertal) human testicular tissues. Comparison was made with carboplatin, which is used as an alternative to cisplatin in order to reduce toxicity in healthy tissues. Methods We developed an organotypic culture system combined with xenografting to determine the effect of clinically-relevant exposure to platinum-based chemotherapeutics on human testis. Human foetal and prepubertal testicular tissues were cultured and exposed to cisplatin, carboplatin or vehicle for 24 h, followed by 24–240 h in culture or long-term xenografting. Survival, proliferation and apoptosis of prepubertal germ stem cell populations (gonocytes and spermatogonia), critical for sperm production in adulthood, were quantified. Results Cisplatin exposure resulted in a significant reduction in the total number of germ cells (− 44%, p < 0.0001) in human foetal testis, which involved an initial loss of gonocytes followed by a significant reduction in spermatogonia. This coincided with a reduction (− 70%, p < 0.05) in germ cell proliferation. Cisplatin exposure resulted in similar effects on total germ cell number (including spermatogonial stem cells) in prepubertal human testicular tissues, demonstrating direct relevance to childhood cancer patients. Xenografting of cisplatin-exposed human foetal testicular tissue demonstrated that germ cell loss (− 42%, p < 0.01) persisted at 12 weeks. Comparison between exposures to human-relevant concentrations of cisplatin and carboplatin revealed a very similar degree of germ cell loss at 240 h post-exposure. Conclusions This is the first demonstration of direct effects of chemotherapy exposure on germ cell populations in human foetal and prepubertal testis, demonstrating platinum-induced loss of all germ cell populations, and similar effects of cisplatin or carboplatin. Furthermore, these experimental approaches can be used to determine the effects of established and novel cancer therapies on the developing testis that will inform fertility counselling and development of strategies to preserve fertility in children with cancer.

Fertility preservation for prepubertal boys: lessons learned from the past and update on remaining challenges towards clinical translation

2020 ◽  
Author(s):  
Christine Wyns ◽  
Marc Kanbar ◽  
Maria Grazia Giudice ◽  
Jonathan Poels
Keyword(s):  
Stem Cells ◽  
Fertility Preservation ◽  
Clinical Application ◽  
Germ Cells ◽  
Testicular Tissue ◽  
Reproductive Age ◽  
Reproductive Capacity ◽  
Patient Counselling ◽  
Final Maturation ◽  
Prepubertal Boys

Abstract BACKGROUND Childhood cancer incidence and survivorship are both on the rise. However, many lifesaving treatments threaten the prepubertal testis. Cryopreservation of immature testicular tissue (ITT), containing spermatogonial stem cells (SSCs), as a fertility preservation (FP) option for this population is increasingly proposed worldwide. Recent achievements notably the birth of non-human primate (NHP) progeny using sperm developed in frozen-thawed ITT autografts has given proof of principle of the reproductive potential of banked ITT. Outlining the current state of the art on FP for prepubertal boys is crucial as some of the boys who have cryopreserved ITT since the early 2000s are now in their reproductive age and are already seeking answers with regards to their fertility. OBJECTIVE AND RATIONALE In the light of past decade achievements and observations, this review aims to provide insight into relevant questions for clinicians involved in FP programmes. Have the indications for FP for prepubertal boys changed over time? What is key for patient counselling and ITT sampling based on the latest achievements in animals and research performed with human ITT? How far are we from clinical application of methods to restore reproductive capacity with cryostored ITT? SEARCH METHODS An extensive search for articles published in English or French since January 2010 to June 2020 using keywords relevant to the topic of FP for prepubertal boys was made in the MEDLINE database through PubMed. Original articles on fertility preservation with emphasis on those involving prepubertal testicular tissue, as well as comprehensive and systematic reviews were included. Papers with redundancy of information or with an absence of a relevant link for future clinical application were excluded. Papers on alternative sources of stem cells besides SSCs were excluded. OUTCOMES Preliminary follow-up data indicate that around 27% of boys who have undergone testicular sampling as an FP measure have proved azoospermic and must therefore solely rely on their cryostored ITT to ensure biologic parenthood. Auto-transplantation of ITT appears to be the first technique that could enter pilot clinical trials but should be restricted to tissue free of malignant cells. While in vitro spermatogenesis circumvents the risk linked to cancer cell contamination and has led to offspring in mice, complete spermatogenesis has not been achieved with human ITT. However, generation of haploid germ cells paves the way to further studies aimed at completing the final maturation of germ cells and increasing the efficiency of the processes. WIDER IMPLICATIONS Despite all the research done to date, FP for prepubertal boys remains a relatively young field and is often challenging to healthcare providers, patients and parents. As cryopreservation of ITT is now likely to expand further, it is important not only to acknowledge some of the research questions raised on the topic, e.g. the epigenetic and genetic integrity of gametes derived from strategies to restore fertility with banked ITT but also to provide healthcare professionals worldwide with updated knowledge to launch proper multicollaborative care pathways in the field and address clinical issues that will come-up when aiming for the child’s best interest.

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