Studies on the effects of intra-uterine contraceptive device : with particular reference on the endometrial changes
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
A. Clinical observation
Among the 2448 subjects, the percentage of the patients experiencing
complications were as the following;
b. Pregnancy rate……………… 1.5%
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
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
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
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
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