Assessment of fertility protection and ovarian reserve with GnRH antagonist in rats undergoing chemotherapy with cyclophosphamide.
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).


CONCLUSIONS
The use of a GnRHant before CPA chemotherapy provided protection of fertility.
Lemos
Claudia N C D
CN
Laboratório de Reprodução Humana Prof Aroldo Fernando Camargos, Hospital das Clínicas, Universidade Federal Minas Gerais, Minas Gerais, Brazil. cclaudian@terra.com.br
Reis
Fernando M
FM
Pena
Guilherme N
GN
Silveira
Laila C
LC
Camargos
Aroldo F
AF
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002452:Cell Count; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D005298:Fertility / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D007247:Infertility, Female / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy / Q000534:rehabilitation; D010053:Ovary / Q000166:cytology / Q000187:drug effects*; D010919:Placebos; D011247:Pregnancy; D018873:Pregnancy Rate; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D006727:Hormone Antagonists; D010919:Placebos; D007987:Gonadotropin-Releasing Hormone; D003520:Cyclophosphamide; C062876:cetrorelix