임신에 관한 질세포학적 연구

Abstract

[한글]

[영문]

Vaginal cytologic is very helpful during pregnancy although it has not been

widely used in obstetrics.

In this paper the etiologic factors of cytologic change, especially those seen

during the last month of pregnancy, the cytologic prediction of delivery, the

cytologic evaluation of prolonged pregnancy, of the pregnancy with unknown

duration, of postmaturity and of abortion will be discussed. The data to be

presented are based on 497 pregnant patients seen Ewha Woman's University Hospital,

Seoul, Korea(374 at the end of pregnancy, 35 having spontaneous abortion, 17

suspected of having abortion and 71 in the first half of a normal pregnancy).

Ⅰ. Cytology during last month of pregnancy

A. Method

Vaginal smears were taken every 5 days beginning to the 36th week of gestation.

(a) The vaginal smear must be made before the manual examination, using a dry

speculum and wooden tongue blades. The smear is taken from the mid portion of the

lateral wall of the vagina and is not contaminated with secretions and cells from

cervix or lower portion of the vagina.

(b) A Papanicolaou stain was done on the lateral vaginal wall cells.

(c) There must be no labor pains or rupture of membranes.

(d) Vaginitis(especially Trichomonas) must be treated with antibiotic

suppositories for 3-4 days before the study.

B. Results

Study of smears from 374 patients has shown 3 types of smears.

(a) Pre-term type: Consist of numerous intermediate cell type clusters.

(b) Term type: The diminution or disappearance of the cell clusters is the main

characteristic of this type. No parabasal cells were seen. The term type begins to

appear in last 15 days and especially during the 8th to 5th day before delivery.

(c) Postmaturity or Postpartum type(Pregnancy regressive type): is composed of an

increased karyopyknotic index(12%) and eosinophilic index(23%) and numerous

parabasal cells. The cell clusters have almost disappeared.

1. Cytologic prediction of delivery:

Of the 247 cases of pre-term type, 34 or 13.77% had spontaneous delivery within

the next 5 days.

Of the 127 cases of the term, 109 or 85.83% deliveried spontaneously within the

next 5 days.

2. Are the modifications mechanical or hormonal?

In the study of 336 cases, the modification of the term type were not the

consequence of any mechanical alteration of cervical effacement, dilation or

engagement, and were not altered by parity, the presenting part, or the presence of

twins.

3. Prolonged pregnancy:

In 84 patients who were more than 1 to 7 weeks beyond their expected day of

delivery, 41 patients showing the pre-term type, and all deliveried within 15 days

alteration to the term type of smear.

One primigravida, who was 55 days after expected date of confinement, revealed no

evidence of postmaturity, 26 patients in excess of 3 or more weeks beyond their

expectd date were able to avoid the risks of artificial induction and showed no

sign of postmaturity.

All 43 patients of term type had normal spontaneous deliveries except 2 with

contracted pelves and one ruptured utrus treated surgically. Pitocin inductions on

the term type were all patients very sucessful.

4. Unknown duration of pregnancy:

In this group, 15 patients of pre-term type, did not deliver for at least 4 days.

Almost all 7 cases of the term type deliveried spontaneously within 5 days.

Delivery time was highly predicable(87-100%) by the use of the cytologic test.

5. Postmaturity:

Of 22 patients who having pregnancy of unknown duration, one showed postmaturity

with evidence of a typical placental insufficiency. The remaining functional area

was only 5cm in diameter, baby weighed 3.1kg, was 50cm in length, deeply stained

with meconeum, and unfortunately died during the induction of delivery.

Ⅱ. Cytology during first half of pregnancy

A. Method:

With the foregoing technic a vginal smear was made monthly in each of the normal

pregnancy group, and every other day in the abortion group.

B. Results:

1. Normal pregnancy group:

71 cases at 6 to 23 weeks gestation showed karyopyknotic index under 13% and the

eosinophilic index was less than 7%. The most significant indices are believed to

be cell clusters ranging from 28 to 31 in 10 fields of low power and cell

clusters/karyopknotic or eosinophilic insex ratio which is larger than 1 in 94 % of

normal early pregnant women.

2. Spontaneous abortion:

All of this group with or without hormone treatment, during 3-19 weeks of

gestation spontaneously aborted. In the study of 34 pre-abortive cases, there was

noted an increas in the karyopyknotic index up to 38%, the eosinophilic index up to

25%, and a decrease in the cell clusters to only 3-4 per 10 low power fields.

3 of the 4 cases of missed abortion showed a significant rise in karyopyknotic

index up to 52%(occasionally 90%), and rise in the eosinophilic index up to

40%(occasionally 91%) and decrease in the cell clusters down to 10. One case was

almost normal except cell clusters had decreased to 10-14.

Of special interest is the fact among 35 abortion cases, although abnormal smears

were found in only 71%(25 cases) on the basis of an increasing karyopyknotic index

or eosinophilic index. However when the quantitative diminution of cell clusters

down to 3-4 per 10 low power fields was added the incidence of abnormal smear was

97% accurate(only one exception). When the finding of inverted cell

clusters/karyopyknotic index or eosinophilic index ratio, C/K or E＜1 was

considered accuracy was 80-100%.

Pseudohormonal effect: The smear taken after progesterone had been given to the

abortive cases showed a decreasing karyopyknotilic index and eosinophilic index to

approximately 50% of the non-treated group, which gives an impression of temporary

improvement. However, the numbers of cell clusters were not significantly changed

or improved.

3. Suspected abortion:

In 17 cases of suspectd abortion with spotting averaging 6.5 days perfectly

normal smears were found. The prognosis even without treatment was excellent in

100%.

Ⅲ. Comment

According to Zandet(1959) the placenta starts to progesterone from the first

month of pregnancy, 25 to 50mg, per day during first half and 280mg, per day during

the last half. Brown cited by von Haam, found that estrogen produced by the

placenta increased from 1mg, per day in the 10th week of pregnancy to 50-100mg, per

day at the end of pregnancy. We know that navicular cells can not be considered as

specifically diagnostic of pregnancy. However, Papanicolaou stressed that larger

nuclei and more a compact grouping is a characteristic of pregnancy. According to

Pundel(1959,1964) the alteration of the vaginal smear at term is a dynamic change

reflecting the results of the estrogen-progesterone balance and the different

degree of vaginal sensitivity. This seems a more logical explanation althouth there

has been some other opinions(Luz 1959, Kamnitzer 1959).

As many authors; Lichtfus and Pundel(1959), Gaudefroy(1959), von Haam(1959),

Kamnitzer(1959) have emphasized, the most important factor in the hormonal

evaluation is the correct technic in preparing the smeats as well as experience in

reading them. the smear film must be uniform, preferably made in one direction.

The changed cytologic finding in postmaturity is a new sign of intrauterine fetal

distress. Luz(1959) found that estrogenic can be demonstrated in prolonged

pregnancy, even earlier before term and is usually associated with decreasing

levels of estrogenic secretion to less than 50% normal. Huruga(1936) states that in

prolonged pregnancy artificial induction caused no reduction of fetal mortality in

comparision with that of a non-inducted group. Eastman(1961) also had same opinion.

We belive that induction without scientific indications is not only unnecessary,

but also harmful. However if the term type of smear repeatedly appears in prolonged

pregnancy, it seems wise to induce labor because factors other than hormonal may be

present.

Most authors agree that the karyopyknotic index and eosinophilic index rise in

pre-abortive stage, but no attention has been paid to the quantitative changes of

cell clusters. Birth(1961) found that the defficiency type(abnormal type) was

present in 38.3% of all the aborting women, and the incidence of abortion, when the

smear indicated a normal pregnancy pattern, was 4.7%. Wood et al states that of 33

cases of abnormal smears 16 cases aborted; Of 12 patients who showed normal type

smears only one patient aborted.

In our experience the quantitative decrease of cell clusters, or invertion of the

cell cluster/Karyopyknotic or eosinophilic index ratio, gives a greater accuracy of

actual incidence of abnormal cytologic changes in all aborting patients, 97% of

patients the former type will abort, to the latter form 80-100% will abort.

Ⅳ. Conclusion

1. So called the "term type" of smear begins to appear 15 days before the time of

spontaneous delivery, and rapidly increased in the 8th to 5th day before delivery.

2. The pregnancy "pre-term" type showed an accuracy of 86% in predicting that

spontaneous delivery would not occur within the next 5 days.

3. The pregnancy "Term type" predicted that spontaneous delivery would occur

within the next 5 days with 85% accuracy.

4. The cytological change seen near term appeared not to be influenced by the

mechanical factors as cervical dilation, effacement or parity. It is suggested that

the changes are the result of hormone withdrawal.

5. Prolonged pregnancy is not always associated with postmaturity, but

postmaturity can occur at any time if placental insufficiency is present. On the

basis of cytological and clinical findings, 84 cases of pregnancy prolonged in

excess of 1-7 weeks beyond the expected date all delivered healthy babies. Under

the cytological control induction of labor was avoided without risk in 26 patients

3-7 weeks beyond their expected date of confinement.

6. Among 17 cases of pregnancy of unknown duration there was one showing typical

postmaturity cytologically. Frequent cytological examination especially on

pregnancics of unknown duration and of duration prolonged, can be very important in

preventing postmaturity as well as prematurity due to limited obstetrical

judgement. We strongly urge that for a correct evaluation of postmaturity the

proper antibiotic vaginal suppositories be routinely instituted(especially for

Trichomonas infrction) during repeated examinations in pregnancy prolonged 10 days

or more. This avoide possible errors from infection. Otherwise it may be too late

for satisfactory smear studies.

7. The following is a very interesting side light to this investigation. A

quantitative diminution or disappearance of cell clusters in spontaneous abortions

is a most sensitive diagnostic and prognostic with accuracy over 90% as comparated

with a 71% accuracy based alone on the increasing karyopyknotic and eosinophilic

index. Also inversion of the cell clusters and karyopyknotic or eosinophilic index

ratio would be another significant sign of poor prognosics with an accuracy of

80-100% in threatened abortion. In general, the karyopyknotic index increased over

38%, eosinophilic index over 25% and is even more increased in midded abortion.

8. Hormonal treatment in a threatened abortion should be given immediately when

the smear shows an abnormal picture, the aborted group had twise the non-abortive

group duration of vaginal spotting.

9. If there is no cytological improvement in repeated smears over a short period

of time, the incidence of abortion is high whether or not treatment is given.

10. Early detection and good management of abortion can be done by a routine

vaginal smear performed especially from 5th week to 3rd month of pregnancy,

considered as most commonest spotting period. We know that the excessive long term

administration of progesterone in early pregnancy may produce an genital

deformities in the female fetus as well as increasing embryonic mortality.

11. If the vaginal smear is normal, hormone treatment is not needed. 17 cases of

clinically suspected abortion who showed normal smear had a 100% good prognosis

even without treatment.

Cytologic examination during prenancy is very important if technically accurate

and by experienced personal. Also, it can be a valuable guide to the proper

hormonal control of modern pregnancy.