Fertility Of Boys Research Articles

Impacts of platinum-based chemotherapy on subsequent testicular function and fertility in boys with cancer.

BACKGROUNDChildren with cancer often face infertility as a long-term complication of their treatment. For boys, compromised testicular function is common after chemotherapy and currently there are no well-established options to prevent this damage. Platinum-based agents are used to treat a wide variety of childhood cancers. However, platinum agents are not currently included in the cyclophosphamide equivalent dose (CED), which is used clinically to assess the risks to fertility posed by combination chemotherapy in children with cancer.OBJECTIVE AND RATIONALEThis was a systematic search of the literature designed to determine the evidence for effects of platinum-based cancer treatment on the prepubertal human testis in relation to subsequent testicular function and fertility.SEARCH METHODSPubMed and EMBASE were searched for articles published in English between 01 January 1966 and 05 April 2020 using search terms including ‘cancer treatment’, ‘chemotherapy’, ‘human’, ‘prepubertal’, ‘testis’, ‘germ cells’, ‘testosterone’ and related terms. s were screened and full-text articles were obtained for those that met the three major inclusion criteria (age ≤12 years at treatment, exposure to platinum-based chemotherapeutic and measure of reproductive function). Screening of bibliographies for full-text articles was used to identify additional studies.OUTCOMESOur initial search identified 1449 articles of which 20 (1.3%) studies (n = 13 759 males) met all inclusion criteria. A control group (healthy individuals or siblings) was included for 5/20 (25%) studies. A total of 10/20 (50%) studies provided sub-analysis of the relative gonadotoxicity of platinum-based agents.The primary outcome measures were: pregnancies and fatherhood; semen analysis; and hormonal function. For pregnancies and fatherhood, three studies (n = 10 453 males) reported negative associations with platinum-agents, including the largest (n = 5640) controlled study (hazard ratio = 0.56, P = 0.0023), whilst two other studies (n = 1781) with platinum sub-analysis reported no association. For semen analysis (based on World Health Organization criteria), platinum-based chemotherapy was associated with azoospermia in one study (n = 129), whilst another (n = 44) found no association and the remainder did not perform platinum-based sub-analysis. For hormone analysis, conflicting results were obtained regarding potential associations between platinum-based agents and elevated FSH (a proxy for impaired spermatogenesis); however, the majority of these studies were based on low numbers of patients receiving platinum-based chemotherapy.WIDER IMPLICATIONSOverall, these results indicate that platinum-based chemotherapy should be included in clinical calculators, for example CED, used to determine gonadotoxicity for childhood cancer treatment. These findings have important implications for clinicians regarding counselling patients and their carer(s) on fertility risk, guiding requirements for fertility preservation strategies (e.g. testicular tissue cryopreservation) and modification of treatments to reduce or eliminate the risk of infertility in childhood cancer survivors.

Effect of selenium on freezing-thawing damage of mice spermatogonial stem cell: a model to preserve fertility in childhood cancers.

During treatment of childhood cancers, fertility of boys may be affected. Therefore, freezing spermatogonial stem cell (SSC) is recommended. However, freezing-thawing process may cause damage to SSCs. This study was conducted to evaluate protective effects of selenium on freezing-thawing damage of mice SSCs using investigation of cell viability and investigation of apoptosis related genes expression including Fas, Caspase3, Bcl2, Bax and P53. SSCs were extracted from 80 6-day-old mice. The SSCs were divided into four groups: cryopreservation along with selenium (low and high dose), vitrification along with selenium (low and high dose), cryopreservation control, and vitrification control. Trypan blue staining and real-time polymerase chain reaction (real-time PCR) were used to investigate cell viability and gene expression, respectively. Comparison of cell viability in the experimental groups did not show a significant association. Expression of Fas and Caspase3 was significantly lower in cryopreservation group with low-dose selenium. Expression of Bcl2 was significantly lower in cryopreservation group with high-dose selenium. Expression of Bax and Caspase3 was significantly lower in vitrification group with low-dose selenium, and expression of P53 was significantly upper. Expression of Bax and Fas was significantly lower in vitrification group with high-dose selenium, and expression of P53 was significantly upper (P<0.001). Selenium had dose dependent effect on apoptosis related genes profile. The only evident effect was the effect of low-dose selenium in cryopreservation on inhibition of apoptosis via extrinsic pathway.

Traitement des patients drépanocytaires par hydroxyurée : efficacité et tolérance

Hydoxyurea is the unique drug having demonstrated an efficacy in preventing recurrences of painful crises, acute chest syndromes and in reducing transfusional needs in patients severely affected with sickle cell disease. However, there is a wide variation in the clinical response to hydroxyurea in sickle cell patients, with children generally experiencing greater benefits than adults. Short- and middle-term tolerances are good. Our uncertainties about long-term tolerance are mainly that we do not know the consequences of the drug on ulterior fertility in boys treated early and for long periods. Hydroxyurea has just been licensed for sickle cell adults and children in Europe. Its prescription for the moment must be restricted to severely affected patients, enrolled in long-term follow-up protocols.

Pediatric fertility preservation: Is it time to offer testicular tissue cryopreservation?

As the effectiveness of cancer treatments has improved, children diagnosed with cancer can enjoy a longer life free of the disease. However, chemotherapeutic regimens alone or in combination with radiation therapy frequently result in azoospermia or infertility. This paper reviews currently and potentially available methods to maintain fertility in boys undergoing chemotherapy or radiation therapy. Whenever possible, chemotherapeutic agents that are less likely to cause azoospermia, should be considered. Hormonal suppression applied prior to and during chemotherapy may protect future male fertility. Cryopreservation of sperm enables men to reproduce in the future. New techniques, such as in vitro fertilization with intra-cytoplasmic sperm injection offer a more promising future for male cancer sufferers. These techniques however, are not applicable to pre-puberty cancer patients. The use of spermatogonial and embryonic stem cells open new possibilities for boys diagnosed with cancer.

Clinical Potential and Putative Risks of Fertility Preservation in Children Utilizing Gonadal Tissue or Germline Stem Cells

Rapid progress in the development of novel experimental strategies to generate fertile gametes from cryo-preserved ovarian and testicular tissue motivates oncologists to investigate ways in which gonadal tissue might be preserved. Childhood cancer patients remain the major pediatric group which can benefit from these techniques. Other potential candidates include patients with systemic diseases, which require gonadotoxic chemotherapy, patients undergoing gonadectomy, patients with Turner or Kleinefelter's syndrome, and boys with cryptorchid testes. This review aims to present an overview of the current state of knowledge in experimental germ stem cell transplantation in higher primates including humans, and the clinical risks and limitations related to such procedures in children. This area of research is discussed in the context of the potential future options that may become available for preserving fertility in boys and girls.

Progeny from sperm obtained after ectopic grafting of neonatal mouse testes.

Ectopic grafting of testicular tissue is a promising new approach that can be used to preserve testicular function. This technique has been used recently to differentiate the neonatal testes of different species, up to the level of complete spermatogenesis. This approach can be applied successfully to generate live progeny using sperm extracted from grafts originating from testes of newborn donors. The sperm are capable of supporting normal development and producing fertile male and female offspring after intracytoplasmic injection into mouse oocytes and embryo transfer into surrogate mothers. The grafted tissue was also capable of significantly normalizing reproductive hormone levels in the castrated recipients. This technique presents new avenues for experimentation. The recipient mouse can be regarded as a living incubator and a culture system of testicular tissue, allowing the experimental manipulation of several aspects of testis development and spermatogenesis. The successful generation of pups indicates that this technique can be used to study the testicular phenotype and to breed mutant or transgenic mouse strains with lethal postnatal phenotypes. The ability to generate sperm from the germ line ex vivo also paves the way for the development of new strategies for preserving fertility in boys undergoing cancer therapy.