Functional and biochemical aspects of laminaria use in first-trimester pregnancy termination B. L YE, M.D.* K. YAMAMOTO,
J.
~.D.
E. TYSON, M.D.
vllinnipeg, iVlanitoba, Canada The effect of laminaria·induced cervical dila~tion on plasma levels of the prostagkirldin metabolite 13, 14-dihydro-15-keto prostaglandin (PGFM) was eva~Wted in women undergoirlQ elective first-trimester pregnancy termination. Seventy-one women were randomly assignEid to either a treatment (n "' 45) or control (n "" 26) group. Cervical dilatation measured at the time of insertion of the laminaria was 3.0 ::>: 0.1 mm compared to 10.2 ± 0.2 mm at the time of removal of the laminaria 14 to 16 hours later (p < 0.001). Peripheral levels of PGFM rose from 28.3 ± 2.4 pg/ml (mean± SEM) to 43.0 ± 2.6 pg/ml at the time of removal of the laminaria (p < 0.001). Peripheral concentrations of PGFM in controls remained unchanged. Peripheral concentrations of PGFM did not correlate with the patient's symptoms. Although the hydrophilic property of laminaria is considered to be the principal mechanism promoting cervi«al dilatation, laminaria may alter the elaboration, release, or degradation of uterine prostaglandin F2 a. Thus, biochemical as well as mechanical factors may enhance cervical dilatation in laminaria-treated women. (AM. J. OasTET. GYNECOL. 142:36, 1982.)
of laminaria tents in the presurgical management of first-trimester pregnancy termination has been proved. 1-a In addition to cervical dilatation, a shortened treatment/abortion time has been accomplished commensurate with lower overall surgical risk to the patient. However, the use of laminaria was abandoned in the past because of significant postabortal morbidity presumably related to the improper sterilization of the laminaria.~ During the last lO years, improved techniques of sterilization have brought about a resurgence of interest in the use of laminaria for cervical dilatation, both for pregnancy termination°- 7 and as an adjunct to the induction oflabor in term gestation. 8 · H
'TIIE EFFICACY
Fwm the Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Manitoba. Supported in part lry grants from the Sellers Foundation and the Richardson Foundation.
RaeiVPdfor publication June 4, 198 I. Revised july 29, 1981. Aaepted August 12, 1981. Reprint requests: Dr.]. E. Tyson, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Manitoba, 59 Emily St., Winnipeg, Manitoba, Canada RJE OW3. *International Exchange Fellow, Departwmt of Obstetrics and Gynecology, Wenzhou Medical College, Wenzhou Zheji.ang, People's Republic of China.
36
The mechanism of action of laminaria is principally due to the hydrophilic properties of the seaweed itself.10 Cervical dilatation will occur over a short time frame and will be enhanced proportionate to the number of laminaria inserted into the cervix during the inducing period. The present study evaluates the impact of the use of laminaria on first-trimester pregnancy termination in healthy, predominantly nulliparous women, including changes in the circulating plasma concentration of the principal prostaglandin F:ro metabolite, 13,14-dihydro15-keto prostaglandin (PGFM). Methods
Seventy-one healthy women previously approved for termination of pregnancy volunteered to participate in the study. Approval for the study was obtained from the Committee on Human Su~jects of the Uni,·ersity of Manitoba, and each volunteer was required to sign an informed consent after having received information on the goals and objectives of the study. The women were randomly assigned to an experimental or control group by means of the last digit of their hospital number. Insertion of laminaria was carried out on the evening prior to the scheduled termination of pregnancy. All terminations were accomplished through the use of suction curettage. 0002-9378/82/010036+04$00.40/0© 1982 The C. V. Mosby(:,,,
\'o!ume 1·42 '\umber I
Prior to insertion of laminaria, each volunteer was examined and the status of cervical dilatation was dett:rmined by means of Hegar dilators. Laminaria were inserted into the cervix according to methods prel·iouslv described.' At least two sterile gauze squares were inserted into the 1·agina to promote retention of the Jaminaria. A sham procedure that included pelvic examination vvith the insertion of gauze squares was performed in controls ..All \\To men ,.vere instructed to report loss of gauze or laminaria as soon as possible. Each woman was admitted to the hospital 15 hours after insertion of laminaria, at which time the gauze squares and the laminaria were removed. Cervical dilatation was measured by means of Hegar dilators, after which the patients returned to the care of their personal phvsicians for the completion of pregnancy termination. These phvsicians rescored the patients' presttrgicai ccnicai dilatation and commented on the ease 11ith 11hich further cen·ical dilatation and suction curctta~c could be performed. Measurement of plasma prostaglandin metabolites. In order to e1·aluate the impact of laminaria on peripheral concentrations of PGFM, 10 ml of whole blood was obtained from an antecubital vein immediatelv prior to the initial pelvic examination and again prior to the second examination some 15 hours later when the laminaria were to be removed. Blood was collected in heparinized tubes that contained 50 t-tg of indomethacin. Samples were centrifuged at 0° C, and plasma was then separated and stored at -20° C until assayed for the metabolite. PCFM* was measured by a radioimmunoassay described in detail elsewhere. 11 Cross-reactivity with PGF 2" or PC ;E 2 in this assay was less than 1%. All samples 11ere run in duplicate and measured against a pht<;m;t pnnl that contained known concentrations of PC; F:\f. The intra-assay coefficient of variation was 8'7c, \\·ith an interassav coefficient of variation of 15'7c. Microbiologic studies. The impact of insertion of laminaria on 1aginal and endocervical flora was evaluated \\ ith aerobic culture of endocervical and vaginal secretions obtained prior to insertion of laminaria and at the time of removal of laminaria. Dat;1 were analyzed by means of the Student's t test. Results
Laminaria and cervical dilatation. Forty-five women undenvcnt insertion of laminaria (Table I). Of these, 2:'1 women had two Jaminaria introduced. There was no
*We are grateful to Dr. N. Dubin and Dr. R. Ghodgaonkar for the generous supply of PGFM antisera used in these studies.
Laminaria use in first-trimester pregnancy termination
37
Table I. Patient characteristics
Age (yr): -s 19 20-24 >25 Parity: Nulliparous Para 1 Para 2 and over Mean gestational age (wk ± SEM)
Controls
Laminaria (n = 45)
(n = 26)
21 (47%) 15 (33%) 9 (20%)
11 (43%) 8 (30%) 7 (27%)
21 (47%) 15 (33%) 9 (20%) 8.95 ± 0.25
13 (50%) 6 (24%) 7 (26%) 9.15 ± 0.28
Table II. Cervical status before and after laminaria Statistical significance
Lamina ria (l\' =
Control (:-J =
3.0 ± 0.1
10.2 ± 0.3
2.8 ± 0.2
3.1 ± 0.2
cf.~)
t = 2{.R9 p < 0.001 Not significant
26)
relationship between the use of two laminaria and the patients' parity. The mean gestational ages for the two groups were comparable. There was a comparable amount of initial cervical dilatation in both laminaria and control groups. On the other hand, a statistically significant increase in cervical diameter was observed in women who retained laminaria (p < 0.001) as shown in Table II. After insertion of laminaria, mild, menstrual-like lower abdominal discomfort was reported b~· H.4o/c of the women. :'-Jo laminaria were lost. Laminaria insertion and plasma PGFM. The concentrations of plasma PGFM before and after insertion of lamin
38
Ye, Yamamoto, and Tyson
.J.tllll
Table III. Plasma PGFM (pg/rnl) before and afler insertion of laminaria After 15 to 16 hours
Pnor· to in1ertion
with laminaril1 in situ
Laminaria ( \: Cumrol ( \:
Statistical significance
43.0:!: 2.7
{
·- .~) .~\· ~
p < 0.001
:H.4 ± 3.1
~ I~)
""
:12.0 ± 4.7
NS
Statistical significance
I
2.ltl I'< 0.05
Table IV. Surgeons' opinions in regard to ease of dilatation Laminaria (S = 42) Nullipara
Very easy Easv
15 4
Moderate Difficult
0 0
I
Para 1
9 4 I ()
I
Para 2
Control(;\' = 20)
I
8 I 0 0
laminaria insertion was followed in l hour by the ingestion of aspirin (ASA, 650 mg) and every 4 hours for live doses, PGFM levels declined during the 16-hour period from 20.7 to 16.5 pg/ml. Impact of laminaria on pregnancy termination. The use of larninaria increased the ease of cervical dilatation in the treated group. The physician experienced moderate to severe difficulty in dilating the cervix of 4
Total
Nullipara
32 (76%) 9 (22%) 1 (2%)
0 6
0
:J 3
I
Para 1
I
Para 2
2
I l
2
()
()
I
Total 3 (15%) 9 (45%) 5 (25%)
:1 (15%)
controls and one study patient experienced an elevation of temperature of 37.5 to ~7.9° Cat 6 and 9 days after suction curettage. Endocervical culture results from swabs taken at the time of the first ele\ation of temperature showed no mrrelation with the culture results obtained during the study period. All three women responded to oral antibiotic therapy over a 7 day period of time. There was no evidence of cenical laceration in any women treated with laminaria.
Comment Prostaglandins may represent the biochemiGll cause of enhanced uterine activity prior to the onset of true labor.'~ Recently. however, Dubin and colleagues'~ found no significant change in the peripheral concentration of PGFM in women undergoing either premature onset of labor or spontaneous labor at term. In that study. elevations in peripheral PGFM were not observed after the onset of labor: however, higher concentrations of PGFM were observed in mixed ft'tal cord blood.'" I ncrernents in the peripheral concentration of PG.FM suggest that either the laminaria or cenical dilatation itself may alter peripheral concentrations of PGF 2" and its metabolite, PGFM. l.t has been suggested that anv stretching of or trauma to tissue could lead to the release of uterine prostaglandins." This latter theory does not gain support from the recent data of Dubin and associates 13 since these authors failed to identifv a significant increase in peripheral plasma PGFM during spontaneous cervical dilatation during active labor. Whether the normally high concentrations of PGFM in pregnancy mask subtle changes in peripheral P(; FM i;;
Volume 142 Number I
not known. The 30% rise in PGFM observed in laminaria-treated women did not correlate with the reported degree of abdominal discomfort which followed the insertion of laminaria. Indeed, the one woman who experienced rhythmical uterine contractions after the insertion of laminaria had increments in peripheral PGFM similar to those of women who experienced no discomfort whatsoever. The significant decline in PGFM noted over the 16hour sampling period, in ASA-treated women, suggests at least that the inhibitors of prostaglandin synthetase decreased the elaboration of prostaglandins by the uterus or the laminaria itself. The latter presumption is based on the finding of PGFM levels in saline used to soak laminaria. In our study, laminaria not only promoted atraumatic cervical dilatation but also may have reduced the intraoperative complications so often encountered in nulliparous women. 14 Almost half the study patients
Laminaria use in first-trimester pregnancy termination
39
were nulliparous; 45% were teen-agers. The use of laminaria appeared to avert trauma, but in two instances the laminaria assumed an "hourglass'' configuration which has been described by other authors 1;; as a complication of usage of laminaria. Infection is not an infrequent complication of firsttrimester pregnancy termination. 16 However, in this series there were no instances of immediate sepsis, and the two febrile cases 6 days after uterine curettage could not be linked bacteriologically to endocervical colonization prior to the insertion of laminaria. Although prostaglandins have been suggested as etiologic agents in dysmenorrhea, JR. 19 the varied pain response observed in our study in no way correlated with peripheral PGFM. Thus, women may display a biologic vulnerability to uterine contractions which does not correlate with the circulating concentration of prostaglandins and their metabolites.
REFERENCES I. Eaton, C. J., Cohn, F., and Bollinger, C. C.: Laminaria tent as a cervical dilator prior to aspiration-type therapeutic abortion, Obstet. Gynecol. 39:533, 1972. 2. Newton, B. W.: Laminaria tent: Relic of the past or modern medical device? AM. J 0BSTET. GYNECOL. 113:442, 1972. 3. Golditch, I. M., and Glasser, M. H.: The use of laminaria tents for cervical dilatation prior to vacuum aspiration abortion, AM.]. 0BSTET. GvNECOL 119:481, 1974. 4. Aiu. P., Berman, R., Krieger, J., et al.: Laminaria: An underutilized clinical adjunct, Clin. Obstet. Gynecol., 1972. 5. Stubblefield, P. G., Naftolin, F., Erigoletto, F., and Ryan, K. j.: Laminaria augmentation of intra-amniotic PGF2a for midtrimester pregnancy termination, Prostaglandins 10:413, 1975. 6. Duenhoelter,J. H., Gant, N. F., and Jimenez,]. M.: Concurrent use of prostaglandin F2 a and laminaria tents for induction of midtrimester abortion, Obstet. Gynecol. 47:469, 1976. 7. Hachamovitch, M., Bracken, M. B., and Simons, H.: Saline-instillation abortion with laminaria and megadose oxytocin, AM. J. 0BSTET. GYNECOL. 135:327, 1979. 8. Cross, W. G., and Pitkin, R. M.: Laminaria as an adjunct in induction of labor, Obstet. Gynecol. 51:606, 1978. 9. Tohan, N., Tejani, N. A., Varanasi, M., and Robins, J.: Ripening of the term cervix with laminaria, Obstet. Gynecol. 54:588, 1979.
10. Manabe, Y.: Laminaria tent for gradual and safe cervical dilatation, AM, j. 0BSTET. GYNECOL. 110:743, 1971. I l. Ghodgaonkar, R. B., Dubin, N. H., Blake, D. A., and King, T. M.: 13,14-Dihydro-I5-keto-prostaglandi n F2a concentrations in human plasma and amniotic fluid, AM. j. 0BSTET. GYNECOL. 134:265, 1979. 12. MacDonald, P. C., Porter, J. C., Schwartz, B. E., and Johnston, J. M.: Initiation of parturition in the human female, Semin. Perinatol. 2:273, 1978. 13. Dubin, N. H., Johnson, J. W. C., Calhoun, S., et al.: Plasma prostaglandin in pregnant women with term and preterm deliveries, Obstet. Gynecol. 57:203, 1981. 14. Olsen, C. E., Nielsen, H. B., and Ostergaard, E.: Complications to therapeutic abortions, lnt. J. Gynaecol. Obstet. 8:823, 1970. I5. Gusdon, J.P., and May, W. J.: Complications caused by difficult removal of lamina ria tents, AM. J. OBSTET. GYNECOL. 121:286, 1975. I6. Jurukovski, J., and Sukaroy, L.: A critical review oflegal abortion, Int. J. Gynaecol. Obstet. 9:111, 1971. 17. Chaudhuri, G.: Intrauterine device: Possible role of prostaglandins. Lancet 1:480, 1971. I 8. Marx, J. L.: Dysmenorrhea: Basic research leads to a rational therapy, Science 205:175, 1979. 19. Willman, E. A., Collins, W. P., and Clayton, S. G.: Studies in the involvement of prostaglandins in uterine symptomatology and pathology, Br . .J. Obstet. Gynaecol. 83:337, 1976.