Complete Abortion
INTRODUCTION
Background: An abortion is the spontaneous or induced loss of an early pregnancy. The period of pregnancy prior to fetal viability outside of the uterus is considered early pregnancy. Most consider early pregnancy to end at 20-24 weeks’ gestation. The term miscarriage is used often in the lay language and refers to spontaneous abortion.
Pathophysiology: A spontaneous abortion is a process that can be divided into 4 stages—threatened, inevitable, incomplete, and complete.
Threatened abortion consists of any vaginal bleeding during early pregnancy without cervical dilatation or change in cervical consistency. Usually, no significant pain exists, although mild cramps may occur. More severe cramps may lead to an inevitable abortion.
Threatened abortion is very common in the first trimester; about 25-30% of all pregnancies have some bleeding during the pregnancy. Less than one half proceed to a complete abortion or miscarriage. On examination, blood or brownish discharge may exist in the vagina. The cervix is not tender, and the cervical os is closed. No fetal tissue or membranes have passed. The ultrasound shows a continuing intrauterine pregnancy. If an ultrasound was not performed previously, it is required at this time to rule out an ectopic pregnancy, which could present similarly. If the uterine cavity is empty on ultrasound, obtaining a human chorionic gonadotropin (hCG) level is necessary to determine if the discriminatory zone has been passed.
The discriminatory zone is the level of hCG beyond which an intrauterine pregnancy is consistently visible. The discriminatory zone may vary depending on a number of factors, including hCG assay type and reference calibration standard used, ultrasound equipment resolution, the skill and experience of the sonographer, and patient factors (eg, obesity, leiomyomas, uterine axis, multiple gestation). Also, the discriminatory zone will vary depending on whether the ultrasound is performed abdominally or vaginally. Therefore, having a universal discriminatory zone is difficult, and it optimally should be calculated at each site. However, some studies recommend that an estimate would be that a gestational sac should be visualized by 5.5 weeks’ gestation; a gestational sac should be visualized with an hCG level of 1500-2400 mIU/mL for transvaginal ultrasound or with an hCG level over 3000 mIU/mL for a transabdominal ultrasound. If the hCG level is higher than the discriminatory zone and no gestational sac is visualized in the uterus, then consider that an ectopic pregnancy may be present.
Inevitable abortion is an early pregnancy with vaginal bleeding and dilatation of the cervix. Typically, the vaginal bleeding is worse than with a threatened abortion, and more cramps are present. No tissue has passed yet.
Incomplete abortion is a pregnancy that is associated with vaginal bleeding, dilatation of the cervical canal, and passage of products of conception. Usually, the cramps are intense, and the vaginal bleeding is heavy. Patients describe passage of tissue, or the examiner observes evidence of tissue passage within the vagina. The ultrasound confirms that some of the products of conception are still present in the uterus.
Complete abortion is a completed miscarriage. Typically, a history of vaginal bleeding, abdominal pain, and passage of tissue exists. After the tissue passes, the patient notes that the pain subsides and the vaginal bleeding significantly diminishes. The examination reveals some blood in the vaginal vault; a closed cervical os; and no tenderness of the cervix, uterus, adnexa, or abdomen. The ultrasound demonstrates an empty uterus.
These 4 stages of abortion described above form a continuum. Most studies do not differentiate separately between the epidemiology and pathophysiology of each entity described above.
A fifth term that does not follow the continuum but is important to be aware of is missed abortion. A missed abortion is a nonviable intrauterine pregnancy that has been retained within the uterus without spontaneous abortion. Typically, no symptoms exist besides amenorrhea, and the patient finds out that the pregnancy stopped earlier when a fetal heartbeat is not observed or heard at the appropriate time. An ultrasound usually confirms the diagnosis. No vaginal bleeding, abdominal pain, passage of tissue, and cervical changes are present.
Frequency:
In the US: The overall miscarriage rate is reported as 15-20%, which means 15-20% of recognized pregnancies result in miscarriage. The frequency of spontaneous miscarriage increases further with maternal age. With the development of highly sensitive assays for hCG levels, pregnancies can be detected prior to the expected next period. When these highly sensitive hCG assays are used early, the magnitude of pregnancy loss significantly increases to about 60-70%. Late implantation by the conceptus beyond the usual 8-10 days after ovulation also has an increased risk of miscarriage.
About 80% of miscarriages occur within the first trimester. The frequency of miscarriage decreases with an increasing gestational age. Recurrent miscarriage, defined as 2-3 pregnancy losses, affects about 1% of all couples.
Internationally: No significant difference exists between international rates and the rates in the United States.
Mortality/Morbidity: A complete abortion is unlikely to cause any significant risk of mortality unless significant blood loss or infection occurs. Morbidity would be increased if an anemia or infection develops. Patients who are pregnant may bleed quickly and significantly. Distinguishing the causes of bleeding during pregnancy is important.
Threatened abortions usually bleed, a viable intrauterine pregnancy is visible on ultrasound, and the cervical canal is closed. A complete abortion will have a history of bleeding and significant cramping with passage of tissue, followed by a marked reduction in bleeding and resolution of cramping. With a complete abortion, the ultrasound demonstrates an empty uterus and the examination is notable for a closed cervical os. Incomplete or inevitable abortions have bleeding and an open cervical os on examination. The ultrasound may show clots or an intrauterine pregnancy.
These latter 2 conditions (incomplete and inevitable abortions) are a cause for concern when significant bleeding or infection occurs. If a suction dilatation and curettage (D&C) is not performed in a timely manner, significant morbidity and mortality may occur. Retained products of conception also may occur after a spontaneous abortion or after a suction D&C. Patients with retained products usually return for medical care with symptoms of increased bleeding, increased cramping, and/or infection. Caring for these patients quickly with intravenous antibiotics is important, and, after the antibiotics are administered, then a suction D&C or a repeat suction D&C is performed. These patients will be at risk for developing Asherman syndrome, which consists of adhesions within the uterine cavity. Patients who develop Asherman syndrome may present with amenorrhea or decreased menstrual flow. Asherman syndrome may compromise future fertility. When significant bleeding occurs, fluid management and transfusions may be required while stabilizing the patient prior to a suction D&C.
A complication of D&C is perforation of the uterus, which may be handled by observation. If the patient shows signs of uncontrolled bleeding on ultrasound, then proceeding to a laparoscopy or laparotomy with cauterization of the bleeding area may be necessary. The choice for laparoscopy or laparotomy depends on the stability of the patient. Occasionally, the perforation is in the area of the uterine vessels or other area where the bleeding is difficult to control and a hysterectomy may be necessary. When bleeding is out of control, the patient easily can go into hypovolemic shock or disseminated intravascular coagulopathy (DIC). Both of these situations need prompt attention and treatment.
Race: Complete abortions may occur in any race without distinction.
Sex: Complete abortions only affect females.
Age: Complete abortions only occur in reproductive-aged women unless in vitro fertilization was used with donor eggs in menopausal women. As women mature, the incidence of spontaneous miscarriages increases. Typically, the distribution of miscarriage rates by age occurs as follows: younger than 35 years old, 15% miscarriage rate; 35-39 years old, 20-25% miscarriage rate; 40-42 years old, about 35% miscarriage rate; and older than 42 years old, about 50% miscarriage rate.
CLINICAL
History: Patients with spontaneous complete abortion usually present with a history of vaginal bleeding, abdominal pain, and passage of tissue. After the tissue passes, the vaginal bleeding and abdominal pain subsides.
Vaginal bleeding usually is heavy.
Quantification of the amount of bleeding is very important because life-threatening hemorrhage may occur. The patient may be able to quantify the number of pads or tampons used over a specified time and qualify the amount that each pad is soaked.
The presence of blood clots suggests heavy bleeding. The presence of blood clots also may be confused with passage of tissue.
Examining the passed material helps clarify the type of abortion occurring.
Abdominal pain is associated with concurrent abortion and resolves with the completion of the abortion.
The pain usually is in the suprapubic area, but reports of pain in one or both lower quadrants are not uncommon.
The pain may radiate to the lower back, buttocks, genitalia, and perineum.
If the pain is occurring only on one side, consider an ectopic pregnancy or a ruptured ovarian cyst as a possible cause.
Consider any reproductive-aged woman presenting with vaginal bleeding to be pregnant until proven otherwise.
Other symptoms, such as fever or chills, are more characteristic of infection, such as in a septic abortion.
Physical: Patients who are pregnant and bleeding vaginally need immediate evaluation.
Estimating the patient’s hemodynamic stability is the first step.
Obtain orthostatic vital signs.
Abdominal and pelvic examinations are next.
Initiate fluid resuscitation early in cases of orthostatic hypotension.
The abdominal examination needs to determine whether or not the state of an acute abdomen is present.
In a complete abortion, the abdomen is benign, with no distension, no rebound, normal bowel sounds, no hepatosplenomegaly, and mild suprapubic tenderness.
Usually, the uterus either is not palpable abdominally or is just slightly above the pubic symphysis.
If rebound tenderness and/or a distended uterus exist, it is unlikely that a complete abortion has occurred. Assume that an ectopic pregnancy occurred, and provide the patient with aggressive fluid resuscitation with 2 IV lines and an emergent laparoscopy (if stable enough) or an emergent exploratory laparotomy.
In the case of a complete abortion, pelvic examination may show some blood on the perineum or vagina but limited active bleeding.
The cervix is nontender to minimally tender, and the cervical canal is closed.
The uterus is smaller than what is expected for dates, and it is nontender to mildly tender.
The adnexa are nontender to mildly tender. Usually, no adnexal masses exist, unless a corpus luteum is still palpable.
In summary, the pelvic examination check list includes assessment of the following:
Source of bleeding (cervical os)
Intensity of bleeding (active, heavy, clots)
Any presence or passage of tissue
Cervical motion tenderness (increases suspicion for ectopic pregnancy)
Cervical os closed for complete or threatened abortion (If it is open, consider inevitable or incomplete abortion.)
Uterine size and tenderness
Adnexal masses (suspicious for ectopic pregnancy)
Causes:
In the first trimester, embryonic causes of spontaneous abortion are the predominant etiology and account for 80-90% of miscarriages.
Genetic abnormalities within the embryo (ie, chromosomal abnormalities) are the most common cause of spontaneous abortion and account for 50-65% of all miscarriages.
The most common single chromosomal anomaly is 45,X karyotype, with an incidence of 14.6%.
Trisomies are the single largest group of chromosomal anomalies and account for approximately one half of all anomalies associated with miscarriage. Trisomy 16 is the most common trisomy found.
Approximately 20% of genetic abnormalities are triploidies.
Teratogenic and mutagenic factors may play a role, but quantification is difficult.
Maternal causes of spontaneous miscarriage include the following:
Genetic: Maternal age is directly related to the aneuploidy risk (>30% in people aged 40 y). Couples with recurrent miscarriages have a 2-3% incidence of a parental chromosomal anomaly (ie, balanced translocation).
Structural abnormalities of the reproductive tract include the following:
Congenital uterine defects (particularly uterine septum)
Fibroids
Cervical incompetence
Iatrogenic causes (ie, Asherman syndrome)
Acute maternal factors include the following:
Corpus luteum deficiency
Active infection (eg, rubella virus, cytomegalovirus, Listeria infection, toxoplasmosis)
Chronic maternal health factors include the following:
Polycystic ovary syndrome
Poorly controlled diabetes mellitus (A successful pregnancy requires much tighter control.)
Renal disease
Systemic lupus erythematosus (SLE)
Untreated thyroid disease
Severe hypertension
Antiphospholipid syndrome
Exogenous factors include the following:
Tobacco
Alcohol
Cocaine
Caffeine (high doses)
DIFFERENTIALS
Anovulation Appendicitis Dysfunctional Uterine Bleeding Dysmenorrhea Ectopic Pregnancy Endometriosis Hemorrhoids Missed Abortion Ovarian Cysts Threatened Abortion Trauma and Pregnancy Urinary Tract Infections in Pregnancy Vaginitis
Other Problems to be Considered:
Abortion, incompleteAbortion, inevitableAcute appendicitisCervical polyps, ectropion, or malignancyOvarian torsionPregnancy, molarPregnancy, subchorionic hemorrhageVaginal/vulvar condylomata
WORKUP
Lab Studies:
Complete blood count (CBC), beta-hCG, blood type and screen (possible crossmatch), possible DIC profile, and urinalysis
CBC will help document the amount of blood loss and whether anemia is present. If the hemoglobin and hematocrit are very low and the patient is symptomatic then transfusions would be warranted. The CBC also will provide evidence regarding an infection, which, in the case of infection, would yield an elevated white blood cell count and a left shift on differential.
Beta-hCG is important to confirm the pregnancy and distinguish it from dysfunctional uterine bleeding or bleeding from another etiology. The hCG level also is important to help distinguish a complete abortion from a threatened abortion or ectopic pregnancy. If the hCG level is above 1500-2000 mIU/mL, then a transvaginal ultrasound should detect a viable intrauterine pregnancy. A level over 3000 mIU/mL should enable one to visualize a viable intrauterine pregnancy by transabdominal ultrasound. If the values are so elevated, the cervical canal is closed, and the patient's history is consistent with passing tissue (which a physician has confirmed), then an empty uterus on ultrasound is consistent with a completed abortion. However, if the hCG is elevated and no history of passing tissue is present and the ultrasound demonstrates an empty uterus, one must assume that an ectopic pregnancy is present until proven otherwise. Low hCG levels (ie, <200 mIU/mL) may make the diagnosis more difficult. Observation and monitoring the hCG levels every few days may be an option if the patient is stable and not complaining of pain. If these low hCG levels plateau and fall, the patient likely will miscarry or have a tubal abortion on her own. However, if the values rise, then follow-up ultrasounds are necessary to determine whether an intrauterine pregnancy or an ectopic pregnancy is present and subsequent appropriate management is necessary.
Blood type and screen (possible crossmatch) is important to determine whether treatment with RhoGAM is appropriate. An Rh-negative woman should receive RhoGAM within 72 hours of miscarriage or ectopic pregnancy to avoid the possibility that the pregnancy has exposed the patient to a positive antigen. If the father of the baby also is Rh negative then the patient can forego the immunoglobulin therapy. It also is important in cases where transfusions are necessary.
DIC profile only is necessary in those cases with significant bleeding. The DIC profile usually consists of a platelet count, fibrinogen level, prothrombin time (PT), and activated partial prothrombin time (aPTT). When significant bleeding occurs and the patient is consuming these factors faster then she can make them, then the initiating event needs to be treated (ie, D&C, hysterectomy) and platelets, coagulation factors (usually administered in the form of fresh frozen plasma or cryoprecipitate), or fibrinogen in addition to packed red blood cells may need to be replaced when transfusing a patient. Whole blood may be transfused as another alternative.
Urinalysis is important to rule out a urinary tract infection. Pregnant women are prone to urinary tract infections due to the progesterone effect on the smooth muscle of the ureters, which causes mild physiologic hydroureters. A cystitis or renal stone also could be present with bleeding but from a urinary source.
Imaging Studies:
Ultrasound of the pelvis using a vaginal probe to rule out an ectopic pregnancy, retained products of conception, hematometra, or other etiologies: Once the discriminatory level is passed, the ultrasound is fairly reliable. Perform other imaging studies as needed.
Procedures:
If the diagnosis truly is a complete abortion, then no further procedures are needed.
Tuesday, June 3, 2008
Threatened Abortion 2
TREATMENT
Medical Care: No effective therapy is available for a threatened intrauterine abortion.
Bed rest, although often advocated, is not effective.
Do not administer progesterone or sedatives. In the majority of instances of threatened abortions that ultimately result in complete abortion, the embryo is already dead; thus, the administration of progesterone drugs is ineffective and only prolongs the natural course of abortion.
Institute appropriate counseling for all patients. A sympathetic attitude and continuing support and follow-up care are important to patients. This includes a tactful explanation about the pathologic process and favorable prognosis when the pregnancy is viable.
Treat any vaginal infections.
Surgical Care: Continued observation is indicated as long as the cervix remains closed, bleeding and cramping are mild, QhCG levels are increasing normally, and a normal embryo/fetus is visualized on follow-up sonogram images. The prognosis worsens with (1) progressively increasing bleeding and cramping, (2) QhCG levels that fall or level off, (3) failure to find sonographic evidence of embryonic/fetal growth, (4) fetal bradycardia, and (5) size smaller than appropriate for dates.
When the pregnancy is confirmed nonviable because the cervical os is dilated or excessive bleeding is present, perform suction curettage. This prevents delayed hemorrhage and infection related to retention of necrotic tissue. It also diminishes the chances for the development of disseminated intravascular coagulation, a rare but potentially life-threatening complication associated with the retention of a dead conceptus for longer than 4 weeks.
In women with minimal intrauterine tissue based on ultrasound images, waiting for spontaneous passage of the products of conception is possible (expectant management).
Currently, evidence is insufficient to support medical therapy (prostaglandins and antiprogesterones) for spontaneous abortions.
MEDICATION
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Drug Category: Oxytocic agents –
Enhance uterine contractility after evacuation and diminish bleeding.
Drug Name
Oxytocin (Pitocin, Syntocinon) -- Promotes contractility of uterine smooth muscle by increasing intracellular calcium. Most effective at or near term. In early pregnancy, high doses produce uterine contractions. Diminishes bleeding after surgical uterine evacuation.
Adult Dose
10-60 U in 1000 mL (NS, D5RL, or LR) IV infusion, titrate to control uterine atony (125-200 mL/h)
Pediatric Dose
<12>12 years: Administer as in adults
Contraindications
Documented hypersensitivity; pregnant patients with severe toxemia, unfavorable fetal positions, and contracting uterus with hypertonic or hyperactive patterns; labor for which vaginal delivery should be avoided, such as invasive cervical carcinoma, cord presentation or prolapse, active herpes genitalis, total placenta previa, and vasa previa
Interactions
Pressor effect of sympathomimetics may increase when used concomitantly with oxytocic drugs, causing postpartum hypertension; inhalation anesthetics may produce adverse cardiovascular effects; cyclopropane may induce hypotension, maternal sinus bradycardia, or abnormal atrioventricular rhythms
Pregnancy
X - Contraindicated in pregnancy
Precautions
Overstimulated uterus can be hazardous to mother and fetus; uterine hypersensitivity may induce hypertonic contractions, even with appropriate administration; intrinsic antidiuretic effect at high doses given over a prolonged period can cause water intoxication
Drug Name
Methylergonovine (Methergine) -- Ergot alkaloid that acts directly on uterine smooth muscle, producing increased tone, frequency, and amplitude of contractions and decreased bleeding.
Adult Dose
0.2 mg PO q4h for 6 doses0.2 mg IM/IV, repeat q2-4h prn
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; pregnancy; induction of labor; threatened spontaneous abortion; toxemia; hypertension
Interactions
Concurrent administration of vasoconstrictors or other ergot alkaloids may produce additive effect (ie, additive peripheral vasoconstriction with dopamine associated with peripheral ischemia and gangrene)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in sepsis, obliterative vascular disease, or hepatic or renal insufficiency
Drug Category: Immunoglobulins –
Suppress immune response and antibody formation.
Drug Name
Rho (D) Immune Globulin (RhoGAM) -- Suppresses immune response of nonsensitized Rho (D)–negative women exposed to fetal Rho (D)–positive blood following a fetomaternal hemorrhage (ie, abdominal trauma, amniocentesis, abortion, ectopic pregnancy, transfusion accident)
Adult Dose
<13>13 weeks' gestation: 300 mcg IM
Pediatric Dose
Administer as in adults
Contraindications
Documented hypersensitivity; patients who have received Rho (D)–positive blood within 3 mo
Interactions
Alters response to live virus vaccines (ie, measles, mumps, rubella, varicella)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in thrombocytopenia, bleeding disorders, or IgA deficiency
FOLLOW-UP
Further Inpatient Care:
Inpatient treatment includes suction curettage for inevitable and complete abortions.
Laparoscopy or laparotomy is available for patients with ectopic pregnancies who are not candidates for methotrexate.
Patients undergoing suction curettage should be observed for 4-6 hours and then discharged if stable.
Further Outpatient Care:
A follow-up visit with an obstetrician/gynecologist should be scheduled for within 1 week.
Serial QhCG levels and TVS evaluations may be required.
If spontaneous abortion occurs, the patient should be seen within 1 week.
Allow sufficient time for counseling.
Etiologies and prognosis can be addressed further at this point.
Include a sensitively approached focus on the patient's emotional reactions.
In/Out Patient Meds:
For patients who are Rh-negative and at less than 13 weeks’ gestation, administer RhoGAM at 50 mcg intramuscularly.
If the patient undergoes suction curettage, any of the following may be administered if needed:
Methergine (0.2 mg PO q4h 6 times) - To diminish postevacuation uterine bleeding
Ibuprofen (800 mg PO q6h prn) - For analgesia
Doxycycline (100 mg PO bid for 4-7 d) - For prophylaxis
Iron supplementation - For anemia
Contraception agent, if desired
Deterrence/Prevention:
Contraceptive counseling
Complications:
Preexisting anemia may make patients more susceptible to hypovolemic shock.
Potential complications from suction curettage include hemorrhage and uterine perforation with possible injury to bowel, bladder, ureter, and uterine artery.
Other complications include the following:
Postabortion bleeding
Retained products of conception
Hematometra
Depression
Anesthesia complications
Prognosis:
In women who have had 1 prior miscarriage, the rate of spontaneous abortion in a subsequent pregnancy is approximately 20%. In women who have had 3 consecutive losses, the rate is 50%.
The live-birth rate after documentation of fetal cardiac activity at 5-6 weeks of gestation in women with 2 or more unexplained spontaneous abortions is approximately 77%.
Patients can be reassured that in most cases, spontaneous abortions do not recur.
Evidence of an association between threatened abortion and birth defects is limited and inconsistent. One epidemiologic study found an increased risk of birth defects (polydactyly, undescended testicle, and hypospadias) in the follow-up observation of patients with threatened abortion. Another study looking at perinatal outcome of pregnancies continuing after threatened abortion found no significant difference in preterm deliveries, low birth weight, and overall perinatal outcome.
Patient Education:
Advise patients to return for follow-up care upon the occurrence of any of the following symptoms:
Profuse vaginal bleeding and/or severe abdominal cramping
Severe pelvic pain
Temperature higher than 38°C (100.4°F)
Passage of tissue
MISCELLANEOUS
Medical/Legal Pitfalls:
Failure to diagnose pregnancy: Every woman of reproductive age with lower abdominal pain and/or vaginal bleeding should have a pregnancy test.
Failure to diagnose an ectopic pregnancy: An ectopic pregnancy must be excluded in every pregnant woman with abdominal pain and/or vaginal bleeding. With early diagnosis, ectopic pregnancy in a patient who is stable can be treated nonsurgically.
Failure to provide important follow-up care: In patients who are being monitored with serial QhCG titers and sonograms, documenting a contact person with telephone number and address is prudent in the event that the patient is lost to follow-up.
Failure to prevent isoimmunization: Unsensitized Rh-negative women should receive the appropriate dose of RhoGAM.
Failure to assess the true intensity of hemorrhage: External bleeding may not accurately reflect total blood loss. Blood can be concealed in the vagina or uterus, or a hemoperitoneum may exist.
Medical Care: No effective therapy is available for a threatened intrauterine abortion.
Bed rest, although often advocated, is not effective.
Do not administer progesterone or sedatives. In the majority of instances of threatened abortions that ultimately result in complete abortion, the embryo is already dead; thus, the administration of progesterone drugs is ineffective and only prolongs the natural course of abortion.
Institute appropriate counseling for all patients. A sympathetic attitude and continuing support and follow-up care are important to patients. This includes a tactful explanation about the pathologic process and favorable prognosis when the pregnancy is viable.
Treat any vaginal infections.
Surgical Care: Continued observation is indicated as long as the cervix remains closed, bleeding and cramping are mild, QhCG levels are increasing normally, and a normal embryo/fetus is visualized on follow-up sonogram images. The prognosis worsens with (1) progressively increasing bleeding and cramping, (2) QhCG levels that fall or level off, (3) failure to find sonographic evidence of embryonic/fetal growth, (4) fetal bradycardia, and (5) size smaller than appropriate for dates.
When the pregnancy is confirmed nonviable because the cervical os is dilated or excessive bleeding is present, perform suction curettage. This prevents delayed hemorrhage and infection related to retention of necrotic tissue. It also diminishes the chances for the development of disseminated intravascular coagulation, a rare but potentially life-threatening complication associated with the retention of a dead conceptus for longer than 4 weeks.
In women with minimal intrauterine tissue based on ultrasound images, waiting for spontaneous passage of the products of conception is possible (expectant management).
Currently, evidence is insufficient to support medical therapy (prostaglandins and antiprogesterones) for spontaneous abortions.
MEDICATION
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Drug Category: Oxytocic agents –
Enhance uterine contractility after evacuation and diminish bleeding.
Drug Name
Oxytocin (Pitocin, Syntocinon) -- Promotes contractility of uterine smooth muscle by increasing intracellular calcium. Most effective at or near term. In early pregnancy, high doses produce uterine contractions. Diminishes bleeding after surgical uterine evacuation.
Adult Dose
10-60 U in 1000 mL (NS, D5RL, or LR) IV infusion, titrate to control uterine atony (125-200 mL/h)
Pediatric Dose
<12>12 years: Administer as in adults
Contraindications
Documented hypersensitivity; pregnant patients with severe toxemia, unfavorable fetal positions, and contracting uterus with hypertonic or hyperactive patterns; labor for which vaginal delivery should be avoided, such as invasive cervical carcinoma, cord presentation or prolapse, active herpes genitalis, total placenta previa, and vasa previa
Interactions
Pressor effect of sympathomimetics may increase when used concomitantly with oxytocic drugs, causing postpartum hypertension; inhalation anesthetics may produce adverse cardiovascular effects; cyclopropane may induce hypotension, maternal sinus bradycardia, or abnormal atrioventricular rhythms
Pregnancy
X - Contraindicated in pregnancy
Precautions
Overstimulated uterus can be hazardous to mother and fetus; uterine hypersensitivity may induce hypertonic contractions, even with appropriate administration; intrinsic antidiuretic effect at high doses given over a prolonged period can cause water intoxication
Drug Name
Methylergonovine (Methergine) -- Ergot alkaloid that acts directly on uterine smooth muscle, producing increased tone, frequency, and amplitude of contractions and decreased bleeding.
Adult Dose
0.2 mg PO q4h for 6 doses0.2 mg IM/IV, repeat q2-4h prn
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; pregnancy; induction of labor; threatened spontaneous abortion; toxemia; hypertension
Interactions
Concurrent administration of vasoconstrictors or other ergot alkaloids may produce additive effect (ie, additive peripheral vasoconstriction with dopamine associated with peripheral ischemia and gangrene)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in sepsis, obliterative vascular disease, or hepatic or renal insufficiency
Drug Category: Immunoglobulins –
Suppress immune response and antibody formation.
Drug Name
Rho (D) Immune Globulin (RhoGAM) -- Suppresses immune response of nonsensitized Rho (D)–negative women exposed to fetal Rho (D)–positive blood following a fetomaternal hemorrhage (ie, abdominal trauma, amniocentesis, abortion, ectopic pregnancy, transfusion accident)
Adult Dose
<13>13 weeks' gestation: 300 mcg IM
Pediatric Dose
Administer as in adults
Contraindications
Documented hypersensitivity; patients who have received Rho (D)–positive blood within 3 mo
Interactions
Alters response to live virus vaccines (ie, measles, mumps, rubella, varicella)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in thrombocytopenia, bleeding disorders, or IgA deficiency
FOLLOW-UP
Further Inpatient Care:
Inpatient treatment includes suction curettage for inevitable and complete abortions.
Laparoscopy or laparotomy is available for patients with ectopic pregnancies who are not candidates for methotrexate.
Patients undergoing suction curettage should be observed for 4-6 hours and then discharged if stable.
Further Outpatient Care:
A follow-up visit with an obstetrician/gynecologist should be scheduled for within 1 week.
Serial QhCG levels and TVS evaluations may be required.
If spontaneous abortion occurs, the patient should be seen within 1 week.
Allow sufficient time for counseling.
Etiologies and prognosis can be addressed further at this point.
Include a sensitively approached focus on the patient's emotional reactions.
In/Out Patient Meds:
For patients who are Rh-negative and at less than 13 weeks’ gestation, administer RhoGAM at 50 mcg intramuscularly.
If the patient undergoes suction curettage, any of the following may be administered if needed:
Methergine (0.2 mg PO q4h 6 times) - To diminish postevacuation uterine bleeding
Ibuprofen (800 mg PO q6h prn) - For analgesia
Doxycycline (100 mg PO bid for 4-7 d) - For prophylaxis
Iron supplementation - For anemia
Contraception agent, if desired
Deterrence/Prevention:
Contraceptive counseling
Complications:
Preexisting anemia may make patients more susceptible to hypovolemic shock.
Potential complications from suction curettage include hemorrhage and uterine perforation with possible injury to bowel, bladder, ureter, and uterine artery.
Other complications include the following:
Postabortion bleeding
Retained products of conception
Hematometra
Depression
Anesthesia complications
Prognosis:
In women who have had 1 prior miscarriage, the rate of spontaneous abortion in a subsequent pregnancy is approximately 20%. In women who have had 3 consecutive losses, the rate is 50%.
The live-birth rate after documentation of fetal cardiac activity at 5-6 weeks of gestation in women with 2 or more unexplained spontaneous abortions is approximately 77%.
Patients can be reassured that in most cases, spontaneous abortions do not recur.
Evidence of an association between threatened abortion and birth defects is limited and inconsistent. One epidemiologic study found an increased risk of birth defects (polydactyly, undescended testicle, and hypospadias) in the follow-up observation of patients with threatened abortion. Another study looking at perinatal outcome of pregnancies continuing after threatened abortion found no significant difference in preterm deliveries, low birth weight, and overall perinatal outcome.
Patient Education:
Advise patients to return for follow-up care upon the occurrence of any of the following symptoms:
Profuse vaginal bleeding and/or severe abdominal cramping
Severe pelvic pain
Temperature higher than 38°C (100.4°F)
Passage of tissue
MISCELLANEOUS
Medical/Legal Pitfalls:
Failure to diagnose pregnancy: Every woman of reproductive age with lower abdominal pain and/or vaginal bleeding should have a pregnancy test.
Failure to diagnose an ectopic pregnancy: An ectopic pregnancy must be excluded in every pregnant woman with abdominal pain and/or vaginal bleeding. With early diagnosis, ectopic pregnancy in a patient who is stable can be treated nonsurgically.
Failure to provide important follow-up care: In patients who are being monitored with serial QhCG titers and sonograms, documenting a contact person with telephone number and address is prudent in the event that the patient is lost to follow-up.
Failure to prevent isoimmunization: Unsensitized Rh-negative women should receive the appropriate dose of RhoGAM.
Failure to assess the true intensity of hemorrhage: External bleeding may not accurately reflect total blood loss. Blood can be concealed in the vagina or uterus, or a hemoperitoneum may exist.
Complete Abortion 2
TREATMENT
Medical Care: A complete abortion usually needs no further treatment, medically or surgically.
In the situation in which a considerable amount of blood loss has occurred, iron therapy or transfusions may be indicated.
If the diagnosis in not correct, the patient is likely to continue to bleed and cramp for an incomplete or inevitable abortion. In these situations, a suction D&C is indicated. If the patient has any signs of infection, start antibiotics prior to the D&C.
An ectopic pregnancy may be treated medically or surgically, depending on the clinical scenario.
Medical therapy consists of methotrexate, which usually is administered in a dose of 50 mg/m2. The effectiveness of medical therapy depends on only applying it to patients who are appropriate candidates based on gestational age, hCG level, ectopic size, patient reliability, proximity to the office or hospital, and health.
Prior to administering the methotrexate, renal and liver function tests are measured and results should be normal. A CBC is warranted, and, if significant anemia exists, then medical therapy is not warranted.
The absolute limits for gestational age, hCG level, ectopic size, and the presence or absence of an embryonic heartbeat are debated in the literature. Despite the debate, the factors that decrease the likelihood of success are older gestational age, higher hCG, larger ectopic size, and the presence of a fetal heartbeat.
The author likes to use a rule of 3s because it is easy to remember. A patient who is less than 3 weeks from expected menses (7 wk from last menstrual period [LMP]), has an hCG level less than 3000 mIU/mL, and has an ectopic size less than 3 cm has a 95% chance of success with methotrexate.
On the day of injection and on days 4 and 7 after the injection, the hCG level is monitored. A 15% drop in the hCG level is expected between day 4 and day 7. From day 1 to day 4, a rise in the hCG level may occur. If a 15% drop in the hCG level occurs on day 7, then the patient is monitored with weekly hCG levels until the level is less than 5 mIU/mL.
Patients may have some cramping or discomfort on the side of the ectopic pregnancy as the hCG declines, but these symptoms should be mild. Typically, patients do not experience bleeding until the hCG level is low.
The authors encourage increased fluid intake to avoid some of the adverse effects of methotrexate. However, this dose of methotrexate is much smaller than that used to treat trophoblastic disease, and most patients have very little problem with taking it.
After methotrexate therapy for an ectopic pregnancy, any plateau or rising of hCG requires evaluation. In some situations, considering a second dose of methotrexate is possible. However, consider surgery as well.
Any symptoms suggesting ectopic rupture (eg, acute pain, rebound tenderness) should immediately direct the physician to the operating room.
Laparoscopy can still be considered if the patient is stable.
A linear salpingostomy with excision of the ectopic pregnancy or partial salpingectomy are the possible procedures.
If the patient is unstable, the same procedures are performed using a laparotomy.
For a complete abortion, the medical care is to treat any remaining anemia and to evaluate the blood type and treat the patient with RhoGAM when indicated.
Prehospital care: Monitor vital signs and provide fluid resuscitation if the patient is hemodynamically stable.
Emergency department care: If they know what to expect, most patients with complete abortions are not treated in the emergency department. Only those with significant blood loss go to the emergency department.
Patients with threatened, inevitable, incomplete, and ectopic pregnancies may go to the emergency department.
Patients with threatened abortions need an ultrasound to confirm the diagnosis and for reassurance. Usually, no other medical therapy is needed. These patients often are counseled to increase fluid intake, remain at bedrest, or add progesterone supplements. However, none of these treatments has been proven effective in a prospective randomized trial.
Abortion, Inevitable, Abortion, Incomplete, and Ectopic Pregnancy are discussed above and in separate articles.
Surgical Care: No surgical care is used for complete abortion.
Inevitable and incomplete abortions require a D&C.
A septic abortion requires antibiotic therapy prior to a D&C. An ectopic pregnancy only is treated medically for the appropriate candidates. The rest require surgery, consisting of linear salpingostomy or partial or complete salpingectomy via laparoscopy or laparotomy.
Consultations: Consult an obstetrician-gynecologist any time uncertainty about the diagnosis exists and to administer treatment.
Diet:
The patient's diet should be regular if the diagnosis truly is a complete abortion.
If any uncertainty about the diagnosis exists, keep the patient nothing by mouth (NPO) until certain that a surgical treatment is not necessary.
Activity: The patient should rest for a few days to 2 weeks for a complete abortion. The rest schedule needs to be adjusted if one of the other diagnoses is correct.
MEDICATION
For a complete abortion, no medication is likely to be needed. Usually, the uterus contracts well after expelling the entire contents and the cervix is closed. The risk for infection is minimal.
Drug Category: Immune globulins –
Used to suppress the immune system when the mother is Rh negative.
Drug Name
Rho (D) immune globulin (RhoGAM) -- Suppresses immune response of mother who is nonsensitized Rh O (D) negative exposed to Rh O (D) positive blood from the fetus as a result of a fetomaternal hemorrhage, abdominal trauma, amniocentesis, abortion, full-term delivery, or transfusion accident.
Adult Dose
<13>13 weeks' gestation: 300 mcg IM
Pediatric Dose
Administer as in adults
Contraindications
Documented hypersensitivity; patients who have received Rho (D)–positive blood within the last 3 mo
Interactions
None reported
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in thrombocytopenia, bleeding disorders, or IgA deficiency
Drug Category: Abortifacients –
Occasionally, the uterus does not contract well, and a clot may form in the uterine cavity. If the physician notes a boggy uterus after expulsion of the products of conception, the physician may consider methylergonovine in the appropriate candidate. In most cases in which a clot forms within the uterus, a surgical D&C finally is warranted.
Drug Name
Methylergonovine (Methergine) -- Acts directly on uterine smooth muscle, causing a sustained tetanic uterotonic effect that reduces uterine bleeding and shortens the third stage of labor.Administer IM during puerperium, delivery of placenta, or after delivering anterior shoulder. Also may be administered IV over no less than 60 sec, but should not be administered routinely because it may provoke hypertension or a stroke. Monitor blood pressure closely when administering IV.
Adult Dose
0.2 mg IM tid for 3 d
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; glaucoma; Tourette syndrome; anxiety
Interactions
Concurrent administration of methylergonovine with vasoconstrictors or other ergot alkaloids may produce additive effect
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in sepsis, obliterative vascular disease, or hepatic or renal insufficiency
Drug Name
Methotrexate (Rheumatrex) -- Antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and embryonic cell reproduction.
Adult Dose
50 mg/m2 IM once
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Interactions
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX; probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides (including TMP-SMZ) can increase MTX plasma levels; may decrease phenytoin plasma levels; may increase plasma levels of thiopurines
Pregnancy
D - Unsafe in pregnancy
Precautions
Has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; fatal reactions reported when administered concurrently with NSAIDs
FOLLOW-UP
Further Inpatient Care:
The follow-up should include monitoring hCG levels until they are less than 5 mIU/mL.
Further Outpatient Care:
With a complete abortion, measure the hCG level weekly until it is less than 5 mIU/mL in situations in which the products of conception were not evaluated by a physician (eg, the products were flushed down the toilet).
If the expelled products of conception are evaluated by a physician and confirmed to be intact and truly products of conception (not a clot), performing any further follow-up tests is not necessary.
Providing reassurance and routine gynecologic care is recommended.
Deterrence/Prevention:
Contraceptive counseling is warranted. Patients should avoid intercourse or use contraception until the hCG levels have become negative. Patients may wish to continue contraception until they are emotionally ready to try again to become pregnant.
Complications:
Complete abortions may be complicated by infection or accumulation of clot in the uterine cavity without expulsion due to uterine atony. Both of these complications are rare.
Occasionally, a decidual cast is passed and is mistaken for products of conception. In these cases, an ectopic pregnancy is likely.
Prognosis:
The prognosis is excellent. After one complete abortion, no increased risk exists for another one. Patients need reassurance. Tender loving care is proven effective therapy in one randomized recurrent pregnancy loss trial.
Patient Education:
The patient needs to hear that one miscarriage does not put her at increased risk for another miscarriage. Her next pregnancy is likely to last to term if she is young and has no other risk factors.
Advise the patient to return to the emergency department if any of the following symptoms occur:
Profuse vaginal bleeding
Severe pelvic pain
Temperature greater than 100°F
Patients may experience intermittent menstrual-like flow and cramps during the following week. The next menstrual period usually occurs in 4-5 weeks.
Patients may resume regular activities when able, but they should refrain from intercourse and douching for approximately 2 weeks.
MISCELLANEOUS
Medical/Legal Pitfalls:
Failure to diagnose correctly may occur in this situation. A presumed completed abortion may be an ectopic pregnancy with passage of clot where the clot was thought to be tissue. Missing an ectopic pregnancy can be a life-threatening situation. Be careful. If uncertainty exists regarding whether the passed tissue is tissue or a clot, have a pathologist evaluate it prior to sending the patient out.
If a suction D&C is performed, then a known complication in a small percentage of cases is Asherman syndrome or intrauterine synechiae. This situation may cause amenorrhea, infertility, or miscarriage in these patients in the future. Be gentle with the curettage, and, if there is difficulty, ultrasound guidance may be helpful. Do not forget that bleeding may be occurring due to DIC, which will not respond to a D&C but needs the missing factors replaced.
Perforation of the uterus may occur if a suction D&C is performed. Pregnant uteri are softer than the unpregnant state, and it is easier to perforate. Uterine perforation may occlude itself naturally because the uterus is a muscle that can undergo contraction and place its own pressure on the site until the bleeding stops. However, uncontrolled internal bleeding from a uterine perforation may require additional surgery, either a laparoscopy or laparotomy to control the bleeding. Occasionally, a hysterectomy may be the last resort to control the bleeding, which would eliminate the patient's ability to conceive in the future. Unrecognized uterine perforations may lead to significant internal bleeding that could be a life threat. Observe patients closely after a D&C and listen when patients complain of unusual symptoms (eg, shoulder pain, unexpectedly significant abdominal pain).
Misdiagnosis of an early intrauterine pregnancy for an ectopic pregnancy and administering methotrexate inappropriately may occur if the physician is not familiar with the laboratory and ultrasound department's discriminatory zone. Thinking about the patient's history and physical examination, differential diagnosis (including multiple gestation), the accuracy of the gestational age, the hCG level (and pattern of hCG levels if checked every 2 d), and ultrasound findings is very important in order to make an appropriate diagnosis. This is an area of rapidly growing malpractice in obstetrics and gynecology.
Medical Care: A complete abortion usually needs no further treatment, medically or surgically.
In the situation in which a considerable amount of blood loss has occurred, iron therapy or transfusions may be indicated.
If the diagnosis in not correct, the patient is likely to continue to bleed and cramp for an incomplete or inevitable abortion. In these situations, a suction D&C is indicated. If the patient has any signs of infection, start antibiotics prior to the D&C.
An ectopic pregnancy may be treated medically or surgically, depending on the clinical scenario.
Medical therapy consists of methotrexate, which usually is administered in a dose of 50 mg/m2. The effectiveness of medical therapy depends on only applying it to patients who are appropriate candidates based on gestational age, hCG level, ectopic size, patient reliability, proximity to the office or hospital, and health.
Prior to administering the methotrexate, renal and liver function tests are measured and results should be normal. A CBC is warranted, and, if significant anemia exists, then medical therapy is not warranted.
The absolute limits for gestational age, hCG level, ectopic size, and the presence or absence of an embryonic heartbeat are debated in the literature. Despite the debate, the factors that decrease the likelihood of success are older gestational age, higher hCG, larger ectopic size, and the presence of a fetal heartbeat.
The author likes to use a rule of 3s because it is easy to remember. A patient who is less than 3 weeks from expected menses (7 wk from last menstrual period [LMP]), has an hCG level less than 3000 mIU/mL, and has an ectopic size less than 3 cm has a 95% chance of success with methotrexate.
On the day of injection and on days 4 and 7 after the injection, the hCG level is monitored. A 15% drop in the hCG level is expected between day 4 and day 7. From day 1 to day 4, a rise in the hCG level may occur. If a 15% drop in the hCG level occurs on day 7, then the patient is monitored with weekly hCG levels until the level is less than 5 mIU/mL.
Patients may have some cramping or discomfort on the side of the ectopic pregnancy as the hCG declines, but these symptoms should be mild. Typically, patients do not experience bleeding until the hCG level is low.
The authors encourage increased fluid intake to avoid some of the adverse effects of methotrexate. However, this dose of methotrexate is much smaller than that used to treat trophoblastic disease, and most patients have very little problem with taking it.
After methotrexate therapy for an ectopic pregnancy, any plateau or rising of hCG requires evaluation. In some situations, considering a second dose of methotrexate is possible. However, consider surgery as well.
Any symptoms suggesting ectopic rupture (eg, acute pain, rebound tenderness) should immediately direct the physician to the operating room.
Laparoscopy can still be considered if the patient is stable.
A linear salpingostomy with excision of the ectopic pregnancy or partial salpingectomy are the possible procedures.
If the patient is unstable, the same procedures are performed using a laparotomy.
For a complete abortion, the medical care is to treat any remaining anemia and to evaluate the blood type and treat the patient with RhoGAM when indicated.
Prehospital care: Monitor vital signs and provide fluid resuscitation if the patient is hemodynamically stable.
Emergency department care: If they know what to expect, most patients with complete abortions are not treated in the emergency department. Only those with significant blood loss go to the emergency department.
Patients with threatened, inevitable, incomplete, and ectopic pregnancies may go to the emergency department.
Patients with threatened abortions need an ultrasound to confirm the diagnosis and for reassurance. Usually, no other medical therapy is needed. These patients often are counseled to increase fluid intake, remain at bedrest, or add progesterone supplements. However, none of these treatments has been proven effective in a prospective randomized trial.
Abortion, Inevitable, Abortion, Incomplete, and Ectopic Pregnancy are discussed above and in separate articles.
Surgical Care: No surgical care is used for complete abortion.
Inevitable and incomplete abortions require a D&C.
A septic abortion requires antibiotic therapy prior to a D&C. An ectopic pregnancy only is treated medically for the appropriate candidates. The rest require surgery, consisting of linear salpingostomy or partial or complete salpingectomy via laparoscopy or laparotomy.
Consultations: Consult an obstetrician-gynecologist any time uncertainty about the diagnosis exists and to administer treatment.
Diet:
The patient's diet should be regular if the diagnosis truly is a complete abortion.
If any uncertainty about the diagnosis exists, keep the patient nothing by mouth (NPO) until certain that a surgical treatment is not necessary.
Activity: The patient should rest for a few days to 2 weeks for a complete abortion. The rest schedule needs to be adjusted if one of the other diagnoses is correct.
MEDICATION
For a complete abortion, no medication is likely to be needed. Usually, the uterus contracts well after expelling the entire contents and the cervix is closed. The risk for infection is minimal.
Drug Category: Immune globulins –
Used to suppress the immune system when the mother is Rh negative.
Drug Name
Rho (D) immune globulin (RhoGAM) -- Suppresses immune response of mother who is nonsensitized Rh O (D) negative exposed to Rh O (D) positive blood from the fetus as a result of a fetomaternal hemorrhage, abdominal trauma, amniocentesis, abortion, full-term delivery, or transfusion accident.
Adult Dose
<13>13 weeks' gestation: 300 mcg IM
Pediatric Dose
Administer as in adults
Contraindications
Documented hypersensitivity; patients who have received Rho (D)–positive blood within the last 3 mo
Interactions
None reported
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in thrombocytopenia, bleeding disorders, or IgA deficiency
Drug Category: Abortifacients –
Occasionally, the uterus does not contract well, and a clot may form in the uterine cavity. If the physician notes a boggy uterus after expulsion of the products of conception, the physician may consider methylergonovine in the appropriate candidate. In most cases in which a clot forms within the uterus, a surgical D&C finally is warranted.
Drug Name
Methylergonovine (Methergine) -- Acts directly on uterine smooth muscle, causing a sustained tetanic uterotonic effect that reduces uterine bleeding and shortens the third stage of labor.Administer IM during puerperium, delivery of placenta, or after delivering anterior shoulder. Also may be administered IV over no less than 60 sec, but should not be administered routinely because it may provoke hypertension or a stroke. Monitor blood pressure closely when administering IV.
Adult Dose
0.2 mg IM tid for 3 d
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; glaucoma; Tourette syndrome; anxiety
Interactions
Concurrent administration of methylergonovine with vasoconstrictors or other ergot alkaloids may produce additive effect
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in sepsis, obliterative vascular disease, or hepatic or renal insufficiency
Drug Name
Methotrexate (Rheumatrex) -- Antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and embryonic cell reproduction.
Adult Dose
50 mg/m2 IM once
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Interactions
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate (MTX); charcoal lowers MTX levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX; probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides (including TMP-SMZ) can increase MTX plasma levels; may decrease phenytoin plasma levels; may increase plasma levels of thiopurines
Pregnancy
D - Unsafe in pregnancy
Precautions
Has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; fatal reactions reported when administered concurrently with NSAIDs
FOLLOW-UP
Further Inpatient Care:
The follow-up should include monitoring hCG levels until they are less than 5 mIU/mL.
Further Outpatient Care:
With a complete abortion, measure the hCG level weekly until it is less than 5 mIU/mL in situations in which the products of conception were not evaluated by a physician (eg, the products were flushed down the toilet).
If the expelled products of conception are evaluated by a physician and confirmed to be intact and truly products of conception (not a clot), performing any further follow-up tests is not necessary.
Providing reassurance and routine gynecologic care is recommended.
Deterrence/Prevention:
Contraceptive counseling is warranted. Patients should avoid intercourse or use contraception until the hCG levels have become negative. Patients may wish to continue contraception until they are emotionally ready to try again to become pregnant.
Complications:
Complete abortions may be complicated by infection or accumulation of clot in the uterine cavity without expulsion due to uterine atony. Both of these complications are rare.
Occasionally, a decidual cast is passed and is mistaken for products of conception. In these cases, an ectopic pregnancy is likely.
Prognosis:
The prognosis is excellent. After one complete abortion, no increased risk exists for another one. Patients need reassurance. Tender loving care is proven effective therapy in one randomized recurrent pregnancy loss trial.
Patient Education:
The patient needs to hear that one miscarriage does not put her at increased risk for another miscarriage. Her next pregnancy is likely to last to term if she is young and has no other risk factors.
Advise the patient to return to the emergency department if any of the following symptoms occur:
Profuse vaginal bleeding
Severe pelvic pain
Temperature greater than 100°F
Patients may experience intermittent menstrual-like flow and cramps during the following week. The next menstrual period usually occurs in 4-5 weeks.
Patients may resume regular activities when able, but they should refrain from intercourse and douching for approximately 2 weeks.
MISCELLANEOUS
Medical/Legal Pitfalls:
Failure to diagnose correctly may occur in this situation. A presumed completed abortion may be an ectopic pregnancy with passage of clot where the clot was thought to be tissue. Missing an ectopic pregnancy can be a life-threatening situation. Be careful. If uncertainty exists regarding whether the passed tissue is tissue or a clot, have a pathologist evaluate it prior to sending the patient out.
If a suction D&C is performed, then a known complication in a small percentage of cases is Asherman syndrome or intrauterine synechiae. This situation may cause amenorrhea, infertility, or miscarriage in these patients in the future. Be gentle with the curettage, and, if there is difficulty, ultrasound guidance may be helpful. Do not forget that bleeding may be occurring due to DIC, which will not respond to a D&C but needs the missing factors replaced.
Perforation of the uterus may occur if a suction D&C is performed. Pregnant uteri are softer than the unpregnant state, and it is easier to perforate. Uterine perforation may occlude itself naturally because the uterus is a muscle that can undergo contraction and place its own pressure on the site until the bleeding stops. However, uncontrolled internal bleeding from a uterine perforation may require additional surgery, either a laparoscopy or laparotomy to control the bleeding. Occasionally, a hysterectomy may be the last resort to control the bleeding, which would eliminate the patient's ability to conceive in the future. Unrecognized uterine perforations may lead to significant internal bleeding that could be a life threat. Observe patients closely after a D&C and listen when patients complain of unusual symptoms (eg, shoulder pain, unexpectedly significant abdominal pain).
Misdiagnosis of an early intrauterine pregnancy for an ectopic pregnancy and administering methotrexate inappropriately may occur if the physician is not familiar with the laboratory and ultrasound department's discriminatory zone. Thinking about the patient's history and physical examination, differential diagnosis (including multiple gestation), the accuracy of the gestational age, the hCG level (and pattern of hCG levels if checked every 2 d), and ultrasound findings is very important in order to make an appropriate diagnosis. This is an area of rapidly growing malpractice in obstetrics and gynecology.
Threatened Abortion 1
Threatened Abortion
INTRODUCTION
Background: Threatened abortion is a clinically descriptive term that applies to women who are at less than 20 weeks' gestation, have vaginal spotting or bleeding, a closed cervical os, and, possibly, mild uterine cramping.
Pathophysiology: Threatened abortions may progress to inevitable, spontaneous, incomplete, or complete abortions.
Threatened abortion
Vaginal spotting or frank bleeding is very common and is experienced in approximately 25% of clinically apparent pregnancies at less than 20 weeks' gestational age. The bleeding and pain that accompany threatened abortion are not usually intense. Threatened abortion rarely manifests with severe vaginal bleeding. Often, the bleeding is temporary and self-limited and probably due to trophoblastic implantation within the decidualized endometrium.
Approximately half the women with threatened abortions abort, and the remainder continue to have viable pregnancies. Approximately 15% of clinically recognized pregnancies spontaneously abort, and 75% of the losses occur in the first 8 weeks of gestation. The loss rate is estimated to be 2-3 times higher with very early and, often, clinically unrecognized pregnancies.
Threatened abortion is defined by the absence of passing/passed tissue and the presence of a closed cervical os. These findings differentiate threatened abortion from later stages of abortion.
Inevitable abortion
Vaginal bleeding is accompanied by dilatation of the cervical canal, no passage of fetal tissue, and, occasionally, gross rupture of the membranes. Bleeding is usually more severe than with threatened abortion and is often associated with abdominal pain.
Incomplete abortion
Vaginal bleeding is usually heavy and accompanied by abdominal pain. The cervical os is open, with passage of only part of the products of conception. Incomplete abortion is more likely to occur at 6-14 weeks of pregnancy. Ultrasonography (if used) reveals that some products of conception are still present in the uterus; these typically appear as echogenic material.
Complete abortion
Patients usually present with a history of bleeding, abdominal pain, and passing of tissue. By the time miscarriage is complete, bleeding and pain have usually subsided and the cervix is closed. Diagnosis may be confirmed by observation of the aborted fetus with the complete placenta. Ultrasound reveals a vacant uterus with close apposition of relatively thin and regular endometrial interfaces.
Frequency:
In the US: The World Health Organization estimates that 15% of all clinically recognizable pregnancies end in spontaneous abortion.
Mortality/Morbidity: Surveillance data from 1987-1990 reveal a total of 1459 pregnancy-related deaths in the United States. Spontaneous and induced abortions account for 5.6% of these deaths.
CLINICAL
History: Any woman of reproductive age with abnormal vaginal bleeding should be considered pregnant until proven otherwise.
Obtain a careful history, including the following:
Menstrual history: Deviations from the normal menstrual period may reflect bleeding from implantation of a normal or abnormal pregnancy, which can make accurate dating difficult.
First date of the last menstrual period (LMP)
Previous menstrual period
Usual menstrual interval
Regularity of menses
Date of conception, if known
Medication use since LMP; alcohol, tobacco, and recreational drug use
Current and past medical problems such as diabetes mellitus, recent infections, bleeding diathesis, thyroid disease, or autoimmune disorders
Surgical history, particularly operations involving the uterus and adnexa
Past obstetric history
Number of term and preterm deliveries
Number of spontaneous and induced abortions
Number of living children and major complications associated with deliveries or abortions (eg, blood transfusions, perforated uterus)
Gynecologic history, including abnormal Papanicolaou test (Pap smear) results, sexually transmitted diseases, and contraception
Patients with spontaneous abortion usually present with vaginal bleeding and/or abdominal pain.
Vaginal bleeding may vary from slight spotting to significant hemorrhage. Quantifying the amount of bleeding (number of soaked pads or tampons) is very important, as is noting whether the bleeding is improving or worsening.
Bleeding from threatened abortions frequently is slight, but it may persist for days or weeks.
The presence of blood clots or tissue may be an important sign of progression of spontaneous abortion.
Associated pain or cramping should be recorded, including the location, severity, and duration of pain.
Other symptoms such as fever or chills are more characteristic of a septic abortion.
Physical: Make an immediate assessment of patients who are hemodynamically unstable or experiencing severe vaginal bleeding, including orthostatic vital signs and abdominal and pelvic examination. If orthostatic hypotension is present, initiate intravenous fluid resuscitation and blood cross-match.
Examine the abdomen, with particular attention to tenderness, bloating, or peritoneal signs suggestive of intraperitoneal hemorrhage.
Identify the source of bleeding by means of a visual speculum and digital pelvic examination of the cervix. Determine whether the bleeding originates from the vaginal walls, the surface of the cervix, or through the cervical os.
Determine the intensity of bleeding, examining for the presence of blood clots or tissue fragments.
Examine for cervical motion tenderness because this finding increases the possibility of ectopic pregnancy.
Determine the status of the cervical os. If open, it indicates an inevitable or incomplete abortion; if closed, it is a threatened abortion.
Examine for uterine size, consistency, and tenderness and for the presence of adnexal tenderness or masses. If a mass is suggested, palpation should be gentle because iatrogenic rupture of an ectopic pregnancy or an ovarian cyst is possible.
If the vaginal or cervical discharge appears abnormal, a wet preparation and cervical cultures (or enzyme-linked immunosorbent assay) for gonorrheal and chlamydial organisms should be performed.
Causes:
Embryonic abnormalities account for approximately 80% of first-trimester abortions.
Chromosomal abnormalities are the most common cause of spontaneous abortion. Autosomal trisomies account for more than half of the abnormal karyotypes (due to nondisjunction or translocation), and monosomy is the next most common anomaly.
More than 90% of cytogenic and morphologic errors are eliminated through spontaneous miscarriages.
Chromosomal abnormalities are found in more than 75% of fetuses aborted in the first trimester.
The rate of chromosomal abnormalities increases with maternal age. In women younger than 30 years, the rate of miscarriage is approximately 12%; thereafter, the rate increases rapidly, exceeding 50% in women older than 45 years.
Maternal factors account for the majority of second-trimester abortions.
Chronic maternal health factors
Maternal insulin-dependent diabetes mellitus: Up to 30% of pregnancies in patients with poorly controlled diabetes mellitus result in spontaneous abortion.
Severe hypertension
Renal disease
Antiphospholipid syndrome
Systemic lupus erythematosus
Thyroid disease
Wilson disease
Acute maternal health factors
Infections (eg, cytomegalovirus, rubella, toxoplasmosis, Listeria, Ureaplasma, Mycoplasma, and syphilis)
Trauma
Abnormalities of the reproductive system
Congenital (eg, septate uterus) or acquired defects (eg, uterine synechiae)
Fibroids
Cervical incompetence
Abnormal placental development
Exogenous factors
Caffeine: Drinking more than 4 cups of coffee per day appears to slightly increase the risk of abortion.
Alcohol
Tobacco
Cocaine
Radiation
DIFFERENTIALS
Appendicitis Benign Cervical Lesions Cervical Cancer Cervicitis Dysfunctional Uterine Bleeding Dysmenorrhea Ectopic Pregnancy Endometriosis Gestational Trophoblastic Neoplasia Ovarian Cysts Pregnancy and Urolithiasis Trauma and Pregnancy Urinary Tract Infections in Pregnancy Vaginitis
Other Problems to be Considered:
Foreign body
WORKUP
Lab Studies:
Beta-human chorionic gonadotropin
The test for human chorionic gonadotropin is qualitative and, if results are positive, quantitative.
It is first detectable as early as 9-11 days following ovulation (which, in most women, is approximately 24 d after the LMP).
When the quantitative human chorionic gonadotropin (QhCG) measurement is greater than 1500 mIU/mL international reference preparation (IRP), a normal intrauterine pregnancy should be visualized on transvaginal sonography (TVS) images. This discriminatory number, the value of QhCG for which a normal intrauterine pregnancy should be seen, is 6500 mIU/mL IRP for transabdominal sonogram. Failure to detect an intrauterine gestational sac when the QhCG value exceeds the discriminatory level indicates a risk of ectopic pregnancy.
Even if results are not readily available, a QhCG level should generally be determined in cases of first-trimester bleeding because serial QhCGs values can be helpful in follow-up care.
The QhCG level generally rises by at least 66% every 48 hours in a viable intrauterine pregnancy. Serial QhCG values that level off or fall before the 10th week of gestation usually indicate an abnormal pregnancy. An abnormally high QhCG level may indicate multiple gestation, gestational trophoblastic disease, or, very rarely, ovarian tumor.
Hemoglobin and hematocrit: These values can be used to establish a baseline and to help detect hemorrhagic anemia.
Blood type and antibody screen
A woman who is Rh negative and has an abortion (either spontaneous or therapeutic) is at a 2-4% risk of becoming Rh-sensitized.
The Rh factor status must be documented for every pregnant patient with vaginal bleeding.
If patients are Rh negative, administer Rho (D) immune globulin (RhoGAM) to prevent isoimmunization.
Serum progesterone level
Progesterone levels rise after ovulation and continue to rise throughout pregnancy.
Several investigators have studied the role of serum progesterone during early pregnancy with regard to the differential diagnosis of early pregnancy disorders. A level of less than 5 ng/mL is invariably associated with pregnancy nonviability, whereas a level greater than 25 ng/mL is almost always associated with a viable pregnancy.
In most clinical settings, the value is 5-15 ng/mL and, therefore, is of limited clinical value. Furthermore, in clinical settings in which the QhCG titers and TVS findings can be correlated promptly, the role of serum progesterone evaluation is limited and may not be cost-effective or available in a timely manner.
Imaging Studies:
Ultrasound is widely available and is the imaging study of choice.
Advantages include safety, bedside use, low cost, and noninvasiveness. Disadvantages include operator dependency.
TVS images can help determine presence of an embryo/fetus, the presence of heart motion, intactness of the choriodecidua, location (intrauterine or extrauterine), and gestational age. Serial or repeat ultrasound examinations may be necessary if the initial scan findings are inconclusive and the patient's condition is stable.
A pregnancy should not be terminated based on findings from a single sonographic examination that demonstrate a lack of fetal heart motion during the embryonic stage (3-5 mm crown-rump length [CRL]) of development. A follow-up scan is usually indicated to confirm the lack of embryonic or fetal activity. In general, an embryo should be seen in a sac larger than 6-9 mm, and embryonic heart motion should be seen when the sac is 10-14 mm in size or when an embryo is longer than 5 mm. Embryos of CRL longer than 5 mm who do not have a heartbeat are nonviable.
In a normal pregnancy, heart motion should be demonstrated on TVS images of embryos that are longer than 5 mm or are of 5-6 weeks' gestation.
Fetal heart activity demonstrated on ultrasound images is associated with a viable outcome in more than 90% of cases.
Early embryonic demise has a variety of appearances, ranging from a gestational sac devoid of a yolk sac or embryo to a yolk sac/embryo complex with no embryonic heart motion.
Patients who experience first-trimester vaginal bleeding may demonstrate areas of retrochorionic hemorrhage on TVS images, which appear as relatively hypoechoic areas behind the chorionic layer. If the hemorrhage is small and remote to the decidua basalis, the chance for pregnancy completion is better than if the hemorrhage extends behind the decidua basalis or is more than 25% of the size of the gestational sac.
INTRODUCTION
Background: Threatened abortion is a clinically descriptive term that applies to women who are at less than 20 weeks' gestation, have vaginal spotting or bleeding, a closed cervical os, and, possibly, mild uterine cramping.
Pathophysiology: Threatened abortions may progress to inevitable, spontaneous, incomplete, or complete abortions.
Threatened abortion
Vaginal spotting or frank bleeding is very common and is experienced in approximately 25% of clinically apparent pregnancies at less than 20 weeks' gestational age. The bleeding and pain that accompany threatened abortion are not usually intense. Threatened abortion rarely manifests with severe vaginal bleeding. Often, the bleeding is temporary and self-limited and probably due to trophoblastic implantation within the decidualized endometrium.
Approximately half the women with threatened abortions abort, and the remainder continue to have viable pregnancies. Approximately 15% of clinically recognized pregnancies spontaneously abort, and 75% of the losses occur in the first 8 weeks of gestation. The loss rate is estimated to be 2-3 times higher with very early and, often, clinically unrecognized pregnancies.
Threatened abortion is defined by the absence of passing/passed tissue and the presence of a closed cervical os. These findings differentiate threatened abortion from later stages of abortion.
Inevitable abortion
Vaginal bleeding is accompanied by dilatation of the cervical canal, no passage of fetal tissue, and, occasionally, gross rupture of the membranes. Bleeding is usually more severe than with threatened abortion and is often associated with abdominal pain.
Incomplete abortion
Vaginal bleeding is usually heavy and accompanied by abdominal pain. The cervical os is open, with passage of only part of the products of conception. Incomplete abortion is more likely to occur at 6-14 weeks of pregnancy. Ultrasonography (if used) reveals that some products of conception are still present in the uterus; these typically appear as echogenic material.
Complete abortion
Patients usually present with a history of bleeding, abdominal pain, and passing of tissue. By the time miscarriage is complete, bleeding and pain have usually subsided and the cervix is closed. Diagnosis may be confirmed by observation of the aborted fetus with the complete placenta. Ultrasound reveals a vacant uterus with close apposition of relatively thin and regular endometrial interfaces.
Frequency:
In the US: The World Health Organization estimates that 15% of all clinically recognizable pregnancies end in spontaneous abortion.
Mortality/Morbidity: Surveillance data from 1987-1990 reveal a total of 1459 pregnancy-related deaths in the United States. Spontaneous and induced abortions account for 5.6% of these deaths.
CLINICAL
History: Any woman of reproductive age with abnormal vaginal bleeding should be considered pregnant until proven otherwise.
Obtain a careful history, including the following:
Menstrual history: Deviations from the normal menstrual period may reflect bleeding from implantation of a normal or abnormal pregnancy, which can make accurate dating difficult.
First date of the last menstrual period (LMP)
Previous menstrual period
Usual menstrual interval
Regularity of menses
Date of conception, if known
Medication use since LMP; alcohol, tobacco, and recreational drug use
Current and past medical problems such as diabetes mellitus, recent infections, bleeding diathesis, thyroid disease, or autoimmune disorders
Surgical history, particularly operations involving the uterus and adnexa
Past obstetric history
Number of term and preterm deliveries
Number of spontaneous and induced abortions
Number of living children and major complications associated with deliveries or abortions (eg, blood transfusions, perforated uterus)
Gynecologic history, including abnormal Papanicolaou test (Pap smear) results, sexually transmitted diseases, and contraception
Patients with spontaneous abortion usually present with vaginal bleeding and/or abdominal pain.
Vaginal bleeding may vary from slight spotting to significant hemorrhage. Quantifying the amount of bleeding (number of soaked pads or tampons) is very important, as is noting whether the bleeding is improving or worsening.
Bleeding from threatened abortions frequently is slight, but it may persist for days or weeks.
The presence of blood clots or tissue may be an important sign of progression of spontaneous abortion.
Associated pain or cramping should be recorded, including the location, severity, and duration of pain.
Other symptoms such as fever or chills are more characteristic of a septic abortion.
Physical: Make an immediate assessment of patients who are hemodynamically unstable or experiencing severe vaginal bleeding, including orthostatic vital signs and abdominal and pelvic examination. If orthostatic hypotension is present, initiate intravenous fluid resuscitation and blood cross-match.
Examine the abdomen, with particular attention to tenderness, bloating, or peritoneal signs suggestive of intraperitoneal hemorrhage.
Identify the source of bleeding by means of a visual speculum and digital pelvic examination of the cervix. Determine whether the bleeding originates from the vaginal walls, the surface of the cervix, or through the cervical os.
Determine the intensity of bleeding, examining for the presence of blood clots or tissue fragments.
Examine for cervical motion tenderness because this finding increases the possibility of ectopic pregnancy.
Determine the status of the cervical os. If open, it indicates an inevitable or incomplete abortion; if closed, it is a threatened abortion.
Examine for uterine size, consistency, and tenderness and for the presence of adnexal tenderness or masses. If a mass is suggested, palpation should be gentle because iatrogenic rupture of an ectopic pregnancy or an ovarian cyst is possible.
If the vaginal or cervical discharge appears abnormal, a wet preparation and cervical cultures (or enzyme-linked immunosorbent assay) for gonorrheal and chlamydial organisms should be performed.
Causes:
Embryonic abnormalities account for approximately 80% of first-trimester abortions.
Chromosomal abnormalities are the most common cause of spontaneous abortion. Autosomal trisomies account for more than half of the abnormal karyotypes (due to nondisjunction or translocation), and monosomy is the next most common anomaly.
More than 90% of cytogenic and morphologic errors are eliminated through spontaneous miscarriages.
Chromosomal abnormalities are found in more than 75% of fetuses aborted in the first trimester.
The rate of chromosomal abnormalities increases with maternal age. In women younger than 30 years, the rate of miscarriage is approximately 12%; thereafter, the rate increases rapidly, exceeding 50% in women older than 45 years.
Maternal factors account for the majority of second-trimester abortions.
Chronic maternal health factors
Maternal insulin-dependent diabetes mellitus: Up to 30% of pregnancies in patients with poorly controlled diabetes mellitus result in spontaneous abortion.
Severe hypertension
Renal disease
Antiphospholipid syndrome
Systemic lupus erythematosus
Thyroid disease
Wilson disease
Acute maternal health factors
Infections (eg, cytomegalovirus, rubella, toxoplasmosis, Listeria, Ureaplasma, Mycoplasma, and syphilis)
Trauma
Abnormalities of the reproductive system
Congenital (eg, septate uterus) or acquired defects (eg, uterine synechiae)
Fibroids
Cervical incompetence
Abnormal placental development
Exogenous factors
Caffeine: Drinking more than 4 cups of coffee per day appears to slightly increase the risk of abortion.
Alcohol
Tobacco
Cocaine
Radiation
DIFFERENTIALS
Appendicitis Benign Cervical Lesions Cervical Cancer Cervicitis Dysfunctional Uterine Bleeding Dysmenorrhea Ectopic Pregnancy Endometriosis Gestational Trophoblastic Neoplasia Ovarian Cysts Pregnancy and Urolithiasis Trauma and Pregnancy Urinary Tract Infections in Pregnancy Vaginitis
Other Problems to be Considered:
Foreign body
WORKUP
Lab Studies:
Beta-human chorionic gonadotropin
The test for human chorionic gonadotropin is qualitative and, if results are positive, quantitative.
It is first detectable as early as 9-11 days following ovulation (which, in most women, is approximately 24 d after the LMP).
When the quantitative human chorionic gonadotropin (QhCG) measurement is greater than 1500 mIU/mL international reference preparation (IRP), a normal intrauterine pregnancy should be visualized on transvaginal sonography (TVS) images. This discriminatory number, the value of QhCG for which a normal intrauterine pregnancy should be seen, is 6500 mIU/mL IRP for transabdominal sonogram. Failure to detect an intrauterine gestational sac when the QhCG value exceeds the discriminatory level indicates a risk of ectopic pregnancy.
Even if results are not readily available, a QhCG level should generally be determined in cases of first-trimester bleeding because serial QhCGs values can be helpful in follow-up care.
The QhCG level generally rises by at least 66% every 48 hours in a viable intrauterine pregnancy. Serial QhCG values that level off or fall before the 10th week of gestation usually indicate an abnormal pregnancy. An abnormally high QhCG level may indicate multiple gestation, gestational trophoblastic disease, or, very rarely, ovarian tumor.
Hemoglobin and hematocrit: These values can be used to establish a baseline and to help detect hemorrhagic anemia.
Blood type and antibody screen
A woman who is Rh negative and has an abortion (either spontaneous or therapeutic) is at a 2-4% risk of becoming Rh-sensitized.
The Rh factor status must be documented for every pregnant patient with vaginal bleeding.
If patients are Rh negative, administer Rho (D) immune globulin (RhoGAM) to prevent isoimmunization.
Serum progesterone level
Progesterone levels rise after ovulation and continue to rise throughout pregnancy.
Several investigators have studied the role of serum progesterone during early pregnancy with regard to the differential diagnosis of early pregnancy disorders. A level of less than 5 ng/mL is invariably associated with pregnancy nonviability, whereas a level greater than 25 ng/mL is almost always associated with a viable pregnancy.
In most clinical settings, the value is 5-15 ng/mL and, therefore, is of limited clinical value. Furthermore, in clinical settings in which the QhCG titers and TVS findings can be correlated promptly, the role of serum progesterone evaluation is limited and may not be cost-effective or available in a timely manner.
Imaging Studies:
Ultrasound is widely available and is the imaging study of choice.
Advantages include safety, bedside use, low cost, and noninvasiveness. Disadvantages include operator dependency.
TVS images can help determine presence of an embryo/fetus, the presence of heart motion, intactness of the choriodecidua, location (intrauterine or extrauterine), and gestational age. Serial or repeat ultrasound examinations may be necessary if the initial scan findings are inconclusive and the patient's condition is stable.
A pregnancy should not be terminated based on findings from a single sonographic examination that demonstrate a lack of fetal heart motion during the embryonic stage (3-5 mm crown-rump length [CRL]) of development. A follow-up scan is usually indicated to confirm the lack of embryonic or fetal activity. In general, an embryo should be seen in a sac larger than 6-9 mm, and embryonic heart motion should be seen when the sac is 10-14 mm in size or when an embryo is longer than 5 mm. Embryos of CRL longer than 5 mm who do not have a heartbeat are nonviable.
In a normal pregnancy, heart motion should be demonstrated on TVS images of embryos that are longer than 5 mm or are of 5-6 weeks' gestation.
Fetal heart activity demonstrated on ultrasound images is associated with a viable outcome in more than 90% of cases.
Early embryonic demise has a variety of appearances, ranging from a gestational sac devoid of a yolk sac or embryo to a yolk sac/embryo complex with no embryonic heart motion.
Patients who experience first-trimester vaginal bleeding may demonstrate areas of retrochorionic hemorrhage on TVS images, which appear as relatively hypoechoic areas behind the chorionic layer. If the hemorrhage is small and remote to the decidua basalis, the chance for pregnancy completion is better than if the hemorrhage extends behind the decidua basalis or is more than 25% of the size of the gestational sac.
Therapeutic Abortion 4
Drug Name
Misoprostol (Cytotec)
Description
Synthetic prostaglandin E1 analog. Abortifacient effect results from increased frequency of uterine contractions. May be used alone or as part of regimen with mifepristone up to 49 d since LMP or with methotrexate up to 63 d since LMP.
Adult Dose
During second trimester (17-24 wk): 200-mcg tab placed in posterior vaginal fornix, repeat in 12 h; if fetus not delivered in 24 h, add 20-mg dinoprostone intravaginal supp q3h until delivery of fetusWith mifepristone: 400 mcg PO 48 h after mifepristoneWith methotrexate: 800 mcg PV 5-7 d after methotrexate, if no vaginal bleeding repeat in 24 h
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity
Interactions
None reported
Pregnancy
X - Contraindicated in pregnancy
Precautions
Caution in patients with renal impairment and in elderly patients
Drug Name
Dinoprostone, PGE2 (Prostin E2 suppository)
Description
Induces uterine contractions by stimulating myometrium. Used during second-trimester medical abortions if fetus does not deliver in 24 h. Also used during instillation technique abortions to make cervix inducible.
Adult Dose
Medical abortion: 20 mg PV q3h until delivery of fetus occurs
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; acute pelvic inflammatory disease; uterine fibroids; cervical stenosis
Interactions
Increased effects of oxytocics
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in patients with anemia, asthma, cervicitis, infected endocervical lesions, acute vaginitis, diabetes mellitus, epilepsy, compromised uteri (ie, fibroid tumors, surgery), cardiovascular disease, hypertension or hypotension, renal or hepatic impairment; associated with GI distress, headache, arrhythmias, angina, uterine rupture, dyspnea, wheezing
Surgical therapy: Surgical abortion techniques available for therapeutic termination of pregnancy include the following:
Manual vacuum aspiration (ie, menstrual extraction)
Suction curettage
Dilation and extraction
Hysterotomy
Hysterectomy
The choice of surgical abortion technique depends on the gestational age of the pregnancy; the expertise of the available medical staff; the clinical importance of obtaining an intact fetus; and the medical, surgical, psychiatric, and anesthetic contraindications to the various techniques. See Surgical Management of Abortion for a detailed discussion of surgical abortion techniques.
Preoperative details: For selective reduction procedures, evaluation of the fetuses using chorionic villus sampling or amniocentesis can assist in selection of the appropriate fetuses for reduction.
The use of ultrasound to assess fetal growth, fetal heart rate, and fetal nuchal thickening can also be helpful in the selection process. Criteria such as nuchal translucency of more than 3 mm, a lag in growth longer than 3 days, or a heart rate less than 80 beats per minute can be used to select the appropriate fetus for reduction.
COMPLICATIONS
As with all interventions, complications are associated with all methods used for termination of pregnancy. For complications associated with surgical abortion, see Surgical Management of Abortion. Medical abortions in the first trimester are safe and well-tolerated procedures. The major problems are decreased effectiveness of medical abortion with increasing gestational age and the long interval between administration of medication to completion of abortion for certain medications (eg, methotrexate, tamoxifen).
Complications and adverse effects associated with specific medications are as follows:
Methotrexate and misoprostol: Complications associated with the proper dose are rare, but the following can occur:
Stomatitis (0.66%)
GI morbidity
Nausea (10-37%)
Vomiting (7-25%)
Diarrhea (2-52%)
Thrombocytopenia
Chemical hepatitis
Failed abortion (4-12%)
Mifepristone and misoprostol
Transfusion (0.1%)
Pain requiring narcotic analgesia (4-15%)
Vomiting (12-44%)
Diarrhea (7-39%)
Failed abortion (2-6%)
Misoprostol and tamoxifen
Vomiting (28%)
Diarrhea (8%)
Failed abortion (8%)
Misoprostol alone
Nausea (24%)
Vomiting (25-26%)
Diarrhea (58%)
Headache (13-15%)
Fever (35%)
Chills (54-57%)
Failed abortion (6-8%)
Complications associated with instillation techniques are as follows:
Hemorrhage requiring transfusion (0.32-1.72%)
Infection
Incomplete abortion
Cervical laceration
Hypernatremia and sodium load (saline)
Muscle necrosis (myometrial injection of saline or urea)
Adverse GI effects
Unintended surgery (0.04-0.08 cases per 100 instillations)
Disseminated intravascular coagulopathy (saline, 658 cases per 100,000 instillations)
Urea instillation abortions are reported to be safer than saline abortions. Prostaglandin-induced second-trimester abortions are safer than saline abortions and have a lower induction-to-completion time.
Of all methods of second-trimester abortion, the safest procedure (using mortality surveillance data) is dilation and extraction. Intermediate risk of mortality occurs with instillation procedures. The highest mortality rates for second-trimester abortions are associated with major surgical procedures (ie, hysterotomy, hysterectomy).
Selective reduction procedures are not included in the statistics for second-trimester abortions. For the rare condition of monochorionic twins, selective reduction cord occlusion techniques are reported by Challis et al to have premature rupture of membranes in up to 30% of cases. The more common method of intracardiac injection techniques for selective reduction is associated with premature rupture of membranes in 13% of triplet pregnancies reduced to twins and in 19.3% of quadruplets reduced to twins. The risk of miscarriage in a pregnancy undergoing selective reduction is inversely proportional to the number of fetuses in the initial pregnancy (ie, quintuplet, 24.8%; triplet, 8.3%)
OUTCOME AND PROGNOSIS
Advantages of medical abortion are as follows:
Can be performed without delay
Avoids anesthesia and surgical risks
Psychological advantage - Patient control
Wider availability of abortion services
Increased patient choice
Advantages of surgical abortion are as follows:
More effective than medical abortion
Shorter completion time
Shorter bleeding duration
No exposure to potential teratogens
Can be performed later in gestational age
Fewer visits
Surgical abortion is 99% effective in terminating pregnancy. Medical abortion using mifepristone and misoprostol has a mean effectiveness of 94%. Medical abortion using methotrexate and misoprostol has effectiveness ranging from 88-96%. Medical abortion in the second trimester using misoprostol has effectiveness ranging from 40-89% within 24 hours. Instillation methods of abortion have effectiveness ranging from 81-86% at 48 hours to 97% at 72 hours.
As with all interventions, complications are associated with all the methods of termination of pregnancy. For complications associated with surgical abortion techniques, see Surgical Management of Abortion.
Medical abortions in the first trimester are very safe and well-tolerated procedures. The major problem is decreased efficacy with increasing gestational age. In the case of methotrexate, a long period of time between administration of medication to abortion is problematic.
First-trimester abortions performed by surgical or medical methods are well tolerated, have little effect on future fertility, and are not associated with long-term psychological consequences. Second-trimester abortions are well known to be associated with increased risk of morbidity and mortality with increasing gestational age. An association of increased risk for preterm delivery after dilation with metal dilators has been reported.
FUTURE AND CONTROVERSIES
Future research is expected to evaluate alternative protocols for medical abortion. Research is expected to continue evaluating other medications for medical abortion, including further research using the following:
Tamoxifen, an antiestrogen that interferes with decidual development in an animal model and is associated with incomplete and threatened abortion in humans
Epostane (3beta-hydroxysteroid dehydrogenase inhibitor), which works by blocking the synthesis of progesterone
The potential exists for wider use of medical management of incomplete and missed abortions as the techniques for medical abortion become commonplace.
Misoprostol (Cytotec)
Description
Synthetic prostaglandin E1 analog. Abortifacient effect results from increased frequency of uterine contractions. May be used alone or as part of regimen with mifepristone up to 49 d since LMP or with methotrexate up to 63 d since LMP.
Adult Dose
During second trimester (17-24 wk): 200-mcg tab placed in posterior vaginal fornix, repeat in 12 h; if fetus not delivered in 24 h, add 20-mg dinoprostone intravaginal supp q3h until delivery of fetusWith mifepristone: 400 mcg PO 48 h after mifepristoneWith methotrexate: 800 mcg PV 5-7 d after methotrexate, if no vaginal bleeding repeat in 24 h
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity
Interactions
None reported
Pregnancy
X - Contraindicated in pregnancy
Precautions
Caution in patients with renal impairment and in elderly patients
Drug Name
Dinoprostone, PGE2 (Prostin E2 suppository)
Description
Induces uterine contractions by stimulating myometrium. Used during second-trimester medical abortions if fetus does not deliver in 24 h. Also used during instillation technique abortions to make cervix inducible.
Adult Dose
Medical abortion: 20 mg PV q3h until delivery of fetus occurs
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; acute pelvic inflammatory disease; uterine fibroids; cervical stenosis
Interactions
Increased effects of oxytocics
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in patients with anemia, asthma, cervicitis, infected endocervical lesions, acute vaginitis, diabetes mellitus, epilepsy, compromised uteri (ie, fibroid tumors, surgery), cardiovascular disease, hypertension or hypotension, renal or hepatic impairment; associated with GI distress, headache, arrhythmias, angina, uterine rupture, dyspnea, wheezing
Surgical therapy: Surgical abortion techniques available for therapeutic termination of pregnancy include the following:
Manual vacuum aspiration (ie, menstrual extraction)
Suction curettage
Dilation and extraction
Hysterotomy
Hysterectomy
The choice of surgical abortion technique depends on the gestational age of the pregnancy; the expertise of the available medical staff; the clinical importance of obtaining an intact fetus; and the medical, surgical, psychiatric, and anesthetic contraindications to the various techniques. See Surgical Management of Abortion for a detailed discussion of surgical abortion techniques.
Preoperative details: For selective reduction procedures, evaluation of the fetuses using chorionic villus sampling or amniocentesis can assist in selection of the appropriate fetuses for reduction.
The use of ultrasound to assess fetal growth, fetal heart rate, and fetal nuchal thickening can also be helpful in the selection process. Criteria such as nuchal translucency of more than 3 mm, a lag in growth longer than 3 days, or a heart rate less than 80 beats per minute can be used to select the appropriate fetus for reduction.
COMPLICATIONS
As with all interventions, complications are associated with all methods used for termination of pregnancy. For complications associated with surgical abortion, see Surgical Management of Abortion. Medical abortions in the first trimester are safe and well-tolerated procedures. The major problems are decreased effectiveness of medical abortion with increasing gestational age and the long interval between administration of medication to completion of abortion for certain medications (eg, methotrexate, tamoxifen).
Complications and adverse effects associated with specific medications are as follows:
Methotrexate and misoprostol: Complications associated with the proper dose are rare, but the following can occur:
Stomatitis (0.66%)
GI morbidity
Nausea (10-37%)
Vomiting (7-25%)
Diarrhea (2-52%)
Thrombocytopenia
Chemical hepatitis
Failed abortion (4-12%)
Mifepristone and misoprostol
Transfusion (0.1%)
Pain requiring narcotic analgesia (4-15%)
Vomiting (12-44%)
Diarrhea (7-39%)
Failed abortion (2-6%)
Misoprostol and tamoxifen
Vomiting (28%)
Diarrhea (8%)
Failed abortion (8%)
Misoprostol alone
Nausea (24%)
Vomiting (25-26%)
Diarrhea (58%)
Headache (13-15%)
Fever (35%)
Chills (54-57%)
Failed abortion (6-8%)
Complications associated with instillation techniques are as follows:
Hemorrhage requiring transfusion (0.32-1.72%)
Infection
Incomplete abortion
Cervical laceration
Hypernatremia and sodium load (saline)
Muscle necrosis (myometrial injection of saline or urea)
Adverse GI effects
Unintended surgery (0.04-0.08 cases per 100 instillations)
Disseminated intravascular coagulopathy (saline, 658 cases per 100,000 instillations)
Urea instillation abortions are reported to be safer than saline abortions. Prostaglandin-induced second-trimester abortions are safer than saline abortions and have a lower induction-to-completion time.
Of all methods of second-trimester abortion, the safest procedure (using mortality surveillance data) is dilation and extraction. Intermediate risk of mortality occurs with instillation procedures. The highest mortality rates for second-trimester abortions are associated with major surgical procedures (ie, hysterotomy, hysterectomy).
Selective reduction procedures are not included in the statistics for second-trimester abortions. For the rare condition of monochorionic twins, selective reduction cord occlusion techniques are reported by Challis et al to have premature rupture of membranes in up to 30% of cases. The more common method of intracardiac injection techniques for selective reduction is associated with premature rupture of membranes in 13% of triplet pregnancies reduced to twins and in 19.3% of quadruplets reduced to twins. The risk of miscarriage in a pregnancy undergoing selective reduction is inversely proportional to the number of fetuses in the initial pregnancy (ie, quintuplet, 24.8%; triplet, 8.3%)
OUTCOME AND PROGNOSIS
Advantages of medical abortion are as follows:
Can be performed without delay
Avoids anesthesia and surgical risks
Psychological advantage - Patient control
Wider availability of abortion services
Increased patient choice
Advantages of surgical abortion are as follows:
More effective than medical abortion
Shorter completion time
Shorter bleeding duration
No exposure to potential teratogens
Can be performed later in gestational age
Fewer visits
Surgical abortion is 99% effective in terminating pregnancy. Medical abortion using mifepristone and misoprostol has a mean effectiveness of 94%. Medical abortion using methotrexate and misoprostol has effectiveness ranging from 88-96%. Medical abortion in the second trimester using misoprostol has effectiveness ranging from 40-89% within 24 hours. Instillation methods of abortion have effectiveness ranging from 81-86% at 48 hours to 97% at 72 hours.
As with all interventions, complications are associated with all the methods of termination of pregnancy. For complications associated with surgical abortion techniques, see Surgical Management of Abortion.
Medical abortions in the first trimester are very safe and well-tolerated procedures. The major problem is decreased efficacy with increasing gestational age. In the case of methotrexate, a long period of time between administration of medication to abortion is problematic.
First-trimester abortions performed by surgical or medical methods are well tolerated, have little effect on future fertility, and are not associated with long-term psychological consequences. Second-trimester abortions are well known to be associated with increased risk of morbidity and mortality with increasing gestational age. An association of increased risk for preterm delivery after dilation with metal dilators has been reported.
FUTURE AND CONTROVERSIES
Future research is expected to evaluate alternative protocols for medical abortion. Research is expected to continue evaluating other medications for medical abortion, including further research using the following:
Tamoxifen, an antiestrogen that interferes with decidual development in an animal model and is associated with incomplete and threatened abortion in humans
Epostane (3beta-hydroxysteroid dehydrogenase inhibitor), which works by blocking the synthesis of progesterone
The potential exists for wider use of medical management of incomplete and missed abortions as the techniques for medical abortion become commonplace.
Therapeutic Abortion 3
TREATMENT
Medical therapy: Medical therapy includes instillation techniques and medical abortion techniques.
Instillation techniques
Instillation agents include hypertonic saline, hypertonic urea, and prostaglandin. All instillation agents function by inducing uterine contractions, which end in the evacuation of the uterine contents.
The instillation technique is performed in a similar fashion for all agents. Selected patients are in the second trimester of pregnancy. The patient empties her bladder, and the abdomen is cleansed with an antiseptic solution. An amniotic fluid pocket can be identified using ultrasound. Alternatively, the skin can be anesthetized using a local anesthetic. An 18-gauge spinal needle is transabdominally introduced into the amniotic sac. Free flow of amniotic fluid is confirmed. (Fluid can be tested with pH paper; urine is acidic, amniotic fluid is basic.) The abortifacient is injected, as follows:
Hypertonic saline: Inject 40 g (ie, 200 mL 20% saline).
Hypertonic urea: Inject 80 g in 5% D5W.
PGF2a: Inject 20-40 mg. Use a test dose of 2.5-5 mg, followed by 17.5-35 mg.
In instillation techniques, the cervix is made inducible by the use of passive dilators (laminaria, Dilapan inserted in cervix) or use of intravaginal prostaglandins (eg, misoprostol, prostaglandin E2 [PGE2] suppositories).
Medical abortion techniques
Medical abortion agents include (1) mifepristone and misoprostol, (2) methotrexate and misoprostol, and (3) misoprostol.
Mifepristone is a progesterone antagonist that blocks the effects of progesterone by competing with endogenous progesterone for receptor binding. The primary effect is on the uterus, where it blocks the effect of progesterone on the endometrium and decidua. The endometrium degenerates and is shed, disrupting the implanted embryo/fetus. The endometrial lining and its contents are expelled. The normal suppression of uterine activity induced in the pregnant uterus by progesterone is lost. The cervix is dilated and softened by poorly understood mechanisms.
Methotrexate is a folic acid antagonist that works by inhibiting dihydrofolate reductase, an enzyme needed to make DNA. In its role as an antimetabolite, methotrexate is toxic to the rapidly dividing cells of the trophoblast.
Misoprostol is a prostaglandin analog that acts by causing uterine contractions, which evacuate the uterine contents.
Mifepristone and misoprostol
Medical abortion using mifepristone and misoprostol at up to 49 days' gestation has been approved by the US Food and Drug Administration (FDA). Patients must meet the following criteria:
Forty-nine days or less from last menstrual period
No contraindications for an outpatient procedure
Capability and willingness to follow the procedures and instructions associated with medical abortion
Willingness to consent to surgical abortion if medical abortion fails
No contraindications for the medications used for medical abortion
The procedure requires 3 visits, as follows:
Day 1
Counseling is performed, and consent is obtained.
History is obtained, and physical examination is performed.
Pregnancy is dated by dates, sizing, and ultrasound.
Hemoglobin and blood type are checked.
Mifepristone 600 mg is given orally. (If the patient vomits 15 min or more after administration, absorption is probably adequate.)
Day 3
RhoGAM is administered if needed.
Misoprostol 400 mg is given orally.
Patients are monitored for 4 hours. (Fifty to 75% abort within 4 h of misoprostol administration.)
Give Tylenol, Tylenol with codeine, or a nonsteroidal anti-inflammatory drug (NSAID) for pain relief. Avoid aspirin and other medications with anticoagulant properties.
Day 15
Assess completion of abortion by physical examination and ultrasound.
Review aftercare measures and contraception.
The following variations on this protocol have been reported in the literature, with low occurrence of adverse effects, good patient acceptance, and comparable effectiveness:
Use up to 56 days
Self-administration of misoprostol 800 mg per vagina on day 3 at home
Repeated dose of misoprostol on day 7 if needed
Methotrexate and misoprostol
See Mifepristone and misoprostol for patient selection criteria. Patients may be up to 63 days from their last menstrual period. The procedure requires a minimum of 3 visits, as follows:
Day 1
See Mifepristone and misoprostol, day 1.
Administer methotrexate 50 mg/m2 intramuscularly instead of mifepristone.
Days 3-5: RhoGAM is administered if needed.
Days 5-7
Misoprostol 800 mg per vagina is self-administered at home.
Alternatively, repeat misoprostol in 24 hours if no vaginal bleeding occurs.
Day 8: Assess for completion of abortion using ultrasound.
If ultrasound reveals an incomplete abortion, repeat misoprostol.
If fetal cardiac activity is present, follow up on day 15.
If fetal cardiac activity is absent, follow up on day 36.
Day 15: Assess for completion of abortion using ultrasound.
If ultrasound reveals an incomplete abortion, repeat misoprostol.
If fetal cardiac activity is present, obtain a surgical abortion.
Days 29-45: Assess for completion of abortion using ultrasound.
If a gestational sac is still observed, obtain a surgical abortion.
If fetal cardiac activity is absent, follow up on day 36.
Misoprostol
For medical abortion in the second trimester (17-24 wk), passive dilators are inserted into the cervix. A 200-mg misoprostol tablet is placed in the posterior vaginal fornix, followed by 2 gauze sponges. The misoprostol dose is repeated in 12 hours, and the laminaria and sponges are removed.
Patients are medicated with promethazine, acetaminophen, diphenoxylate, intravenous/ intramuscular analgesics as needed for pain, fever, nausea, and diarrhea. If the fetus does not deliver in 24 hours, add a 20-mg dinoprostone intravaginal suppository every 3 hours until delivery of the fetus occurs. Add intravenous oxytocin 20-30 U/L of Ringer lactate solution to run at 150 mL/h after delivery of the fetus.
Selective reduction
The techniques available for selective reduction include the following:
Intracardiac injection (potassium chloride or digoxin)
Cord occlusion techniques
Embolization with alcohol, enbucrilate gel
Nd:YAG laser photocoagulation
Fetoscope cord ligation
Bipolar cord coagulation
Monopolar cord coagulation
Drug Category:
Abortifacient agents - Used to produce abortions.
Drug Name
Hypertonic saline, 20% sodium chloride injection (Intra-amniotic injection 20%)
Description
Used in second trimester of pregnancy to induce uterine contractions that end in the evacuation of the uterine contents. In instillation techniques, cervix is made inducible by passive dilators (ie, laminaria, Dilapan inserted in cervix) or intravaginal prostaglandins (eg, misoprostol, PGE2 suppositories).
Adult Dose
Inject 40 g (200 mL) transabdominally into amniotic sac
Pediatric Dose
Not established
Contraindications
Increased intra-amniotic pressure, blood disorders (ie, coagulation factor deficiencies, thrombocytopenia, fibrinolytic defects)
Interactions
Terbutaline may antagonize effect on uterine activity; indomethacin may increase time from induction to abortion
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in patients with cardiac disease, hypertension, epilepsy, serious renal impairment, or pelvic adhesions
Drug Name
Hypertonic urea, urea 40-50% injection (Ureaphil)
Description
Used in second trimester of pregnancy to induce uterine contractions that end in the evacuation of the uterine contents. In instillation techniques, cervix is made inducible by passive dilators (ie, laminaria, Dilapan inserted in cervix) or intravaginal prostaglandins (eg, misoprostol, PGE2 suppositories).
Adult Dose
Inject 80 g (40-50% solution in D5W) transabdominally into amniotic sac
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; severe renal impairment; frank liver disease; intracranial bleeding; sickle cell anemia
Interactions
Aspirin may increase time from induction to abortion
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Monitor for fluid and electrolyte imbalances
Drug Name
Dinoprost, PGF2a (Prostin F2 Alpha)
Description
Not commercially available in the United States. Used in second trimester of pregnancy to induce uterine contractions that end in the evacuation of the uterine contents. Use a test dose of 2.5-5 mg followed by 17.5-35 mg. In instillation techniques, cervix is made inducible by passive dilators (ie, laminaria, Dilapan inserted in cervix) or intravaginal prostaglandins (eg, misoprostol, PGE2 suppositories).
Adult Dose
Inject 20-40 mg transabdominally into amniotic sac
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; acute pelvic inflammatory disease; wanted pregnancy
Interactions
Increased effect or toxicity of oxytocic agent
Pregnancy
X-Contraindicated in pregnancy
Precautions
Caution in patients with anemia, asthma, diabetes mellitus, epilepsy, compromised uterus (ie, fibroid tumors, surgery), cardiovascular disease, hypertension or hypotension, renal or hepatic impairment; associated with GI distress, flushing, headache, arrhythmias, angina, uterine rupture, dyspnea, wheezing, blurred vision
Drug Name
Mifepristone, RU-486 (Mifeprex)
Description
Progesterone antagonist. Competes with endogenous progesterone for receptor binding on the endometrium and decidua. Normal suppression of uterine activity induced in the pregnant uterus by progesterone is lost. Endometrium degenerates and is shed, disrupting the implanted embryo/fetus. Endometrial lining and its contents are then expelled. The cervix is dilated and softened by poorly understood mechanisms.
Adult Dose
<49 days since LMP: 600 mg mifepristone PO as single dose, follow in 48 h with 400 mcg misoprostol PO Alternative: 600 mg mifepristone PO as single dose, follow in 48 h with 800 mcg misoprostol PO; may repeat misoprostol on day 7 prn; regimen may be effective up to 56 d since LMP
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; anticoagulant therapy; bleeding disorders; contraceptive devices (IUDs); ectopic pregnancy; adrenal insufficiency
Interactions
Decreases effect of corticosteroids; increases levels of warfarin, alfentanil, benzodiazepine (ie, alprazolam, triazolam, midazolam); antiretroviral protease inhibitors; calcium channel blockers (ie, nifedipine, diltiazem, verapamil); carbamazepine; cilostazol; cyclosporine; fentanyl; atorvastatin, lovastatin, simvastatin, cerivastatin (removed from US market 8/8/01); quinidine; quinine; sertraline; adverse cardiac effects, cisapride, dofetilide, pimozide
Pregnancy
X - Contraindicated in pregnancy
Precautions
Caution in patients with cardiovascular disease, pulmonary disease (ie, asthma, COPD), diabetes mellitus, renal or hepatic impairment
Drug Name
Methotrexate (Folex PFS, Rheumatrex)
Description
Folic acid antagonist inhibits dihydrofolate reductase, an enzyme needed to make DNA. Antimetabolite property is toxic to the rapidly dividing cells of trophoblast. Methotrexate and misoprostol regimen may be used up to 63 d since LMP.
Adult Dose
50 mg/m2 IM or 50 mg PO, followed by 800 mcg misoprostol PV 5-7 d later, may repeat misoprostol in 24 h if no vaginal bleeding occurs
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Interactions
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity; may increase plasma levels of thiopurines
Pregnancy
D- Unsafe in pregnancy
Precautions
Has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)
Medical therapy: Medical therapy includes instillation techniques and medical abortion techniques.
Instillation techniques
Instillation agents include hypertonic saline, hypertonic urea, and prostaglandin. All instillation agents function by inducing uterine contractions, which end in the evacuation of the uterine contents.
The instillation technique is performed in a similar fashion for all agents. Selected patients are in the second trimester of pregnancy. The patient empties her bladder, and the abdomen is cleansed with an antiseptic solution. An amniotic fluid pocket can be identified using ultrasound. Alternatively, the skin can be anesthetized using a local anesthetic. An 18-gauge spinal needle is transabdominally introduced into the amniotic sac. Free flow of amniotic fluid is confirmed. (Fluid can be tested with pH paper; urine is acidic, amniotic fluid is basic.) The abortifacient is injected, as follows:
Hypertonic saline: Inject 40 g (ie, 200 mL 20% saline).
Hypertonic urea: Inject 80 g in 5% D5W.
PGF2a: Inject 20-40 mg. Use a test dose of 2.5-5 mg, followed by 17.5-35 mg.
In instillation techniques, the cervix is made inducible by the use of passive dilators (laminaria, Dilapan inserted in cervix) or use of intravaginal prostaglandins (eg, misoprostol, prostaglandin E2 [PGE2] suppositories).
Medical abortion techniques
Medical abortion agents include (1) mifepristone and misoprostol, (2) methotrexate and misoprostol, and (3) misoprostol.
Mifepristone is a progesterone antagonist that blocks the effects of progesterone by competing with endogenous progesterone for receptor binding. The primary effect is on the uterus, where it blocks the effect of progesterone on the endometrium and decidua. The endometrium degenerates and is shed, disrupting the implanted embryo/fetus. The endometrial lining and its contents are expelled. The normal suppression of uterine activity induced in the pregnant uterus by progesterone is lost. The cervix is dilated and softened by poorly understood mechanisms.
Methotrexate is a folic acid antagonist that works by inhibiting dihydrofolate reductase, an enzyme needed to make DNA. In its role as an antimetabolite, methotrexate is toxic to the rapidly dividing cells of the trophoblast.
Misoprostol is a prostaglandin analog that acts by causing uterine contractions, which evacuate the uterine contents.
Mifepristone and misoprostol
Medical abortion using mifepristone and misoprostol at up to 49 days' gestation has been approved by the US Food and Drug Administration (FDA). Patients must meet the following criteria:
Forty-nine days or less from last menstrual period
No contraindications for an outpatient procedure
Capability and willingness to follow the procedures and instructions associated with medical abortion
Willingness to consent to surgical abortion if medical abortion fails
No contraindications for the medications used for medical abortion
The procedure requires 3 visits, as follows:
Day 1
Counseling is performed, and consent is obtained.
History is obtained, and physical examination is performed.
Pregnancy is dated by dates, sizing, and ultrasound.
Hemoglobin and blood type are checked.
Mifepristone 600 mg is given orally. (If the patient vomits 15 min or more after administration, absorption is probably adequate.)
Day 3
RhoGAM is administered if needed.
Misoprostol 400 mg is given orally.
Patients are monitored for 4 hours. (Fifty to 75% abort within 4 h of misoprostol administration.)
Give Tylenol, Tylenol with codeine, or a nonsteroidal anti-inflammatory drug (NSAID) for pain relief. Avoid aspirin and other medications with anticoagulant properties.
Day 15
Assess completion of abortion by physical examination and ultrasound.
Review aftercare measures and contraception.
The following variations on this protocol have been reported in the literature, with low occurrence of adverse effects, good patient acceptance, and comparable effectiveness:
Use up to 56 days
Self-administration of misoprostol 800 mg per vagina on day 3 at home
Repeated dose of misoprostol on day 7 if needed
Methotrexate and misoprostol
See Mifepristone and misoprostol for patient selection criteria. Patients may be up to 63 days from their last menstrual period. The procedure requires a minimum of 3 visits, as follows:
Day 1
See Mifepristone and misoprostol, day 1.
Administer methotrexate 50 mg/m2 intramuscularly instead of mifepristone.
Days 3-5: RhoGAM is administered if needed.
Days 5-7
Misoprostol 800 mg per vagina is self-administered at home.
Alternatively, repeat misoprostol in 24 hours if no vaginal bleeding occurs.
Day 8: Assess for completion of abortion using ultrasound.
If ultrasound reveals an incomplete abortion, repeat misoprostol.
If fetal cardiac activity is present, follow up on day 15.
If fetal cardiac activity is absent, follow up on day 36.
Day 15: Assess for completion of abortion using ultrasound.
If ultrasound reveals an incomplete abortion, repeat misoprostol.
If fetal cardiac activity is present, obtain a surgical abortion.
Days 29-45: Assess for completion of abortion using ultrasound.
If a gestational sac is still observed, obtain a surgical abortion.
If fetal cardiac activity is absent, follow up on day 36.
Misoprostol
For medical abortion in the second trimester (17-24 wk), passive dilators are inserted into the cervix. A 200-mg misoprostol tablet is placed in the posterior vaginal fornix, followed by 2 gauze sponges. The misoprostol dose is repeated in 12 hours, and the laminaria and sponges are removed.
Patients are medicated with promethazine, acetaminophen, diphenoxylate, intravenous/ intramuscular analgesics as needed for pain, fever, nausea, and diarrhea. If the fetus does not deliver in 24 hours, add a 20-mg dinoprostone intravaginal suppository every 3 hours until delivery of the fetus occurs. Add intravenous oxytocin 20-30 U/L of Ringer lactate solution to run at 150 mL/h after delivery of the fetus.
Selective reduction
The techniques available for selective reduction include the following:
Intracardiac injection (potassium chloride or digoxin)
Cord occlusion techniques
Embolization with alcohol, enbucrilate gel
Nd:YAG laser photocoagulation
Fetoscope cord ligation
Bipolar cord coagulation
Monopolar cord coagulation
Drug Category:
Abortifacient agents - Used to produce abortions.
Drug Name
Hypertonic saline, 20% sodium chloride injection (Intra-amniotic injection 20%)
Description
Used in second trimester of pregnancy to induce uterine contractions that end in the evacuation of the uterine contents. In instillation techniques, cervix is made inducible by passive dilators (ie, laminaria, Dilapan inserted in cervix) or intravaginal prostaglandins (eg, misoprostol, PGE2 suppositories).
Adult Dose
Inject 40 g (200 mL) transabdominally into amniotic sac
Pediatric Dose
Not established
Contraindications
Increased intra-amniotic pressure, blood disorders (ie, coagulation factor deficiencies, thrombocytopenia, fibrinolytic defects)
Interactions
Terbutaline may antagonize effect on uterine activity; indomethacin may increase time from induction to abortion
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in patients with cardiac disease, hypertension, epilepsy, serious renal impairment, or pelvic adhesions
Drug Name
Hypertonic urea, urea 40-50% injection (Ureaphil)
Description
Used in second trimester of pregnancy to induce uterine contractions that end in the evacuation of the uterine contents. In instillation techniques, cervix is made inducible by passive dilators (ie, laminaria, Dilapan inserted in cervix) or intravaginal prostaglandins (eg, misoprostol, PGE2 suppositories).
Adult Dose
Inject 80 g (40-50% solution in D5W) transabdominally into amniotic sac
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; severe renal impairment; frank liver disease; intracranial bleeding; sickle cell anemia
Interactions
Aspirin may increase time from induction to abortion
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Monitor for fluid and electrolyte imbalances
Drug Name
Dinoprost, PGF2a (Prostin F2 Alpha)
Description
Not commercially available in the United States. Used in second trimester of pregnancy to induce uterine contractions that end in the evacuation of the uterine contents. Use a test dose of 2.5-5 mg followed by 17.5-35 mg. In instillation techniques, cervix is made inducible by passive dilators (ie, laminaria, Dilapan inserted in cervix) or intravaginal prostaglandins (eg, misoprostol, PGE2 suppositories).
Adult Dose
Inject 20-40 mg transabdominally into amniotic sac
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; acute pelvic inflammatory disease; wanted pregnancy
Interactions
Increased effect or toxicity of oxytocic agent
Pregnancy
X-Contraindicated in pregnancy
Precautions
Caution in patients with anemia, asthma, diabetes mellitus, epilepsy, compromised uterus (ie, fibroid tumors, surgery), cardiovascular disease, hypertension or hypotension, renal or hepatic impairment; associated with GI distress, flushing, headache, arrhythmias, angina, uterine rupture, dyspnea, wheezing, blurred vision
Drug Name
Mifepristone, RU-486 (Mifeprex)
Description
Progesterone antagonist. Competes with endogenous progesterone for receptor binding on the endometrium and decidua. Normal suppression of uterine activity induced in the pregnant uterus by progesterone is lost. Endometrium degenerates and is shed, disrupting the implanted embryo/fetus. Endometrial lining and its contents are then expelled. The cervix is dilated and softened by poorly understood mechanisms.
Adult Dose
<49 days since LMP: 600 mg mifepristone PO as single dose, follow in 48 h with 400 mcg misoprostol PO Alternative: 600 mg mifepristone PO as single dose, follow in 48 h with 800 mcg misoprostol PO; may repeat misoprostol on day 7 prn; regimen may be effective up to 56 d since LMP
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; anticoagulant therapy; bleeding disorders; contraceptive devices (IUDs); ectopic pregnancy; adrenal insufficiency
Interactions
Decreases effect of corticosteroids; increases levels of warfarin, alfentanil, benzodiazepine (ie, alprazolam, triazolam, midazolam); antiretroviral protease inhibitors; calcium channel blockers (ie, nifedipine, diltiazem, verapamil); carbamazepine; cilostazol; cyclosporine; fentanyl; atorvastatin, lovastatin, simvastatin, cerivastatin (removed from US market 8/8/01); quinidine; quinine; sertraline; adverse cardiac effects, cisapride, dofetilide, pimozide
Pregnancy
X - Contraindicated in pregnancy
Precautions
Caution in patients with cardiovascular disease, pulmonary disease (ie, asthma, COPD), diabetes mellitus, renal or hepatic impairment
Drug Name
Methotrexate (Folex PFS, Rheumatrex)
Description
Folic acid antagonist inhibits dihydrofolate reductase, an enzyme needed to make DNA. Antimetabolite property is toxic to the rapidly dividing cells of trophoblast. Methotrexate and misoprostol regimen may be used up to 63 d since LMP.
Adult Dose
50 mg/m2 IM or 50 mg PO, followed by 800 mcg misoprostol PV 5-7 d later, may repeat misoprostol in 24 h if no vaginal bleeding occurs
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency
Interactions
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity; may increase plasma levels of thiopurines
Pregnancy
D- Unsafe in pregnancy
Precautions
Has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)
Therapeutic Abortion 2
RELEVANT ANATOMY AND CONTRAINDICATIONS
Relevant Anatomy: Adequate evaluation of uterine size is mandatory. Physical examination may be inadequate for uterine sizing because of the following factors:
Obesity
Patient apprehension with voluntary guarding
Presence of a retroverted uterus
Firm abdominal musculature
Uterine leiomyoma
Obtaining ultrasound confirmation of gestational age is common practice when a therapeutic abortion is planned. Anticipating potential complications associated with the abortion procedure is important.
Consider anatomic problems that may contribute to technical difficulties during an abortion. Make every attempt to minimize complications because of their impact on a patient who may already experience considerable compromise. A small, stenotic, or scarred cervical os may impair the cervical dilation necessary for safe surgical terminations of pregnancy.
The presence of uterine leiomyomas may make uterine sizing erroneous and the dilation of the cervix difficult or impossible and may contribute to increased blood loss at the time of either surgical or medical abortion procedures.
Abnormal placentation (ie, placenta previa, placenta accreta, placenta percreta) is associated with high parity and previous uterine surgery. This issue must be addressed carefully. Abnormal placentation requires surgical intervention with careful consideration of the anticipated amount of blood loss. The selected surgical abortion method should cause minimal blood loss and be of limited invasiveness. For certain patients, special interventions, such as embolization using interventional radiology techniques, may be needed on a standby basis.
The presence of uterine anomalies (eg, uterus didelphys, unicornuate uterus, septate uterus) may make entering and emptying of the uterus complicated. If surgical abortion is selected, ultrasound guidance during the procedure may be helpful. The abortion of a multiple gestation may make surgical abortions more challenging, and the use of ultrasound guidance is helpful. Data are not available for the use of medical abortion in this setting.
Careful consideration of the choice of anesthesia must be based on the medical, psychiatric, and emotional condition of the patient. Consultation with anesthetists, medical specialists, and psychiatric specialists may be necessary to determine the best choice of anesthesia for an individual patient. In general, local anesthesia affords the greatest safety. General anesthesia for surgical abortions is associated with greater overall risk of anesthesia complications and hemorrhage.
Contraindications: Absolute contraindications to termination of pregnancy are virtually unknown. In the face of significant maternal risk of medical or psychiatric morbidity/mortality, continuation of pregnancy usually presents far greater risk than termination of pregnancy. A particular type of abortion procedure or the timing of abortion may be contraindicated based on the current medical, surgical, or psychiatric condition of a patient. For example, medical abortion is contraindicated in patients with the following conditions:
Clotting disorders
Severe liver diseases
Renal diseases
Severe cardiac diseases
Long-term steroid use
Medical conditions or use of medications that preclude the use of medical abortion medications
Adrenal failure
Undiagnosed adnexal masses
Ectopic pregnancy (except with use of methotrexate)
Medical abortion should be performed with caution in patients with the following conditions:
Severe anemia
Poorly controlled bowel disease (may cause an exacerbation of symptoms)
Surgical abortion is contraindicated in patients with the following conditions:
Hemodynamic instability
Profound anemia
Profound thrombocytopenia
Instillation abortion techniques are contraindicated in patients with the following conditions:
Active pelvic infections
Inability to tolerate a solute load (saline only)
Asthma, glaucoma, epilepsy, hypertensive cardiovascular disease, pulmonary hypertension (prostaglandin F2a [PGF2a])
Fetal demise (saline, urea)
The rare patient with placenta accreta or placenta percreta may require consideration of laparotomy with hysterotomy/hysterectomy despite the increased morbidity and mortality risks associated with these procedures.
Multifetal reduction of pregnancy has inherent risks of rupture of membranes, preterm labor, preterm delivery, and infection, which must be balanced against the benefits of the procedure. Special circumstances, such as the selection of the presenting fetus for reduction, may present a greater risk of loss of the entire pregnancy and must be considered in the risk-benefit analysis.
In patients with significant medical or surgical risk, the choice of abortion procedure must be individualized. All abortion methods may present relative or absolute contraindications for some patients. In the face of limited or absent data for a specific clinical situation, the choice of abortion method is based on the best collective medical judgment of the team of clinicians caring for the patient. WORKUP
Lab Studies:
Surgical abortion: Pregnancy test, CBC count, and blood typing are the minimum laboratory studies required for surgical abortion.
A pregnancy test is required to exclude non–pregnancy-related causes of secondary amenorrhea.
A CBC count is required to identify patients with significant anemia, who are at risk if excessive blood loss occurs. Transfusion may be needed, particularly in second-trimester abortions. Patients with severe anemia are best treated in a setting where transfusion is available.
Blood typing is required so that Rh-negative women can be identified and given RhoGAM to prevent Rh sensitization in subsequent pregnancies.
Screening for common sexually transmitted diseases (STDs) should be addressed in geographic areas of high prevalence, in age groups at high risk (ie, <25 y), and in at-risk groups (eg, those with histories of STDs, multiple sex partners, substance abuse).
Additional laboratory testing is dictated by the medical history and physical examination findings.
Coagulation studies are indicated for patients with conditions such as a history of coagulopathy, hematologic malignancies, hemorrhage with previous surgical procedures, petechiae, bruising, and hepatosplenomegaly.
Liver function tests are indicated for patients with conditions such as hepatitis, alcohol abuse, metastatic cancer, hepatomegaly, and jaundice.
Renal function tests are indicated for patients with conditions such as renal disease, recurrent urinary tract infections, oliguria, hematuria, and proteinuria.
Medical abortion: Pregnancy test, CBC count, and blood typing are the minimum laboratory studies required for medical abortion.
In cases of methotrexate use, platelet count, electrolytes, liver function tests, and BUN and creatinine levels are required. Thrombocytopenia and chemical hepatitis are rare (in the doses used for medical abortion) but known complications of methotrexate use.
Electrolyte assays are necessary in patients who develop significant vomiting associated with the use of medical abortion techniques.
See Surgical abortion for other laboratory studies and indications for their use.
Instillation techniques
A pregnancy test and CBC count are required; see Surgical abortion for indications.
Platelets, coagulation studies, liver function tests, and renal function tests are recommended as baseline testing for instillation methods because of the risk of coagulopathy, vomiting, and diarrhea associated with this method.
Selective reduction: No specific laboratory tests are required; however, specific laboratory tests may be ordered for individual patients based on history and physical examination findings.
Imaging Studies:
Baseline ultrasounds are routinely used in medical abortion, surgical abortion, and instillation abortion techniques.
A chest radiograph may be indicated depending on history and physical examination findings.
Other Tests:
Chorionic villus sampling or amniocentesis for fetal chromosome evaluation may be indicated depending on maternal age, obstetric history, family history, or ultrasound findings.
Diagnostic Procedures:
Specialized testing is needed for certain indications.
For example, fetal umbilical cord blood sampling is indicated when fetal blood must be obtained for diagnostic testing.
An ECG may be indicated depending on maternal age, history, physical examination findings, and anesthesia requirements.
Histologic Findings: Collecting tissue for pathologic examination is generally impossible for first-trimester medical abortion and is not part of the recommended protocol. Collection of tissue for pathologic examination for surgical abortion and second-trimester medical abortion is routine. The obligation to collect tissue from abortion procedures is determined by state abortion regulations and must be addressed in a state-by-state manner. The need to collect tissue for diagnosis of fetal anomalies is addressed on a case-by-case basis. The same state and federal statutes apply for medical and surgical abortions despite the fact that the laws were written for surgical abortion.
Relevant Anatomy: Adequate evaluation of uterine size is mandatory. Physical examination may be inadequate for uterine sizing because of the following factors:
Obesity
Patient apprehension with voluntary guarding
Presence of a retroverted uterus
Firm abdominal musculature
Uterine leiomyoma
Obtaining ultrasound confirmation of gestational age is common practice when a therapeutic abortion is planned. Anticipating potential complications associated with the abortion procedure is important.
Consider anatomic problems that may contribute to technical difficulties during an abortion. Make every attempt to minimize complications because of their impact on a patient who may already experience considerable compromise. A small, stenotic, or scarred cervical os may impair the cervical dilation necessary for safe surgical terminations of pregnancy.
The presence of uterine leiomyomas may make uterine sizing erroneous and the dilation of the cervix difficult or impossible and may contribute to increased blood loss at the time of either surgical or medical abortion procedures.
Abnormal placentation (ie, placenta previa, placenta accreta, placenta percreta) is associated with high parity and previous uterine surgery. This issue must be addressed carefully. Abnormal placentation requires surgical intervention with careful consideration of the anticipated amount of blood loss. The selected surgical abortion method should cause minimal blood loss and be of limited invasiveness. For certain patients, special interventions, such as embolization using interventional radiology techniques, may be needed on a standby basis.
The presence of uterine anomalies (eg, uterus didelphys, unicornuate uterus, septate uterus) may make entering and emptying of the uterus complicated. If surgical abortion is selected, ultrasound guidance during the procedure may be helpful. The abortion of a multiple gestation may make surgical abortions more challenging, and the use of ultrasound guidance is helpful. Data are not available for the use of medical abortion in this setting.
Careful consideration of the choice of anesthesia must be based on the medical, psychiatric, and emotional condition of the patient. Consultation with anesthetists, medical specialists, and psychiatric specialists may be necessary to determine the best choice of anesthesia for an individual patient. In general, local anesthesia affords the greatest safety. General anesthesia for surgical abortions is associated with greater overall risk of anesthesia complications and hemorrhage.
Contraindications: Absolute contraindications to termination of pregnancy are virtually unknown. In the face of significant maternal risk of medical or psychiatric morbidity/mortality, continuation of pregnancy usually presents far greater risk than termination of pregnancy. A particular type of abortion procedure or the timing of abortion may be contraindicated based on the current medical, surgical, or psychiatric condition of a patient. For example, medical abortion is contraindicated in patients with the following conditions:
Clotting disorders
Severe liver diseases
Renal diseases
Severe cardiac diseases
Long-term steroid use
Medical conditions or use of medications that preclude the use of medical abortion medications
Adrenal failure
Undiagnosed adnexal masses
Ectopic pregnancy (except with use of methotrexate)
Medical abortion should be performed with caution in patients with the following conditions:
Severe anemia
Poorly controlled bowel disease (may cause an exacerbation of symptoms)
Surgical abortion is contraindicated in patients with the following conditions:
Hemodynamic instability
Profound anemia
Profound thrombocytopenia
Instillation abortion techniques are contraindicated in patients with the following conditions:
Active pelvic infections
Inability to tolerate a solute load (saline only)
Asthma, glaucoma, epilepsy, hypertensive cardiovascular disease, pulmonary hypertension (prostaglandin F2a [PGF2a])
Fetal demise (saline, urea)
The rare patient with placenta accreta or placenta percreta may require consideration of laparotomy with hysterotomy/hysterectomy despite the increased morbidity and mortality risks associated with these procedures.
Multifetal reduction of pregnancy has inherent risks of rupture of membranes, preterm labor, preterm delivery, and infection, which must be balanced against the benefits of the procedure. Special circumstances, such as the selection of the presenting fetus for reduction, may present a greater risk of loss of the entire pregnancy and must be considered in the risk-benefit analysis.
In patients with significant medical or surgical risk, the choice of abortion procedure must be individualized. All abortion methods may present relative or absolute contraindications for some patients. In the face of limited or absent data for a specific clinical situation, the choice of abortion method is based on the best collective medical judgment of the team of clinicians caring for the patient. WORKUP
Lab Studies:
Surgical abortion: Pregnancy test, CBC count, and blood typing are the minimum laboratory studies required for surgical abortion.
A pregnancy test is required to exclude non–pregnancy-related causes of secondary amenorrhea.
A CBC count is required to identify patients with significant anemia, who are at risk if excessive blood loss occurs. Transfusion may be needed, particularly in second-trimester abortions. Patients with severe anemia are best treated in a setting where transfusion is available.
Blood typing is required so that Rh-negative women can be identified and given RhoGAM to prevent Rh sensitization in subsequent pregnancies.
Screening for common sexually transmitted diseases (STDs) should be addressed in geographic areas of high prevalence, in age groups at high risk (ie, <25 y), and in at-risk groups (eg, those with histories of STDs, multiple sex partners, substance abuse).
Additional laboratory testing is dictated by the medical history and physical examination findings.
Coagulation studies are indicated for patients with conditions such as a history of coagulopathy, hematologic malignancies, hemorrhage with previous surgical procedures, petechiae, bruising, and hepatosplenomegaly.
Liver function tests are indicated for patients with conditions such as hepatitis, alcohol abuse, metastatic cancer, hepatomegaly, and jaundice.
Renal function tests are indicated for patients with conditions such as renal disease, recurrent urinary tract infections, oliguria, hematuria, and proteinuria.
Medical abortion: Pregnancy test, CBC count, and blood typing are the minimum laboratory studies required for medical abortion.
In cases of methotrexate use, platelet count, electrolytes, liver function tests, and BUN and creatinine levels are required. Thrombocytopenia and chemical hepatitis are rare (in the doses used for medical abortion) but known complications of methotrexate use.
Electrolyte assays are necessary in patients who develop significant vomiting associated with the use of medical abortion techniques.
See Surgical abortion for other laboratory studies and indications for their use.
Instillation techniques
A pregnancy test and CBC count are required; see Surgical abortion for indications.
Platelets, coagulation studies, liver function tests, and renal function tests are recommended as baseline testing for instillation methods because of the risk of coagulopathy, vomiting, and diarrhea associated with this method.
Selective reduction: No specific laboratory tests are required; however, specific laboratory tests may be ordered for individual patients based on history and physical examination findings.
Imaging Studies:
Baseline ultrasounds are routinely used in medical abortion, surgical abortion, and instillation abortion techniques.
A chest radiograph may be indicated depending on history and physical examination findings.
Other Tests:
Chorionic villus sampling or amniocentesis for fetal chromosome evaluation may be indicated depending on maternal age, obstetric history, family history, or ultrasound findings.
Diagnostic Procedures:
Specialized testing is needed for certain indications.
For example, fetal umbilical cord blood sampling is indicated when fetal blood must be obtained for diagnostic testing.
An ECG may be indicated depending on maternal age, history, physical examination findings, and anesthesia requirements.
Histologic Findings: Collecting tissue for pathologic examination is generally impossible for first-trimester medical abortion and is not part of the recommended protocol. Collection of tissue for pathologic examination for surgical abortion and second-trimester medical abortion is routine. The obligation to collect tissue from abortion procedures is determined by state abortion regulations and must be addressed in a state-by-state manner. The need to collect tissue for diagnosis of fetal anomalies is addressed on a case-by-case basis. The same state and federal statutes apply for medical and surgical abortions despite the fact that the laws were written for surgical abortion.
Therapeutic Abortion 1
Therapeutic Abortion
INTRODUCTION
Therapeutic abortion is defined as the termination of pregnancy before fetal viability in order to preserve maternal health. In its broadest definition, therapeutic abortion can be performed to (1) save the life of the mother, (2) preserve the health of the mother, (3) terminate a pregnancy that would result in the birth of a child with defects incompatible with life or associated with significant morbidity, (4) terminate a nonviable pregnancy, or (5) selectively reduce a multifetal pregnancy.
The vast majority of abortions performed in the United States are elective. Pregnancy-related conditions that threaten maternal life are rare and difficult to define precisely. The decision to terminate a pregnancy for medical indications is generally a multidisciplinary decision involving the obstetrician, a specialist in the disease entity in question, the patient, the patient's family, and others.
The methods used to terminate pregnancy vary according to gestational age, the indication for termination, and medical and surgical considerations relevant to the mother. Abortion can be accomplished by surgical or medical means.
Most of this article is devoted to the discussion of indications for therapeutic abortion and medical methods for termination of pregnancy. An in-depth discussion of surgical abortion is covered in Surgical Management of Abortion.
History of the Procedure: Termination of pregnancy has been practiced since ancient times and by all cultures. The indications and social context for termination of pregnancy vary with culture and time.
The use of abortion to preserve the life of the mother has been widely accepted. Early Jewish scholars' interpretation of the Talmud required that the fetus be destroyed if it posed a threat to the mother during delivery. The ancient Greeks allowed abortion under certain circumstances. Ancient Romans did not consider a fetus a person until after birth, and abortion was practiced widely. Early Christians had varying practices regarding abortion. By 1869, the Catholic church declared abortion a sin punishable by excommunication.
In the United States, legislation regarding abortion has varied with the times. Before 1800, no statutes addressed the subject of abortion. The first antiabortion legislation appeared in the 1820s; the preservation of pregnant women's health was the motivating force. During this time, the mortality rate from abortion was high, while the mortality rate from childbirth was less than 3%. By 1900, abortion in the United States at any time during pregnancy was a crime, with the exception of therapeutic abortion performed to save the mother's life.
During the 1950s, the practice of medicine came under increasing scrutiny, and guidelines were set to define the indications for therapeutic abortion. The guidelines allowed therapeutic abortion if (1) pregnancy would "gravely impair the physical and mental health of the mother," (2) the child born was likely to have "grave physical and mental defects," or (3) the pregnancy was the result of rape or incest (Mcfarlane, 1993). In the United States, the legalization of abortion by Roe v Wade in 1973 upheld the fundamental right of a woman to determine whether to continue her pregnancy.
Problem: US statistics indicate that the vast majority of abortions are elective. Therapeutic abortion is rare. The ability to define therapeutic abortion performed for maternal indications is difficult because of the subjective nature of decisions made about potential morbidity and mortality in pregnant women. A variety of medical conditions in pregnant women have the potential to affect health and cause complications that may be life threatening.
Prenatal screening in the form of prenatal diagnostic screening continues to improve the antepartum diagnosis of fetal anomalies. The decision to continue or terminate a pregnancy complicated by fetal anomalies is a difficult decision. The most difficult decisions are associated with anomalies that are unpredictable or highly variable in their expression.
The increase in the use of assisted reproductive technologies has been associated with an enormous increase in multifetal pregnancies. These pregnancies are complicated by increased fetal morbidity and mortality rates, which are largely caused by prematurity and growth retardation. Selective reduction has been introduced as a technology to improve perinatal outcomes in these pregnancies and has been successful in reducing preterm deliveries and associated morbidity and mortality.
Frequency: Approximately 3-5% of all newborns have a recognizable birth defect. According to Cunningham and MacDonald, the suggested causes of fetal anomalies are as follows:
Genetic (ie, chromosomal) (20-25%)
Fetal infections (3-5%)
Maternal disease (4%)
Drugs/medications (<1%)
Unknown (65-70%)
Medical complications during pregnancy encompass a wide array of medical problems, to include the following:
Hypertensive disorders
Diabetes mellitus
Hematologic disorders
Cardiovascular diseases
Thromboembolic disorders
Thyroid and parathyroid diseases
Pituitary disorders
Adrenal disorders
Renal diseases
Hepatic diseases
GI tract disorders
Pulmonary diseases
Infectious diseases
Neurologic diseases
Psychiatric disorders
Malignancies
The diseases tend to occur in frequencies compatible with those of nonpregnant age-matched women. Providing an in-depth review of this wide array of medical problems is beyond the scope of this article.
The most common cancers found in pregnant women mirror those found in their nonpregnant counterparts, to include the following:
Cervical cancer (1 case per 2200 pregnancies)
Breast cancer (1 case per 3000 pregnancies)
Melanoma (0.14-2.8 cases per 1000 pregnancies)
Ovarian cancer
Thyroid cancer
Leukemia (rare)
Lymphoma
Colorectal carcinoma (0.10-1.0 cases per 1000 pregnancies)
The total incidence of malignancy during pregnancy is estimated at 1 case per 1000 pregnancies.
As previously noted, the number of multifetal pregnancies has increased enormously because of the use of assisted reproductive technologies. Twins have increased in frequency from 1 set per 90 pregnancies to 1 set per 45 pregnancies. Higher-order multifetal pregnancies have quadrupled in the past 20 years.
Clinical: Patients in need of therapeutic termination of pregnancy can be identified at any gestational age; however, the consideration of therapeutic abortion is generally limited to pregnancies at 24 weeks' gestation or less. Many patients are in the second trimester of pregnancy because of the timing of fetal assessment tools (eg, triple screen, amniocentesis, ultrasound).
INDICATIONS
The indications for therapeutic abortion, in its broadest definition, are as follows:
To save the life of the pregnant woman
To preserve the health of the pregnant woman
To terminate a pregnancy that would result in the birth of a child with defects incompatible with life or associated with significant morbidity
To terminate a nonviable pregnancy
To selectively reduce a multifetal pregnancy
Therapeutic abortions to save the life of the mother or to preserve the health of the mother are rare events. The decision should be based on the collaborative agreement of a multidisciplinary team. At minimum, the team should consist of the patient, the obstetrician, a specialist with knowledge of the disease in question, an expert in genetic counseling, and a neonatologist. Additional members may include spiritual counselors, nurses, psychologists/psychiatrists, intensive care specialists, ethicists, and family members.
The decision to terminate the pregnancy includes consideration of the effect of the pregnancy on disease outcome, the effect of treatment on fetal outcome, the gestational age of the pregnancy, the level of attachment of the patient to the pregnancy, the desires of the patient and the father, and the availability of family resources/support. This complex situation requires thought and excellent communication among the involved parties regarding the short- and long-term consequences of the decision to abort or continue the pregnancy. The decision must be individualized for each patient. There must be an inherent acceptance of the subjective nature of decisions made in this area. The clinical situations may be rare, and clinical data available may be anecdotal, incomplete, and/or inconclusive.
Commonly accepted medical indications for therapeutic termination of pregnancy include severe hypertensive vascular disease, cardiac disease with cardiac decompensation, and certain malignancies.
Malignancy
Cervical cancer is the most common malignancy affecting pregnant women. Invasive cervical cancer is treated with surgery or radiation; both treatment modalities result in fetal death for the previable fetus. Delay of therapy is the only option that allows fetal salvage in this setting. Treatment delays to allow fetal maturation have been successfully attempted in stages IA and IB. Treatment delays for advanced disease (stages IIB-IV) are controversial. All decisions regarding delay must be individualized and must consider other factors that affect the prognosis (eg, HIV status).
The prognosis for patients with breast cancer is not adversely affected by continuation of pregnancy. The decision to terminate a pregnancy complicated by breast cancer in the first and second trimesters is determined by the degree to which the pregnancy impairs effective treatment and whether treatment presents a risk to the fetus.
The prognosis for patients with melanoma is not improved by therapeutic abortion. Metastatic spread of melanoma to the placenta and fetus has been reported but is very rare. This type of spread has also been reported with lymphoma, leukemia, breast cancer, lung cancer, and stomach cancer and should be addressed when counseling at-risk patients.
Fetal conditions
A pregnancy in which the fetus has defects that are either incompatible with life or associated with significant morbidity can be an indication for therapeutic abortion. The number of fetal conditions that can be identified during pregnancy is always expanding because of improvements in technology available for antenatal diagnosis. The following fetal conditions are identifiable:
Chromosomal disorders
X-linked disorders
Metabolic disorders
Neural tube defects
Structural anomalies associated with exposure to teratogens
Structural anomalies of multifactorial or unknown etiology
Multifetal pregnancies
Multifetal pregnancies are associated with high fetal morbidity and mortality rates. In this setting, morbidity and mortality are associated with high rates of preterm delivery and growth retardation. Preterm birth rates at less than 33 weeks' gestation are 8 times higher for twins and 24 times higher for triplets compared with singleton pregnancies. Each additional fetus in a pregnancy reduces the length of the pregnancy by approximately 3.6 weeks. After birth, the mortality rates for infants born in multiple pregnancies remain elevated from birth to age 5 years, even after controlling for growth restriction.
Multifetal reduction has been shown to reduce the risk of preterm delivery for the remaining fetuses. However, the incidence of prematurity in reduced pregnancies appears to remain higher than in spontaneous pregnancies of the same fetal number. An overall reduction in morbidity-improved survival rates occurs in reduced pregnancies compared with pregnancies in which reduction is not performed.
INTRODUCTION
Therapeutic abortion is defined as the termination of pregnancy before fetal viability in order to preserve maternal health. In its broadest definition, therapeutic abortion can be performed to (1) save the life of the mother, (2) preserve the health of the mother, (3) terminate a pregnancy that would result in the birth of a child with defects incompatible with life or associated with significant morbidity, (4) terminate a nonviable pregnancy, or (5) selectively reduce a multifetal pregnancy.
The vast majority of abortions performed in the United States are elective. Pregnancy-related conditions that threaten maternal life are rare and difficult to define precisely. The decision to terminate a pregnancy for medical indications is generally a multidisciplinary decision involving the obstetrician, a specialist in the disease entity in question, the patient, the patient's family, and others.
The methods used to terminate pregnancy vary according to gestational age, the indication for termination, and medical and surgical considerations relevant to the mother. Abortion can be accomplished by surgical or medical means.
Most of this article is devoted to the discussion of indications for therapeutic abortion and medical methods for termination of pregnancy. An in-depth discussion of surgical abortion is covered in Surgical Management of Abortion.
History of the Procedure: Termination of pregnancy has been practiced since ancient times and by all cultures. The indications and social context for termination of pregnancy vary with culture and time.
The use of abortion to preserve the life of the mother has been widely accepted. Early Jewish scholars' interpretation of the Talmud required that the fetus be destroyed if it posed a threat to the mother during delivery. The ancient Greeks allowed abortion under certain circumstances. Ancient Romans did not consider a fetus a person until after birth, and abortion was practiced widely. Early Christians had varying practices regarding abortion. By 1869, the Catholic church declared abortion a sin punishable by excommunication.
In the United States, legislation regarding abortion has varied with the times. Before 1800, no statutes addressed the subject of abortion. The first antiabortion legislation appeared in the 1820s; the preservation of pregnant women's health was the motivating force. During this time, the mortality rate from abortion was high, while the mortality rate from childbirth was less than 3%. By 1900, abortion in the United States at any time during pregnancy was a crime, with the exception of therapeutic abortion performed to save the mother's life.
During the 1950s, the practice of medicine came under increasing scrutiny, and guidelines were set to define the indications for therapeutic abortion. The guidelines allowed therapeutic abortion if (1) pregnancy would "gravely impair the physical and mental health of the mother," (2) the child born was likely to have "grave physical and mental defects," or (3) the pregnancy was the result of rape or incest (Mcfarlane, 1993). In the United States, the legalization of abortion by Roe v Wade in 1973 upheld the fundamental right of a woman to determine whether to continue her pregnancy.
Problem: US statistics indicate that the vast majority of abortions are elective. Therapeutic abortion is rare. The ability to define therapeutic abortion performed for maternal indications is difficult because of the subjective nature of decisions made about potential morbidity and mortality in pregnant women. A variety of medical conditions in pregnant women have the potential to affect health and cause complications that may be life threatening.
Prenatal screening in the form of prenatal diagnostic screening continues to improve the antepartum diagnosis of fetal anomalies. The decision to continue or terminate a pregnancy complicated by fetal anomalies is a difficult decision. The most difficult decisions are associated with anomalies that are unpredictable or highly variable in their expression.
The increase in the use of assisted reproductive technologies has been associated with an enormous increase in multifetal pregnancies. These pregnancies are complicated by increased fetal morbidity and mortality rates, which are largely caused by prematurity and growth retardation. Selective reduction has been introduced as a technology to improve perinatal outcomes in these pregnancies and has been successful in reducing preterm deliveries and associated morbidity and mortality.
Frequency: Approximately 3-5% of all newborns have a recognizable birth defect. According to Cunningham and MacDonald, the suggested causes of fetal anomalies are as follows:
Genetic (ie, chromosomal) (20-25%)
Fetal infections (3-5%)
Maternal disease (4%)
Drugs/medications (<1%)
Unknown (65-70%)
Medical complications during pregnancy encompass a wide array of medical problems, to include the following:
Hypertensive disorders
Diabetes mellitus
Hematologic disorders
Cardiovascular diseases
Thromboembolic disorders
Thyroid and parathyroid diseases
Pituitary disorders
Adrenal disorders
Renal diseases
Hepatic diseases
GI tract disorders
Pulmonary diseases
Infectious diseases
Neurologic diseases
Psychiatric disorders
Malignancies
The diseases tend to occur in frequencies compatible with those of nonpregnant age-matched women. Providing an in-depth review of this wide array of medical problems is beyond the scope of this article.
The most common cancers found in pregnant women mirror those found in their nonpregnant counterparts, to include the following:
Cervical cancer (1 case per 2200 pregnancies)
Breast cancer (1 case per 3000 pregnancies)
Melanoma (0.14-2.8 cases per 1000 pregnancies)
Ovarian cancer
Thyroid cancer
Leukemia (rare)
Lymphoma
Colorectal carcinoma (0.10-1.0 cases per 1000 pregnancies)
The total incidence of malignancy during pregnancy is estimated at 1 case per 1000 pregnancies.
As previously noted, the number of multifetal pregnancies has increased enormously because of the use of assisted reproductive technologies. Twins have increased in frequency from 1 set per 90 pregnancies to 1 set per 45 pregnancies. Higher-order multifetal pregnancies have quadrupled in the past 20 years.
Clinical: Patients in need of therapeutic termination of pregnancy can be identified at any gestational age; however, the consideration of therapeutic abortion is generally limited to pregnancies at 24 weeks' gestation or less. Many patients are in the second trimester of pregnancy because of the timing of fetal assessment tools (eg, triple screen, amniocentesis, ultrasound).
INDICATIONS
The indications for therapeutic abortion, in its broadest definition, are as follows:
To save the life of the pregnant woman
To preserve the health of the pregnant woman
To terminate a pregnancy that would result in the birth of a child with defects incompatible with life or associated with significant morbidity
To terminate a nonviable pregnancy
To selectively reduce a multifetal pregnancy
Therapeutic abortions to save the life of the mother or to preserve the health of the mother are rare events. The decision should be based on the collaborative agreement of a multidisciplinary team. At minimum, the team should consist of the patient, the obstetrician, a specialist with knowledge of the disease in question, an expert in genetic counseling, and a neonatologist. Additional members may include spiritual counselors, nurses, psychologists/psychiatrists, intensive care specialists, ethicists, and family members.
The decision to terminate the pregnancy includes consideration of the effect of the pregnancy on disease outcome, the effect of treatment on fetal outcome, the gestational age of the pregnancy, the level of attachment of the patient to the pregnancy, the desires of the patient and the father, and the availability of family resources/support. This complex situation requires thought and excellent communication among the involved parties regarding the short- and long-term consequences of the decision to abort or continue the pregnancy. The decision must be individualized for each patient. There must be an inherent acceptance of the subjective nature of decisions made in this area. The clinical situations may be rare, and clinical data available may be anecdotal, incomplete, and/or inconclusive.
Commonly accepted medical indications for therapeutic termination of pregnancy include severe hypertensive vascular disease, cardiac disease with cardiac decompensation, and certain malignancies.
Malignancy
Cervical cancer is the most common malignancy affecting pregnant women. Invasive cervical cancer is treated with surgery or radiation; both treatment modalities result in fetal death for the previable fetus. Delay of therapy is the only option that allows fetal salvage in this setting. Treatment delays to allow fetal maturation have been successfully attempted in stages IA and IB. Treatment delays for advanced disease (stages IIB-IV) are controversial. All decisions regarding delay must be individualized and must consider other factors that affect the prognosis (eg, HIV status).
The prognosis for patients with breast cancer is not adversely affected by continuation of pregnancy. The decision to terminate a pregnancy complicated by breast cancer in the first and second trimesters is determined by the degree to which the pregnancy impairs effective treatment and whether treatment presents a risk to the fetus.
The prognosis for patients with melanoma is not improved by therapeutic abortion. Metastatic spread of melanoma to the placenta and fetus has been reported but is very rare. This type of spread has also been reported with lymphoma, leukemia, breast cancer, lung cancer, and stomach cancer and should be addressed when counseling at-risk patients.
Fetal conditions
A pregnancy in which the fetus has defects that are either incompatible with life or associated with significant morbidity can be an indication for therapeutic abortion. The number of fetal conditions that can be identified during pregnancy is always expanding because of improvements in technology available for antenatal diagnosis. The following fetal conditions are identifiable:
Chromosomal disorders
X-linked disorders
Metabolic disorders
Neural tube defects
Structural anomalies associated with exposure to teratogens
Structural anomalies of multifactorial or unknown etiology
Multifetal pregnancies
Multifetal pregnancies are associated with high fetal morbidity and mortality rates. In this setting, morbidity and mortality are associated with high rates of preterm delivery and growth retardation. Preterm birth rates at less than 33 weeks' gestation are 8 times higher for twins and 24 times higher for triplets compared with singleton pregnancies. Each additional fetus in a pregnancy reduces the length of the pregnancy by approximately 3.6 weeks. After birth, the mortality rates for infants born in multiple pregnancies remain elevated from birth to age 5 years, even after controlling for growth restriction.
Multifetal reduction has been shown to reduce the risk of preterm delivery for the remaining fetuses. However, the incidence of prematurity in reduced pregnancies appears to remain higher than in spontaneous pregnancies of the same fetal number. An overall reduction in morbidity-improved survival rates occurs in reduced pregnancies compared with pregnancies in which reduction is not performed.
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