Fifteen mature female rhesus monkeys were mated and operated upon to recover preimplantation uterine embryos. This resulted in the recovery of 25 embryos or unfertilized ava in 43 attempts. The same animals were fitted with plastic intrauterine devices (IUDs) and the recovery procedure was repeated. In this series 61 recovery attempts yielded only 10 embryos, 7 of which were sectioned and analyzed by transmission electron microscopy. This approach revealed the ultrastructural details of embryo degeneration and leukocyte association seen in embryos recovered from IUD-bearing animals. Samples of peripheral venous blood were analyzed for levels of ovarian steroids at the time of embryo recovery. The results are discussed in relation to the mechanism of action of IUDs.

IN spite of intensive research during the past 15 yr the precise mechanism whereby an intrauterine device (IUD) exerts its contraceptive action is unclear. There is wide agreement that the effect is intra- rather than extrauterine, and is probably elicited after arrival of the conceptus in the uterine cavity and before its attachment to the endometrium1. The most plausible suggestion seems to be that the device acts as a foreign body and provides a sterile inflammatory reaction in the endometrium which in some unknown way renders the uterine cavity hostile to preimplantation embryos1,2. The presence of large numbers of inflammatory cells, consisting mainly of neutrophils and, to a lesser extent, macrophages, is a constant feature of the endometrial reaction in IUD-bearing women and other mammals. In some species there is a high positive correlation, in the presence of an IUD, between the concentration of leukocytes in the uterine fluid and the suppression of implantation (for example, in the rabbit3). So far, however, there has been no direct proof of a consistent association between leukocytes and unimplanted embryos in IUD-fitted primates. This paper provides evidence for such an association in the rhesus monkey.

The immunochemical composition of uterine flushings and blood plasma taken from baboons, either with or without intrauterine contraceptive devices (IUD's), in the early secretory phase of the cycle was determined by quantitative electrophoresis. Characteristic, but dissimilar, patterns were obtained from the flushings and plasma; they were unaffected by the presence of an IUD. Nine components were demonstrable in the uterine flushings, and at least as many were found in the plasma. In the IUD-fitted animals, the level of one uterine component, considered to be transferrin (electrophoretic mobility [Mr] = 0.50), was significantly raised, while that of a blood plasma constituent (Mr = 0.17) was significantly lowered. The relation of these findings to comparable studies in women and lower mammals and their possible implications on the mode of action of IUD's are discussed.

The composition of uterine fluids collected from pro-oestrous rats with unilateral intrauterine sutures was determined by immunoelectrophoresis and gel filtration.

Neat uterine fluid from the IUD horn of pro-oestrous mice is slightly more toxic than control horn fluid to mouse morulae and 2-cell eggs in culture. The toxic action is completely eliminated when IUD-horn fluid is diluted with culture medium. The effects of various chemical compounds that may be elevated in the IUD horn were also tested in the egg culture system. Only a few of the compounds were found to be toxic. The significance of these results in relation to the contraceptive effect of the device is discussed.

A method is outlined for obtaining uterine flushings per vaginam from adult baboons without the need for laparotomy. Evidence for the validity of the flushing technique is given. The effects of intrauterine contraceptive devices (IUD's) on the cellular and protein composition (determined by disc electrophoresis in polyacrylamide) of the flushings obtained by this method are described. Polymorphonuclear leukocytes and, to a lesser extent, mononuclear cells were present more frequently and in increased numbers in animals with IUD's. The disc electrophoretograms of the flushings did not differ markedly either between individual baboons or after insertion of an IUD. A system for coding the protein band patterns found in flushings is described; a maximum of 18 bands was observed. Most, but not all, bands were present in blood plasma. One of the uterine-specific proteins may be identical with the glycoprotein previously demonstrated in tubal fluid of women and monkeys. An extra protein band tended to appear in baboon uterine flushings collected after ovulation. Blastokinin does not seem to occur in the uterine fluid of baboons.

SUMMARY Saline flushings from the uterine horns of rats with unilateral silk sutures (IUD's) were obtained at pro-oestrus, oestrus and on Day 5 of pseudopregnancy, and examined chemically. Protein and reducing sugar were invariably present and significantly increased in horns containing an IUD. The number of protein bands identified by disc electrophoresis varied between individual animals, but showed no marked differences between the experimental and control horns at either pro-oestrus or oestrus. Among enzymes, amylase activity was consistently raised on the IUD side compared with the control side; it was also significantly higher in the IUD horn during pseudopregnancy than in the control horns at pro-oestrus and oestrus. Lysozyme activity was found at pro-oestrus in IUD horns but not in the control horns; at oestrus and during pseudopregnancy little activity was measurable. Proteinase activity, using haemoglobin as substrate, was significantly increased in IUD horns at acid pH, but undetectable at pH 7·7; with casein as substrate at pH 7·7, activity was usually present but did not vary significantly between the two sides. Trypsin activity was also measurable at pH 7·7, but was unchanged in the presence of an IUD. Ribonuclease and phosphatase were usually detectable at pro-oestrus and oestrus, but their activities were not significantly altered by an IUD; on Day 5 of pseudopregnancy, however, much lower levels were found in both horns. Neither hyaluronidase nor neuraminidase could be detected in any flushings assayed. The possible biological implications of these findings are discussed.

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)

Summary. In the baboon, the presence of an IUD slightly shortens the length of the menstrual cycle and prolongs that of menstruation. Sexual skin changes showed that the part of the cycle shortened was the detumescent (= secretory) phase, the tumescent (= proliferative) phase remaining unaffected. Plasma progesterone levels during the latter half of the cycle were not affected by the IUD, but the onset of menstruation in experimental animals was associated with a higher blood concentration of progesterone than that present in controls. It is concluded that an IUD does not interfere with luteal function in the baboon.

Journal Article MECHANISMS OF ACTION OF INTRA-UTERINE CONTRACEPTIVE DEVICES IN WOMEN AND OTHER MAMMALS Get access P. ECKSTEIN, M.A. M.D. B.Chir. D.Sc. P. ECKSTEIN, M.A. M.D. B.Chir. D.Sc. Department of Anatomy The Medical School University of Birmingham Search for other works by this author on: Oxford Academic PubMed Google Scholar British Medical Bulletin, Volume 26, Issue 1, January 1970, Pages 52–59, https://doi.org/10.1093/oxfordjournals.bmb.a070743 Published: 01 January 1970

The presence of an infra-uterine device (IUD) slightly shortens the length of the menstrual cycle and prolongs that of menstruation in baboons. Sexual skin changes showed that the part of the cycle shortened was the deturgescent phase; the turgescent phase remained unaffected. Blood progesterone levels during the latter half of the cycle were unaffected by the IUD, but the onset of menstruation in experimental females occurred when significantly higher blood levels of progesterone were present compared with those in controls.It is suggested that an IUD does not alter ovarian function but may affect uterine responsiveness to progesterone in the baboon.