Medical methods of abortion

The recommended method for medical abortion is mifepristone, a progesterone receptor antagonist, followed 1–2 days later by misoprostol, a synthetic prostaglandin analogue. This regimen is effective and appropriate at any gestation[17].

Mifepristone is administered orally and the recommended dose is 200 mg. Level 1B evidence from a randomized trial showed that a dose of 200 mg of mifepristone is as effective as 400 mg or 600 mg[18]. This study used vaginal gemeprost rather than misoprostol, but level III evidence from large case series using oral misoprostol following 200 mg or 600 mg of mifepristone confirmed that there was no difference in efficacy between the two doses of mifepristone, with a reduced cost of the lower dose. This applies at all gestational ages[19].

Gemeprost is a prostaglandin E1 analogue, which was used routinely for a number of years. It is much more expensive than misoprostol, requires refrigeration and can only be administered vaginally. A series of studies reviewed in a UK RCOG guideline[2] demonstrated that misoprostol is equally, if not more effective than gemeprost in early medical abortion, cervical priming and medical abortion from 13 to 24 weeks of gestation[2]. Misoprostol is therefore the prostaglandin analogue of choice for abortion care. A number of other prostaglandins, such as sulprostone and prostaglandin F2α, are no longer used because of their adverse side effects and relative lack of efficacy.

Several of the recommended regimens and routes of administration of mifepristone and misoprostol are outside their product licenses. However, the European Economic Community Council Directive 65/65/EEC specifically permits doctors to use “licensed medicines for indications or in doses or by routes of administration outside the recommendations given in the licence”[20].

Women should be informed before a drug is prescribed for an unlicenced indication. Mifepristone and misoprostol can be dispensed by pharmacists and administered by nurses and midwives, provided a medical practitioner has prepared and signed an individual prescription.

Early medical abortion for pregnancies up to 9 weeks (63 days) of gestation

Mifepristone with misoprostol is highly effective, safe and acceptable up to 9 weeks of gestation. Efficacy rates up to 98% are reported[21]. Mifepristone 200 mg orally followed 24–48 h later by misoprostol 800 mcg administered by the vaginal, buccal or sublingual routes is recommended. Women should be advised of the greater risk of adverse effects with nonvaginal routes. Side effects include nausea, vomiting, diarrhea and fever.

At 7–9 weeks of gestation, if abortion has not occurred 4 h after administration of misoprostol, a second dose of misoprostol 400 mcg may be administered vaginally or orally depending on the woman’s preference and amount of bleeding[2].

Very few abortions under Ground E in the UK are performed under 9 weeks of gestation. There were only 20 such cases in England and Wales in 2012[15].

Medical abortion at 9–13 weeks of gestation

The recommended method for medical abortion between 9 and 13 weeks of gestation is mifepristone 200 mg administered orally followed 36–48 h later by misoprostol 800 mcg administered vaginally. A maximum of four further doses of misoprostol 400 mcg may be administered at 3-hourly intervals, orally or vaginally until expulsion of the products of conception occurs[2].

In a consecutive series of 483 women at 9–13 weeks of gestation, managed with mifepristone 200 mg followed 36–48 h later by repeated doses of misoprostol, the complete abortion rate was 95% and was gestation dependent[22]. In this series, up to five doses of misoprostol were permitted.

In a randomized trial involving 368 women at 10–13 weeks of gestation, participants were randomly allocated to medical or surgical abortion[23]. Complete abortion rates were 95% in the medical group and 98% in the surgical group, which was not significant. There were more adverse events in the medical group, but 70% of the women in this group indicated that they would opt for the same method in the future compared to 79% in the surgical group.

Medical abortion at 13–24 weeks of gestation

For medical abortion between 13 and 24 weeks of gestation, the following regimen is recommended. Mifepristone 200 mg administered orally followed 36–48 h later by misoprostol 800 mcg administered vaginally (or 400 mcg orally), then misoprostol 400 mcg orally, sublingually or vaginally at 3-hourly intervals, up to a maximum of four further doses[2].

Second-trimester medical abortion with mifepristone followed by a prostaglandin analogue is effective and is associated with shorter induction-to-abortion intervals than methods using a prostaglandin analogue alone. Evidence from a randomized trial of second trimester medical abortion showed that as for the first trimester, mifepristone at a dose of 200 mg is effective[24].

In a study of 386 consecutive cases between 12 and 20 weeks of gestation, an abortion rate of 97.9% was reported. If abortion was not completed by 15 h, a second dose of 200 mg mifepristone was given and the course of prostaglandin analogue repeated starting 24 h later. Treatment was completed within 36 h in over 99% of women.

A randomized trial comparing gemeprost and vaginal misoprostol 36–48 h after 200 mg mifepristone at 12–20 weeks’ gestation found no significant difference in complete abortion rates. Surgical evacuation rates and adverse effect profiles were similar in the two groups[25].

A systematic review, which included 40 randomized controlled trials (RCTs) addressing various agents and methods of administration for medical abortion between 12 and 28 weeks of gestation, concluded that the combination of mifepristone and misoprostol appeared to have the highest efficacy and shortest abortion time interval. The optimal route for administering misoprostol was vaginally, preferably using tablets at 3-hourly intervals. Further conclusions from this review were limited by the variable gestational age ranges and medical regimens of the included trials[17].

In countries where mifepristone is unavailable, misoprostol alone is a reasonable alternative. A higher total dose is needed and the induction to abortion interval is longer than with the combined regime, resulting in a higher incidence of side effects. However, the abortion will be completed within 24–36 h in 80–90% of women[26].

A meta-analysis of randomized trials comparing gemeprost with misoprostol showed that vaginal misoprostol compared to gemeprost was associated with a reduced need for opiate analgesia and surgical evacuation of the uterus[26].

Over 24 weeks of gestation

Over 24 weeks of gestation, the regimens used for medical abortion will generally be the same as for induction of labor. The dose of misoprostol should be reduced due to the greater sensitivity of the uterus to prostaglandins at higher gestational age. There is a lack of clinical studies to recommend specific doses. The International Federation of Gynecology and Obstetrics recommendations are misoprostol 25 mcg vaginally 6-hourly or orally at 2-hourly intervals based on the World Health Organization (WHO) guidance for induction of labor[27].

Regimens for delayed expulsion

There are few studies that report regimens for women who do not complete the abortion within 24 h. According to some protocols, if abortion does not occur, a further dose of mifepristone is given, followed by repeated vaginal misoprostol 12 h later[28]. A woman who fails to expel the fetus during the second day would receive a third dose of mifepristone followed by gemeprost 1 mg every 3 h. There is insufficient consensus to set a guideline for women who have a failed or delayed medical abortion. For women going on to a second or third day, D&E would be an appropriate option[28]. If possible, the woman should be given a preference of which way to proceed.

The Society of Obstetricians and Gynaecologists of Canada have advocated the use of intramuscular 15-methyl prostaglandin F2α (Hemabate) in women not responding to conventional therapy. It is successful in 95% cases within 10–20 h. The recommended dose for failed late second trimester abortion is 250 mcg by deep intramuscular injection repeated every 2 h as required. The total dose ranges from 1250–2500 mcg[29]. Hysterotomy is essentially a classical cesarean section that is rarely indicated as a method of abortion. It has a much greater morbidity and mortality than any other technique and should only be considered as a last resort after all medical therapies have failed.

Surgical evacuation of placenta

The placenta is usually expelled within a short time of the fetus. An injection of oxytocin may be given to help expulsion of the placenta. If the placenta is not delivered within 1–2 h, an infusion of 10 units oxytocin in 500 mL of normal saline at a rate of 2 mL per min or other uterotonic drugs may be given[30]. After expulsion, the placenta should be examined to ensure it is complete, and the woman observed in hospital to monitor vital signs and vaginal blood loss. If the uterus is not contracting well and bleeding persists, the uterine cavity should be explored to see whether there are any retained products of conception. Routine surgical evacuation of the uterus is not required following medical abortion. It should only be undertaken if there is clinical evidence that the abortion is incomplete or the woman starts bleeding excessively[2].

Medical abortion and prior cesarean section

The cesarean section rate is increasing worldwide. Although many studies have described the risk of complications with subsequent vaginal birth after a cesarean section, experience with second trimester abortion is limited. Uterine rupture, hemorrhage, hysterotomy and hysterectomy are possible complications of a second-trimester medical abortion in women with a uterine scar.

A systematic review concluded that although the use of misoprostol for second-trimester medical abortion was safe for women with one prior cesarean section, it was associated with incidence rates of 0.4% for uterine rupture and 0.2% for need for transfusion; the hysterectomy rate was 0%[31]. In another review, the reported risk of uterine rupture was less than 0.3%[32].

There are little data on the risk of uterine rupture for women with two or more cesarean deliveries. In a retrospective review of 279 women between 14–26 weeks of gestation, the overall rate of uterine rupture was 1.1%[33]. No uterine ruptures occurred among the 60 women with one prior cesarean, even though they received multiple low doses of misoprostol vaginally. However, 3 of 26 (11.5%) women with two or more prior cesarean sections had a scar rupture. One woman with three previous cesarean sections was at 24 weeks of gestation and underwent hysterectomy. Two women each with two prior cesarean sections were at 16 and 20 weeks, respectively, and both had a laparotomy and repair of the scar. In this study, half of the routine misoprostol dose was used in the women with a uterine scar resulting in a longer time from induction to abortion and higher total doses of misoprostol.

A study evaluating the safety and efficacy of vaginal misoprostol for midtrimester medical abortion in 31 women with three or more prior cesarean deliveries concluded that it was safe and acceptably effective[34]. Owing to the lack of randomized trials, there are no conclusions about the safety and effectiveness of the administration routes or misoprostol dosage used in women with a prior uterine scar, or the time allowed between doses. Until then, management of women in this situation should be made on a case-by-case basis, after consideration of the number of cesarean sections and gestational age. Careful monitoring is required during the abortion procedure and awareness of the risk of uterine rupture by all staff.

Pain relief for medical abortion

Abdominal pain is one of the most common adverse effects of medical abortion and is most likely to be felt in the first few hours after prostaglandin analogue administration[35]. Analgesia should therefore be offered to all women with a range of options available to meet their needs.

There is a lack of research evidence to inform the choice of analgesic regimen. In a systematic review of pain control in medical abortion, only 10 of 361 articles identified met the inclusion criteria[7]. Oral paracetamol has been shown not to reduce pain more than placebo during medical abortion and is therefore not recommended. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a possible first-line treatment. They inhibit the production of endogenous prostaglandins, which are important messengers responsible for uterine contractions, cramps and pain sensation. The main positive finding of a systematic review was that ibuprofen given after the onset of pain reduced further analgesic use[36].

In a randomized study examining the effect of paracetamol and codeine or diclofenac given with the first dose of misoprostol to women undergoing medical abortion between 13 and 22 weeks of gestation, women using diclofenac had a reduced need for opiate injections[37]. NSAIDs do not interfere with the action of misoprostol or mifepristone on inducing cervical ripening, uterine contractility or the time to abortion and expulsion of the products of conception[36].

Studies have shown that analgesic requirements and the perception of pain are significantly higher in younger women, those at a higher gestational age, with a longer induction-to-abortion interval and with a greater number of misoprostol doses. Conversely it is less in older, parous women and those at lower gestations. However, none of these factors is sufficiently predictive to be useful in the management of individual cases[38]. The role of advanced or prophylactic analgesia, conscious sedation and paracervical block and their effectiveness, as well as women’s satisfaction and acceptability need further research.

Side effects

Side effects, including nausea, vomiting and diarrhea are characteristics of prostaglandin administration and are caused by a stimulatory effect on the gastrointestinal tract. Fever and chills can also occur and are more common with misoprostol than gemeprost. They are self-limiting and not indicative of infection and antipyrexial therapy is appropriate for symptomatic relief.

Surgical methods

Dilatation and evacuation

D&E preceded by cervical priming is a safe and effective method of surgical abortion for pregnancies above 14 weeks of gestation. Specialized training is required. Adequate prior cervical dilatation is particularly important (see “Cervical priming” below).

A 14–16 mm cannula is inserted into the uterine cavity and the amniotic fluid aspirated. When nothing further can be suctioned, usually after 1–2 min, Bierer or Sopher ovum forceps are introduced into the uterine cavity to remove fetal parts and other pregnancy tissue. Ultrasound guidance during D&E is helpful to locate fetal parts and reduce the risk of complications. Whenever possible, the evacuation should be completed from the lower uterine cavity and reaching high into the uterus avoided. After evacuation, the pregnancy tissue should be examined to ensure complete abortion.