Preserving fertility: using cyclophosphamide and other cytotoxics in young people

Ledingham, David; Plant, Michael; Mustafa, Fayez; Patil, Bhimanagouda S.

doi:10.1136/practneurol-2019-002247

Cited by 5 publications

(4 citation statements)

References 9 publications

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“…In antibody-negative AIE, rituximab is preferable over cyclophosphamide due to its more favorable safety profile. 5,128,129 In general, however, input from a specialist in autoimmune neurology is recommended prior to administering second-line immunotherapies given their prolonged immunosuppressive effect and unique toxicities (e.g., infertility with cyclophosphamide, discussed later on). For ease of administration, rituximab may be administered as two intravenous infusions of 1 g, two weeks apart, rather than four 375 mg/m 2 infusions for 4 weeks.…”

Section: Acute Second-line Treatment In Patients With Cell Surface An...mentioning

confidence: 99%

Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults

Hahn,

Budhram,

Alikhani

et al. 2024

Can. J. Neurol. Sci.

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Autoimmune encephalitis is increasingly recognized as a neurologic cause of acute mental status changes with similar prevalence to infectious encephalitis. Despite rising awareness, approaches to diagnosis remain inconsistent and evidence for optimal treatment is limited. The following Canadian guidelines represent a consensus and evidence (where available) based approach to both the diagnosis and treatment of adult patients with autoimmune encephalitis. The guidelines were developed using a modified RAND process and included input from specialists in autoimmune neurology, neuropsychiatry and infectious diseases. These guidelines are targeted at front line clinicians and were created to provide a pragmatic and practical approach to managing such patients in the acute setting.

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Section: Acute Second-line Treatment In Patients With Cell Surface An...mentioning

confidence: 99%

Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults

Hahn,

Budhram,

Alikhani

et al. 2024

Can. J. Neurol. Sci.

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“…CP is a cytotoxic drug with known potential side effects on female gonadal functions, including infertility and other reproductive complications. 53 This drug works by inhibiting normal immune function and interfering with the production of DNA in rapidly dividing cells. As a result, CP can severely affect the female reproductive system, leading to changes in hormone levels, ovarian failure, and other fertility problems.…”

Section: Cytotoxic Properties Of Cp On Female Gonadal Functionsmentioning

confidence: 99%

“…Long-term treatment with CP can also cause permanent infertility. 53 In some cases, ovarian tissue may be damaged, making it impossible for fertilization and implantation of an embryo. Additionally, exposure to CP can lead to a decrease in ovarian follicles, which can put women at increased risk for early menopause.…”

Section: Cytotoxic Properties Of Cp On Female Gonadal Functionsmentioning

confidence: 99%

Cytotoxic Properties of Cyclophosphamide: A Focus on Its Mechanistic Impacts on Male Gonadal Functions

Olowe,

Oyovwi,

Nwangwa

et al. 2024

J Explor Res Pharmacol

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Cyclophosphamide (CP) is a potent chemotherapeutic agent utilized in the treatment of various types of cancer. However, in addition to its efficacy in combating cancer, CP also has severe side effects, including damage to male gonadal functions. This paper aims to explore the cytotoxic properties of CP and its mechanistic impacts on male gonadal functions. The search strategy was conducted using several reviewed articles indexed in PubMed, Science Direct, EBSCO, Scopus, Cochrane Library, Sage Journals, and Google Scholar. CP is an alkylating agent that damages cancer cell DNA, inhibiting growth and division. It also affects healthy cells, leading to severe cytotoxicity. In male gonadal tissues, CP damages germ cells, Leydig cells, and Sertoli cells, causing decreased sperm count, testosterone levels, and disruption of the blood-testis barrier. The metabolism of CP in the liver generates reactive oxygen species, leading to oxidative damage and cell death. Moreover, CP also affects the hypothalamic-pituitary-gonadal axis, regulating male gonadal functions. CP disrupts the production and secretion of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone, resulting in a decrease in testosterone levels and impaired spermatogenesis. Additionally, CP exerts its cytotoxic effects by inhibiting the proliferation and differentiation of germ cells, leading to a decrease in sperm production. It also affects Leydig cells, which are responsible for the production of testosterone, thus decreasing testosterone levels. In conclusion, CP exhibits potent cytotoxic properties that not only affect cancer cells but also severely damage male gonadal functions. The mechanisms involved in CP-induced gonadal toxicity include oxidative stress and disruption of the hypothalamic-pituitary-gonadal axis. Therefore, it is crucial to consider the potential gonadal toxicity of CP when prescribing it for cancer treatment and to closely monitor the gonadal functions of male patients

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“…Notably, chemotherapy often involves alkylating agents with high testicular toxicity (Hiraga and Ozaki, 2021;Tanaka and Ozaki, 2021). Alkylating agents tend to cross-link sperm DNA double strands, impeding DNA synthesis and RNA transcription and eventually resulting in DNA breakage (Qiu et al, 1995;Ledingham et al, 2020). Damage to spermatogonia DNA within the seminiferous tubules can temporarily halt spermatogenesis, leading to azoospermia.…”

Section: Introductionmentioning

confidence: 99%

Pre- and post-chemotherapy spermatogenesis in male patients with malignant bone and soft tissue tumors

Takeshima,

Mimura,

Aoki

et al. 2023

Front. Pharmacol.

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Introduction: Malignant bone and soft tissue tumors, commonly called sarcomas, predominantly originate in bone and soft tissues and typically affect individuals at a younger age. Following the resection of the primary tumor, treatment often necessitates radiation therapy and gonadotoxic chemotherapy, the specifics of which depend on the disease’s stage Conversely, there is a notable concern regarding the potential loss of fertility due to these treatments. Consequently, it is recommended that men consider sperm cryopreservation before initiating treatment. This study aims to assess spermatogenesis in male patients diagnosed with malignant bone and soft tissue tumors before and after chemotherapy.Methods: This study involved 34 male patients diagnosed with malignant bone and soft tissue tumors and subsequently underwent sperm cryopreservation before initiating treatment. Medical records included details about the primary disease, age, marital status at presentation, semen analysis results, treatment regimen and number of courses, post-treatment semen analysis, renewal status and outcomes.Results: The mean age at the time of sperm cryopreservation was 22.8 years. The median semen volume was 2.5 mL, sperm concentration was 32.6 million/ml, and sperm motility was 38.5%. Following chemotherapy, semen analysis was conducted on 12 patients, with ifosfamide being the predominant drug used in all cases. Among these 12 patients, eight retained viable spermatozoa, and two successfully achieved spontaneous pregnancies resulting in live births. In one of the remaining four cases where no sperm were detected in ejaculate, a live birth was achieved through intracytoplasmic sperm injection using cryopreserved sperm.Discussion: While ifosfamide, the primary chemotherapy drug for patients with malignant bone and soft tissue tumors, was associated with severe impairments in spermatogenesis, recovery of spermatogenesis was observed in many cases. However, there were instances of prolonged azoospermia. Even in such cases, assisted reproduction using cryopreserved sperm remained viable for achieving parenthood. In light of these findings, offering patients the opportunity for fertility preservation is advisable.

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Preserving fertility: using cyclophosphamide and other cytotoxics in young people

Cited by 5 publications

References 9 publications

Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults

Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults

Cytotoxic Properties of Cyclophosphamide: A Focus on Its Mechanistic Impacts on Male Gonadal Functions

Pre- and post-chemotherapy spermatogenesis in male patients with malignant bone and soft tissue tumors

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