Abstract

<strong>Objective: </strong> To assess the effect of gonadotropin-releasing hormone analogue (GnRHa) on the preservation of ovarian function against cyclophosphamide-induced gonadal toxicity. <strong>Materials and Methods: </strong> In a controlled, experimental study, 64 female mice were divided into four groups: control (C), triptorelin acetate (T), cyclophosphamide (CY), and triptorelin plus cyclophosphamide (T+CY) groups. Mice in the group (T) were subcutaneously injected with GnRHa (triptorelin acetate) in a dose of 0.5 mg/kg daily for 21 days. In contrast, mice in the (CY) group and (T+CY) group were injected intraperitoneally with 75 mg/kg of CY on day 15. After 21 days, half of the mice in each group were sacrificed, and their ovaries were removed. The rest of the mice in each group were left without any intervention for an additional 21 days, and the same procedures were repeated to assess the ovarian follicles. <strong> </strong> <strong>Results: </strong> There was significant depletion of ovarian follicles in the CY group compared to the control group (p<0.05). There were significant decreases in the number of secondary and antral follicles at late stage as compared to early stage in the CY group (p<0.05). There was also a significant increase in the number of primordial and primary follicles in the T+CY group as compared with the CY group early post-treatment, while the increase was significant in all follicles after 42 days (p<0.05). <strong>Conclusion: </strong> Cyclophosphamide destroys primordial and primary follicles at an early stage while damage in secondary and antral follicles was prominent after 42 days. Triptorelin acetate reduces the toxic effect of CY; it has early and late protective effects and preserves ovarian function in mice.

Highlights

  • In recent years, cancer treatments have greatly improved, leading to a significant increase in the survival of patients of reproductive age

  • The use of chemotherapies has been concomitant with gonadotoxic effect and loss of ovarian function.[1]

  • We studied the possible protective effect of triptorelin acetate on CY-exposed mouse ovaries through the examination of the ovaries of mice treated with both CY and triptorelin

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Summary

Introduction

Cancer treatments have greatly improved, leading to a significant increase in the survival of patients of reproductive age. The use of chemotherapies has been concomitant with gonadotoxic effect and loss of ovarian function.[1] Young women with cancer should be aware of the potential effects of chemotherapy on gonads and counseled to preserve fertility and ovarian function.[2]. Cyclophosphamide (CY) is an alkylating cytotoxic agent that is used widely as an anti-neoplastic and immunosuppressive agent and is proved to lead to impaired fertility through the destruction of ovarian follicles and development of premature ovarian failure.[3] Non-cycling cells are less susceptible to fatal damage from cytotoxic agents, so hormonal suppression may participate in ovarian protection.[4]. Several modalities have been suggested to preserve ovarian function following chemotherapy. These include prior invitro fertilization cycles with embryo cryopreservation, ovarian tissue cryopreservation and less-costly, more convenient pre-treatment with gonadotropin-releasing hormone analogues (GnRHa).[5]

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