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  • Title: Early luteal phase administration of mifepristone inhibits preimplantation embryo development and viability in the rhesus monkey.
    Author: Ghosh D, Kumar PG, Sengupta J.
    Journal: Hum Reprod; 1997 Mar; 12(3):575-82. PubMed ID: 9130762.
    Abstract:
    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.
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