scholarly journals FERTILITY PRESERVATION: Testicular transplantation for fertility preservation: clinical potential and current challenges

Reproduction ◽  
2019 ◽  
Vol 158 (5) ◽  
pp. F1-F14 ◽  
Author(s):  
Karen R Kilcoyne ◽  
Rod T Mitchell
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Testicular Tissue ◽  
Careful Consideration ◽  
Current Status ◽  
Testicular Transplantation ◽  
Future Fertility ◽  
Successful Transplantation ◽  
Normal Offspring ◽  
Clinical Potential

Transplantation of testicular tissues and cells has been proposed as a future clinical option for patients who have had testicular tissue cryopreserved prior to receiving gonadotoxic therapies. Whilst this approach remains experimental, success using animal models and successful transplantation of ovarian tissue resulting in live births in female patients provides optimism for the development of clinical applications involving transplantation of testicular tissue in males. Careful consideration must be given to patient groups that may benefit from this approach in the future. Current research is focused on optimising patient selection, methods for tissue cryopreservation and development of transplantation techniques that might restore sperm production or future fertility in males. Crucially, attention must be focused on ensuring safety of transplantation, including eliminating the potential for infection or re-introducing malignancy. Furthermore the genetic/epigenetic integrity of any gametes generated must be ensured to allow generation of normal offspring. This review will provide an overview of the current status of transplantation of testicular tissue and cells for fertility preservation in males.

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  

Inconsistencies in fertility preservation for young people with cancer in the UK

2021 ◽  
pp. archdischild-2021-321873
Author(s):  
Hannah L Newton ◽  
Helen M Picton ◽  
Amanda Jane Friend ◽  
Catherine M Hayden ◽  
Mark Brougham ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Testicular Tissue ◽  
Mature Oocyte ◽  
Paediatric Oncology ◽  
Advisory Panel ◽  
Funding Source ◽  
Tissue Storage ◽  
The Uk ◽  
Age Range

ObjectiveTo assess the utilisation of and funding structure for fertility preservation for children diagnosed with cancer in the UK.DesignSurvey of paediatric oncologists/haematologists. Questionnaires were sent electronically with reminder notifications to non-responders.SettingUK Paediatric Oncology Principal Treatment Centres (PTCs).ParticipantsPaediatric oncologists/haematologists with an interest in the effects of treatment on fertility representing the 20 PTCs across the UK.Main outcome measuresReferral practices, sources and length of funding for storage of gametes or gonadal tissue for children diagnosed with cancer in the preceding 12 months.ResultsResponses were received from 18 PTCs (90%) with responses to 98.3% of questions. All centres had referred patients for fertility preservation: ovarian tissue collection/storage 100% (n=18 centres), sperm banking 100% (n=17; one centre was excluded due to the age range of their patients), testicular tissue storage 83% (n=15), mature oocyte collection 35% (n=6; one centre was excluded due to the age range of their patients). All centres with knowledge of their funding source reported sperm cryopreservation was NHS funded. Only 60% (n=9) centres reported the same for mature oocyte storage. Of the centres aware of their funding source, half reported that ovarian and testicular tissue storage was funded by charitable sources; this increased in England compared with the rest of the UK.ConclusionsInequality exists in provision of fertility preservation for children with cancer across the UK. There is lack of formalised government funding to support international guidelines, with resultant geographical variation in care. Centralised funding of fertility preservation for children and young adults is needed alongside establishment of a national advisory panel to support all PTCs.

scholarly journals Female Fertility Preservation through Stem Cell-based Ovarian Tissue Reconstitution In Vitro and Ovarian Regeneration In Vivo

2019 ◽  
Vol 13 ◽  
pp. 117955811984800 ◽  
Author(s):  
Taichi Akahori ◽  
Dori C Woods ◽  
Jonathan L Tilly
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Mammalian Species ◽  
Reproductive Age ◽  
Embryo Cryopreservation ◽  
Novel Approach ◽  
Future Fertility ◽  
Female Fertility Preservation

Historically, approaches designed to offer women diagnosed with cancer the prospects of having a genetically matched child after completion of their cytotoxic treatments focused on the existing oocyte population as the sole resource available for clinical management of infertility. In this regard, elective oocyte and embryo cryopreservation, as well as autologous ovarian cortical tissue grafting posttreatment, have gained widespread support as options for young girls and reproductive-age women who are faced with cancer to consider. In addition, the use of ovarian protective therapies, including gonadotropin-releasing hormone agonists and sphingosine-1-phosphate analogs, has been put forth as an alternative way to preserve fertility by shielding existing oocytes in the ovaries in vivo from the side-effect damage caused by radiotherapy and many chemotherapeutic regimens. This viewpoint changed with the publication of now numerous reports that adult ovaries of many mammalian species, including humans, contain a rare population of oocyte-producing germ cells—referred to as female germline or oogonial stem cells (OSCs). This new line of study has fueled research into the prospects of generating new oocytes, rather than working with existing oocytes, as a novel approach to sustain or restore fertility in female cancer survivors. Here, we overview the history of work from laboratories around the world focused on improving our understanding of the biology of OSCs and how these cells may be used to reconstitute “artificial” ovarian tissue in vitro or to regenerate damaged ovarian tissue in vivo as future fertility-preservation options.

scholarly journals Analysing culture methods of frozen human ovarian tissue to improve follicle survival

2021 ◽  
Vol 2 (1) ◽  
pp. 59-68
Author(s):  
Briet D Bjarkadottir ◽  
Charlotte A Walker ◽  
Muhammad Fatum ◽  
Sheila Lane ◽  
Suzannah A Williams
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Follicle Growth ◽  
Polycarbonate Membrane ◽  
Culture Systems ◽  
Human Ovarian Tissue ◽  
Future Fertility ◽  
Health And Development ◽  
Low Volume

In vitro follicle growth is a potential fertility preservation method for patients for whom current methods are contraindicated. Currently, this method has only been successful using fresh ovarian tissue. Since many patients who may benefit from this treatment currently have cryopreserved ovarian tissue in storage, optimising in vitro follicle growth (IVG) for cryopreserved-thawed tissue is critical. This study sought to improve the first step of IVG by comparing different short-term culture systems for cryopreserved-thawed human ovarian tissue, in order to yield a higher number of healthy multilayer follicles. We compared two commonly used culture media (αMEM and McCoy’s 5A), and three plate conditions (300 µL, 1 mL on a polycarbonate membrane and 1 mL in a gas-permeable plate) on the health and development of follicles after 6 days of culture. A total of 5797 follicles from three post-pubertal patients (aged 21.3 ± 2.3 years) were analysed across six different culture conditions and non-cultured control. All culture systems supported follicle development and there was no difference in developmental progression between the different conditions tested. Differences in follicle morphology were evident with follicles cultured in low volume conditions having significantly greater odds of being graded as morphologically normal compared to other conditions. Furthermore, culture in a low volume of αMEM resulted in the highest proportion of morphologically normal primary and multilayer follicles (23.8% compared to 6.3-19.9% depending on condition). We, therefore, recommend culturing cryopreserved human ovarian tissue in a low volume of αMEM to support follicle health and development. Lay summary Ovaries contain a large number of follicles, each containing an immature egg and other important cells. Cancer treatments can lead to long-lasting negative side effects to the ovaries including the destruction of follicles, resulting in infertility. One strategy to preserve fertility is freezing of ovaries or ovarian tissue in girls and women undergoing cancer treatment. The long-term aim is to thaw and grow their ovarian tissue in the laboratory to obtain mature eggs, which can then be fertilised. In this study, we compared six different methods of growing previously frozen human ovarian tissue in order to best support follicle growth and health. We found that using the lowest amount of αMEM medium (a specific type of nutrient-rich growth solution) resulted in the highest proportion of healthy follicles. Improving the methods used to grow ovarian tissue, particularly frozen tissue, is important for future fertility preservation.

O-042 Assisted Reproductive Technology (ART) in Europe 2018 and development of a strategy of vigilance. preliminary results generated from european registers by ESHRE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Wyns ◽  
CH De Geyter ◽  
C Calhaz-Jorge ◽  
MS Kupka ◽  
T Motrenko ◽  
...  
Keyword(s):  
Data Collection ◽  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Testicular Tissue ◽  
European Countries ◽  
Human Reproduction ◽  
Fresh Embryo Transfer ◽  
Preimplantation Genetic Testing ◽  
Continuous Increase ◽  
Reported Data

Abstract Study question What are the reported data on cycles in ART, IUI and fertility preservation interventions in 2018 as compared to previous years, as well as the main trends over the years? Summary answer AUTHOR: The 22th ESHRE report on ART and IUI shows a progressive increase in reported treatment cycle numbers in Europe, a small decrease in the number of transfers (IVF + ICSI) with more than one embryo with a trend to decreasing multiple delivery rates, higher pregnancy and delivery rates after FER compared to fresh IVF and ICSI cycles, and outcomes for IUI cycles similar to previous years. What is known already Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been collected, analysed by the European IVF-monitoring Consortium (EIM) and reported in 21 manuscripts published in Human Reproduction and Human Reproduction Open. Study design, size, duration Yearly collection of European medically assisted reproduction (MAR) data by EIM for ESHRE. The data on treatments performed between January 1 and December 31 2018 in 34 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organisations. Participants/materials, setting, methods In all, 1004 clinics offering ART services in 34 countries reported a total of 827 545 treatment cycles, involving 132 332 with IVF, 342 589 with ICSI, 260 013 with frozen embryo replacement (FER), 44 854 with preimplantation genetic testing (PGT), 42 869 with egg donation (ED), 406 with IVM of oocytes and 4482 cycles with frozen oocyte replacement (FOR). European data on IUI using husband/partner’s semen (IUI-H) and donor semen (IUI-D) were reported from 783 institutions offering IUI in 24 and 20 countries, respectively. A total of 132 624 treatments with IUI-H and 43 140 treatments with IUI-D were included. A total of 12 609 fertility preservation (FP) interventions from 13 countries including oocyte, ovarian tissue, semen and testicular tissue banking in pre-and postpubertal patients were reported. Main results and the role of chance In total, 1004 IVF clinics participated (93.4% of registered clinics in the participating countries). Next to these also 783 IUI units reported their data. In the 34 reporting countries, after IVF the clinical pregnancy rates (PR) per aspiration and per transfer in 2018 were similar to those observed in 2017 (28.7% and 41.6% versus 29.4% and 39.0%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2017 (26.3% en 40.9% versus 27.3% and 40.2%). After FER with own embryos the PR per thawing is still on the rise, from 30.2% in 2017 to 33.0% in 2018. After ED the PR per fresh embryo transfer was 49.8% (49.2% in 2017) and per FOR 39.6% (43.3% in 2017). In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and ≥4 embryos in 51.1%, 45.4%, 3.4% and 0.1% of all treatments, respectively (corresponding to 46.0%, 49.2%, 4.5% and 0.3% in 2017). This resulted in a proportion of singleton, twin and triplet DRs of 86.9%, 12.8% and 0.3%, respectively (compared to 85.5%, 14.2% and 0.3%, respectively in 2017). Treatments with FER in 2017 resulted in twin and triplet DR of 9.3% and 0.1%, respectively (versus 11.2% and 0.2% in 2017). After IUI, the DRs remained similar at 9.1% after IUI-H (8.9% in 2017) and at 12.3% after IUI-D (12.4% in 2017). Twin and triplet DRs after IUI-H were 8.4% and 0.3%, respectively (in 2017: 8.1% and 0.3%) and 6.7% and 0.2% after IUI-D (in 2017: 6.9% and 0.2%). The majority of FP interventions included the cryopreservation of ejaculated sperm (n = 8 257 from 13 countries) and of oocytes (n = 3230 from 13 countries). Limitations, reasons for caution As the methods of data collection and levels of completeness of reported data vary among European countries, the results should be interpreted with caution. For this abstract a number of countries was not able to provide adequate data about the number of centers and initiated cycles and deliveries. Wider implications of the findings The 22nd ESHRE report on ART and IUI shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Being already the largest data collection on MAR in Europe, continuous efforts to stimulate data collection and reporting strive for future quality control and completeness of the data and offer higher transparency and vigilance in the field of reproductive medicine. Trial registration number: Study funding: Funding source:

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.

Fertility preservation in borderline ovarian tumor patients and survivors

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Marine Poulain ◽  
Jessica Vandame ◽  
Chloé Tran ◽  
Sonia Koutchinsky ◽  
Paul Pirtea ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Conservative Surgery ◽  
Reproductive Technologies ◽  
Minimal Invasive ◽  
Oocyte Cryopreservation ◽  
Ovarian Tissue Cryopreservation ◽  
Ovarian Cortex ◽  
Estrogen Exposure ◽  
Future Fertility

AbstractBorderline ovarian tumors (BOTs) represent around 15% of all epithelial ovarian cancer. Around one third of those patients is under 40 and has not completed childbearing when the tumor is diagnosed. Cancer survivors are more and more concerned about their future fertility since a large proportion of those with BOTs are young. Whatever the tumor stage, information regarding future fertility after treatment and fertility preservation (FP) options must be delivered to all patients before treatment. A multidisciplinary team will discuss and propose personalized treatment and FP strategies. Nowadays, the FP options offered to patients with BOT are the followings: i) minimal invasive conservative surgery, ii) oocyte cryopreservation after controlled ovarian stimulation (COS) or in vitro maturation (IVM) and iii) ovarian tissue cryopreservation. Generally, the most common strategy to preserve future fertility is represented by minimal invasive conservative surgery. However, with the remarkable success and evolution of assisted reproductive technologies (ART) – notably progress and efficiency in COS and oocyte vitrification – have led to offer another potential approach for FP consisting in oocyte cryopreservation. Several COS protocols, such as random start or dual stimulation associating tamoxifen or aromatase inhibitors with gonadotropins provide similar results when compared to standard protocols while providing safety by minimizing the risk of high estrogen exposure. When COS is contraindicated, oocyte cryopreservation can still be possible throw IVM. Even though, oocyte competence after IVM is lower than that obtained after COS. A less used approach is cryopreservation of ovarian tissue, consisting in freezing ovarian cortex fragments for a future thawing and graft. Some concerns and limitations regard the ovarian cortex graft and the risk of reintroducing malignant cells once performed. Nonetheless, the latter it is the only option in prepubertal patients.

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.

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