Mechanism of action of IUDs: an ultrastructural view.

Endometrial samples from 64 women using different types of IUDs were used to study the ultrastructural changes of the human endometrium as influenced by nonmedicated and copper devices, using SEM and TEM in an attempt to explain the physiological mechanism of their actions. The absence of cytoplasmic macro-apocrine secretory granules with copper devices and their defective separation with nonmedicated IUDs support the theory that the IUD interferes with the carbohydrate metabolism and secretory function of the endometrial cells. It also indicates that IUDs may function through the interference with the blastocyst-endometrial interaction and blastocyst survival. The change in the intrauterine environment due to the absence of normal secretion may also affect sperm capacitation and/or the acrosomal reaction, with subsequent failure of fertilization. The absence of ciliated cells at the site of copper IUD contact zone and their defective ciliation away from it in the presence of normal steroid function may indicate an effect of the copper ions on the estrogen receptors. The asynchronous development of the endometrium and blastocyst mechanism of IUD function was not supported in this study. The occurrence of intermenstrual bleeding with IUDs is governed by 2 factors: 1) the pressure exerted by the IUD causing endothelial vascular injury and release of erythrocytes into endometrial stroma; and 2) the increased stromal hydrostatic pressure which acts as a force against the basal lamina and epithelial integrity. This was proven by the loss of normal microvillous pattern of the endometrial cells even away from the copper IUD, which support the rigidity of the cellular membranes.

Ultrastructural changes in human endometrium with copper and nonmedicated IUDs in utero.

Scanning and transmission electron microscopy were used for a study of the surface and glandular ultrastructure of human endometrium in the presence of different types of IUDs at comparable phases of the menstrual cycle. The aim of the study was to compare the effect of the nonmedicated with the copper and multiload copper devices to further explain the differences in their contraceptive potencies and their mechanism of action. The endometrium was evaluated at and away from the IUD; emphasis was put on the ultrastructure of endometrial gland openings, secretory activity, cellular glycogen content, ciliated cells, microvillous pattern, and kinocilia. The changes of the surface ultrastructure of the endometrium in the presence of copper IUDs were more extensive in this study than those previously reported. There seems to be a direct relationship between the amount of copper incorporated in the device, the degree of ultrastructure changes, and the area of endometrium involved. Copper devices affect the endometrial cells away from the IUD. The altered secretory function with disturbed macroapocrine secretion, the abnormality of ciliated cells, and the defective microvillous growth seem to interfere with the physiologic and functional integrity of the endometrium, reducing the chances of contraception in the presence of copper IUDs.

IUD-induced uterine bleeding.

PIP: IUD-induced bleeding may occur in the form of 1) an increase in the menstrual blood loss at cyclical periods, 2) increased duration of bleeding at periods, and 3) intermenstrual bleeding and spotting (1-4). The type of device used, surface area, duration of usage, the variable individual response to the same type of IUD, the cultural and social background of the woman, previous menstrual pattern and amount of blood previously lost, different thresholds of discomfort in different women, and parity may exert influences on the frequency of bleeding, acceptance, and indication and motivation for the IUD removal due to bleeding. With the exception of the progestasert IUDs, all devices increase (MBL) menstrual blood loss by 50-100% over preinsertion levels. Compared to inert devices, copper IUDs are associated with less MBL. Few studies have been done to analyze the pattern of (IMB) intermenstrual bleeding in IUD users. The frequency of IMB is about 40% in the 1st cycle for women using copper devices but the amount of blood lost in these cases is minimal. The incidence of IMB with copper devices is higher than with inert IUDs. 30% of all IUD users are expected to experience a prolonged menstrual cycle. It appears that in spite of the reduction of MBL with progestasert IUDs, they are associated with a prolongation of menstrual periods, more so than the copper and the inert devices. The pathogenesis of bleeding disturbances in IUD users is multifactorial and different etiologies have been suggested for different types of bleeding disturbances. Local increase in fibrinolytic activity is the most accepted cause for the increase of menstrual blood loss. All IUDs, with the exception of the progestasert, increase fibrinolytic activity of the endometrium. Various factors come into play in the pathogenesis of IUD-induced bleeding. The distortion of the endometrial vasculature by the presence of IUD can be explained by 1) the direct effect of the device on the superficial vessels causing abrasions and erosions with possible irregular bleeding and/or 2) the pressure distortion of the IUD, probably transmitted through endometrial tissue and resulting in endothelian injuries with defect formation in the small superficial vessels of the functional zone of the endometrium. The injury of vessel will lead to interstitial hemorrhage with the release of blood in an irregular pattern to the uterine cavity. The defective hemostatic mechanism in the IUD-exposed endometrium also contributes to the bleeding.^ieng

Ultrastructure responses of human endometrium to inert and copper IUDs as viewed by scanning electron microscopy.

PIP: The surface ultrastructure of endometrium of patients wearing inert and variable types of copper IUDs was studied by using scanning electron microscopy and the breadth of vision the technique allows. The inert and copper device effects were compared during various phases of the menstrual cycle. 4 micrographs depict the results of comparisons of sites of impression of the various IUDs in hysterectomized specimens. It was hoped that ultrastructural variations may provide a clue to the different efficacies of the various devices, perhaps pointing to a mechanism of action difference among the IUDs tested. The endometrial surface was evaluated at and away from the site of IUD impression with emphasis on the ultrastructure of the endometrial gland openings, ciliated cells, kinocilia, nonciliated cells, microvilli, and secretory granules. The micrographs showed that the endometrium was more influenced by the copper IUDs than by inert devices; this was especially true away from the IUD impression site. In general, the degree of ultrastructural change in copper IUDs was related to the amount of incorporated copper. Altered secretory function and cellular metabolism seemed to interfere with the physiological integrity of the endometrium, thereby increasing the antifertility potency of the IUDs.^ieng