Human mitotic and meiotic chromosome damage following in vivo exposure to methotrexate

Melnyk, John; Duffy, David M.; Sparkes, Robert S.

doi:10.1111/j.1399-0004.1971.tb00251.x

Cited by 32 publications

(2 citation statements)

References 11 publications

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“…The second question is related to the possible genotoxic effect on sperm chromosomes induced by the mutagenic effects of MTX during the different maturation stages of spermatogenesis and leading to potentially abnormal effects on the offspring. MTX has been shown to induce micronuclei formation upon multiple doses in rats 17 and to increase chromosomal damage in bone marrow cells of treated patients 18,19 . Because of its biological mechanism of action, MTX is theoretically susceptible to induce sperm chromosomal abnormalities, potentially leading to abnormal pregnancy outcomes (i.e., fetal deaths and/or congenital abnormalities) if conception occurs during treatment or < 3 months after completion (i.e., one spermatogenic cycle).…”

Section: Discussionmentioning

confidence: 99%

Paternal Exposure to Methotrexate and Pregnancy Outcomes

Beghin

Cournot²,

Vauzelle³

et al. 2011

J Rheumatol

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Section: Discussionmentioning

confidence: 99%

Paternal Exposure to Methotrexate and Pregnancy Outcomes

Beghin

Cournot²,

Vauzelle³

et al. 2011

J Rheumatol

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“…Despite having normal semen parameters, men treated with methotrexate had increased sperm oxidative stress and DNA fragmentation compared with control subjects (54). Case reports by Martin et al and Melnyk et al, however, found that in their patients who used low-dose and high-dose methotrexate, respectively, chromosomal ploidy and structural abnormalities did not differ significantly compared with normal patients (55,56).…”

Section: Methotrexate and Spermatogenesismentioning

confidence: 91%

Acute anejaculation, hypogonadism, and fertility preservation in the setting of neurosarcoidosis: case report and literature review

Darves-Bornoz

Brannigan

et al. 2020

F&S Reports

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Objective: To examine fertility preservation techniques in the setting of neurosarcoidosis, and to review the impact of corticosteroid and methotrexate therapy on fertility. Design: Case report of a patient with infertility secondary to anejaculation associated with spinal neurosarcoidosis, treated with systemic corticosteroids and methotrexate. Setting: Academic tertiary-care hospital. Patient(s): A 39-year-old man presented with neurosarcoidosis complicated by acute anejaculation, erectile dysfunction, and hypogonadism. He underwent fertility consultation and sperm cryopreservation before initiating methotrexate therapy. His pretreatment total testosterone was low, at 157 ng/dL. Intervention(s): Unsuccessful pharmacologic therapy and penile vibratory stimulation (PVS) were followed by microdissection testicular sperm extraction (microTESE). Clomiphene was administered for optimization of spermatogenesis before microTESE. Main Outcome Measure(s): Vials of cryopreserved sperm, testis histopathology, and serum testosterone levels. Result(s): Eight vials of viable sperm were harvested by means of micro-TESE and cryopreserved. Despite intraoperative appearance of hypospermatogenesis, 90% of seminiferous tubules had active germ cell sloughing. Total testosterone increased to 278 ng/dL 2 months after initiating clomiphene. Conclusion(s):Conventional fertility preservation techniques may be effective in the setting of neurosarcoidosis-induced infertility owing to largely intact spermatogenesis. PVS, though not effective for this patient, should be considered along with electroejaculation, given high success rates in other patients with neurogenic anejaculation. Corticosteroid-mediated hypogonadism also must be considered in these patients, because it can negatively affect downstream spermatogenesis. In addition, evidence for the impact of paternal methotrexate exposure on fertility is limited and requires further investigation. As such, fertility consultation before initiating methotrexate is highly recommended. (Fertil Steril Rep Ò 2020;1:317-25. Ó2020 by American Society for Reproductive Medicine.

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Cytogenetic studies of bone marrow in breast cancer patients after adjuvant chemotherapy

Nowell̀

Glick

Bucolo

et al. 1981

Cancer

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Bone marrow chromosome studies were done on three patients who developed acute nonlymphocytic leukemia 5 to 19 months after completion of adjuvant chemotherapy for breast cancer, and on 17 breast cancer patients without hematologic disease 2 to 30 months after similar adjuvant therapy. Clones of cells with multiple cytogenetic abnormalities were demonstrated in two of the three leukemic patients. No chromosomally abnormal clones or evidence of increased chromosome damage was found in the 17 nonleukemic individuals. Although leukemias induced by chemotherapy, and particularly by alkylating agents, typically show multiple cytogenetic alterations, it appears that patients recently exposed to these agents, but without obvious hematopoietic disorders, do not have a high frequency of aberrant marrow clones. Additional approaches may be needed for early identification of patients at increased risk for chemotherapy-induced leukemia.

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Human mitotic and meiotic chromosome damage following in vivo exposure to methotrexate

Cited by 32 publications

References 11 publications

Paternal Exposure to Methotrexate and Pregnancy Outcomes

Paternal Exposure to Methotrexate and Pregnancy Outcomes

Acute anejaculation, hypogonadism, and fertility preservation in the setting of neurosarcoidosis: case report and literature review

Cytogenetic studies of bone marrow in breast cancer patients after adjuvant chemotherapy

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