A randomized trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion at 13–20 weeks gestation

Haitham Hamoda1,2, Premila W. Ashok1, Gillian M.M. Flett1 and Allan Templeton1

1 Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen Maternity Hospital, Foresterhill, Aberdeen AB25 2ZD, UK

2 To whom correspondence should be addressed. Email: ogy262{at}abdn.ac.uk


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
BACKGROUND: Several studies have now reported the successful use of the sublingual administration of misoprostol for medical abortion in the first trimester. The objective of this study was to assess the acceptability to women, the efficacy of the regimen, as well as the acceptability to staff of sublingual versus vaginal administration of misoprostol following mifepristone for medical abortion at 13–20 weeks gestation. METHODS: Women were randomized by opening consecutive sealed envelopes generated using random number tables. Mifepristone (200 mg) was followed 36–48 h later by sublingual administration of misoprostol 600 µg or vaginal misoprostol 800 µg. This was followed by 3 hourly doses of misoprostol 400 µg administered sublingually or vaginally. RESULTS: A total of 76 women were randomized. Of women in the sublingual group, 24 (66.7%) expressed satisfaction with the route of misoprostol administration compared with 25 (62.5%) in the vaginal group. A higher proportion in the sublingual group used intramuscular opiates. There was no significant difference in the surgical evacuation rate between the sublingual (three out of 36 women, 8.3%) and vaginal groups (one out of 40, 2.5%), (P=0.26) and acceptability to staff was the same for both methods. CONCLUSIONS: Sublingual administration of misoprostol following mifepristone is an acceptable and effective alternative to vaginal administration for medical abortion at 13–20 weeks gestation. However, women should be advised about the greater likelihood of requiring stronger analgesia.

Key words: medical abortion/midtrimester/mifepristone/misoprostol/sublingual


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
During 2002, a total of 176 689 abortions were carried out in England and Wales, of which 10.8% were between 13 and 19 weeks gestation. Of these, 10 987 (58%) were carried out using vacuum aspiration, 4461 (24%) using dilatation and evacuation (D&E) and 3317 (18%) using medical methods (Department of Health Bulletin, 2003Go). During 2003, a total of 12 217 abortions were carried out in Scotland. Of these, 52.7% were undertaken using medical methods. A total of 904 (7.4%) abortions were >14 weeks gestation (Information and Statistics Division Scotland, 2004Go).

Published evidence provides reassurance on the safety and efficacy of medical abortion using mifepristone in combination with a prostaglandin analogue, as well as D&E for termination of pregnancy in the midtrimester (Darney and Sweet, 1989; Ngai et al., 2000Go; Tang et al., 2001Go; Autry et al., 2002Go; Bartley and Baird, 2002Go; Ashok et al., 2004Go). The Royal College of Obstetricians and Gynaecologists evidence-based Clinical Guidelines state that medical abortion is an appropriate, safe and effective method for midtrimester abortion. The Guidelines also state that conventional suction termination would be an appropriate method for gestations between 12 and 15 weeks, while D&E would be a safe and effective option for gestations above 15 weeks when undertaken by specialist practitioners with a sufficient workload to maintain their skills (Royal College of Obstetricians and Gynaecologists, 2004Go).

El-Refaey and Templeton (1995)Go showed that vaginal administration of misoprostol was more effective and better tolerated compared with oral administration in the context of medical abortion up to 63 days gestation. It has been reported, however, that women prefer the oral route of administration and find it more convenient (Ho et al., 1997Go). Several studies have now reported the successful use of the sublingual route of misoprostol administration for medical abortion in the first trimester (Tang and Ho, 2001Go; Tang et al.Go, 2002aGo, 2003Go; Hamoda et al., 2003Go). This route avoids the inconvenience of vaginal administration, bypasses the first pass liver effect and offers additional choice to women undergoing abortion.

We carried out this randomized trial to compare the acceptability as well as the efficacy of the sublingual and vaginal routes of misoprostol administration following mifepristone in the context of medical abortion at 13–20 weeks gestation.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
The study was carried out at the Aberdeen Royal Infirmary during the period April 2003–September 2004 with approval from the Grampian Research and Ethics Committee. Women with a viable singleton intrauterine pregnancy (confirmed by ultrasound scan) requesting medical abortion between 13 and 20 weeks gestation were asked to participate. Exclusion criteria were: women under the age of 16 years, severe asthma, haemorrhagic disorders and treatment with anticoagulants, known allergy to prostaglandins, history of cardiac disease, smoking over the age of 35 years with ECG abnormalities, and breast feeding. Women wishing to participate gave written consent and were randomized to sublingual or vaginal administration by opening consecutive sealed opaque envelopes generated using random number tables. These were prepared by one of the authors (H.H.) who did not take part in recruitment. The study was not blinded and did not use placebo control tablets, so that both staff and women were aware of the route of administration used. This was necessary in order to assess the acceptability to patient and staff of the route of administration used.

Gestational age was estimated by ultrasound scan measurement in all cases. Samples for full blood count, blood group and rubella antibody titres were assessed at the initial clinic consultation and no further blood samples were taken on admission. All women were screened for Chlamydia trachomatis and those up to the age of 20 years also received prophylactic antibiotic treatment (azithromycin and metronidazole) on the day of misoprostol administration, as per hospital protocol.

Outcome measures assessed included the acceptability of the route of misoprostol administration to the women and side effects experienced, efficacy of the method and acceptability of the route of misoprostol administration to the staff based on their assessment of the patient.

Women received mifepristone 200 mg administered orally under nursing supervision. They were allowed home and re-admitted to hospital 36–48 h later for misoprostol administration. Women in the sublingual group received misoprostol 600 µg, given sublingually, while those in the vaginal group received a dose of 800 µg administered vaginally. This was followed by 3 hourly doses of misoprostol 400 µg administered sublingually or vaginally to a maximum of five doses in total (initial dose plus four doses of 400 µg). After delivery of the fetus and placenta, syntometrine (ergometrine 500 µg and oxytocin 5 IU) was given to women intramuscular. Surgical evacuation was offered to women if the placenta was not delivered within 1 h of delivery of the fetus. The regimen used for the vaginal group was based on cumulative experience (Ashok and Templeton, 1999Go; Ashok et al., 2004Go), while the regimen and doses used for the sublingual group were based on our previous pilot work for early first trimester abortion and the reported absorption pharmacokinetics studies for the different routes of misoprostol administration (Tang et al., 2002bGo; Hamoda et al., 2003Go). Successful outcome was defined as abortion occurring with five doses of misoprostol, i.e. within 15 h of the administration of the first dose of misoprostol, i.e. within 3 h of the fifth dose of misoprostol. The induction to abortion interval was defined as the time interval in hours from administration of misoprostol to passing the products of conception.

If abortion did not occur within this regimen (within 3 h of the fifth dose of misoprostol), the treatment was considered unsuccessful and further treatment followed standard hospital protocols for the management of failed midtrimester medical abortion as reported by Ashok et al. (Ashok and Templeton, 1999Go; Ashok et al., 2004Go). This involved offering further medical treatment including mifepristone 200 mg orally and further vaginal administration of misoprostol.

Following administration of misoprostol, the pulse, blood pressure and temperature were monitored hourly. Analgesia was administered as required. Prescriptions used included: oral analgesia (paracetamol and dihydrocodeine); non-steroidal anti-inflammatory agents (diclofenac sodium), given rectally; and parenteral analgesia (intramuscular opiates). Women may have been offered more than one dose or a combination of analgesia. The strongest preparation used was recorded and reported in this study. Products of conception were identified by visual inspection. Women were observed on the ward for 2 h after the abortion, before being discharged home.

A questionnaire was given to the women to assess side effects experienced (nausea, vomiting, diarrhoea, shivering, lethargy, headache, hot flushes, dizziness and unpleasant taste in the mouth) and also the acceptability of the route of misoprostol administration used. Women who expressed dissatisfaction were asked about the reasons for dissatisfaction and were given a list of options to choose from. These included: ‘unpleasant taste in the mouth’, ‘did not like the tablets’, ‘tablets did not completely dissolve’, ‘side effects experienced’ and ‘other’, where women were asked to mention any other reasons for dissatisfaction. Vaginal bleeding was assessed using a menstrual chart and recordings were subdivided using a 5-point scale to represent the severity of bleeding. The values were added to give a total vaginal bleeding score (TVBS) as used in previous studies (Ashok et al., 2002Go; Hamoda et al., 2004Go). Women were asked to complete the study questionnaire after abortion and prior to being discharged home. Pain severity was self-evaluated by women using visual analogue scales (Belanger et al., 1989Go; Ashok et al., 2002Go). Three visual analogue scales were used to assess the overall pain experienced, the most severe pain experienced and the pain relief achieved following analgesia. The scales used a 100 mm line with ‘painless’ at the 0 mm mark and ‘unbearable’ at the 100 mm mark for the former two scales, and ‘not at all’ and ‘very much’ for the latter scale.

Follow-up of women was carried out by the general practitioner (GP), Family Planning Clinic, Genito-Urinary Medicine Clinic or at the hospital. Women who were subsequently admitted to hospital with heavy bleeding suggestive of incomplete abortion were offered surgical evacuation or a medical regimen of up to three further doses of misoprostol 400 µg, as per hospital protocol. A notification system is in place for patients re-admitted with complications, and the details of re-admission were entered on the hospital termination of pregnancy database. Women were asked for permission to contact their GP 8 weeks following abortion to inquire about complications encountered following abortion, and written consent was obtained from those who gave permission.

The sample size was calculated using the Altman's nomogram (Gore and Altman, 1992Go), and based on previous studies (El-Refaey et al., 1993Go, El-Refaey and Templeton 1995Go; Webster et al., 1996Go). A sample size of 70 patients, using 80% power and at the 5% level of significance, would detect a difference of 0.67 on the Altman's nomogram. This would be equivalent to a difference of 2 h in the induction to abortion interval between the two groups, and this has been reported to be a clinically significant difference in patient acceptability (El-Refaey et al., 1993Go, El-Refaey and Templeton 1995Go; Webster et al., 1996Go).

Data were entered on a PC-held database and were analysed using the Statistical Package for Social Sciences (SPSS Version 13). Distribution of the samples was assessed using the Kolmogorov–Smirnov Z test. Variables that were normally distributed are presented as means and SDs and were analysed using the independent and paired t-test, while data not normally distributed are presented as medians and range and were analysed using the Mann–Whitney U-test. The {chi}2 or Fisher's exact tests were used as appropriate for independent nominal data. Confidence intervals (CIs) were used where appropriate, and statistical significance was defined as a P-value of <0.05. Analysis was by intention to treat, and the trial findings were reported following the CONSORT Guidelines.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
The study design and the number of women recruited to the study are shown in Figure 1, while the characteristics of the women in the study are shown in Table I. A total of 31 (86.1%) questionnaires were returned for women in the sublingual group, while 37 (92.5%) were returned for those in the vaginal group. Of the women in the sublingual group who did not complete the study questionnaire, two decided to continue with the pregnancy, a further two withdrew from the study before receiving treatment, while one continued with the study and had a complete abortion, but did not complete the study questionnaire. Of the three in the vaginal group who did not complete the questionnaire, two continued with the pregnancy while one withdrew from the study before having treatment. The acceptability data for the route of misoprostol administration for the women taking part in the study and for members of staff looking after them (based on their assessment of the patient) are shown in Table II. The side effects experienced by women in the study are shown in Table III. The incidence of lethargy and hot flushes was higher for women in the vaginal group, while that for unpleasant taste in the mouth was higher in the sublingual group. The woman who expressed dissatisfaction in the sublingual group mentioned the unpleasant taste in the mouth as the reason for her dissatisfaction, while the one in the vaginal group mentioned the tablets not dissolving as the reason. A further five patients who were either satisfied or answered ‘don't know' inadvertently answered this question. Of these, two in the sublingual group and one in the vaginal group experienced an unpleasant taste in the mouth. One woman in the sublingual group mentioned the tablets not dissolving, while another woman in the same group mentioned the side effects experienced with the tablets. The median (range) time required for admitting the patients (including the administration of the first dose of misoprostol) was 15 (10–25) min for those in the sublingual group and 20 (10–30) min for women in the vaginal group (P=0.30).



View larger version (17K):
[in this window]
[in a new window]
 
Figure 1. Study design and number of women recruited

 

View this table:
[in this window]
[in a new window]
 
Table I. The characteristics of the women in the sublingual and vaginal groups

 

View this table:
[in this window]
[in a new window]
 
Table II. Satisfaction with the route of misoprostol administration in the sublingual and vaginal groups for the women taking part in the study and members of staff attending them

 

View this table:
[in this window]
[in a new window]
 
Table III. Side effects experienced by women in the sublingual and vaginal groups

 
The outcomes of treatment and features of abortion for women in the sublingual and vaginal groups are shown in Table IV. The indications for surgery in women in the sublingual group were incomplete abortion with retained placenta and bleeding in two women [one of these was commenced on the failed medical abortion regimen (Ashok and Templeton, 1999Go; Ashok et al., 2004Go) and aborted after receiving a further (sixth) dose of misoprostol, but subsequently required surgery], while the third patient had surgical evacuation for incomplete abortion with heavy bleeding [the latter went on to receive the failed medical abortion regimen (Ashok and Templeton, 1999Go; Ashok et al., 2004Go) and aborted after receiving a total of eight doses of misoprostol, but subsequently required surgical evacuation]. One patient in the vaginal group had surgical evacuation for incomplete abortion with heavy bleeding. None of the patients aborted on mifepristone alone. All women apart from one aborted within 24 h, while one in the sublingual group had an induction to abortion interval of 29 h 35 min. Abortion was confirmed prior to discharge from hospital in all cases.


View this table:
[in this window]
[in a new window]
 
Table IV. Abortion outcomes and features of treatment for women in the sublingual and vaginal groups

 
A total of eight (22.2%) women in the sublingual group and 12 (30.0%) in the vaginal group attended follow-up with their GP, at the Family Planning Clinic or at the Genito-Urinary Medicine Clinic, while the remainder did not attend clinic follow-up.

One woman in the sublingual group required additional oxytocics following abortion for haemostatic control. Complications that required hospital admission within 8 weeks of abortion included pyrexia (temperature of >38°C) in one woman in the vaginal group, while five (two in the sublingual group, three in the vaginal group) were treated for suspected pelvic infection. One woman in the vaginal group received a blood transfusion, while one in the sublingual group was admitted to hospital 16 days following abortion and received further doses of misoprostol for incomplete abortion with heavy bleeding.

Complications were also assessed through questionnaires sent out to women's GPs 8 weeks following abortion. These were sent out for 61 (80.3%) women who gave us permission to contact their GP 8 weeks following abortion, and of these a total of 47 (61.8%) questionnaires were returned [25 (53.2%) women in the sublingual and 22 (46.8%) in the vaginal groups]. A total of 17 women had consulted their GP with problems related to the abortion. These included: irregular bleeding (10) suspected pelvic infection (one), psychological problems (anxiety, depression or emotional problems) (four), pelvic pain (one), lethargy (one) and contraceptive advice (five women). One woman attended with problems related to heroin addiction and methadone maintenance.


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
This randomized trial compared the sublingual route of misoprostol administration with the vaginal route following mifepristone in the context of medical abortion between 13 and 20 weeks gestation. The majority of women in both groups were satisfied with the route of misoprostol administration used. The findings suggested no difference in efficacy between the two routes of administration, although the study was not sufficiently powered to detect a clinically significant difference in this respect. There was no difference in the prevalence of gastrointestinal side effects between the two groups, although women in the sublingual group were more likely to experience an unpleasant taste in the mouth, while those in the vaginal group had a higher incidence of lethargy and hot flushes. There was no significant difference in pain scores as assessed by the visual analogue scales, although a higher proportion of women in the sublingual group used intramuscular opiates compared with those in the vaginal group, and this needs to be considered when interpreting the responses given for the visual analogue scales. Research is needed to evaluate the analgesia requirement, and the pain levels experienced by women before and after receiving analgesia, in order to assess these findings further.

The power size calculation was based on previous reports on this research topic, on the hypothesis that a reduction in the induction to abortion interval is likely to improve the acceptability to women (El-Refaey et al., 1993Go, El-Refaey and Templeton 1995Go; Webster et al., 1996Go). The calculation was not based on efficacy as a total sample size of 2842 women would have been required to show a 3% difference in efficacy with 80% power. Given the efficacy demonstrated in other reports assessing this route of administration (Tang and Ho, 2001Go; Tang et al., 2002aGo, 2003Go; Hamoda et al., 2003Go) and the level of acceptability, the clinical relevance of such a sample size would be doubtful.

The study was not blinded and both the women and the staff attending them were aware of the route of misoprostol administration. A primary outcome for the study was the acceptability of the route of misoprostol administration. Awareness of the route of administration would have allowed women to assess this based on their experience. However, most did not have experience with the route of administration other than the one used. This could have introduced bias and needs to be taken into consideration when interpreting the data.

The majority of women declined follow-up. However, abortion was confirmed in hospital and prior to home discharge in all cases. Furthermore, the Aberdeen Royal Infirmary is the only referral hospital within a 50 mile radius for both gynaecological and maternity cases, and all complications requiring hospital admission would have been referred. A notification system is in place for patients re-admitted with abortion complications, and the details of re-admission are entered on the database. It has been suggested that giving women simple instructions and advice about detecting complications would be a suitable alternative to follow-up, with little evidence that mandatory follow-up visits detect conditions that women could not learn to recognize themselves (Grimes, 1997Go; Grossman et al., 2004Go).

A randomized trial from Hong Kong compared the sublingual with the vaginal route of misoprostol administration in the context of medical abortion between 12 and 20 weeks gestation (Tang et al., 2004Go). Misoprostol was given alone (without mifepristone) in 3 hourly doses of 400 µg. The study reported no difference in the rate of successful abortion at 48 h, although the success rate at 24 h was significantly higher in the vaginal group. The median induction to abortion interval was 13.8 h for the sublingual group and 12.0 h for the vaginal group. More women in the sublingual group expressed satisfaction with the route of misoprostol administration they were allocated, compared with those in the vaginal group. There was no significant difference in the prevalence of gastrointestinal side effects or the need for analgesia for women in the two groups, although a higher proportion of women in the vaginal group had pyrexia. Nearly all the women in our study aborted within 24 h of receiving misoprostol, and the induction to abortion interval for both study groups was less than half of that noted by Tang et al. (2004)Go. This could be related to the pre-treatment with mifepristone in our study and the higher initial dose of misoprostol used. Further research is needed to assess the optimal regimen for use in this context.

A study on the pharmacokinetics of the sublingual, vaginal and oral routes of misoprostol administration with medical abortion showed that the sublingual route had a shorter time to peak concentration, higher serum peak concentration and greater area under the curve concentration compared with vaginal administration (Tang et al., 2002bGo). This might explain the higher prevalence of side effects reported with the sublingual route of misoprostol administration in the early first trimester of pregnancy (Hamoda et al., 2003Go; Tang et al., 2003Go). The pharmacokinetics study, however, used a single dose of misoprostol 400 µg and only measured serum levels up to 6 h. At the end of 6 h, serum levels were higher in the vaginal group compared with the sublingual group and this might explain the similar prevalence of prostaglandin-related gastrointestinal side effects noted in our study as these women received several doses of misoprostol and had a longer induction to abortion interval compared with those reported for women in the early first trimester (Hamoda et al., 2003Go; Tang et al., 2003Go). This and the higher initial dose of misoprostol used in the vaginal group could explain the higher incidence of hot flushes noted in the vaginal group in our study. These findings are consistent with those of Tang et al. (2004)Go which showed a higher incidence of fever with vaginal administration. Further research is needed to assess the absorption kinetics for higher doses and repeated doses of misoprostol in the context of medical abortion.

Aronsson et al. (2004)Go reported a study on the effect of misoprostol on uterine contractility following different routes of administration (sublingual, vaginal and oral). The time from start of treatment to start of effect (increase in uterine tonus) and to maximum tonus elevation was shorter with sublingual compared with vaginal administration. The study also showed that the increase in uterine activity 2 h after administration and thereafter was similar for both the sublingual and vaginal groups. These findings suggest that sublingual administration results in a more rapid effect on uterine contractility and may explain the higher requirement for intramuscular opiates (and hence presumably a higher perception of pain) noted in the sublingual group in our study.


    Conclusion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
This study suggests that sublingual administration of misoprostol following mifepristone is an acceptable and effective alternative to vaginal administration in the context of medical abortion at 13–20 weeks. However, women who received misoprostol sublingually were more likely to require stronger analgesia preparations compared with those receiving misoprostol vaginally. Sublingual administration offers additional choice to women, in particular those wishing to avoid vaginal administration.


    Acknowledgements
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
We wish to thank Louise Craigie, Morag McBain and Jane Beattie from the Pregnancy Advisory Service for their contribution to this study.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
Aronsson A, Bygdeman M and Gemzell-Danielsson K (2004) Effects of misoprostol on uterine contractility following different routes of administration. Hum Reprod 19, 81–84.[Abstract/Free Full Text]

Ashok PW and Templeton A (1999) Nonsurgical mid-trimester termination of pregnancy: a review of 500 consecutive cases. Br J Obstet Gynaecol 106, 706–710.[ISI][Medline]

Ashok PW, Kidd A, Flett GMM, Fitzmaurice A, Graham W and Templeton A (2002) A randomized comparison of medical abortion and surgical vacuum aspiration at 10–13 weeks gestation. Hum Reprod 17, 92–98.[Abstract/Free Full Text]

Ashok PW, Templeton A, Wagaarachchi PT and Flett GMM (2004) Midtrimester medical termination of pregnancy: a review of 1002 consecutive cases. Contraception 69, 51–58.[CrossRef][ISI][Medline]

Autry AM, Hayes EC, Jacobson GF and Kirby RS (2002) A comparison of medical induction and dilation and evacuation for second-trimester abortion. Am J Obstet Gynecol 187, 393–397.[CrossRef][ISI][Medline]

Bartley J and Baird DT (2002) A randomised study of misoprostol and gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy. Br J Obstet Gynaecol 109, 1290–1294.

Belanger E, Melzack R and Lauzon P (1989) Pain of first-trimester abortion: a study of psychosocial and medical predictors. Pain 36, 339–350.[CrossRef][ISI][Medline]

Darney PD and Sweet RL (1989) Routine intraoperative ultrasonography for second trimester abortion reduces incidence of uterine perforation. J Ultrasound Med 8, 71–75.[Abstract]

Department of Health Bulletin 2003/23 (2003) Abortion Statistics for England and Wales 2002. London.

El-Refaey H and Templeton A (1995) Induction of abortion in the second trimester by a combination of misoprostol and mifepristone: a randomized comparison between two misoprostol regimens. Hum Reprod 10, 475–478.[Abstract]

El-Refaey H, Hinshaw K and Templeton A (1993) The abortifacient effect of misoprostol in the second trimester. A randomized comparison with gemeprost in patients pre-treated with mifepristone (RU486). Hum Reprod 8, 1744–1746.[Abstract]

El-Refaey H, Rajasekar D, Abdalla M, Calder L and Templeton A (1995) Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med 332, 983–987.[Abstract/Free Full Text]

Gore SM and Altman DG (1992) Statistics in Practice. British Medical Association, London.

Grimes DA (1997) Medical abortion in early pregnancy: a review of the evidence. Obstet Gynecol 89, 790–796.[Abstract/Free Full Text]

Grossman D, Ellertson C, Grimes DA and Walker D (2004) Routine follow-up visits after first-trimester induced abortion. Obstet Gynecol 103, 738–745.[Abstract/Free Full Text]

Hamoda H, Ashok PW, Dow J, Flett GMM and Templeton A (2003) A pilot study of mifepristone in combination with sublingual or vaginal misoprostol for medical termination of pregnancy up to 63 days gestation. Contraception 68, 335–338.[CrossRef][ISI][Medline]

Hamoda H, Ashok PW, Flett GMM and Templeton A (2004) A randomized controlled comparison of sublingual and vaginal administration of misoprostol for cervical priming before first-trimester surgical abortion. Am J Obstet Gynecol 190, 55–59.[CrossRef][ISI][Medline]

Ho PC, Ngai SW, Liu KL, Wong GC and Lee SW (1997) Vaginal misoprostol compared with oral misoprostol in termination of second-trimester pregnancy. Obstet Gynecol 90, 735–738.[Abstract/Free Full Text]

Information and Statistics Division Scotland (2004) Abortion Statistics in Scotland 2003. ISD Scotland Health Briefing, Edinburgh.

Ngai SW, Tang OS and Ho PC (2000) Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg every 3 h) misoprostol when combined with mifepristone in termination of second trimester pregnancy. Hum Reprod 15, 2205–2208.[Abstract/Free Full Text]

Royal College of Obstetricians and Gynaecologists (2004) The care of women requesting induced abortion. Evidence-based Clinical Guideline number 7.

Tang OS and Ho PC (2001) Pilot study on the use of sublingual misoprostol for medical abortion. Contraception 64, 315–317.[CrossRef][ISI][Medline]

Tang OS, Thong KJ and Baird DT (2001) Second trimester medical abortion with mifepristone and gemeprost: a review of 956 cases. Contraception 64, 29–32.[CrossRef][ISI][Medline]

Tang OS, Miao BY, Lee SWH and Ho PC (2002a) Pilot study on the use of repeated doses of sublingual misoprostol in termination of pregnancy up to 12 weeks gestation: efficacy and acceptability. Hum Reprod 17, 654–658.[Abstract/Free Full Text]

Tang OS, Schweer H, Seyberth HW, Lee SWH and Ho PC (2002b) Pharmacokinetics of different routes of administration of misoprostol. Hum Reprod 17, 332–336.[Abstract/Free Full Text]

Tang OS, Chan CC, Ng EH, Lee SW and Ho PC (2003) A prospective, randomized, placebo-controlled trial on the use of mifepristone with sublingual or vaginal misoprostol for medical abortions of less than 9 weeks gestation. Hum Reprod 18, 2315–2318.[Abstract/Free Full Text]

Tang OS, Lau WN, Chan CC and Ho PC (2004) A prospective randomised comparison of sublingual and vaginal misoprostol in second trimester termination of pregnancy. Br J Obstet Gynaecol 111, 1001–1005.

Webster D, Penney GC and Templeton A (1996) A comparison of 600 and 200 mg mifepristone prior to second trimester abortion with the prostaglandin misoprostol. Br J Obstet Gynaecol 103, 706–709.[ISI][Medline]

Submitted on February 17, 2005; resubmitted on March 15, 2005; accepted on March 23, 2005.





This Article
Abstract
Full Text (PDF )
All Versions of this Article:
20/8/2348    most recent
dei037v1
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Request Permissions
Google Scholar
Articles by Hamoda, H.
Articles by Templeton, A.
PubMed
PubMed Citation
Articles by Hamoda, H.
Articles by Templeton, A.