피임용자궁내장치가 子宮內膜에 미치는 영향에 관한 연구

Abstract

[한글]

[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.