Gertrude van Wagenen

Interception: The use of postovulatory estrogens to prevent implantation

Abstract The administration of high dosages of estrogen in the postovulatory period appears to be effective in lowering pregnancy rates following mid-cycle exposure to the 0.3 to 0.03 per cent range. While nausea is encountered in approximately half the patients, no serious side effects have been noted except for one case of acute pulmonary edema. The incidence of ectopic pregnancy appears to be elevated. No fetal abnormalities were noted in infant macaque monkeys born when marginal maternal doses were given.

Compounds interfering with ovum implantation and development. 3. The role of estrogens.

The administration of ORF-3858 and certain estrogens postcoitally in the primate appears to prevent implantation of the ovum.Abstract The administration of ORF-3858 and certain estrogens postcoitally in the primate appears to prevent implantation of the ovum.

Compounds Interfering with Ovum Implantation and Development: II. Synthetic Estrogens and Antiestrogens

Studies were carried out on a group of synthetic estrogens and antie strogens (clomiphene U-11555A a 23 diphenylindene derivative U-1110 0A a dihydronaphthalene and ORF-3858 2-methyl-3-ethyl-4-phenyl-delta 4-c yclohexenecarboxylic acid) to determine their effects as postcoital contraceptive agents in the rabbit and macaque monkey. Most proved effective with direct action on the implantation site in the rabbit but only ORF-3858 showed no evidence of teratogenicity and was found effective postcoitally in the primate.

Effects of postovulatory estrogen on progesterone and prostaglandin F levels ih the monkey

Abstract Estrogen administration during the luteal phase of the menstrual cycle resulted in rapid decline of progesterone levels in the peripheral plasma of 13 out of 16 cycles in macaque monkeys. In most instances, values returned to normal whether or not estrogen was continued. In more than half the animals, there was also a rise in plasma prostaglandin F.

A note on development of the secondary palate in the rhesus monkey (Macaca mulatta).

STANDARDS of normal embryonic and foetal morphogenesis in the rhesus monkey are seldom available on the basis of known conception age. Nevertheless, such information is mandatory, for example, in experimental mammalian teratology. Investigations on the development of congemtal defects in common laboratory animals such as rodents are based on known conception age. Extension and confirmation of such findings by studies on primates requires similar precision in experimental design. This communication is offered in the belief that the critical nature of the specimens available justifies a report of their structure, in spite of the sparsity of numbers. Five monkey embryos of 40, 46, 65, 74 and 85 days conception age were among those which had been obtained by hysterotomy following timed mating, in the course of studies on gonadal morphogenesis (VAN WAGENEN and SIMPSON, 1965). Crown-rump lengths at these ages are of the order of 19,25, 55, 85 and 110 mm, respectively. As is customary in the Yale Obstetrics Monkey Colony, full records were available on the health of both parents, and on the uneventful course of pregnancy. The embryos were viable and showed all external evidences of normality at the time of their removal. The photographs show the stages of formation of the secondary palate in the first three of these embryos. They may be related to comparable stages in human embryos, such as those shown in the atlas of KRAUS, KITAMURA and LATHAM (1966). There are, of course, restrictions on the comparability with such human material: (I) As those authors remark, the human material is commonly obtained as a result of spontaneous abortions, with the consequent possibility of foetal disorders. Disorders are unlikely in the present material. (2) The age of human conceptuses is almost invariably estimated rather than accurately timed, as here. The stage of palate formation in the 40-day rhesus embryo is shown clearly (Fig. I). It agrees well with that illustrated by KRAUS et al. (1966, p. 365) for the 3942-day human embryo. It should be remarked that when the mouth was first opened the palatine processes were disposed in a ventro-medial direction, with the tongue between them, as shown in the 41-day-old normal human specimens (Zoc. cit., pp. 44-52). In the 46-day rhesus embryo the palatine processes have undergone their translo-cation to the horizontal position and have fused both in their midregion and rostrally (this latter not being shown in the photograph). That this is …

Abortifacient and teratogenic effects of triacetyl-6-azauridine in the monkey

Abstract Triacetyl-6-azauridine, developed as an antineoplastic agent, has been shown to be highly embryotoxic in rodents. To test the abortifacient effect in an infrahuman primate where the entire pregnancy could be followed, the drug was given to macaque monkeys as soon as pregnancy was diagnosed (day 21 to 28 after insemination). In 14 pregnancies the treatment at different dosages induced 13 delayed abortions between the thirty-sixth and one hundred and thirty-first day. No correlation could be made between dosage, weight of animal, and time of abortion. One pregnancy carried to term when fetal dystocia required a hysterotomy, and a teratogenic male infant was delivered. A new approach was necessary to avoid teratogenesis and the delayed abortions. The drug was then given after insemination at the end of 50 menstrual cycles on days 27 to 30. This was thought to make possible the evaluation of its capacity to prevent pregnancy. Three pregnancies were identified and ended early in abortions on days 23, 24, and 30. Since one out of 5 matings in this colony usually results in pregnancy it is possible that other implantations were interrupted without overt evidence.

The antifertility activity of dl-cis-bisdehydrodoisynolic acid methyl ether☆

Abstract dl-cis-Bisdehydrodoisynolic acid methyl ether proved a highly effective antifertility agent when administered postcoitally in the rabbit. Like other estrogens, the compound lowered the carbonic anhydrase levels in the pregnant rabbit uterus. The lowered values appeared tobe dose related. Administration of 2 mg/day orally for 6 days following midcycle mating in the macaque monkey resulted in only one pregnancy in 98 positive matings. When given in a dose of 25 mg/day for 3 days starting on the 24–33 day of the cycle there were two pregnancies out of 41 matings. These represent significantly lower pregnancy rates than encountered in untreated matings in the primate colony.

Excretion of 17-ketosteroids in the rhesus monkey.

Summary An attempt was made to study the excretion of 17-ketosteroids in Rhesus monkey urine. No 17-ketosteroids could be detected by ultraviolet adsorption, sulfuric acid and infra-red spectra following chromatography of Zimmermann-material. This suggests that values quoted in the literature, based on Zimmermann reaction alone have led to erroneous conclusions.