Effect of Two Non-Steroidal Antifertility Agents on Pregnancy in Mice

Abstract

Summary. The antifertility effects of two non-steroidal compounds, clomiphene and a diphenylindene derivative (U-11555A), were studied in the mouse, using two different methods. First, the effects of various concentrations of the compounds on the in-vitro development of two-cell mouse embryos into blastocysts were investigated. Second, the oral doses of the compounds which were necessary to block pregnancy in mice were determined. It was found that the inhibitory doses for mice are somewhat higher than for rats. Although it is impossible to make direct comparisons between the effective in-vivo and in-vitro doses, the inhibitory concentrations seem to be of nearly the same order in both cases.

Effect of centchroman on tubal transport and preimplantation embryonic development in rats

“…While the compound has been shown to inhibit decidualization in rats and mice (Kamboj et al, 1973;Singh & Kamboj, 1981), no evidence of the entry of centchroman or any other nonsteroidal oestrogen/ antioestrogen into the uterine milieu is so far available in the literature. Some nonsteroidal antioestrogens, such as clomiphene, tamoxifen, nafoxidine, U-11555A and CI-628, inhibit preimplan¬ tation embryonic development in vitro (Thomson, 1968;Andrade, Guimaraes & Guerra, 1972; Pugh & Sumano, 1979; Sengupta, Roy & Manchanda, 1981;Roy, Sengupta, Paria & Manchanda, 1982), but we have observed an increased rate of cleavage and blastocyst formation in animals treated post-coitally with a contraceptive dose of centchroman. It therefore seems that centchro¬ man administered orally does not enter the genital tract milieu in concentrations sufficient to affect embryonic development and that the inhibition observed with the other antioestrogens in vitro might only be due to their nonphysiological concentrations in the medium.…”

Effects of a Nonsteroidal Antifertility Agent (U-11100a) on Pregnancy in Mice

“…If, for purposes of discussion, one assumes an even distribution of the ingested com¬ pound throughout the body, a concentration of 10 pg/g would be present in all areas. This is in contrast to the tubai retention caused in mice by clomiphene and U-l 1555A (Thomson, 1968b). It was noticed in scoring the pregnancy experiments that the foetuses of mice treated with sub-effective doses of U-11100A were both fewer in number and smaller in size than those of the controls.…”

Clomiphene Citrate-Initiated Ovulation: A Clinical Update

“…[212][213][214] Inhibition of uterine implantation, diminished fetal survival, and a blastocytotoxic effect have also been described. [215][216][217][218][219][220][221][222][223][224][225][226][227][228][229][230][231] However, of 58 infants with birth defects reported to Merrell National Laboratories, 8 were born to 7 of 15 mothers who received an inadvertent course of clomiphene citrate during the first 6 weeks after conception. 197 Thus, aside from sporadic and otherwise inadvertent administration during pregnancy, the usual preconceptional administration of clomiphene citrate in humans and its clearance kinetics would seem to make gestational exposure unlikely.…”