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C. E. ADAMS and P. ECKSTEIN

The effects of various intra-uterine devices on pregnancy in the rabbit were recently described by us (Adams & Eckstein, 1964, 1965). All of them produced increased prenatal mortality, both before and after implantation. While it was established that the devices exerted their contraceptive effect after the eggs entered the uterus, no insight into the more specific aspects of their action was obtained. That it may be complex is indicated by the finding reported below, that two minor variants of the same device, differing only in their mode of attachment to the uterine wall, may produce markedly different effects. Our observations are based on eighteen pregnancies in sixteen does, five nulliparous and eleven primiparous, all of which were included in our earlier study (Adams & Eckstein, 1965). At laparotomy,
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W. G. BREED, ANNE FRASER, P. ECKSTEIN and P. V. PEPLOW

In a recent paper, Sagiroglu & Sagiroglu (1970) reported findings which have a bearing on the mechanism of action of intrauterine devices (IUDs) in women. By preparing smears directly from Lippes loops ('coil smears') immediately after their removal from the uterus, they claim to have found `up to 50,000 macrophages on each slide', equivalent to `more than one million' per device in situ. They think that these cells have so far been overlooked by other workers and believe that they are capable of phagocytosing spermatozoa entering the uterus and, in the event of fertilization, the blastocyst.

Although the authors (Sagiroglu & Sagiroglu, 1970; Sagiroglu, 1971) show photomicrographs of the macrophages, they have so far given no detailed description of them. Similar cells, interpreted as macrophages, were also found by Joshi (1971)

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P. R. Hurst, Kathryn Jefferies, Karin J. Dawson and P. Eckstein

Summary. Embryos were collected from the oviducts and uterine horns of mice bearing a unilateral IUD and of non-IUD control mice at various times p.c., examined for the presence or absence of polymorphonuclear leukocytes (PMNLs) and cultured. Normal numbers of embryos were obtained on the IUD side at 48 h p.c., but reduced numbers were recovered at 60–66 and 72 h p.c. The numbers of embryos that hatched from those collected from control, IUD-bearing and contralateral non-IUD bearing tracts were, respectively, 81, 29 and 36% for 48-h embryos, 78, 47 and 51% for 60–66-h embryos, and 88, 47 and 54% for 72-h embryos. At 48 h and 60–66 h p.c. the arrest of development occurred at the expanded blastocyst stage, but at 72 h p.c. some compacted morulae were affected. Some embryos associated with PMNLs at collection developed normally when the PMNLs were dispersed before culture. An initial association with leukocytes is therefore not necessarily detrimental to the subsequent in-vitro development of the embryo in mice.

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P. R. Hurst, Kathryn Jefferies, P. Eckstein and A. G. Wheeler

The mouse uterus reacts to a unilateral intrauterine device (IUD) by developing partial-to-complete sterility in both the IUD- and contralateral horn (Doyle & Margolis, 1966; Marston & Kelly, 1969; Martin & Finn, 1970). Fertilization, tubal transport and development of embryos appear to be unaffected in such animals, but the numbers of embryos that can be recovered by flushing the uterus at the time at which they can be expected to have entered the horns are smaller than those recoverable from controls (Marston & Kelly, 1969; and our unpublished data). Flushing therefore does not distinguish between intrauterine death or premature expulsion of embryos from the mouse uterus. In an attempt to discover the fate of embryos in IUD-bearing mice the following histological experiment was undertaken.

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J. H. MARSTON, W. A. KELLY and P. ECKSTEIN

Summary.

In the naturally cyclic rhesus monkey, the presence of an intra-uterine device (IUD) did not obviously disturb the processes of (a) transport of the ovulated egg through the Fallopian tube; (b) transport of spermatozoa through the female genital tract; (c) fertilization, and (d) early embryonic development within the Fallopian tube.

Correlation of observations on egg recovery with those on the morphological age of the corpus luteum suggested that transport of the naturally ovulated egg through the Fallopian tube was completed within 3 to 4 days after ovulation in both the control and IUD monkeys.

Eggs could be recovered from the uteri of control monkeys, but usually not from those of IUD monkeys. It was concluded that the presence of an IUD probably induced pre-implantation destruction of embryos within the uterus of the naturally cyclic rhesus monkey.

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W. A. KELLY, J. H. MARSTON and P. ECKSTEIN

Summary.

Morphological observations made on forty-nine uteri from twenty-three control and twenty-six IUD rhesus monkeys killed between Days 15 and 20 of their natural menstrual cycle, were related to the physiological condition of the corresponding ovary.

The only differences between control and IUD specimens of similar luteal age were the presence of (a) a markedly flattened surface epithelium in areas of contact with the IUD; (b) erosion of the surface epithelium and underlying stroma, with fibrosis and extensive leucocytic infiltration, in the lateral angles of the uterine lumen; (c) polymorphonuclear leucocytes lying immediately beneath the surface epithelium, together with variable leucocytic infiltration into the epithelium and the underlying stroma. These changes were not related to the physiological state of the ovary, previous surgery of the uterus, or to the length of time the IUD was retained in the uterine lumen.

A deciduomal reaction could be induced both in ovariectomized, hormonally-stimulated and in naturally cyclic monkeys as a response to endometrial trauma. In both groups, there was no difference in the appearance and proliferation of the deciduomal reaction in control and IUD monkeys.

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J. H. MARSTON, W. A. KELLY and P. ECKSTEIN

In the rhesus monkey, Macaca mulatta, mechanical traumatization of the endometrium at the sensitive stage of the menstrual cycle, or under the appropriate hormonal conditions, induces a superficial deciduomal reaction which is similar to the epithelial plaque formed during implantation (Hisaw, 1935; Hisaw, Greep & Fevold, 1937; Wislocki & Streeter, 1938; Rossman, 1940). A deciduomal reaction can be induced in the same way when the uterus contains an IUD (Kelly, Marston & Eckstein, 1969) and this suggests that the endometrium's sensitivity and responsiveness to a traumatic stimulus is not affected by the presence of an IUD. Mechanical trauma injures all the endometrial tissues, but the naturally implanting blastocyst provides quite a different stimulus, which is likely to affect just the surface epithelium of the endometrium. We have, therefore, extended our previous study and induced a deciduomal

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J. H. MARSTON, W. A. KELLY and P. ECKSTEIN

Summary.

Attempts to compare the pattern of myometrial activity in restrained, fully conscious, control and IUD rhesus monkeys by using a chronically implanted, strain-gauge transducer attached to the external surface of the uterus, were not successful.

'Egg transfers' were made to the uterus on Days 15 and 18 of the menstrual cycle using fertilized rabbit eggs and radio-active silver-110m-coated, resin spheres as natural and artificial substitutes for monkey eggs. There was no marked difference in the rate of egg recovery from control and IUD monkeys at 48 hr after transfer.

It was concluded that premature expulsion of the eggs from the uterus was not the principal contraceptive effect of an IUD in the rhesus monkey.

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W. A. KELLY, J. H. MARSTON and P. ECKSTEIN

Summary.

Groups of twenty-one IUD and twenty-four control rhesus monkeys were regularly mated with males of proved fertility. None of the IUD females became pregnant, but a total of eighteen pregnancies occurred in fifteen of the control monkeys.

A series of observations on the ovaries of control and IUD monkeys examined at laparotomy and autopsy showed that the presence of an IUD affected neither the occurrence nor the timing of ovulation within the natural menstrual cycle.

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P. ECKSTEIN, W. A. KELLY and J. H. MARSTON

Summary.

This paper describes the techniques used in preparing and supervising rhesus monkeys during a series of experiments to investigate the effects of an intra-uterine device (IUD) upon the processes of conception.

Observations made in the course of these experiments established that the presence of an IUD had no biologically significant effect on either the periodicity or the duration of menstruation.