Summary of abortion methods appropriate for use in abortion services in the UK by gestational age in weeks[1]
Whilst the majority of induced abortions are performed in the first trimester, most abortions for fetal abnormality are not undertaken until the second trimester. The optimal method of second trimester abortion continues to be debated[14]. Surgical abortion by dilatation and evacuation preceded by cervical preparation is safe, effective and preferred by women in the second trimester, yet it is offered in relatively few cases in the UK for abortion under Ground E [15]. In a UK randomized controlled trial of abortion methods for fetal abnormality, 100% of women in the surgical group stated that they would prefer that treatment again against 53% in the medical induction group (P < 0.001)[16].
In the USA, dilatation and evacuation (D&E) is the primary method of second trimester abortion for any indication and one-third of fetal medicine specialists provide D&E. Whilst D&E is the most commonly used method at gestations over 14 weeks by independent sector providers in England, very few gynecologists in the NHS in the UK perform D&E. Women value choice and the RCOG endorses surgical abortion in the second trimester[2]. However, surgical abortion in the second trimester is not a core surgical skill for trainees in obstetrics and gynecology in the UK, and it is only an optional requirement for the small proportion of trainees who undertake the advanced training skills module in Abortion Care. Addressing these training issues and developing services within the NHS should be a priority.
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
Vacuum aspiration
Vacuum aspiration is the recommended technique of surgical abortion up to 14 weeks of gestation[2]. Either electric or manual vacuum aspiration may be used, as both are effective and acceptable to women and clinicians. Vacuum aspiration is preferable to sharp curettage for surgical abortion. Comparative trials of evacuation methods for miscarriage management found that vacuum aspiration is associated with less blood loss, less pain and shorter procedure times than sharp curettage[39]. Comparing flexible and rigid cannulae, one randomized trial found no statistically significant differences in cervical injury, febrile morbidity, blood transfusion, antibiotic use or incomplete evacuations between them[40].
During vacuum aspiration, the uterus should be emptied using the suction cannula and blunt forceps if required. The UK RCOG guideline[2] does not recommend routine sharp curettage to ensure the cavity is empty. The “gritty” sensation experienced when the uterus clamps down on the cannula should provide sufficient reassurance that all the products of conception have been removed. The risks of sharp curettage include Asherman’s syndrome. Access to ultrasound may be useful in some cases but routine use is not a requirement[2].
Vacuum aspiration may also be performed between 14 to 16 weeks of gestation. Large-bore cannulae and suction tubing are required for the procedure [41]. Cannulae over 12 mm in diameter may not be readily available in the UK, in which case forceps are used to remove larger fetal parts.
The method of choice at gestations above 13 weeks will depend on the available resources and the skills and experience of local clinicians.
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.
Cervical priming
Cervical priming should be considered in all cases prior to surgical abortion as it may be beneficial, in particular if risk factors for cervical injury or uterine perforation exist. These risk factors include less than 18 years of age, advanced gestational age, particularly in multiparae, cervical anomalies or previous surgery, or when a less experienced surgeon is operating. It is unclear at what gestation cervical priming should be routine, but the risk of complications tends to increase after 9 weeks. The current WHO recommendation is that cervical preparation may be considered at any gestational age but is recommended at 12 weeks of gestation and above[21].
The following regimens are recommended for cervical preparation up to 14 weeks of gestation. Misoprostol 400 mcg administered vaginally 3 h prior to surgery or sublingually 2–3 h prior to surgery. Sublingual administration is superior to vaginal administration but is associated with more side effects. Gemeprost 1 mg vaginally 3 h or mifepristone 200 mg orally 36–48 h before surgery are effective and licenced for this indication. Gemeprost is expensive compared to misoprostol. The length of time that mifepristone has to be administered before the procedure makes it less practical[42].
Up to 18 weeks’ gestation, misoprostol 800 mcg vaginally or 400 mcg sublingually or mifepristone 200mg are also acceptable for cervical preparation[42]. Few randomized controlled trials (RCTs) exist from which to determine the optimal regimen for cervical dilatation before D&E, particularly after 20 weeks of gestation.
A recent systematic review found that osmotic dilators were superior to prostaglandins throughout the second trimester with respect to cervical dilatation and in reducing the procedure time in the early second trimester[43].
All methods are generally safe, although their efficacy and adverse effects vary. No published study has investigated whether pharmacologic methods of cervical priming reduce uncommon complications, such as uterine perforation and cervical laceration. However, they do reduce the duration of the abortion procedure, which is important with increasing gestational age when mechanical cervical dilatation becomes more difficult. The adverse effects experienced with cervical priming, such as pain, need to be considered against the reduced time taken to complete the procedure.
Based on randomized trials, the routine use of uterotonic medication at the time of vacuum aspiration is of no benefit. However, the use of oxytocin is likely to be effective in reducing excessive blood loss[2]. Ergometrine is not recommended because of the high risk of postoperative vomiting.
The use of NSAIDs for analgesia does not reduce the efficacy of cervical priming with misoprostol[44].
Complications of abortion
Incomplete abortion
Incomplete abortion can occur following either medical or surgical abortion. The incidence is higher in women undergoing medical abortion[45].
Symptoms include vaginal bleeding and abdominal pain and signs of infection may be present. Diagnosis should be based on clinical criteria as ultrasound scanning is unreliable because of its low specificity.
Management of incomplete abortion may be surgical or medical. Rates of surgical evacuation vary according to diagnostic criteria, intervention thresholds and the woman’s preference. Vacuum aspiration is recommended over dilatation and curettage for uterine evacuation, as it is associated with less blood loss, less pain and shorter procedure times[46].
Comparing the rate of surgical intervention after medical and surgical abortion up to 9 weeks in a partially randomized study, significantly more women undergoing medical abortion required surgical intervention, 6% compared to 2% of women undergoing surgical abortion. The results were similar at 10–13 weeks of gestation (5% versus 2%) [47]. In a registry-based study of more than 42,000 women undergoing induced abortion up to 9 weeks of gestation, 6% of women having medical abortions needed surgical intervention for retained products of conception compared to fewer than 1% having surgical abortion[45].
Incomplete abortion may be treated medically using misoprostol. The recommended dose and route of administration for this indication is either 600 mcg orally or 400 mcg sublingually[21]. The presence of bleeding may decrease misoprostol absorption when administered vaginally; thus, a nonvaginal route is generally preferable, although vaginal administration of 400–800 mcg has been used effectively. In a systematic review of women with incomplete miscarriage, there were no differences in the rates of complete abortion or of adverse events between vacuum aspiration and misoprostol, although there were more unplanned surgical interventions with the use of misoprostol[48].
Hemorrhage
The incidence of hemorrhage after surgical abortion is low, ranging from 0.7 to 1.5 in 1,000 with vacuum aspiration up to 14 weeks and increases in the midtrimester to 5.6–8.6 in 1,000. It has been reported as high as 21 per 1,000 with late second trimester D&E. The risk of hemorrhage requiring transfusion in early medical abortion is 1.3 per 1000 and 6 per 1,000 in second trimester abortion[2].
Hemorrhage associated with induced abortion can result from retained products of conception, trauma to the cervix, bleeding disorders or rarely, uterine perforation. Depending on the cause, appropriate treatment may include evacuation of the uterus and administration of uterotonic drugs to stop the bleeding, intravenous fluid replacement, and, in severe cases, blood transfusion, replacement of clotting factors, laparoscopy or exploratory laparotomy. Because of the low incidence of hemorrhage using vacuum aspiration, oxytocic drugs are not routinely needed, although they may be indicated with D&E at gestations above 14 weeks.
Prolonged menstrual-like bleeding is an expected effect of medical methods of abortion. On average, vaginal bleeding gradually diminishes over about 2 weeks after expulsion of products of conception but in individual cases, bleeding and spotting may persist for up to 45 days. Such bleeding is rarely heavy enough to constitute an emergency. Surgical evacuation may be performed in cases where the bleeding is heavy or prolonged, is causing anemia, or when there is evidence of infection. Major hemorrhage is rare and is usually associated with prolonged retention of the placenta.
Infection
Infection of varying severity may occur after induced abortion when the genital tract is more susceptible to ascending organisms. It is usually caused by existing infection; screening and prophylactic antibiotics reduces the risk.
All women should be offered screening for Chlamydia trachomatis and undergo a risk assessment for other sexually transmitted infections (for example, human immunodeficiency virus, gonorrhea, syphilis), and be screened for them if appropriate[2].
A systematic review has shown that antibiotic prophylaxis at the time of first-trimester surgical abortion is effective in preventing pelvic inflammatory disease[49]. The antibiotic of choice is determined by the local epidemiology of genital tract infections, including sexually transmitted infections.
The UK RCOG guideline[2] recommends offering antibiotic prophylaxis effective against anerobes and C. trachomatis for surgical abortion (grade A recommendation) and for medical abortion (Grade C recommendation). The following regimens are suitable for use in the UK: metronidazole 1 g rectally or 800 mg orally prior to or at the time of abortion. Unless a woman has tested negative for C. trachomatis then either azithromycin 1 g orally or doxycycline 100 mg orally twice daily for 7 days, starting on the day of the abortion should be given.
There are few data on the incidence of clinically significant pelvic infection after medical abortion, but it occurs possibly less frequently than after vacuum aspiration. Whilst the WHO recommends universal prophylaxis for surgical abortion, it does not do so for medical abortion[21].
Post-abortion infection causes short-term morbidity and may result in tubal damage, leading to subfertility and increased risk of ectopic pregnancy. Many of the symptoms of pelvic infection are nonspecific and precise diagnosis is difficult; therefore, women with pelvic pain, abdominal or adnexal tenderness, vaginal discharge and fever should be treated with broad-spectrum antibiotics.
Rare cases of anerobic infection with little or no fever have been reported from North America following medical abortion where the women had Clostridium-related toxic shock, and cases have been reported during the postpartum period following a normal delivery[50]. There is no evidence that prophylactic antibiotic treatment during medical abortion would eliminate these rare fatal cases of serious infection[21].
Uterine perforation
Uterine perforation usually goes undetected and resolves without the need for intervention. A study of more than 700 women undergoing laparoscopic sterilization at the time of a first-trimester abortion found a rate of uterine perforation of 2%. However, 12 out of the 14 perforations were small and would not have been recognized had laparoscopy not been performed[51]. When uterine perforation is suspected, observation and antibiotic treatment is required. Laparoscopy is the investigation of choice if available and deemed necessary. If the laparoscopic findings and/or clinical condition of the woman suggest damage to the bowel, blood vessels or other structures, laparotomy may be necessary.
Serious complications, such as uterine rupture, major hemorrhage and cervical tear, are rare. The vast majority of women who have a properly performed induced abortion will not suffer any long-term effects on their general or reproductive health. Studies have shown that there is no association between safely induced first-trimester abortion and adverse outcomes in subsequent pregnancies[52]. Although second-trimester abortions have not been studied as extensively, there is no evidence of an increased risk of adverse outcomes in subsequent pregnancies[21].
