Human Reproduction, Vol 12, 430-435, Copyright © 1997 by Oxford University Press
HM Fraser, SF Lunn, KD Morris and R Deghenghi
The determination of the efficacy of gonadotrophin-releasing hormone (GnRH)
antagonists in blocking the luteinizing hormone (LH) surge and luteal
function is important for our understanding of the control of the menstrual
cycle and for clinical application. GnRH antagonists have failed to block
the LH surge reliably in the non-human primate. The aim of the study was to
utilize high dose GnRH antagonist treatment administered during the late
follicular phase of the menstrual cycle to block the pre-ovulatory LH
surge. It was postulated that the LH surge would be prevented in all
animals, but if this failed subsequent luteal function would be blocked by
continued suppression of LH, since the early corpus luteum is susceptible
to inhibition by GnRH antagonist treatment. A group of 16 adult female
stumptailed macaques (Macaca arctoides) with regular menstrual cycles were
selected. The GnRH antagonist
[N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-(Hci)6, Lys(iPr)8,D- Ala10]GnRH
(Antarelix) (concentration 10 mg/ml) was administered as three daily s.c.
injections, at a dose of 1 mg/kg on days 11, 12 and 13 of the follicular
phase of the menstrual cycle. Of nine macaques in which it was judged that
the treatment was commenced within 1 day of the expected LH surge (serum
oestradiol >400 pmol/l), six demonstrated a decline in serum oestradiol
concentrations, a total block of the LH/follicle stimulating hormone (FSH)
surge and inhibition of ovulation as judged by an absence of a rise in
progesterone concentrations. In the three other animals in this category, a
partial LH surge occurred, but this failed to result in a functional corpus
luteum. In a further three animals treatment was initiated on the day of
the LH surge, and again there was absence of a subsequently functional
corpus luteum. These results show that GnRH is involved at the time of the
mid-cycle LH/FSH surge in the non-human primate. Initiation of high dose
GnRH antagonist treatment during the periovulatory period abolishes luteal
function irrespective of its effects upon the LH surge because of its
long-term action and resultant withdrawal of luteal support.
ARTICLES
Initiation of high dose gonadotrophin-releasing hormone antagonist treatment during the late follicular phase in the macaque abolishes luteal function irrespective of effects upon the luteinizing hormone surge
MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.
![]()
CiteULike
Connotea
Del.icio.us What's this?