Laminaria, induced fetal demise and misoprostol in late
abortion
Warren M. Hern*
Director,
Assistant Clinical Professor, Department of Obstetrics and
Gynecology, University of Colorado Health Sciences Center, Denver, CO,
Received 13 April 2001; received in revised form 20 July
2001; accepted
Reprinted by permission of the International
Federation of Gynecology and Obstetrics
International
Journal of Gynecology & Obstetrics 75
(2001) 279-286 www.elsevier.com/locate/ijgo
Abstract
Objectives: To
analyze and determine the safety and effectiveness of induced fetal demise as an
adjunctive method in outpatient abortion for patients with advanced pregnancies
and to evaluate the independent effect of intrauterine misoprostol administered
after amniotomy in late abortion.
Methods: During a 9-year
period, 1677 abortions were performed for patients whose pregnancies ranged from
18 through 34 menstrual weeks in an outpatient facility. Of these, 832 were performed by one
physician. Techniques for
performing all the abortions included induction of fetal demise by intrauterine
fetal injection of digoxin and/or hyperosmolar urea, serial multiple laminaria
treatment of the cervix, amniotomy, oxytocin induction of labor, and assisted
delivery or surgical evacuation of the fetus and placenta. In the last 411 of the 832 patients
whose abortions were performed by one physician, misoprostol was placed in the
lower uterine segment following amniotomy in order to enhance labor induction,
cervical ripening, and fetal expulsion.
Results: Of the entire group
of 1677 cases, the median gestational age was 22 menstrual weeks. The median procedure time for all cases
was 10 min. Measured median blood
loss was 125 ml. Blood loss and
procedure time increased with length of gestation, but these were not affected
by misoprostol. There were three
major complications (0.2%) in the overall series. Among patients seen by one physician (N
– 832), amniotomy-to-procedure time was shorter by 26 min for patients receiving
misoprostol, and there was 27% more variability in amniotomy-to-procedure time
among patients not receiving misoprostol.
Complication rates for patients receiving misoprostol were the same as
for those not receiving misoprostol.
There were no major complications in the 832 patients seen by one
physician, no uterine rupture or perforations, and no cervical lacerations. Conclusions: Outpatient abortion may be
performed safely from 18 through 34 menstrual weeks using combined surgical and
medical procedures. Use of
intrauterine post-amniotomy misoprostol was associated with reduced
amniotomy-to-procedure time and reduced variability in the
amniotomy-to-procedure time.
© International Federation of Gynecology and Obstetrics. All rights
reserved.
Keywords:
Abortion; Misoprostol; Induced fetal demise; Laminaria
1.
Introduction
Current techniques in late abortion are eclectic, combining medical and
surgical components, hygroscopic dilation of the cervix, pre-operative induced
fetal demise, and the use of intraoperative ultrasonographic guidance. Termination of pregnancy in the second
trimester and beyond presents formidable obstacles, even when inter-current
illness or complications of pregnancy are not present. These challenges are accentuated when a
patient has a history of cesarean delivery, cervical scarring, metabolic or
cardiovascular illness, or the presence of uterine myomata or multiple
gestation. During the past few
years, misoprostol has come into wide use in the management of cervical dilation
for term labor and for therapeutic abortion. Numerous studies document the use and
effects of intravaginal misoprostol in late abortion (defined here as
termination of a pregnancy of ≥ 20 menstrual weeks’ gestation) [1 – 12]. Most studies are characterized by a
small number of patients with different dosage regimes, but all focus on
inpatient abortion achieved by induction of labor. Some studies contain a large proportion
of cases in which spontaneous fetal demise had already occurred.
Other reports have described the use of misoprostol in the management of
premature rupture of membranes at term, applying misoprostol in several ways [13
– 16].
The
induction of fetal demise by intrafetal injection of digoxin or other materials
prior to late abortion has become widely practiced during the past 20 years, but
only one published report describes this activity [17]. In a more recent study, a randomized
clinical trial including 126 patients seeking abortions at 20 – 23.1 weeks found
that intra-amniotic digoxin infusion as a means of causing fetal demise resulted
in more vomiting but did not increase efficacy in late abortion [18].
This
report analyzes the experience with 1677 consecutive patients with gestations
ranging from 18 through 34 weeks whose abortions were performed by five
different physicians in an ambulatory extramural setting at a single
institution. We review techniques,
including pre-operative induced fetal demise, used to enhance the safety and
efficacy of this procedure, procedure outcome variables, and overall
complication rates. Particular
attention is given to the independent effects of misoprostol on safety and
various outcome variables in these procedures.
2. Materials and
methods
All
procedures were performed over a period of 9 years ending in May, 1999 in a
single private office outpatient facility located across the street from a
community hospital. The facility
has been specially equipped and staffed to provide assistance for women seeking
late abortion. Patients receive
individual counseling and personal support throughout their experience at the
clinic. Real-time diagnostic
ultrasound is performed on all patients during the pre-operative
evaluation. Most patients come to
the facility by way of referral.
Twenty-six of the patients in the current report were included in a
previous monograph which focused on the experience of 124 selected patients
ending pregnancies for fetal anomaly or genetic disorder. These pregnancies were terminated by a
variety of techniques during a 10-year period which overlapped the current
reporting period by approximately 2 years [17].
The
routine protocol after ultrasound evaluation and counseling included placement
of one or more laminaria in the cervix on day 1, replaced by several laminaria
(up to 20, depending on size of the laminaria) in the cervix on day 2 in one
sitting or in two sittings 6 h apart, and performance of the abortion on day
3. The serial multiple laminaria
pre-operative treatment protocol of 2 days was used for all patients except
those who experienced spontaneous labor and fetal expulsion after the first
day.
In
all patients, induced fetal demise was accomplished by intrafetal injection of
digoxin 1.5 – 2 mg on day 1 or 2 under direct ultrasound visualization. In patients with gestations 24 menstrual
weeks or greater, 40 g of hyperosmolar urea was injected intrafetally following
injection of the digoxin. On the
third day of treatment, an intravenous (i.v.) line was placed in order to permit
an infusion of Ringer’s lactate solution and the administration of i.v.
medications. The most recently
inserted laminaria were removed under direct visualization. At that time, the membranes were
routinely ruptured under ultrasound visualization using a packing forceps or, if
the membranes were visible, with a sharp instrument such as an amniohook or
single-tooth tenaculum. Following
amniotomy, a 12-mm cannula was inserted into the uterine cavity, and the
amniotic fluid was allowed to drain as completely as possible without the use of
vacuum. In the second half of the
series, amniotic fluid removal was done routinely under direct ultrasound
visualization so as to minimize residual amniotic fluid in the uterus,
theoretically minimizing the risk of amniotic fluid embolism. An attempt to induce labor was not made
until a clear flow of amniotic fluid was established and the risk of amniotic
fluid embolism presumably reduced.
Amniotic fluid was measured as accurately as possible.
Immediately before the amniotomy, a long-acting paracervical block was
placed using 12 ml of bupivacaine (Marcaine) 0.25% (Winthrop Pharmaceuticals,
New York, NY). Sixty units of
oxytocin were added to 1000 ml of Ringer’s lactate infusion for a 10 units per h
infusion to induce labor except in patients with a previous history of cesarean
delivery. Due to the known risk of
uterine rupture with abortion in someone with a history of previous cesarean
delivery, patients with this history received either no oxytocin stimulation or
very light stimulation (2 units/h) for the purpose of maintaining uterine tone
[19].
When
patients became uncomfortable because of oxytocin-induced labor, they were given
meperidine 50-100 mg intramuscularly (i.m.) approximately 30 min before the
anticipated expulsion or dilation and evacuation (D & E) procedure. When fetal expulsion was determined by
pelvic exam to be imminent, the patient was placed in an operating room where
the expulsion was facilitated and controlled by the physician. If expulsion did not begin to occur
within a few hours after the artificial rupture of membranes, or if the patient
began bleeding heavily, D & E was performed. The D & E procedure was performed
under paracervical and/or pudendal block anesthesia using up to 20 ml of 1%
lidocaine placed immediately before the procedure.
In
the case of assisted fetal expulsion, delivery of the fetus was carefully
controlled by the physician so as to minimize the risk of cervical or perineal
laceration. This was sometimes
accomplished by sharp dissection of presenting fetal parts. For all patients in this series, forceps
evacuation of the uterus was routinely accomplished under direct intraoperative
ultrasound visualization. The
placenta was delivered immediately in most cases by traction on the umbilical
cord or forceps removal when it was adherent. Intravenous infusion of oxytocin was
increased after delivery of the fetal skull, and 0.2 mg of methylergonovine
maleate was given i.m. upon delivery of the placenta.
In
the last 411 patients of this overall series, 200-400 μg of misoprostol
(Cytotec©; G.D. Searle & Co.) was placed with forceps in the lower uterine
segment a few centimeters past the internal os following amniotomy and removal
of amniotic fluid. Only the first
12 patients received less that 400 μg of misoprostol, which became the routine
dose. All these patients were seen
by one physician (W.M.H.).
Procedure time at the time of completion of the abortion was measured
from the time the physician actively began assisting with fetal expulsion, when
the uterine cavity was entered with instruments or from the beginning of the
delivery of the fetus, whichever came first, until completion of the procedure
by final curettage and vacuum aspiration.
Amniotomy-to-procedure time was measured from the time of the amniotomy
to the beginning of the procedure.
The effect of misoprostol administration on this variable is reported as
well as its apparent effect, if any, on blood loss and procedure time. Blood loss was determined for all
patients by directly measuring the blood volume in the collecting basin at the
time of the abortion and by removing clots with the gloved hand from the fluid
in the basin and measuring the volume of clots.
Post-operative tissue examination included weighing the fetus and
placenta separately and carefully measuring fetal parts, including foot length,
biparietal diameter, crown-rump length, rump-shoulder length, abdominal
diameter, and chest diameter. The
method of measurement of fetal parts has been described previously [20]. Diagnosis of actual fetal age according
to fetal foot length is based on previously established values
[20].
Patients were routinely observed in the recovery room for 1-2 h or more,
depending on patient response and the appearance of complications. All patients received routine antibiotic
prophylaxis after the intrafetal injection and continuing after the abortion
procedure. The standard protocol
was 200 mg of doxycycline orally immediately after intrafetal injection followed
by 100 mg of doxycycline twice a day for 5 days. Patients allergic to doxycycline were
given erythromycin. Cultures for
gonorrhea and chlamydia were done only in cases that appeared to be at higher
than usual risk for these infections based on history and/or the presence of a
mucopurulent cervicitis at the time of the initial exam. Rh-immune globulin was administered to
all patients who were Rh-negative.
All
patients were strongly encouraged to return for follow-up examination if
possible and were given forms to send in when they could not return in person
for an examination. Arrangements
were made for follow-up with the referring or other local physician when the
patient came from a long distance, and for the follow-up physician to return a
brief report. Standard follow-up
instructions included a recommendation for examination at 4 weeks after the
abortion.
We
defined major complications using criteria at the Centers for Disease Control:
major unintended surgery, hemorrhage requiring transfusion, or pelvic infection
with 2 or more days of fever and a peak of at least 40ºC or with hospitalization
for 11 or more days [21]. A minor
complication was defined as any of the following: an operative or post-operative
problem that required uterine aspiration or suture of a cervical laceration,
infection (indicated by uterine tenderness at follow-up examination) responding
to antibiotic therapy or more than a transitory fever of 38ºC or more on two or
more occasions, a total blood loss of more than 500 ml, and documented evidence
of coagulopathy not requiring transfusion [21].
In
terms of study design, this is a retrospective historical nested case
series. The data reported here were
generated by a review of consecutive charts for all patients who had an abortion
procedure that included induced fetal demise with intrafetal injection of
digoxin since
3.
Results
Most
patients came from throughout the United States and Canada. Several came directly from other foreign
countries, principally located in Europe and Central and South America. One-fourth of all patients were from
outside Colorado. Patient ages
ranged from 12 to 47, with a mean age of 23 and a median age of 21. Fifteen percent of all patients were age
16 or younger, and 35% of the patients were between 17 and 21 years of age. Pre-operative estimates of fetal age
ranged from 18 to 34 menstrual weeks.
Follow-up contact was obtained with 60.4% of all patients, of whom half
(30.2%) received follow-up exams at this office. Ninety-one patients (5.4%) had a history
of previous cesarean section, and 11.6% (N=196) of all patients sought
assistance because of a diagnosed fetal anomaly or fetal genetic disorder. Abortion procedures were performed by
five different physicians, of whom one (W.M.H.) performed half (N=832), another
performed one-third (N=565), and another performed 16% (N=266). Forty-seven patients (2.8%) experienced
a spontaneous rupture of membranes prior to the final treatment phase and are
not included in the amniotomy-to-procedure time analysis. There were nine cases of twins (0.5%),
all of which are included in all analyses.
The
final estimate of gestational age as defined by measurable fetal foot length
[20] was 18-34 menstrual weeks, with a median of 22. The median procedure time for all cases
was 10 min, with a mean of 12.5 and a range of 1 to 227. The median blood loss was 125 ml, with a
mean of 163 and a range of 5-2500.
Procedure time and blood loss increased with length of gestation (Table
1); linear regression analysis showed that gestational length accounted for 10%
of blood loss (adjusted r² = 0.102, P
<0.001) and for 27% of procedure time (adjusted r² = 0.274, P<0.001).
Table 1
Median blood loss and procedure time by length of
gestation (N =
1677)
Weeks’ gestation
Blood loss (ml) Procedure time
(min)
N
18 – 19
75
8
211
20 - 21
125
9
354
22 - 23
100
10
485
24 - 25
125
12
349
26 – 27 150
13.5
214
28 – 29
138
15.5
42
30 – 31
125
17
15
32 – 33
250
30
5
34 +
635
65.5
2
Blood loss was generally low and within acceptable limits, but 63
patients (3.8%) experienced a blood loss of more than 500 ml. Three patients (0.2%) in the overall
series experienced a major complication, blood transfusion, of whom two patients
were transfused because of disseminated intravascular coagulation (DIC)
syndrome. The third patient who
received a transfusion experienced a cervical laceration, uterine atony, and
blood loss of 2500 ml.
Six
percent (N = 101) of patients experienced minor complications. Of these, 27 patients (1.6%) required
re-aspiration for retained tissue.
Five patients (0.3%) experienced sepsis or chorioamnionitis during the
treatment, all associated with spontaneous rupture of membranes prior to
initiation of the abortion procedure.
Three of these patients were referred to us because of spontaneous
rupture of membranes of several days’ duration after 20 menstrual weeks in a
desired pregnancy. There were two
cases of cervical laceration, both sutured primarily, one patient with a
prochlorperazine (Compazine) reaction treated with benzotropine mesylate
(Cogentin), and one case of suspected amniotic fluid embolism, not proved. In the last case, the patient
experienced sudden dyspnea and headache, became cyanotic, and was taken
immediately to the hospital emergency room, where her signs and symptoms were
already diminishing. No evidence of
amniotic fluid embolism could be found by lung scan or change in laboratory
values. Disseminated intravascular
coagulopathy did not develop.
There were no cases of uterine perforation, uterine rupture, or
post-operative infection. Patients
with a history of cesarean section did not experience an increased rate of minor
complications and experienced none of the major
complications.
3.1
Misoprostol use
Because variability among physicians was greater for several outcome
variables such as blood loss, procedure times, and amniotomy-to-procedure times
than the variation of these observations for patients by whether or not they
received misoprostol, comparison of results for patients receiving misoprostol
are made only for those patients (N = 832) treated by one physician
(W.M.H.).
Misoprostol use was begun for all patients in March, 1997. On the recommendation of colleagues
practicing obstetrics, 200-400 μg of misoprostol was placed in the lower uterine
segment following amniotomy and release of all amniotic fluid. Since it appeared that 200 μg had little
effect for the first 12 patients, the dose was increased to 400 μg, and that
became the standard dose for all patients thereafter.
The
411 patients receiving misoprostol were compared with the previous 421
successive patients whose abortions were also performed by the same physician
(W.M.H.). The patients in both
these groups were similar, with a median age of 22 and a median gestational
length of 23 menstrual weeks.
Fifty-three percent of these patients had follow-up contact, of whom
22.6% (N = 188) had their follow-up exams at the clinic. Thirteen percent of these patients (N =
108/832) were terminating the pregnancy because of fetal anomaly or genetic
disorder. Among the patients with a
history of cesarean delivery, 24 received misoprostol and 26 did not.
Patients receiving misoprostol at the time of amniotomy experienced a
median blood loss of 175 ml vs. 150 ml for those who did not receive misoprostol
(P = 0.082). Median procedure time
for patients receiving misoprostol was the same (10 min) as for those not
receiving misoprostol. Blood loss
and procedure times increased with length of gestation for both treatment and
control groups (P<0.001). Length
of gestation had no effect on the amniotomy-to-procedure times (P = 0.709). Mean values for these outcome variables
are show in Table 2.
Excluding patients who experienced spontaneous rupture of membranes prior
to the scheduled amniotomy and procedure (N = 12) and those having
amniotomy-to-procedure times of less than 10 min (N = 15) because fetal
expulsion was imminent at the time of amniotomy, median amniotomy-to-procedure
times were shorter by 26 min for patients receiving misoprostol (162 min vs.136
min; P<0.001), and there was 27% more variability among controls not
receiving misoprostol (S.D.=133 vs. S.D.=105).
Table 2 Mean blood loss,
procedure times, amniotomy-to-procedure times
Weeks No
Cytotec
Cytotec
Total
gestation
__________________________________
____________________________________
N Blood Procedure Amniotomy-to-
N
Blood Procedure Amniotomy-to- N
Loss
time
proc. time
loss
time
proc. time
(ml)
(min)
(min)
(ml)
(min)
(min)
18 – 19
22 100
6
180
41
100
8
155
63
20 – 21
92 150
8
175.5
76
150
8.5
134.5
168
22 – 23 128 125
9
160
114
175
9
142 241
24 – 25 108 150
12
145
72
175
11
133.5
180
26 – 27
62 175
13.5
172
80
200
13
121
142
28 – 29
5 425
30
190
18
225
12
167.5
23
30 – 31
3 375
22
120
6 150 16
71
9
32 – 33
1 50
30
55
2 300
44.5
266.5
3
34
0
-
-
-
2 635
65.5
219.5
2
421 150 10
161.5
411
175
10
137
832
Treatment and control
groups by menstrual week of gestation (W.M.H. cases only; N =
832).
In
the single-physician (N = 832) series, there were 39 minor complications (4.7%)
of which 29 were blood loss of more than 500 ml and five were in patients
requiring re-aspiration (0.6%).
Three patients (0.4%), previously described in the overall series,
presented with long-standing premature rupture of membranes and developed sepsis
during treatment. Two other minor
complications, previously described, were those of a prochlorperazine
(Compazine) reaction and a suspected amniotic fluid embolism that could not be
documented.
Including only the minor complications of excessive blood loss and
re-aspiration, a Χ²-test comparing misoprostol vs. control patients showed no
difference in complication rates (P = 0.531); Table 3). There were also no differences among
patients with a history of previous cesarean delivery (P = 0.500).
Table 3 Minor
complications by treatment groupª
No misoprostol
Misoprostol
Total
No minor complications
404
394
798
Minor complications
17
17
34
Total
421
411
832
W.M.H. cases only, N =
832, Χ² = 0.531
ª Includes only
minor complications of excessive bleeding (>500 ml) or
re-aspiration
In
this series by one physician, there were no cases of cervical laceration,
uterine rupture or uterine perforation, and there were no major
complications.
4. Discussion
Advances in completing late abortion appear to include
comprehensive use of both surgical and medical treatments. A fundamental feature of this
comprehensive approach is the use of serial multiple laminaria treatment for
cervical dilation [22,23].
Another strategy that we feel enhances safety is the pre-operative
induction of fetal demise by intrafetal injection performed 24-48 h prior to the
abortion. In a previous series,
fetal demise and induction of labor was accomplished by the intra-amniotic
infusion of hyperosmolar urea on the same day as the abortion procedure
[24]. In the current series, the
induction of fetal demise as much as 2-3 days before the induction of labor
and/or D & E procedure appeared to produce fetal maceration, cervical
softening, dilation, and effacement, and appeared to minimize both blood loss
and procedure duration. This was
especially true in more advanced pregnancies (26 + menstrual weeks’ duration)
and in cases in which a lower uterine segment myoma may have otherwise made
successful labor induction or D & E impossible. One such case for the indication of
severe fetal hydrocephaly (>10 cm) at 34 menstrual weeks was characterized by
an anterior lower uterine intramural myoma 12 cm in diameter. Induced fetal demise, serial multiple
laminaria treatment for 3 days prior to the abortion procedure, misoprostol
treatment, and percutaneous cephalocentesis with the withdrawal of >200 ml of
fetal cerebrospinal fluid permitted a dilation and evacuation procedure to be
accomplished without complication.
Careful and complete removal of all amniotic fluid under direct
ultrasound visualization may diminish the risk of fatal or sublethal amniotic
fluid embolism with an associated disseminated intravascular coagulation (DIC)
syndrome. The use of local
anesthesia is generally associated with lower risks of morbidity and mortality
[25]. Uterine tone is maintained
with local anesthesia and the conscious patient can report unusual pain
immediately. Assisted fetal
expulsion in the operating room or D & E procedure under conditions of fetal
maceration, adequate cervical preparation, and placental necrosis was associated
in our series in low amounts of measured blood loss.
The
protocol combining serial multiple laminaria treatment, pre-operative induced
fetal demise, and rupture of membranes with induction of labor backed up by D
& E provides satisfactory outcomes in our clinical
setting.
In
this series, the use of misoprostol was associated with reduced
amniotomy-to-procedure times and reduced variability in these times. This is a great advantage in an
outpatient setting. Inclusion of
misoprostol in the protocol did not increase the complication rates, but it may
have enhanced patient comfort by diminishing the total length of time involved
in the abortion procedure day. This
apparent result remains to be studied by more rigorous means and
analysis.
Acknowledgment
I
wish to acknowledge the essential assistance of Erica Shafer in preparing these
data.
References
(1) Jain JK, Mishell DR Jr. A comparison of misoprostol with and
without laminaria tents of induction of second-
trimester
abortion. Am J Obstet Gynecol
1996;175(1):173-177.
(2) Phillips K, Berry C, Mathers AM. Uterine rupture during second trimester
termination of pregnancy using
mifepristone and
a prostaglandin. Eur J Obstet
Gynecol Reprod Biol 1996;65(2):175-176.
(3) Wong KS, Ngai CS, Chan KS, Tang LC,
Ho PC. Termination of second
trimester pregnancy with gemeprost
and misoprostol:
a randomized double-blind placebo-controlled trial. Contraception
1996;54(1):23-25.
(4) Ho PC, Ngai SW, Liu KL, Wong GC, Lee
SW. Vaginal misoprostol compared with oral misoprostol in
termination of second-trimester pregnancy. Obstet Gynecol
1997;90(5):735-738.
(5) Srisomboon J, Pongpisuttinun S.
Efficacy of intracervicovaginal misoprostol in second-trimester
pregnancy
termination: a
comparison between live and dead fetuses.
J Obstet Gynaecol Res 1998;24(1):1-5.
(6) Herabutya Y, O-Prasertsawat P. Second
trimester abortion using intravaginal misoprostol. Int J Gynecol
Obstet
1998;60(2):161-165.
(7) Dickenson JE,Godfrey M, Evans SF.
Efficacy of intravaginal misoprostol in second-trimester
pregnancy
termination: a randomized controlled trial. J Matern Fetal Med
1998;7(3):115-119.
(8) Wong KS, Ngai CS, Wong AY, Tank LC,
Ho PC. Vaginal misoprostol compared with gemeprost in
termination of second trimester pregnancy. A randomized trial.
Contraception 1998;58(4):207-210.
(9) Jain JK, Kao J, Mishell Jr DR. A
comparison of two dosing regimens of intravaginal misoprostol for
second-
trimester
termination. Obstet Gynecol 1999;93(4):571-575.
[10] Chen M, Shih JC, Chiu WT,
Hsieh FJ. Separation of cesarean scar during second trimester
intravaginal
misoprostol abortion. Obstet Gynecol 1999;94(5 Part
1):840.
[11] Perry KG Jr, Rinehart BK,
Terrone DA, martin RW, May WL, Roberts WE. Second-trimester
uterine
evacuation: a comparison of intra-amniotic (15S)-15-methyl-prostaglandin
F2alpha and intravaginal
misoprostol. Am J Obstet Gynecol 1999;181(5 Pt
1):1057-1061.
[12] Wong KS, Ngai CS, Yeo EL,
Tang LC, Ho PC. A comparison of two regimens of intravaginal misoprostol
for
termination of second trimester pregnancy: a randomized comparative
trial. Hum Reprod 2000;15(3):709-712.
[13] Ngai SW, To WK, Lao T, Ho PC. Cervical priming with
oral misoprostol in pre-labor rupture of membranes at
term.
Obstet Gynecol 1996;87(6):923-926.
[14] Sanchez-Ramos L, Chen AH, Kaunitz AM, Gaudier FL,
Delke I. Labor induction with intravaginal misoprostol
in term
premature rupture of membranes: a randomized study. Obstet Gynecol
1997;89(6):909-912.
[15] Bennet BB. Uterine rupture during induction of
labor at term with intravaginal misoprostol. Obstet
Gynecol
1997;89(5
Pt 2):832-833.
[16] Wing DA, Paul RH. Induction of labor with
misoprostol for premature rupture of membranes beyond
thirty-six
weeks’ gestation. Am J Obstet Gynecol
1998;179:94-99.
[17] Hern WM, Zen C, Ferguson KA, Hart V, Haseman MV.
Outpatient abortion for fetal anomaly and fetal death
from 15-34
menstrual weeks’ gestation: techniques and clinical management. Obstet Gynecol
1993;81:301-306.
[18] Jackson RA, Teplin VL,Drey EA, Thomas IJ, Darney
PD. Digoxin to facilitate late second-trimester abortion:
a
randomized, masked, placebo-controlled trial. Obstet Gynecol
2001;97:471-476.
[19] Chapman ST, Crispens M, Owen J, Savage K.
Complications of midtrimester pregnancy termination: the effect
of prior
cesarean delivery. Am J Obstet Gynecol 1996;175:889-892.
[20] Hern WM. Correlation of fetal age and measurements
between 10 and 26 weeks of gestation. Obstet Gynecol
1984;63:26-32.
[21] Grimes DA, Schulz KF, Cates W Jr, Tyler CW. The
Joint Program for the Study of Abortion/CDC: a
preliminary report. In Hern WM, Andrikopoulos B, editors. Abortion in the
Seventies. New York: National
Abortion
Federation, 1977:41-46.
[22] Hern WM, Oakes A. Multiple laminaria treatment in
early midtrimester outpatient suction abortion. Adv
Planned
Parent 1977;12:93-97.
[23] Hern WM. Abortion Practice. Boulder, CO: Alpenglo
Graphics, 1990:122-156.
[24] Hern WM. Serial multiple laminaria and adjunctive
urea in late outpatient dilation and evacuation abortion.
Obstet
Gynecol 1984;63:543-549.
[25] Atrash HK, Cheek TG, Hogue
1988;158:420-424.
*
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