Effects of the gonadotropin-releasing hormone antagonist cetrorelix in the early postimplantation period on rat pregnancy.
OBJECTIVE
The effect of cetrorelix given in the early implantation period on rat pregnancy was investigated.


METHODS
Forty-nine virgin Sprague-Dawley rats were randomized into six groups. At the 4th or 8th days of sperm plug, groups received 15, 75, 150 μg/kg cetrorelix or saline. Three subjects were randomly selected from each group and sacrificed at 11th gestational day for histomorphometric analysis. The remaining subjects were allowed to complete their pregnancy period. Volumes of total conceptus, labyrinth zone, transitional zone, giant cell zone, and exocoelomic cavity were calculated according to Cavalieri's principle.


RESULTS
Subjects receiving cetrorelix at 15 or 150 μg doses at the 4th day (D4) and those receiving cetrorelix at 150 μg dose at the 8th day (D8) of pregnancy delivered later than the controls. On necropsy examination at the 11th day, mean embryo weights of the cetrorelix 15 D4, 150 D4, 15 D8 and 75 D8 groups were found to be significantly lower than that of the controls (p<0.05). On histomorphometric evaluation, volumes of the fetuses and the amniotic sacs were decreased by cetrorelix at all doses studied dose dependently. Gross congenital anomalies were observed in the pups of three rats of the cetrorelix 150 D4 and D8 groups.


CONCLUSIONS
The results of this study suggest that cetrorelix in the early post-implantation period may lead to serious side effects in the rat.
Yeditepe University, Faculty of Medicine, Istanbul, Turkey. niyazitug@hotmail.com
Niyazi
N
Tug
Unal
U
Uslu
Alev
A
Cumbul
Signem
S
Eyuboglu
Cetin
C
Cam
Ates
A
Karateke
Bayram
B
Yilmaz
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000650:Amnion / Q000187:drug effects / Q000473:pathology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005831:Genital Diseases, Female / Q000188:drug therapy; D005865:Gestational Age; D015726:Giant Cells / Q000187:drug effects / Q000473:pathology; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix