Maternal exposure to cyclophosphamide during prepubertal life does not affect the cryosusceptibility of in vitro derived mouse embryos.

Abstract: Prepubertal exposure to gonadotoxic chemotherapy, such as cyclophosphamide (CY), poses a significant risk to long-term fertility by depleting ovarian reserve and impairing oocyte quality. Such treatments are commonly administered to young girls with cancer, and when these individuals later seek assisted reproductive technologies (ARTs), concerns arise regarding the developmental competence and cryotolerance of resulting embryos. Using a mouse model, this study evaluated the impact of prepubertal CY exposure (2 successive weekly doses of 75 mg/kg body weight at 2 weeks of age) on the cryosusceptibility of embryos derived via in vitro fertilization (IVF) at their reproductive phase. Oocytes were collected from superovulated females six weeks post-CY treatment and fertilized in vitro, and the resulting cleavage stage embryos were subjected to vitrification-warming. Embryo survival and quality were assessed by blastocyst formation, inner cell mass (ICM) proliferation in vitro, and the expression of key pluripotency markers (Oct4, Sox2, and Nanog). Results showed no significant differences between CY-exposed and control groups in terms of post-warming survival or marker expression. These findings suggest that maternal CY exposure during the prepubertal period does not adversely affect the cryo-resilience of IVF-derived embryos, offering reassurance for childhood cancer survivors seeking ART treatment. Lay summary: Chemotherapy given during childhood can harm future fertility, especially in girls who have not yet gone through puberty. One common chemotherapy drug, cyclophosphamide (CY), may reduce the number and quality of eggs in the ovaries. Cancer survivors may be more likely to need IVF (in vitro fertilization) or other fertility treatments, given the impact of the treatment on their fertility. In this study, a mouse model was used to understand whether early-life exposure to CY affects the ability of embryos (created through IVF) to survive freezing and thawing, a common part of IVF treatments. The study found that embryos from mice exposed to CY before puberty survived the freezing process just as well as those from unexposed mice. The quality and health of these embryos, measured by their development and important growth markers, were also similar. These findings provide hopeful news for young girls who receive certain types of chemotherapy, who may still have the option to use IVF in the future without increased risk of embryo damage during freezing.