INTRODUCTION — Second-trimester pregnancy termination may be performed with medication or surgery. Surgical termination, or dilation and evacuation (D&E), requires dilating the cervix followed by surgical extraction of products of conception. Medication termination, or induction abortion, involves the administration of medication through one of a variety of routes to induce labor and deliver the fetus. Both methods are safe and effective, and each offers different advantages and disadvantages.
Patients may choose medication abortion if they prefer more awareness of the termination process, if they prefer an intact fetus, or if they want to avoid surgery. An intact fetus may be desirable if the patient desires to hold the fetus or, in cases of fetal anomalies, if an intact fetus is beneficial for a morphologic evaluation. In some health care settings, there is more access to second-trimester induction abortion than surgical abortion.
Second-trimester induction termination is reviewed here. An overview of second-trimester pregnancy termination and the technique for surgical abortion are discussed separately. First-trimester medication abortion is also discussed separately. (See "Overview of second-trimester pregnancy termination" and "First-trimester pregnancy termination: Medication abortion".)
PREPROCEDURE PREPARATION — Patients who desire second-trimester induction termination require preoperative evaluation to establish gestational age, assess general medical status, and identify any medical factors that may impact the choice of induction versus surgical termination. Many of the medical factors favoring medical abortion are "provider-dependent," in that they derive from a specific provider's skill in a particular situation.
Choice of procedure is discussed in detail separately. (See "Overview of second-trimester pregnancy termination", section on 'Choosing dilation and evacuation versus induction termination'.)
Laws regarding abortion vary by country and by state in the United States. Most states restrict abortion after viability, although the definition of viability varies by state and maternal-fetal exemptions that countermand the viability statute vary by state. Clinicians offering abortion must be familiar with restrictions in their own locality.
Laboratory testing — The role of laboratory testing for hemoglobin or hematocrit, Rh typing (and administration of Rhogam to Rh-negative individuals), and chlamydia and/or gonorrhea is described in detail separately. (See "Overview of pregnancy termination", section on 'Laboratory testing' and "Overview of pregnancy termination", section on 'Alloimmunization prevention'.)
Prophylactic antibiotics — Prophylactic antibiotics are not typically advised for second-trimester medication abortion. The Society of Family Planning (SFP) advises that prophylactic antibiotics may lower the risk of serious infection but advises against universal use . (See 'Infection' below.)
The issue of antibiotic prophylaxis is similar for first-trimester medication abortion, which is discussed in detail separately. (See "First-trimester pregnancy termination: Medication abortion", section on 'Limited role of prophylactic antibiotics'.)
Cervical dilation — There is no evidence that osmotic cervical dilation facilitates induction when using modern prostaglandin (PG) analogs [2,3]. Special "precervical ripening" is no longer indicated during the second trimester prior to induction abortion.
In a randomized trial including 347 patients undergoing medical termination of pregnancy between 15 0/7 and 27 6/7 weeks gestation, those receiving cervical preparation plus misoprostol compared with misoprostol alone had similar induction-to-abortion intervals; complication rates were also similar between groups .
Induced fetal demise — Clinicians may induce demise prior to abortion either to facilitate the abortion procedure or to prevent live birth. SFP 2010 guidelines advise that induction of fetal demise prior to medical abortion might shorten induction-to-abortion interval, particularly if potassium chloride (KCl) is utilized, though this is based on one small retrospective study using a PGE2 regimen . More information is needed regarding the impact of different feticidal regimens on induction-to-abortion intervals among patients undergoing misoprostol termination.
To induce fetal demise, there are several options, including intracardiac KCl or intrafetal and intraamniotic digoxin.
Induced fetal demise is discussed in detail separately. (See "Induced fetal demise".)
Anesthesia — Patients undergoing medical induction can receive analgesia or anesthesia similar to that used for obstetric labor induction. Intermittent narcotic administration suffices for some patients, while others desire epidural anesthesia since this completely eliminates pain during more prolonged inductions. (See "Pharmacologic management of pain during labor and delivery".)
Type of prostaglandin — Instillation abortion with saline or urea has now been largely abandoned due to risks such as hypernatremia, coagulopathy, and hemorrhage [6,7]. In comparison with current methods of labor induction abortion (typically with misoprostol), randomized trial data show that instillation abortion results in longer induction times and higher rates of both blood transfusion and retained placenta .
Oxytocin, the most commonly used induction agent at later gestational ages, fails to induce labor as effectively as other single-agent therapies at midtrimester because the uterus has relatively fewer oxytocin receptors at less than 20 weeks of gestation. Oxytocin is associated with longer induction-abortion intervals than newer methods, as well as higher risks of side effects such as postpartum hemorrhage and even water intoxication [8,9]. Patients desiring medical abortion in the second trimester now have safer, more effective options, utilizing PG agents either alone or in combination with progesterone antagonists.
Several PG agents have been used to induce abortion:
●Misoprostol and gemeprost, both PGE1 analogs, are the most common medications used for induction abortion.
Comparative studies have found that both misoprostol and gemeprost induce labor more effectively and with fewer side effects than other PGs (eg, carboprost, sulprostone) and single-agent oxytocin or oxytocin in combination with other types of PGs [10-14]. Both misoprostol and gemeprost induce labor at a variety of gestational ages . The dose decreases as pregnancy advances because the uterus becomes more sensitive to PG with decreasing dose requirements as pregnancy advances.
Misoprostol is typically the preferred agent due to lower rates of certain adverse effects and complications and based on practical considerations. Gemeprost and misoprostol have been found to have similar efficacy in randomized trials [16-20]. As an example, in one trial of 81 patients between 12 to 25 weeks of gestation, pregnancy termination with misoprostol (200 mcg every 12 hours) compared with gemeprost (1 mg every three hours) resulted in a significantly higher rate of complete abortion (61 versus 32 percent) but a longer induction-to-abortion interval (27.8 versus 14.5 hours). The mean blood loss was significantly lower in the misoprostol group. Patients treated with misoprostol had fewer adverse effects (eg, nausea, vomiting).
The advantages of misoprostol in comparison with gemeprost are reduced need for narcotic analgesia, less frequent need for surgical evacuation of the uterus, more routes of administration, is less expensive, and does not require refrigeration .
●Carboprost, a PGF2alpha analog, results in more systemic side effects than PGE analogs .
●Sulprostone, a PGE2 analog, has fallen out of favor because it has been associated with myocardial infarction .
Route and regimen — The route of administration, dose, and dosing interval of misoprostol vary across protocols. There are limited high-quality data to establish the optimal protocol. In general, misoprostol administered by the buccal route has been found to have higher bioavailability than oral and with fewer adverse effects. Sublingual administration has similar efficacy to vaginal dosing. However, for first-trimester medication abortion, many experts advise avoiding vaginal administration due to concerns regarding infection. A systematic review of randomized trials found that the vaginal route was preferable although, among multiparous patients, sublingual administration appeared equally effective . A subsequent randomized trial found that vaginal or sublingual dosing was associated with a shorter time to induction completion than oral dosing .
General principles of the dose, route of administration, and timing of misoprostol are discussed in detail separately. (See "Misoprostol as a single agent for medical termination of pregnancy", section on 'Drug administration' and "First-trimester pregnancy termination: Medication abortion", section on 'Misoprostol'.)
For the second trimester, the dose of misoprostol ranges from 200 to 800 mcg. In regimens using misoprostol or gemeprost alone, median induction-to-abortion intervals are approximately 12 to 16 hours . The abortion time interval is decreased with more frequent dosing. Two randomized trials demonstrated a significantly shorter induction time with vaginal administration of misoprostol 400 mcg every three hours compared with every six hours, without a significant increase in side effects [24,25].
Use of mifepristone — Mifepristone is an antiprogestin that competitively blocks both progesterone and glucocorticoid receptors. By opposing the activity of progesterone, mifepristone elicits a variety of effects that make the uterus more susceptible to abortion. These effects include cervical dilation, decidual necrosis, increased endogenous PG production, and increasing uterine sensitivity to exogenously administered PG. Mifepristone administration gradually elicits a fivefold increase in sensitivity to PG 24 to 48 hours after its administration . The synergy between mifepristone and PG permits greater efficacy of PG at lower doses, potentially minimizing side effects .
Mifepristone and misoprostol have been consistently found to be safe and effective in second-trimester induction abortion [11,23,28]. Mifepristone used in combination with misoprostol is the most effective method of inducing delivery in the second trimester . Many different regimens utilizing mifepristone and misoprostol, alone or in combination, result in fetal expulsion within 24 hours during more than 90 percent of inductions [30,31]. In our practice, we begin inductions 24 hours after mifepristone administration, but we advise practitioners that beginning inductions within 12 hours is also safe and effective . Certainly, providers have considerable latitude to accommodate patients' personal needs and the availability of induction services without fear of compromising safety.
The World Health Organization (WHO), American College of Obstetricians and Gynecologists (ACOG), Society of Family Planning (SFP), and Royal College of Obstetricians and Gynaecologists (RCOG) recommend regimens in which mifepristone precedes use of either misoprostol or gemeprost [30,33-35].
Use of mifepristone followed by oxytocin compared with mifepristone followed by misoprostol was compared in one randomized trial that found no significant difference in success rate (100 versus 96 percent). Time to fetal expulsion was longer in the oxytocin group (11.3 versus 7.0 hours), but the rate of fever and shivers was lower .
A systematic review analyzed results from 20 randomized trials and nine observational studies . Pooled data demonstrated that administration of misoprostol 12 to 24 hours after mifepristone modestly increased induction-abortion intervals by one to two hours. The overall abortion times, the time from administration of mifepristone to delivery, were substantially lower, though primarily because practitioners started inductions earlier. Another study compared a regimen that initiated mifepristone at the same time as misoprostol with a regimen in which misoprostol began 24 hours later. Although taking both medicines simultaneously decreased efficacy at 24 hours and resulted in increased total use of misoprostol, the overall time of the abortion process and the number of clinic visits were reduced .
Medical society protocols — ACOG recommends the following protocols for second-trimester induction abortion :
●Mifepristone 200 mg, administered orally, followed by:
•Misoprostol 800 mcg, administered vaginally, followed by 400 mcg, administered vaginally or sublingually every three hours for up to a maximum of five doses.
•Misoprostol 400 mcg, administered buccally every three hours for up to a maximum of five doses also may be used.
●If mifepristone is not available:
•Misoprostol 400 mcg, administered vaginally or sublingually every three hours for up to five doses. Vaginal dose is superior to sublingual dose for nulliparous patients.
•A vaginal loading dose of 600 to 800 mcg of misoprostol, followed by 400 mcg administered vaginally or sublingually every three hours may be more effective.
●If misoprostol is not available:
•Oxytocin 20 to 100 units, infused intravenously over three hours, followed by one hour without oxytocin to allow diuresis. Oxytocin dose may be slowly increased to a maximum of 300 units over three hours.
●If cervical dilation occurs but the patient does not deliver after five doses of misoprostol, we continue with additional doses of misoprostol until the fetus delivers. While the medical society protocols do not provide specific instruction on how to proceed in this situation, our practice is based on a retrospective study in which 17 percent of patients undergoing medical induction between 14 and 24 weeks required more than five doses of misoprostol; 60 percent of those patients (47 patients) required one or two additional doses prior to delivery of the fetus, and the maximum dose required was 12 . Complication rates (eg, chorioamnionitis, postpartum hemorrhage, retained placenta) were similar among those who received ≤5 versus ≥6 misoprostol tablets.
●However, if cervical dilation does not occur after five doses of misoprostol, options include:
•Discontinue induction and restart the process with misoprostol after 12 to 24 hours.
•Proceed with cervical preparation (eg, osmotic dilators, intracervical Foley balloon) followed by either administration of misoprostol or oxytocin. (See "Induction of labor: Techniques for preinduction cervical ripening", section on 'Balloon catheter' and "Induction of labor: Techniques for preinduction cervical ripening", section on 'Hygroscopic dilators'.)
•Convert to a surgical abortion if cervical dilation is adequate and a skilled provider is available.
We do not change our practice for patients with a prior hysterotomy (eg, cesarean birth, myomectomy). While these patients are at risk of uterine scar dehiscence, there is no evidence to support deviating from the ACOG/RCOG protocols. There is no evidence justifying alteration of medical induction regimens among patients with scarred uteri.
Termination after 23 weeks is not common in the United States, and an optimal regimen has not been established. When pregnancy termination is performed at ≥24 weeks, the indication is generally a fetal anomaly. For gestational ages 24 to 28 weeks, the SFP has published a systematic review and guidelines for pregnancy termination from 24 to 28 weeks; these include data and recommendations for pregnancy termination and labor induction for fetal demise . For mifepristone-misoprostol regimens, seven observational studies were included and showed that a dosing regimen of misoprostol 200 mcg or 400 mcg every four hours is associated with 24-hour expulsion rates of 80 to 97 percent, with mean expulsion times ranging from 8.5 to 13.6 hours. The SFP advised that mifepristone 200 mg or 600 mg be followed by misoprostol 36 to 48 hours later.
Misoprostol-only regimens for this gestational age range are discussed separately. (See "Misoprostol as a single agent for medical termination of pregnancy", section on 'Accepted regimens'.)
Use of other medications — There is variation in the approach to second-trimester abortion across medical settings. In China, approximately 7.63 million abortions were performed in 2007 . The most common method of second-trimester abortion in China has been intraamniotic injection of ethacridine lactate, a dye with antiseptic properties. A systematic review of 15 randomized trials conducted in China evaluated mifepristone combined with misoprostol versus intraamniotic injection of ethacridine lactate and found that mifepristone/misoprostol has lower failures rates (2 to 6 percent versus 7 to 21 percent, risk ratio 0.37, 95% CI 0.17-0.80) and shorter time of labor (an average of 1.9 hours shorter). More gastrointestinal side effects occurred in the mifepristone/misoprostol group, but cervical injury was more frequent in the ethacridine lactate group.
OUTCOME AND COMPLICATIONS — Second-trimester surgical abortion is a safe and effective procedure. Most terminations are completed as inductions, but some patients require a surgical procedure for a retained placenta. In addition to retained products of conception, potential complications include uterine rupture, cervical laceration, hemorrhage, and infection.
Incomplete abortion — Incomplete abortion is more common in second-trimester induction abortion than in surgical abortion (1 to 7 versus 0 percent) [33,41,42].
Retained placenta — In induction procedures with mifepristone and misoprostol, 2 to 10 percent of patients have a retained placenta [23,43,44]. Induction protocols that include misoprostol inductions less commonly require surgical intervention for delivery of the placenta than induction with other agents, though rates of retained placenta are higher for all medical methods compared with dilation and evacuation (D&E) [41,42,45].
Traditionally, in an induction abortion, clinicians have performed curettage if the placenta remained undelivered 30 to 120 minutes following delivery of the fetus. This is based upon reports regarding a technique that is now used infrequently, hyperosmolar saline and prostaglandin E2 (PGE2), which was associated with higher rates of complications with an increasing interval from the delivery of the fetus to the placenta [46,47]. With misoprostol inductions, some data suggest that waiting for up to four hours is acceptable. As an example, in one retrospective study of 233 patients who underwent second-trimester induction with misoprostol, 59 percent of placentas delivered within one hour of fetal expulsion. The overall rate of surgical intervention for retained placenta was 6 percent, and 11 of 14 surgical procedures were performed to expedite hospital discharge . An interval of four or more hours for the delivery of the placenta was not associated with increased morbidity.
As a result of this study for hemodynamically stable patients, we manage delivery of the placenta expectantly for four hours after delivery of the fetus before intervening to remove the placenta.
Uterine rupture — Uterine rupture can occur in patients with a scarred or unscarred uterus . In a systematic review of second-trimester abortion with misoprostol, the risk of uterine rupture among patients with prior cesarean birth was 0.28 percent, whereas the risk in patients without prior cesarean was 0.04 percent . The Society for Family Planning (SFP) in the United States supports second-trimester induction abortion in patients with prior cesarean birth . No studies have evaluated the safety of medical abortion among patients with uterine scarring secondary to prior myomectomy or surgery for correction of müllerian uterine anomalies.
Cervical laceration — Cervical laceration may occur in either induction or surgical abortion. (See "Second-trimester pregnancy termination: Dilation and evacuation", section on 'Cervical laceration'.)
Infection — The medications used for induction abortion, particularly misoprostol, often result in pyrexia, which makes it difficult to evaluate the rate of infection. A literature review by the SFP reported a 1 to 3 percent incidence of infection, not solely pyrexia, following second-trimester medication abortion .
Hemorrhage — Hemorrhage resulting in transfusion complicates less than 1 percent of induction terminations. The risk of hemorrhage increases with gestational age and duration of induction. Common causes include retained products of conception, uterine atony, and trauma to the lower genital tract . Although clinicians often treat postabortal atony similar to postpartum atony, the second-trimester uterus has fewer oxytocin receptors, limiting response to high-dose oxytocin. Carboprost 250 mcg intramuscularly every 15 minutes up to eight doses and low-dose cervical vasopressin have both been described in the setting of postabortal hemorrhage . Balloon tamponade with intrauterine balloon catheters, uterine compression sutures, and angiographic embolization might become necessary in more severe cases of hemorrhage [53-55]. Intractable hemorrhage refractory to other therapy can require hysterectomy.
Other complications — Meaningful mortality data, stratified according to induction regimen used, are unavailable. Given a very low number of deaths reported annually for all second-trimester abortions, it is unlikely that any commonly used medical regimen confers a significant risk of maternal death.
FOLLOW-UP — Follow-up for second-trimester induction abortion, including contraception options and methods to suppress lactation, is the same as for surgical abortion and discussed in detail separately. (See "Overview of second-trimester pregnancy termination", section on 'Postprocedure considerations' and "Contraception: Postabortion".)
SPECIAL CIRCUMSTANCES — Management of patients with special issues of concern (eg, uterine anomalies, low-lying placenta, multiple gestation) is discussed separately. (See "Overview of second-trimester pregnancy termination", section on 'Special circumstances'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pregnancy termination".)
SUMMARY AND RECOMMENDATIONS
●Clinical significance – Second-trimester pregnancy termination may be performed with medication or surgery. Medical induction (also referred to as medication or medical abortion) is performed using solely medications and results in an intact fetus, which may be preferable for a patient in certain circumstances. (See 'Introduction' above.)
•Laboratory testing – The role of laboratory testing for hemoglobin or hematocrit, Rh typing (and administration of Rhogam to Rh-negative individuals), and chlamydia and/or gonorrhea are described in detail separately. (See 'Laboratory testing' above and "Overview of pregnancy termination", section on 'Laboratory testing' and "Overview of pregnancy termination", section on 'Alloimmunization prevention'.)
•Prophylactic antibiotics – Prophylactic antibiotics are not typically advised for second-trimester medication abortion. (See 'Prophylactic antibiotics' above.)
•Osmotic dilators – Osmotic dilators do not facilitate second-trimester medical abortion. Some clinicians use osmotic dilators if there is a high likelihood of conversion of the procedure to a surgical uterine evacuation. (See 'Cervical dilation' above.)
•Induced fetal demise – Feticidal injections are often given to prevent live birth. Another potential goal of induced fetal demise is to facilitate labor induction. (See 'Induced fetal demise' above.)
•Anesthesia – Patients undergoing induction termination can receive analgesia or anesthesia similar to that used for obstetric labor induction. Intermittent narcotic administration suffices for some patients, while others desire epidural anesthesia. (See 'Anesthesia' above.)
●Protocol – Protocols for induction abortion vary, and generally include a prostaglandin (PG), usually misoprostol, with or without mifepristone. Prior protocols using hypertonic saline (increased risk of hypernatremia, coagulopathy, and hemorrhage) and oxytocin (longer induction to abortion intervals, increased risk of hemorrhage and water intoxication) have been largely abandoned. (See 'Protocol' above.)
•An example of a protocol is (see 'Medical society protocols' above):
-Mifepristone 200 mg, administered orally, plus:
Misoprostol 800 mcg, administered vaginally, followed by 400 mcg, administered vaginally or sublingually every three hours for up to a maximum of five doses.
Misoprostol 400 mcg, administered buccally every three hours for up to a maximum of five doses also may be used.
●Complications – Potential complications of induction abortion include retained placenta, uterine rupture, cervical laceration, infection, or hemorrhage. (See 'Outcome and complications' above.)
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