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Comparison of large single and small multiple doses of cyclophosphamide exposure in mice during early prepubertal age on fertility outcome.
Sci Rep
December 2024
Centre of Excellence in Clinical Embryology, Department of Reproductive Science, Kasturba Medical College, Manipal. Manipal Academy of Higher Education, Manipal, 576 104, India.
Cyclophosphamide (CY) exposure is known to affect the ovary and impair fertility. Clinically, treatment is generally given over multiple doses, but research models have generally used single doses. The relative effects of administering multiple small doses of CY in the prepubertal period are not elucidated.
View Article and Find Full Text PDFEvidence of apoptosis as an early event leading to cyclophosphamide-induced primordial follicle depletion in a prepubertal mouse model.
Front Endocrinol (Lausanne)
October 2024
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Introduction: The mechanisms leading to ovarian primordial follicle depletion following gonadotoxic chemotherapy with cyclophosphamide and other cytotoxic drugs are currently understood through two main explanatory theories: apoptosis and over-activation. Discrepancies between the findings of different studies investigating these mechanisms do not allow to reach a firm conclusion. The heterogeneity of cell types in ovaries and their different degrees of sensitivity to damage, cell-cell interactions, periodical follicle profile differences, model age-dependent differences, and differences of exposure durations of tested drugs may partially explain the discrepancies among studies.
View Article and Find Full Text PDFSemen analysis and reproductive hormones in boys with classical Hodgkin lymphoma treated according to the EuroNet-PHL-C2 protocol.
Hum Reprod
November 2024
Pediatric Oncology, Cancer Center Amsterdam, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Study Question: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters?
Summary Answer: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility.
What Is Known Already: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy.
The impact of treatment for childhood classical Hodgkin lymphoma according to the EuroNet-PHL-C2 protocol on serum anti-Müllerian Hormone.
Hum Reprod
August 2024
Pediatric Oncology, Cancer Center Amsterdam, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Study Question: What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)?
Summary Answer: Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL.
What Is Known Already: Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy.
Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro.
Hum Reprod
February 2024
Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
Study Question: What are the effects of cyclophosphamide exposure on the human ovary and can anti-Mullerian hormone (AMH) and rapamycin protect against these?
Summary Answer: Exposure to cyclophosphamide compromises the health of primordial and transitional follicles in the human ovarian cortex and upregulates PI3K signalling, indicating both direct damage and increased follicular activation; AMH attenuates both of these chemotherapy-induced effects, while rapamycin attenuates only PI3K signalling upregulation.
What Is Known Already: Studies primarily in rodents demonstrate that cyclophosphamide causes direct damage to primordial follicles or that the primordial follicle pool is depleted primarily through excessive initiation of follicle growth. This increased follicular activation is mediated via upregulated PI3K signalling and/or reduced local levels of AMH production due to lost growing follicles.
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