PACE REVIEW Medical management of first-trimester induced abortion and miscarriage Shamim Amis Jonathon Evans-Jones MRCOG FKCOG urgical evacuation is the mainstay of treatment in the effects of bleeding per vaginum, diarrhoea and vomiting. In UK for first-trimester termination of pregnancy and a randomised trial, where 1 mg versus 0.5 mg of gemeprost Smiscarriage and, although a niinor procedure, it has an was compared, the complete abortion rate was similar for associated considerable morbidity and mortality.' Induced the two groups (98-100%), although the incidence of abortion in the UK is now a safe procedure but on a global adverse effects was significantly lower in the latter group.'O scale continues to be a major cause of maternal mortality.2 Misoprosto1 is a synthetic analogue of prostaglandin E, and Medical management would provide a safe and effective causes increased uterine contractility with a low incidence of alternative. Many women would prefer to be given the other unwanted effects." The main advantages over choice and avoid the risks associated with anaesthesia and gemeprost are that it does not require refngeration, is cheaper surgery.l Recent studies have confirmed high acceptability and can be administered orally or vaginally. One gemeprost rates, showing that 8496% of women would choose pessary costs &22, whereas the equivalent dose of misoprostol medical treatment for a subsequent abortion." is just over The uterotonic properties are enkanced if women are pretreated with rmfepristone, reflecting the effect BACKGROUND of antiprogesterones in increasing sensitivity to prostaglandins. The drugs used for medically induced abortion in the UK When misoprostol is used in combination with mifepristone, include an antiprogesterone,mifepristone, and several prost- the vaginal route has been shown to be superior to the onl aglandin analogues, including gemeprost and misoprostol. route (95% versus 87%, respe~tively).'~The incidence of Mifepristone is the 11P-dimethyl-amino-phenyl derivative of adverse effects was also reduced in the former group. %s is norethindrone and has a high affinity for progesterone and an unlicensed use of misoprostol and should be emphasised glucocorticoid receptors5 Receptor binding in the placenta is to the patient prior to its administration.'* followed by inefficient transcription of progesterone genes, so that mifepristone effectively blocks the progesterone recep- GUIDELINES FOR MEDICAL TERMINATION tors in the decidua, myometrium and cervix. This usually Details relating to orgarhtional, clinical and supportive results in termination of the pregnancy. When mifepristone aspects of abortion care are given in the evidence-based is used alone, the success rate is variable and never greater guidehe produced by the RCOG.'j The earlier the termination than 8896.6.7This is increased to 9496% when mifepristone is performed, the more effective is the procedure, with a lower is combined with a prostaglandin such as gemeprost or risk of complications. At six to seven weeks, medical termin- misoprostol. The recommended dose of oral mifepristone is ation is the method of choice and is effedive in 97.5% of cases. 600 mg followed by 1 mg of gemeprost given 48 hours later. The effectiveness falls to 93% for gemeprost and 89.1% for However, subsequent studies have shown that a lower dose misoprostol at between seven and nine weeks. The latter of nlifepristone (200 mg) is equally effective."9 induces less powerful uterine contrac7ions at th~~ Gemeprost is a prostaglandin El analogue and is effective An ultrasound determination of gestational age will help in 95% of cases in combination with mifepristone at less than improve efficacy and confirm that the pregnancy is intra- 63 days of amenorrhoea. Initial studies were with a dose of uterine. If the fetus is found to be non-viable, this might help 1 mg. The high efficacy is associated with increased adverse to allay some of the guilt and anxiety felt by women The Ohstetn'ciun G Gynaecologist April 2002 Vol. 3 No. 2 Medicul munugement offirst-trimester induced abortion and miscam’age PA- mw undergoing a termination of pregnancy. l8 century has interest in this field been rekindled.2’ As well as Within the UK, mifepristone must be administered on avoiding complications of surgery, it is also less expensive licensed premises or in a hospital. Prostaglandins are then than surgery) with a saving of A50 per case.26 administered 3648 hours later, with the patient being kept Various effjcacy rates for medical treatment of miscar- under observation for four to six hours. Facilities for riages have been cited. Factors determining success are the immediate suction curettage should be available in the event type of miscarriage, the gestation, the type, dose and route of excessive vaginal bleeding. A two-week follow-up is of administration of medication and whether an ultrasound important, with a repeat pregnancy test and an ultrasound scan is used to assess completion. scan if products of conception have not been identified. The efficacy of medical treatment for silent miscarriage Women who are rhesus (D) negative should be given anti- varies from 52% to 929’6, depending on the doses of D rhesus immunoglobulin simultaneously. Contraindications mifepristone and misoprostol.2’z28Nielsen et al.27used lower to medical termination are shown in Tuble 1. oral doses of both and defined success objectively using transvaginal ultrasound to detect retained products. Vaginal misoprostol is effective in 88% of cases.‘‘) In silent miscarriage A bvoi u te the progesterone level is already low and therefore the Pregnancy of more than 63 days antiprogesterone may be omitted. This has important implic- 0 Suspected ectopic pregnancy ations in countries where mifepristone is unavailabk. Further 0 Adrenal insufficiency studies in the UK indicate that the success rate with 0 Long-term glucocorticoid therapy 0 Haemoglobinopathies or anticoagulant therapy mifepristone and vaginal misoprostol is similar to that seen in 0 Anaemia induced abortion. 0 Known allergy to mifepristone or prostaglandin In the case of incomplete miscarriage, use of either oral 0 Smokers over 35 years of age 0 Potphyria misoprostol (400 mg) alone or intramuscular sulprostone Re1RelativeRtive (0.5mg) has been shown to be effective in 95% of cases. a.0 Hypertension Sulprostone was withdrawn after three cases of myocardial Ia Severe asthmaI infar~tion.~~Subsequent studies have shown a lower success rate of misoprostol in incomplete nliscaniages ADVERSE EFJ3CTS AND COMPLICATIONS ([email protected]%).31~3’The discrepancy between these two studies The most common adverse effects are gastrointestinal and (de Jonge et al.jl and Cliung et aZ.jz)can be explained by the are mainly related to the prostaglandins. Besides nausea and difference in the mean duration of amenorrhoea (80 and 66 vomiting, headaches, dizziness and tiredness can occur. days, respectively) and the use of pelvic ultrasound. The Haemorrhage requiring transfusion is a recognised complic- morbidity in those treated medically was lower than in those ation of both surgical and medical treatment and the risk requiring surgery (1.7% versus 6.6%),3 increases with gestational age. Blood loss before nine weeks In the only published patient-centred partdly randomised of gestation is similar for both methods.I8 Significant blood controlled trial comparing the medical method with surgd loss necessitating a transfusion occurs in 0.7-1% of evacuation, dlferent regimens of misoprostol and mife- Abdominal pain requiring analgesia, and in particular pristone were used for silent and incomplete parented analgesia, is greater with medical abortion than Complete evacuation of the utetus was assessed by history with surgical abortion (28.5-350/0).~~~’~This is not surprising and clinical examination, without resorting to pelvic ultra- as the woman is fully conscious during medical treatment. sound. The overall success rate was 93% for the medical Approximately 5% of women require surgical curettage method and 98% for surgery (P=0.004). In the case of silent following medical treatment. l9 The continuing pregnancy misamage, the efficacy was greatest for those pregnancies of rate after rnifepristone and gemeprost is 0.3%. If oral miso- less than ten weeks or with a sac diameter of less than 24 mm prostol is used, the risk can be as high as 7%.13 Although (92-94%) and was not statistically signiticantly different from there has been no reported fetal abnormality with mife- that of surgery. In women with incomplete miscarriage, the pristone, misoprnstol has been associated with defective success rate for both methods was 100%. formation of the frontal and temporal regions of the skull Gemeprost used alone for miscarriage is effective in 77% and limbs, due to vascular disr~iptioii.~~,~*In view of this, it of cases at gestations of less than 13 weeks.33 The dis- is recommended that unsuccessful medical termination advantages of using gemeprost rather than misoprostol should be followed by surgical evacuation. have already been mentioned. The proportion of women requesting medical treatment MEDICAL MANAGEMENT for miscarriage is the Same as the proportion requesting Miscarriage commonly occurs in 15-209’6 of pregnancies medical termination (20%),3,2i although with experience within the first trimester. The routine management of such this is likely to increase. The main reasons stated were cases is still surgical evacuation. Although medical manage- avoidance of general anaesthesia or surgery (57%) and ment of miscarriage with herbal remedies was known feeling ’more natural’ and ‘in control’ of the process (36%). before the 13th century, only in the last decade of the 20th The acceptability of medical treatment over surgery was the 713e Obstetriciun & Gynaecologist ilpril2001 Vol. 3 AO. 2 89 pkw;zm Shamim Amis, Jonathon Evansgones same for both incomplete and silent miscarriages of less 11 Norman p.,Thong KJ, Haird u1’.Ulerine contractilily and induction (if than ten weeks. Both these trials (Henshaw et ~1.~and abortion in early pregnancy by rnisoprostol and mifepristone.