Assessment of fertility protection and ovarian reserve with GnRH antagonist in rats undergoing chemotherapy with cycloph
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METHODOLOGY
Assessment of fertility protection and ovarian reserve with GnRH antagonist in rats undergoing chemotherapy with cyclophosphamide Methodology
Claudia NCD Lemos*, Fernando M Reis, Guilherme N Pena, Laila C Silveira and Aroldo F Camargos
Abstract Background: Reproductive function following chemotherapy is of increasing importance given that survival rates are improving. We assessed whether a gonadotropin-releasing hormone antagonist (GnRHant; cetrorelix) could promote ovarian protection against damage due to chemotherapy. Methods: Forty-two female Wistar rats were used in this study. Animals were divided into four groups: group I (n = 9) received placebo twice; group II (n = 12) received placebo + cyclophosphamide (CPA); group III (n = 12) received GnRHant + CPA; and group IV (n = 9) received GnRHant + placebo. After medication, the estrous cycle was studied through vaginal smears. Rats were mated, pregnancy was documented and the number of live pups evaluated. Afterwards, rat ovaries were removed and prepared for histological studies. The ovarian cross-sectional area was measured and follicles were counted. Results: Cyclic changes in vaginal smears were observed in all but one animal after treatment, but group II had a significantly lower rate of animals with proestrus or estrus (p < 0.01). The offspring was markedly reduced by CPA treatment (group II, 3.00 +/- 1.33 pups vs. group I, 11.44 +/- 0.78 pups, p < 0.01) and this effect was partly reversed by pre-treatment with GnRHant (group III, 7.00 +/- 1.31 pups). The ovarian cross-sectional area was not significantly different between groups, neither was the number of individual follicle types. However, rats in Group IV had a higher total number of ovarian follicles than those in the control group (17.1 +/- 1.22 vs. 10.9 +/- 0.70, p < 0.05). Conclusion: The use of a GnRHant before CPA chemotherapy provided protection of fertility. Background Current advances in cancer treatment have substantially increased the survival of reproductive age women with cancer [1-4] and, as survival rates improve, the quality of life of these patients deserves more attention. The loss of reproductive function is one of the most important adverse effects of chemotherapy. Cancer treatment with DNA alkylating agents, such as cyclophosphamide (CPA), can lead to impaired fertility or ovarian failure, resulting in premature menopause [5]. CPA is widely used in the treatment of malignant neoplasms and some autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus. * Correspondence: [email protected] 1
Laboratório de Reprodução Humana Prof Aroldo Fernando Camargos, Hospital das Clínicas, Universidade Federal Minas Gerais, Minas Gerais, Brazil
New strategies have been developed to prevent the adverse effects of chemotherapy on ovarian function. Dividing cells are known to be more sensitive to the cytotoxic effects of the alkylating agents than are cells at rest. It has been suggested that inhibition of the pituitarygonadal axis would re
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