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Prostaglandin-F2α levels in normal saline-induced mid-trimester abortions
CONTRACEPTION
PROSTAGLANDIN-F2, LRVRLB IN ISORNAL BALIRR-INDUCED MID-TPINRBTBR ABORT10108 K. Chandra',
I. Gupta', V. Dhawan2, N.K. Ganguly'
'Department of Obstetrics and Gynaecology, and 'Experimental Institute of Medical Education and Medicine, Postgraduate Research, Chandigarh, India
Abstract
In 20 mid-trimester abortion seekers induced by extraamniotic instillation of normal saline, serial estimation of prostaglandin F2,e (PGF2c) in the plasma and extra-ovular It was observed that PGF2e was space were carried out. undetectable in both plasma and the extra-ovular space prior to the onset of induction, and was first detected in the extra-ovular fluid 2 hours after the onset of induction, prior to oxytocin infusion. In the subsequent samples, the prostaglandin concentration in plasma as well as in the extra-ovular fluid was found to rise, with levels in the latter showing a more significant rise with time as compared to the former. Thus, this study confirms the hypothesis that the mechanism of action of extra-ovular normal saline instillation in mid-trimester termination of pregnancy is the result of separation of fetal membranes from the uterine wall, leading to the release of prostaglandins which, in turn, causes uterine contractions leading to abortion.
Reprint
Requests:
I. Gupta Additional Professor Department of Obstetrics & Gynecology Postgraduate Institute of Medical Education and Research Chandigarh-160012, India
Submitted for publication December 3, 1990 Accepted for publication May 6, 1991
JULY 1991 VOL. 44 NO. 1
99
CONTRACEPTION
Introduction Prostaglandins (PG) are known to have a significant role in the process of human labour and abortion (1,2). It that it is release of been hypothesised the has of lysosomal prostaglandins following activation enzymes from the decidual cells of the uterus, during mid-trimester using extra-amniotic Emcredil termination of pregnancy hypertonic instillation (3), as well as intra-amniotic saline (4), that initiates uterine contractions leading to Based on the same hypothesis, extra-amniotic abortion. normal saline instillation was used to achieve mid-trimester abortion with favourable results (3,5). The present study undertaken to determine the role of was, therefore, prostaglandin (PGF2e) in mid-trimester abortion with extranormal instillation of saline, by means of amniotic simultaneous measurements of the levels of PGF2, in the space at extra-ovular specific time and the plasma To the best of our knowledge, no studies are intervals. available to date wherein prostaglandins have been estimated in the extra-ovular space. Materials
and Methods
The study was conducted among 20 mid-trimester abortion seekers from the Medical Termination of Pregnancy Clinic of and Obstetrics Gynaecology at the the Department of Postgraduate Institute of Medical Education and Research, The prostaglandin levels were estimated in Chandigarh. plasma samples as well as samples of fluid from the extraovular space in the 20 subjects undergoing mid-trimester abortion with extra-amniotic instillation of normal saline. complete history thorough physical After a and with pregnancy of 12 to 20 examination, 20 subjects completed weeks of gestation, estimated by the date of the last menstrual period and ultrasonography, were included in subjects with previous caesarean section or any the study. other operation on the uterus, like myomectomy, hysterotomy excluded, so were subjects with were and metroplasty, untreated vaginitis and cervicitis. Blood Samples Five ml of blood was collected from the antecubital vein into a wide-mouthed tube at 0 hour, i.e., before the insertion of the Foley catheter, then at 2 hours, just before starting the oxytocin drip, and subsequently every 4 and the last sample was taken at the time of hourly, Venous plasma was separated and PGF2e assay abortion. performed as described below.
100
JULY
VOL. 44 NO. 1
CONTRACEPTION
Fluid Samoles The fluid samples were collected from the extraamniotic space through a Foley catheter. The first (zero of hour) sample was collected prior to the instillation normal saline by injecting 5-7 ml of normal saline and then withdrawing it after 2 minutes. The subsequent samples were collected at 2 hours, and then every 4 hourly, until the catheter was spontaneously expelled. PGF2e assay was then done by the same method as used for plasma samples. Prostaslandin
Assay
PGF2, was extracted by the method described by Salmon with a few modifications (6). Briefly, plasma was acidified to pH 3 with hydrochloric aid and PGF2c was extracted with The sample was vortex mixed, diethyl ether (8 volumes). and the supernatant was evaporated under a centrifuged stream of nitrogen. Then, it was reconstituted in phosphate buffered saline (pH 7.4) and kept at -7OOC for further processing by radioimmunoassay. standard from purchased Sigma, USA. PGF2a Radiolabelled PGF2, (3ztEGF2a) 50 uci/mmol was purchased from Amersham, England. Antiserum for PGF2, was obtained from Pasteur Institute, Paris, France. The assay sensitivity was 1.5 pg/tube, and inter-assay and intra-assay coefficients of variation were ~15% and <9%, respectively. Reproducibility of the assay: Standard buffer solutions of PGF2, were repeatedly analysed by the above method and the reproducibility was found to be the same. Specificity of the assay: The inhibition of 3H-PGF2a binding to the antiserum by a series of prostaglan&n and related compounds was assessed. The mass of each PG which caused inhibition of binding of 50% 3H-PGF2a to the antiserum was determined and the relative cross-reactions were calculated. The cross-reactivity of PGF2, antisera with other major prostaglandins was ~1%. Procedure Under all aseptic precautions, a bimanual pelvic examination was performed. The posterior vaginal wall was retracted by a Sim's speculum. The anterior lip of the cervix was held with a volsellum and the vagina and cervix were cleansed with Betadine solution.
JULY 1991 VOL. 44 NO. 1
101
CONTRACEPTION A No. 14 Foley catheter was then inserted through the external OS into the extra-ovular space as high as possible, and the balloon was inflated. The zero-hour fluid sample and blood sample were collected, followed by instillation of 150 ml of normal saline and the catheter was clamped. The second sample of local fluid and blood was taken at 2 hours, after which the oxytocin infusion was started, with 5 units in 500 ml of 5% dextrose at the rate of 45 drops per minute. The concentration was increased by 5 units every 30 minutes until uterine contractions were established at 4-5 minute intervals. Subsequently, samples were collected every 4 hourly.
The procedure was considered llsuccessfullU if expulsion of the fetus, with or without the placenta, occurred within 30 hours after the instillation of normal saline extraamniotically.
Analysis of variance was used to determine whether the values were significantly different from one another at various time intervals from instillation. The correlation between the plasma and fluid PG level was assessed by measuring the coefficient of correlation. Results The mean plasma level of PGF2, was undetectable at 0 hour and 2 hours after the induction of abortion. A gradual, continuous rise of prostaglandin was observed subsequently (Figure), from 23k12.7 pg/ml (mean+SRM) 6 hours after induction to 162.2k59.9 pg/ml at 18 hours, which was statistically significant (P cO.01). Comparing the 6-hour and 14-hour plasma PGF2a levels also showed a significant difference. However, the difference in PG levels between that at 6 hours and 10 hours, 10 hours and 14 hours, 14 hours and 18 hours, was not statistically significant. Although the mean PG level in plasma decreased from 162.22k59.87 at 18 hours to 81.25242.24 at 22 hours, this difference was found to be statistically insignificant. PGF2, was undetectable in the extra-ovular fluid at 0 hour, but was present 2 hours after the induction of abortion (mean PG level 17.5k5.5 pg/ml). Subsequently, a statistically significant rise was observed to occur every 4 hourly, until 22 hours after induction, following which the catheter was expelled (Table). The difference in mean PGF2cl levels at 2 hours and 6 hours, 6 hours and 10 hours, 10 hours and 14 hours, 14 hours and 18 hours, 18 hours and 22 hours, was all statistically significant.
102
JULY 1991 VOL. 44 NO. 1
CONTRACEPTION
H -
Extra-ovular fluid PG level Plasma PG level
/
‘“U 2
6
10
14
16
22
26
-HOURS
Figure.
Mean plasma and extra-ovular fluid PG levels of 20 women in the study.
A comparison of the mean plasma and fluid levels of the 20 subjects showed a positive correlation between the two (r=0.814, P ~0.05) which was significant; the fluid level being significantly higher (t=2.79, P CO.05) than the plasma level at all time intervals. DiSaUsSion
In the present study, it was observed that both the plasma and extra-ovular prostaglandin levels were undetectable at the onset of induction. This could be explained by the fact that the uterus at mid-gestation is normally quiescent with no spontaneous uterine activity to be associated with detectable PG levels (4). extra-ovular The fluid samples were collected to estimate the prostaglandin levels locally, which would probably be a more accurate estimate of the released prostaglandin close to its probable site of synthesis. It was observed that PGF2, appeared in the extra-ovular space by 2 hours after normal saline instillation, and prior to oxytocin infusion, showing thereby that local synthesis of prostaglandin due to decidual damage had been initiated; however, still undetectable PGF2o levels were, in the plasma. Subsequently, from 6 hours, the plasma level was
JULY 1991 VOL. 44 NO. 1
103
UO
17.5~5.47
UD
UD
PLASMA PG LEVEL h/ml)
FLUID PG LEVEL kg/ml)
2
0
TIME INTERVAL (Hours)
426.25L60.45
84.16222.85
10
IN RELATION
906.92+117.10
1090+245.82
162.22+59.67
18
1200+601.78
81.2532.24
22
OF ABORTION (MEAN + S.E.M.)
X1.78+38.70
14
INTERVAL AFTER INDUCTION
192.75252.02
23512.69
6
~0 THE TIME
PLASMA AND EXTRA-OVULAR FLUID PG LEVELS OF THE 20 SUBJECTS
TABLE
-
503
26
112.75212.95
At Abortion
CONTRACEPTION found to rise gradually and reached significance 14 hours This, presumably, was because after the onset of induction. being released from the damaged prostaglandin, after enters extra-amniotic space and decidual cells, the subsequently into the amniotic fluid and vascular system of the body. space The prostaglandin levels in the extra-ovular showed a significant rise with the passage of time, to reach a peak 2 to 4 hours before the expulsion of the conceptus immediately before abortion could not be (the levels measured as the catheter had been expelled). The above findings are consistent with the hypothesis forward by Gustavii suggested that the (7), who Put which intra-amniotic hypertonic solutions mechanism by induce uterine contraction involves the release of lysosomal enzymes from damaged decidual cells, which then initiate the "arachidonic acid cascade" by liberating arachidonic acid phospholipids, resulting in prostaglandin from cellular activity of PG synthesis by the synthetase. These then diffuse into adjoining prostaglandins the may myometrium and initiate uterine contractions. A study undertaken by Ivanisevic (8) also validated this hypothesis. In the present study, PG release may, similarly, have followed decidual damage due to the presence of extra-ovular normal saline. In this study, the appearance of PG in the extra-ovular space, unlike in the plasma, as early as 2 hours after normal saline instillation also correlated well with the findings of Vassilakos et al.(g) of decidual necrosis as early as 2 hours after intra-amniotic hypertonic saline instillation for mid-trimester abortion. Another factor which could possibly have contributed to the release of prostaglandin locally is the insertion of the catheter in the extra-ovular space which, by itself, is known to initiate uterine contractions (10). Studies have been performed which have shown that oxytocin, itself, can stimulate PGF2, synthesis (4,ll). In the present study, oxytocin infusion was started 2 hours after extra-amniotic normal saline instillation, prior to which PGF2c was already detectable in the extra-ovular space. This implies that the release of extra-ovular PGF2c is independent of exogenously administered oxytocin. However, the subsequent significant rise of prostaglandins could have been potentiated by oxytocin infusion. interval Similarly, the relatively short induction-abortion (17 hours, 4 minutes) in the present study, as compared to where normal saline or Emcredil alone was used those (12,13), is perhaps because of an increased uterine response to oxytocin resulting from increased PGF2e synthesis.
JULY 1991 VOL. 44 NO. 1
105
CONTRACEPTION
Thus, the present study established that PGF2e is released locally into the extra-ovular space following extra-amniotic normal saline instillation. This solution is physiological, hence, non-toxic to body tissues, and most probably acts by separating fetal membranes from the uterine wall resulting in decidual damage, release of lysosomal enzymes and prostaglandin. References 1.
2. 3. 4.
5. 6. 7.
8. 9. 10.
11. 12. 13.
Appearance of prostaglandin F2e in human Karim SMM. blood during labour. Brit Med J 1968;4:618. Green K, Beguin F, Bygdeman M, Toppazada M, Wiguist N. Prostaglandins in fertility control. Prostaglandins 1972;2:189. Lalramzauva B, Gupta I, Dhall GI. Mid-trimester abortion by extra-amniotic Emcredil versus normal saline. Aust NE J Obstet Gynaecol 1989;29:299. Fuchs AR, Rasmussen AB, Rehnstrom J, Toth M. Prostaglandin F2e, oxytocin, and uterine activation in hypertonic saline-induced abortion. Am J Obstet Gynecol 1984;150:27. Extra-amniotic physiological Gupta I, Mahajan U. saline instillation for mid-trimester abortion. Nat1 Med J India 1990;3:11. Radioimmunoassay for 6-keto-prostaglandin Salmon JA. Fla* Prostaglandins 1978;15:383. Gustavii B. Studies on the mode of action of intraamniotically and extra-amniotically injected hypertonic saline in therapeutic abortion. Acta Obstet Gynaecol Stand Suppl 1973;25:1. Ivanisevic M, Djelmis J. Amniotic fluid and maternal plasma prostaglandins in hypertonic saline-induced abortion. Int J Gynaecol Obstet 1990;31:355. Vassilakos P, Wyss R, Stastny J. Decidual changes during hypertonic saline-induced abortions. AmJ Obstet Gynecol 1974;119:889. Ingemanson CA. Legal abortion by extra-amniotic instillation of Rivanol in combination with rubber catheter insertion into the uterus after the twelfth week of pregnancy. Am J Obstet Gynecol 1973;115:211. Wilson T, Liggins CC, Whittaker DJ. Oxytocin stimulates the release of arachidonic acid and PGF2e from human decidual cells. Prostaglandins 1988;35:771. Gustavii B. Sweeping of fetal membrane by a physiological saline solution - Effect on decidual cells. Am J Obstet Gynecol 1974;120:531. Blum M. Experience with the induction of second trimester abortion by extra-amniotic physiological saline infusion - Report of 127 cases. Europ J Obstet Gynaecol Reprod Biol 1980;10:183.
JULY 1991 VOL. 44 NO. 1
PROSTAGLANDIN-F2, LRVRLB IN ISORNAL BALIRR-INDUCED MID-TPINRBTBR ABORT10108 K. Chandra',
I. Gupta', V. Dhawan2, N.K. Ganguly'
'Department of Obstetrics and Gynaecology, and 'Experimental Institute of Medical Education and Medicine, Postgraduate Research, Chandigarh, India
Abstract
In 20 mid-trimester abortion seekers induced by extraamniotic instillation of normal saline, serial estimation of prostaglandin F2,e (PGF2c) in the plasma and extra-ovular It was observed that PGF2e was space were carried out. undetectable in both plasma and the extra-ovular space prior to the onset of induction, and was first detected in the extra-ovular fluid 2 hours after the onset of induction, prior to oxytocin infusion. In the subsequent samples, the prostaglandin concentration in plasma as well as in the extra-ovular fluid was found to rise, with levels in the latter showing a more significant rise with time as compared to the former. Thus, this study confirms the hypothesis that the mechanism of action of extra-ovular normal saline instillation in mid-trimester termination of pregnancy is the result of separation of fetal membranes from the uterine wall, leading to the release of prostaglandins which, in turn, causes uterine contractions leading to abortion.
Reprint
Requests:
I. Gupta Additional Professor Department of Obstetrics & Gynecology Postgraduate Institute of Medical Education and Research Chandigarh-160012, India
Submitted for publication December 3, 1990 Accepted for publication May 6, 1991
JULY 1991 VOL. 44 NO. 1
99
CONTRACEPTION
Introduction Prostaglandins (PG) are known to have a significant role in the process of human labour and abortion (1,2). It that it is release of been hypothesised the has of lysosomal prostaglandins following activation enzymes from the decidual cells of the uterus, during mid-trimester using extra-amniotic Emcredil termination of pregnancy hypertonic instillation (3), as well as intra-amniotic saline (4), that initiates uterine contractions leading to Based on the same hypothesis, extra-amniotic abortion. normal saline instillation was used to achieve mid-trimester abortion with favourable results (3,5). The present study undertaken to determine the role of was, therefore, prostaglandin (PGF2e) in mid-trimester abortion with extranormal instillation of saline, by means of amniotic simultaneous measurements of the levels of PGF2, in the space at extra-ovular specific time and the plasma To the best of our knowledge, no studies are intervals. available to date wherein prostaglandins have been estimated in the extra-ovular space. Materials
and Methods
The study was conducted among 20 mid-trimester abortion seekers from the Medical Termination of Pregnancy Clinic of and Obstetrics Gynaecology at the the Department of Postgraduate Institute of Medical Education and Research, The prostaglandin levels were estimated in Chandigarh. plasma samples as well as samples of fluid from the extraovular space in the 20 subjects undergoing mid-trimester abortion with extra-amniotic instillation of normal saline. complete history thorough physical After a and with pregnancy of 12 to 20 examination, 20 subjects completed weeks of gestation, estimated by the date of the last menstrual period and ultrasonography, were included in subjects with previous caesarean section or any the study. other operation on the uterus, like myomectomy, hysterotomy excluded, so were subjects with were and metroplasty, untreated vaginitis and cervicitis. Blood Samples Five ml of blood was collected from the antecubital vein into a wide-mouthed tube at 0 hour, i.e., before the insertion of the Foley catheter, then at 2 hours, just before starting the oxytocin drip, and subsequently every 4 and the last sample was taken at the time of hourly, Venous plasma was separated and PGF2e assay abortion. performed as described below.
100
JULY
VOL. 44 NO. 1
CONTRACEPTION
Fluid Samoles The fluid samples were collected from the extraamniotic space through a Foley catheter. The first (zero of hour) sample was collected prior to the instillation normal saline by injecting 5-7 ml of normal saline and then withdrawing it after 2 minutes. The subsequent samples were collected at 2 hours, and then every 4 hourly, until the catheter was spontaneously expelled. PGF2e assay was then done by the same method as used for plasma samples. Prostaslandin
Assay
PGF2, was extracted by the method described by Salmon with a few modifications (6). Briefly, plasma was acidified to pH 3 with hydrochloric aid and PGF2c was extracted with The sample was vortex mixed, diethyl ether (8 volumes). and the supernatant was evaporated under a centrifuged stream of nitrogen. Then, it was reconstituted in phosphate buffered saline (pH 7.4) and kept at -7OOC for further processing by radioimmunoassay. standard from purchased Sigma, USA. PGF2a Radiolabelled PGF2, (3ztEGF2a) 50 uci/mmol was purchased from Amersham, England. Antiserum for PGF2, was obtained from Pasteur Institute, Paris, France. The assay sensitivity was 1.5 pg/tube, and inter-assay and intra-assay coefficients of variation were ~15% and <9%, respectively. Reproducibility of the assay: Standard buffer solutions of PGF2, were repeatedly analysed by the above method and the reproducibility was found to be the same. Specificity of the assay: The inhibition of 3H-PGF2a binding to the antiserum by a series of prostaglan&n and related compounds was assessed. The mass of each PG which caused inhibition of binding of 50% 3H-PGF2a to the antiserum was determined and the relative cross-reactions were calculated. The cross-reactivity of PGF2, antisera with other major prostaglandins was ~1%. Procedure Under all aseptic precautions, a bimanual pelvic examination was performed. The posterior vaginal wall was retracted by a Sim's speculum. The anterior lip of the cervix was held with a volsellum and the vagina and cervix were cleansed with Betadine solution.
JULY 1991 VOL. 44 NO. 1
101
CONTRACEPTION A No. 14 Foley catheter was then inserted through the external OS into the extra-ovular space as high as possible, and the balloon was inflated. The zero-hour fluid sample and blood sample were collected, followed by instillation of 150 ml of normal saline and the catheter was clamped. The second sample of local fluid and blood was taken at 2 hours, after which the oxytocin infusion was started, with 5 units in 500 ml of 5% dextrose at the rate of 45 drops per minute. The concentration was increased by 5 units every 30 minutes until uterine contractions were established at 4-5 minute intervals. Subsequently, samples were collected every 4 hourly.
The procedure was considered llsuccessfullU if expulsion of the fetus, with or without the placenta, occurred within 30 hours after the instillation of normal saline extraamniotically.
Analysis of variance was used to determine whether the values were significantly different from one another at various time intervals from instillation. The correlation between the plasma and fluid PG level was assessed by measuring the coefficient of correlation. Results The mean plasma level of PGF2, was undetectable at 0 hour and 2 hours after the induction of abortion. A gradual, continuous rise of prostaglandin was observed subsequently (Figure), from 23k12.7 pg/ml (mean+SRM) 6 hours after induction to 162.2k59.9 pg/ml at 18 hours, which was statistically significant (P cO.01). Comparing the 6-hour and 14-hour plasma PGF2a levels also showed a significant difference. However, the difference in PG levels between that at 6 hours and 10 hours, 10 hours and 14 hours, 14 hours and 18 hours, was not statistically significant. Although the mean PG level in plasma decreased from 162.22k59.87 at 18 hours to 81.25242.24 at 22 hours, this difference was found to be statistically insignificant. PGF2, was undetectable in the extra-ovular fluid at 0 hour, but was present 2 hours after the induction of abortion (mean PG level 17.5k5.5 pg/ml). Subsequently, a statistically significant rise was observed to occur every 4 hourly, until 22 hours after induction, following which the catheter was expelled (Table). The difference in mean PGF2cl levels at 2 hours and 6 hours, 6 hours and 10 hours, 10 hours and 14 hours, 14 hours and 18 hours, 18 hours and 22 hours, was all statistically significant.
102
JULY 1991 VOL. 44 NO. 1
CONTRACEPTION
H -
Extra-ovular fluid PG level Plasma PG level
/
‘“U 2
6
10
14
16
22
26
-HOURS
Figure.
Mean plasma and extra-ovular fluid PG levels of 20 women in the study.
A comparison of the mean plasma and fluid levels of the 20 subjects showed a positive correlation between the two (r=0.814, P ~0.05) which was significant; the fluid level being significantly higher (t=2.79, P CO.05) than the plasma level at all time intervals. DiSaUsSion
In the present study, it was observed that both the plasma and extra-ovular prostaglandin levels were undetectable at the onset of induction. This could be explained by the fact that the uterus at mid-gestation is normally quiescent with no spontaneous uterine activity to be associated with detectable PG levels (4). extra-ovular The fluid samples were collected to estimate the prostaglandin levels locally, which would probably be a more accurate estimate of the released prostaglandin close to its probable site of synthesis. It was observed that PGF2, appeared in the extra-ovular space by 2 hours after normal saline instillation, and prior to oxytocin infusion, showing thereby that local synthesis of prostaglandin due to decidual damage had been initiated; however, still undetectable PGF2o levels were, in the plasma. Subsequently, from 6 hours, the plasma level was
JULY 1991 VOL. 44 NO. 1
103
UO
17.5~5.47
UD
UD
PLASMA PG LEVEL h/ml)
FLUID PG LEVEL kg/ml)
2
0
TIME INTERVAL (Hours)
426.25L60.45
84.16222.85
10
IN RELATION
906.92+117.10
1090+245.82
162.22+59.67
18
1200+601.78
81.2532.24
22
OF ABORTION (MEAN + S.E.M.)
X1.78+38.70
14
INTERVAL AFTER INDUCTION
192.75252.02
23512.69
6
~0 THE TIME
PLASMA AND EXTRA-OVULAR FLUID PG LEVELS OF THE 20 SUBJECTS
TABLE
-
503
26
112.75212.95
At Abortion
CONTRACEPTION found to rise gradually and reached significance 14 hours This, presumably, was because after the onset of induction. being released from the damaged prostaglandin, after enters extra-amniotic space and decidual cells, the subsequently into the amniotic fluid and vascular system of the body. space The prostaglandin levels in the extra-ovular showed a significant rise with the passage of time, to reach a peak 2 to 4 hours before the expulsion of the conceptus immediately before abortion could not be (the levels measured as the catheter had been expelled). The above findings are consistent with the hypothesis forward by Gustavii suggested that the (7), who Put which intra-amniotic hypertonic solutions mechanism by induce uterine contraction involves the release of lysosomal enzymes from damaged decidual cells, which then initiate the "arachidonic acid cascade" by liberating arachidonic acid phospholipids, resulting in prostaglandin from cellular activity of PG synthesis by the synthetase. These then diffuse into adjoining prostaglandins the may myometrium and initiate uterine contractions. A study undertaken by Ivanisevic (8) also validated this hypothesis. In the present study, PG release may, similarly, have followed decidual damage due to the presence of extra-ovular normal saline. In this study, the appearance of PG in the extra-ovular space, unlike in the plasma, as early as 2 hours after normal saline instillation also correlated well with the findings of Vassilakos et al.(g) of decidual necrosis as early as 2 hours after intra-amniotic hypertonic saline instillation for mid-trimester abortion. Another factor which could possibly have contributed to the release of prostaglandin locally is the insertion of the catheter in the extra-ovular space which, by itself, is known to initiate uterine contractions (10). Studies have been performed which have shown that oxytocin, itself, can stimulate PGF2, synthesis (4,ll). In the present study, oxytocin infusion was started 2 hours after extra-amniotic normal saline instillation, prior to which PGF2c was already detectable in the extra-ovular space. This implies that the release of extra-ovular PGF2c is independent of exogenously administered oxytocin. However, the subsequent significant rise of prostaglandins could have been potentiated by oxytocin infusion. interval Similarly, the relatively short induction-abortion (17 hours, 4 minutes) in the present study, as compared to where normal saline or Emcredil alone was used those (12,13), is perhaps because of an increased uterine response to oxytocin resulting from increased PGF2e synthesis.
JULY 1991 VOL. 44 NO. 1
105
CONTRACEPTION
Thus, the present study established that PGF2e is released locally into the extra-ovular space following extra-amniotic normal saline instillation. This solution is physiological, hence, non-toxic to body tissues, and most probably acts by separating fetal membranes from the uterine wall resulting in decidual damage, release of lysosomal enzymes and prostaglandin. References 1.
2. 3. 4.
5. 6. 7.
8. 9. 10.
11. 12. 13.
Appearance of prostaglandin F2e in human Karim SMM. blood during labour. Brit Med J 1968;4:618. Green K, Beguin F, Bygdeman M, Toppazada M, Wiguist N. Prostaglandins in fertility control. Prostaglandins 1972;2:189. Lalramzauva B, Gupta I, Dhall GI. Mid-trimester abortion by extra-amniotic Emcredil versus normal saline. Aust NE J Obstet Gynaecol 1989;29:299. Fuchs AR, Rasmussen AB, Rehnstrom J, Toth M. Prostaglandin F2e, oxytocin, and uterine activation in hypertonic saline-induced abortion. Am J Obstet Gynecol 1984;150:27. Extra-amniotic physiological Gupta I, Mahajan U. saline instillation for mid-trimester abortion. Nat1 Med J India 1990;3:11. Radioimmunoassay for 6-keto-prostaglandin Salmon JA. Fla* Prostaglandins 1978;15:383. Gustavii B. Studies on the mode of action of intraamniotically and extra-amniotically injected hypertonic saline in therapeutic abortion. Acta Obstet Gynaecol Stand Suppl 1973;25:1. Ivanisevic M, Djelmis J. Amniotic fluid and maternal plasma prostaglandins in hypertonic saline-induced abortion. Int J Gynaecol Obstet 1990;31:355. Vassilakos P, Wyss R, Stastny J. Decidual changes during hypertonic saline-induced abortions. AmJ Obstet Gynecol 1974;119:889. Ingemanson CA. Legal abortion by extra-amniotic instillation of Rivanol in combination with rubber catheter insertion into the uterus after the twelfth week of pregnancy. Am J Obstet Gynecol 1973;115:211. Wilson T, Liggins CC, Whittaker DJ. Oxytocin stimulates the release of arachidonic acid and PGF2e from human decidual cells. Prostaglandins 1988;35:771. Gustavii B. Sweeping of fetal membrane by a physiological saline solution - Effect on decidual cells. Am J Obstet Gynecol 1974;120:531. Blum M. Experience with the induction of second trimester abortion by extra-amniotic physiological saline infusion - Report of 127 cases. Europ J Obstet Gynaecol Reprod Biol 1980;10:183.
JULY 1991 VOL. 44 NO. 1