CONTRACEPTION
Mifepristone (RU 486) for Induced Abortion
D-R.
Cervical Priming Prior to Surgically in the Late First Trimester
Urqubart
and
A.A.
Templeton
Department of Obstetrics & Gynaecology University of Aberdeen Aberdeen Maternity Aospital Scotland
ABSTRACT Mifepristone (RU 486; Roussel-Uclaf, Paris, France) is an antiprogesterone agent, which has been used successfully in combination with prostaglandin for early pregnancy medical abortion. Forty primigravidae were studied from 10 - 13 weeks of gestation. Women were randomly allocated to receive either placebo or a 600 mg single oral dose of Mifepristone 48 hours prior to vacuum aspiration under general anaesthesia. An objective mechanical method was used to assess the dilatation In 35% of the treated patients, of the cervix at surgery. there was no need for further dilatation prior to evacuation of the uterus. All patients in the placebo group required further dilatation fp < 0.001). In those patients receiving Mifepristone who did require further dilatation, the initial dilatation of the cervix was significantly greater (p < 0.01) and significantly less force was required to dilate the cervix to 9 mm (p < 0.001). Perioperative blood loss was reduced. effects. There were no serious complications or side Mifepristone for cervical priming is safe and effective and has advantages over prostaglandins and hydrophilic cervical dilators.
Correspondence
to:
Professor A.A. Templeton & Gynaecology, Dept. of Obstetrics Aberdeen Maternity Hospital, Cornhill Road, Aberdeen,Scotland AB9 2ZD.
Submitted for publication March 15, 1990 Accepted for publication May 22, 1990
AUGUST 1990 VOL. 42 NO. 2
191
CONTRACEPTION INTRODUCTION Despite new developments in medical methods of induced using abortion, the antiprogesterone agent Mifepristone in combination with a small dose of prostaglandin, the need for surgical termination procedures is likely to continue.1-4 This late first trimester and early is especially true in the second trimester, when a medical approach may result in high rates of incomplete abortion with unacceptable side effects and complication rates. Vacuum aspiration is a safe procedure for first trimester termination,5 of dilatation and the modified technique and evacuation is safer than prostaglandin-induced abortion in the early second trimester.6 However, forceful dilatation of the cervical canal can be associated with cervical laceration which may increase midtrimester losses in subsequent pregnancies7 and the incidence Technically difficult dilatations are of preterm delivery.e also associated with an increased frequency of haemorrhage, incomplete evacuation of the uterine contents (predisposing to infection and need for repeat curettage) and uterine the It is therefore advantageous if a degree of perforations.g softening and dilatation (priming) can be achieved cervical Several methods have been used prior to surgical termination. that achieve Previous studies have shown preto this. operative treatment with prostaglandins results in dilatation a significant decrease in blood loss of the cervical canal,l" complications.X2 at surgeryll and frequency of operative effective cervical the length of Although for ripening, hospital stay is increased and gastro-intestinal side effects remain a problem despite the development of new uterospecific prostaglandin analogues.13 cervix Hydrophilic dilators inserted into the swell gradually and are as effective as the prostaglandins for cervical preparation prior to termination.X3*14 surgical the dilators require insertion by medical staff. A However, false passage may be created or bleeding may be induced. the dilator may fall out, and this Despite accurate placement, might not be discovered until the start of the operation when it would no longer be possible to provide effective cervical ripening. A well oral compound that is capable of tolerated with a cervical softening and dilatation low Llducing would have distinct advantages incidence of adverse effects, over the existing cervical priming agents used in clinical practice.
(RU for
192
The progesterone receptor blocking agent, Mifepristone 486; Roussel-Uclaf, Paris, France), has so far been used early pregnancy medical abortion, either a10ne,1S*16 or
AUGUST 1990 VOL. 42 NO. 2
CONTRACEPTION
in combination with prostaglandin.3*4 A marked cervical priming effect has been reported to be present at uterine evacuation in those women treated with Mifepristone alone who had incomplete abortion.z7*Xe Studies in the guinea pig have shown that Mifepristone causes cervical dilatation and softening without inducing uterine contractions.1* Two recent studies in late first trimester human pregnancy termination conclude that Mifepristone is a useful cervical ripener.=T2 The aim of the present study was to evaluate objectively the effect of Mifepristone on the force required to dilate the human cervix in primigravid patients undergoing late first trimester surgically induced abortion.
PATIENTS
AND
METHODS
The study was approved by the Ethical Committee of The University of Aberdeen and the Grampian Health Board. Forty women were recruited from patients about to undergo late first trimester legal pregnancy termination. All patients were healthy women in their first pregnancy and aged between 18 and 35 years. Each patient had between 70 and 91 days of amenorrhoea from the first day of the last menstrual period. The presence of a single viable fetus of the correct size for gestational age was confirmed by ultrasound in all cases. Patients were excluded if they had previously undergone any form of cervical surgery or dilatation, or if there were any All patients gave symptoms or signs of threatened abortion. written informed consent. Women were (according to a randomly allocated predetermined schedule) to receive either placebo or a single 48 hours prior to vacuum 600 mg oral dose of Mifepristone aspiration. Both were blind to the women and surgeon administration of Mifepristone the drug. The placebo and tablets were supplied by ROUSSell Laboratories UK. Vacuum aspiration was performed by one of us (DRU) under general anaesthesia. The technique of general anaesthesia was different standardised to avoid effect that the any have on cervical inhalational anaesthetic agents might resistance or blood loss. All patients had anaesthesia induced intravenous (Diprivan, ICI) and with propofol maintained with intermittent repeat doses while spontaneously breathing a mixture of oxygen and nitrous oxide. Oxytocic Prior to induction of agents were not given routinely. anaesthesia, patients were questioned as to any bleeding or pain experienced in the 48 hours after drug administration. The presence of any bleeding from the uterus was noted. The baseline dilatation of the cervix and the force required to dilate the cervix to 9 mm was measured using a modified version of an instrument specially designed to measure force (in Newtons) required to pass a series of dilators graduated The in 1 mm steps from 3 - 9 mm through the cervix (201. forces for each dilator were summated to determine the total
AUGUST 1990 VOL. 42 NO. 2
CONTRACEPTION force applied to the dilators. The baseline dilatation was taken as the largest dilator which could be passed through the cervical OS without producing a reading, i.e. meeting resistance. Any complications were recorded and the contents of the aspiration jar measured as an estimate of blood loss. Patients were asked to return for follow-up fourteen days after termination so that any delayed complications could be determined.
Statistical
Analvsis
Comparison between the two groups was made by chi-squared Students t-test using the Minitab analysis or an unpaired Statistical package (Minitab, Pennsylvania State University).
RESULTS women were recruited and randomly allocated to Forty receive either placebo or 600 mg of Mifepristone orally 48 The two were hours prior to vacuum aspiration. groups comparable in terms of age, weight and gestational age (Table I). no patient bled prior to returning In the placebo group, to hospital for vacuum aspiration. Four patients reported lower abdominal cramping pain after tablet administration. One patient made contact the day following tablet administration to say that she no longer wished to undergo termination. The was broken and the patient was informed that she code fortunately had not taken an active drug. No other side of therapy were effects or complications reported. In the active group receiving 600 mg Mifepristone, four patients reported light vaginal bleeding prior to return to hospital for vacuum aspiration. The presence of uterine bleeding was confirmed in all four cases at vaginal cleansing under general anaesthesia prior to termination. Five patients experienced mild period-like low abdominal pain after receiving Mifepristone. One patient severe suffered pain requiring hospital admission and opiate analgesia 36 hours after drug administration. The pain subsided rapidly with conservative measures; there was no vaginal bleeding. Uncomplicated vacuum aspiration was carried out as planned the following morning. Two patients vomited within 2 hours of tablet administration in the Mifepristone group. There were no other complications. The findings at surgery are shown in Table II. All 19 patients who received placebo and underwent vacuum aspiration required further dilatation of the cervix to allow passage of a number 8 Karman suction curette. The mean baseline dilatation was 5.8 mm. A mean force of 24.5 N was required to dilate the cervix to 9 mm. The mean blood loss in the placebo group was 305 ml.
194
AUGUST 1990 VOL. 42 NO. 2
CONTRACEPTION
Table
I
Patient
Characteristics
Mifepristone
Placebo
Age
(years)
Weight
(Kg)
Gestation
(days)
Results
21.6
( 4.31
20.8
(2.8)
59.5
(11.4)
56.6
(7.8)
77.7
( 6.8)
76.2
(6.8)
are
Means
(S-D.)
I
In the 20 patients receiving 600 mg Mifepristone 48 hours prior to surgery, only 13 patients (65%) required further dilatation of the cervix. In 7 patients, the cervix was already dilated to more than 9 mm, and a number 8 Karman curette was able to be easily inserted directly into the uterine cavity without further dilatation. In the 13 patients in whom cervical resistance was met before 9 mm of dilatation, the mean baseline dilatation was 7.0 mm and only 9.5 N of force were required to achieve a dilatation of 9 mm. The mean blood loss was 125 ml. The 2 patients who vomited after Mifepristone administration had the lowest baseline dilatation and required the greatest force to dilate the cervix to 9 mm in the treated group. One patient in each group required an oxytocic agent for primary haemorrhage (with good effect). At who all patients follow-up one month after termination, attended had complete abortion on clinical grounds. Mifepristone the placebo and The difference between Those patients receiving groups was statistically significant. Mifepristone were significantly less likely to require further dilatation lp < 0.0011. In those Mifepristone-treated patients baseline did the mean who further dilatation, require dilatation of the cervix was significantly greater than in the placebo group (p < 0.01) and significantly less force was the sufficiently to allow required to dilate the cervix passage of a number 8 Karman curette (9 mm; p < 0.001). There was a significant reduction in perioperative blood loas in the Mifepristone-treated group (p < 0.01).
AUGUST 1990 VOL. 42 NO. 2
195
Surgery
* Excluding the 7 patients who did the passage of a number 8 Karman
any
(1.1)
*7.0
)
(1.1)
5.8
Initial dilation of cervix (mm)
in Treated
not require curette.
p < 0.001
65
20
% Requiring further dilatation
at
Mifepristone
No. of 'atients
Findings
100
Clinical
19
II
Placebo
Table
Groups
( 5.7)
(12.1)
dilatation
9.5
24.5
Force required to dilate cervix to 9 mm (N)
Control
futher
and
( 72)
(198)
to allow
p < 0.01
125
305
Blood loss (ml)
CONTRACEPTION It is noteworthy that in the seven patients in whom Mifepristone had induced sufficient cervical dilatation to allow curettage to be performed without further dilatation, only light bleeding was preoperatively by reported four patients, three patients had no bleeding whatsoever.
DISCUSSION The present study avoids the notorious difficulties inherent in the subjective assessment of cervical stiffness by using an objective method. The validity and reliability of the force measuring set of dilators has previously been established."O Mifepristone is an effective cervical dilating agent when given 48 hours prior to vacuum aspiration in the late first trimester. Less force (if any) is required to dilate the cervix, and the procedure is easier to carry out. It can therefore be expected that both immediate and long-term complications of abortion perforation, (e.g. incomplete evacuation, subsequent mid-trimester abortion and preterm delivery) will be reduced. The treatment is acceptable and appears to be associated with fewer adverse side effects than either prostaglandins or cervical hydrophilic dilators. Four women (20%) experienced vaginal bleeding light after Mifepristone administration. No patient required blood transfusion or emergency One curettage. patient reported severe pain requiring opiate analgesia, but had no vaginal bleeding. She had been warned that light vaginal bleeding or mild period cramps might be experienced. Hospital admission, reassurance and analgesia effective were and sufficient to delay termination until the planned time the following day. The patient was anxious and living alone. Fortunately, the one patient who changed her mind and elected to continue the pregnancy after entering into the study was in the placebo arm of the trial. This emphasizes the importance of counselling the administration of prior to Mifepristone for pregnancy termination. In most cases, an incomplete course of Mifepristone will induce uterine bleeding and abortion (albeit incomplete). If this does not occur and should be warned that the pregnancy continues, patients Mifepristone crosses the placenta,2z and its effect on the fetus is as yet unknown. Patients should be advised that the Mifepristone should be ingestion of a single dose of the pregnancy under terminate considered a commitment to strict medical supervision. There is evidence to suggest that the cervical priming effects of Mifepristone are present at 24 hoursz2 and clinical studies in the mid-trimester have not been able to demonstrate additional benefit from exposure to Mifepristone for any longer than 24 hours.z3-24 A shorter time interval between Mifepristone administration and surgery would reduce the small incidence of preoperative bleeding and the risk of abortion occurring prior to return to hospital for termination.
AUGUST 19W VOL. 42 NO. 2
197
CONTRACEPTION Further studies are required to evaluate the optimal dose schedules for cervical priming in the late first trimester.
ACKNOWLEDGEMENTS Mifepristone and Roussel Laboratories, Middlesex.
placebo tablets were Broadwater Park,
kindly supplied by Denham, Uxbridge,
REFERENCES 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
198
Efficacy of Durlot F, Dubois C, Brunerie J, Frydman, R. for preprogesterone antogonist RU 486 (Mifepristone) operative cervical dilatation during first trimester abortion. Hum Reprod 1988; 3: 583-84. Radestad A, Christensen NJ, Stromberg L. Induced cervical with Mifepristone in first trimester abortion. ripening Contraception 1988; 38: 301-12. of therapeutic abortion in Rodger MW, Baird DT. Induction with with Mifepristone in combination early pregnancy prostaglandin pessary. Lancet 1987; ii: 1415-18. Baird DT. Early pregnancy termination: a Cameron IT, comoarison between vacuum aspiration and medical abortion using prostaglandin (16,16-dimethyl-trans-A2-PGE1 methyl 486. Br J Obstet ester) or the antiproqestoqen RU Gynaecol 1988; 95: 271-76. Paintin DB. Legal abortion in England and Wales. In: Ciba Abortion: Medical Progress and Foundation Symposium. 1985; 115: 4 - 20. Social Implications. London:Pitman, Cates W Jr, Tyler CW Jr. MidGrimes DA, Schulz KF, trimester abortion by dilatation and evacuation: a safe and practical alternative. N Engl J Med 1977; 296: 114145. PH, Ramcharan S, Berendes H. Pellegrin Harlap S, Shiono F. Prospective study of spontaneous fetal losses after induced abortions. N Engl J Med 1979; 301: 677-81. Lumley J. Very low birthweight (less than 1,500 g) and previous induced abortion: Victoria 1982 - 1983. Aust & NZ J Obstet Gynecol 1986; 26: 268-72. Moberg P. Uterine perforation in connection with vacuum aspiration for legal abortion. Inter J Gynecol Obstet 1976; 14: 77-80. Welch C, Elder MG. Cervical dilatation with 16,16dimethyl-transester vaginal pessaries surgica+ O-PGEI methyl before termination of first trimester pregnancies. Br J Obstet Gynecol 1982; 89: 849-52. Chen JK, Elder MG. Preoperative cervical dilatation by vaginal pessaries containing prostaglandin El analogue. Obstet Gynecol 1983; 62: 339-42. World Health Organisation Prostaglandin Task Force. Vaginal administration of 15-methyl PGFPumethyl ester for preoperative cervical dilatation. Contraception 1981; 23: 251-59.
AUGUST 1990 VOL. 42 NO. 2
CONTRACEPTION 13.
14.
15.
16.
17.
18.
19.
20.
21. 22.
23.
24.
Helm CW, Davies N, Beard RJ. A comparison of gemeprost and (Cervagem) pessaries Lamicel tents for cervical preparation for abortion by dilatation and suction. Br J Obstet Gynaecol 1988; 95: 911-15. World Health Organisation. comparison of Randomised different prostaglandin analogues and laminaria tents for preoperative cervical dilatation. Contraception 1986; 34: 237-51. Hermann WL, Wiess R, Riondel A et al. The effect of the antiprogesterone steroid in women: interruption of the menstrual cycle and of early pregnancy. Comptes Rendus Acad Sci Paris 1982; 294: 933-38. Grimes DA, Mishell DR, Shoupe D, Lacarra M. Early abortion with a single dose of the antiprogestin RU 486. Am J Obstet Gynecol 1988; 158: 1307-12. Elia D. Clinical study of RU 486 in early pregnancy. In: Baulieu EE, Segal SJ, eds. The Antiprogestin Steroid RU 486 and Human Fertility Control. New York: Plenum Press, 1985: 211-220. Termination of with Kovacs L. very early pregnancy different doses of RU 486: A phase I controlled clinical trial. In: Baulieu EE, Segal SJ, eds. The Antiprogestin Steroid RU 486 and Human Fertility Control. New 1985: 221-234. York:Plenum Press, SS, Fahnrich, M. et al The mechanism of Elger W, Quing action of new antiprogestins. In: Diczfalusy E, Bygdeman Fertility Regulation Today and Tomorrow. New eds. M, 1987: 75-94. York:Raven Press, GS, McManus TJ, Coutts JRT, Calder AA. Fisher J, Anthony measuring during cervical Use of a force instrument J Med Engineering and Technology 1981; 5: dilatation. 194-5. A. Transplacental passage of Frydman R, Taylor S, Ulmann, Lancet 1985; ii: 1252. Mifepristone. The use of RU 486 for cervical World Health Organisation. preparation in first trimester pregnancy termination by Brit J Obstet Gynaecol 1990; 97: 260vacuum aspiration. 66. Templeton AA. Efficacy Urquhart DR, Bahzad C, of the prior to Mifepristone 486) antiprogestin (RU prostaglandin termination of pregnancy. Hum Reprod 1989; 4: 202-3. Templeton AA. effects of Urquhart DR, The clinical various time Mifepristone at intervals prior to midabortion. Hum Reprod 1990. In trimester prostaglandin press.
AUGUST 1990 VOL. 42 NO. 2
199
Mifepristone (RU 486) for Induced Abortion
D-R.
Cervical Priming Prior to Surgically in the Late First Trimester
Urqubart
and
A.A.
Templeton
Department of Obstetrics & Gynaecology University of Aberdeen Aberdeen Maternity Aospital Scotland
ABSTRACT Mifepristone (RU 486; Roussel-Uclaf, Paris, France) is an antiprogesterone agent, which has been used successfully in combination with prostaglandin for early pregnancy medical abortion. Forty primigravidae were studied from 10 - 13 weeks of gestation. Women were randomly allocated to receive either placebo or a 600 mg single oral dose of Mifepristone 48 hours prior to vacuum aspiration under general anaesthesia. An objective mechanical method was used to assess the dilatation In 35% of the treated patients, of the cervix at surgery. there was no need for further dilatation prior to evacuation of the uterus. All patients in the placebo group required further dilatation fp < 0.001). In those patients receiving Mifepristone who did require further dilatation, the initial dilatation of the cervix was significantly greater (p < 0.01) and significantly less force was required to dilate the cervix to 9 mm (p < 0.001). Perioperative blood loss was reduced. effects. There were no serious complications or side Mifepristone for cervical priming is safe and effective and has advantages over prostaglandins and hydrophilic cervical dilators.
Correspondence
to:
Professor A.A. Templeton & Gynaecology, Dept. of Obstetrics Aberdeen Maternity Hospital, Cornhill Road, Aberdeen,Scotland AB9 2ZD.
Submitted for publication March 15, 1990 Accepted for publication May 22, 1990
AUGUST 1990 VOL. 42 NO. 2
191
CONTRACEPTION INTRODUCTION Despite new developments in medical methods of induced using abortion, the antiprogesterone agent Mifepristone in combination with a small dose of prostaglandin, the need for surgical termination procedures is likely to continue.1-4 This late first trimester and early is especially true in the second trimester, when a medical approach may result in high rates of incomplete abortion with unacceptable side effects and complication rates. Vacuum aspiration is a safe procedure for first trimester termination,5 of dilatation and the modified technique and evacuation is safer than prostaglandin-induced abortion in the early second trimester.6 However, forceful dilatation of the cervical canal can be associated with cervical laceration which may increase midtrimester losses in subsequent pregnancies7 and the incidence Technically difficult dilatations are of preterm delivery.e also associated with an increased frequency of haemorrhage, incomplete evacuation of the uterine contents (predisposing to infection and need for repeat curettage) and uterine the It is therefore advantageous if a degree of perforations.g softening and dilatation (priming) can be achieved cervical Several methods have been used prior to surgical termination. that achieve Previous studies have shown preto this. operative treatment with prostaglandins results in dilatation a significant decrease in blood loss of the cervical canal,l" complications.X2 at surgeryll and frequency of operative effective cervical the length of Although for ripening, hospital stay is increased and gastro-intestinal side effects remain a problem despite the development of new uterospecific prostaglandin analogues.13 cervix Hydrophilic dilators inserted into the swell gradually and are as effective as the prostaglandins for cervical preparation prior to termination.X3*14 surgical the dilators require insertion by medical staff. A However, false passage may be created or bleeding may be induced. the dilator may fall out, and this Despite accurate placement, might not be discovered until the start of the operation when it would no longer be possible to provide effective cervical ripening. A well oral compound that is capable of tolerated with a cervical softening and dilatation low Llducing would have distinct advantages incidence of adverse effects, over the existing cervical priming agents used in clinical practice.
(RU for
192
The progesterone receptor blocking agent, Mifepristone 486; Roussel-Uclaf, Paris, France), has so far been used early pregnancy medical abortion, either a10ne,1S*16 or
AUGUST 1990 VOL. 42 NO. 2
CONTRACEPTION
in combination with prostaglandin.3*4 A marked cervical priming effect has been reported to be present at uterine evacuation in those women treated with Mifepristone alone who had incomplete abortion.z7*Xe Studies in the guinea pig have shown that Mifepristone causes cervical dilatation and softening without inducing uterine contractions.1* Two recent studies in late first trimester human pregnancy termination conclude that Mifepristone is a useful cervical ripener.=T2 The aim of the present study was to evaluate objectively the effect of Mifepristone on the force required to dilate the human cervix in primigravid patients undergoing late first trimester surgically induced abortion.
PATIENTS
AND
METHODS
The study was approved by the Ethical Committee of The University of Aberdeen and the Grampian Health Board. Forty women were recruited from patients about to undergo late first trimester legal pregnancy termination. All patients were healthy women in their first pregnancy and aged between 18 and 35 years. Each patient had between 70 and 91 days of amenorrhoea from the first day of the last menstrual period. The presence of a single viable fetus of the correct size for gestational age was confirmed by ultrasound in all cases. Patients were excluded if they had previously undergone any form of cervical surgery or dilatation, or if there were any All patients gave symptoms or signs of threatened abortion. written informed consent. Women were (according to a randomly allocated predetermined schedule) to receive either placebo or a single 48 hours prior to vacuum 600 mg oral dose of Mifepristone aspiration. Both were blind to the women and surgeon administration of Mifepristone the drug. The placebo and tablets were supplied by ROUSSell Laboratories UK. Vacuum aspiration was performed by one of us (DRU) under general anaesthesia. The technique of general anaesthesia was different standardised to avoid effect that the any have on cervical inhalational anaesthetic agents might resistance or blood loss. All patients had anaesthesia induced intravenous (Diprivan, ICI) and with propofol maintained with intermittent repeat doses while spontaneously breathing a mixture of oxygen and nitrous oxide. Oxytocic Prior to induction of agents were not given routinely. anaesthesia, patients were questioned as to any bleeding or pain experienced in the 48 hours after drug administration. The presence of any bleeding from the uterus was noted. The baseline dilatation of the cervix and the force required to dilate the cervix to 9 mm was measured using a modified version of an instrument specially designed to measure force (in Newtons) required to pass a series of dilators graduated The in 1 mm steps from 3 - 9 mm through the cervix (201. forces for each dilator were summated to determine the total
AUGUST 1990 VOL. 42 NO. 2
CONTRACEPTION force applied to the dilators. The baseline dilatation was taken as the largest dilator which could be passed through the cervical OS without producing a reading, i.e. meeting resistance. Any complications were recorded and the contents of the aspiration jar measured as an estimate of blood loss. Patients were asked to return for follow-up fourteen days after termination so that any delayed complications could be determined.
Statistical
Analvsis
Comparison between the two groups was made by chi-squared Students t-test using the Minitab analysis or an unpaired Statistical package (Minitab, Pennsylvania State University).
RESULTS women were recruited and randomly allocated to Forty receive either placebo or 600 mg of Mifepristone orally 48 The two were hours prior to vacuum aspiration. groups comparable in terms of age, weight and gestational age (Table I). no patient bled prior to returning In the placebo group, to hospital for vacuum aspiration. Four patients reported lower abdominal cramping pain after tablet administration. One patient made contact the day following tablet administration to say that she no longer wished to undergo termination. The was broken and the patient was informed that she code fortunately had not taken an active drug. No other side of therapy were effects or complications reported. In the active group receiving 600 mg Mifepristone, four patients reported light vaginal bleeding prior to return to hospital for vacuum aspiration. The presence of uterine bleeding was confirmed in all four cases at vaginal cleansing under general anaesthesia prior to termination. Five patients experienced mild period-like low abdominal pain after receiving Mifepristone. One patient severe suffered pain requiring hospital admission and opiate analgesia 36 hours after drug administration. The pain subsided rapidly with conservative measures; there was no vaginal bleeding. Uncomplicated vacuum aspiration was carried out as planned the following morning. Two patients vomited within 2 hours of tablet administration in the Mifepristone group. There were no other complications. The findings at surgery are shown in Table II. All 19 patients who received placebo and underwent vacuum aspiration required further dilatation of the cervix to allow passage of a number 8 Karman suction curette. The mean baseline dilatation was 5.8 mm. A mean force of 24.5 N was required to dilate the cervix to 9 mm. The mean blood loss in the placebo group was 305 ml.
194
AUGUST 1990 VOL. 42 NO. 2
CONTRACEPTION
Table
I
Patient
Characteristics
Mifepristone
Placebo
Age
(years)
Weight
(Kg)
Gestation
(days)
Results
21.6
( 4.31
20.8
(2.8)
59.5
(11.4)
56.6
(7.8)
77.7
( 6.8)
76.2
(6.8)
are
Means
(S-D.)
I
In the 20 patients receiving 600 mg Mifepristone 48 hours prior to surgery, only 13 patients (65%) required further dilatation of the cervix. In 7 patients, the cervix was already dilated to more than 9 mm, and a number 8 Karman curette was able to be easily inserted directly into the uterine cavity without further dilatation. In the 13 patients in whom cervical resistance was met before 9 mm of dilatation, the mean baseline dilatation was 7.0 mm and only 9.5 N of force were required to achieve a dilatation of 9 mm. The mean blood loss was 125 ml. The 2 patients who vomited after Mifepristone administration had the lowest baseline dilatation and required the greatest force to dilate the cervix to 9 mm in the treated group. One patient in each group required an oxytocic agent for primary haemorrhage (with good effect). At who all patients follow-up one month after termination, attended had complete abortion on clinical grounds. Mifepristone the placebo and The difference between Those patients receiving groups was statistically significant. Mifepristone were significantly less likely to require further dilatation lp < 0.0011. In those Mifepristone-treated patients baseline did the mean who further dilatation, require dilatation of the cervix was significantly greater than in the placebo group (p < 0.01) and significantly less force was the sufficiently to allow required to dilate the cervix passage of a number 8 Karman curette (9 mm; p < 0.001). There was a significant reduction in perioperative blood loas in the Mifepristone-treated group (p < 0.01).
AUGUST 1990 VOL. 42 NO. 2
195
Surgery
* Excluding the 7 patients who did the passage of a number 8 Karman
any
(1.1)
*7.0
)
(1.1)
5.8
Initial dilation of cervix (mm)
in Treated
not require curette.
p < 0.001
65
20
% Requiring further dilatation
at
Mifepristone
No. of 'atients
Findings
100
Clinical
19
II
Placebo
Table
Groups
( 5.7)
(12.1)
dilatation
9.5
24.5
Force required to dilate cervix to 9 mm (N)
Control
futher
and
( 72)
(198)
to allow
p < 0.01
125
305
Blood loss (ml)
CONTRACEPTION It is noteworthy that in the seven patients in whom Mifepristone had induced sufficient cervical dilatation to allow curettage to be performed without further dilatation, only light bleeding was preoperatively by reported four patients, three patients had no bleeding whatsoever.
DISCUSSION The present study avoids the notorious difficulties inherent in the subjective assessment of cervical stiffness by using an objective method. The validity and reliability of the force measuring set of dilators has previously been established."O Mifepristone is an effective cervical dilating agent when given 48 hours prior to vacuum aspiration in the late first trimester. Less force (if any) is required to dilate the cervix, and the procedure is easier to carry out. It can therefore be expected that both immediate and long-term complications of abortion perforation, (e.g. incomplete evacuation, subsequent mid-trimester abortion and preterm delivery) will be reduced. The treatment is acceptable and appears to be associated with fewer adverse side effects than either prostaglandins or cervical hydrophilic dilators. Four women (20%) experienced vaginal bleeding light after Mifepristone administration. No patient required blood transfusion or emergency One curettage. patient reported severe pain requiring opiate analgesia, but had no vaginal bleeding. She had been warned that light vaginal bleeding or mild period cramps might be experienced. Hospital admission, reassurance and analgesia effective were and sufficient to delay termination until the planned time the following day. The patient was anxious and living alone. Fortunately, the one patient who changed her mind and elected to continue the pregnancy after entering into the study was in the placebo arm of the trial. This emphasizes the importance of counselling the administration of prior to Mifepristone for pregnancy termination. In most cases, an incomplete course of Mifepristone will induce uterine bleeding and abortion (albeit incomplete). If this does not occur and should be warned that the pregnancy continues, patients Mifepristone crosses the placenta,2z and its effect on the fetus is as yet unknown. Patients should be advised that the Mifepristone should be ingestion of a single dose of the pregnancy under terminate considered a commitment to strict medical supervision. There is evidence to suggest that the cervical priming effects of Mifepristone are present at 24 hoursz2 and clinical studies in the mid-trimester have not been able to demonstrate additional benefit from exposure to Mifepristone for any longer than 24 hours.z3-24 A shorter time interval between Mifepristone administration and surgery would reduce the small incidence of preoperative bleeding and the risk of abortion occurring prior to return to hospital for termination.
AUGUST 19W VOL. 42 NO. 2
197
CONTRACEPTION Further studies are required to evaluate the optimal dose schedules for cervical priming in the late first trimester.
ACKNOWLEDGEMENTS Mifepristone and Roussel Laboratories, Middlesex.
placebo tablets were Broadwater Park,
kindly supplied by Denham, Uxbridge,
REFERENCES 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
198
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