Impact of Imatinib on the Fertility of Male Patients with Chronic Myelogenous Leukaemia in the Chronic Phase

Chang, Xiao-hui; Zhou, Lin; Chen, Xiaoxia; Baoli, Xu; Cheng, Yubin; Sun, Shujun; Fang, Meiyun; Xiang, Yang

doi:10.1007/s11523-017-0521-6

Cited by 32 publications

(22 citation statements)

References 22 publications

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“…This non-selective enzymatic inhibition may interfere with the steps of spermato-and spermiogenesis: sporadic reports indicated that IMA affects the human reproductive system [14,15]. The most comprehensive report included the semen samples of 48 IMA-treated CML males and proved that IMA is secreted to the semen, reduces sperm survival and activity, but does not significantly affect the levels of gonadotrophic hormones and sexual steroids [16].…”

Section: Introductionmentioning

confidence: 99%

Pregnancy outcomes of women whom spouse fathered children after tyrosine kinase inhibitor therapy for chronic myeloid leukemia: A systematic review

et al. 2020

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Introduction The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized the therapy of chronic myeloid leukemia (CML). Although the efficacy of TKIs is beyond dispute, conception-related safety issues are still waiting to be explored, particularly in males. This systematic review aimed to summarize all available evidence on pregnancy outcomes of female spouses of male CML patients who fathered children after TKI treatment for CML. Methods We performed a systematic search in seven electronic databases for studies that reported on male CML patients who did or did not discontinue TKI treatment before conceiving, and the pregnancy outcomes of their female spouse are available. The search centered on the TKI era (from 2001 onward) without any other language or study design restrictions. Results Out of a total of 38 potentially eligible papers, 27 non-overlapping study cohorts were analyzed. All were descriptive studies (case or case series studies). Altogether, 428 pregnancies from 374 fathers conceived without treatment discontinuation, 400 of which (93.5%) ended up in a live birth. A total of ten offspring with a malformation (2.5%) were reported: six with imatinib (of 313 live births, 1.9%), two with nilotinib (of 26 live births, 7.7%), one with dasatinib (of 43 live births, 2.3%), and none with bosutinib (of 12 live births). Data on CML status were scarcely reported. Only nine pregnancies (from nine males) and no malformation were reported in males who discontinued TKI treatment before conception. Conclusion Malformations affected, on average 2.5% of live births from fathers who did not discontinue TKI treatment before conception, which is comparable with the rate of malformations in the general population. Large-scale studies with representative samples are awaited to confirm our results.

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Section: Introductionmentioning

confidence: 99%

Pregnancy outcomes of women whom spouse fathered children after tyrosine kinase inhibitor therapy for chronic myeloid leukemia: A systematic review

et al. 2020

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“…Moreover, the inverse correlation between treatment of haematological disorders and gonadal function was depicted in several clinical trials, 49 where drugs used for treating chronic myelogenous leukaemia lead to detrimental effects on spermatogenesis without impairing sex hormone levels 50 . Similarly, hydroxyurea used for sickle cell anaemia leads to a significant semen impairment related to the duration of the treatment 51 . These results are further strengthened by the known efficacy of several oligo‐nutrients, fundamental for haematopoietic development, in the treatment of slight reduction in semen quality 52 .…”

Section: Discussionmentioning

confidence: 99%

Multilevel approach to male fertility by machine learning highlights a hidden link between haematological and spermatogenetic cells

Santi

Spaggiari

Casonati³

et al. 2020

Andrology

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Background Male infertility represents a complex clinical condition requiring an accurate multilevel assessment, in which machine learning technology, combining large data series in non‐linear and highly interactive ways, could be innovatively applied. Methods A longitudinal, observational, retrospective, big data study was carried out, applying for the first time the ML in the context of male infertility. A large database including all semen samples collected between 2010 and 2016 was generated, together with blood biochemical examinations, environmental temperature and air pollutants exposure. First, the database was analysed with principal component analysis and multivariable linear regression analyses. Second, classification analyses were performed, in which patients were a priori classified according to semen parameters. Third, machine learning algorithms were applied in a training phase (80% of the entire database) and in a tuning phase (20% of the data set). Finally, conventional statistical analyses were applied considering semen parameters and those other variables extracted during machine learning. Results The final database included 4239 patients, aggregating semen analyses, blood and environmental parameters. Classification analyses were able to recognize oligozoospermic, teratozoospermic, asthenozoospermic and patients with altered semen parameters (0.58 accuracy, 0.58 sensitivity and 0.57 specificity). Machine learning algorithms detected three haematological variables, that is lymphocytes number, erythrocyte distribution and mean globular volume, significantly related to semen parameters (0.69 accuracy, 0.78 sensitivity and 0.41 specificity). Conclusion This is the first machine learning application to male fertility, detecting potential mathematical algorithms able to describe patients' semen characteristics changes. In this setting, a possible hidden link between testicular and haematopoietic tissues was suggested, according to their similar proliferative properties.

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“…In two studies performed in patients undergoing treatment with male AQA, a reduction in the concentrate of sperm in the ejaculation was identified, as well as a reduction in the ejaculation and in the sperm survival, in addition to verifying the appearance of anomalies in its forms. 28,35 In seven clinical trials performed on female patients, there was a reduction in AFC and an increase in amenorrhea in the patients. 22,24,27,30,36,39,43 In vitro assays were also considered for the analysis of the effects of AQA on female fertility; in two studies, there was an increase in follicular density in addition to presenting a greater amount of atretic follicle.…”

Section: Antineoplastic Chemotherapy Agents Modulate Serum Hormonal Smentioning

confidence: 99%

Cytotoxic Activity of Antineoplastic Agents on Fertility: A Systematic Review

Moura

Monteiro

2020

Rev Bras Ginecol Obstet

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Objective To analyze the long-term effects of antineoplastic treatments on patient fertility. Selection of Studies The studies were selected through the New PubMed, Scielo and Lilacs databases along with references used for the creation of the present work. For the selection of studies, articles published between the periods from January 1, 2015 to April 6, 2020 in the English, Portuguese and Spanish languages were used. As inclusion criteria: cohort studies and studies conducted in vitro. As exclusion criteria: review articles, reported cases, studies that do not address thematic reproduction, studies that do not address the cancer theme, articles that used animals, articles that address the preservation of fertility and articles in duplicate in the bases. Data Collection The collected data included: age of the patient at the beginning of treatment, type of neoplasm, type of antineoplastic treatment, chemotherapy used, radiotherapy dosage, radiotherapy site, effect of antineoplastic agents on fertility and number of patients in the study. Data Synthesis Thirty studies were evaluated, antineoplastic chemotherapy agents and radiotherapy modulate serum hormone levels, reduces germ cell quantities and correlated with an increase in sterility rates. The effects mentioned occur in patients in the prepubertal and postpubertal age. Conclusion Antineoplastic treatments have cytotoxic effects on the germ cells leading to hormonal modulation, and pubertal status does not interfere with the cytotoxic action of therapies.

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Impact of Imatinib on the Fertility of Male Patients with Chronic Myelogenous Leukaemia in the Chronic Phase

Abstract: These results suggest that imatinib crosses the blood-testis barrier and reduces sperm density, sperm count, survival rates, and activity in CML-CP patients. However, imatinib did not affect the structure of reproductive organs or sex hormone levels.

Cited by 32 publications

References 22 publications

Pregnancy outcomes of women whom spouse fathered children after tyrosine kinase inhibitor therapy for chronic myeloid leukemia: A systematic review

Pregnancy outcomes of women whom spouse fathered children after tyrosine kinase inhibitor therapy for chronic myeloid leukemia: A systematic review

Multilevel approach to male fertility by machine learning highlights a hidden link between haematological and spermatogenetic cells

Cytotoxic Activity of Antineoplastic Agents on Fertility: A Systematic Review

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