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피임용자궁내장치가 子宮內膜에 미치는 영향에 관한 연구

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[영문] The history of intra-uterine contraceptive device (IUCD) reaches back over several decades. However it was not until 1920's when German physicians began to use this device as the method for the prevention of pregnancy. Although there were variable responses on this method, the effectiveness of such device for contraception was well recognized. The main reason against its use was a fear for the complications which might arise after the application. Inflammation, perforation and even carcinomas were feared. Up until 1950's only sporadic interests on this matter appeared in the medical field. With the problems of rocketing population increase, a demand for a safe, easily applicable and effective contraceptive method became very acute. The field of intra-uterine contraceptive device investigation was encouragingly enlightened by the publications of Oppenheimer and Ishihama in 1959 who reported much favorable results on the safety and effectiveness of this method. Following this, many pertinent data have accumulated in the world medical literature concerning IUCD and in many parts of the world the polyethylene loop insertion has been accepted as the method of choice. This immediately forces us to assay its hazards very carefully. It is true that there have been sporadic reports on the bacteriologic and histologic effects of such device, however, these reports are in many was contradictory and fragmentary. Particulary there have been no reports dealing with the histochemical changes of the endometrial tissues in these situation. Furthermore, it is not yet clearly known how this device is so effective in preventing pregnancy. It is the purpose of this paper to descrive the clinical and histological effects on the endometrial tissues which might be related to insertion of IUCD and to characterize the histochemical changes so p개duced. Materials and Methods: All cases were selected among the patients registered in the Family Planning Clinic of Yonsei University. A total of 2448 cases were selected for careful clinical appraisals. Each individual was questioned, interviewed and examined as to their subjective and objective symptoms before and after insertion of IUCD. A particular attention was paid on the complications. Among these a total of 231 cases were selected and subjected to endometrial biopsy according to the month of use. The tissues were either fixed into 10% neutral formalin or alcohol for paraffin sections or frozen sections were made according to the needs for various staining procedures. The stains utilized were as follows; 1. Hematoxylin & eosin 2. Periodic acid Schiff reaction 3. Toluidine blue for metachromasia 4. Methyl-green pyronin 5. Oil red O. 6. Alkaline phosphatase Results A. Clinical observation Among the 2448 subjects, the percentage of the patients experiencing complications were as the following; a. Infection………………………0.0% b. Pregnancy rate……………… 1.5% c. Expulsion………………………4.7% d. Bleeding………………………13.4% e. Pain……………………………13.3% f. Removal……………………… 11.3% g. Menorrhagia………………… 17.4% B. Histological and Histochemical features 1. Hematoxyline & eosin stain The cases belonging to the histological proliferative phase were 143 and the secretory phase 66. The cases belonging to undetermined phase were 22. In general, the histological features were more or less similar to the normal endometrium. When abnormalities were noted, these were of minor degree. Among the abnormal changes, the cases showing hyperplasia accounted for 12 cases. These showed abnormally grouped dialted glands with slightly hyperplastic epithelial cells but no frank anaplasia was ever observed. This phenomenon was particularly more common in cases of proliferative phase. A total all cases showed a slight to moderate degree of focal inflammatory changes. These were characterized by focal infiltration of small numbers of leukocytes in the interstitial tissue, and no necrosis was observed. One interesting phenomenon was that many cases in proliferative phase showed irregular dilation of endometrial glands with tortuosity eventually producing the so-called "gland-in-gland" pattern. The interstitial tissue showed edematous changes particularly all throughout the duration of insertion but as the time lapsed the edema subsided and even showed focal fibrosis. The most interesting of all was the fact that the clinically dated phase and the microscopic phase did not match in 27 cases. These mostly belonged to the proliferative endometrium which should have been secretory according to the clinical appraisal. 2. Periodic acid Schiff reaction(PAS) In the proliferative endometrium the PAS positive material is noted, as granules, in the cytoplasm of gland cells and became more intense in the early secretory endometrium. During the secretory phase there was a large amount of PAS positive material in the gland lumen. The stromal cells showed a fairly uniform positive reaction in the proliferative phase within the cytoplasam of spindle cells. In secretory endometrium the vicinity of the gland convolutions became largely positive. 3. Metachromasia by Toluidine blue stain During the proliferative phase, the metachromasia was noted in the cytoplasm of superficial surfacer epithelium. In the secretory endometrium. In the secretory endometrium was also noted around the gland convolutions. At times, the edematous areas of the stroma gave intense metachromasia. 4. Methyl-green Pyronin The ribose nucleic acid was demonstrated evenly within the cytoplasm of surface epithelium in prolifer ative endometrium. The gland epithelial cells showed presence of RNA at the upper pole of nucleus. The stroma gave weak reaction. The late stage of proliferative phase showed strong reaction within the cytoplasm of surface epithelical cells and the gland epithelium likewise gave positive stains. The stroma showed strong staining in the cytoplasm of spindle cells in secretory endometirum but later this faded away. 5. Oil red O A small amount of fat droplets appeared in the surface epithelial cells in the proliferative endometrium. In the secretory endometrium there were fat droplets within the lumen of glands and gradually the amount increased. All stages showed negative fat stain in the stroma but during the secretory phase there appeared a very small amount of fat droplets discernible at the upper pole of stromal cell nuclei. The glandular epithelial cells contained much fat in the infra-nuclear position. 6. Alkaline phasphatase The proliferative endometrium showed positive stains in the cytoplasm of superficial surface epithelial cells. The staines becma estronger at the late proliferative phase. The secretory endometrium showed only staines in the cytoplasm at the upper pole of nuclei. The late secretory endometrium only showed positive stains in the walls of blood vessels. The stroma did not react all throughout the stages. Comment and Conclusion The observed clinical features show very clearly that this method is highly effective in preventing pregnancy. The pregnancy rate of 1.5 means indeed the superior quality. Oppenheimer's series noted 2.4% failure rate. Halton in his large series noted 1.5% failure rate. Ishihama's cases showed 1.3% pregnancies. The observed complications during this investigation can be listed as minor among which the bleeding could be listed as the most serious though in serveral these ven were indeed minor. All of the listed complications were also experienced by the investigators on their subjects which correspond fairly closely on its percentage. opinions have varied on the effects of a foreign body on the endometrium. Arnold, Ishihama, Oppenheimer and Carleton considered the ring or loop to be essentially harmless. Rozin and Eherling, Bowles and Sussex cited individual cases reported in which there was endometrial inflammation of infection. As have been pointed out in the results, there was no significant infection in our cases studied and the inflammatory changes observed in the endometrium was of minor and focal one. No necrosis was observed. The hyperplasia observed may need a comment. This was not in form of an anaplastic change but just showed grouped hyperplastic glands. This may be in keeping with the Graefenberg's idea of a "non-inflammatory hypertrophy" which he believes is the mechanism of action in preventing pregnancy. The most interesting feature of the endometrium in 27 cases was the discrepancy between the clinical phase and histologic phase. This is not clearly understood with the present investigation but perhaps this may be due to some hormonal changes which might have been caused by insertion of IUCD. The histochemical studies more or less corresponded to that of normal endometrium and there was no significant alterations in the basis staining pattern in all materials examined. With the data obtained above, it is concluded that 1) The polyethylene loop insertion in the uterine cavity is sagfe and widely applicable method of choice for the prevention of pregnancy. The pregnancy rate was only 1.5 in our series. 2) Histologically the endometrium showed essentially normal pattern except for hyperplasia (12cases), mild focal inflammation (11cases) and focal recent bleeding. These were considered to be of minor degree and not clinically significant. The most interesting feature was the discrepancy in the clinical phase and histological phase of the endometrium. 3) The histochemical features were more or less similar to the normal endometrial tissue.
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