Human Reproduction, Vol 12, 575-582, Copyright © 1997 by Oxford University Press
D Ghosh, PG Kumar and J Sengupta
It is generally believed that progesterone is essential for inducing the
changes in oviduct and uterus necessary for embryo viability and
implantation in a number of mammalian species. The aim of this study was,
in the rhesus monkey, to examine in conception cycles with and without
early luteal phase antiprogestin (mifepristone; RU 486) treatment: (i) the
growth status of preimplantation embryos and (ii) the implantation ability
of the preimplantation embryo after transfer to a synchronous-cycle
surrogate recipient. A total of 43 proven fertile rhesus monkeys were
randomly placed in the control (group 1, n = 18) and mifepristone (group 2,
n = 25) groups. All monkeys cohabited with proven fertile male monkeys on
cycle days 8-16 and were injected with vehicle alone [benzyl benzoate:olive
oil, 1:4 (v/v), s.c.] for group 1 and with mifepristone (2 mg/kg body
weight s.c.) for group 2, on day 2 after the presumed day of ovulation. A
total of 12 preimplantation embryos [premorula (n = 1), morula (n = 2),
zona- encased (n = 7) and zona-free (n = 1) blastocysts and degenerate
embryos (n = 1)] were recovered from 17 ovulatory, mated cycles in group 1
on day 6 after ovulation. In group 2, of the 23 ovulated cycles, 12
preimplantation embryos [premorula (n = 2), morula (n = 7), zona-encased
blastocyst (n = 1), and degenerate embryos (n = 2)] were retrieved. Despite
no significant difference in the recovery rate between the two groups,
early luteal phase RU 486 exposure induced delay (P < 0.01) in
preimplantation embryo growth, primarily at the morula-blastocyst
transition stage. Nine of the embryos from group 1 and seven of the embryos
from group 2 recovered on day 6 were transferred to naturally synchronized,
non-mated and untreated surrogate recipients. In group 1, five embryos
implanted (55%) and, of these, three (60%) gave rise to live infants
through natural delivery; implantation was assessed from extension of the
cycle (i.e. no menstrual bleeding) and rise in concentrations of oestradiol
and progesterone from day 10 of conception; rectal palpation was performed
on cycle day 50 to confirm clinical pregnancy. In group 2, however, there
was not a single case of establishment of pregnancy following transfer of
embryos retrieved from mifepristone-exposed monkeys. Thus, preimplantation
embryos recovered from RU 486-exposed monkeys failed to establish evolutive
implantation and pregnancy, while significant (P < 0.02) success was
observed in transfers of embryos from the control group. We postulate that
progesterone-mediated actions are involved in mediating the growth and
viability of preimplantation-stage embryos in the rhesus monkey.
ARTICLES
Early luteal phase administration of mifepristone inhibits preimplantation embryo development and viability in the rhesus monkey
Department of Physiology, All India Institute of Medical Sciences, New Delhi.
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