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Children undergoing chemotherapy to treat childhood cancers are at risk of infertility in adulthood due to drug cytotoxicity ( Allen et al. 2018 ). The development of fertility preservation strategies is therefore vital, particularly for
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Paediatric Integrated Cancer Service, VIC, Australia
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prioritised. Female fertility is governed by the quantity and quality of oocytes, which are stored in the ovary within primordial follicles. Cytotoxic chemotherapy, in addition to radiotherapy and surgery, has long been the mainstay of many cancer treatment
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Chemotherapy exposure may reduce fertility in males. Adult men may cryopreserve sperm prior to commencing cancer therapy; however, for pre-pubertal males who do not produce sperm, fertility preservation remains experimental. At present, no human
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The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
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lack of knowledge of their impact on reproductive function. For many years, the mainstays of cancer treatment have been surgery, radiotherapy, and chemotherapy, with cytotoxic chemotherapy being the main systemic approach to cancer drug therapy
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The aim of this study was to identify pitfalls in ovarian tissue cryopreservation protocol from referral to surgical procedure and to analyze factors associated with chemotherapy exposure of the cryopreserved tissue and decreased ovarian function in a cohort of young girls at high risk of infertility.
The study population comprised 200 girls eligible for ovarian tissue cryopreservation between 2002 and 2020 at the Children's Hospital of the University Central Hospital of Helsinki (Finland). Analyses included evaluation of the proportion of patients who underwent ovarian tissue cryopreservation, factors associated with patient selection and timing of ovarian tissue cryopreservation, and ovarian function during long-term follow-up in relation to oncological treatments. Lack of counselling was identified as the major reason for not receiving ovarian tissue cryopreservation. A longer interval from scheduling gonadotoxic therapy to cryopreservation correlated with a higher exposure to alkylating agents of the ovarian tissue. The long-term ovarian function was mainly influenced by age at the time of gonadotoxic treatment. Current selection criteria for ovarian tissue cryopreservation should be implemented in order to stratify patients at risk of infertility and timely identify those at higher risk, especially in relation to age and pubertal stage. Efforts to increase healthcare providers’ awareness and facilitate guided timing in relation to the treatment protocols are needed to guarantee early access to ovarian tissue cryopreservation for all patients at high risk of infertility.
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Monash IVF Group, Sydney, NSW, Australia
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Graphical abstract
Abstract
Sperm cryopreservation is a valuable tool for the long-term preservation of male fertility. Thus, determining the optimal technique for isolating spermatozoa post-thaw is vital to ensure recovery of the highest quality spermatozoa with minimal iatrogenic damage. This not only enhances the chances of successful conception but also reduces the risk of genetic damage in the embryo. To address this issue, human semen samples were cryopreserved using a slow freezing protocol and Quinn's Advantage™ Sperm Freeze medium. The samples were subsequently thawed and subjected to three types of sperm isolation procedures: direct swim-up, density gradient centrifugation, and electrophoretic separation using the Felix™ device. Cryopreservation led to the anticipated loss of sperm motility and vitality in association with increases in lipid peroxidation and DNA damage. Following sperm selection, all three isolation techniques resulted in an increase in sperm motility which was particularly evident with the swim-up and Felix™ procedures. The latter also significantly improved sperm vitality. There were no differences between sperm separation techniques with respect to morphology, and mitochondrial reactive oxygen species generation remained essentially unchanged when cell vitality was taken into account. By contrast, major differences were observed in DNA integrity and lipid aldehyde formation, where Felix™ isolated cells exhibiting significantly less DNA damage than the other isolation procedures as well as lower levels of 4-hydroxynonenal formation. Electrophoretic sperm isolation, therefore, offers significant advantages over alternative separation strategies, in terms of the quality of the gametes isolated and the time taken to achieve the isolation.
Lay Summary
Long-term storage of sperm is vital to assisted reproductive technology because it permits the preservation of fertility that might be compromised as a result of factors such as chemotherapy or vasectomy. This goal can be achieved via cryopreservation – the freezing of cells to −196°C. When the sperm are subsequently required for conception, they must be carefully separated from the cryopreservation medium in a manner that maximizes the chances of successful conception and minimizes the risk of genetic defects in the offspring. In this paper, three isolation techniques were compared for their ability to separate ideal sperm from semen and media following cryopreservation. It was found that cryopreservation led to lower levels of motility and vitality and created higher levels of DNA and cell membrane damage. Of the three techniques compared, only cells separated on the basis of their size and electric charge (electrophoretic isolation) exhibited significantly lower levels of DNA fragmentation.
Department of Paediatric Endocrinology, Royal Hospital for Children and Young People, Edinburgh, UK
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offered to all men due to receive any treatment with a risk of impaired fertility (e.g. chemotherapy or radiotherapy). But what about when spermatogenesis is impaired? In this series, Dr Sarah Martins Da Silva will discuss the options and practicalities in
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Department of Paediatric Oncology and Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
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criteria included ovarian cancer and prior chemotherapy or radiation treatment. As part of the consent process, permission to use tissue in research had been obtained. Cortical strips were cryopreserved using slow freezing by the Oxford Cell and Tissue
Oogonial stem cells: the unexpected superheroes
The time has come for stem cell technologies to be used in fertility studies
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technology is successful, it has the potential to be used to preserve fertility for women before they undergo chemotherapy or radiation treatments or to restore fertility in women who already underwent treatment, are menopausal or have POF. We also aim to
Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, Utah, USA
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Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, Utah, USA
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Department of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, Utah, USA
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). Additionally, stimulation of AKT phosphorylation and inhibition of PTEN in cortical fragments of ovaries from human patients receiving chemotherapy were able to activate primordial follicles and produced two live human births ( Kawamura et al. 2013 , Suzuki
