Factors affecting the outcome of early medical abortion: a review of 4132 consecutive cases

Authors


* Dr P. W. Ashok, Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen Maternity Hospital, Foresterhill, Cornhill Road, Aberdeen AB25 2ZD, UK.

Abstract

Objective To assess the outcome of a regimen of a reduced dose of mifepristone followed by one or two doses of vaginal misoprostol as a non-surgical method for termination of pregnancy.

Design Prospective observational study.

Setting Aberdeen Royal Infirmary, Aberdeen, Scotland.

Population Women seeking abortion under the 1967 Abortion Act.

Methods Factors influencing the outcome in a consecutive series of 4132 women undergoing early medical abortion in one Scottish teaching hospital since 1994.

Main outcome measures Complete abortion rates following one or two doses of misoprostol. The effect of age, gestation, previous pregnancy and previous termination on complete abortion rates following the medical regimen.

Results Of the 4132 women, 95 (2.3%) aborted within 48 hours of mifepristone and a further 3942 (95.4%) achieved complete abortion following administration of one or two doses of misoprostol. Thus, the overall complete abortion rate was 97.7% (4037/4131). A total of 94 (2.3%) women required surgical intervention of whom 13 (0.3%) had a continuing pregnancy. Following change of the regimen to include the possibility of two doses of misoprostol the continuing pregnancy rates were significantly reduced (OR = 5.88) and gestation ceased to have an effect on overall efficacy. Women who had a previous abortion were more likely to have a failed medical abortion (OR = 2.09), while women with no previous termination, but a previous live birth were more likely to have a failed abortion (OR = 2.03).

Conclusion Mifepristone in combination with one to two doses of vaginal misoprostol is an effective regimen for early medical abortion. The option of administering two doses of misoprostol significantly reduced the ongoing pregnancy rates and abolished the effect of gestation on overall efficacy. Previous termination was the strongest predictor of failed medical abortion.

Introduction

The anti-progestogen mifepristone in combination with a prostaglandin analogue provides a suitable non-surgical method for termination of pregnancy up to 63 days amenorrhoea and now increasingly at all gestations1–3. Although the Royal College of Obstetricians (RCOG) recommends that ideally abortion services must offer a choice of methods of abortion4, in England and Wales early medical abortion is only provided by 41% of National Health Service (NHS) units and 53% of specialised non-NHS units5.

In the UK, mifepristone in a 600 mg dose in combination with 1 mg of the prostaglandin E1 analogue, gemeprost, has been licensed for early medical abortion since 1991. However, a number of randomised studies have indicated that a reduced dose of 200 mg of mifepristone is equally effective6–8. Similarly, the prostaglandin E1 analogue, misoprostol, has been shown to be an effective alternative to gemeprost9–12. Moreover, it can be administered orally or vaginally and does not require special storage conditions12.

This series is a continuum to our previously reported experience with a regimen comprising 200 mg mifepristone followed by vaginal administration of 800 μg of misoprostol13. Our previous report showed that the failure and ongoing pregnancy rates were higher at gestations >50–63 days when compared with gestations less than 49 days.

We now present our experience in a consecutive series of 4132 women with a modified regimen of up to two doses of misoprostol following administration of mifepristone. We studied the factors that affected the outcome of medical abortion in addition to assessing the efficacy of the modified regimen.

Methods

A consecutive series of 4132 women with pregnancies of up to 63 days of amenorrhoea undergoing induced abortion under the terms of the 1967 Abortion Act in one Scottish NHS gynaecology unit were studied between January 1994 and November 2001. At these gestations, women presenting for termination were given a choice of medical or surgical methods. The assessment of gestational age was based on ultrasound measurement (crown rump length) in 3989 women (96.5%) and on menstrual history alone in 143 (3.5%).

Following appropriate counselling, each woman received a single tablet of 200 mg of mifepristone, swallowed under supervision. Unless abortion occurred following administration of mifepristone alone (confirmed by ultrasound scan in patients who gave a history of heavy bleeding), women were admitted as a day case to the gynaecology unit 36–48 hours later and four tablets (a total of 800 μg) of misoprostol were inserted into the posterior vaginal fornix by a nurse. If passage of products of conception had not been observed by nursing staff within 6 hours, a speculum examination was undertaken and any products of conception in the vagina or cervical os were removed. Since July 1997 (following our initial review of 2000 consecutive women13), if abortion was not imminent after 4 hours of prostaglandin administration women were given a second dose of misoprostol (400 μg) vaginally or orally depending on the amount of bleeding assessed clinically.

Following administration of prostaglandin, women were observed in the ward for 4–6 hours and given oral (paracetamol 500 mg plus dihydrocodeine 10 mg) or parenteral (morphine 10 mg) analgesia 4 to 6 hourly, as required. Pulse, blood pressure, temperature and systemic symptoms were monitored hourly following misoprostol administration. Women were discharged home following abortion or after 8 hours if abortion had not occurred and did not appear imminent. Abortion was confirmed by visualising products of conception or by an ultrasound scan if necessary. Few women had serial hCG performed to confirm abortion.

All women were offered a follow up appointment within two weeks of the termination, at the hospital, with the referring doctor or the genitourinary medicine clinic. Those few women who were discharged without passage of products of conception being confirmed after the second dose of misoprostol were given a hospital follow up appointment and a telephone number for contacting staff if they were concerned at any time. Follow up of these women included ultrasound assessment and surgical evacuation of the uterus undertaken if necessary.

For each woman, the outcome of the medical abortion regimen was classified into one of the following categories: (i) complete abortion (requiring no further treatment), (ii) incomplete abortion (products of conception passed but clinical or ultrasound signs of incomplete abortion), (iii) missed abortion (no products passed and ultrasound evidence of retained gestation sac but no cardiac activity), and (iv) continuing pregnancy (no products passed and cardiac activity present on ultrasound).

Success was defined as complete uterine evacuation without the need for surgical intervention following administration of the regimen. The induction-to-abortion interval was defined as the time interval (in hours) from administration of prostaglandin to passage of products of conception.

Data were analysed using the SPSS for Windows Statistical Package14. Continuous variables with a normal distribution are presented as means and standard deviations and comparison was made by using the independent t test. Non-parametric continuous variables are presented as medians and ranges, assessed for normality and comparison was made using the Mann–Whitney U test. Comparisons between groups were made using the χ2 test or Fishers exact test as appropriate for independent nominal data. Differences were regarded as statistically significant if P < 0.05. Confidence intervals (95%) will be applied where appropriate. Kaplan–Meier survival analysis was used to compare (by means of the log rank test) the cumulative abortion rates in relation to parity, previous termination and gestation. Comparisons were also made between results before and after the change in the regimen to two doses of prostaglandin where needed.

Logistic regression was carried out with the dependent variable successful abortion and the independent variables age, gestation, previous pregnancy, live birth and termination. Logistic regression was applied to assess the effect of gestation, age and previous pregnancy on the induction-to-abortion interval.

Results

A total of 4132 women had early medical abortion during the period January 1994 to November 2001. All data were collected prospectively.

The mean [SD] age of the 4132 women was 26.15 [6.7] years. Of 4074 women for whom parity was documented, 1923 (47.2%) were primigravida, 1606 (39.4%) had at least one previous live birth and 1054 (25.9%) had a previous termination. The mean gestation was 50.8 [7.8] days of amenorrhoea. Of the 4132 women, 2012 (48.7%) were at gestations of ≤49 days and 2120 (51.3%) were at gestations of 50–63 days at the time of commencing treatment. There was no significant difference in age, parity or previous termination at gestations ≤49 and 50–63 days. Infection screening, which included screening for Chlamydia trachomatis was done in 3745 (90.6%) women, of whom 176 (4.7%) women were found to be positive for Chlamydia.

A total of 2000 (48.4%) women were included in the initial analysis using a single dose of prostaglandin and 2132 (51.6%) women in the subsequent analysis since protocols were changed using up to two doses of prostaglandin if required.

Of the 4132 women, one took mifepristone and decided to continue with the pregnancy, with 4131 consecutive women being compliant with the regimen. This was a multiparous woman at 56 days of gestation at the time of administration of mifepristone who delivered a healthy baby at 39 weeks of gestation. This woman has been excluded from further analysis.

Of the 4131 women, 95 (2.3%) aborted within 48 hours of mifepristone administration alone, confirmed on ultrasound and received no further treatment. Among the 4036 women who went on to receive misoprostol, complete abortion without the need for surgical intervention occurred in 3942 (97.7%). Thus, the overall, complete abortion rate was 4037/4131 (97.7%). The outcome of treatment is shown in Fig. 1.Table 1 shows the indications for surgical intervention. A total of 94 women (2.3%) required surgical intervention for the following indications: 66 (1.6%) surgical evacuations were undertaken because of incomplete abortion, 11 (0.3%) for missed abortion, 13 (0.3%) because of continuing pregnancy and 4 (0.1%) women underwent evacuation as an adjunct to (negative) laparoscopy undertaken to exclude ectopic pregnancy.

Figure 1.

Outcome of medical treatment.

Table 1.  Outcome in relation to gestation. Values are given as n (%) and mean [SD].
 Total (n= 4131)Up to 49 days (n= 2012, 48.7%)50–63 days (n= 2119, 51.3%)OR95% CI
  1. *Known in 1624 and 1833 women at ≤49 and 50–63 days of gestation, respectively.

Analgesia required (n= 4136)1991 (48.1)925/1516 (61.0)1066/1630 (65.4)0.820.71 to 0.95
Aborted with mifepristone95 (2.3)65 (3.2)30 (1.4)2.31.50 to 3.59
Induction-to-abortion interval* (hours)4.0 [1.6]3.9 [1.7]4.1 [1.6]−0.39 to −0.17
Complete abortion4037 (97.7)1972 (98.0)2065 (97.5)1.280.85 to 1.94
Total surgical intervention94 (2.3)40 (2.0)54 (2.5)0.770.51 to 1.17
Indications for uterine evacuation
Incomplete abortion66 (1.6)32 (1.6)34 (1.6)1.030.64 to 1.68
Missed abortion11 (0.3)4 (0.2)7 (0.3)1.660.48 to 5.69
Continuing pregnancy13 (0.3)2 (0.1)11 (0.5)5.241.16 to 23.68
Laparoscopy4 (0.1)2 (0.1)2 (0.1)  
Day cases3993 (96.7)1948 (96.8)2045 (96.5)1.10.78 to 1.54

Of the 94 women who required surgical intervention, 10 had surgery on the day of misoprostol treatment (six to achieve haemostasis, one as an adjunct to a negative laparoscopy for suspected ectopic pregnancy and three because of patient preference following failure to abort on the day of treatment). The remaining 84 women underwent surgical intervention at intervals of 1–60 days following the medical regimen. A total of 66 (70.2%) evacuations were undertaken within 14 days of the regimen and a total of 10 (0.2%) evacuations were required to achieve haemostasis.

Of the 4036 women who received the full mifepristone/misoprostol regimen, 3830 (94.9%) were observed to pass products of conception while in the ward. Of the 206 (5.1%) women who failed to abort while under observation, 43 had surgical evacuation of the uterus and 162 subsequently had complete abortion confirmed by ultrasound examination either prior to discharge from hospital or at the hospital follow up visit. One woman who had not aborted in the ward failed to attend for follow up. The passage of products of conception at home was subsequently confirmed by this patient's general practitioner.

Treatment outcomes are summarised in Table 1 for women in the two gestation groups, ≤49 and 50–63 days. Although women in the lower gestation band were significantly more likely to abort after mifepristone alone (OR = 2.3, 95% CI = 1.50 to 3.59), there was no significant difference in the overall efficacy between the two groups (OR = 0.77, 95% CI = 0.51 to 1.17). However, the continuing pregnancy rates were higher in the higher gestational band (OR = 5.24, 95% CI = 1.16 to 23.68). Table 2 shows the complete abortion and failure rates in relation to gestation (by week).

Table 2.  Efficacy in relation to gestation by week. Values are given as n (%).
Gestation (weeks)Total (n= 4131)Initial regimenModified regimen
TotalFailureTotalFailureTotalFailure
≤ 5191 (4.6)3 (1.6)87 (4.3)0 (0.0)104 (4.9)3 (2.9)
≤ 6667 (16.1)11 (1.6)285 (14.3)2 (0.7)382 (17.9)9 (2.4)
≤ 71154 (27.9)26 (2.3)556 (27.8)12 (2.2)598 (28.1)14 (2.3)
≤ 81269 (30.8)27 (2.1)604 (30.9)12 (1.9)653 (30.6)15 (2.3)
≤ 9850 (20.6)27 (3.2)433 (22.8)23 (5.0)394 (18.5)4 (1.0)
Total4131 (100)94 (2.3)2000 (100)49 (2.5)2131 (100)45 (2.1)
P (χ2)0.300.0010.56

Table 3 shows the outcome in relation to previous pregnancy. Women who had a previous pregnancy were older compared with women who did not have a previous pregnancy. The surgical intervention rate was higher in women who had a previous pregnancy compared with those who did not have a previous pregnancy (OR = 2.27, 95% CI = 1.43 to 3.6).

Table 3.  Outcome in relation to previous pregnancy including previous live births and terminations. n= 4073 (98.6%). Values are given as n (%) and mean [SD].
 Previous pregnancy (n= 2150, 52.8%)No previous pregnancy (n= 1923, 46.6%)OR95% CI
  1. *Known in 1820/2150 (84.7%) with a previous pregnancy and 1597/1923 (83.0%) with no previous pregnancy.

Age (years)29.4 [6.5]22.5 [4.9]6.45 to 7.17
Gestation51.0 [8.0]51.0 [7.7]−0.58 to 0.37
Analgesia required (n= 3145)916/1652 (55.4)1074/1493 (71.9)0.480.41 to 0.56
Aborted on mifepristone49 (2.3)45 (2.3)0.970.64 to 1.46
Induction-to-abortion interval* (hours)4.0 [1.6]3.9 [1.6]−0.04 to 0.17
Surgical evacuation (n= 91)65 (3.0)26 (1.4)2.271.43 to 3.60
Continuing pregnancy9 (0.4)4 (0.2)2.010.62 to 6.55

Of the 4131 women, parity was known in 4073 (98.6%) women of whom 1605 (39.4%) had a previous live birth. The outcome between those women who had a previous live birth and those who did not have a live birth is shown in Table 4. Women who had a previous live birth were significantly older (P < 0.0001) and were also more likely to have had a previous termination (P < 0.0001). There was no significant association between parity and gestation at presentation (P= 0.33). The failure rates were significantly higher in multiparous (3.1%) compared with nulliparous women (1.7%) (OR = 1.81, 95% CI = 1.19 to 2.76).

Table 4.  Outcome in relation to previous live birth. n= 4073 (98.6%). Values are given as n (%) and mean [SD].
 Previous live birth (n= 1605, 39.4%)No previous live birth (n= 2468, 60.6%)OR95% CI
  1. *Known in 1360/1570 (86.6%) with a previous live birth and 2045/2409(84.9%) with no previous live birth.

Age (years)30.8 [6.3]23.1 [5.2]7.26 to 8.00
Previous termination576 (35.9)478 (19.4)2.332.02 to 2.68
Gestation50.7 [8.1]50.9 [7.7]−0.74 to 0.25
Analgesia required (n= 3145)615/1228 (50.1)1375/1917 (71.7)0.390.34 to 0.49
Aborted on mifepristone35 (2.2)59 (2.4)0.910.59 to 1.38
Induction-to-abortion interval* (hours)4.0 [1.6]4.0 [1.6]−0.10 to 0.11
Surgical evacuation (n= 91)49 (3.1)42 (1.7)1.811.19 to 2.76
Continuing pregnancy7 (0.4)6 (0.2)1.790.60 to 5.35

Of the total 4131 women in the study, previous termination details were known in 4073 (98.6%) women. Of these, 1054 (25.9%) had a previous termination of pregnancy and 3019 (74.1%) gave no past history of induced abortion. Table 5 shows the outcome between the two groups. The overall failure rate (OR = 2.09, 95% CI = 1.37 to 3.19) and continuing pregnancy rates (OR = 2.46, 95% CI = 0.82 to 7.34) were higher in women who had a previous termination.

Table 5.  Outcome in relation to previous termination of pregnancy. n= 4073 (98.6%). Values are given as n (%) and mean [SD].
 Previous termination of pregnancy (n= 1054, 25.9%)No previous termination of pregnancy (n= 3019, 74.1%)OR95% CI
  1. *Induction-to-abortion interval was known in 884/1028 (86.0%) who had a previous termination and 2521/2951 (85.4%) who had no previous termination.

Age (years)28.0 [6.1]25.5 [6.9]2.10 to 2.98
Live births576 (54.6)1029 (34.1)2.332.02 to 2.68
Gestation50.7 [7.8]50.9 [7.8]−0.72 to 0.37
Analgesia required (n= 3145)495/817 (60.6)1495/2328 (64.2)0.850.72 to 1.00
Aborted on mifepristone (n= 94)26 (2.5)68 (2.3)1.090.69 to 1.73
Induction-to-abortion interval* (hours)4.0 [1.6]4.0 [1.7]0.06 to 0.18
Continued pregnancy6 (0.6)7 (0.2)2.460.82 to 7.34
Surgical evacuation (n= 91)38 (3.6)53 (1.8)2.091.37 to 3.19

The effect of previous termination was analysed on the outcome complete abortion for nulliparous women and multiparous women. Of the 1054 women who had a previous termination, 3.5% (22/576) who had a previous live birth and 3.3% (16/478) who had no previous live birth required surgical intervention (OR 1.14, 95% CI = 0.59 to 2.20). Of the 3019 women who had no history of induced abortion, 2.6% (27/1029) who a previous live birth and 1.3% (26/1990) had no previous live birth required surgical intervention (OR = 2.03, 95% CI = 1.18 to 3.50).

Treatment outcomes are summarised in Table 6 for women in the two treatment groups, using the initial regimen (a single dose of prostaglandin) and following change in the regimen (using two doses). Although there was no difference in women requiring surgical intervention (OR = 1.16, 95% CI = 0.77 to 1.75) between the two groups, the ongoing pregnancy rate was significantly lower following two doses of prostaglandin (OR = 5.88, 95% CI = 1.30 to 26.59).

Table 6.  Induction-to-abortion interval was known in 269 women (93.7%) who had a previous termination and in 647 (90.9%) who had no previous termination.
 One dose of prostaglandin (n= 2000, 48.4%)Two doses of prostaglandin (n= 2131, 51.6%)OR95% CI
Gestation (days)49.8 [7.5]51.8 [8.0]−2.43 to −1.49
Aborted on mifepristone39 (2.0)56 (2.6)0.730.48 to 1.11
Induction-to-abortion interval* (hours)4.2 [1.7]4.3 [1.8]−1.24 to 1.02
Complete abortion1951 (97.5)2086 (97.9)0.850.57 to 1.29
Total surgical intervention49 (2.5)45 (2.1)1.160.77 to 1.75
Indications for uterine evacuation
Incomplete27 (1.4)39 (1.8)1.310.80 to 2.14
Missed7 (0.4)4 (0.2)0.530.15 to 1.8
Continuing pregnancy11 (0.6)2 (0.1)5.881.30 to −26.59
Laparoscopy4 (0.2)0

Prior to changing the regime, 2000 women were included in the initial analysis. Of these 928 (46.4%) were at ≤49 days of gestation and 1072 (53.6%) were at 50–63 days of gestation. The complete abortion rate in the lower gestation band was 98.5% (914/928) compared with 96.7% (1037/1072) in the higher band with a significant difference between the two groups (P= 0.01). The ongoing pregnancy rates were 0.2% (2/914) and 0.8% (9/1037) in the lower and higher gestational bands, respectively (P= 0.18). Linear regression was used to assess the effect of gestation on the outcome complete abortion. The likelihood of a complete abortion decreased with increasing gestation (t= 3.88, P < 0.0001).

A total of 2131 women were included in the analysis since the regimen was changed to administer a second dose of prostaglandin if required. Of these, 1084 (50.9%) women were at ≤49 days of gestation and 1047 (49.1%) were at 50–63 days of gestation. The complete abortion rate in the lower gestation band was 97.6% (1058/1084) compared with 98.2% (1028/1047) in the higher band with no significant difference between the two groups (OR = 0.75, 95% CI = 0.41 to 1.36). There were only two ongoing pregnancies (0.2%) at 50–63 days of gestation compared with none in the lower gestational band. Linear regression was used to assess the effect of gestation on the outcome complete abortion. Gestation had no effect on complete abortion following change of the regimen (t=−1.29, P= 0.19).

Table 2 shows the failure rates in relation to gestation (by week) using the initial regimen (single dose) and the modified regimen (two doses if required). Following the use of two doses of prostaglandin, gestation had no effect on the outcome measure complete abortion.

The mean age [SD] in years of women having a failed medical abortion was 28.2 [6.0] and of those having a successful abortion was 26.09 [6.7] (95% CI = 0.73 to 3.5). Older women presented at earlier gestations compared with younger women (P= 0.01). Women who were parous (P < 0.0001) and had a previous termination (P < 0.0001) were older than those who did not (see Tables 3–5).

The induction-to-abortion interval could be accurately determined for 3457 women (85.7%). Of these, 2249 (65.1%) aborted within four hours of receiving misoprostol, 3174 (91.8%) within 6 hours, 3410 (98.6%) within 8 hours and 3453 (99.9%) within 10 hours of receiving misoprostol. The mean [SD] induction-to-abortion interval was 4.0 [1.6] hours (Fig. 1). There was no significant difference in the induction-to-abortion interval in relation to parity (P= 0.92), previous termination (P= 0.35) or number of doses of prostaglandin used (P= 0.85). However, the mean induction-to-abortion interval was significantly longer in women in the higher gestational band (50–63 days) compared with those at gestations ≤49 days (P < 0.0001) (Fig. 2).

Figure 2.

Induction-to-abortion interval in related to gestational group.

Linear regression was used to assess the effect of interactions of gestation (P < 0.001), age (P= 0.001) and previous pregnancy (P= 0.22) on the induction-to-abortion interval. The final model showed that gestation (t= 4.08, P < 0.0001) and age (t= 3.43, P= 0.001) had a significant influence on the induction-to-abortion interval, with the induction-to-abortion interval being longer at higher gestations and in older women. Previous pregnancy (t=−0.66, P= 0.50) had no effect on the induction-to-abortion interval.

The last 2131 women studied were offered an additional dose of prostaglandin if products of conception were not passed within 4 hours of the first dose. A total of 490 (23.6%) required a second dose of whom 441 (90.0%) were in the higher gestational band (OR = 15.38, 95% CI = 11.25 to 21.02).

Data on analgesia use were recorded for 3146 women (77.1%) women studied. Of these, 1155 (36.7%) required no analgesia, 1845 (58.6%) required oral analgesia only and 147 (4.7%) required parenteral opiate analgesia.

Women who had no previous pregnancy (P < 0.0001), no previous live birth (P < 0.0001) and those at 50–63 days of gestation (P= 0.01) required more analgesia than those with a previous pregnancy, live birth or at lower gestations. There was no association between previous termination (P= 0.06) and analgesia requirements.

Of the 502 women who were given a second dose of prostaglandin, 373 (74.3%) required analgesia. However, only 1615 (62.0%) of the 2606 women given a single dose of misoprostol required analgesia. The difference between the two groups was statistically significant (P < 0.0001, OR = 0.56, 95% CI = 0.45 to 0.69).

Each of the independent variables age, gestation, previous pregnancy, previous live birth and previous termination were analysed against the dependent variable complete abortion. Initially, age (OR= 1.04, 95% CI = 1.01 to 1.07), previous pregnancy (OR = 2.27, 95% CI = 1.43 to 3.60), previous live birth (OR = 1.81, 95% CI = 1.19 to 2.76) and previous termination (OR = 2.09, 95% CI = 1.37 to 3.19) had a significant effect on the dependent variable complete abortion. Gestation at termination (OR = 1.02, 95% CI = 0.99 to 1.05) had no effect on complete abortion. Multiple regression was then carried out to assess the influence of the variables age, gestation and previous pregnancy on the dependent variable complete abortion. The variable previous pregnancy (OR = 1.89, 95% CI = 1.11 to 3.16) was the only variable that had a significant effect on the outcome complete abortion, with women with no previous pregnancy more likely to have a complete abortion.

Multivariate analysis was carried out to study the effect of the dependent variable age, gestation, previous live birth and previous termination on the outcome complete abortion. There was a significant association between women who had no previous termination and successful abortion (OR = 1.77, 95% CI = 1.14 to 2.75).

Multivariate analysis was carried out to assess the effect of the independent variables age, gestation, previous live birth and previous termination on the dependent variable continuing pregnancy. Gestation at termination (OR = 1.01, 95% CI = 0.99 to 1.04) was the only variable that was associated with the dependent variable ongoing pregnancy with a higher chance of an ongoing pregnancy with advancing gestation.

A total of 10 women (0.2%) required haemostatic uterine evacuation and 43 women (1.0%) received oxytocics at the time of abortion because of heavy bleeding. Eight women (0.2%) required blood transfusion in association with the termination procedure. Six women were over 49 days of gestation and two were ≤49 days. Two women at 49 and 63 days of gestation required a blood transfusion on the day of termination due to heavy bleeding. The other five women were admitted with a history of heavy bleeding (within two weeks following the procedure), four of whom required surgical evacuation of the uterus for incomplete abortion and one woman was found to have a haemoglobin of 7 g/dl.

The management of 3993 of the 4131 women (96.7%) was completed on a day case basis, with 138 women (3.3%) requiring an overnight stay. A total of 46 (1.1%) women had an unscheduled visit to hospital due to problems associated with the termination procedure of whom 10 required antibiotics for presumed pelvic infection.

A total of 2732 women (66.1%) agreed to attend hospital for a follow up appointment of whom 2074 (75.9%) attended the hospital. Among these women, the most common problems reported were continued pain, vaginal bleeding and offensive discharge. A total of 66 women with symptoms of this type (2.4% of those seen for hospital follow up) were prescribed antibiotics for presumed genital tract infection. Additionally, 10 women with unscheduled visits were prescribed antibiotics (76/2778, 2.7%).

Discussion

In 1998 we published an initial review of 2000 consecutive women undergoing medical abortion using a low dose of mifepristone in combination with vaginal misoprostol13. More recently, Bartley et al.15 reviewed 3161 consecutive women undergoing medical abortion in routine clinical practice using a low dose of mifepristone in combination with vaginal gemeprost. Although there have been a number multicentre trials evaluating the efficacy of medical abortion using various regimes6,16,17, to our knowledge, this series represents the largest reported series in routine clinical practice in a single centre.

Our initial review of 2000 consecutive women showed that with increasing gestation, the surgical intervention rate was significantly higher13. Following this review, our regimen was modified to offer a second dose of misoprostol 4 hours after the first dose should abortion not be imminent. Following this modification, gestation ceased to have an effect on the efficacy of the regimen. When medical abortion was first introduced in France, it was only available up to ≤49 days of gestation, since the failure rates were thought to be higher with increasing gestation. In the UK, early medical abortion is available up to 63 days of gestation, although in most countries it is not carried out at later gestations (49–63 days) in view of the higher failure rates with increasing gestation. Spitz et al.18 showed that the failure rate in women undergoing medical abortion using mifepristone and a single dose of oral misoprostol was significantly higher with increasing gestation with an efficacy of only 77% at 57–63 days of gestation. The very low efficacy in this study may be attributed to the route of misoprostol used since it has been shown that the vaginal route is more effective than the oral route12. More recently, Bartley et al.15 showed that gestation was a strong predictor of successful medical abortion using 0.5–1 mg gemeprost vaginally. In our initial analysis using a single dose of vaginal misoprostol, the failure rate was higher with advancing gestation13. Hence, it is not only the route of administration of misoprostol that abolished the effect of gestation on successful outcome, it is the number of doses of prostaglandins used. We have also shown that using up to three doses of prostaglandins at 10–13 weeks of gestation has a success rate of up to 95–97%1,2.

Although administration of two doses of prostaglandin had no significant effect in the surgical evacuation rates among women at higher or lower gestations (P= 0.22), the ongoing pregnancy rates fell from 0.6% to 0.1% (P= 0.008). The ongoing pregnancy rates in this series is the lowest reported to date, which has been around 0.4% in the WHO multicentre trial6, 3% reported with oral misoprostol19 and 1.4% with vaginal gemeprost15. The low ongoing pregnancy rates in this study may be due to the route of administration of misoprostol and the number of doses administered. It is imperative to interrupt the pregnancy because of the possibility of birth defects following administration of misoprostol20.

It has been suggested that independently, previous pregnancy (both previous live birth and termination) have a significant effect on the outcome of treatment. However, multivariate analysis in this study showed that women who had no previous termination were more likely to have a successful abortion as shown by Spitz et al.18 although we have no explanation for this finding at present. Bartley et al.15 showed that previous pregnancy in addition to gestation was a strong predictor of successful outcome in women undergoing medical abortion with the failure rate being higher in multiparous women. Initially, we found an association between previous live birth and outcome but after adjusting for confounding factors the association was no longer found to be significant. However, when we excluded women who had a previous termination and assessed the effect of parity on the outcome complete abortion, we found that multiparous women were more likely to have a failed medical abortion (OR = 2.03). We found no significant association between gestation and successful outcome and this may be attributable to the number of doses of prostaglandin used since our initial review showed an association13.

Our study also showed a significant association between analgesia use and gestation as seen in other studies18,21. A similar association has also been seen among analgesia use, previous pregnancy and live birth15,21. Women who required two doses of prostaglandin were more like to require analgesia compared with those who required a single dose. Spitz et al.18 studied 2121 women in 17 sites undergoing early medical abortion using mifepristone and oral misoprostol (400 μg), with 68% requiring oral analgesia, in addition to 29% requiring narcotic analgesia. Westhoff et al.21 studied the predictors of analgesia use in the same group of women studied by Spitz et al. and found that the clinic providing care was the most important determinant of who received narcotic analgesia. In our study that was carried out in a single centre, nearly 63% required oral analgesia and all women were administered narcotic analgesia as per protocol. However, only 4.7% required additional parenteral opiates. Should we have resorted to administering non-narcotic analgesia as first line pain relief, the usage of narcotic analgesia in our study may have been much lower that the above studies18,21.

Conclusion

Mifepristone (200 mg) in combination with one to two doses of vaginal misoprostol is an effective regimen for early medical abortion. Addition of a second dose of misoprostol reduces the ongoing pregnancy rates significantly and abolishes the effect of gestation on successful outcome. Previous termination was the strongest predictor of failed medical abortion. However, in women with no previous termination, multiparity was also associated with a higher failure rate.

Acknowledgements

The authors wish to thank the research fellows who have contributed to the development of this study. They would also like to thank the Pregnancy Counselling Sisters for their invaluable contribution to the service.

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